Imaging Single Photocatalytic Turnovers in Photoredox Catalysis for Efficient DrugSynthesis

Photoredox catalysis has been widely used in organic synthesis over the past decade. It has attracted significant attention from the pharmaceutical industry and has been employed in the discovery of drugs and bioactive compounds. To improve photocatalytic efficiency and product yield, a fundamental understanding of the mechanism and kinetics of the photocatalytic cycle is essential. Currently, photoredox catalysis is primarily studied at the ensemble level using the Stern-Volmer method. Although the quenching of photoexcited photoredox catalysts (PCs) has been extensively investigated, significant challenges remain due to the inherent limitations of ensemble measurements. To address the challenges, we propose to study photoredox catalysis at single-molecule level by monitoring the redox state of individual PCs in real time. Because a single PC can only exist in one redox state at any given moment, elementary photocatalytic turnovers can be decoupled and investigated independently. Real-time observation of a PC’s redox state is achieved by tracking its photoluminescence (PL) intensity. Reversible switching between redox states results in the photoblinking of the PC under continuous photoexcitation. The feasibility of this approach is demonstrated through the study of eosin Y (EY)-catalyzed photoredox reactions. We confirmed that photocatalytic turnovers induce photoblinking in single EY molecules. From the PL intensity trajectories of individual EY molecules, we extracted qualitative insights into the reaction mechanism and quantitative information on turnover kinetics, dynamics, and PC heterogeneity. We aim to investigate the mechanism, kinetics, and dynamics of photoredox catalysis for the synthesis of drug-relevant and bioactive compounds. Specifically, we will correlate product yield with photocatalytic turnover kinetics and efficiency, and establish property-performance relationships for PCs. Two major classes of PCs will be examined: xanthene dyes and Ir(ppy)3. The proposed research is both significant and innovative. Scientifically, it is expected to generate new fundamental insights into photoredox catalysis, ultimately contributing to improved photocatalytic efficiency and product yields. Technologically, the project will establish a novel in-operando method for studying photoredox catalysis, applicable to a broad range of PCs and catalytic systems. From a training and education perspective, the integration of photoredox catalysis with single-molecule imaging will offer undergraduate students interdisciplinary research experience, preparing them for careers in biomedical research and the pharmaceutical industry. Project Number: 1R15GM159261-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of General Medical Sciences (NIGMS) | Principal Investigator: Chunming Liu | Institution: UNIVERSITY OF AKRON, AKRON, OH | Award Amount: $554,078 | Activity Code: R15 | Study Section: Chemical Synthesis and Biosynthesis Study Section[CSB] View on NIH RePORTER: https://reporter.nih.gov/project-details/11361187