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  • Review Article
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Interrogating biological systems using visible-light-powered catalysis

Abstract

Light-powered catalysis has found broad utility as a chemical transformation strategy, with widespread impact on energy, environment, drug discovery and human health. A noteworthy application impacting human health is light-induced sensitization of cofactors for photodynamic therapy in cancer treatment. The clinical adoption of this photosensitization approach has inspired the search for other photochemical methods, such as photoredox catalysis, to influence biological discovery. Over the past decade, light-mediated catalysis has enabled the discovery of valuable synthetic transformations, propelling it to become a highly utilized chemical synthesis strategy. The reaction components required to achieve a photoredox reaction are identical to photosensitization (catalyst, light source and substrate), making it ideally suited for probing biological environments. In this Review, we discuss the therapeutic application of photosensitization and advancements made in developing next-generation catalysts. We then highlight emerging uses of photoredox catalytic methods for protein bioconjugation and probing complex cellular environments in living cells.

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Fig. 1: Photoredox catalysis and photosensitization are ideally suited for probing biological environments.
Fig. 2: Photophysical chemistry of photosensitizers and photoredox catalysts.
Fig. 3: Clinical and emerging applications of photodynamic therapy.
Fig. 4: Biomolecule modification and crosslinking via photocatalysis.
Fig. 5: Visible-light-mediated in vivo crosslinking.
Fig. 6: Visible-light-mediated uncaging strategies.
Fig. 7: Ligand-directed photocatalytic protein labelling or degradation.
Fig. 8: Proximity-driven photocatalytic labelling in live cells.

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Acknowledgements

The authors thank Troy Moore and Sharon Wilhelm for helpful discussion during manuscript preparation. The authors also thank Yi Zheng of Yizheng Illustrations for figure design work.

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C.M.K. and N.B.B. researched data for the article. All authors contributed to discussion of content. K.R., R.C.O. and O.O.F. contributed to writing, reviewing and editing the manuscript before submission.

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K.R., C.M.K., N.B.B., R.C.O. and O.O.F. are/were employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, during the preparation of this manuscript.

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Ryu, K.A., Kaszuba, C.M., Bissonnette, N.B. et al. Interrogating biological systems using visible-light-powered catalysis. Nat Rev Chem 5, 322–337 (2021). https://doi.org/10.1038/s41570-021-00265-6

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