Mechanism Inversion in Visible Light-Induced Photoclick Reactions

Photoclick chemistry has emerged as a powerful methodology for achieving precise spatial and temporal control in photochemical transformations, enabling various applications ranging from surface functionalization, polymer conjugation, and photo-cross-linking to bioimaging and protein labeling. Despite significant advances, the absence of an unambiguous structure-property-mechanism relationship limits the design and application of photoclick systems in biological and material contexts. Herein, we report a novel strategy for tuning the reactivity and reaction mechanism of photoclick reactions of 9,10-phenanthrenequinone (PQ) with electron-rich alkenes (ERAs) through the design of 2,2'-substituted PQ derivatives incorporating electron-withdrawing groups (EWGs) and electron-donating groups (EDGs). Our experimental studies reveal that the reaction rate via a direct pathway involving the direct coupling between PQ and ERA gradually declines, while that of the triplet-triplet energy transfer-mediated pathway increases with the stepwise change of substitutions from EWGs to EDGs. Theoretical calculations and transient absorption spectroscopy measurements show that these observations can be traced back to the excited-state energy-level inversion between ¹nπ* and ¹ππ* states, which directly affects intersystem crossing yields. Furthermore, the reaction pathways can be modulated by changing the polarity of the solvent. These remarkable findings provide valuable mechanistic insights and establish a robust platform for the rational tuning of the reactivity and selectivity of PQ-ERA photoclick reactions using visible light while offering a unique strategy for the control of photochemical applications in complex environments.