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

Research output: Contribution to journalArticle

17 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 - 2015

Fingerprint

Ruthenium
Cobalt
4-methylimidazole
Electrons
Proteins
Histidine
Light
Thrombin
Chemical activation
Ligands
Schiff Bases
Nuclear magnetic resonance spectroscopy
Oxidation-Reduction
Catalytic Domain
Magnetic Resonance Spectroscopy
Metals
Irradiation
Therapeutics

ASJC Scopus subject areas

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

Cite this

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.

In: Journal of the American Chemical Society, Vol. 137, No. 9, 2015, p. 3379-3385.

Research output: Contribution to journalArticle

Holbrook, Robert J. ; Weinberg, David J. ; Peterson, Mark D. ; Weiss, Emily A ; Meade, Thomas J. / Light-activated protein inhibition through photoinduced electron transfer of a ruthenium(II)-cobalt(III) bimetallic complex. In: Journal of the American Chemical Society. 2015 ; Vol. 137, No. 9. pp. 3379-3385.
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