Light-activated protein inhibition through photoinduced electron transfer of a ruthenium(II)-cobalt(III) bimetallic complex.

ABSTRACT: 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 ?-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 ?-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.

SUBMITTER: Holbrook RJ 

PROVIDER: S-EPMC4487626 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature