@article{son_wu_dou_fujita_cao_liu_lindsey_2023, title={Article Tethered Indoxyl-Glucuronides for Enzymatically Triggered Cross-Linking}, volume={28}, ISSN={["1420-3049"]}, DOI={10.3390/molecules28104143}, abstractNote={Indoxyl-glucuronides, upon treatment with β-glucuronidase under physiological conditions, are well known to afford the corresponding indigoid dye via oxidative dimerization. Here, seven indoxyl-glucuronide target compounds have been prepared along with 22 intermediates. Of the target compounds, four contain a conjugatable handle (azido-PEG, hydroxy-PEG, or BCN) attached to the indoxyl moiety, while three are isomers that include a PEG-ethynyl group at the 5-, 6-, or 7-position. All seven target compounds have been examined in indigoid-forming reactions upon treatment with β-glucuronidase from two different sources and rat liver tritosomes. Taken together, the results suggest the utility of tethered indoxyl-glucuronides for use in bioconjugation chemistry with a chromogenic readout under physiological conditions.}, number={10}, journal={MOLECULES}, author={Son, Juno and Wu, Zhiyuan and Dou, Jinghuai and Fujita, Hikaru and Cao, Phuong-Lien Doan and Liu, Qihui and Lindsey, Jonathan S.}, year={2023}, month={May} }
 @article{nguyen_tran_wang_zhang_wu_taniguchi_lindsey_2023, title={Four Routes to 3-(3-Methoxy-1,3-dioxopropyl)pyrrole, a Core Motif of Rings C and E in Photosynthetic Tetrapyrroles}, volume={28}, ISSN={["1420-3049"]}, url={https://doi.org/10.3390/molecules28031323}, DOI={10.3390/molecules28031323}, abstractNote={The photosynthetic tetrapyrroles share a common structural feature comprised of a β-ketoester motif embedded in an exocyclic ring (ring E). As part of a total synthesis program aimed at preparing native structures and analogues, 3-(3-methoxy-1,3-dioxopropyl)pyrrole was sought. The pyrrole is a precursor to analogues of ring C and the external framework of ring E. Four routes were developed. Routes 1–3 entail a Pd-mediated coupling process of a 3-iodopyrrole with potassium methyl malonate, whereas route 4 relies on electrophilic substitution of TIPS-pyrrole with methyl malonyl chloride. Together, the four routes afford considerable latitude. A long-term objective is to gain the capacity to create chlorophylls and bacteriochlorophylls and analogues thereof by facile de novo means for diverse studies across the photosynthetic sciences.}, number={3}, journal={MOLECULES}, author={Nguyen, Khiem Chau and Tran, Anh Thu Nguyen and Wang, Pengzhi and Zhang, Shaofei and Wu, Zhiyuan and Taniguchi, Masahiko and Lindsey, Jonathan S.}, year={2023}, month={Feb} }
 @article{sato_wu_dou_son_lindsey_2023, title={Indoxyl-glucosides bearing tethers for enzymatically triggered cross-linking}, volume={47}, ISSN={["1369-9261"]}, DOI={10.1039/d2nj06267d}, abstractNote={Tethered indoxyl-glucosides upon treatment with β-glucosidase under physiological conditions afford the corresponding indigoid dye via oxidative dimerization.}, number={17}, journal={NEW JOURNAL OF CHEMISTRY}, author={Sato, Daisuke and Wu, Zhiyuan and Dou, Jinghuai and Son, Juno and Lindsey, Jonathan S. S.}, year={2023}, month={May}, pages={8223–8242} }
 @article{nguyen tran_wu_chung_nalaoh_lindsey_2023, title={Synthesis of model southern rim structures of photosynthetic tetrapyrroles and phyllobilins}, volume={7}, ISSN={["1369-9261"]}, url={http://dx.doi.org/10.1039/d3nj02515b}, DOI={10.1039/d3nj02515b}, abstractNote={Two simple pyrroles react in two simple reactions to afford a dipyrromethane analogue of the southern rim of native tetrapyrroles and their catabolites.}, journal={NEW JOURNAL OF CHEMISTRY}, author={Nguyen Tran, Anh Thu and Wu, Zhiyuan and Chung, Duy T. M. and Nalaoh, Phattananawee and Lindsey, Jonathan S.}, year={2023}, month={Jul} }
 @article{liu_rong_wu_taniguchi_bocian_holten_lindsey_2022, title={Panchromatic Absorbers Tethered for Bioconjugation or Surface Attachment}, volume={27}, ISSN={["1420-3049"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85139868890&partnerID=MN8TOARS}, DOI={10.3390/molecules27196501}, abstractNote={The syntheses of two triads are reported. Each triad is composed of two perylene-monoimides linked to a porphyrin via an ethyne unit, which bridges the perylene 9-position and a porphyrin 5- or 15-position. Each triad also contains a single tether composed of an alkynoic acid or an isophthalate unit. Each triad provides panchromatic absorption (350–700 nm) with fluorescence emission in the near-infrared region (733 or 743 nm; fluorescence quantum yield ~0.2). The syntheses rely on the preparation of trans-AB-porphyrins bearing one site for tether attachment (A), an aryl group (B), and two open meso-positions. The AB-porphyrins were prepared by the condensation of a 1,9-diformyldipyrromethane and a dipyrromethane. The installation of the two perylene-monoimide groups was achieved upon the 5,15-dibromination of the porphyrin and the subsequent copper-free Sonogashira coupling, which was accomplished before or after the attachment of the tether. The syntheses provide relatively straightforward access to a panchromatic absorber for use in bioconjugation or surface-attachment processes.}, number={19}, journal={MOLECULES}, author={Liu, Rui and Rong, Jie and Wu, Zhiyuan and Taniguchi, Masahiko and Bocian, David F. and Holten, Dewey and Lindsey, Jonathan S.}, year={2022}, month={Oct} }
 @article{wu_dou_nguyen_eppley_siwawannapong_zhang_lindsey_2022, title={Tailoring the AIE Chromogen 2-(2-Hydroxyphenyl)benzothiazole for Use in Enzyme-Triggered Molecular Brachytherapy}, volume={27}, ISSN={["1420-3049"]}, DOI={10.3390/molecules27248682}, abstractNote={A targeted strategy for treating cancer is antibody-directed enzyme prodrug therapy, where the enzyme attached to the antibody causes conversion of an inactive small-molecule prodrug into an active drug. A limitation may be the diffusion of the active drug away from the antibody target site. A related strategy with radiotherapeutics entails enzymatically promoted conversion of a soluble to insoluble radiotherapeutic agent, thereby immobilizing the latter at the target site. Such a molecular brachytherapy has been scarcely investigated. In distinct research, the advent of molecular designs for aggregation-induced emission (AIE) suggests translational use in molecular brachytherapy. Here, several 2-(2-hydroxyphenyl)benzothiazole substrates that readily aggregate in aqueous solution (and afford AIE) were elaborated in this regard. In particular, (1) the 2-(2-hydroxyphenyl) unit was derivatized to bear a pegylated phosphodiester that imparts water solubility yet undergoes enzymatic cleavage, and (2) a p-phenol unit was attached to the benzo moiety to provide a reactive site for final-step iodination (here examined with natural abundance iodide). The pegylated phosphodiester-iodinated benzothiazole undergoes conversion from aqueous-soluble to aqueous-insoluble upon treatment with a phosphatase or phosphodiesterase. The aggregation is essential to molecular brachytherapy, whereas the induced emission of AIE is not essential but provides a convenient basis for research development. Altogether, 21 compounds were synthesized (18 new, 3 known via new routes). Taken together, blending biomedical strategies of enzyme prodrug therapy with materials chemistry concerning substances that undergo AIE may comprise a step forward on the long road toward molecular brachytherapy.}, number={24}, journal={MOLECULES}, author={Wu, Zhiyuan and Dou, Jinghuai and Nguyen, Kathy-Uyen and Eppley, Jayden C. and Siwawannapong, Kittipan and Zhang, Yunlong and Lindsey, Jonathan S.}, year={2022}, month={Dec} }
 @article{fujita_zhang_wu_lindsey_2020, title={Chromogenic agents built around a multifunctional double-triazine framework for enzymatically triggered cross-linking under physiological conditions}, volume={44}, ISSN={["1369-9261"]}, DOI={10.1039/c9nj06187h}, abstractNote={An “A2BC”-type bioconjugatable compound (1) that enables enzymatically triggered cross-linking chemistry has been designed and synthesized. The compound contains two indoxyl-glucoside units (A units), which upon action of a glucosidase undergo oxidative dimerization to form a water-insoluble indigoid dye. The other two moieties are azide (B, for click chemistry) and (C) a triazine-chloride or a coumarin dye; the former enables substitution with a nucleophile while the latter provides for ratiometric sensing of the extent of indigoid dye formation. A 7-component building block synthesis relies on successive substitution of 2 cyanuric chloride (2,4,6-trichloro-1,3,5-triazine) molecules with 5 other constituents (2A, B, C, and a piperazine–sulfobetaine moiety); the latter bear oligoethylene glycol (i.e., PEG) or aminoalkyl tethers. The substitution reactions of cyanuric chloride proceed almost entirely at room temperature with control achieved by the order of nucleophile reactivity (aliphatic amine > phenol ≫ aliphatic alcohol) and the nature of a chosen base. Treatment of 1 with glucosidase under physiological conditions in aqueous solution gave an indigoid solution and a precipitate (∼1 : 9 ratio) that were characterized by absorption spectrometry (including multicomponent analysis), dynamic light-scattering spectroscopy, and optical microscopy. Ratiometric absorption of the integral coumarin dye with the indigoid scaffold showed a low yield (3%) of oligomerization, which suggests future molecular designs might employ longer linkers and/or substituents with greater water solubility.}, number={10}, journal={NEW JOURNAL OF CHEMISTRY}, author={Fujita, Hikaru and Zhang, Yunlong and Wu, Zhiyuan and Lindsey, Jonathan S.}, year={2020}, month={Mar}, pages={3856–3867} }
 @article{zhang_wu_takashima_nguyen_matsumoto_lindsey_2020, title={Engineering of an archaeal phosphodiesterase to trigger aggregation-induced emission (AIE) of synthetic substrates}, volume={44}, ISSN={["1369-9261"]}, DOI={10.1039/d0nj03208e}, abstractNote={Aggregation-induced emission (AIE) probes that can be triggered by enzymatic activity are sought for applications across the life sciences. The compound 2-(2-hydroxyphenyl)benzothiazole (HBT) is non-fluorescent in solution but exhibits AIE. To adapt HBT for potential clinical applications, two phosphoester derivatives (1 and 2) were prepared. For extension to molecular brachytherapy (delivery of a radionuclide), one phosphoester derivative (3) was prepared wherein a bromine atom is incorporated as a site for subsequent radioiodide substitution. Each probe 1–3 requires phosphatase action to engender AIE. For specificity in diagnostic and therapeutic applications, a heterologous (i.e., foreign to humans) enzyme was sought for conversion of 1–3 from aqueous-soluble to aqueous-insoluble form. Here, an archaeal phosphodiesterase PDE-MJ0936 (wild-type) was systematically engineered for activity toward 1–3. PDE-MJ0936 is a hyperthermal enzyme (activity at 70 °C and pH 9.8) and exists as a dimer, which together limit life science applications. Ten PDE mutants were engineered by site-directed mutagenesis to achieve a monomeric structure, wider substrate scope, and elastic substrate docking under physiological conditions. Among the mutants, PDE-C141D exhibited efficient activity towards bis(4-nitrophenyl)phosphate (Km = 0.28 mM, kcat = 3.0 s−1 and kcat/Km = 1.1 × 104 M−1 s−1) and efficiently hydrolyzed 3 at 37 °C and pH 7.0, conditions under which PDE-MJ0936 is silent. The substrates 1–3 are relatively resistant to alkaline phosphatase, PDE-MJ0936 and fetal bovine serum. The development of enzymatically triggered substrates and the complementary heterologous enzymes may support diverse applications in the life sciences.}, number={33}, journal={NEW JOURNAL OF CHEMISTRY}, author={Zhang, Yunlong and Wu, Zhiyuan and Takashima, Ippei and Nguyen, Kathy-Uyen and Matsumoto, Nobuyuki and Lindsey, Jonathan S.}, year={2020}, month={Sep}, pages={14266–14277} }
 @article{fujita_dou_matsumoto_wu_lindsey_2020, title={Enzymatically triggered chromogenic cross-linking agents under physiological conditions}, volume={44}, ISSN={["1369-9261"]}, DOI={10.1039/c9nj04126e}, abstractNote={Oxidative dimerization of an indoxyl moiety, released by glycosidase action in aqueous solution, yields an indigoid dye in formats that enable bioconjugation and molecular cross-linking.}, number={3}, journal={NEW JOURNAL OF CHEMISTRY}, author={Fujita, Hikaru and Dou, Jinghuai and Matsumoto, Nobuyuki and Wu, Zhiyuan and Lindsey, Jonathan S.}, year={2020}, month={Jan}, pages={719–743} }
 @article{fujita_jing_krayer_allu_veeraraghavaiah_wu_jiang_diers_magdaong_mandal_et al._2019, title={Annulated bacteriochlorins for near- infrared photophysical studies}, volume={43}, ISSN={["1369-9261"]}, DOI={10.1039/c9nj01113g}, abstractNote={Bacteriochlorins with phenaleno or benzo annulation absorb at 913 or 1033 nm and exhibit excited-state lifetimes of 150 or 7 ps, suggesting applications in photoacoustic imaging.}, number={19}, journal={NEW JOURNAL OF CHEMISTRY}, author={Fujita, Hikaru and Jing, Haoyu and Krayer, Michael and Allu, Srinivasarao and Veeraraghavaiah, Gorre and Wu, Zhiyuan and Jiang, Jianbing and Diers, James R. and Magdaong, Nikki Cecil M. and Mandal, Amit K. and et al.}, year={2019}, month={May}, pages={7209–7232} }
 @article{wu_fujita_magdaong_diers_hood_allu_niedzwiedzki_kirmaier_bocian_holten_et al._2019, title={New molecular design for blue BODIPYs}, volume={43}, ISSN={["1369-9261"]}, DOI={10.1039/c9nj01114e}, abstractNote={Dihydro analogues of BODIPYs exhibit spectral features (Φf ∼ 0.4–0.9) resembling aminocoumarins and suggest applications for broad-band photosensitization or where large Stokes shifts are desired.}, number={19}, journal={NEW JOURNAL OF CHEMISTRY}, author={Wu, Zhiyuan and Fujita, Hikaru and Magdaong, Nikki Cecil M. and Diers, James R. and Hood, Don and Allu, Srinivasarao and Niedzwiedzki, Dariusz M. and Kirmaier, Christine and Bocian, David F. and Holten, Dewey and et al.}, year={2019}, month={May}, pages={7233–7242} }