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

Robert J. Holbrook, David J. Weinberg, Mark D. Peterson, Emily A. Weiss, Thomas J. Meade

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18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3379-3385
Number of pages7
JournalJournal of the American Chemical Society
Volume137
Issue number9
DOIs
Publication statusPublished - Feb 2015

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ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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