These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
2 files

Lewis Acid Coordination Redirects S-Nitrosothiol Reduction

submitted on 20.01.2020, 20:48 and posted on 22.01.2020, 06:41 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.


NIH R01GM126205

NSF CHE–1255641

NSF ACI-1053575


Email Address of Submitting Author


Georgetown University, Department of Chemistry



ORCID For Submitting Author


Declaration of Conflict of Interest

No conflicts of interest.