Photoredox Catalysis in Medicinal Chemistry: A Modern Approach to the Synthesis of Bioactive Molecules

Author

Mr. Vinod Matole, Miss. Shraddha Birajdar, Mr. Abhishek Kirkol, Miss. Asmita Kasture, Mr. Avinash Rajput, Miss. Aarti Deshmukh, Mr. Samarth Shinde

Abstract

 Photoredox catalysis has developed from a specialized photochemical technique into a broadly useful platform for modern medicinal chemistry. By using light-activated catalysts to control single-electron or energy-transfer events, photoredox reactions can generate reactive intermediates under comparatively mild conditions. This capability enables carbon–carbon and carbon–heteroatom bond formation, C–H functionalization, reductive and oxidative coupling, heterocycle construction, late-stage diversification, and selective modification of complex drug-like molecules. These transformations are particularly valuable in medicinal chemistry because rapid preparation of structurally diverse analogues is central to structure–activity relationship studies and lead optimization. Visible-light photoredox chemistry can also complement conventional transition-metal catalysis and, in some cases, replace multistep functional-group manipulations with direct transformations. Organic photocatalysts, iridium and ruthenium complexes, semiconductor systems, and emerging earth-abundant-metal catalysts have all contributed to the field. Recent developments extend photoredox chemistry toward peptide functionalization, protein bioconjugation, isotopic labelling, DNA-encoded libraries, and chemical-biology applications. Despite its advantages, issues including photon penetration, reactor design, scale-up, catalyst cost, oxygen sensitivity, reproducibility, and photochemical safety remain important. This review discusses the principles, catalyst classes, reaction mechanisms, medicinal-chemistry applications, sustainability aspects, challenges, and future opportunities of photoredox catalysis, with emphasis on its role in the synthesis and diversification of bioactive molecules.

Keywords

Photoredox catalysis; visible light; medicinal chemistry; photocatalyst; radical chemistry; C–H functionalization; late-stage functionalization; drug discovery; bioactive molecules; green synthesis.

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References

1. Shaw MH, Twilton J, MacMillan DWC. Photoredox Catalysis in Organic Chemistry. J Org Chem. 2016;81(16):6898-6926. doi:10.1021/acs.joc.6b01449.
2. Narayanam JMR, Stephenson CRJ. Visible light photoredox catalysis: applications in organic synthesis. Chem Soc Rev. 2011;40:102-113. doi:10.1039/B913880N.
3. Bogdos MK, Pinard E, Murphy JA. Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry. Beilstein J Org Chem. 2018;14:2035-2064. doi:10.3762/bjoc.14.179.
4. Skubi KL, Blum TR, Yoon TP. Dual catalytic photochemical processes. Chem Rev. 2016;116:10035-10074.
5. Prier CK, Rankic DA, MacMillan DWC. Visible light photoredox catalysis with transition metal complexes: applications in organic synthesis. Chem Rev. 2013;113:5322-5363.
6. Romero NA, Nicewicz DA. Organic photoredox catalysis. Chem Rev. 2016;116:10075-10166.
7. Nicholls TP, Leonori D, Bissember AC. Applications of visible light photoredox catalysis to the synthesis of natural products and related compounds.

J Chem Soc Perkin Trans 1 / Nat Prod Rep. 2016;33:1248-1254. doi:10.1039/C6NP00070C.

8. Cresswell AJ, Eey STC, Denmark SE. Catalytic, stereospecific synthesis of organoboron compounds using photoredox chemistry. Angew Chem Int Ed. 2015.
9. MacMillan DWC. Photoredox catalysis in the pharmaceutical industry. Chem Eng News / related industrial perspectives.
10. Skubi KL, Swords WB, Hofstetter H, Yoon TP. Combining photoredox and transition metal catalysis in organic synthesis. Chem Rev. 2021.
11. Pitre SP, Overman LE. Strategic Use of Visible-Light Photoredox Catalysis in Natural Product Synthesis. Chem Rev. 2022;122(2):1717-1751. doi:10.1021/acs.chemrev.1c00247.
12. Nocera DG. The merging of photochemistry and electrochemistry. J Am Chem Soc. 2012.
13. Twilton J, Le C, Zhang P, Shaw MH, Evans RW, MacMillan DWC. The merger of transition metal and photoredox catalysis. Nat Rev Chem. 2017;1:0052.
14. Huang X, Webster RD, Harrold ND, et al. Photoredox-catalyzed C-H functionalization reactions. Chem Rev. 2022;122 / related review literature.doi:10.1021/acs.chemrev.1c00311.
15. Visible-Light Photocatalysis as an Enabling Technology for Drug Discovery: A Paradigm Shift for Chemical Reactivity. ACS Med Chem Lett. 2020. doi:10.1021/acsmedchemlett.0c00436.
16. Photochemistry in Medicinal Chemistry and Chemical Biology. 2024 review literature.
17. Yang Y, Huang X, Jin Y. Photoinduced ligand-to-metal charge transfer (LMCT) in organic synthesis: reaction modes and research advances. Chem Commun. 2025;61:1944-1961. doi:10.1039/D4CC06099G.
18. Huxter VM. Advancing Organic Photoredox Catalysis: Mechanistic Insight through Time-Resolved Spectroscopy. J Phys Chem Lett. 2024;15:7945-7953. doi:10.1021/acs.jpclett.4c00895.
19. Visible and Near-Infrared Photopharmacology: Wavelength-Redshift Strategies for Spatiotemporally Precise Therapeutics. J Med Chem. 2026;69(3):1878-1915. doi:10.1021/acs.jmedchem.5c02041.
20. Emerging Roles of Photoredox Catalysis in Biomedical Research. 2026.