The research team led by Prof. Jin Yong Lee of the Department of Chemistry (co-first author Ph. D. Jong Hyeon Lim) has developed a novel photoredox catalytic system, PC-Tz, based on bioorthogonally activatable photoredox catalysis through collaborative research with research teams led by Prof. Mingle Li (Shenzhen University), Prof. Joseph Fox (University of Delaware), Marc Vendrell (University of Edinburgh), and Prof. Jong Seung Kim (Korea University). The research was published in Journal of the American Chemical Society (IF: 14.4) in December 2024 under the title "Bioorthogonal Activation of Deep Red Photoredox Catalysis Inducing Pyroptosis."

Traditional photodynamic therapy (PDT) has been established as an important technique in cancer treatment, but its therapeutic efficacy has been limited by low activation efficiency and biocompatibility issues in hypoxic environments. To address these challenges, this study introduces an innovative bioorthogonal photoredox catalytic technology. The PC-Tz system employs a unique design where its catalytic activity is suppressed by the 1,2,4,5-tetrazine structure and restored through selective reactions with trans-cyclooctene (TCO) within cells.

The developed PC-Tz system promotes the oxidation of nicotinamide adenine dinucleotide (NADH) in a selective activation mechanism, effectively manipulating the mitochondrial electron transport chain (ETC) under hypoxic conditions in cancer cells. Professor Lee’s team utilized density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations to investigate the effects of TCO binding on the activation of the photoredox catalysis of PC-Tz. Moreover, the team employed a conductor-like polarizable continuum model (CPCM) to optimize the structural changes of PC-Tz before and after TCO binding, elucidating the energy state transitions and reaction mechanisms induced by light irradiation. This novel photoredox catalytic system is expected to contribute significantly to advancements in light-controlled therapeutic strategies for cancer, paving the way for the precise design of bioorthogonal photoredox catalysts for future medical applications.

*Title: Bioorthogonal Activation of Deep Red Photoredox Catalysis Inducing Pyroptosis.