title: 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 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.
authors: Department of Chemistry, Northwestern University , Evanston, Illinois 60208, United States.
authors: Robert J
authors: RJ
authors: Holbrook
authors: David J
authors: DJ
authors: Weinberg
authors: Mark D
authors: MD
authors: Peterson
authors: Emily A
authors: EA
authors: Weiss
authors: Thomas J
authors: TJ
authors: Meade
mesh_terms: D003035:Cobalt / Q000737:chemistry*; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology; D004579:Electron Transport; D006639:Histidine / Q000378:metabolism; D007093:Imidazoles / Q000737:chemistry; D008024:Ligands; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D055668:Photochemical Processes; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D012428:Ruthenium / Q000737:chemistry*; D012545:Schiff Bases / Q000737:chemistry; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D056831:Coordination Complexes; D007093:Imidazoles; D008024:Ligands; D011480:Protease Inhibitors; D012545:Schiff Bases; D003035:Cobalt; D006639:Histidine; D012428:Ruthenium; D013917:Thrombin; C023439:4-methylimidazole