Light-activated protein inhibition through photoinduced electron transfer of a ruthenium(II)–cobalt(III) bimetallic complex
Abstract
In this paper, 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. Finally, these results convey a strategy for light activation of inorganic therapeutic agents through PET utilizing redox-active metal centers.
- Authors:
-
- Northwestern Univ., Evanston, IL (United States)
- Publication Date:
- Research Org.:
- Northwestern Univ., Evanston, IL (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC)
- OSTI Identifier:
- 1345974
- Grant/Contract Number:
- AC05-06OR23100
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Journal of the American Chemical Society
- Additional Journal Information:
- Journal Volume: 137; Journal Issue: 9; Journal ID: ISSN 0002-7863
- Publisher:
- American Chemical Society (ACS)
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Holbrook, Robert J., Weinberg, David J., Peterson, Mark D., Weiss, Emily A., and Meade, Thomas J. Light-activated protein inhibition through photoinduced electron transfer of a ruthenium(II)–cobalt(III) bimetallic complex. United States: N. p., 2015.
Web. doi:10.1021/jacs.5b00342.
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. United States. https://doi.org/10.1021/jacs.5b00342
Holbrook, Robert J., Weinberg, David J., Peterson, Mark D., Weiss, Emily A., and Meade, Thomas J. Wed .
"Light-activated protein inhibition through photoinduced electron transfer of a ruthenium(II)–cobalt(III) bimetallic complex". United States. https://doi.org/10.1021/jacs.5b00342. https://www.osti.gov/servlets/purl/1345974.
@article{osti_1345974,
title = {Light-activated protein inhibition through photoinduced electron transfer of a ruthenium(II)–cobalt(III) bimetallic complex},
author = {Holbrook, Robert J. and Weinberg, David J. and Peterson, Mark D. and Weiss, Emily A. and Meade, Thomas J.},
abstractNote = {In this paper, 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. Finally, these results convey a strategy for light activation of inorganic therapeutic agents through PET utilizing redox-active metal centers.},
doi = {10.1021/jacs.5b00342},
journal = {Journal of the American Chemical Society},
number = 9,
volume = 137,
place = {United States},
year = {Wed Feb 11 00:00:00 EST 2015},
month = {Wed Feb 11 00:00:00 EST 2015}
}
Web of Science
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