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Title: 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:
 [1];  [1];  [1];  [1];  [1]
  1. 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. doi: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. doi: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 = {2015},
month = {2}
}

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