@article{springer_taniguchi_krayer_ruzie_diers_niedzwiedzki_bocian_lindsey_holten_2014, title={Photophysical properties and electronic structure of retinylidene-chlorin-chalcones and analogues}, volume={13}, number={4}, journal={Photochemical & Photobiological Sciences}, author={Springer, J. W. and Taniguchi, M. and Krayer, M. and Ruzie, C. and Diers, J. R. and Niedzwiedzki, D. M. and Bocian, D. F. and Lindsey, J. S. and Holten, D.}, year={2014}, pages={634–650} }
 @article{yang_ruzie_krayer_diers_niedzwiedzki_kirmaier_lindsey_bocian_holten_2013, title={Photophysical Properties and Electronic Structure of Bacteriochlorin-Chalcones with Extended Near-Infrared Absorption}, volume={89}, ISSN={["1751-1097"]}, DOI={10.1111/php.12053}, abstractNote={AbstractSynthetic bacteriochlorins enable systematic tailoring of substituents about the bacteriochlorin chromophore and thereby provide insights concerning the native bacteriochlorophylls of bacterial photosynthesis. Nine free‐base bacteriochlorins (eight prepared previously and one prepared here) have been examined that bear diverse substituents at the 13‐ or 3,13‐positions. The substituents include chalcone (3‐phenylprop‐2‐en‐1‐onyl) derivatives with groups attached to the phenyl moiety, a “reverse chalcone” (3‐phenyl‐3‐oxo‐1‐enyl), and extended chalcones (5‐phenylpenta‐2,4‐dien‐1‐onyl, retinylidenonyl). The spectral and photophysical properties (τs, Φf, Φic, Φisc, τT, kf, kic, kisc) of the bacteriochlorins have been characterized. The bacteriochlorins absorb strongly in the 780–800 nm region and have fluorescence quantum yields (Φf) in the range 0.05–0.11 in toluene and dimethylsulfoxide. Light‐induced electron promotions between orbitals with predominantly substituent or macrocycle character or both may give rise to some net macrocycle ↔ substituent charge‐transfer character in the lowest and higher singlet excited states as indicated by density functional theory (DFT) and time‐dependent DFT calculations. Such calculations indicated significant participation of molecular orbitals beyond those (HOMO − 1 to LUMO + 1) in the Gouterman four‐orbital model. Taken together, the studies provide insight into the fundamental properties of bacteriochlorins and illustrate designs for tuning the spectral and photophysical features of these near‐infrared‐absorbing tetrapyrrole chromophores.}, number={3}, journal={PHOTOCHEMISTRY AND PHOTOBIOLOGY}, author={Yang, Eunkyung and Ruzie, Christian and Krayer, Michael and Diers, James R. and Niedzwiedzki, Dariusz M. and Kirmaier, Christine and Lindsey, Jonathan S. and Bocian, David F. and Holten, Dewey}, year={2013}, pages={586–604} }
 @article{huang_mroz_zhiyentayev_sharma_balasubramanian_ruzie_krayer_fan_borbas_yang_et al._2010, title={In Vitro Photodynamic Therapy and Quantitative Structure-Activity Relationship Studies with Stable Synthetic Near-Infrared-Absorbing Bacteriochlorin Photosensitizers}, volume={53}, ISSN={["1520-4804"]}, DOI={10.1021/jm901908s}, abstractNote={Photodynamic therapy (PDT) is a rapidly developing approach to treating cancer that combines harmless visible and near-infrared light with a nontoxic photoactivatable dye, which upon encounter with molecular oxygen generates the reactive oxygen species that are toxic to cancer cells. Bacteriochlorins are tetrapyrrole compounds with two reduced pyrrole rings in the macrocycle. These molecules are characterized by strong absorption features from 700 to >800 nm, which enable deep penetration into tissue. This report describes testing of 12 new stable synthetic bacteriochlorins for PDT activity. The 12 compounds possess a variety of peripheral substituents and are very potent in killing cancer cells in vitro after illumination. Quantitative structure-activity relationships were derived, and subcellular localization was determined. The most active compounds have both low dark toxicity and high phototoxicity. This combination together with near-infrared absorption gives these bacteriochlorins great potential as photosensitizers for treatment of cancer.}, number={10}, journal={JOURNAL OF MEDICINAL CHEMISTRY}, author={Huang, Ying-Ying and Mroz, Pawel and Zhiyentayev, Timur and Sharma, Sulbha K. and Balasubramanian, Thiagarajan and Ruzie, Christian and Krayer, Michael and Fan, Dazhong and Borbas, K. Eszter and Yang, Eunkyung and et al.}, year={2010}, month={May}, pages={4018–4027} }
 @article{huang_huang_mroz_tegos_zhiyentayev_sharma_lu_balasubramanian_krayer_ruzie_et al._2010, title={Stable Synthetic Cationic Bacteriochlorins as Selective Antimicrobial Photosensitizers}, volume={54}, ISSN={["1098-6596"]}, DOI={10.1128/aac.00125-10}, abstractNote={ABSTRACT
          
            Photodynamic inactivation is a rapidly developing antimicrobial treatment that employs a nontoxic photoactivatable dye or photosensitizer in combination with harmless visible light to generate reactive oxygen species that are toxic to cells. Tetrapyrroles (e.g., porphyrins, chlorins, bacteriochlorins) are a class of photosensitizers that exhibit promising characteristics to serve as broad-spectrum antimicrobials. In order to bind to and efficiently penetrate into all classes of microbial cells, tetrapyrroles should have structures that contain (i) one or more cationic charge(s) or (ii) a basic group. In this report, we investigate the use of new stable synthetic bacteriochlorins that have a strong absorption band in the range 720 to 740 nm, which is in the near-infrared spectral region. Four bacteriochlorins with 2, 4, or 6 quaternized ammonium groups or 2 basic amine groups were compared for light-mediated killing against a Gram-positive bacterium (
            Staphylococcus aureus
            ), a Gram-negative bacterium (
            Escherichia coli
            ), and a dimorphic fungal yeast (
            Candida albicans
            ). Selectivity was assessed by determining phototoxicity against human HeLa cancer cells under the same conditions. All four compounds were highly active (6 logs of killing at 1 μM or less) against
            S. aureus
            and showed selectivity for bacteria over human cells. Increasing the cationic charge increased activity against
            E. coli
            . Only the compound with basic groups was highly active against
            C. albicans.
            Supporting photochemical and theoretical characterization studies indicate that (i) the four bacteriochlorins have comparable photophysical features in homogeneous solution and (ii) the anticipated redox characteristics do not correlate with cell-killing ability. These results support the interpretation that the disparate biological activities observed stem from cellular binding and localization effects rather than intrinsic electronic properties. These findings further establish cationic bacteriochlorins as extremely active and selective near-infrared activated antimicrobial photosensitizers, and the results provide fundamental information on structure-activity relationships for antimicrobial photosensitizers.
          }, number={9}, journal={ANTIMICROBIAL AGENTS AND CHEMOTHERAPY}, author={Huang, Liyi and Huang, Ying-Ying and Mroz, Pawel and Tegos, George P. and Zhiyentayev, Timur and Sharma, Sulbha K. and Lu, Zongshun and Balasubramanian, Thiagarajan and Krayer, Michael and Ruzie, Christian and et al.}, year={2010}, month={Sep}, pages={3834–3841} }
 @article{mroz_huang_szokalska_zhiyentayev_janjua_nifli_sherwood_ruzie_borbas_fan_et al._2010, title={Stable synthetic bacteriochlorins overcome the resistance of melanoma to photodynamic therapy}, volume={24}, ISSN={["0892-6638"]}, DOI={10.1096/fj.09-152587}, abstractNote={Cutaneous malignant melanoma remains a therapeutic challenge, and patients with advanced disease have limited survival. Photodynamic therapy (PDT) has been successfully used to treat many malignancies, and it may show promise as an antimelanoma modality. However, high melanin levels in melanomas can adversely affect PDT effectiveness. Herein the extent of melanin contribution to melanoma resistance to PDT was investigated in a set of melanoma cell lines that markedly differ in the levels of pigmentation;3 new bacteriochlorins successfully overcame the resistance. Cell killing studies determined that bacteriochlorins are superior at (LD50≈0.1 µM) when compared with controls such as the FDA‐approved Photofrin (LD50≈10 µM) and clinically tested LuTex (LD50≈=1 µM). The melanin content affects PDT effectiveness, but the degree of reduction is significantly lower for bacteriochlorins than for Photofrin. Microscopy reveals that the least effective bacteriochlorin localizes predominantly in lysosomes, while the most effective one preferentially accumulates in mitochondria. Interestingly all bacteriochlorins accumulate in melanosomes, and subsequent illumination leads to melanosomal damage shown by electron microscopy. Fluorescent probes show that the most effective bacteriochlorin produces significantly higher levels of hydroxyl radicals, and this is consistent with the redox properties suggested by molecular‐orbital calculations. The best in vitro performing bacteriochlorin was tested in vivo in a mouse melanoma model using spectrally resolved fluorescence imaging and provided significant survival advantage with 20% of cures (P<0.01).—Mroz, P., Huang, Y.‐Y., Szokalska, A., Zhiyentayev, T., Janjua, S., Nifli, A.‐P., Sherwood, M. E., Ruzié, C., Borbas, K. E., Fan, D., Krayer, M., Balasubramanian, T., Yang, E., Kee, H. L., Kirmaier, C., Diers, J. R., Bocian, D. F., Holten, D., Lindsey, J. S., Hamblin, M. R. Stable synthetic bacteriochlorins overcome the resistance of melanoma to photodynamic therapy. FASEB J. 24, 3160–3170 (2010). www.fasebj.org}, number={9}, journal={FASEB JOURNAL}, author={Mroz, Pawel and Huang, Ying-Ying and Szokalska, Angelika and Zhiyentayev, Timur and Janjua, Sahar and Nifli, Artemissia-Phoebe and Sherwood, Margaret E. and Ruzie, Christian and Borbas, K. Eszter and Fan, Dazhong and et al.}, year={2010}, month={Sep}, pages={3160–3170} }
 @article{krayer_balasubramanian_ruzie_ptaszek_cramer_taniguchi_lindsey_2009, title={Refined syntheses of hydrodipyrrin precursors to chlorin and bacteriochlorin building blocks}, volume={13}, ISSN={["1099-1409"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-70450189510&partnerID=MN8TOARS}, DOI={10.1142/S1088424609001406}, abstractNote={ Bromo-substituted hydrodipyrrins are valuable precursors to synthetic bromo-chlorins and bromo-bacteriochlorins, which in turn are versatile substrates for derivatization in pursuit of diverse molecular designs. 8-bromo-2,3-dihydro-1-(1,1-dimethoxymethyl)-3,3-dimethyldipyrrin (1) is a crucial precursor in the rational synthesis of the bacteriochlorin building block 3,13-dibromo-8,8,18,18-tetramethylbacteriochlorin ( H2BC-Br3Br13) . 8-bromo-2,3,4,5-tetrahydro-1,3,3-trimethyldipyrrin (2) is a crucial precursor in the rational synthesis of the analogous 3,13-disubstituted chlorin building block (e.g. H2C-Br3M10Br13 ). The routes to 1 and 2 share a common precursor, namely 4-bromo-2-(2-nitroethyl)-1-N-tosylpyrrole (6-Ts), which is derived from pyrrole-2-carboxaldehyde. The prior seven-step synthesis of 1 from pyrrole-2-carboxaldehyde has limited access to H2BC-Br3Br13 given the large excesses of materials, extensive reliance on column chromatography, and low overall yield (1.4%). Refined procedures for synthesis of the common precursor 6-Ts as well as 1 and 2 afford the advantages of (1) diminished consumption of solvents and reagents, (2) limited or no use of chlorinated solvents, (3) limited or no chromatography, and (4) improved yields of most steps. Streamlined procedures enable the final two or three transformations to be performed without purification of intermediates. The new procedures facilitate the expedient preparation of 1 and 2 at the multigram scale. }, number={10}, journal={JOURNAL OF PORPHYRINS AND PHTHALOCYANINES}, publisher={World Scientific Pub Co Pte Lt}, author={Krayer, Michael and Balasubramanian, Thiagarajan and Ruzie, Christian and Ptaszek, Marcin and Cramer, David L. and Taniguchi, Masahiko and Lindsey, Jonathan S.}, year={2009}, month={Oct}, pages={1098–1110} }