@article{jiang_scholle_jin_wei_wang_ghiladi_2024, title={Chlorophyllin as a photosensitizer in photodynamic antimicrobial materials}, volume={2}, ISSN={["1572-882X"]}, DOI={10.1007/s10570-024-05758-3}, journal={CELLULOSE}, author={Jiang, Chenyu and Scholle, Frank and Jin, Fangyu and Wei, Qufu and Wang, Qingqing and Ghiladi, Reza A.}, year={2024}, month={Feb} }
 @article{shi_liu_wu_zhu_deng_yao_xiao_lorimer_ghiladi_xu_et al._2024, title={Serum binding folate receptor autoantibodies lower in autistic boys and positively-correlated with folate}, volume={172}, ISSN={["1950-6007"]}, DOI={10.1016/j.biopha.2024.116191}, journal={BIOMEDICINE & PHARMACOTHERAPY}, author={Shi, Ai and Liu, Di and Wu, Huiwen and Zhu, Rui and Deng, Ying and Yao, Lulu and Xiao, Yaqian and Lorimer, George H. and Ghiladi, Reza A. and Xu, Xinjie and et al.}, year={2024}, month={Mar} }
 @article{lucas_kim_ghiladi_2023, title={Celebrating Kenneth D. Karlin for his ACS Award for Distinguished Service in the Advancement of Inorganic Chemistry}, volume={241}, ISSN={["1873-3344"]}, DOI={10.1016/j.jinorgbio.2023.112142}, abstractNote={Capillary electrophoresis was used to estimate the solvolytic dissociation rate (kd) of metal complexes of deferasirox (DFX, H3L), a drug used to treat iron overload. Inert CoIIIL23− did not dissociate. The estimated kd value for FeIIIL23− was (2.7 ± 0.3) × 10−4 s−1 (298 K, pH 7.4). The kd values of other complexes (AlIIIL23−, NiIIL24−, and MnIIL−) were in the range 10−3–10−4 s−1. In contrast, ZnIIL− and CuIIL− were too labile to allow kd estimation. The fact that the half-life of FeIIIL23− (43.3 min) is shorter than the blood half-life of DFX (8–16 h) implies that the blood concentration of DFX should be high enough to prevent dissociation of FeIIIL23−. The possibility of a safer iron-chelation therapy that avoids excretion of other essential metal ions such as ZnII is discussed, highlighting the importance of selectivity in terms of kinetic stability.}, journal={JOURNAL OF INORGANIC BIOCHEMISTRY}, author={Lucas, Heather R. and Kim, Eunsuk and Ghiladi, Reza A.}, year={2023}, month={Apr} }
 @article{aktar_serrano_ghiladi_franzen_2023, title={Comparative study of the binding and activation of 2,4-dichlorophenol by dehaloperoxidase A and B}, volume={247}, ISSN={["1873-3344"]}, DOI={10.1016/j.jinorgbio.2023.112332}, abstractNote={The dehaloperoxidase-hemoglobin (DHP), first isolated from the coelom of a marine terebellid polychaete, Amphitrite ornata, is an example of a multi-functional heme enzyme. Long known for its reversible oxygen (O2) binding, further studies have established DHP activity as a peroxidase, oxidase, oxygenase, and peroxygenase. The specific reactivity depends on substrate binding at various internal and external binding sites. This study focuses on comparison of the binding and reactivity of the substrate 2,4-dichlorophenol (DCP) in the isoforms DHPA and B. There is strong interest in the degradation of DCP because of its wide use in the chemical industry, presence in waste streams, and particular reactivity to form dioxins, some of the most toxic compounds known. The catalytic efficiency is 3.5 times higher for DCP oxidation in DHPB than DHPA by a peroxidase mechanism. However, DHPA and B both show self-inhibition even at modest concentrations of DCP. This phenomenon is analogous to the self-inhibition of 2,4,6-trichlorophenol (TCP) at higher concentration. The activation energies of the electron transfer steps in DCP in DHPA and DHPB are 19.3 ± 2.5 and 24.3 ± 3.2 kJ/mol, respectively, compared to 37.2 ± 6.5 kJ/mol in horseradish peroxidase (HRP), which may be a result of the more facile electron transfer of an internally bound substrate in DHPA. The x-ray crystal structure of DHPA bound with DCP determined at 1.48 Å resolution, shows tight substrate binding inside the heme pocket of DHPA (PDB 8EJN). This research contributes to the studies of DHP as a naturally occurring bioremediation enzyme capable of oxidizing a wide range of environmental pollutants.}, journal={JOURNAL OF INORGANIC BIOCHEMISTRY}, author={Aktar, Mst Sharmin and Serrano, Vesna and Ghiladi, Reza and Franzen, Stefan}, year={2023}, month={Oct} }
 @article{deng_zang_li_sun_mei_bai_shang_deng_xiao_ghiladi_et al._2023, title={Hydrothermally Derived Green Carbon Dots from Broccoli Water Extracts: Decreased Toxicity, Enhanced Free-Radical Scavenging, and Anti-Inflammatory Performance}, volume={2}, ISSN={["2373-9878"]}, DOI={10.1021/acsbiomaterials.2c01537}, abstractNote={Biomass carbon dots (CDs) derived from natural plants possess the advantages of low cost, photostability, and excellent biocompatibility, with potential applications in chemical sensing, bioimaging, and nanomedicine. However, the development of biomass CDs with excellent antioxidant activity and good biocompatibility is still a challenge. Herein, we propose a hypothesis for enhancing the antioxidant capacity of biomass CDs based on precursor optimization, extraction solvent, and other conditions with broccoli as the biomass. Compared to broccoli water extracts, broccoli powders, and broccoli organic solvent extracts, CDs derived from broccoli water extracts (BWE-CDs) have outstanding antioxidant properties due to the abundant C═C, carbonyl, and amino groups on their surface. After optimization of the preparation condition, the obtained BWE-CDs exhibit excellent free-radical scavenging activity with an EC50 of 68.2 μg/mL for DPPH• and 22.4 μg/mL for ABTS•+. Cytotoxicity and zebrafish embryotoxicity results indicated that BWE-CDs have lower cytotoxicity and better biocompatibility than that of CDs derived from organic solvents. In addition, BWE-CDs effectively scavenged reactive oxygen species (ROS) in A549 cells, 293T cells, and zebrafish, as well as eliminating inflammation in LPS-stimulated zebrafish. Mechanistic studies showed that the anti-inflammatory effect of BWE-CDs was dependent on the direct reaction of CDs with free radicals, the regulation of NO levels, and the upregulation of the expression of SOD and GPX-4. This work indicates that the antioxidant activity of CDs could be enhanced by using solvent extracts of biomass as precursors, and the obtained BWE-CDs exhibit characteristics of greenness, low toxicity, and excellent antioxidant and anti-inflammatory activities, which suggests the potential promising application of BWE-CDs as an antioxidant nanomedicine for inflammatory therapy.}, journal={ACS BIOMATERIALS SCIENCE & ENGINEERING}, author={Deng, Wen-wen and Zang, Chuan-ru and Li, Qiu-chen and Sun, Bo and Mei, Xue-ping and Bai, Lu and Shang, Xin-miao and Deng, Ying and Xiao, Ya-qian and Ghiladi, Reza A. and et al.}, year={2023}, month={Feb} }
 @article{lucas_kim_ghiladi_2023, title={Journal of Inorganic Biochemistry - Karlin Special Issue}, volume={241}, ISSN={["1873-3344"]}, DOI={10.1016/j.jinorgbio.2023.112143}, abstractNote={The Cytochrome P450 (CYP450) superfamily has been the subject of intense research for over six decades. Here the HU227 strain of E. coli, lacking the δ-aminolevulinic acid (δ-ALA) synthase gene, was employed, along with [5-13C] δ-ALA, in the heterologous expression of P450cam harboring a prosthetic group labeled with 13C at the four methine carbons (Cm) and pyrrole Cα positions. The product was utilized as a proof of principle strategy for defining and refining solution phase active site structure in cytochrome P450cam, providing proton-to-proton distances from 13CmH to protons on bound substrate or nearby amino acid residues, using short mixing time 2D or 3D NOESY-HMQC methods. The results reveal the interesting finding that 2D 13C-filtered NOESY-HMQC can be used to obtain distances between protons on labeled 13C to positions of protons nearby in the active site, confirming the utility of this NMR-based approach to probing active site structure under physiological conditions. Such 13C-heme-filtered NOE data complement X-ray crystallographic and T1-based NMR measurements; and, may also be of potentially significant utility in furnishing experimental distance constraints in validations of docking routines commonly employed for determining the relative affinities and binding orientations of drug candidates with CYP450s.}, journal={JOURNAL OF INORGANIC BIOCHEMISTRY}, author={Lucas, Heather R. and Kim, Eunsuk and Ghiladi, Reza A.}, year={2023}, month={Apr} }
 @article{yun_serrano_ghiladi_2023, title={Oxidation of bisphenol A (BPA) and related compounds by the multifunctional catalytic globin dehaloperoxidase}, volume={238}, ISSN={["1873-3344"]}, DOI={10.1016/j.jinorgbio.2022.112020}, abstractNote={Dehaloperoxidase (DHP) from the marine polychaete Amphitrite ornata is a multifunctional enzyme that possesses peroxidase, peroxygenase, oxidase and oxygenase activities. Herein, we investigated the reactivity of DHP B with bisphenol A (BPA) and related compounds (bisphenol E, bisphenol F, tetrachlorobisphenol A, 2,2′-biphenol, 3,3′-biphenol, 4,4′-biphenol, and 3,3′-dibromo-4,4′-biphenol). As a previously unknown substrate for DHP B, BPA (as a representative substrate) is an endocrine disruptor widely used in polycarbonate and epoxy resins, thus resulting in human exposure. Reactivity studies with these substrates were investigated using high performance liquid chromatography (HPLC), and their corresponding oxidation products were determined by mass spectrometry (GC–MS/ LC-MS). BPA undergoes oxidation in the presence of DHP B and hydrogen peroxide yielding two cleavage products (4-isopropenylphenol and 4-(2-hydroxypropan-2-yl)phenol), and oligomers with varying degrees of oxidation. 18O-labeling studies confirmed that the O-atom incorporated into the products was derived exclusively from water, consistent with substrate oxidation via a peroxidase-based mechanism. The X-ray crystal structures of DHP bound with bisphenol E (1.48 Å), bisphenol F (1.75 Å), 2,2′-biphenol (1.90 Å) and 3,3′-biphenol (1.30 Å) showed substrate binding sites are in the distal pocket of the heme cofactor, similar to other previously studied DHP substrates. Stopped-flow UV–visible spectroscopy was utilized to investigate the mechanistic details and enzyme oxidation states during substrate turnover, and a reaction mechanism is proposed. The data presented here strongly suggest that DHP B can catalyze the oxidation of bisphenols and biphenols, thus providing evidence of how infaunal invertebrates can contribute to the biotransformation of these marine pollutants.}, journal={JOURNAL OF INORGANIC BIOCHEMISTRY}, author={Yun, Dongju and Serrano, Vesna and Ghiladi, Reza A.}, year={2023}, month={Jan} }
 @article{wells_ciftci_peddinti_ghiladi_vediyappan_spontak_govind_2023, title={Preventing the spread of life-threatening gastrointestinal microbes on the surface of a continuously self-disinfecting block polymer}, volume={652}, ISSN={["1095-7103"]}, DOI={10.1016/j.jcis.2023.08.088}, abstractNote={Highly persistent, drug-resistant and transmissible healthcare pathogens such as Clostridioides difficile (C. difficile) and Candida auris (C. auris) are responsible for causing antibiotic-associated fatal diarrhea and invasive candidiasis, respectively. In this study, we demonstrate that these potentially lethal gastrointestinal microbes can be rapidly inactivated on the solid surface of a self-disinfecting anionic block polymer that inherently generates a water surface layer that is highly acidic (pH < 1) upon hydration. Due to thermodynamic incompatibility between its chemical sequences, the polymer spontaneously self-organizes into a nanostructure that enables proton migration from the interior of a film to the surface via contiguous nanoscale hydrophilic channels, as discerned here by scanning electron and atomic force microscopies, as well as X-ray photoelectron spectroscopy. Here, we report that two strains of C. difficile in the vegetative state and two species of Candida, Candida albicans (C. albicans) and C. auris, are, in most cases, inactivated to the limit of minimum detection. Corresponding electron and optical microscopy images reveal that, upon exposure to the hydrated polymer, the outer microbial membranes display evidence of damage and intracellular material is expelled. Combined with our previous studies of rapid bacterial and viral inactivation, these antimicrobial results are highly encouraging and, if translatable to clinical conditions in the form of self-standing polymer films or coatings, are expected to benefit the welfare of patients in healthcare facilities by continuously preventing the spread of these potentially dangerous microbes.}, journal={JOURNAL OF COLLOID AND INTERFACE SCIENCE}, author={Wells, Kacie M. and Ciftci, Yusuf and Peddinti, Bharadwaja S. T. and Ghiladi, Reza A. and Vediyappan, Govindsamy and Spontak, Richard J. and Govind, Revathi}, year={2023}, month={Dec}, pages={718–726} }
 @article{wu_yang_guo_zhang_ghiladi_bayram_wang_2023, title={The role of sound stimulation in production of plant secondary metabolites}, volume={13}, ISSN={["2192-2209"]}, DOI={10.1007/s13659-023-00409-9}, abstractNote={Abstract Sound vibration is one of natural stimuli trigging physiological changes in plants. Recent studies showed that sound waves stimulated production of a variety of plant secondary metabolites, including flavonoids, in order to enhance seed germination, flowering, growth or defense. In this review, we examine the potential role of sound stimulation on the biosynthesis of secondary metabolites and the followed cascade of physiological changes in plants, from the perspective of transcriptional regulation and epigenetic regulation for the first time. A systematic summary showed that a wide range of factors may regulate the production of secondary metabolites, including plant species, growth stage, sound types, sound frequency, sound intensity level and exposure time, etc. Biochemical and physiological changes due to sound stimulation were thoroughly summarized as well, for secondary metabolites can also act as a free radical scavenger, or a hormone signaling molecule. We also discussed the limits of previous studies, and the future application of sound waves in biosynthesis of plant secondary metabolites.}, number={1}, journal={NATURAL PRODUCTS AND BIOPROSPECTING}, author={Wu, Li and Yang, Ning and Guo, Meng and Zhang, Didi and Ghiladi, Reza A. and Bayram, Hasan and Wang, Jun}, year={2023}, month={Dec} }
 @article{malewschik_carey_serrano_ghiladi_2022, title={Bridging the functional gap between reactivity and inhibition in dehaloperoxidase B from Amphitrite ornata: Mechanistic and structural studies with 2,4-and 2,6-dihalophenols}, volume={236}, ISSN={["1873-3344"]}, DOI={10.1016/j.jinorgbio.2022.111944}, abstractNote={The multifunctional catalytic globin dehaloperoxidase (DHP) from the marine worm Amphitrite ornata was shown to catalyze the H2O2-dependent oxidation of 2,4- and 2,6-dihalophenols (DXP; X = F, Cl, Br). Product identification by LC-MS revealed multiple monomeric products with varying degrees of oxidation and/or dehalogenation, as well as oligomers with n up to 6. Mechanistic and 18O-labeling studies demonstrated sequential dihalophenol oxidation via peroxidase and peroxygenase activities. Binding studies established that 2,4-DXP (X = Cl, Br) have the highest affinities of any known DHP substrate. X-ray crystallography identified different binding positions for 2,4- and 2,6-DXP substrates in the hydrophobic distal pocket of DHP. Correlation between the number of halogens and the substrate binding orientation revealed a halogen-dependent binding motif for mono- (4-halophenol), di- (2,4- and 2,6-dihalophenol) and trihalophenols (2,4,6-trihalopenol). Taken together, the findings here on dihalophenol reactivity with DHP advance our understanding of how these compounds bridge the inhibitory and oxidative functions of their mono- and trihalophenol counterparts, respectively, and provide further insight into the protein structure-function paradigm relevant to multifunctional catalytic globins in comparison to their monofunctional analogs.}, journal={JOURNAL OF INORGANIC BIOCHEMISTRY}, author={Malewschik, Talita and Carey, Leiah M. and Serrano, Vesna and Ghiladi, Reza A.}, year={2022}, month={Nov} }
 @article{moreno-chicano_carey_axford_beale_doak_duyvesteyn_ebrahim_henning_monteiro_myles_et al._2022, title={Complementarity of neutron, XFEL and synchrotron crystallography for defining the structures of metalloenzymes at room temperature}, volume={9}, ISSN={["2052-2525"]}, DOI={10.1107/S2052252522006418}, abstractNote={The determination of the structure of the multifunctional globin dehaloperoxidase using multiple room-temperature methods is described. Structures obtained by serial femtosecond crystallography, serial synchrotron crystallography, neutron diffraction and serial Laue crystallography are compared and two oxidation states of the enzyme are contrasted.}, journal={IUCRJ}, author={Moreno-Chicano, Tadeo and Carey, Leiah M. and Axford, Danny and Beale, John H. and Doak, R. Bruce and Duyvesteyn, Helen M. E. and Ebrahim, Ali and Henning, Robert W. and Monteiro, Diana C. F. and Myles, Dean A. and et al.}, year={2022}, month={Sep}, pages={610–624} }
 @article{jin_liao_wang_shen_jiang_zhang_wei_ghiladi_2022, title={Dual-functionalized luminescent/photodynamic composite fabrics: Synergistic antibacterial activity for self-disinfecting textiles}, volume={587}, ISSN={["1873-5584"]}, DOI={10.1016/j.apsusc.2022.152737}, abstractNote={For the purpose of developing self-disinfecting photodynamic textiles with enhanced antibacterial activity, here we report a scalable and facile method to immobilize the long persistent phosphor SrAl2O4:Eu2+, Dy3+ (SAOED) and the photosensitizer Rose Bengal onto cotton fabric (CF) by knife coating and photocrosslinking methods. The resultant composite material, termed SAOED/RB-CF, exhibited superior synergistic antibacterial efficacy capable of 99.999% (5 log units, detection limit) and 99.986% (3.9 log units) photoinactivation against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA), respectively, under visible-light illumination (Xenon lamp). Mechanistic studies employing both substrate photooxidation and EPR spin-trapping methods demonstrated an enhanced yield of singlet oxygen (1O2) production compared to the RB/CF material alone (without the phosphor), suggesting that the light emitted from the phosphorescence of the photoexcited SAOED could be absorbed by the RB photosensitizer under dark conditions, resulting in effective synergistic pathogen inactivation. In addition, the SAOED/RB-CF composite fabric possessed excellent abrasion resistance, mechanical strength and color fastness. Our findings suggest that the integration of long persistent phosphors into photodynamic materials may provide a new avenue to explore for developing composite fabrics as applied materials in infection control applications for use in both healthcare environments and consumer textiles.}, journal={APPLIED SURFACE SCIENCE}, author={Jin, Fangyu and Liao, Shiqin and Wang, Qingqing and Shen, Huiying and Jiang, Chenyu and Zhang, Jiawen and Wei, Qufu and Ghiladi, Reza A.}, year={2022}, month={Jun} }
 @article{tian_hong_li_qiu_li_qin_ghiladi_yin_2022, title={Electrospinning membranes with Au@carbon dots: Low toxicity and efficient antibacterial photothermal therapy}, volume={142}, ISSN={["2772-9508"]}, DOI={10.1016/j.bioadv.2022.213155}, abstractNote={As bacterial infections continue to pose a significant challenge to healthcare globally, new therapeutic strategies, interventions, and complementary approaches that address both infection prevention and treatment are needed. As one such strategy, photothermal therapy (PTT) as a non-chemotherapeutic approach is considered a safe and potentially efficient strategy to combat bacterial infections, particularly for antibiotic-resistant pathogens given that PTT operates via a temperature-dependent process against which the development of bacterial resistance is unlikely. Here, we prepared Au@CDs composite nanoparticles (Au@CD) comprised of gold nanoparticles (AuNPs) and carbon dots (N,S-CDs), and investigated their use as a photothermal agent in PTT. The presence of the CDs as surface decorations conferred improved photothermal conversion efficiency, photostability, and biocompatibility to the Au@CD when compared to the parent AuNPs. To investigate if the Au@CD could serve as a PTT wound dressing and accelerate tissue repair, they were embedded within a PVA membrane via electrospinning. The resultant Au@CD membrane exhibited excellent biocompatibility and photothermal antimicrobial activity. In vitro photothermal antibacterial inactivation studies confirmed their efficacy against S. aureus and E. coli (99 + % inactivation of both pathogens under NIR irradiation). Moreover, in vivo studies employing Kunming male mice with S. aureus-infected wounds on their backs were chosen as a trauma model, with the Au@CD membranes serving as wound dressings. The results showed that a local temperature increased up to 50 °C upon NIR irradiation could effectively eradicate bacteria at the wound site, reduce the risk of bacterial infection, suppress inflammation as well as improve collagen deposition and angiogenesis, all of which together facilitated wound closure and resulted in a better therapeutic effect than the controls. Taken together, this work confirms that NIR-irradiated Au@CD-based membranes and related materials are promising photothermal antimicrobial platforms for wound dressings and related healthcare applications.}, journal={BIOMATERIALS ADVANCES}, author={Tian, Hua and Hong, Jixuan and Li, Changgui and Qiu, Yuheng and Li, Mengting and Qin, Ziyu and Ghiladi, Reza A. and Yin, Xueqiong}, year={2022}, month={Nov} }
 @article{shen_liao_jiang_zhang_wei_ghiladi_wang_2022, title={In situ grown bacterial cellulose/MoS2 composites for multi-contaminant wastewater treatment and bacteria inactivation}, volume={277}, ISSN={["1879-1344"]}, DOI={10.1016/j.carbpol.2021.118853}, abstractNote={For the purpose of developing multifunctional water purification materials capable of degrading organic pollutants while simultaneously inactivating microorganisms from contaminated wastewater streams, we report here a facile and eco-friendly method to immobilize molybdenum disulfide into bacterial cellulose via a one-step in-situ biosynthetic method. The resultant nanocomposite, termed BC/MoS2, was shown to possess a photocatalytic activity capable of generating •OH from H2O2, while also exhibiting photodynamic/photothermal mechanisms, the combination of which exhibits synergistic activity for the degradation of pollutants as well as for bacterial inactivation. In the presence of H2O2, the BC/MoS2 nanocomposite exhibited excellent antibacterial efficacy upwards of 99.9999% (6 log units) for the photoinactivation of both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus upon infrared (IR) lamp illumination (100 W, 760 nm ≤ λ ≤ 5000 nm, 15 cm vertical distance; 5 min). Mechanistic studies revealed synergistic pathogen inactivation resulting from the combination of photocatalytically generated •OH and hyperthermia induced by the photothermal conversion of the near-IR light. In addition, the BC/MoS2 nanocomposite also showed excellent photodegradation activity for common aqueous contaminants in the presence of H2O2, including malachite green (a textile dye), catechol violet (a phenol) and formaldehyde. Taken together, our findings demonstrate that sustainable materials such as BC/MoS2 have potential applications in wastewater treatment and microorganism disinfection.}, journal={CARBOHYDRATE POLYMERS}, author={Shen, Huiying and Liao, Shiqin and Jiang, Chenyu and Zhang, Jiawen and Wei, Qufu and Ghiladi, Reza A. and Wang, Qingqing}, year={2022}, month={Feb} }
 @article{popescu_dinh_chen_miller_washburn_mcguire_dumarieh_d'antonio_ghiladi_2022, title={Mossbauer studies of the ferryl, ferrous and ferric states of dehaloperoxidase from A. ornata}, volume={234}, ISSN={["1873-3344"]}, DOI={10.1016/j.jinorgbio.2022.111867}, abstractNote={Dehaloperoxidase (DHP) is a multi-functional catalytic globin from the marine worm A. ornata, whose physiological functions include oxygen transport and oxidation of toxic substrates present in its habitat. In the Fe(III) state, DHPA has an isomer shift of 0.42 mm/s, characteristic for high-spin heme proteins. Changes in pH have subtle effects on the electronic structure of DHP in the Fe(III) state detectable in the high-field spectra, which show a pH-dependent mixture of species with different zero-field splittings between 5 and 18 cm-1. The short-lived intermediate obtained by direct reaction of the Fe(III) enzyme with H2O2 has an isomer shift of 0.10 mm/s, indicative of an Fe(IV)-oxo state and of an S = 1 electronic ground state confirmed by variable field studies. The O2-bound state of DHP has an isomer shift of 0.28 mm/s and a high-field spectrum characteristic for diamagnetic heme complexes, similarly to other haemoglobins. Overall, the isomer shift and quadrupole splitting of DHP in the four states studied are expectedly similar to both peroxidases and to myoglobin. The differences in electronic structure between DHP and other heme proteins and enzyme are observed in the high-field Mössbauer spectra of the ferric state, which show pH-dependent zero-field splittings suggesting a heme site in which the ligand field strength at the iron ion is tuned by pH. This tunability is correlated with variable electron-donating properties of the iron, which can perform multiple functions.}, journal={JOURNAL OF INORGANIC BIOCHEMISTRY}, author={Popescu, C. V. and Dinh, Thanhminh and Chen, Hongli and Miller, Danielle and Washburn, Anastasia and McGuire, Ashlyn and Dumarieh, Rania and D'Antonio, Jennifer and Ghiladi, Reza A.}, year={2022}, month={Sep} }
 @article{thompson_shay_serrano_dumarieh_ghiladi_franzen_2021, title={A new inhibition mechanism in the multifunctional catalytic hemoglobin dehaloperoxidase as revealed by the DHP A(V59W) mutant: A spectroscopic and crystallographic study}, volume={25}, ISSN={["1099-1409"]}, DOI={10.1142/S1088424621500826}, abstractNote={As multifunctional catalytic hemoglobins, dehaloperoxidase isoenzymes A and B (DHP A and B) are among the most versatile hemoproteins in terms of activities displayed. The ability of DHP to bind over twenty different substrates in the distal pocket might appear to resemble the promiscuousness of monooxygenase enzymes, yet there are identifiable substrate-specific interactions that can steer the type of oxidation (O-atom vs. electron transfer) that occurs inside the DHP distal pocket. Here, we have investigated the DHP A(V59W) mutant in order to probe the limits of conformational flexibility in the distal pocket as it relates to the genesis of this substrate-dependent activity differentiation. The X-ray crystal structure of the metaquo DHP A(V59W) mutant (PDB 3K3U) and the V59W mutant in complex with fluoride [denoted as DHP A(V59W-F)] (PDB 7MNH) show significant mobility of the tryptophan in the distal pocket, with two parallel conformations having W59-N[Formula: see text] H-bonded to a heme-bound ligand (H2O or F[Formula: see text], and another conformation [observed only in DHP A(V59W-F)] that brings W59 sufficiently close to the heme as to preclude axial ligand binding. UV-vis and resonance Raman spectroscopic studies show that DHP A(V59W) is 5-coordinate high spin (5cHS) at pH 5 and 6-coordinate high spin (6cHS) at pH 7, whereas DHP A(V59W-F) is 6cHS from pH 5 to 7. Enzyme assays confirm robust peroxidase activity at pH 5, but complete loss of activity at pH 7. We find no evidence that tryptophan plays a role in the oxidation mechanism ([Formula: see text]. radical formation). Instead, the data reveal a new mechanism of DHP inhibition, namely a shift towards a non-reactive form by OH[Formula: see text] ligation to the heme-Fe that is strongly stabilized (presumably through H-bonding interactions) by the presence of W59 in the distal cavity.}, number={7-8}, journal={JOURNAL OF PORPHYRINS AND PHTHALOCYANINES}, author={Thompson, Matthew K. and Shay, Madeline R. and Serrano, Vesna and Dumarieh, Rania and Ghiladi, Reza A. and Franzen, Stefan}, year={2021}, month={Jul}, pages={756–771} }
 @misc{malewschik_ghiladi_2021, title={Dehaloperoxidase: An enzymatic Swiss army knife}, volume={441}, ISSN={["1873-3840"]}, DOI={10.1016/j.ccr.2021.213976}, abstractNote={The hemoglobin from the marine worm Amphitrite ornata has been found to possess multiple enzymatic activities in addition to its O2-transport function. Named dehaloperoxidase (DHP), this globin employs four mechanisms for substrate oxidation as a defense mechanism against toxic metabolites, spanning electron- (peroxidase and oxidase) and O-atom (peroxygenase and oxygenase) transfer. As such, DHP can be defined as a multifunctional catalytic hemoglobin. Given that its peroxidase function is already well established in the literature, this review aims to provide further structural and mechanistic details into the other three activities performed by DHP, with a particular emphasis on its peroxygenase activity.}, journal={COORDINATION CHEMISTRY REVIEWS}, author={Malewschik, Talita and Ghiladi, Reza A.}, year={2021}, month={Aug} }
 @article{wang_ke_chen_wang_yang_cao_liu_wei_ghiladi_wang_2021, title={Porous protoporphyrin IX-embedded cellulose diacetate electrospun microfibers in antimicrobial photodynamic inactivation}, volume={118}, ISSN={0928-4931}, url={http://dx.doi.org/10.1016/j.msec.2020.111502}, DOI={10.1016/j.msec.2020.111502}, abstractNote={Motivated by the need for self-disinfecting materials that can be used to reduce the surface transmission of harmful microbes to healthy hosts, here we prepared a photodynamic antimicrobial membrane comprised of electrospun cellulose diacetate (CA) microfibers into which the photosensitizer protoporphyrin IX (PpIX) was in situ embedded. The resultant porous PpIX-embedded CA (PpIX/CA) microfibrous membranes were prepared with two different photosensitizer loadings: 5 and 10 wt% PpIX with respect to CA (85 and 170 nmol PpIX/mg membrane, respectively). The singlet oxygen (1O2) generated by the embedded photosensitizer was confirmed by electron paramagnetic resonance spectroscopic studies through generation of the TEMPO radical, and its photooxidation efficiency was further investigated using potassium iodide as a model substrate. Antibacterial photodynamic inactivation studies showed that the PpIX/CA membrane achieved a 99.8% reduction in Gram-positive S. aureus after illumination (Xe lamp, 65 ± 5 mW/cm2, λ ≥ 420 nm; 30 min), with a lower level of reduction (86.6%) for Gram-negative E. coli. Potentiation with potassium iodide was found to be an effective way to further enhance the antimicrobial efficacy of the PpIX/CA microfibrous membrane, achieving 99.9999% (6 log units) inactivation of both S. aureus and E. coli in the presence of 25 and 100 mM KI, respectively. These findings indicate that the electrospun CA microfibrous membrane is an ideal matrix for a photosensitizer such as PpIX to be embedded and effectively sensitized upon visible light illumination, and its antimicrobial photodynamic inactivation efficiency could be strongly enhanced with the increased KI addition, showing a promising future for its use in pathogen transmission defensive materials.}, journal={Materials Science and Engineering: C}, publisher={Elsevier BV}, author={Wang, Tingting and Ke, Huizhen and Chen, Shiping and Wang, Jian and Yang, Wushi and Cao, Xiuming and Liu, Jingyan and Wei, Qufu and Ghiladi, Reza A. and Wang, Qingqing}, year={2021}, month={Jan}, pages={111502} }
 @article{peddinti_downs_yan_smith_ghiladi_mhetar_tocchetto_griffiths_scholle_spontak_2021, title={Rapid and Repetitive Inactivation of SARS-CoV-2 and Human Coronavirus on Self-Disinfecting Anionic Polymers}, volume={8}, ISSN={["2198-3844"]}, DOI={10.1002/advs.202003503}, abstractNote={While the ongoing COVID‐19 pandemic affirms an urgent global need for effective vaccines as second and third infection waves are spreading worldwide and generating new mutant virus strains, it has also revealed the importance of mitigating the transmission of SARS‐CoV‐2 through the introduction of restrictive social practices. Here, it is demonstrated that an architecturally‐ and chemically‐diverse family of nanostructured anionic polymers yield a rapid and continuous disinfecting alternative to inactivate coronaviruses and prevent their transmission from contact with contaminated surfaces. Operating on a dramatic pH‐drop mechanism along the polymer/pathogen interface, polymers of this archetype inactivate the SARS‐CoV‐2 virus, as well as a human coronavirus surrogate (HCoV‐229E), to the minimum detection limit within minutes. Application of these anionic polymers to frequently touched surfaces in medical, educational, and public‐transportation facilities, or personal protection equipment, can provide rapid and repetitive protection without detrimental health or environmental complications.}, number={11}, journal={ADVANCED SCIENCE}, author={Peddinti, Bharadwaja S. T. and Downs, Sierra N. and Yan, Jiaqi and Smith, Steven D. and Ghiladi, Reza A. and Mhetar, Vijay and Tocchetto, Roger and Griffiths, Anthony and Scholle, Frank and Spontak, Richard J.}, year={2021}, month={Jun} }
 @article{wang_mei_bai_zhou_liu_yao_ahluwalia_ghiladi_su_shu_et al._2021, title={Serum nitrite and nitrate: A potential biomarker for post-covid-19 complications}, volume={175}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2021.08.237}, abstractNote={Nitric oxide (NO) plays an important role in cardiovascular and immune systems. Quantification of blood nitrite and nitrate, two relatively stable metabolites of NO (generally as NOx), has been acknowledged, in part, representing NO bioactivity. Dysregulation of NOx had been reported in SARS-CoV-2 infected populations, but whether patients recovered from COVID-19 disease present with restored NOx is unknown. In this study, serum NO2- and NO3- were quantified and analyzed among 109 recovered adults in comparison to a control group of 166 uninfected adults. Nitrite or nitrate levels were not significantly different among mild-, common-, severe- and critical-type patients. However, these recovered patients had dramatically lower NO2- and NO2-/NO3- than the uninfected group (p < 0.0001), with significantly higher NO3- levels (p = 0.0023) than the uninfected group. Nitrate and nitrite/nitrate were positively and negatively correlated with patient age, respectively, with age 65 being a turning point among recovered patients. These results indicate that low NO2-, low NO2-/NO3- and high NO3- may be potential biomarkers of long-term poor or irreversible outcomes after SARS-CoV-2 infection. It suggests that NO metabolites might serve as a predictor to track the health status of recovered COVID-19 patients, highlighting the need to elucidate the role of NO after SARS-CoV-2 infection.}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Wang, Jun and Mei, Fanghua and Bai, Lu and Zhou, Suhua and Liu, Di and Yao, Lulu and Ahluwalia, Amrita and Ghiladi, Reza A. and Su, Lei and Shu, Tong and et al.}, year={2021}, month={Nov}, pages={216–225} }
 @article{shen_jiang_li_wei_ghiladi_wang_2021, title={Synergistic Photodynamic and Photothermal Antibacterial Activity of In Situ Grown Bacterial Cellulose/MoS2-Chitosan Nanocomposite Materials with Visible Light Illumination}, volume={13}, ISSN={["1944-8252"]}, DOI={10.1021/acsami.1c08178}, abstractNote={Owing to the rise in prevalence of multidrug-resistant pathogens attributed to the overuse of antibiotics, infectious diseases caused by the transmission of microbes from contaminated surfaces to new hosts are an ever-increasing threat to public health. Thus, novel materials that can stem this crisis, while also functioning via multiple antimicrobial mechanisms so that pathogens are unable to develop resistance to them, are in urgent need. Toward this goal, in this work, we developed in situ grown bacterial cellulose/MoS2-chitosan nanocomposite materials (termed BC/MoS2-CS) that utilize synergistic membrane disruption and photodynamic and photothermal antibacterial activities to achieve more efficient bactericidal activity. The BC/MoS2-CS nanocomposite exhibited excellent antibacterial efficacy, achieving 99.998% (4.7 log units) and 99.988% (3.9 log units) photoinactivation of Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus, respectively, under visible-light illumination (xenon lamp, 500 W, λ ≥ 420 nm, and 30 min). Mechanistic studies revealed that the use of cationic chitosan likely facilitated bacterial membrane disruption and/or permeability, with hyperthermia (photothermal) and reactive oxygen species (photodynamic) leading to synergistic pathogen inactivation upon visible-light illumination. No mammalian cell cytotoxicity was observed for the BC/MoS2-CS membrane, suggesting that such composite nanomaterials are attractive as functional materials for infection control applications.}, number={26}, journal={ACS APPLIED MATERIALS & INTERFACES}, author={Shen, Huiying and Jiang, Chenyu and Li, Wei and Wei, Qufu and Ghiladi, Reza A. and Wang, Qingqing}, year={2021}, month={Jul}, pages={31193–31205} }
 @article{fang_jiang_su_shu_liu_lai_ghiladi_wang_2021, title={The role of NO in COVID-19 and potential therapeutic strategies}, volume={163}, ISSN={0891-5849}, url={http://dx.doi.org/10.1016/j.freeradbiomed.2020.12.008}, DOI={10.1016/j.freeradbiomed.2020.12.008}, abstractNote={Nitric oxide (NO) is a free radical playing an important pathophysiological role in cardiovascular and immune systems. Recent studies reported that NO levels were significantly lower in patients with COVID-19, which was suggested to be closely related to vascular dysfunction and immune inflammation among them. In this review, we examine the potential role of NO during SARS-CoV-2 infection from the perspective of the unique physical, chemical and biological properties and potential mechanisms of NO in COVID-19, as well as possible therapeutic strategies using inhaled NO. We also discuss the limits of NO treatment, and the future application of this approach in prevention and therapy of COVID-19.}, journal={Free Radical Biology and Medicine}, publisher={Elsevier BV}, author={Fang, Wanyi and Jiang, Jingrui and Su, Lei and Shu, Tong and Liu, Huan and Lai, Shenghan and Ghiladi, Reza A. and Wang, Jun}, year={2021}, month={Feb}, pages={153–162} }
 @misc{nong_wu_ghiladi_guan_2021, title={The structural appeal of metal-organic frameworks in antimicrobial applications}, volume={442}, ISSN={["1873-3840"]}, DOI={10.1016/j.ccr.2021.214007}, abstractNote={Diseases caused by microorganisms have significantly impacted public health. Metal–organic frameworks (MOFs) and MOF-based materials with unique physical and chemical properties have shown promise as candidates for potent antimicrobial agents. In this review, the structural characteristics of MOFs that are demonstrated to be the main structural determinants in microorganism inactivation are discussed, with a particular focus on the type(s) of metal clusters, organic ligands, nanoparticles, and pores employed. A comprehensive overview of antimicrobial applications of MOFs and MOF-based composites on wound dressings, nano-pharmaceuticals, protective materials, antimicrobial surfaces, food preservation, and environmental decontamination will be presented in terms of these four structural elements. Last but not least, the future prospects of MOFs in antimicrobial applications as well as potential opportunities and challenges, are also elaborated.}, journal={COORDINATION CHEMISTRY REVIEWS}, author={Nong, Wenqian and Wu, Jun and Ghiladi, Reza A. and Guan, Yongguang}, year={2021}, month={Sep} }
 @article{ghareeb_peddinti_kisthardt_scholle_spontak_ghiladi_2021, title={Toward Universal Photodynamic Coatings for Infection Control}, volume={8}, ISSN={["2296-858X"]}, DOI={10.3389/fmed.2021.657837}, abstractNote={The dual threats posed by the COVID-19 pandemic and hospital-acquired infections (HAIs) have emphasized the urgent need for self-disinfecting materials for infection control. Despite their highly potent antimicrobial activity, the adoption of photoactive materials to reduce infection transmission in hospitals and related healthcare facilities has been severely hampered by the lack of scalable and cost-effective manufacturing, in which case high-volume production methods for fabricating aPDI-based materials are needed. To address this issue here, we examined the antimicrobial efficacy of a simple bicomponent spray coating composed of the commercially-available UV-photocrosslinkable polymer N-methyl-4(4'-formyl-styryl)pyridinium methosulfate acetal poly(vinyl alcohol) (SbQ-PVA) and one of three aPDI photosensitizers (PSs): zinc-tetra(4-N-methylpyridyl)porphine (ZnTMPyP4+), methylene blue (MB), and Rose Bengal (RB). We applied these photodynamic coatings, collectively termed SbQ-PVA/PS, to a variety of commercially available materials. Scanning electron microscopy (SEM) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) confirmed the successful application of the coatings, while inductively coupled plasma-optical emission spectroscopy (ICP-OES) revealed a photosensitizer loading of 0.09-0.78 nmol PS/mg material. The antimicrobial efficacy of the coated materials was evaluated against methicillin-susceptible Staphylococcus aureus ATCC-29213 and human coronavirus strain HCoV-229E. Upon illumination with visible light (60 min, 400-700 nm, 65 ± 5 mW/cm2), the coated materials inactivated S. aureus by 97-99.999% and HCoV-229E by 92-99.999%, depending on the material and PS employed. Photobleaching studies employing HCoV-229E demonstrated detection limit inactivation (99.999%) even after exposure for 4 weeks to indoor ambient room lighting. Taken together, these results demonstrate the potential for photodynamic SbQ-PVA/PS coatings to be universally applied to a wide range of materials for effectively reducing pathogen transmission.}, journal={FRONTIERS IN MEDICINE}, author={Ghareeb, C. Roland and Peddinti, Bharadwaja S. T. and Kisthardt, Samantha C. and Scholle, Frank and Spontak, Richard J. and Ghiladi, Reza A.}, year={2021}, month={Jul} }
 @article{nie_jiang_wu_chen_lv_wang_liu_narh_cao_ghiladi_et al._2020, title={Carbon quantum dots: A bright future as photosensitizers for in vitro antibacterial photodynamic inactivation}, volume={206}, ISSN={1011-1344}, url={http://dx.doi.org/10.1016/j.jphotobiol.2020.111864}, DOI={10.1016/j.jphotobiol.2020.111864}, abstractNote={Carbon nanomaterials have increasingly gained the attention of the nano-, photo- and biomedical communities owing to their unique photophysical properties. Here, we facilely synthesized carbon quantum dots (CQDs) in a one-pot solvothermal reaction, and demonstrated their utility as photosensitizers for in vitro antibacterial photodynamic inactivation (aPDI). The bottom-up synthesis employed inexpensive and sustainable starting materials (citric acid), used ethanol as an environmentally-friendly solvent, was relatively energy efficient, produced minimal waste, and purification was accomplished simply by filtration. The CQDs were characterized by both physical (TEM, X-ray diffraction) and spectroscopic (UV–visible, fluorescence, and ATR-FTIR) methods, which together confirmed their nanoscale dimensions and photophysical properties. aPDI studies demonstrated detection limit inactivation (99.9999 + %) of Gram-negative Escherichia coli 8099 and Gram-positive Staphylococcus aureus ATCC-6538 upon visible light illumination (λ ≥ 420 nm, 65 ± 5 mW/cm2; 60 min). Post-illumination SEM images of the bacteria incubated with the CQDs showed perforated and fragmented cell membranes consistent with damage from reactive oxygen species (ROS), and mechanistic studies revealed that the bacteria were inactivated by singlet oxygen, with no discernable roles for other ROS (e.g., superoxide or hydroxyl radicals). These findings demonstrated that CQDs can be facilely prepared, operate via a Type II mechanism, and are effective photosensitizers for in vitro aPDI.}, journal={Journal of Photochemistry and Photobiology B: Biology}, publisher={Elsevier BV}, author={Nie, Xiaolin and Jiang, Chenyu and Wu, Shuanglin and Chen, Wangbingfei and Lv, Pengfei and Wang, Qingqing and Liu, Jingyan and Narh, Christopher and Cao, Xiuming and Ghiladi, Reza A. and et al.}, year={2020}, month={May}, pages={111864} }
 @article{wang_chen_dong_lv_zheng_cao_wei_ghiladi_wang_2020, title={Color-Variable Photodynamic Antimicrobial Wool/Acrylic Blended Fabrics}, volume={13}, ISSN={1996-1944}, url={http://dx.doi.org/10.3390/ma13184141}, DOI={10.3390/ma13184141}, abstractNote={Towards the goal of developing scalable, economical and effective antimicrobial textiles to reduce infection transmission, here we prepared color-variable photodynamic materials comprised of photosensitizer (PS)-loaded wool/acrylic (W/A) blends. Wool fibers in the W/A blended fabrics were loaded with the photosensitizer rose bengal (RB), and the acrylic fibers were dyed with a variety of traditional cationic dyes (cationic yellow, cationic blue and cationic red) to broaden their color range. Investigations on the colorimetric and photodynamic properties of a series of these materials were implemented through CIELab evaluation, as well as photooxidation and antibacterial studies. Generally, the photodynamic efficacy of these dual-dyed fabrics was impacted by both the choice, and how much of the traditional cationic dye was employed in the dyeing of the W/A fabrics. When compared with the PS-only singly-dyed material, RB-W/A, that showed a 99.97% (3.5 log units; p = 0.02) reduction of Staphylococcus aureus under visible light illumination (λ ≥ 420 nm, 60 min), the addition of cationic dyes led to a slight decrease in the photoinactivation ability of the dual-dyed fabrics, but was still able to achieve a 99.3% inactivation of S. aureus. Overall, our findings demonstrate the feasibility and potential applications of low cost and color variable RB-loaded W/A blended fabrics as effective self-disinfecting textiles against pathogen transmission.}, number={18}, journal={Materials}, publisher={MDPI AG}, author={Wang, Tingting and Chen, Wangbingfei and Dong, Tingting and Lv, Zihao and Zheng, Siming and Cao, Xiuming and Wei, Qufu and Ghiladi, Reza A. and Wang, Qingqing}, year={2020}, month={Sep}, pages={4141} }
 @article{sun_zheng_yang_zhang_cheng_ghiladi_ma_wang_deng_2020, title={One-pot method based on deep eutectic solvent for extraction and conversion of polydatin to resveratrol from Polygonum cuspidatum}, volume={343}, ISSN={0308-8146}, url={http://dx.doi.org/10.1016/j.foodchem.2020.128498}, DOI={10.1016/j.foodchem.2020.128498}, abstractNote={The acquisition of resveratrol from Polygonum cuspidatum is complicated and costs organic solvents due to extraction and hydrolysis of its corresponding glycoside (polydatin). In this work, a novel one-pot method based on deep eutectic solvent (DES) was developed for simultaneous extraction and conversion of polydatin to resveratrol from Polygonum cuspidatum for the first time. The extraction yield of resveratrol by DES-based one-pot method were significantly higher than that of water, methanol and ethanol. After optimization by One-Variable-at-a-Time and response surface methodology, the extraction yield of resveratrol reached 12.26 ± 0.14 mg/g within 80 min. The conversation efficiency of polydatin to resveratrol in Polygonum cuspidatum from five different origins was more than 96.3%. Scanning electron microscope results indicated the selected DES disrupted plant cell walls to enhance the yield of resveratrol. The results indicated that one green method was successfully established for efficient extraction and conversion of polydatin to resveratrol from Polygonum cuspidatum.}, journal={Food Chemistry}, publisher={Elsevier BV}, author={Sun, Bo and Zheng, Yun-Long and Yang, Sheng-Kuan and Zhang, Jia-Ru and Cheng, Xin-Yue and Ghiladi, Reza and Ma, Zhuo and Wang, Jun and Deng, Wen-Wen}, year={2020}, month={Nov}, pages={128498} }
 @article{peddinti_morales-gagnon_pourdeyhimi_scholle_spontak_ghiladi_2020, title={Photodynamic Coatings on Polymer Microfibers for Pathogen Inactivation: Effects of Application Method and Composition}, volume={13}, ISSN={1944-8244 1944-8252}, url={http://dx.doi.org/10.1021/acsami.0c16953}, DOI={10.1021/acsami.0c16953}, abstractNote={A substantial increase in the risk of hospital-acquired infections (HAIs) has greatly impacted the global healthcare industry. Harmful pathogens adhere to a variety of surfaces and infect personnel on contact, thereby promoting transmission to new hosts. This is particularly worrisome in the case of antibiotic-resistant pathogens, which constitute a growing threat to human health worldwide and require new preventative routes of disinfection. In this study, we have incorporated different loading levels of a porphyrin photosensitizer capable of generating reactive singlet oxygen in the presence of O2 and visible light in a water-soluble, photo-cross-linkable polymer coating, which was subsequently deposited on polymer microfibers. Two different application methods are considered, and the morphological and chemical characteristics of these coated fibers are analyzed to detect the presence of the coating and photosensitizer. To discern the efficacy of the fibers against pathogenic bacteria, photodynamic inactivation has been performed on two different bacterial strains, Staphylococcus aureus and antibiotic-resistant Escherichia coli, with population reductions of >99.9999 and 99.6%, respectively, after exposure to visible light for 1 h. In response to the current COVID-19 pandemic, we also confirm that these coated fibers can inactivate a human common cold coronavirus serving as a surrogate for the SARS-CoV-2 virus.}, number={1}, journal={ACS Applied Materials & Interfaces}, publisher={American Chemical Society (ACS)}, author={Peddinti, Bharadwaja S. T. and Morales-Gagnon, Nicolas and Pourdeyhimi, Behnam and Scholle, Frank and Spontak, Richard J. and Ghiladi, Reza A.}, year={2020}, month={Dec}, pages={155–163} }
 @article{wang_xu_shen_cao_wei_ghiladi_wang_2020, title={Photoinactivation of bacteria by hypocrellin-grafted bacterial cellulose}, volume={27}, ISSN={0969-0239 1572-882X}, url={http://dx.doi.org/10.1007/s10570-019-02852-9}, DOI={10.1007/s10570-019-02852-9}, number={2}, journal={Cellulose}, publisher={Springer Science and Business Media LLC}, author={Wang, Tingting and Xu, Lei and Shen, Huiying and Cao, Xiuming and Wei, Qufu and Ghiladi, Reza A. and Wang, Qingqing}, year={2020}, month={Jan}, pages={991–1007} }
 @article{alvarado_argyropoulos_scholle_peddinti_ghiladi_2019, title={A facile strategy for photoactive nanocellulose-based antimicrobial materials}, volume={21}, ISSN={1463-9262 1463-9270}, url={http://dx.doi.org/10.1039/C9GC00551J}, DOI={10.1039/c9gc00551j}, abstractNote={Anti-infective materials based upon renewable nanocellulose–porphyrin conjugates photodynamically inactivated four strains of drug-resistant bacteria and two viruses by 99.999+%.}, number={12}, journal={Green Chemistry}, publisher={Royal Society of Chemistry (RSC)}, author={Alvarado, David Ramirez and Argyropoulos, Dimitris S. and Scholle, Frank and Peddinti, Bharadwaja S. T. and Ghiladi, Reza A.}, year={2019}, pages={3424–3435} }
 @article{peddinti_scholle_ghiladi_spontak_2019, title={Antimicrobial Thermoplastic Elastomers: Strategic Pathways for the Future of Broad-Spectrum Anti-Infective Materials}, volume={261}, number={1}, journal={Rubber World}, author={Peddinti, B. and Scholle, F. and Ghiladi, R.A. and Spontak, R.}, year={2019}, month={Oct}, pages={67–77} }
 @article{stoll_scholle_zhu_zhang_ghiladi_2019, title={BODIPY-embedded electrospun materials in antimicrobial photodynamic inactivation}, volume={18}, ISSN={1474-905X 1474-9092}, url={http://dx.doi.org/10.1039/C9PP00103D}, DOI={10.1039/c9pp00103d}, abstractNote={Drug-resistant pathogens, particularly those that result in hospital acquired infections (HAIs), have emerged as a critical priority for the World Health Organization. To address the need for self-disinfecting materials to counter the threat posed by the transmission of these pathogens from surfaces to new hosts, here we investigated if a cationic BODIPY photosensitizer, embedded via electrospinning into nylon and polyacrylonitrile (PAN) nanofibers, was capable of inactivating both bacteria and viruses via antimicrobial photodynamic inactivation (aPDI). Materials characterization, including fiber morphology and the degree of photosensitizer loading, was assessed by scanning electron microscopy (SEM), thermal gravimetric analysis (TGA), and UV-visible diffuse reflectance spectroscopy (UV-Vis DRS), and demonstrated that the materials were comprised of nanofibers (125–215 nm avg. diameter) that were thermostable to >300 °C. The antimicrobial potencies of the resultant Nylon-BODIPY ^(+) and PAN-BODIPY ^(+) nanofiber materials were evaluated against four strains of bacteria recognized by the World Health Organization as either critical or high priority pathogens: Gram-positive strains methicillin-resistant S. aureus (MRSA; ATCC BAA-44) and vancomycin-resistant E. faecium (VRE; ATCC BAA-2320), and Gram-negative strains multidrug-resistant A. baumannii (MDRAB; ATCC BAA-1605) and NDM-1 positive K. pneumoniae (KP; ATCC BAA-2146). Our results demonstrated the detection limit (99.9999%; 6 log units reduction in CFU mL^−1) photodynamic inactivation of three strains upon illumination (30–60 min; 40–65 ± 5 mW cm^−2; 400–700 nm): MRSA, VRE, and MDRAB, but only minimal inactivation (47–75%) of KP. Antiviral studies employing PAN-BODIPY ^(+) against vesicular stomatitis virus (VSV), a model enveloped virus, revealed complete inactivation. Taken together, the results demonstrate the potential for electrospun BODIPY ^(+)-embedded nanofiber materials as the basis for pathogen-specific anti-infective materials, even at low photosensitizer loadings.}, number={8}, journal={Photochemical & Photobiological Sciences}, publisher={Royal Society of Chemistry (RSC)}, author={Stoll, Kevin R. and Scholle, Frank and Zhu, Jiadeng and Zhang, Xiangwu and Ghiladi, Reza A.}, year={2019}, pages={1923–1932} }
 @article{moreno-chicano_ebrahim_axford_appleby_beale_chaplin_duyvesteyn_ghiladi_owada_sherrell_et al._2019, title={High-throughput structures of protein–ligand complexes at room temperature using serial femtosecond crystallography}, volume={6}, ISSN={2052-2525}, url={http://dx.doi.org/10.1107/S2052252519011655}, DOI={10.1107/S2052252519011655}, abstractNote={The ability to rapidly obtain structures of protein–ligand complexes using X-ray crystallography is central to drug discovery, but the typical cryocooling of samples and the effects of the X-ray beam may distort the observed ligand binding. X-ray free-electron lasers (XFELs) have the promise to solve these issues, but methods to rapidly produce structures of protein–ligand complexes at XFELs have not yet been realized. Here, an efficient solution using high-throughput, fixed-target serial femtosecond crystallography at an XFEL is demonstrated.}, number={6}, journal={IUCrJ}, publisher={International Union of Crystallography (IUCr)}, author={Moreno-Chicano, Tadeo and Ebrahim, Ali and Axford, Danny and Appleby, Martin V. and Beale, John H. and Chaplin, Amanda K. and Duyvesteyn, Helen M. E. and Ghiladi, Reza A. and Owada, Shigeki and Sherrell, Darren A. and et al.}, year={2019}, month={Oct}, pages={1074–1085} }
 @article{peddinti_scholle_vargas_smith_ghiladi_spontak_2019, title={Inherently self-sterilizing charged multiblock polymers that kill drug-resistant microbes in minutes}, volume={6}, ISSN={2051-6347 2051-6355}, url={http://dx.doi.org/10.1039/C9MH00726A}, DOI={10.1039/c9mh00726a}, abstractNote={To combat the growing global healthcare threat from drug-resistant pathogens, we demonstrate that midblock-sulfonated block polymers can kill 99.9999% of “superbugs,” including bacteria and viruses, in just 5 minutes due to an abrupt pH reduction.}, number={10}, journal={Materials Horizons}, publisher={Royal Society of Chemistry (RSC)}, author={Peddinti, Bharadwaja S. T. and Scholle, Frank and Vargas, Mariana G. and Smith, Steven D. and Ghiladi, Reza A. and Spontak, Richard J.}, year={2019}, pages={2056–2062} }
 @article{chariou_wang_desai_park_robbins_recum_ghiladi_steinmetz_2019, title={Let There Be Light: Targeted Photodynamic Therapy Using High Aspect Ratio Plant Viral Nanoparticles}, volume={19}, ISSN={1616-5187 1616-5195}, url={http://dx.doi.org/10.1002/mabi.201800407}, DOI={10.1002/mabi.201800407}, abstractNote={The development of plant viral nanoparticles (VNP) loaded with different molecular versions of a photodynamic drug is described. Specifically, tobacco mosaic virus (TMV) and tobacco mild green mosaic virus (TMGMV) are developed as drug carriers that encapsulate the monocationic, dicationic, tricationic, and tetracationic versions of a porphyrin-based photosensitizer drug (Zn-Por). While TMV has been extensively explored for various nanotechnology applications, this is the first study investigating TMGMV for medical applications. Light-activated cancer cell killing of Zn-Por-loaded VNPs is studied in vitro using melanoma and cervical cancer models. Native and nucleolin-targeted VNP drug carriers are developed and their efficacy assessed. A fivefold increase in cancer cell killing is observed using nucleolin-targeted TMV loaded with tricationic Zn-Por and displaying the nucleolin-specific F3 peptide.}, number={5}, journal={Macromolecular Bioscience}, publisher={Wiley}, author={Chariou, Paul L. and Wang, Lu and Desai, Cian and Park, Jooneon and Robbins, Leanna K. and Recum, Horst A. and Ghiladi, Reza A. and Steinmetz, Nicole F.}, year={2019}, month={Feb}, pages={1800407} }
 @inproceedings{jiang_scholle_ghiladi_2019, title={Mn-doped Zn/S quantum dots as photosensitizers for antimicrobial photodynamic inactivation}, ISBN={9781510623682 9781510623699}, url={http://dx.doi.org/10.1117/12.2510934}, DOI={10.1117/12.2510934}, abstractNote={The survival of pathogens on surfaces is a major contributor to infection transmission, and drives the development of selfsterilizing surfaces. Here, we have investigated if manganese-doped zinc sulfide quantum dots (Mn:ZnS QDs) can be used as photosensitizers for their potential application in surface disinfection via antimicrobial photodynamic inactivation (aPDI). A small library of Mn:ZnS QDs capped with 3-mercaptopropionic acid was synthesized using a hydrothermal approach in which both the amount of manganese (0-30 at.%) and heating period (9 – 20 h) were varied. The resultant Mn:ZnS QDs were shown by transmission electron microscopy to vary in size from 2.6-3.9 Å as a function of heating time, and exhibited a strong emission band at ~598 nm (λex = 325 nm). Upon excitation of 5%-Mn:ZnS QDs at 514 nm, a near-IR emission band attributable to singlet oxygen phosphorescence was observed at 1278 nm, confirming that these QDs may function as photosensitizers via a Type II mechanism. The aPDI efficacy of the Mn:ZnS QDs was evaluated against both Gram-positive [methicillin-resistant S. aureus (MRSA; ATCC-44), vancomycin-resistant E. faecium (VRE; ATCC-2320)], and Gram-negative [multidrug-resistant A. baumannii (MDRAB; ATCC-1605), NDM-1 positive K. pneumoniae (KP; ATCC-2146)] bacteria. Our best results demonstrated detection limit photodynamic inactivation (6 log units reduction) of KP, MDRAB, and MRSA upon illumination (30 min; 65±5 mW/cm2; 400-700 nm), but only a ~1 log unit reduction against VRE. Together with antiviral studies of Zika virus that showed ~3 log units of inactivation, these findings demonstrate the utility of Mn:ZnS QDs as photosensitizers for aPDI.}, booktitle={Photonic Diagnosis and Treatment of Infections and Inflammatory Diseases II}, publisher={SPIE}, author={Jiang, Chenyu and Scholle, Frank and Ghiladi, Reza A.}, editor={Dai, Tianhong and Wu, Mei X. and Popp, JürgenEditors}, year={2019}, month={Mar} }
 @article{malewschik_de serrano_mcguire_ghiladi_2019, title={The multifunctional globin dehaloperoxidase strikes again: Simultaneous peroxidase and peroxygenase mechanisms in the oxidation of EPA pollutants}, volume={673}, ISSN={0003-9861}, url={http://dx.doi.org/10.1016/j.abb.2019.108079}, DOI={10.1016/j.abb.2019.108079}, abstractNote={The multifunctional catalytic hemoglobin dehaloperoxidase (DHP) from the terebellid polychaete Amphitrite ornata was found to catalyze the H2O2-dependent oxidation of EPA Priority Pollutants (4-Me-o-cresol, 4-Cl-m-cresol and pentachlorophenol) and EPA Toxic Substances Control Act compounds (o-, m-, p-cresol and 4-Cl-o-cresol). Biochemical assays (HPLC/LC-MS) indicated formation of multiple oxidation products, including the corresponding catechol, 2-methylbenzoquinone (2-MeBq), and oligomers with varying degrees of oxidation and/or dehalogenation. Using 4-Br-o-cresol as a representative substrate, labeling studies with 18O confirmed that the O-atom incorporated into the catechol was derived exclusively from H2O2, whereas the O-atom incorporated into 2-MeBq was from H2O, consistent with this single substrate being oxidized by both peroxygenase and peroxidase mechanisms, respectively. Stopped-flow UV-visible spectroscopic studies strongly implicate a role for Compound I in the peroxygenase mechanism leading to catechol formation, and for Compounds I and ES in the peroxidase mechanism that yields the 2-MeBq product. The X-ray crystal structures of DHP bound with 4-F-o-cresol (1.42 Å; PDB 6ONG), 4-Cl-o-cresol (1.50 Å; PDB 6ONK), 4-Br-o-cresol (1.70 Å; PDB 6ONX), 4-NO2-o-cresol (1.80 Å; PDB 6ONZ), o-cresol (1.60 Å; PDB 6OO1), p-cresol (2.10 Å; PDB 6OO6), 4-Me-o-cresol (1.35 Å; PDB 6ONR) and pentachlorophenol (1.80 Å; PDB 6OO8) revealed substrate binding sites in the distal pocket in close proximity to the heme cofactor, consistent with both oxidation mechanisms. The findings establish cresols as a new class of substrate for DHP, demonstrate that multiple oxidation mechanisms may exist for a given substrate, and provide further evidence that different substituents can serve as functional switches between the different activities performed by dehaloperoxidase. More broadly, the results demonstrate the complexities of marine pollution where both microbial and non-microbial systems may play significant roles in the biotransformations of EPA-classified pollutants, and further reinforces that heterocyclic compounds of anthropogenic origin should be considered as environmental stressors of infaunal organisms.}, journal={Archives of Biochemistry and Biophysics}, publisher={Elsevier BV}, author={Malewschik, Talita and de Serrano, Vesna and McGuire, Ashlyn H. and Ghiladi, Reza A.}, year={2019}, month={Sep}, pages={108079} }
 @article{feese_gracz_boyle_ghiladi_2019, title={Towards microbe-targeted photosensitizers: Synthesis, characterization and in vitro photodynamic inactivation of the tuberculosis model pathogen M. smegmatis by porphyrin-peptide conjugates}, volume={23}, ISSN={1088-4246 1099-1409}, url={http://dx.doi.org/10.1142/S1088424619501505}, DOI={10.1142/S1088424619501505}, abstractNote={Porphyrin-peptide conjugates have a breadth of potential applications, including use in photodynamic therapy, boron neutron capture therapy, as fluorescence imaging tags for tracking subcellular localization, as magnetic resonance imaging (MRI) positive-contrast reagents and as biomimetic catalysts. Here, we have explored three general routes to porphyrin-peptide conjugates using the Cu(I)-catalyzed Huisgen-Medal-Sharpless 1,3-dipolar cycloaddition of peptide-containing azides with a terminal alkyne-containing porphyrin, thereby generating porphyrin-peptide conjugates (PPCs) comprised of a cationic porphyrin coupled to short antimicrobial peptides. In addition to characterizing the PPCs using a variety of spectroscopic (UV-vis, [Formula: see text]H- and [Formula: see text]C-NMR) and mass spectrometric methods, we evaluated their efficacy as photosensitizers for the in vitro photodynamic inactivation of Mycobacterium smegmatis as a model for the pathogen Mycobacterium tuberculosis. Difficulties that needed to be overcome for the efficient synthesis of PPCs were the limited solubility of the quaternized pyridyl porphyrin in common solvents, undesired (de)metallation and transmetallation, and chromatographic purification. Photodynamic inactivation studies of a small library of PPCs against Mycobacterium smegmatis confirmed our hypothesis that the porphyrin-based photosensitizer maintains its ability to efficiently inactivate bacteria when conjugated to a small peptide by upwards of 5–6 log units (99.999[Formula: see text]%) using white light illumination (400–700 nm, 60 mW/cm[Formula: see text], 30 min). Further, hemolysis assays revealed the lack of toxicity of the PPCs against sheep blood at concentrations employed for in vitro photodynamic inactivation. Taken together, the results demonstrated the ability of PPCs to maintain their antimicrobial photodynamic inactivation efficacy when possessing a short cationic peptides for enabling the potential targeting of pathogens in vivo.}, number={11n12}, journal={Journal of Porphyrins and Phthalocyanines}, publisher={World Scientific Pub Co Pte Lt}, author={Feese, Elke and Gracz, Hanna S. and Boyle, Paul D. and Ghiladi, Reza A.}, year={2019}, month={Dec}, pages={1414–1439} }
 @article{chen_chen_li_wang_wei_ghiladi_wang_2019, title={Wool/Acrylic Blended Fabrics as Next-Generation Photodynamic Antimicrobial Materials}, volume={11}, ISSN={1944-8244 1944-8252}, url={http://dx.doi.org/10.1021/acsami.9b09625}, DOI={10.1021/acsami.9b09625}, abstractNote={The adoption of self-sterilizing materials to reduce infection transmission in hospitals and related healthcare facilities has been hampered by the availability of scalable, cost-effective, and potent antimicrobial textiles. Here, we investigated if photodynamic materials comprised of photosensitizer-embedded wool/acrylic blends were able to mediate the photodynamic inactivation of Gram-positive and Gram-negative bacteria. A small library of wool/acrylic (W/A) blended fabrics was constructed wherein the wool fibers were embedded with rose Bengal (RB) as a photosensitizer, and the acrylic fibers were dyed with a traditional cationic yellow X-8GL dye, thereby enabling a broader color palette than was achievable with a single photosensitizer. The resultant photodynamic materials were characterized by physical (SEM, DSC, TGA, tensile strength), spectroscopic (fluorescence), colorimetric (K/S and CIELab values), and color fastness (against rubbing, washing) studies, and their photooxidation of the model substrate potassium iodide demonstrated the ability of these materials to generate microbicidal reactive oxygen species (i.e., singlet oxygen) upon illumination. Our best results yielded the photodynamic inactivation of Gram-positive S. aureus (99.98%) and B. subtilis (99.993%) by ~4 log units upon illumination with visible light (60 min; 65±5 mW/cm2; λ ≥ 420 nm), although more modest activity was observed against Gram-negative P. aeruginosa and E. coli (1-2 log units pathogen reduction). While there were no statistically significant differences for dual-dyed materials that were produced through either sequential or simultaneous dyeing steps, it was noted that high loadings of the cationic yellow X-8GL dye did inhibit the antimicrobial activity of the RB photosensitizer, with the dual-dyed materials able to mediate a 2.9 log unit reduction against S. aureus at a 1% o.w.f X-8GL loading. These findings indicate that the antimicrobial photodynamic inactivation of dual-dyed materials is independent of the dyeing process itself, yet exhibits limitations on the loading of the traditional dye with regards to the activity of the photosensitizer. Taken together, the results suggest the feasibility of photosensitizer-embedded blended fabrics produced through a one-step dyeing process as a low-cost and scalable method for creating effective self-disinfecting textiles for infection prevention, and whose inclusion of a second traditional dye for color variation will further benefit their adoption from a commercial standpoint.}, number={33}, journal={ACS Applied Materials & Interfaces}, publisher={American Chemical Society (ACS)}, author={Chen, Wangbingfei and Chen, Jiang and Li, Ling and Wang, Xinyi and Wei, Qufu and Ghiladi, Reza A. and Wang, Qingqing}, year={2019}, month={Jul}, pages={29557–29568} }
 @article{carey_gavenko_svistunenko_ghiladi_2018, title={How nature tunes isoenzyme activity in the multifunctional catalytic globin dehaloperoxidase from Amphitrite ornata}, volume={1866}, ISSN={1570-9639}, url={http://dx.doi.org/10.1016/j.bbapap.2017.11.004}, DOI={10.1016/j.bbapap.2017.11.004}, abstractNote={The coelomic hemoglobin of Amphitrite ornata, termed dehaloperoxidase (DHP), is the first known multifunctional catalytic globin to possess biologically-relevant peroxidase and peroxygenase activities. Although the two isoenzymes of DHP, A and B, differ in sequence by only 5 amino acids out of 137 residues, DHP B consistently exhibits a greater activity than isoenzyme A. To delineate the contributions of each amino acid substitution to the activity of either isoenzyme, the substitutions of the five amino acids were systematically investigated, individually and in combination, using 22 mutants. Biochemical assays and mechanistic studies demonstrated that the mutants that only contained the I9L substitution showed increased i) kcat values (peroxidase activity), ii) 5-Br-indole conversion and binding affinity (peroxygenase activity), and iii) rate of Compound ES formation (enzyme activation). Whereas the X-ray structures of the oxyferrous forms of DHP B (L9I) (1.96Å), DHP A (I9L) (1.20Å), and WT DHP B (1.81Å) showed no significant differences, UV-visible spectroscopy (ASoret/A380 ratio) revealed that the I9L substitution increased the 5-coordinate high-spin heme population characterized by the "open" conformation (i.e., distal histidine swung out of the pocket), which likely favors substrate binding. The positioning of the distal histidine closer to the heme cofactor in the solution state also appears to facilitate activation of DHP via the Compound ES intermediate. Taken together, the studies undertaken here shed light on the structure-function relationship in dehaloperoxidase, but also help to establish the foundation for understanding how enzymatic activity can be tuned in isoenzymes of a multifunctional catalytic globin.}, number={2}, journal={Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics}, publisher={Elsevier BV}, author={Carey, Leiah M. and Gavenko, Roman and Svistunenko, Dimitri A. and Ghiladi, Reza A.}, year={2018}, month={Feb}, pages={230–241} }
 @article{mcguire_carey_de serrano_dali_ghiladi_2018, title={Peroxidase versus Peroxygenase Activity: Substrate Substituent Effects as Modulators of Enzyme Function in the Multifunctional Catalytic Globin Dehaloperoxidase}, volume={57}, ISSN={0006-2960 1520-4995}, url={http://dx.doi.org/10.1021/ACS.BIOCHEM.8B00540}, DOI={10.1021/ACS.BIOCHEM.8B00540}, abstractNote={The dehaloperoxidase-hemoglobin (DHP) from the terebellid polychaete Amphitrite ornata is a multifunctional hemoprotein that catalyzes the oxidation of a wide variety of substrates, including halo/nitrophenols, haloindoles, and pyrroles, via peroxidase and/or peroxygenase mechanisms. To probe whether substrate substituent effects can modulate enzyme activity in DHP, we investigated its reactiviy against a panel of o-guaiacol substrates given their presence (from native/halogenated and non-native/anthropogenic sources) in the benthic environment that A. ornata inhabits. Using biochemical assays supported by spectroscopic, spectrometric, and structural studies, DHP was found to catalyze the H2O2-dependent oxidative dehalogenation of 4-haloguaiacols (F, Cl, and Br) to 2-methoxybenzoquinone (2-MeOBQ). 18O labeling studies confirmed that O atom incorporation was derived exclusively from water, consistent with substrate oxidation via a peroxidase-based mechanism. The 2-MeOBQ product further reduced DHP to its oxyferrous state, providing a link between the substrate oxidation and O2 carrier functions of DHP. Nonnative substrates resulted in polymerization of the initial substrate with varying degrees of oxidation, with 2-MeOBQ identified as a minor product. When viewed alongside the reactivity of previously studied phenolic substrates, the results presented here show that simple substituent effects can serve as functional switches between peroxidase and peroxygenase activities in this multifunctional catalytic globin. More broadly, when recent findings on DHP activity with nitrophenols and azoles are included, the results presented here further demonstrate the breadth of heterocyclic compounds of anthropogenic origin that can potentially disrupt marine hemoglobins or function as environmental stressors, findings that may be important when assessing the environmental impact of these pollutants (and their metabolites) on aquatic systems.}, number={30}, journal={Biochemistry}, publisher={American Chemical Society (ACS)}, author={McGuire, Ashlyn H. and Carey, Leiah M. and de Serrano, Vesna and Dali, Safaa and Ghiladi, Reza A.}, year={2018}, month={Jun}, pages={4455–4468} }
 @article{peddinti_scholle_ghiladi_spontak_2018, title={Photodynamic Polymers as Comprehensive Anti-Infective Materials: Staying Ahead of a Growing Global Threat}, volume={10}, ISSN={1944-8244 1944-8252}, url={http://dx.doi.org/10.1021/ACSAMI.8B09139}, DOI={10.1021/ACSAMI.8B09139}, abstractNote={To combat the global threat posed by surface-adhering pathogens that are becoming increasingly drug-resistant, we explore the anti-infective efficacy of bulk thermoplastic elastomer films containing ∼1 wt % zinc-tetra(4- N-methylpyridyl)porphine (ZnTMPyP4+), a photoactive antimicrobial that utilizes visible light to generate singlet oxygen. This photodynamic polymer is capable of inactivating five bacterial strains and two viruses with at least 99.89% and 99.95% success, respectively, after exposure to noncoherent light for 60 min. Unlike other anti-infective methodologies commonly requiring oxidizing chemicals, carcinogenic radiation, or toxic nanoparticles, our approach is nonspecific and safe/nontoxic, and sustainably relies on the availability of just oxygen and visible light.}, number={31}, journal={ACS Applied Materials & Interfaces}, publisher={American Chemical Society (ACS)}, author={Peddinti, Bharadwaja S.T. and Scholle, Frank and Ghiladi, Reza A. and Spontak, Richard J.}, year={2018}, month={Jul}, pages={25955–25959} }
 @article{chen_wang_ge_wei_ghiladi_wang_2018, title={Photooxidation Properties of Photosensitizer/Direct Dye Patterned Polyester/Cotton Fabrics}, volume={19}, ISSN={1229-9197 1875-0052}, url={http://dx.doi.org/10.1007/S12221-018-8068-4}, DOI={10.1007/S12221-018-8068-4}, number={8}, journal={Fibers and Polymers}, publisher={Springer Science and Business Media LLC}, author={Chen, Wangbingfei and Wang, Weiwei and Ge, Xiaodong and Wei, Qufu and Ghiladi, Reza Arman and Wang, Qingqing}, year={2018}, month={Aug}, pages={1687–1693} }
 @article{wang_chen_zhang_ghiladi_wei_2018, title={Preparation of photodynamic P(MMA-co-MAA) composite nanofibers doped with MMT: A facile method for increasing antimicrobial efficiency}, volume={457}, ISSN={0169-4332}, url={http://dx.doi.org/10.1016/J.APSUSC.2018.06.041}, DOI={10.1016/J.APSUSC.2018.06.041}, abstractNote={We report the preparation of photodynamic materials from electrospun nanofibers of P(MMA-co-MAA) co-polymer that were doped with montmorillonite (MMT), and further functionalized with the cationic photosensitizer methylene blue (MB). The resultant composite nanofibers were characterized by spectroscopic (infrared, UV − vis, fluorescence) and physical (SEM/TEM, gravimetric) methods. Addition of MMT (0–6 wt%) in the electrospinning process increased the adsorption of the methylene blue photosensitizer from 21.5 mg (67.1 μmol)/g P(MMA-co-MAA) parent copolymer to 30.0 mg (93.8 μmol)/g P(MMA-co-MAA)/MMT-6 composite nanofibers. The MB-decorated P(MMA-co-MAA)/MMT-6 composite nanofibers showed a 99.997% (4.8 log units) and 97% (1.8 log units) reduction in CFU/mL against Staphylococcus aureus (ATCC-6538) and Escherichia coli strain 8099, respectively, after visible light illumination (LED lamp, 30 min, 35 ± 5 mW/cm2), demonstrating that the increased photosensitizer loading attributable to MMT doping led to a 1–2 log unit increase in photodynamic inactivation efficacy over the non-doped MB-decorated P(MMA-co-MAA) parent copolymer (99.9% and 84% reduction for S. aureus and E. coli, respectively). The results demonstrate that MMT and similar additives may be a universal method for increasing the adsorption capacity of cationic photosensitizers in electrospun nanofibers, thereby generating materials with improved photodynamic inactivation efficacy without significantly changing the fiber morphology, cost, or ease of production.}, journal={Applied Surface Science}, publisher={Elsevier BV}, author={Wang, Qingqing and Chen, Wangbingfei and Zhang, Quan and Ghiladi, Reza A. and Wei, Qufu}, year={2018}, month={Nov}, pages={247–255} }
 @article{dong_ghiladi_wang_cai_wei_2018, title={Protoporphyrin IX conjugated bacterial cellulose via diamide spacer arms with specific antibacterial photodynamic inactivation against Escherichia coli}, volume={25}, ISSN={0969-0239 1572-882X}, url={http://dx.doi.org/10.1007/s10570-018-1697-3}, DOI={10.1007/s10570-018-1697-3}, number={3}, journal={Cellulose}, publisher={Springer Science and Business Media LLC}, author={Dong, Jiancheng and Ghiladi, Reza A. and Wang, Qingqing and Cai, Yibing and Wei, Qufu}, year={2018}, month={Feb}, pages={1673–1686} }
 @article{dong_ghiladi_wang_cai_wei_2018, title={Protoporphyrin-IX conjugated cellulose nanofibers that exhibit high antibacterial photodynamic inactivation efficacy}, volume={29}, ISSN={0957-4484 1361-6528}, url={http://dx.doi.org/10.1088/1361-6528/aabb3c}, DOI={10.1088/1361-6528/aabb3c}, abstractNote={Towards the development of anti-infective nanoscale materials employing a photodynamic mechanism of action, we report the synthesis, physical properties (SEM, mechanical strength, water contact angle), spectroscopic characterization (infrared, Raman, DRUV), and evaluation of antibacterial efficacy of porphyrin-conjugated regenerated cellulose nanofibers, termed RC-TETA-PPIX-Zn. Cellulose acetate was electrospun to produce nanofibers, thermally treated to enhance mechanical strength, and finally hydrolyzed to produce regenerated cellulose (RC) nanofibers that possessed a high surface area and nanofibrous structure. Covalent grafting of a protoporphyrin IX (PPIX) photosensitizer using epichlorohydrin/triethylenetetramine (TETA), followed by zinc chelation, afforded RC-TETA-PPIX-Zn. The high surface area afforded by the nanofibers and efficient photosensitizer conjugation led to a very high loading of 412 nmol PPIX/mg material, corresponding to a degree of substitution of 0.1. Antibacterial efficacy was evaluated against Staphylococcus aureus (ATCC-6538) and Escherichia coli (ATCC-8099), with our best results achieving detection limit inactivation (99.999+%) of both bacteria after only 20 min illumination (Xe lamp, λ ≥ 420 nm). No statistically significant loss in antibacterial activity was observed when using nanofibers that had been ‘photo-aged’ with 5 h of pre-illumination to simulate the effects of photobleaching. Post aPDI, scanning electron microscopy revealed that the bacteria had undergone cell membrane leakage, consistent with oxidative damage caused by photo-generated reactive oxygen species. Taken together, the conjugation strategy employed here provides a scalable, facile and efficient route to creating nanofibrous materials from natural polymers with a high photosensitizer loading, enabling the use of commercially-available neutral porphyrin photosensitizers, such as PPIX, in the design and synthesis of potent anti-infective nanomaterials.}, number={26}, journal={Nanotechnology}, publisher={IOP Publishing}, author={Dong, Jiancheng and Ghiladi, Reza A and Wang, Qingqing and Cai, Yibing and Wei, Qufu}, year={2018}, month={May}, pages={265601} }
 @article{dong_ghiladi_wang_cai_wei_2018, title={Protoporphyrin-IX conjugated cellulose nanofibers that exhibit high antibacterial photodynamic inactivation efficacy}, volume={29}, number={26}, journal={Nanotechnology}, author={Dong, J. C. and Ghiladi, R. A. and Wang, Q. Q. and Cai, Y. B. and Wei, Q. F.}, year={2018} }
 @article{carey_kim_mccombs_swartz_kim_ghiladi_2018, title={Selective tuning of activity in a multifunctional enzyme as revealed in the F21W mutant of dehaloperoxidase B from Amphitrite ornata}, volume={23}, ISSN={0949-8257 1432-1327}, url={http://dx.doi.org/10.1007/s00775-017-1520-x}, DOI={10.1007/s00775-017-1520-x}, abstractNote={["Possessing both peroxidase and peroxygenase activities with a broad substrate profile that includes phenols, indoles, and pyrroles, the enzyme dehaloperoxidase (DHP) from Amphitrite ornata is a multifunctional catalytic hemoglobin that challenges many of the assumptions behind the well-established structure-function paradigm in hemoproteins. While previous studies have demonstrated that the F21W variant leads to attenuated peroxidase activity in DHP, here we have studied the impact of this mutation on peroxygenase activity to determine if it is possible to selectively tune DHP to favor one function over another. Biochemical assays with DHP B (F21W) revealed minimal decreases in peroxygenase activity of 1.2-2.1-fold as measured by 4-nitrophenol or 5-Br-indole substrate conversion, whereas the peroxidase activity catalytic efficiency for 2,4,6-trichlorophenol (TCP) was more than sevenfold decreased. Binding studies showed a 20-fold weaker affinity for 5-bromoindole (K ", {:sub=>"d"}, " = 2960 ± 940 μM) in DHP B (F21W) compared to WT DHP B. Stopped-flow UV/visible studies and isotope labeling experiments together suggest that the F21W mutation neither significantly changes the nature of the catalytic intermediates, nor alters the mechanisms that have been established for peroxidase and peroxygenase activities in DHP. The X-ray crystal structure (1.96 Å; PDB 5VLX) of DHP B (F21W) revealed that the tryptophan blocks one of the two identified TCP binding sites, specifically TCP", {:sub=>"interior"}, ", suggesting that the other site, TCP", {:sub=>"exterior"}, ", remains viable for binding peroxygenase substrates. Taken together, these studies demonstrate that blocking the TCP", {:sub=>"interior"}, " binding site in DHP selectively favors peroxygenase activity at the expense of its peroxidase activity."]}, number={2}, journal={JBIC Journal of Biological Inorganic Chemistry}, publisher={Springer Science and Business Media LLC}, author={Carey, Leiah M. and Kim, Kyung Beom and McCombs, Nikolette L. and Swartz, Paul and Kim, Cheal and Ghiladi, Reza A.}, year={2018}, month={Mar}, pages={209–219} }
 @article{wallat_wek_chariou_carpenter_ghiladi_steinmetz_pokorski_2017, title={Fluorinated polymer–photosensitizer conjugates enable improved generation of ROS for anticancer photodynamic therapy}, volume={8}, ISSN={1759-9954 1759-9962}, url={http://dx.doi.org/10.1039/C7PY00522A}, DOI={10.1039/c7py00522a}, abstractNote={Photodynamic therapy (PDT) is an adjuvant, non-invasive cancer treatment that is often limited by the photosensitizer solubility and the availability of oxygen in the tumor environment during treatment. This study describes the use of a water-dispersible fluorous polymer to deliver a small molecule photosensitizer with the goal of overcoming these limitations. Covalent conjugation of the photosensitizer to a fluorous polymer demonstrated enhanced singlet oxygen production, showing the potential to improve the PDT efficacy in hypoxic tumor environments. Cellular uptake and efficiency were evaluated using models for squamous cell carcinoma and melanoma. The high fluorine content of the photosensitizer-conjugated polymer drove self-assembly into micellar nanoparticles that showed uptake into both cancer cell lines, inducing cell death when exposed to broad based white light, but was non-toxic otherwise. Taken together these results demonstrate that the fluorous polymer platform serves as an effective delivery system for small molecule photosensitizers while increasing the generation of toxic reactive oxygen species.}, number={20}, journal={Polymer Chemistry}, publisher={Royal Society of Chemistry (RSC)}, author={Wallat, Jaqueline D. and Wek, Kristen S. and Chariou, Paul L. and Carpenter, Bradley L. and Ghiladi, Reza A. and Steinmetz, Nicole F. and Pokorski, Jonathan K.}, year={2017}, pages={3195–3202} }
 @article{mccombs_moreno-chicano_carey_franzen_hough_ghiladi_2017, title={Interaction of Azole-Based Environmental Pollutants with the Coelomic Hemoglobin from Amphitrite ornata: A Molecular Basis for Toxicity}, volume={56}, ISSN={0006-2960 1520-4995}, url={http://dx.doi.org/10.1021/acs.biochem.7b00041}, DOI={10.1021/acs.biochem.7b00041}, abstractNote={The toxicities of azole pollutants that have widespread agricultural and industrial uses are either poorly understood or unknown, particularly with respect to how infaunal organisms are impacted by this class of persistent organic pollutant. To identify a molecular basis by which azole compounds may have unforeseen toxicity on marine annelids, we examine here their impact on the multifunctional dehaloperoxidase (DHP) hemoglobin from the terebellid polychaete Amphitrite ornata. Ultraviolet-visible and resonance Raman spectroscopic studies showed an increase in the six-coordinate low-spin heme population in DHP isoenzyme B upon binding of imidazole, benzotriazole, and benzimidazole (Kd values of 52, 82, and 110 μM, respectively), suggestive of their direct binding to the heme-Fe. Accordingly, atomic-resolution X-ray crystal structures, supported by computational studies, of the DHP B complexes of benzotriazole (1.14 Å), benzimidazole (1.08 Å), imidazole (1.08 Å), and indazole (1.12 Å) revealed two ligand binding motifs, one with direct ligand binding to the heme-Fe, and another in which the ligand binds in the hydrophobic distal pocket without coordinating the heme-Fe. Taken together, the results demonstrate a new mechanism by which azole pollutants can potentially disrupt hemoglobin function, thereby improving our understanding of their impact on infaunal organisms in marine and aquatic environments.}, number={17}, journal={Biochemistry}, publisher={American Chemical Society (ACS)}, author={McCombs, Nikolette L. and Moreno-Chicano, Tadeo and Carey, Leiah M. and Franzen, Stefan and Hough, Michael A. and Ghiladi, Reza A.}, year={2017}, month={Apr}, pages={2294–2303} }
 @article{mccombs_smirnova_ghiladi_2017, title={Oxidation of pyrrole by dehaloperoxidase-hemoglobin: chemoenzymatic synthesis of pyrrolin-2-ones}, volume={7}, ISSN={["2044-4761"]}, url={http://dx.doi.org/10.1039/c7cy00781g}, DOI={10.1039/c7cy00781g}, abstractNote={The use of oxidoreductases as biocatalysts in the syntheses of functionalized, monomeric pyrroles has been a challenge owing to, among a number of factors, undesired polypyrrole formation. Here, we have investigated the ability of dehaloperoxidase (DHP), the coelomic hemoglobin from the terebellid polychaete Amphitrite ornata, to catalyze the H2O2-dependent oxidation of pyrroles as a new class of substrate for this enzyme. Substrate oxidation was observed for all compounds employed (pyrrole, N-methylpyrrole, 2-methylpyrrole, 3-methylpyrrole and 2,5-dimethylpyrrole) under both aerobic and anaerobic conditions. Using pyrrole as a representative substrate, only a single oxidation product, 4-pyrrolin-2-one, was observed, and notably without formation of polypyrrole. Reactivity could be initiated from all three biologically relevant oxidation states for this catalytic globin: ferric, ferrous and oxyferrous. Isotope labeling studies determined that the O-atom incorporated into the 4-pyrrolin-2-one product was derived exclusively from H2O2, indicative of a peroxygenase mechanism. Consistent with this observation, single- and double-mixing stopped-flow UV-visible spectroscopic studies supported Compound I, but not Compounds ES or II, as the catalytically-relevant ferryl intermediate involved in pyrrole oxidation. Electrophilic addition of the ferryl oxygen to pyrrole is proposed as the mechanism of O-atom transfer. The results demonstrate the breadth of chemical reactivity afforded by dehaloperoxidase, and provide further evidence for establishing DHP as a multifunctional globin with practical applications as a biocatalyst.}, number={14}, journal={CATALYSIS SCIENCE & TECHNOLOGY}, author={McCombs, Nikolette L. and Smirnova, Tatyana and Ghiladi, Reza A.}, year={2017}, month={Jul}, pages={3104–3118} }
 @article{masarapu_patel_chariou_hu_gulati_carpenter_ghiladi_shukla_steinmetz_2017, title={Physalis Mottle Virus-Like Particles as Nanocarriers for Imaging Reagents and Drugs}, volume={18}, ISSN={1525-7797 1526-4602}, url={http://dx.doi.org/10.1021/ACS.BIOMAC.7B01196}, DOI={10.1021/ACS.BIOMAC.7B01196}, abstractNote={Platform technologies based on plant virus nanoparticles (VNPs) and virus-like particles (VLPs) are attracting the attention of researchers and clinicians because the particles are biocompatible, biodegradable, noninfectious in mammals, and can readily be chemically and genetically engineered to carry imaging agents and drugs. When the Physalis mottle virus (PhMV) coat protein is expressed in Escherichia coli, the resulting VLPs are nearly identical to the viruses formed in vivo. Here, we isolated PhMV-derived VLPs from ClearColi cells and carried out external and internal surface modification with fluorophores using reactive lysine-N-hydroxysuccinimide ester and cysteine-maleimide chemistries, respectively. The uptake of dye-labeled particles was tested in a range of cancer cells and monitored by confocal microscopy and flow cytometry. VLPs labeled internally on cysteine residues were taken up with high efficiency by several cancer cell lines and were colocalized with the endolysosomal marker LAMP-1 within 6 h, whereas VLPs labeled externally on lysine residues were taken up with lower efficiency, probably reflecting differences in surface charge and the propensity to bind to the cell surface. The infusion of dye and drug molecules into the cavity of the VLPs revealed that the photosensitizer (PS), Zn-EpPor, and the drugs crystal violet, mitoxantrone (MTX), and doxorubicin (DOX) associated stably with the carrier via noncovalent interactions. We confirmed the cytotoxicity of the PS-PhMV and DOX-PhMV particles against prostate cancer, ovarian and breast cancer cell lines, respectively. Our results show that PhMV-derived VLPs provide a new platform technology for the delivery of imaging agents and drugs, with preferential uptake into cancer cells. These particles could therefore be developed as multifunctional tools for cancer diagnosis and therapy.}, number={12}, journal={Biomacromolecules}, publisher={American Chemical Society (ACS)}, author={Masarapu, Hema and Patel, Bindi K. and Chariou, Paul L. and Hu, He and Gulati, Neetu M. and Carpenter, Bradley L. and Ghiladi, Reza A. and Shukla, Sourabh and Steinmetz, Nicole F.}, year={2017}, month={Nov}, pages={4141–4153} }
 @article{du_lucia_ghiladi_2016, title={A Novel Approach for Rapid Preparation of Monophasic Microemulsions That Facilitates Penetration of Woody Biomass}, volume={4}, ISSN={2168-0485 2168-0485}, url={http://dx.doi.org/10.1021/acssuschemeng.5b01601}, DOI={10.1021/acssuschemeng.5b01601}, abstractNote={Microemulsions are a straightforward, efficient, and highly useful complex media for flooding/wetting substrates as a result of their low surface tension and viscosity. Among the four broad general classes of microemulsions (Winsor-I, -II, -III, and -IV), Winsor-IV is by far considered the ideal microemulsion type within the context of woody biomass pretreatment because it is a single phase. In the present study, a never-before reported titration method was developed with the intent of providing a rapid online determination of Winsor-IV type microemulsion formulations under fixed surfactant concentrations for expressly treating woody biomass. A total of 108 surfactant-oil–water formulations based on a sodium dodecylsulfate/pentanol/water/sodium chloride/dodecane system were investigated for their phase behavior, 54 of which yielded Winsor-IV type microemulsions. The ability of the selected microemulsions to affect the crystallinity of cellulose was studied by X-ray diffraction as was the synergetic effect...}, number={3}, journal={ACS Sustainable Chemistry & Engineering}, publisher={American Chemical Society (ACS)}, author={Du, Xueyu and Lucia, Lucian A. and Ghiladi, Reza A.}, year={2016}, month={Feb}, pages={1665–1672} }
 @article{du_lucia_ghiladi_2016, title={Development of a Highly Efficient Pretreatment Sequence for the Enzymatic Saccharification of Loblolly Pine Wood}, volume={4}, ISSN={2168-0485 2168-0485}, url={http://dx.doi.org/10.1021/acssuschemeng.6b00198}, DOI={10.1021/acssuschemeng.6b00198}, abstractNote={The efficient pretreatment of lignocellulosic materials for bioenergy production is a critical step upon which efficient saccharification is highly dependent, particularly in softwoods due to both their high lignin content and condensed lignin structures. In the present study, preliminary pretreatment steps (e.g., Wiley milling, acetone extraction, autohydrolysis, and disc refining) and economical subsequent/core-pretreatment steps (e.g., reagents immersion, hydrothermolysis, dilute acid hydrolysis, and ionic liquids treatment) were systematically investigated to identify which combinations led to effective enzymatic saccharification of loblolly pine wood, the dominant softwood resource in the US. The results demonstrated that 85% phosphoric acid based immersions were highly efficient for both cellulose crystallinity degradation and enzymatic hydrolysis, and thus can be included as core pretreatment steps. The highest glucan recovery yield obtained was 93.0% after enzymatic hydrolysis when a pretreatment ...}, number={7}, journal={ACS Sustainable Chemistry & Engineering}, publisher={American Chemical Society (ACS)}, author={Du, Xueyu and Lucia, Lucian A. and Ghiladi, Reza A.}, year={2016}, month={Jun}, pages={3669–3678} }
 @article{lee_carpenter_wen_ghiladi_steinmetz_2016, title={High Aspect Ratio Nanotubes Formed by Tobacco Mosaic Virus for Delivery of Photodynamic Agents Targeting Melanoma}, volume={2}, ISSN={2373-9878 2373-9878}, url={http://dx.doi.org/10.1021/acsbiomaterials.6b00061}, DOI={10.1021/acsbiomaterials.6b00061}, abstractNote={Melanoma is a highly aggressive cancer that is unresponsive to many traditional therapies. Recently, photodynamic therapy has shown promise in its treatment as an adjuvant therapy. However, conventional photosensitizers are limited by poor solubility and limited accumulation within target tissue. Here, we report the delivery of a porphyrin-based photosensitizer encapsulated within a plant viral nanoparticle. Specifically, we make use of the hollow, high aspect ratio nanotubes formed by the nucleoprotein components of tobacco mosaic virus (TMV) to encapsulate the drug for delivery and targeting of cancer cells. The cationic photosensitizer was successfully and stably loaded into the interior channel of TMV via electrostatic interactions. Cell uptake and efficacy were evaluated using a model of melanoma. The resulting TMV-photosensitizer exhibited improved cell uptake and efficacy when compared to free photosensitizer, making it a promising platform for improved therapy of melanoma.}, number={5}, journal={ACS Biomaterials Science & Engineering}, publisher={American Chemical Society (ACS)}, author={Lee, Karin L. and Carpenter, Bradley L. and Wen, Amy M. and Ghiladi, Reza A. and Steinmetz, Nicole F.}, year={2016}, month={Apr}, pages={838–844} }
 @article{franzen_ghiladi_lebioda_dawson_2016, title={Multi-functional hemoglobin dehaloperoxidases}, number={4}, journal={Heme peroxidases}, author={Franzen, S. and Ghiladi, R. A. and Lebioda, L. and Dawson, J.}, year={2016}, pages={218–244} }
 @article{mccombs_d’antonio_barrios_carey_ghiladi_2016, title={Nonmicrobial Nitrophenol Degradation via Peroxygenase Activity of Dehaloperoxidase-Hemoglobin fromAmphitrite ornata}, volume={55}, ISSN={0006-2960 1520-4995}, url={http://dx.doi.org/10.1021/acs.biochem.6b00143}, DOI={10.1021/acs.biochem.6b00143}, abstractNote={The marine hemoglobin dehaloperoxidase (DHP) from Amphitrite ornata was found to catalyze the H2O2-dependent oxidation of nitrophenols, an unprecedented nonmicrobial degradation pathway for nitrophenols by a hemoglobin. Using 4-nitrophenol (4-NP) as a representative substrate, the major monooxygenated product was 4-nitrocatechol (4-NC). Isotope labeling studies confirmed that the O atom incorporated was derived exclusively from H2O2, indicative of a peroxygenase mechanism for 4-NP oxidation. Accordingly, X-ray crystal structures of 4-NP (1.87 Å) and 4-NC (1.98 Å) bound to DHP revealed a binding site in close proximity to the heme cofactor. Peroxygenase activity could be initiated from either the ferric or oxyferrous states with equivalent substrate conversion and product distribution. The 4-NC product was itself a peroxidase substrate for DHP, leading to the secondary products 5-nitrobenzene-triol and hydroxy-5-nitro-1,2-benzoquinone. DHP was able to react with 2,4-dinitrophenol (2,4-DNP) but was unreactive against 2,4,6-trinitrophenol (2,4,6-TNP). pH dependence studies demonstrated increased reactivity at lower pH for both 4-NP and 2,4-DNP, suggestive of a pH effect that precludes the reaction with 2,4,6-TNP at or near physiological conditions. Stopped-flow UV-visible spectroscopic studies strongly implicate a role for Compound I in the mechanism of 4-NP oxidation. The results demonstrate that there may be a much larger number of nonmicrobial enzymes that are underrepresented when it comes to understanding the degradation of persistent organic pollutants such as nitrophenols in the environment.}, number={17}, journal={Biochemistry}, publisher={American Chemical Society (ACS)}, author={McCombs, Nikolette L. and D’Antonio, Jennifer and Barrios, David A. and Carey, Leiah M. and Ghiladi, Reza A.}, year={2016}, month={Apr}, pages={2465–2478} }
 @article{stanley_scholle_zhu_lu_zhang_situ_ghiladi_2016, title={Photosensitizer-Embedded Polyacrylonitrile Nanofibers as Antimicrobial Non-Woven Textile}, volume={6}, ISSN={2079-4991}, url={http://dx.doi.org/10.3390/nano6040077}, DOI={10.3390/nano6040077}, abstractNote={Toward the objective of developing platform technologies for anti-infective materials based upon photodynamic inactivation, we employed electrospinning to prepare a non-woven textile comprised of polyacrylonitrile nanofibers embedded with a porphyrin-based cationic photosensitizer; termed PAN-Por(+). Photosensitizer loading was determined to be 34.8 nmol/mg material; with thermostability to 300 °C. Antibacterial efficacy was evaluated against four bacteria belonging to the ESKAPE family of pathogens (Staphylococcus aureus; vancomycin-resistant Enterococcus faecium; Acinetobacter baumannii; and Klebsiella pneumonia), as well as Escherichia coli. Our results demonstrated broad photodynamic inactivation of all bacterial strains studied upon illumination (30 min; 65 ± 5 mW/cm2; 400–700 nm) by a minimum of 99.9996+% (5.8 log units) regardless of taxonomic classification. PAN-Por(+) also inactivated human adenovirus-5 (~99.8% reduction in PFU/mL) and vesicular stomatitis virus (>7 log units reduction in PFU/mL). When compared to cellulose-based materials employing this same photosensitizer; the higher levels of photodynamic inactivation achieved here with PAN-Por(+) are likely due to the combined effects of higher photosensitizer loading and a greater surface area imparted by the use of nanofibers. These results demonstrate the potential of photosensitizer-embedded polyacrylonitrile nanofibers to serve as scalable scaffolds for anti-infective or self-sterilizing materials against both bacteria and viruses when employing a photodynamic inactivation mode of action.}, number={4}, journal={Nanomaterials}, publisher={MDPI AG}, author={Stanley, Sarah and Scholle, Frank and Zhu, Jiadeng and Lu, Yao and Zhang, Xiangwu and Situ, Xingci and Ghiladi, Reza}, year={2016}, month={Apr}, pages={77} }
 @article{wen_lee_cao_pangilinan_carpenter_lam_veliz_ghiladi_advincula_steinmetz_2016, title={Utilizing Viral Nanoparticle/Dendron Hybrid Conjugates in Photodynamic Therapy for Dual Delivery to Macrophages and Cancer Cells}, volume={27}, ISSN={1043-1802 1520-4812}, url={http://dx.doi.org/10.1021/acs.bioconjchem.6b00075}, DOI={10.1021/acs.bioconjchem.6b00075}, abstractNote={Photodynamic therapy (PDT) is a promising avenue for greater treatment efficacy of highly resistant and aggressive melanoma. Through photosensitizer attachment to nanoparticles, specificity of delivery can be conferred to further reduce potential side effects. While the main focus of PDT is the destruction of cancer cells, additional targeting of tumor-associated macrophages also present in the tumor microenvironment could further enhance treatment by eliminating their role in processes such as invasion, metastasis, and immunosuppression. In this study, we investigated PDT of macrophages and tumor cells through delivery using the natural noninfectious nanoparticle cowpea mosaic virus (CPMV), which has been shown to have specificity for the immunosuppressive subpopulation of macrophages and also targets cancer cells. We further explored conjugation of CPMV/dendron hybrids in order to improve the drug loading capacity of the nanocarrier. Overall, we demonstrated effective elimination of both macrophage and tumor cells at low micromolar concentrations of the photosensitizer when delivered with the CPMV bioconjugate, thereby potentially improving melanoma treatment.}, number={5}, journal={Bioconjugate Chemistry}, publisher={American Chemical Society (ACS)}, author={Wen, Amy M. and Lee, Karin L. and Cao, Pengfei and Pangilinan, Katrina and Carpenter, Bradley L. and Lam, Patricia and Veliz, Frank A. and Ghiladi, Reza A. and Advincula, Rigoberto C. and Steinmetz, Nicole F.}, year={2016}, month={Apr}, pages={1227–1235} }
 @article{carpenter_situ_scholle_bartelmess_weare_ghiladi_2015, title={Antiviral, Antifungal and Antibacterial Activities of a  BODIPY-Based Photosensitizer}, volume={20}, ISSN={1420-3049}, url={http://dx.doi.org/10.3390/molecules200610604}, DOI={10.3390/molecules200610604}, abstractNote={Antimicrobial photodynamic inactivation (aPDI) employing the BODIPY-based photosensitizer 2,6-diiodo-1,3,5,7-tetramethyl-8-(N-methyl-4-pyridyl)-4,4′-difluoro-boradiazaindacene (DIMPy-BODIPY) was explored in an in vitro assay against six species of bacteria (eight total strains), three species of yeast, and three viruses as a complementary approach to their current drug-based or non-existent treatments. Our best results achieved a noteworthy 5–6 log unit reduction in CFU at 0.1 μM for Staphylococcus aureus (ATCC-2913), methicillin-resistant S. aureus (ATCC-44), and vancomycin-resistant Enterococcus faecium (ATCC-2320), a 4–5 log unit reduction for Acinetobacter baumannii ATCC-19606 (0.25 μM), multidrug resistant A. baumannii ATCC-1605 (0.1 μM), Pseudomonas aeruginosa ATCC-97 (0.5 μM), and Klebsiella pneumoniae ATCC-2146 (1 μM), and a 3 log unit reduction for Mycobacterium smegmatis mc2155 (ATCC-700084). A 5 log unit reduction in CFU was observed for Candida albicans ATCC-90028 (1 μM) and Cryptococcus neoformans ATCC-64538 (0.5 μM), and a 3 log unit reduction was noted for Candida glabrata ATCC-15545 (1 μM). Infectivity was reduced by 6 log units in dengue 1 (0.1 μM), by 5 log units (0.5 μM) in vesicular stomatitis virus, and by 2 log units (5 μM) in human adenovirus-5. Overall, the results demonstrate that DIMPy-BODIPY exhibits antiviral, antibacterial and antifungal photodynamic inactivation at nanomolar concentrations and short illumination times.}, number={6}, journal={Molecules}, publisher={MDPI AG}, author={Carpenter, Bradley and Situ, Xingci and Scholle, Frank and Bartelmess, Juergen and Weare, Walter and Ghiladi, Reza}, year={2015}, month={Jun}, pages={10604–10621} }
 @inbook{franzen_ghiladi_lebioda_dawson_2015, title={Chapter 10. Multi-functional Hemoglobin Dehaloperoxidases}, volume={2016-January}, ISBN={9781849739115}, ISSN={2045-5488}, url={http://dx.doi.org/10.1039/9781782622628-00218}, DOI={10.1039/9781782622628-00218}, abstractNote={The protein known as dehaloperoxidase-hemoglobin (DHP) from the terebellid polychaete Amphitrite ornata has provided us with an example of a multi-functional protein that challenges many of the assumptions behind the structure–function correlation owing to its dual roles as an oxygen transport globin and a peroxidase. In this chapter, we will present an overview of the peroxidase function of DHP, and will describe the mechanism of the oxidative dehalogenation reaction carried out by this enzyme when initiated from both the ferric and oxyferrous states by the addition of hydrogen peroxide. The structural and electronic properties of the heme active site will also be discussed in the context of the proximal and distal cavities and the corresponding charge relays. The question of small molecule binding will be addressed, with a particular emphasis on the inhibitor binding site and the current understanding of internal versus external substrate binding. Finally, the deactivation of DHP and its physiological role will be presented.}, number={4}, booktitle={Heme Peroxidases}, publisher={Royal Society of Chemistry}, author={Franzen, Stefan and Ghiladi, Reza A. and Lebioda, Lukasz and Dawson, John}, year={2015}, month={Oct}, pages={218–244} }
 @article{muli_carpenter_mayukh_ghiladi_mcgrath_2015, title={Dendritic near-IR absorbing zinc phthalocyanines for antimicrobial photodynamic therapy}, volume={56}, ISSN={0040-4039}, url={http://dx.doi.org/10.1016/j.tetlet.2015.01.076}, DOI={10.1016/j.tetlet.2015.01.076}, abstractNote={Abstract Design, synthesis, characterization, and photodynamic activity of dendritic, water-soluble zinc phthalocyanine (ZnPc) isomers 1a and 1b are described. Bearing terminal triethylene glycol (TEG) moieties as water solubilizing groups that were attached to the Pc core using Cu(I) catalyzed alkyne–azide cycloaddition (CuAAC), 1a and 1b are readily soluble in H2O, polar aprotic, and protic organic solvents. UV/Vis analyses indicate that the Q band of the non-peripheral ZnPc 1b is ca. 80 nm red-shifted relative to the peripheral one with absorption at 805 nm (distilled water). 1a and 1b have log D7.4 values of 0.22 and 0.05, respectively, suggesting that the non-peripheral substitution improved the overall hydrophilicity. Aggregation studies indicate that non-peripherally substituted 1b is significantly less aggregated in aqueous media than peripherally substituted 1a. Singlet oxygen generation studies are reported. Both ZnPcs showed negligible dark toxicity on bacteria and yeast with 10 μM 1a and 1b. Illumination (400–850 nm) of Pseudomonas aeruginosa with 10 μM of 1a produced a 90% cell inactivation while Acinetobacter baumannii with 10 μM 1b showed detection limit (99.9999+%) cell inactivation, demonstrating the antimicrobial photoactivity of these dyes.}, number={23}, journal={Tetrahedron Letters}, publisher={Elsevier BV}, author={Muli, Dominic K. and Carpenter, Bradley L. and Mayukh, Mayank and Ghiladi, Reza A. and McGrath, Dominic V.}, year={2015}, month={Jun}, pages={3541–3545} }
 @article{carpenter_scholle_sadeghifar_francis_boltersdorf_weare_argyropoulos_maggard_ghiladi_2015, title={Synthesis, Characterization, and Antimicrobial Efficacy of Photomicrobicidal Cellulose Paper}, volume={16}, ISSN={["1526-4602"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84938937944&partnerID=MN8TOARS}, DOI={10.1021/acs.biomac.5b00758}, abstractNote={Toward our goal of scalable, antimicrobial materials based on photodynamic inactivation, paper sheets comprised of photosensitizer-conjugated cellulose fibers were prepared using porphyrin and BODIPY photosensitizers, and characterized by spectroscopic (infrared, UV-vis diffuse reflectance, inductively coupled plasma optical emission) and physical (gel permeation chromatography, elemental, and thermal gravimetric analyses) methods. Antibacterial efficacy was evaluated against Staphylococcus aureus (ATCC-2913), vancomycin-resistant Enterococcus faecium (ATCC-2320), Acinetobacter baumannii (ATCC-19606), Pseudomonas aeruginosa (ATCC-9027), and Klebsiella pneumoniae (ATCC-2146). Our best results were achieved with a cationic porphyrin-paper conjugate, Por((+))-paper, with inactivation upon illumination (30 min, 65 ± 5 mW/cm(2), 400-700 nm) of all bacterial strains studied by 99.99+% (4 log units), regardless of taxonomic classification. Por((+))-paper also inactivated dengue-1 virus (>99.995%), influenza A (∼ 99.5%), and human adenovirus-5 (∼ 99%). These results demonstrate the potential of cellulose materials to serve as scalable scaffolds for anti-infective or self-sterilizing materials against both bacteria and viruses when employing a photodynamic inactivation mode of action.}, number={8}, journal={BIOMACROMOLECULES}, author={Carpenter, Bradley L. and Scholle, Frank and Sadeghifar, Hasan and Francis, Aaron J. and Boltersdorf, Jonathan and Weare, Walter W. and Argyropoulos, Dimitris S. and Maggard, Paul A. and Ghiladi, Reza A.}, year={2015}, month={Aug}, pages={2482–2492} }
 @article{barrios_d’antonio_mccombs_zhao_franzen_schmidt_sombers_ghiladi_2014, title={Peroxygenase and Oxidase Activities of Dehaloperoxidase-Hemoglobin from Amphitrite ornata}, volume={136}, ISSN={0002-7863 1520-5126}, url={http://dx.doi.org/10.1021/ja500293c}, DOI={10.1021/ja500293c}, abstractNote={The marine globin dehaloperoxidase‐hemoglobin (DHP) from Amphitrite ornata was found to catalyze the H2O2‐dependent oxidation of monohaloindoles, a previously unreported class of substrate for DHP. Using 5‐Br‐indole as a representative substrate, the major monooxygenated products were found to be 5‐Br‐2‐oxindole and 5‐Br‐3‐oxindolenine. Isotope labeling studies confirmed that the oxygen atom incorporated was derived exclusively from H2O2, indicative of a previously unreported peroxygenase activity for DHP. Peroxygenase activity could be initiated from either the ferric or oxyferrous states with equivalent substrate conversion and product distribution. It was found that 5‐Br‐3‐oxindole, a precursor of the product 5‐Br‐3‐oxindolenine, readily reduced the ferric enzyme to the oxyferrous state, demonstrating an unusual product‐driven reduction of the enzyme. As such, DHP returns to the globin‐active oxyferrous form after peroxygenase activity ceases. Reactivity with 5‐Br‐3‐oxindole in the absence of H2O2 also yielded 5,5’‐Br2‐indigo above the expected reaction stoichiometry under aerobic conditions, and O2‐concentration studies demonstrated dioxygen consumption. Non‐enzymatic and anaerobic controls both confirmed the requirements for DHP and molecular oxygen in the catalytic generation of 5,5’‐Br2‐indigo, and together suggest a novel oxidase activity for DHP.}, number={22}, journal={Journal of the American Chemical Society}, publisher={American Chemical Society (ACS)}, author={Barrios, David A. and D’Antonio, Jennifer and McCombs, Nikolette L. and Zhao, Jing and Franzen, Stefan and Schmidt, Andreas C. and Sombers, Leslie A. and Ghiladi, Reza A.}, year={2014}, month={May}, pages={7914–7925} }
 @article{dumarieh_d'antonio_deliz-liang_smirnova_svistunenko_ghiladi_2013, title={Tyrosyl Radicals in Dehaloperoxidase}, volume={288}, ISSN={0021-9258 1083-351X}, url={http://dx.doi.org/10.1074/JBC.M113.496497}, DOI={10.1074/JBC.M113.496497}, abstractNote={Background: The catalytically active species in dehaloperoxidase (DHP) contains both a ferryl heme and a tyrosyl radical. Results: Radicals were shown to form on three tyrosines (Tyr-28, Tyr-34 and Tyr-38) in DHP. Conclusion: Mutants that lacked tyrosines showed increases in the rates of both substrate oxidation and heme bleaching. Significance: Tyrosyl radical formation is an evolutionary adaptation to protect the enzyme from irreversibly oxidizing itself. Dehaloperoxidase (DHP) from Amphitrite ornata, having been shown to catalyze the hydrogen peroxide-dependent oxidation of trihalophenols to dihaloquinones, is the first oxygen binding globin that possesses a biologically relevant peroxidase activity. The catalytically competent species in DHP appears to be Compound ES, a reactive intermediate that contains both a ferryl heme and a tyrosyl radical. By simulating the EPR spectra of DHP activated by H2O2, Thompson et al. (Thompson, M. K., Franzen, S., Ghiladi, R. A., Reeder, B. J., and Svistunenko, D. A. (2010) J. Am. Chem. Soc. 132, 17501–17510) proposed that two different radicals, depending on the pH, are formed, one located on either Tyr-34 or Tyr-28 and the other on Tyr-38. To provide additional support for these simulation-based assignments and to deduce the role(s) that tyrosyl radicals play in DHP, stopped-flow UV-visible and rapid-freeze-quench EPR spectroscopic methods were employed to study radical formation in DHP when three tyrosine residues, Tyr-28, Tyr-34, and Tyr-38, were replaced either individually or in combination with phenylalanines. The results indicate that radicals form on all three tyrosines in DHP. Evidence for the formation of DHP Compound I in several tyrosine mutants was obtained. Variants that formed Compound I showed an increase in the catalytic rate for substrate oxidation but also an increase in heme bleaching, suggesting that the tyrosines are necessary for protecting the enzyme from oxidizing itself. This protective role of tyrosines is likely an evolutionary adaptation allowing DHP to avoid self-inflicted damage in the oxidative environment.}, number={46}, journal={Journal of Biological Chemistry}, publisher={American Society for Biochemistry & Molecular Biology (ASBMB)}, author={Dumarieh, Rania and D'Antonio, Jennifer and Deliz-Liang, Alexandria and Smirnova, Tatyana and Svistunenko, Dimitri A. and Ghiladi, Reza A.}, year={2013}, month={Oct}, pages={33470–33482} }
 @article{dumarieh_d'antonio_deliz-liang_smirnova_svistunenko_ghiladi_2013, title={Tyrosyl radicals in dehaloperoxidase how nature deals with evolving an oxygen-binding globin to a biologically relevant peroxidase}, volume={288}, number={46}, journal={Journal of Biological Chemistry}, author={Dumarieh, R. and D'Antonio, J. and Deliz-Liang, A. and Smirnova, T. and Svistunenko, D. A. and Ghiladi, R. A.}, year={2013}, pages={33470–33482} }
 @article{svistunenko_worrall_chugh_haigh_ghiladi_nicholls_2012, title={Ferric haem forms of Mycobacterium tuberculosis catalase-peroxidase probed by EPR spectroscopy: Their stability and interplay with pH}, volume={94}, ISSN={0300-9084}, url={http://dx.doi.org/10.1016/j.biochi.2012.02.021}, DOI={10.1016/j.biochi.2012.02.021}, abstractNote={Low temperature EPR spectroscopy was used to characterise Mycobacterium tuberculosis catalase-peroxidase in its resting ferric haem state. Several high spin ferric haem forms and no low spin forms were found in the enzyme samples frozen in methanol on dry ice. The EPR spectra depended not only on the pH but also on the buffer type. As a general trend, the higher the pH, the greater the ‘rhombic’ fraction of the high spin ferric haem that was observed. The rhombic form was characterised by well separated two lines in the g = 6 region whereas in the ‘axial’ form the two lines overlap. This pH dependence of the equilibrium of axial and rhombic ferric haem forms is also seen in rapidly freeze-quenched samples. Different high spin ferric haem forms were monitored during a 3 week storage of the enzyme at 4 °C. For some forms, extremal dependences, i.e. those progressing via maxima or minima over storage time, were found. This indicates that the mechanism of the time-dependent transition from one high spin ferric haem form to another must be more complex than a simple single site oxidation.}, number={6}, journal={Biochimie}, publisher={Elsevier BV}, author={Svistunenko, Dimitri A. and Worrall, Jonathan A.R. and Chugh, Snehpriya B. and Haigh, Sarah C. and Ghiladi, Reza A. and Nicholls, Peter}, year={2012}, month={Jun}, pages={1274–1280} }
 @article{franzen_sasan_sturgeon_lyon_battenburg_gracz_dumariah_ghiladi_2012, title={Nonphotochemical Base-Catalyzed Hydroxylation of 2,6-Dichloroquinone by H2O2Occurs by a Radical Mechanism}, volume={116}, ISSN={1520-6106 1520-5207}, url={http://dx.doi.org/10.1021/jp208536x}, DOI={10.1021/jp208536x}, abstractNote={Kinetic and structural studies have shown that peroxidases are capable of the oxidation of 2,4,6-trichlorophenol (2,4,6-TCP) to 2,6-dichloro-1,4-benzoquinone (2,6-DCQ). Further reactions of 2,6-DCQ in the presence of H(2)O(2) and OH(-) yield 2,6-dichloro-3-hydroxy-1,4-benzoquinone (2,6-DCQOH). The reactions of 2,6-DCQ have been monitored spectroscopically [UV-visible and electron spin resonance (ESR)] and chromatographically. The hydroxylation product, 2,6-DCQOH, has been observed by UV-visible and characterized structurally by (1)H and (13)C NMR spectroscopy. The results are consistent with a nonphotochemical base-catalyzed oxidation of 2,6-DCQ at pH > 7. Because H(2)O(2) is present in peroxidase reaction mixtures, there is also a potential role for the hydrogen peroxide anion (HOO(-)). However, in agreement with previous work, we observe that the nonphotochemical epoxidation by H(2)O(2) at pH < 7 is immeasurably slow. Both room-temperature ESR and rapid-freeze-quench ESR methods were used to establish that the dominant nonphotochemical mechanism involves formation of a semiquinone radical (base -catalyzed pathway), rather than epoxidation (direct attack by H(2)O(2) at low pH). Analysis of the kinetics using an Arrhenius model permits determination of the activation energy of hydroxylation (E(a) = 36 kJ/mol), which is significantly lower than the activation energy of the peroxidase-catalyzed oxidation of 2,4,6-TCP (E(a) = 56 kJ/mol). However, the reaction is second order in both 2,6-DCQ and OH(-) so that its rate becomes significant above 25 °C due to the increased rate of formation of 2,6-DCQ that feeds the second-order process. The peroxidase used in this study is the dehaloperoxidase-hemoglobin (DHP A) from Amphitrite ornata , which is used to study the effect of a catalyst on the reactions. The control experiments and precedents in studies of other peroxidases lead to the conclusion that hydroxylation will be observed following any process that leads to the formation of the 2,6-DCQ at pH > 7, regardless of the catalyst used in the 2,4,6-TCP oxidation reaction.}, number={5}, journal={The Journal of Physical Chemistry B}, publisher={American Chemical Society (ACS)}, author={Franzen, Stefan and Sasan, Koroush and Sturgeon, Bradley E. and Lyon, Blake J. and Battenburg, Benjamin J. and Gracz, Hanna and Dumariah, Rania and Ghiladi, Reza}, year={2012}, month={Jan}, pages={1666–1676} }
 @article{carpenter_feese_sadeghifar_argyropoulos_ghiladi_2012, title={Porphyrin-Cellulose Nanocrystals: A Photobactericidal Material that Exhibits Broad Spectrum Antimicrobial Activity (vol 88, pg 495, 2012)}, volume={88}, ISSN={["0031-8655"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84863678900&partnerID=MN8TOARS}, DOI={10.1111/j.1751-1097.2012.01191.x}, abstractNote={Bradley L. Carpenter, Elke Feese, Hasan Sadeghifar, Dimitris S. Argyropoulos and Reza A. Ghiladi* Department of Chemistry, North Carolina State University, Raleigh, NC Department of Forest Biomaterials, North Carolina State University, Raleigh, NC Department of Chemistry, University of Helsinki, Helsinki, Finland Department of Chemistry, Science and Research Branch, Islamic Azad University, Mazandaran, Iran}, number={4}, journal={PHOTOCHEMISTRY AND PHOTOBIOLOGY}, author={Carpenter, Bradley L. and Feese, Elke and Sadeghifar, Hasan and Argyropoulos, Dimitris S. and Ghiladi, Reza A.}, year={2012}, pages={1034–1034} }
 @article{carpenter_feese_sadeghifar_argyropoulos_ghiladi_2012, title={Porphyrin-Cellulose Nanocrystals: A Photobactericidal Material that Exhibits Broad Spectrum Antimicrobial Activity†}, volume={88}, ISSN={0031-8655}, url={http://dx.doi.org/10.1111/j.1751-1097.2012.01117.x}, DOI={10.1111/j.1751-1097.2012.01117.x}, abstractNote={Abstract}, number={3}, journal={Photochemistry and Photobiology}, publisher={Wiley}, author={Carpenter, Bradley L. and Feese, Elke and Sadeghifar, Hasan and Argyropoulos, Dimitris S. and Ghiladi, Reza A.}, year={2012}, month={Mar}, pages={527–536} }
 @article{ghiladi_rheingold_siegler_karlin_2012, title={Synthesis and characterization of new trinuclear copper complexes}, volume={389}, ISSN={0020-1693}, url={http://dx.doi.org/10.1016/j.ica.2012.02.020}, DOI={10.1016/j.ica.2012.02.020}, abstractNote={This report describes our approach towards modeling the copper cluster active sites of nitrous oxide reductase and the multicopper oxidases/oxygenases. We have synthesized two mesitylene-based trinucleating ligands, MesPY1 and MesPY2, which employ bis(2-picolyl)amine (PY1) and bis(2-pyridylethyl)amine (PY2) tridentate copper chelates, respectively. Addition of cuprous salts to these ligands leads to the isolation of tricopper(I) complexes [(Mes-PY1)CuI3(CH3CN)3](ClO4)3·0.25Et2O (1) and [(Mes-PY2)CuI3](PF6)3 (3). Each of the three copper centers in 1 is most likely four-coordinate, with ligated acetonitrile as the fourth ligand; by contrast, the copper centers in 3 are three-coordinate, as determined by X-ray crystallography. The synthesis of [(Mes-PY1)CuII3(CH3CN)2(CH3OH)2](ClO4)6·(CH3OH) (2) was accomplished by addition of three equivalents of the copper(II) salt, Cu(ClO4)2·6H2O, to the ligand. The structure of 2 shows that two of the copper centers are tetracoordinate (with MeCN solvent ligation), but have additional weak axial (fifth ligand) interactions with the perchlorate anions; the third copper is unique in that it is coordinated by two MeOH solvent molecules, making it overall five-coordinate. For complexes 2 and 3, one copper ion center is located on the opposite side of the mesitylene plane as the other two. These observations, although in the solid state, must be taken into account for future studies where intramolecular tricopper(I)/O2 (or other small molecules of interest) interactions in solution are desirable.}, journal={Inorganica Chimica Acta}, publisher={Elsevier BV}, author={Ghiladi, Reza A. and Rheingold, Arnold L. and Siegler, Maxime A. and Karlin, Kenneth D.}, year={2012}, month={Jul}, pages={131–137} }
 @article{zhao_de serrano_dumarieh_thompson_ghiladi_franzen_2012, title={The Role of the Distal Histidine in H2O2 Activation and Heme Protection in both Peroxidase and Globin Functions}, volume={116}, ISSN={1520-6106 1520-5207}, url={http://dx.doi.org/10.1021/jp300014b}, DOI={10.1021/jp300014b}, abstractNote={The distal histidine mutations of dehaloperoxidase-hemoglobin A (DHP A) to aspartate (H55D) and asparagine (H55N) have been prepared to study the role played by the distal histidine in both activation and protection against oxidation by radicals in heme proteins. The H55D and H55N mutants of DHP A have ~6-fold and ~11-fold lower peroxidase activities than wild type enzyme toward the oxidation of 2,4,6-trichlorophenol (TCP) to yield 2,6-dichloroquinone (DCQ) in the presence of H(2)O(2). The origin of the lower rate constants may be the solvent-exposed conformations of distal D55 and N55, which would have the dual effect of destabilizing the binding of H(2)O(2) to the heme iron, and of removing the acid-base catalyst necessary for the heterolytic O-O bond cleavage of heme-bound H(2)O(2) (i.e., compound 0). The partial peroxidase activity of H55D can be explained if one considers that there are two conformations of the distal aspartate (open and closed) by analogy with the distal histidine. We hypothesize that the distal aspartate has an active conformation in the distal pocket (closed). Although the open form is observed in the low-temperature X-ray crystal structure of ferric H55D, the closed form is observed in the FTIR spectrum of the carbonmonoxy form of the H55D mutant. Consistent with this model, the H55D mutant also shows inhibition of TCP oxidation by 4-bromophenol (4-BP). Consistent with the protection hypothesis, compound ES, the tyrosyl radical-containing ferryl intermediate observed in WT DHP A, was not observed in H55D.}, number={40}, journal={The Journal of Physical Chemistry B}, publisher={American Chemical Society (ACS)}, author={Zhao, Junjie and de Serrano, Vesna and Dumarieh, Rania and Thompson, Matt and Ghiladi, Reza A. and Franzen, Stefan}, year={2012}, month={Sep}, pages={12065–12077} }
 @article{franzen_thompson_ghiladi_2012, title={The dehaloperoxidase paradox}, volume={1824}, ISSN={1570-9639}, url={http://dx.doi.org/10.1016/j.bbapap.2011.12.008}, DOI={10.1016/j.bbapap.2011.12.008}, abstractNote={The dual functions of the dehaloperoxidase-hemoglobin of Amphitrite ornata leads to a paradox. Peroxidase and hemoglobin functions require ferric and ferrous resting states, respectively. Assuming that hemoglobin function is the dominant function, the starting point for peroxidase activation would be the oxyferrous state. Activation of that state leads to the ferryl intermediate, followed by one-electron oxidation of the substrate, which results in the ferric state. Since no exogenous reductant is known, there is no return to the ferrous form or hemoglobin function. The observation that an internal binding site for 4-bromophenol leads to inhibition leads to a further paradox that the enzyme would be inhibited immediately upon activation under ambient conditions in benthic ecosystems where the inhibitor, 4-bromophenol is present in greater concentration than the substrate, 2,4,6-tribromophenol. In this review, we explore the unresolved aspects of the reaction scheme that leads to the apparent paradox. Recent data showing activation of the oxyferrous state, an extremely high reduction potential and exogenous reduction by the 2,6-dibromoquinone product present a potential resolution of the paradox. These aspects are discussed in the context of control of reactivity radical pathways and reactivity by the motion of the distal histidine, H55, which in turn is coupled to the binding of substrate and inhibitor.}, number={4}, journal={Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics}, publisher={Elsevier BV}, author={Franzen, Stefan and Thompson, Matthew K. and Ghiladi, Reza A.}, year={2012}, month={Apr}, pages={578–588} }
 @article{thompson_franzen_ghiladi_reeder_svistunenko_2011, title={Decay of Compound ES in Dehaloperoxidase-Hemoglobin}, volume={100}, ISSN={0006-3495}, url={http://dx.doi.org/10.1016/j.bpj.2010.12.1275}, DOI={10.1016/j.bpj.2010.12.1275}, abstractNote={Dehaloperoxidase (DHP) is a respiratory hemoglobin (Hb) that catalyzes the conversion of trihalophenols to dihaloquinones in the presence of hydrogen peroxide. Ferric heme states of the resting DHP and the free radical intermediates formed under H2O2 treatment were studied by low temperature EPR spectroscopy in the range of reaction time of 50 ms - 2 min at three different pH values. Two high spin ferric heme forms were identified in the resting enzyme and assigned to the open and closed conformations of the distal histidine, His55. Two free radicals were found in DHP activated by H2O2: the radical associated with Compound ES has been assigned to Tyr34, the other radical - to Tyr38. The Tyr34 radical is formed with a very high relative yield (almost 100% of heme), atypical of other globins. The HPLC analysis of the reaction products showed a pH dependent formation of covalent heme-to-protein cross-links. The stable DHP Compound RH formed under H2O2 in the absence of substrates is proposed to be a state with the ferric heme covalently cross-linked to Tyr34. A kinetic model of the experimental data suggests that formation of Compound RH or the Tyr38 radical are two alternative routes of Compound ES decay. Which route is taken depends on the conformation of His55: in the less populated closed conformation, the Tyr38 radical is formed, but in the major open conformation, Compound ES decays yielding Compound RH, a product of safe termination of the two oxidizing equivalents of H2O2 when no substrate is available.}, number={3}, journal={Biophysical Journal}, publisher={Elsevier BV}, author={Thompson, Matthew K. and Franzen, Stefan and Ghiladi, Reza A. and Reeder, Brandon J. and Svistunenko, Dimitri A.}, year={2011}, month={Feb}, pages={194a} }
 @article{d’antonio_d’antonio_de serrano_gracz_thompson_ghiladi_bowden_franzen_2011, title={Functional Consequences of the Creation of an Asp-His-Fe Triad in a 3/3 Globin}, volume={50}, ISSN={0006-2960 1520-4995}, url={http://dx.doi.org/10.1021/bi201368u}, DOI={10.1021/bi201368u}, abstractNote={The proximal side of dehaloperoxidase-hemoglobin A (DHP A) from Amphitrite ornata has been modified via site-directed mutagenesis of methionine 86 into aspartate (M86D) to introduce an Asp-His-Fe triad charge relay. X-ray crystallographic structure determination of the metcyano forms of M86D [Protein Data Bank (PDB) entry 3MYN ] and M86E (PDB entry 3MYM ) mutants reveal the structural origins of a stable catalytic triad in DHP A. A decrease in the rate of H(2)O(2) activation as well as a lowered reduction potential versus that of the wild-type enzyme was observed in M86D. One possible explanation for the significantly lower activity is an increased affinity for the distal histidine in binding to the heme Fe to form a bis-histidine adduct. Resonance Raman spectroscopy demonstrates a pH-dependent ligation by the distal histidine in M86D, which is indicative of an increased trans effect. At pH 5.0, the heme Fe is five-coordinate, and this structure resembles the wild-type DHP A resting state. However, at pH 7.0, the distal histidine appears to form a six-coordinate ferric bis-histidine (hemichrome) adduct. These observations can be explained by the effect of the increased positive charge on the heme Fe on the formation of a six-coordinate low-spin adduct, which inhibits the ligation and activation of H(2)O(2) as required for peroxidase activity. The results suggest that the proximal charge relay in peroxidases regulate the redox potential of the heme Fe but that the trans effect is a carefully balanced property that can both activate H(2)O(2) and attract ligation by the distal histidine. To understand the balance of forces that modulate peroxidase reactivity, we studied three M86 mutants, M86A, M86D, and M86E, by spectroelectrochemistry and nuclear magnetic resonance spectroscopy of (13)C- and (15)N-labeled cyanide adducts as probes of the redox potential and of the trans effect in the heme Fe, both of which can be correlated with the proximity of negative charge to the N(δ) hydrogen of the proximal histidine, consistent with an Asp-His-Fe charge relay observed in heme peroxidases.}, number={44}, journal={Biochemistry}, publisher={American Chemical Society (ACS)}, author={D’Antonio, Edward L. and D’Antonio, Jennifer and de Serrano, Vesna and Gracz, Hanna and Thompson, Matthew K. and Ghiladi, Reza A. and Bowden, Edmond F. and Franzen, Stefan}, year={2011}, month={Nov}, pages={9664–9680} }
 @article{feese_sadeghifar_gracz_argyropoulos_ghiladi_2011, title={Photobactericidal Porphyrin-Cellulose Nanocrystals: Synthesis, Characterization, and Antimicrobial Properties}, volume={12}, ISSN={1525-7797 1526-4602}, url={http://dx.doi.org/10.1021/bm200718s}, DOI={10.1021/bm200718s}, abstractNote={Adherence and survival of pathogenic bacteria on surfaces leading to concomitant transmission to new hosts significantly contributes to the proliferation of pathogens, which in turn considerably increases the threat to human health, particularly by antibiotic-resistant bacteria. Consequently, more research into effective surface disinfection and alternative materials (fabrics, plastics, or coatings) with antimicrobial and other bioactive characteristics is desirable. This report describes the synthesis and characterization of cellulose nanocrystals that were surface-modified with a cationic porphyrin. The porphyrin was appended onto the cellulose surface via the Cu(I)-catalyzed Huisgen-Meldal-Sharpless 1,3-dipolar cycloaddition having occurred between azide groups on the cellulosic surface and porphyrinic alkynes. The resulting, generally insoluble, crystalline material, CNC-Por (5), was characterized by infrared and diffusion (1)H NMR spectroscopies, gel permeation chromatography, and thermogravimetric analysis. Although only suspended, and not dissolved, in an aqueous system, CNC-Por (5) showed excellent efficacy toward the photodynamic inactivation of Mycobacterium smegmatis and Staphylococcus aureus , albeit only slight activity against Escherichia coli . The synthesis, properties, and activity of CNC-Por (5) described herein serve as a benchmark toward our overall objectives of developing novel, potent, bioactive, photobactericidal materials that are effective against a range of bacteria, with potential utilization in the health care and food preparation industries.}, number={10}, journal={Biomacromolecules}, publisher={American Chemical Society (ACS)}, author={Feese, Elke and Sadeghifar, Hasan and Gracz, Hanna S. and Argyropoulos, Dimitris S. and Ghiladi, Reza A.}, year={2011}, month={Oct}, pages={3528–3539} }
 @article{d’antonio_ghiladi_2011, title={Reactivity of Deoxy- and Oxyferrous Dehaloperoxidase B fromAmphitrite ornata:Identification of Compound II and Its Ferrous–Hydroperoxide Precursor}, volume={50}, ISSN={0006-2960 1520-4995}, url={http://dx.doi.org/10.1021/bi200311u}, DOI={10.1021/bi200311u}, abstractNote={Dehaloperoxidase (DHP) from the terebellid polychaete Amphitrite ornata is a bifunctional enzyme that possesses both hemoglobin and peroxidase activities. The bifunctional nature of DHP as a globin peroxidase appears to be at odds with the traditional starting oxidation state for each individual activity. Namely, reversible oxygen binding is only mediated via a ferrous heme in globins, and peroxidase activity is initiated from ferric centers and to the exclusion of the oxyferrous oxidation state from the peroxidase cycle. Thus, to address what appears to be a paradox, herein we report the details of our investigations into the DHP catalytic cycle when initiated from the deoxy- and oxyferrous states using biochemical assays, stopped-flow UV-visible, and rapid-freeze-quench electron paramagnetic resonance spectroscopies, and anaerobic methods. We demonstrate the formation of Compound II directly from deoxyferrous DHP B upon its reaction with hydrogen peroxide and show that this occurs both in the presence and in the absence of trihalophenol. Prior to the formation of Compound II, we have identified a new species that we have preliminarily attributed to a ferrous-hydroperoxide precursor that undergoes heterolysis to generate the aforementioned ferryl intermediate. Taken together, the results demonstrate that the oxyferrous state in DHP is a peroxidase competent starting species, and an updated catalytic cycle for DHP is proposed in which the ferric oxidation state is not an obligatory starting point for the peroxidase catalytic cycle of dehaloperoxidase. The data presented herein provide a link between the peroxidase and oxygen transport activities, which furthers our understanding of how this bifunctional enzyme is able to unite its two inherent functions in one system.}, number={27}, journal={Biochemistry}, publisher={American Chemical Society (ACS)}, author={D’Antonio, Jennifer and Ghiladi, Reza A.}, year={2011}, month={Jul}, pages={5999–6011} }
 @article{ghiladi_dumarieh_d'antonio_2011, title={Site(s) of Tyrosyl Radical Formation in Dehaloperoxidase A and B}, volume={100}, ISSN={0006-3495}, url={http://dx.doi.org/10.1016/j.bpj.2010.12.2258}, DOI={10.1016/j.bpj.2010.12.2258}, abstractNote={Dehaloperoxidase (DHP) is a dual-function hemoprotein that, in addition to being the putative coelomic hemoglobin of Amphitrite ornata, exhibits a broad substrate specificity for the catalytic oxidation of mono-, di-, and trisubstituted halophenols, thus distinguishing DHP as the first globin shown to possess a biologically relevant peroxidase activity. Both isoenzymes of DHP, termed A and B, have been shown to oxidize trihalophenols to dihaloquinones in a dehalogenation reaction that utilizes hydrogen peroxide as the oxidant. We have shown that the initially formed heme intermediate in wild-type DHP is not Compound I as is often the case in peroxidases, but rather is a combination of an iron(IV)-oxo and a tyrosyl radical that together have similarity to the Compound ES intermediate of cytochrome c peroxidase. In order to possibly identify the site(s) of this radical species in DHP, we have studied the tyrosine mutants DHP A (Y34F), DHP A (Y38F), DHP A (Y34F/Y38F), DHP B (Y28F), DHP B (Y38F), and DHP B (Y28F/Y38F), and studied their reaction with hydrogen peroxide using a combination of stopped-flow UV-visible and rapid-freeze quench electron paramagnetic resonance spectroscopies. Spectroscopic evidence for the formation of both Compound I and Compound ES will be presented. We have further characterized these mutants using biochemical assays to determine their effect on the catalytic activity of the enzyme, and relate these results to the structure of the heme active site and the formation of the catalytically-attenuated species Compound RH. Such mutagenesis studies of DHP provide critical insight into the mechanistic details of the H2O2-dependent oxidative dehalogenation reaction catalyzed by dehaloperoxidase, present a clearer description of the function of DHP at the molecular level, and lead to a better understanding of the paradigms of globin structure-function relationships.}, number={3}, journal={Biophysical Journal}, publisher={Elsevier BV}, author={Ghiladi, Reza A. and Dumarieh, Rania and D'Antonio, Jennifer}, year={2011}, month={Feb}, pages={379a} }
 @article{ghiladi_d'antonio_dumarieh_2010, title={Characterization of the Radical Intermediates of Dehaloperoxidase A and B from Amphitrite Ornata}, volume={98}, ISSN={0006-3495}, url={http://dx.doi.org/10.1016/j.bpj.2009.12.3511}, DOI={10.1016/j.bpj.2009.12.3511}, abstractNote={The enzyme intermediates of dehaloperoxidase (DHP) from the marine worm Amphitrite ornata are unique within both the globin and cytochrome c peroxidase superfamilies. Both isoenzymes of DHP, termed A and B, have been shown to oxidize trihalophenols to dihaloquinones in a dehalogenation reaction that utilizes hydrogen peroxide as a co-substrate. We have shown that the initially formed heme intermediate in this reaction is not Compound I as is often the case in peroxidases, but rather is a combination of an iron(IV)-oxo (Compound II) and a tyrosyl radical that together have similarity to the Compound ES intermediate of cytochrome c peroxidase. In order to possibly identify the origin of this radical species in DHP, we have expressed the tyrosine mutants DHP A (Y34F), DHP A (Y38F), DHP A (Y34F/Y38F), and DHP B (Y38F), and studied their reaction with hydrogen peroxide using a combination of stopped-flow UV-visible and rapid-freeze quench electron paramagnetic resonance spectroscopies. Although each mutant exhibited an average signal at g ≈ 2.0058 confirming the presence of a protein radical, significant differences in the lineshape and width of each radical was observed. We have further characterized these mutants using biochemical assays to determine their effect on the catalytic activity of the enzyme, and relate these results to the structure of the heme active site. Such mutagenesis studies of DHP provide critical insight into the mechanistic details of the H2O2-dependent oxidative dehalogenation reaction catalyzed by dehaloperoxidase, present a clearer description of the function of DHP at the molecular level, and lead to a better understanding of the paradigms of globin structure-function relationships.}, number={3}, journal={Biophysical Journal}, publisher={Elsevier BV}, author={Ghiladi, Reza A. and D'Antonio, Jennifer and Dumarieh, Rania}, year={2010}, month={Jan}, pages={641a} }
 @article{thompson_franzen_ghiladi_reeder_svistunenko_2010, title={Compound ES of Dehaloperoxidase Decays via Two Alternative Pathways Depending on the Conformation of the Distal Histidine}, volume={132}, ISSN={0002-7863 1520-5126}, url={http://dx.doi.org/10.1021/ja106620q}, DOI={10.1021/ja106620q}, abstractNote={Dehaloperoxidase (DHP) is a respiratory hemoglobin (Hb) that has been shown to catalyze the conversion of trihalophenols to dihaloquinones in the presence of hydrogen peroxide. Ferric heme states of the resting DHP and the free radical intermediates formed under H2O2 treatment were studied by low-temperature electron paramagnetic resonance spectroscopy in the range of reaction times from 50 ms to 2 min at three different pH values. Two high-spin ferric heme forms were identified in the resting enzyme and assigned to the open and closed conformations of the distal histidine, His55. Two free radicals were found in DHP activated by H2O2: the radical associated with Compound ES (the enzyme with the heme in the oxoferryl state and a radical on the polypeptide chain) has been assigned to Tyr34, and the other radical has been assigned to Tyr38. The Tyr34 radical is formed with a very high relative yield (almost 100% of heme), atypical of other globins. High-performance liquid chromatography analysis of the reaction products showed a pH-dependent formation of covalent heme-to-protein cross-links. The stable DHP Compound RH, formed under H2O2 in the absence of the trihalophenol substrates, is proposed to be a state with the ferric heme covalently cross-linked to Tyr34. A kinetic model of the experimental data suggests that formation of Compound RH and formation of the Tyr38 radical are two alternative routes of Compound ES decay. Which route is taken depends on the conformation of His55: in the less populated closed conformation, the Tyr38 radical is formed, but in the major open conformation, Compound ES decays, yielding Compound RH, a product of safe termination of the two oxidizing equivalents of H2O2 when no substrate is available.}, number={49}, journal={Journal of the American Chemical Society}, publisher={American Chemical Society (ACS)}, author={Thompson, Matthew K. and Franzen, Stefan and Ghiladi, Reza A. and Reeder, Brandon J. and Svistunenko, Dimitri A.}, year={2010}, month={Dec}, pages={17501–17510} }
 @article{cade_dlouhy_medzihradszky_salas-castillo_ghiladi_2010, title={Isoniazid-resistance conferring mutations in Mycobacterium tuberculosis KatG: Catalase, peroxidase, and INH-NADH adduct formation activities}, volume={19}, ISSN={0961-8368 1469-896X}, url={http://dx.doi.org/10.1002/pro.324}, DOI={10.1002/pro.324}, abstractNote={Mycobacterium tuberculosis catalase‐peroxidase (KatG) is a bifunctional hemoprotein that has been shown to activate isoniazid (INH), a pro‐drug that is integral to frontline antituberculosis treatments. The activated species, presumed to be an isonicotinoyl radical, couples to NAD+/NADH forming an isoniazid‐NADH adduct that ultimately confers anti‐tubercular activity. To better understand the mechanisms of isoniazid activation as well as the origins of KatG‐derived INH‐resistance, we have compared the catalytic properties (including the ability to form the INH‐NADH adduct) of the wild‐type enzyme to 23 KatG mutants which have been associated with isoniazid resistance in clinical M. tuberculosis isolates. Neither catalase nor peroxidase activities, the two inherent enzymatic functions of KatG, were found to correlate with isoniazid resistance. Furthermore, catalase function was lost in mutants which lacked the Met‐Tyr‐Trp crosslink, the biogenic cofactor in KatG which has been previously shown to be integral to this activity. The presence or absence of the crosslink itself, however, was also found to not correlate with INH resistance. The KatG resistance‐conferring mutants were then assayed for their ability to generate the INH‐NADH adduct in the presence of peroxide (t‐BuOOH and H2O2), superoxide, and no exogenous oxidant (air‐only background control). The results demonstrate that residue location plays a critical role in determining INH‐resistance mechanisms associated with INH activation; however, different mutations at the same location can produce vastly different reactivities that are oxidant‐specific. Furthermore, the data can be interpreted to suggest the presence of a second mechanism of INH‐resistance that is not correlated with the formation of the INH‐NADH adduct.}, number={3}, journal={Protein Science}, publisher={Wiley}, author={Cade, Christine E. and Dlouhy, Adrienne C. and Medzihradszky, Katalin F. and Salas-Castillo, Saida Patricia and Ghiladi, Reza A.}, year={2010}, month={Mar}, pages={458–474} }
 @article{d’antonio_d’antonio_thompson_bowden_franzen_smirnova_ghiladi_2010, title={Spectroscopic and Mechanistic Investigations of Dehaloperoxidase B fromAmphitrite ornata}, volume={49}, ISSN={0006-2960 1520-4995}, url={http://dx.doi.org/10.1021/bi100407v}, DOI={10.1021/bi100407v}, abstractNote={Dehaloperoxidase (DHP) from the terebellid polychaete Amphitrite ornata is a bifunctional enzyme that possesses both hemoglobin and peroxidase activities. Of the two DHP isoenzymes identified to date, much of the recent focus has been on DHP A, whereas very little is known pertaining to the activity, substrate specificity, mechanism of function, or spectroscopic properties of DHP B. Herein, we report the recombinant expression and purification of DHP B, as well as the details of our investigations into its catalytic cycle using biochemical assays, stopped-flow UV-visible, resonance Raman, and rapid freeze-quench electron paramagnetic resonance spectroscopies, and spectroelectrochemistry. Our experimental design reveals mechanistic insights and kinetic descriptions of the dehaloperoxidase mechanism which have not been previously reported for isoenzyme A. Namely, we demonstrate a novel reaction pathway in which the products of the oxidative dehalogenation of trihalophenols (dihaloquinones) are themselves capable of inducing formation of oxyferrous DHP B, and an updated catalytic cycle for DHP is proposed. We further demonstrate that, unlike the traditional monofunctional peroxidases, the oxyferrous state in DHP is a peroxidase-competent starting species, which suggests that the ferric oxidation state may not be an obligatory starting point for the enzyme. The data presented herein provide a link between the peroxidase and oxygen transport activities which furthers our understanding of how this bifunctional enzyme is able to unite its two inherent functions in one system.}, number={31}, journal={Biochemistry}, publisher={American Chemical Society (ACS)}, author={D’Antonio, Jennifer and D’Antonio, Edward L. and Thompson, Matthew K. and Bowden, Edmond F. and Franzen, Stefan and Smirnova, Tatyana and Ghiladi, Reza A.}, year={2010}, month={Aug}, pages={6600–6616} }
 @article{de serrano_d'antonio_franzen_ghiladi_2010, title={Structure of dehaloperoxidase B at 1.58 A resolution and structural characterization of the AB dimer from Amphitrite ornata}, volume={66}, ISSN={0907-4449}, url={http://dx.doi.org/10.1107/S0907444910004580}, DOI={10.1107/S0907444910004580}, abstractNote={As members of the globin superfamily, dehaloperoxidase (DHP) isoenzymes A and B from the marine annelid Amphitrite ornata possess hemoglobin function, but they also exhibit a biologically relevant peroxidase activity that is capable of converting 2,4,6-trihalophenols to the corresponding 2,6-dihaloquinones in the presence of hydrogen peroxide. Here, a comprehensive structural study of recombinant DHP B, both by itself and cocrystallized with isoenzyme A, using X-ray diffraction is presented. The structure of DHP B refined to 1.58 A resolution exhibits the same distal histidine (His55) conformational flexibility as that observed in isoenzyme A, as well as additional changes to the distal and proximal hydrogen-bonding networks. Furthermore, preliminary characterization of the DHP AB heterodimer is presented, which exhibits differences in the AB interface that are not observed in the A-only or B-only homodimers. These structural investigations of DHP B provide insights that may relate to the mechanistic details of the H(2)O(2)-dependent oxidative dehalogenation reaction catalyzed by dehaloperoxidase, present a clearer description of the function of specific residues in DHP at the molecular level and lead to a better understanding of the paradigms of globin structure-function relationships.}, number={5}, journal={Acta Crystallographica Section D Biological Crystallography}, publisher={International Union of Crystallography (IUCr)}, author={de Serrano, Vesna and D'Antonio, Jennifer and Franzen, Stefan and Ghiladi, Reza A.}, year={2010}, month={Apr}, pages={529–538} }
 @article{serrano_d'antonio_franzen_ghiladi_2010, title={Structure of dehaloperoxidase B at 1.58 angstrom resolution and structural characterization of the AB dimer from Amphitrite ornata}, volume={66}, journal={Acta Crystallographica. Section D, Biological Crystallography}, author={Serrano, V. and D'Antonio, J. and Franzen, S. and Ghiladi, R. A.}, year={2010}, pages={529–538} }
 @article{feducia_dumarieh_gilvey_smirnova_franzen_ghiladi_2009, title={Characterization of Dehaloperoxidase Compound ES and Its Reactivity with Trihalophenols†}, volume={48}, ISSN={0006-2960 1520-4995}, url={http://dx.doi.org/10.1021/bi801916j}, DOI={10.1021/bi801916j}, abstractNote={Dehaloperoxidase (DHP), the oxygen transport hemoglobin from the terebellid polychaete Amphitrite ornata, is the first globin identified to possess a biologically relevant peroxidase activity. DHP has been shown to oxidize trihalophenols to dihaloquinones in a dehalogenation reaction that uses hydrogen peroxide as a substrate. Herein, we demonstrate that the first detectable intermediate following the addition of hydrogen peroxide to ferric DHP contains both a ferryl heme and a tyrosyl radical, analogous to Compound ES of cytochrome c peroxidase. Furthermore, we provide a detailed kinetic description for the reaction of preformed DHP Compound ES with the substrate 2,4,6-trichlorophenol and demonstrate the catalytic competency of this intermediate in generating the product 2,4-dichloroquinone. Using rapid-freeze-quench electron paramagnetic resonance spectroscopy, we detected a g approximately 2.0058 signal confirming the presence of a protein radical in DHP Compound ES. In the absence of substrate, DHP Compound ES evolves to a new species, Compound RH, which is functionally unique to dehaloperoxidase. We propose that this intermediate plays a protective role against heme bleaching. While unreactive toward further oxidation, Compound RH can be reduced and subsequently bind dioxygen, generating oxyferrous DHP, which may represent the catalytic link between peroxidase and oxygen transport activities in this bifunctional protein.}, number={5}, journal={Biochemistry}, publisher={American Chemical Society (ACS)}, author={Feducia, Jeremiah and Dumarieh, Rania and Gilvey, Lauren B. G. and Smirnova, Tatyana and Franzen, Stefan and Ghiladi, Reza A.}, year={2009}, month={Feb}, pages={995–1005} }
 @article{feese_ghiladi_2009, title={Highly efficient in vitro photodynamic inactivation of Mycobacterium smegmatis}, volume={64}, ISSN={1460-2091 0305-7453}, url={http://dx.doi.org/10.1093/jac/dkp278}, DOI={10.1093/jac/dkp278}, abstractNote={OBJECTIVES
Efforts to control tuberculosis (TB) have been hampered by the emergence of multiple-drug resistant strains, necessitating pursuit of alternative approaches to the current antibiotic-based treatments. Herein, we explore the feasibility of photodynamic inactivation (PDI) of mycobacteria.


METHODS
In vitro PDI studies employing Mycobacterium smegmatis as a surrogate for Mycobacterium tuberculosis were performed examining photosensitizer (PS) type, concentration and light dose. M. smegmatis was grown to a concentration of 10(8) colony forming units (cfu) per mL, resuspended in PBS-0.5% Tween-80-containing buffer, incubated with the PS for 5 min and subsequently illuminated with white light (400-700 nm) at a fluence rate of 60 mW/cm(2) for 1, 5, 15 or 30 min (equivalent to 3.4, 18, 54 or 108 J/cm(2)). The percentage survival was determined by the ratio of the colony count from illuminated and non-illuminated control cell suspensions. The PSs examined were 5,10,15,20-tetrakis(1-methyl-4-pyridinyl)porphyrin tetratosylate (TMPyP), 5,10,15,20-tetrakis(4-N,N,N-trimethylanilinium)porphyrin tetrachloride (TNMAP), methylene blue (MB), 5,10,15,20-tetrakis(4-sulphonatophenyl)porphyrin (TSPP), 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin-Pd(II) (TCPP-Pd) and phthalocyanine tetrasulphonic acid (PhCS).


RESULTS
Our best results demonstrate that PDI of M. smegmatis can achieve a noteworthy 5-6 log unit reduction in cfu (99.999% + viable cell eradication) when cationic PSs are employed in the nanomolar concentration range. Anionic PSs did not effectively mediate PDI of mycobacteria due to their inability to associate with the negatively charged mycobacterial cell membrane.


CONCLUSIONS
PDI of M. smegmatis was found to be highly efficient in reducing the number of viable cells in vitro when cationic PSs were employed.}, number={4}, journal={Journal of Antimicrobial Chemotherapy}, publisher={Oxford University Press (OUP)}, author={Feese, Elke and Ghiladi, Reza A.}, year={2009}, month={Aug}, pages={782–785} }
 @article{maiti_woertink_ghiladi_solomon_karlin_2009, title={Molecular Oxygen and Sulfur Reactivity of a Cyclotriveratrylene Derived Trinuclear Copper(I) Complex}, volume={48}, ISSN={0020-1669 1520-510X}, url={http://dx.doi.org/10.1021/ic900975y}, DOI={10.1021/ic900975y}, abstractNote={Our continuing efforts into developing copper coordination chemistry relevant to dioxygen-processing copper proteins has led us to design and synthesize a cyclotriveratrylene (CTV)-based trinucleating ligand, CTV-TMPA, which employs tetradentate tris(2-pyridylmethyl)-amine chelates (TMPA) for their copper ion binding sites. Binding of three copper ions per CTV-TMPA unit was established by various chemical and spectroscopic methods such as UV-vis and resonance Raman (rR) spectroscopies. The following complexes were observed: A tricopper(I) complex [(CTV-TMPA)Cu(I)(3)](3+) (1), a CO adduct [(CTV-TMPA)Cu(I)(3)(CO)(3)](3+) (1-CO; nu(C=O) = 2094 cm(-1)), a triphenylphosphine adduct [(CTV-TMPA)Cu(I)(3)(PPh(3))(3)](3+) (1-PPh(3)), a tricopper(II) complex [(CTV-TMPA)Cu(II)(3)](3+) (1-Ox), and its tris-monochloride or tris-monobromide adducts. Also, introduction of dioxygen to the -80 degrees C solutions of 1 leads to O(2)-adducts, the first example of a synthetic copper complex which can stabilize a mononuclear Cu(II)-superoxo and dinuclear peroxo species simultaneously within one complex {[Cu] = 1.53 mM in THF: (mu-1,2-peroxo complex, lambda(max) = 543 (epsilon 9650) nm): nu(O-O) = 825 ((Delta(18)O(2)) = -47) cm(-1); nu(Cu-O) = 506 ((Delta(18)O(2)) = -26) cm(-1): (superoxo complex, lambda(max) = 427 (epsilon 3150) nm): nu(O-O) = 1129 ((Delta(18)O(2)) = -60) cm(-1); nu(Cu-O) = 463 ((Delta(18)O(2)) = -27) cm(-1)}. Elemental sulfur reacts reversibly with 1 leading to a (proposed) hexanuclear species [{(CTV-TMPA)Cu(II)(3)}(2)(mu-1,2-S(2)(2-))(3)](6+) (1-S) {lambda(max) = 544 (epsilon 7270) nm}, possessing one dicopper(II)-disulfide structural type: {THF solvent) nu(S-S) = 489 ((Delta(34)S) = -10) cm(-1); nu(Cu-S) = 307 ((Delta(34)S) = -5) cm(-1)}. Derivation of spectroscopic, structural, and chemical conclusions were aided by the study of a close mononuclear analogue with one pyridyl group of the TMPA parent possessing a 6-CH(2)OCH(3) substituent, this being part of the CTV-TMPA architecture.}, number={17}, journal={Inorganic Chemistry}, publisher={American Chemical Society (ACS)}, author={Maiti, Debabrata and Woertink, Julia S. and Ghiladi, Reza A. and Solomon, Edward I. and Karlin, Kenneth D.}, year={2009}, month={Sep}, pages={8342–8356} }
 @article{ghiladi_dumarieh_thompson_wang_smirnova_franzen_2009, title={Spectroscopic Probes of the Reactive Intermediates of Dehaloperoxidase from Amphitrite ornata}, volume={96}, ISSN={0006-3495}, url={http://dx.doi.org/10.1016/j.bpj.2008.12.2240}, DOI={10.1016/j.bpj.2008.12.2240}, abstractNote={The enzyme intermediates of dehaloperoxidase (DHP) from the marine worm Amphitrite ornata are unique within both the globin and cytochrome c peroxidase superfamilies. DHP has been shown to oxidize trihalophenols to dihaloquinones in a dehalogenation reaction that uses hydrogen peroxide as a substrate. We show that the initially formed heme intermediate in this reaction is not Compound I as is often the case in peroxidases, but rather is a combination of Compound II and a tyrosyl radical that has similarity to the Compound ES intermediate of cytochrome c peroxidase. Using stopped-flow UV-visible spectroscopy, we provide a detailed kinetic description for the reaction of pre-formed DHP Compound II and tyrosyl radical with the substrate 2,4,6-trichlorophenol, and demonstrate the catalytic competency of this intermediate in generating the product 2,4-dichloroquinone. Furthermore, using rapid-freeze-quench electron paramagnetic resonance spectroscopy, we detected a signal at g ≈ 2.0058, confirming the presence of a protein radical in DHP Compound II, and assign it as a tyrosyl radical based upon mutagenesis studies and structural arguments. In the absence of a halophenol substrate, the DHP Compound II + tyrosyl radical intermediate decomposes to a new and significantly less active species, termed Compound RH, which is unique to dehaloperoxidase. We propose that this intermediate plays a protective role against heme bleaching. While unreactive toward further oxidation, Compound RH can be reduced and subsequently bind dioxygen, generating oxyferrous DHP, which may represent the catalytic link between the peroxidase and oxygen-transport activities in this bifunctional protein.}, number={3}, journal={Biophysical Journal}, publisher={Elsevier BV}, author={Ghiladi, Reza A. and Dumarieh, Rania and Thompson, Matthew and Wang, Zao and Smirnova, Tatyana and Franzen, Stefan}, year={2009}, month={Feb}, pages={437a} }
 @misc{ghiladi_2008, title={Book Review of Organic Synthesis with Enzymes in Non-Aqueous Media}, volume={130}, ISSN={0002-7863 1520-5126}, url={http://dx.doi.org/10.1021/ja807826g}, DOI={10.1021/ja807826g}, abstractNote={ADVERTISEMENT RETURN TO ISSUEPREVBook ReviewNEXTBook Review of Organic Synthesis with Enzymes in Non-Aqueous MediaReza A. GhiladiView Author Information North Carolina State UniversityCite this: J. Am. Chem. Soc. 2008, 130, 45, 15218–15219Publication Date (Web):October 15, 2008Publication History Received3 October 2008Published online15 October 2008Published inissue 12 November 2008https://doi.org/10.1021/ja807826gCopyright © 2008 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views254Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (71 KB) Get e-AlertsSUBJECTS:Biocatalysis,Organic synthesis,Peptides and proteins,Solvents,Stereoselectivity Get e-Alerts}, number={45}, journal={Journal of the American Chemical Society}, publisher={American Chemical Society (ACS)}, author={Ghiladi, Reza A.}, year={2008}, month={Nov}, pages={15218–15219} }
 @article{ghiladi_chufán_del río_solomon_krebs_huynh_huang_moënne-loccoz_kaderli_honecker_et al._2007, title={Further Insights into the Spectroscopic Properties, Electronic Structure, and Kinetics of Formation of the Heme−Peroxo−Copper Complex [(F8TPP)FeIII−(O22-)−CuII(TMPA)]+}, volume={46}, ISSN={0020-1669 1520-510X}, url={http://dx.doi.org/10.1021/ic061726k}, DOI={10.1021/ic061726k}, abstractNote={In the further development and understanding of heme−copper O2-reduction chemistry inspired by the active-site chemistry in cytochrome c oxidase, we describe a dioxygen adduct, [(F8TPP)FeIII−(O22-)−CuII(TMPA)](ClO4) (3), formed by addition of O2 to a 1:1 mixture of the porphyrinate−iron(II) complex (F8TPP)FeII (1a) {F8TPP = tetrakis(2,6-difluorophenyl)porphyrinate dianion} and the copper(I) complex [(TMPA)CuI(MeCN)](ClO4) (1b) {TMPA = tris(2-pyridylmethyl)amine}. Complex 3 forms in preference to heme-only or copper-only binuclear products, is remarkably stable {t1/2 (RT; MeCN) ≈ 20 min; λmax = 412 (Soret), 558 nm; EPR silent}, and is formulated as a peroxo complex on the basis of manometry {1a/1b/O2 = 1:1:1}, MALDI-TOF mass spectrometry {16O2, m/z 1239 [(3 + MeCN)+]; 18O2, m/z 1243}, and resonance Raman spectroscopy {ν(O-O) = 808 cm-1; Δ16O2/18O2 = 46 cm-1; Δ16O2/16/18O2 = 23 cm-1}. Consistent with a μ-η2:η1 bridging peroxide ligand, two metal−O stretching frequencies are observed {ν(Fe-O) = 533 cm-1, ν(F...}, number={10}, journal={Inorganic Chemistry}, publisher={American Chemical Society (ACS)}, author={Ghiladi, Reza A. and Chufán, Eduardo E. and del Río, Diego and Solomon, Edward I. and Krebs, Carsten and Huynh, Boi Hanh and Huang, Hong-wei and Moënne-Loccoz, Pierre and Kaderli, Susan and Honecker, Marcus and et al.}, year={2007}, month={May}, pages={3889–3902} }
 @article{ghiladi_medzihradszky_rusnak_ortiz de montellano_2005, title={Correlation between Isoniazid Resistance and Superoxide Reactivity in Mycobacterium tuberculosis KatG}, volume={127}, ISSN={0002-7863 1520-5126}, url={http://dx.doi.org/10.1021/ja054366t}, DOI={10.1021/ja054366t}, abstractNote={Isoniazid is an antituberculosis prodrug that requires activation by the catalase-peroxidase (KatG) of Mycobacterium tuberculosis. The activated species, presumed to be an isonicotinoyl radical, couples to NADH forming an isoniazid-NADH adduct that ultimately confers antitubercular activity. We have compared the catalytic properties of three KatGs associated with isoniazid resistance (resistance mutation KatGs, (RM)KatGs: R104L, H108Q, S315T) to wild-type enzyme and two additional lab mutations (wild-type phenotype KatGs, (WTP)KatGs: WT KatG, Y229F, R418L). Neither catalase nor peroxidase activities, nor the presence/absence of the Met-Tyr-Trp cross-link (as probed by LC/MS on tryptic digests of the protein), exhibited any correlation with isoniazid resistance. The yields of isoniazid-NADH adduct formed were determined to be 1-5, 4-12, and 20-70-fold greater for the (WTP)KatGs than the (RM)KatGs for the compound I, II, and III pathways, respectively, strongly suggesting a role for oxyferrous KatG (supported by superoxide consumption measurements) that correlates with drug resistance. Stopped-flow UV-visible spectroscopic studies revealed that all KatGs were capable of forming both compound II and III intermediates. Rates of compound II decay were accelerated 4-12-fold in the presence of isoniazid (vs absence) for the (WTP)KatGs but were unaffected by the drug for the (RM)KatGs. A mechanism for isoniazid resistance which accounts for the observed reactivity for each of the compound I, II, and III intermediates is proposed and suggests that the compound III pathway may be the primary factor in determining overall isoniazid resistance by specific KatG mutants, with secondary contributions arising from the compound I and II pathways.}, number={38}, journal={Journal of the American Chemical Society}, publisher={American Chemical Society (ACS)}, author={Ghiladi, Reza A. and Medzihradszky, Katalin F. and Rusnak, Frank M. and Ortiz de Montellano, Paul R.}, year={2005}, month={Sep}, pages={13428–13442} }
 @article{ghiladi_medzihradszky_ortiz de montellano_2005, title={Role of the Met−Tyr−Trp Cross-Link inMycobacterium tuberculosis Catalase-Peroxidase (KatG) As Revealed by KatG(M255I)}, volume={44}, ISSN={0006-2960 1520-4995}, url={http://dx.doi.org/10.1021/bi051463q}, DOI={10.1021/bi051463q}, abstractNote={Catalase-peroxidases (KatGs) are bifunctional enzymes possessing both catalase and peroxidase activities. Four crystal structures of different KatGs revealed the presence of a novel Met-Tyr-Trp cross-link which has been suggested to impart catalatic activity to the KatGs. To decipher the individual roles of the two cross-links in the Met-Tyr-Trp adduct, we have focused on recombinant Mycobacterium tuberculosis KatG(M255I). UV-visible spectroscopic and mass spectrometric studies of the peptide fragments resulting from tryptic digestion of KatG(M255I) confirmed the presence of the single Tyr-Trp cross-link, as well as a 2e- oxidized form which is postulated to be an intermediate generated during Met-Tyr-Trp cross-link formation. KatG(M255I) lacking the Tyr-Trp cross-link was also prepared, and incubation with peroxyacetic acid, but not 2-methyl-1-phenyl-2-propyl hydroperoxide, resulted in complete formation of the Tyr-Trp cross-link. A mechanism for Tyr-Trp autocatalytic formation by KatG compound I is proposed from these studies. Optical stopped-flow studies with KatG(M255I) were performed, allowing characterization of compounds I, II, and III. Interestingly, two compound II intermediates were identified: (KatG*)(Por)Fe(III)-OH, where KatG* represents a protein-based radical, and oxoferryl (KatG)(Por)Fe(IV)=O. Insight into the contributions of the individual Tyr-Trp and Met-Tyr cross-links to catalase activity is presented, as is the overall contribution of the Met-Tyr-Trp cross-link to the structure-function-spectroscopy relationship and catalase-peroxidase mechanism in KatG.}, number={46}, journal={Biochemistry}, publisher={American Chemical Society (ACS)}, author={Ghiladi, Reza A. and Medzihradszky, Katalin F. and Ortiz de Montellano, Paul R.}, year={2005}, month={Nov}, pages={15093–15105} }
 @article{ghiladi_knudsen_medzihradszky_ortiz de montellano_2005, title={The Met-Tyr-Trp Cross-link in Mycobacterium tuberculosis Catalase-peroxidase (KatG)}, volume={280}, ISSN={0021-9258 1083-351X}, url={http://dx.doi.org/10.1074/jbc.m502486200}, DOI={10.1074/jbc.M502486200}, abstractNote={Catalase-peroxidases (KatG) are bifunctional enzymes possessing both catalase and peroxidase activities. Three crystal structures of different KatGs revealed the presence of a novel Met-Tyr-Trp cross-link that has been suggested to impart catalatic activity to the KatGs. High-performance liquid chromatographic separation of the peptide fragments resulting from tryptic digestion of recombinant Mycobacterium tuberculosis WT KatG identified a peptide with unusual UV-visible spectroscopic features attributable to the Met255-Tyr229-Trp107 cross-link, whose structure was confirmed by mass spectrometry. WT KatG lacking the Met-Tyr-Trp cross-link was prepared, making possible studies of its formation under oxidizing conditions that generate either compound I (peroxyacetic acid, PAA) or compound II (2-methyl-1-phenyl-2-propyl hydroperoxide, MPPH). Incubation of this “cross-link-free” WT KatG with PAA revealed complete formation of the Met-Tyr-Trp structure after six equivalents of peracid were added, whereas MPPH was unable to promote cross-link formation. A mechanism for Met-Tyr-Trp autocatalytic formation by KatG compound I is proposed from these studies. Optical stopped-flow studies of WT KatG and KatG(Y229F), a mutant in which the cross-link cannot be formed, were performed with MPPH and revealed an unusual compound II spectrum for WT KatG, best described as (P·)FeIII, where P· represents a protein-based radical. This contrasts with the oxoferryl compound II spectrum observed for KatG(Y229F) under identical conditions. The structure-function-spectroscopy relationship in KatG is discussed with relevance to the role that the Met-Tyr-Trp cross-link plays in the catalase-peroxidase mechanism.}, number={24}, journal={Journal of Biological Chemistry}, publisher={American Society for Biochemistry & Molecular Biology (ASBMB)}, author={Ghiladi, Reza A. and Knudsen, Giselle M. and Medzihradszky, Katalin F. and Ortiz de Montellano, Paul R.}, year={2005}, month={Apr}, pages={22651–22663} }
 @article{ghiladi_huang_mo�nne-loccoz_stasser_blackburn_woods_cotter_incarvito_rheingold_karlin_2004, title={Heme-copper/dioxygen adduct formation relevant to cytochrome c oxidase: spectroscopic characterization of [(6L)FeIII-(O22?)-CuII]+}, volume={10}, ISSN={0949-8257 1432-1327}, url={http://dx.doi.org/10.1007/s00775-004-0609-1}, DOI={10.1007/s00775-004-0609-1}, abstractNote={In the further development and understanding of heme-copper dioxygen reactivity relevant to cytochrome c oxidase O(2)-reduction chemistry, we describe a high-spin, five-coordinate dioxygen (peroxo) adduct of an iron(II)-copper(I) complex, [((6)L)Fe(II)Cu(I)](BArF(20)) (1), where (6)L is a tetraarylporphyrinate with a tethered tris(2-pyridylmethyl)amine chelate for copper. Reaction of 1 with O(2) in MeCN affords a remarkably stable [t(1/2) (rt; MeCN) approximately 60 min] adduct, [((6)L)Fe(III)-(O(2) (2-))-Cu(II)](+) (2) [EPR silent; lambda(max)=418 (Soret), 561 nm], formulated as a peroxo complex based on manometry (1:O(2)=1:1; spectrophotometric titration, -40 degrees C, MeCN), mass spectrometry {MALDI-TOF-MS: (16)O(2), m/z 1191 ([((6)L)Fe(III)-((16)O(2) (2-))-Cu(II)](+)); (18)O(2), m/z 1195}, and resonance Raman spectroscopy (nu((O-O))=788 cm(-1); Delta(16)O(2)/(18)O(2)=44 cm(-1); Delta(16)O(2)/(16/18)O(2)=22 cm(-1)). (1)H and (2)H NMR spectroscopy (-40 degrees C, MeCN) reveals that 2 is the first heme-copper peroxo complex which is high-spin, with downfield-shifted pyrrole resonances (delta(pyrrole)=75 ppm, s, br) and upfield shifted peaks at delta= -22, -35, and -40 ppm, similar to the pattern observed for the mu-oxo complex [((6)L)Fe(III)-O-Cu(II)](BAr(F)) (3) (known S=2 system, antiferromagnetically coupled high-spin Fe(III) and Cu(II)). The corresponding magnetic moment measurement (Evans method, CD(3)CN, -40 degrees C) also confirms the S=2 spin state, with mu(B)=4.9. Structural insights were obtained from X-ray absorption spectroscopy, showing Fe-O (1.83 A) and Cu-O (1.882 A) bonds, and an Fe...Cu distance of 3.35(2) A, suggestive of a mu-1,2-peroxo ligand present in 2. The reaction of 2 with cobaltocene gives 3, differing from the observed full reduction seen with other heme-Cu peroxo complexes. Finally, thermal decomposition of 2 yields 3, with concomitant release of 0.5 mol O(2) per mol 2, as confirmed quantitatively by an alkaline pyrogallol dioxygen scavenging solution.}, number={1}, journal={JBIC Journal of Biological Inorganic Chemistry}, publisher={Springer Science and Business Media LLC}, author={Ghiladi, Reza A. and Huang, Hong-wei and Mo�nne-Loccoz, Pierre and Stasser, Jay and Blackburn, Ninian J. and Woods, Amina S. and Cotter, Robert J. and Incarvito, Christopher D. and Rheingold, Arnold L. and Karlin, Kenneth D.}, year={2004}, month={Dec}, pages={63–77} }
 @article{ghiladi_cabelli_ortiz de montellano_2004, title={Superoxide Reactivity of KatG:  Insights into Isoniazid Resistance Pathways in TB}, volume={126}, ISSN={0002-7863 1520-5126}, url={http://dx.doi.org/10.1021/ja031728t}, DOI={10.1021/ja031728t}, abstractNote={To gain insight into the mechanism of INH activation by KatG and to understand how resistance is conferred by the single active-site point mutation of KatG(S315T), we have employed pulse radiolysis as the means to initiate a catalytic pathway capable of mimicking the in vivo oxidation of isoniazid (INH). Radiolysis of a solution containing WT KatG revealed two intermediates: compound III (oxyferrous KatG) [415 (Soret), 545, 580 nm] formed [k1 = (4.47 +/- 0.91) x 105 M-1 s-1] in the absence of INH and compound II (410 (Soret), 540, 575 nm) formed [k1 = (4.43 +/- 0.69) x 105 M-1 s-1] in the presence of INH, with a comparison of the rates suggesting that compound III (rate-limiting) precedes compound II formation. By contrast, radiolysis of KatG(S315T) only led to compound III formation, whether INH was present [k1 = (4.72 +/- 0.99) x 105 M-1 s-1] or not [k1 = (4.51 +/- 1.38) x 105 M-1 s-1]. HPLC studies to determine the rates of INH-NADH adduct formation (an inhibitor of InhA) as catalyzed by KatG were also performed employing various oxidants: air [WT: (7.18 +/- 1.25) x 10-4, S315T: (0.74 +/- 0.39) x 10-4], superoxide (SOTS-1) [WT: (9.22 +/- 1.10) x 10-4, S315T: not detected], and tert-butylhydroperoxide [WT: (20.5 +/- 1.13) x 10-4, S315T: (10.15 +/- 0.19) x 10-4]. Taken together, the results from the pulse radiolysis work as well as the InhA inhibitor studies allow us to propose a mechanism capable of correlating the inability for the oxyferrous intermediate of KatG(S315T) to oxidize ("activate") INH to the suppressed formation of the INH-NADH adduct, thereby leading to INH resistance in Mycobacterium tuberculosis.}, number={15}, journal={Journal of the American Chemical Society}, publisher={American Chemical Society (ACS)}, author={Ghiladi, Reza A. and Cabelli, Diane E. and Ortiz de Montellano, Paul R.}, year={2004}, month={Apr}, pages={4772–4773} }
 @article{kretzer_ghiladi_lebeau_liang_karlin_2003, title={Synthesis and Characterization of Reduced Heme and Heme/Copper Carbonmonoxy Species}, volume={42}, ISSN={0020-1669 1520-510X}, url={http://dx.doi.org/10.1021/ic020521i}, DOI={10.1021/ic020521i}, abstractNote={Carbon monoxide readily binds to heme and copper proteins, acting as a competitive inhibitor of dioxygen. As such, CO serves as a probe of protein metal active sites. In our ongoing efforts to mimic the active site of cytochrome c oxidase, reactivity toward carbon monoxide offers a unique opportunity to gain insight into the binding and spectroscopic characteristics of synthetic model compounds. In this paper, we report the synthesis and characterization of CO-adducts of ((5/6)L)Fe(II), [((5/6)L)Fe(II)...Cu(I)](B(C(6)F(5))(4)), and [(TMPA)Cu(I)(CH(3)CN)](B(C(6)F(5))(4)), where TMPA = tris(2-pyridylmethyl)amine and (5/6)L = a tetraarylporphyrinate tethered in either the 5-position ((5)L) or 6-position ((6)L) to a TMPA copper binding moiety. Reaction of ((5/6)L)Fe(II) [in THF (293 K): UV-vis 424 (Soret), 543-544 nm; (1)H NMR delta(pyrrole) 52-59 ppm (4 peaks); (2)H NMR (from ((5)L-d(8))Fe(II)) delta(pyrrole) 53.3, 54.5, 55.8, 56.4 ppm] with CO in solution at RT yielded ((5/6)L)Fe(II)-CO [in THF (293 K): UV-vis 413-414 (Soret), 532-533 nm; IR nu(CO)(Fe) 1976-1978 cm(-1); (1)H NMR delta(pyrrole) 8.8 ppm; (2)H NMR (from ((5)L-d(8))Fe(II)-CO) delta(pyrrole) 8.9 ppm; (13)C NMR delta((CO)Fe) 206.8-207.1 ppm (2 peaks)]. Experiments repeated in acetonitrile, acetone, toluene, and dichloromethane showed similar spectroscopic data. Binding of CO resulted in a change from five-coordinate, high-spin Fe(II) to six-coordinate, low-spin Fe(II), as evidenced by the upfield shift of the pyrrole resonances to the diamagnetic region ((1)H and (2)H NMR spectra). Addition of CO to [((5/6)L)Fe(II)...Cu(I)](B(C(6)F(5))(4)) [in THF (293 K): UV-vis ((6)L only) 424 (Soret), 546 nm; (1)H NMR delta(pyrrole) 54-59 ppm (multiple peaks); (2)H NMR (from [((5)L-d(8))Fe(II).Cu(I)](B(C(6)F(5))(4))) delta(pyrrole) 53.4 ppm (br)] gave the bis-carbonyl adduct [((5/6)L)Fe(II)-CO...Cu(I)-CO](B(C(6)F(5))(4)) [in THF (293 K): UV-vis ((6)L only) 413 (Soret), 532 nm; IR nu(CO)(Fe) 1971-1973 cm(-1), nu(CO)(Cu) 2091-2093 cm(-1), approximately 2070(sh) cm(-1); (1)H NMR delta(pyrrole) 8.7-8.9 ppm; (2)H NMR (from [((5)L-d(8))Fe(II)-CO...Cu(I)-CO](B(C(6)F(5))(4))) delta(pyrrole) 8.9 ppm; (13)C NMR delta((CO)Fe) 206.8-208.1 ppm (2 peaks), delta((CO)Cu) 172.4 ((5)L), 178.2 ((6)L) ppm]. Experiments in acetonitrile, acetone, and toluene exhibited spectral features similar to those reported. The [((5/6)L)Fe(II)-CO.Cu(I)-CO](B(C(6)F(5))(4)) compounds yielded (CO)(Fe) spectra analogous to those seen for ((5/6)L)Fe(II)-CO and (CO)(Cu) spectra similar to those seen for [(TMPA)Cu(I)-CO](B(C(6)F(5))(4)) [in THF (293 K): IR nu(CO)(Cu) 2091 cm(-1), approximately 2070(sh) cm(-1); (13)C NMR delta((CO)Cu) 180.3 ppm]. Additional IR studies were performed in which the [((5)L)Fe(II)-CO...Cu(I)-CO](B(C(6)F(5))(4)) in solution was bubbled with argon in an attempt to generate the iron-only mono-carbonyl [((5)L)Fe(II)-CO.Cu(I)](B(C(6)F(5))(4)) species; in coordinating solvent or with axial base present, decreases in characteristic IR-band intensities revealed complete loss of CO from copper and variable loss of CO from the heme.}, number={9}, journal={Inorganic Chemistry}, publisher={American Chemical Society (ACS)}, author={Kretzer, Ryan M. and Ghiladi, Reza A. and Lebeau, Estelle L. and Liang, Hong-Chang and Karlin, Kenneth D.}, year={2003}, month={May}, pages={3016–3025} }
 @article{thompson_kretzer_lebeau_scaltrito_ghiladi_lam_rheingold_karlin_meyer_2003, title={Synthesis, Characterization, and Laser Flash Photolysis Reactivity of a Carbonmonoxy Heme Complex}, volume={42}, ISSN={0020-1669 1520-510X}, url={http://dx.doi.org/10.1021/ic026307b}, DOI={10.1021/ic026307b}, abstractNote={We present here the synthesis, characterization, and flash photolysis study of [(F(8)TPP)Fe(II)(CO)(THF)] (1) [F(8)TPP = tetrakis(2,6-difluorophenyl)porphyrinate(2-)]. Complex 1 crystallizes from THF/heptane solvent system as a tris-THF solvate, [(F(8)TPP)Fe(II)(CO)(THF)].3THF (1.3THF), with ferrous ion in the porphyrin plane (C(61)H(52)F(8)FeN(4)O(5); a = 11.7908(2) A, b = 20.4453(2) A, c = 39.9423(3), alpha = 90 degrees, beta = 90 degrees, gamma = 90 degrees; orthorhombic, P2(1)2(1)2(1), Z = 8; Fe-N(4)(av) = 2.00 A; N-Fe-N (all) = 90.0 degrees ). This complex (as 1.THF) has also been characterized by (1)H NMR [six-coordinate, low-spin heme; CD(3)CN, RT, delta 8.82 (s, pyrrole-H, 8H), 7.89 (s, para-phenyl-H, 8H), 7.46 (s, meta-phenyl-H, 4H), 3.58 (s, THF, 8H), 1.73 (s, THF, 8H)], (2)H NMR (pyrrole-deuterated analogue) [(F(8)TPP-d(8))Fe(II)(CO)(THF)] [THF, RT, delta 8.78 ppm (s, pyrrole-D)], (13)C NMR (on (13)CO-enriched adduct) [THF-d(8), RT, delta 206.5 ppm; CD(2)Cl(2), RT, delta 206.1 ppm], UV-vis [THF, RT, lambda(max), 411 (Soret), 525 nm], and IR [293 K, solution, nu(CO) 1979 cm(-)(1) (THF), 1976 cm(-)(1) (acetone), 1982 cm(-)(1) (CH(3)CN)] spectroscopies. In order to more fully understand the intricacies of solvent-ligand binding (as compared to CO rebinding to the photolyzed heme), we have also synthesized the bis-THF adduct [(F(8)TPP)Fe(II)(THF)(2)]. Complex 2 also crystallizes from THF/heptane solvent system as a bis-THF solvate, [(F(8)TPP)Fe(II)(THF)(2)].2THF (2.2THF), with ferrous iron in the porphyrin plane (C(60)H(52)F(8)FeN(4)O(4); a = 21.3216(3) A, b = 12.1191(2) A, c = 21.0125(2) A, alpha = 90 degrees, beta = 105.3658(5) degrees, gamma = 90 degrees; monoclinic, C2/c, Z = 4; Fe-N(4)(av) = 2.07 A; N-Fe-N (all) = 90.0 degrees ). Further characterization of 2 includes UV-vis [THF, lambda(max), 421 (Soret), 542 nm] and (1)H NMR [six-coordinate, high spin heme; THF-d(8), RT, delta 56.7 (s, pyrrole-H, 8H), 8.38 (s, para-phenyl-H, 8H), 7.15 (s, meta-phenyl-H, 4H)] spectroscopies. Flash photolysis studies employing 1 were able to resolve the CO rebinding kinetics in both THF and cyclohexane solvents. In CO saturated THF [[CO] approximately 5 mM] and at [1] congruent with 5 microM, the conversion of [(F(8)TPP)Fe(II)(THF)(2)] (produced after photolytic displacement of CO) to [(F(8)TPP)Fe(II)(CO)(THF)] was monoexponential, with k(obs) = 1.6 (+/-0.2) x 10(4) s(-)(1). Reduction in [CO] by vigorous Ar purging gave k(obs) congruent with 10(3) s(-)(1) in cyclohexane. The study presented in this report lays the foundation for applying fast-time scale studies based on CO flash photolysis to the more complicated heterobimetallic heme/Cu systems.}, number={17}, journal={Inorganic Chemistry}, publisher={American Chemical Society (ACS)}, author={Thompson, David W. and Kretzer, Ryan M. and Lebeau, Estelle L. and Scaltrito, Donald V. and Ghiladi, Reza A. and Lam, Kin-Chung and Rheingold, Arnold L. and Karlin, Kenneth D. and Meyer, Gerald J.}, year={2003}, month={Aug}, pages={5211–5218} }
 @article{ghiladi_karlin_2002, title={Low-Temperature UV−Visible and NMR Spectroscopic Investigations of O2 Binding to (6L)FeII, a Ferrous Heme Bearing Covalently Tethered Axial Pyridine Ligands}, volume={41}, ISSN={0020-1669 1520-510X}, url={http://dx.doi.org/10.1021/ic0103547}, DOI={10.1021/ic0103547}, abstractNote={In this report, we describe the reversible dioxygen reactivity of ((6)L)Fe(II) (1) [(6)L = partially fluorinated tetraphenylporphyrin with covalently appended TMPA moiety; TMPA = tris(2-pyridylmethyl)amine] using a combination of low-temperature UV-vis and multinuclear ((1)H and (2)H) NMR spectroscopies. Complex 1, or its pyrrole-deuterated analogue ((6)L-d(8))Fe(II) (1-d(8)), exhibits downfield shifted pyrrole resonances (delta 28-60 ppm) in all solvents utilized [CH(2)Cl(2), (CH(3))(2)C(O), CH(3)CN, THF], indicative of a five-coordinate high-spin ferrous heme, even when there is no exogenous axial solvent ligand present (i.e., in methylene chloride). Furthermore, ((6)L)Fe(II) (1) exhibits non-pyrrolic upfield and downfield shifted peaks in CH(2)Cl(2), (CH(3))(2)C(O), and CH(3)CN solvents, which we ascribed to resonances arising from the intra- or intermolecular binding of a TMPA-pyridyl arm to the ferrous heme. Upon exposure to dioxygen at 193 K in methylene chloride, ((6)L)Fe(II) (1) [UV-vis: lambda(max) = 433 (Soret), 529 (sh), 559 nm] reversibly forms a dioxygen adduct [UV-vis: lambda(max) = 422 (Soret), 542 nm], formulated as the six-coordinate low-spin [delta(pyrrole) 9.3 ppm, 193 K] heme-superoxo complex ((6)L)Fe(III)-(O(2)(-)) (2). The coordination of the tethered pyridyl arm to the heme-superoxo complex as axial base ligand is suggested. In coordinating solvents such as THF, reversible oxygenation (193 K) of ((6)L)Fe(II) (1) [UV-vis: lambda(max) = 424 (Soret), 542 nm] also occurs to give a similar adduct ((6)L)Fe(III)-(O(2)(-)) (2) [UV-vis: lambda(max) = 418 (Soret), 537 nm. (2)H NMR: delta(pyrrole) 8.9 ppm, 193 K]. Here, we are unable to distinguish between a bound solvent ligand or tethered pyridyl arm as axial base ligand. In all solvents, the dioxygen adducts decompose (thermally) to the ferric-hydroxy complex ((6)L)Fe(III)-OH (3) [UV-vis: lambda(max) = 412-414 (Soret), 566-575 nm; approximately delta(pyrrole) 120 ppm at 193 K]. This study on the O(2)-binding chemistry of the heme-only homonuclear ((6)L)Fe(II) (1) system lays the foundation for a more complete understanding of the dioxygen reactivity of heterobinuclear heme-Cu complexes, such as [((6)L)Fe(II)Cu(I)](+), which are models for cytochrome c oxidase.}, number={9}, journal={Inorganic Chemistry}, publisher={American Chemical Society (ACS)}, author={Ghiladi, Reza A. and Karlin, Kenneth D.}, year={2002}, month={May}, pages={2400–2407} }
 @article{ghiladi_kretzer_guzei_rheingold_neuhold_hatwell_zuberbühler_karlin_2001, title={(F8TPP)FeII/O2 Reactivity Studies {F8TPP = Tetrakis(2,6-difluorophenyl)porphyrinate(2−)}:  Spectroscopic (UV−Visible and NMR) and Kinetic Study of Solvent-Dependent (Fe/O2= 1:1 or 2:1) Reversible O2-Reduction and Ferryl Formation}, volume={40}, ISSN={0020-1669 1520-510X}, url={http://dx.doi.org/10.1021/ic0105866}, DOI={10.1021/ic0105866}, abstractNote={In this report, we describe in detail the O(2)-binding chemistry of the metalloporphyrin (F(8)TPP)Fe(II) (1). This complex was synthesized from aqueous dithionite reduction of (F(8)TPP)Fe(III)-Cl (X-ray structure reported: C(55)H(36)ClF(8)FeN(4)O; a = 13.6517(2) A, b = 13.6475(2) A, c = 26.3896(4), alpha = 90 degrees, beta = 89.9776(4) degrees, gamma = 90 degrees; monoclinic, P2(1)/c, Z = 4). Complex 1 crystallizes from toluene/heptane solvent system as a bis(toluene) solvate, (F(8)TPP)Fe(II).(C(7)H(8))(2), with ferrous ion in the porphyrin plane (C(58)H(36)F(8)FeN(4); a = 20.9177(2) A, b = 11.7738(2) A, c = 19.3875(2), alpha = 90 degrees, beta = 108.6999(6) degrees, gamma = 90 degrees; monoclinic, C2/c, Z = 4; Fe-N(4)(av) = 2.002 A; N-Fe-N (all) = 90.0 degrees ). Close metal-arene contacts are also observed at 3.11-3.15 A. Upon oxygenation of 1 at 193 K in coordinating solvents, UV-visible and (2)H and (19)F NMR spectroscopies revealed the presence of a reversibly formed dioxygen adduct, formulated as the heme-superoxo complex (S)(F(8)TPP)Fe(III)-(O(2)(-)) (2) (S = solvent) [(i) tetrahydrofuran (THF) solvent: UV-visible, 416 (Soret), 536 nm; (2)H NMR: delta(pyrrole) 8.9 ppm; (ii) EtCN solvent: UV-visible, 414 (Soret), 536 nm; (iii) acetone solvent: UV-visible, 416 (Soret), 537 nm; (2)H NMR: delta(pyrrole) 8.9 ppm]. Dioxygen-uptake manometry (THF, 193 K) revealed an O(2):1 oxygenation stoichiometry of 1.02:1, consistent with the heme-superoxo formulation of 2. Stopped-flow UV-visible spectrophotometry studies of the (F(8)TPP)Fe(II) (1)/O(2) reaction in EtCN and THF solvents were able to provide kinetic and thermodynamic insight into the reversible formation of 2 [(i) EtCN: Delta H degrees = -40 +/- 5 kJ/mol; Delta S degrees = -105 +/- 23 J/(K mol); k(1) = (5.57 +/- 0.04) x 10(3) M(-)(1) s(-)(1) (183 K); Delta H(++) = 38.6 +/- 0.2 kJ/mol; Delta S(++) = 42 +/- 1 J/(K mol); (ii) THF: Delta H* = -37.5 +/- 0.4 kJ/mol; Delta S* = -109 +/- 2 J/(K mol)]. The (F(8)TPP)Fe(II) (1)/O(2) reaction was also examined at reduced temperatures in noncoordinating solvents (toluene, CH(2)Cl(2)), where UV-visible and (2)H and (19)F NMR spectroscopies also revealed the presence of a reversibly formed adduct, formulated as the peroxo-bridged dinuclear complex [(F(8)TPP)Fe(III)](2)-(O(2)(2)(-)) (3) [CH(2)Cl(2): UV-visible, 414 (Soret), 535 nm; (2)H NMR, delta(pyrrole) 17.5 ppm]. Dioxygen-uptake spectrophotometric titrations revealed a stoichiometry of 2 (F(8)TPP)Fe(II) (1) per O(2) upon full formation of 3. Addition of a nitrogenous base, 4-(dimethylamino)pyridine, to a cold solution of 3 in dichloromethane gave rapid formation of the iron(IV)-oxo ferryl species (DMAP)(F(8)TPP)Fe(IV)==O (4), based upon UV-visible [417 (Soret), 541 nm] and (2)H NMR (delta(pyrrole) = 3.5 ppm) spectroscopic characterization. These detailed investigations into the O(2)-adducts and "ferryl" species formed from (F(8)TPP)Fe(II) (1) may be potentially important for a full understanding of our ongoing heme-copper oxidase model studies, which employ 1 or similar "tethered" (i.e., covalently attached Cu-chelate) porphyrin analogues in heme/Cu heterobinuclear systems.}, number={23}, journal={Inorganic Chemistry}, publisher={American Chemical Society (ACS)}, author={Ghiladi, Reza A. and Kretzer, Ryan M. and Guzei, Ilia and Rheingold, Arnold L. and Neuhold, Yorck-Michael and Hatwell, Karen R. and Zuberbühler, Andreas D. and Karlin, Kenneth D.}, year={2001}, month={Nov}, pages={5754–5767} }
 @article{ghiladi_hatwell_karlin_huang_moënne-loccoz_krebs_huynh_marzilli_cotter_kaderli_et al._2001, title={Dioxygen Reactivity of Mononuclear Heme and Copper Components Yielding A High-Spin Heme−Peroxo−Cu Complex}, volume={123}, ISSN={0002-7863 1520-5126}, url={http://dx.doi.org/10.1021/ja010602y}, DOI={10.1021/ja010602y}, abstractNote={ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTDioxygen Reactivity of Mononuclear Heme and Copper Components Yielding A High-Spin Heme−Peroxo−Cu ComplexReza A. Ghiladi, Karen R. Hatwell, Kenneth D. Karlin, Hong-wei Huang, Pierre Moënne-Loccoz, Carsten Krebs, Boi Hanh Huynh, Lisa A. Marzilli, Robert J. Cotter, Susan Kaderli, and Andreas D. ZuberbühlerView Author Information Department of Chemistry, The Johns Hopkins University Charles and 34th Streets, Baltimore, Maryland 21218 Department of Biochemistry and Molecular Biology Oregon Graduate Institute, Beaverton, Oregon 97006 Department of Physics, Emory University Atlanta, Georgia 30322 Department of Pharmacology and Molecular Sciences The Johns Hopkins School of Medicine Baltimore, Maryland 21205 Institute für Anorganische Chemie, University of Basel CH-4056 Basel, Switzerland Cite this: J. Am. Chem. Soc. 2001, 123, 25, 6183–6184Publication Date (Web):June 1, 2001Publication History Received6 March 2001Published online1 June 2001Published inissue 1 June 2001https://doi.org/10.1021/ja010602yCopyright © 2001 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views749Altmetric-Citations76LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (52 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Oxides,Pyrroles,Quantum mechanics,Resonance structures,Saturation Get e-Alerts}, number={25}, journal={Journal of the American Chemical Society}, publisher={American Chemical Society (ACS)}, author={Ghiladi, Reza A. and Hatwell, Karen R. and Karlin, Kenneth D. and Huang, Hong-wei and Moënne-Loccoz, Pierre and Krebs, Carsten and Huynh, Boi Hanh and Marzilli, Lisa A. and Cotter, Robert J. and Kaderli, Susan and et al.}, year={2001}, month={Jun}, pages={6183–6184} }
 @article{moënne-loccoz_richter_huang_wasser_ghiladi_karlin_de vries_2000, title={Nitric Oxide Reductase from Paracoccus denitrificans Contains an Oxo-Bridged Heme/Non-Heme Diiron Center}, volume={122}, ISSN={0002-7863 1520-5126}, url={http://dx.doi.org/10.1021/ja0016295}, DOI={10.1021/ja0016295}, abstractNote={ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTNitric Oxide Reductase from Paracoccus denitrificans Contains an Oxo-Bridged Heme/Non-Heme Diiron CenterPierre Moënne-Loccoz, Oliver-M. H. Richter, Hong-wei Huang, Ian M. Wasser, Reza A. Ghiladi, Kenneth D. Karlin, and Simon de VriesView Author Information Department of Biochemistry and Molecular Biology Oregon Graduate Institute of Science and Technology Beaverton, Oregon 97006 Kluyver Laboratory for Biotechnology Delft University of Technology 2628 BC Delft, The Netherlands Department of Chemistry, The Johns Hopkins University Baltimore, Maryland 21218 Cite this: J. Am. Chem. Soc. 2000, 122, 38, 9344–9345Publication Date (Web):September 13, 2000Publication History Received12 May 2000Revised17 August 2000Published online13 September 2000Published inissue 1 September 2000https://doi.org/10.1021/ja0016295Copyright © 2000 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views512Altmetric-Citations85LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (45 KB) Get e-AlertsSUBJECTS:Bioinorganic chemistry,Diirons,Iron,Ligands,Peptides and proteins Get e-Alerts}, number={38}, journal={Journal of the American Chemical Society}, publisher={American Chemical Society (ACS)}, author={Moënne-Loccoz, Pierre and Richter, Oliver-M. H. and Huang, Hong-wei and Wasser, Ian M. and Ghiladi, Reza A. and Karlin, Kenneth D. and de Vries, Simon}, year={2000}, month={Sep}, pages={9344–9345} }
 @article{ju_ghiladi_lee_van strijdonck_woods_cotter_young_karlin_1999, title={Dioxygen Reactivity of Fully Reduced [LFeII···CuI]+Complexes Utilizing Tethered Tetraarylporphyrinates:  Active Site Models for Heme-Copper Oxidases}, volume={38}, ISSN={0020-1669 1520-510X}, url={http://dx.doi.org/10.1021/ic9900511}, DOI={10.1021/ic9900511}, abstractNote={For O2-reactivity studies aimed at modeling aspects of heme-copper oxidase enzyme function, use of heterobinucleating ligands (6-pyridyl (6L) or 5-pyridyl (5L) connection) gives rise to iron(II) (with “empty-tether”), 2a and 2b, and [LFeII···CuI]+ complexes, 3a and 3b, respectively. Reduced complexes 2 and 3 can exist in high-, intermediate-, or low-spin iron(II) configurations, depending on the solvent employed. Reaction of dioxygen with both 3a and 3b leads to a biomimetic reductive O−O bond cleavage forming μ-oxo species [(L)FeIII−O−CuII]+ (4a, 4b). The X-ray structure of 4a is reported.}, number={10}, journal={Inorganic Chemistry}, publisher={American Chemical Society (ACS)}, author={Ju, Telvin D. and Ghiladi, Reza A. and Lee, Dong-Heon and van Strijdonck, Gino P. F. and Woods, Amina S. and Cotter, Robert J. and Young, Victor G. and Karlin, Kenneth D.}, year={1999}, month={May}, pages={2244–2245} }
 @article{dioxygen reactivity of fully reduced [lfeii⋯cui]+ complexes utilizing tethered tetraarylporphyrinates: active site models for heme-copper oxidases_1999, volume={38}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0001509852&partnerID=MN8TOARS}, number={10}, journal={Inorganic Chemistry}, year={1999}, pages={2244–2245} }
 @article{ghiladi_ju_lee_moënne-loccoz_kaderli_neuhold_zuberbühler_woods_cotter_karlin_1999, title={Formation and Characterization of a High-Spin Heme-Copper Dioxygen (Peroxo) Complex}, volume={121}, ISSN={0002-7863 1520-5126}, url={http://dx.doi.org/10.1021/ja992296i}, DOI={10.1021/ja992296i}, abstractNote={ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTFormation and Characterization of a High-Spin Heme-Copper Dioxygen (Peroxo) ComplexReza A. Ghiladi, Telvin D. Ju, Dong-Heon Lee, Pierre Moënne-Loccoz, Susan Kaderli, Yorck-Michael Neuhold, Andreas D. Zuberbühler, Amina S. Woods, Robert J. Cotter, and Kenneth D. KarlinView Author Information Department of Chemistry, The Johns Hopkins University Charles & 34th Streets, Baltimore, Maryland 21218 Department of Biochemistry and Molecular Biology Oregon Graduate Institute, Beaverton, Oregon 97006 Institute für Anorganische Chemie University of Basel, CH-4056 Basel, Switzerland Department of Pharmacology and Molecular Sciences The Johns Hopkins School of Medicine Baltimore, Maryland 21205 Cite this: J. Am. Chem. Soc. 1999, 121, 42, 9885–9886Publication Date (Web):October 8, 1999Publication History Received5 July 1999Published online8 October 1999Published inissue 1 October 1999https://doi.org/10.1021/ja992296iCopyright © 1999 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views709Altmetric-Citations66LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (83 KB) Get e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Adducts,Ligands,Pyrroles,Reactivity,Saturation Get e-Alerts}, number={42}, journal={Journal of the American Chemical Society}, publisher={American Chemical Society (ACS)}, author={Ghiladi, Reza A. and Ju, Telvin D. and Lee, Dong-Heon and Moënne-Loccoz, Pierre and Kaderli, Susan and Neuhold, Yorck-Michael and Zuberbühler, Andreas D. and Woods, Amina S. and Cotter, Robert J. and Karlin, Kenneth D.}, year={1999}, month={Oct}, pages={9885–9886} }