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Light-Activated Protein Inhibition through Photoinduced Electron Transfer of a Ruthenium(II)–Cobalt(III) Bimetallic Complex

Holbrook, Robert J., Weinberg, David J., Peterson, Mark D., Weiss, Emily A., Meade, Thomas J.
Journal of the American Chemical Society 2015 v.137 no.9 pp. 3379-3385
active sites, cobalt, electron transfer, histidine, irradiation, ligands, nuclear magnetic resonance spectroscopy, ruthenium, schiff bases, thrombin
We describe a mechanism of light activation that initiates protein inhibitory action of a biologically inert Co(III) Schiff base (Co(III)-sb) complex. Photoinduced electron transfer (PET) occurs from a Ru(II) bipyridal complex to a covalently attached Co(III) complex and is gated by conformational changes that occur in tens of nanoseconds. Reduction of the Co(III)-sb by PET initiates displacement of the inert axial imidazole ligands, promoting coordination to active site histidines of α-thrombin. Upon exposure to 455 nm light, the rate of ligand exchange with 4-methylimidazole, a histidine mimic, increases by approximately 5-fold, as observed by NMR spectroscopy. Similarly, the rate of α-thrombin inhibition increases over 5-fold upon irradiation. These results convey a strategy for light activation of inorganic therapeutic agents through PET utilizing redox-active metal centers.