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Lewis Acid Coordination Redirects S-Nitrosothiol Reduction

preprint
submitted on 20.01.2020 and posted on 22.01.2020 by Valiallah Hosseininasab, Alison C. McQuilken, Abolghasem (Gus) Bakhoda, Jeffery A. Bertke, Qadir K. Timerghazin, Timothy H. Warren
S-Nitrosothiols (RSNOs) serve as air-stable reservoirs for nitric oxide in biology and are responsible for a myriad of physiological responses. While copper enzymes promote NO release from RSNOs by serving as Lewis acids capable of intramolecular electron-transfer, redox innocent Lewis acids separate these two functions to reveal the effect of coordination on structure and reactivity. The synthetic Lewis acid B(C6F5)3 coordinates to the RSNO oxygen atom in adducts RSNO-B(C6F5)3, leading to profound changes in the RSNO electronic structure and reactivity. Although RSNOs possess relatively negative reduction potentials (-1.0 to -1.1 vs. NHE), B(C6F5)3 coordination increases their reduction potential by over 1 V into the physiologically accessible +0.1 V vs. NHE. Outer-sphere chemical reduction results in formation of the Lewis acid stabilized hyponitrite dianion trans-[LA–O–N=N–O–LA]2– (LA = B(C6F5)3) that releases N2O upon acidification. Mechanistic and computational studies support initial reduction to the [RSNO-B(C6F5)3]•/- radical-anion susceptible to N-N coupling prior to loss of RSSR.

Funding

NIH R01GM126205

NSF CHE–1255641

NSF ACI-1053575

History

Email Address of Submitting Author

thw@georgetown.edu

Institution

Georgetown University, Department of Chemistry

Country

USA

ORCID For Submitting Author

0000-0001-9217-8890

Declaration of Conflict of Interest

No conflicts of interest.

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