Flavin bioorthogonal photocatalysis toward platinum substrates

Catalytic reactions that use metal complexes as substrates, rather than catalysts, are nearly unknown. We recently demonstrated that certain flavins (FLs) are potent redox photocatalysts capable of converting PtIV anticancer prodrug complexes into PtII drugs in the biological environment. Herein, we investigate the mechanism of these artificial photocatalytic reactions employing four different free flavins, namely, riboflavin (Rf), flavin mononucleotide (FMN), tetra-O-acetyl riboflavin (TARF) and lumiflavin (Lf), and the flavoprotein miniSOG (mini Singlet Oxygen Generator), together with a panel of PtIV substrates conveniently selected. NMR, steady-state, and time-resolved optical spectroscopy studies highlight that light activation of FLs in the presence of NADH as electron donor (pH 7-7.5) eventually leads to the generation of the reduced FLH- species which catalyzes the PtIV-to-PtII conversion with turnover frequency (TOF) values ranging between 1.3 and 30 min-1 and turnover number (TON) values reaching 500. Comparable catalytic efficiency is also found for reactions performed in cell culture medium. Density functional theory suggests that activation via reduction of the PtIV complexes may be influenced by H-bonding interactions between the FL catalyst and the metal substrate and confirms that both the isoalloxazine and ribityl moieties of the FLs determine the catalytic efficiency of the process. The FMN-containing miniSOG is a less effective catalyst (TOFs < 5.6 min-1) because the formation of the doubly reduced FMNH- competes with an electron transfer reaction involving the protein matrix which quenches the FMN excited state to give a singly reduced FMN N.-