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

摘要

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 ran 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.