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Lewis Acid Coordination Redirects S‐Nitrosothiol Signaling Output
Author(s) -
Hosseininasab Valiallah,
McQuilken Alison C.,
Bakhoda Abolghasem Gus,
Bertke Jeffery A.,
Timerghazin Qadir K.,
Warren Timothy H.
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202001450
Subject(s) - chemistry , lewis acids and bases , reactivity (psychology) , intramolecular force , coordination sphere , stereochemistry , redox , coordination complex , electron transfer , medicinal chemistry , one electron reduction , molecule , catalysis , organic chemistry , electrochemistry , medicine , alternative medicine , electrode , pathology , metal
S‐Nitrosothiols (RSNOs) serve as air‐stable reservoirs for nitric oxide in biology. While copper enzymes promote NO release from RSNOs by serving as Lewis acids for 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(C 6 F 5 ) 3 coordinates to the RSNO oxygen atom, leading to profound changes in the RSNO electronic structure and reactivity. Although RSNOs possess relatively negative reduction potentials, B(C 6 F 5 ) 3 coordination increases their reduction potential by over 1 V into the physiologically accessible +0.1 V vs. NHE. Outer‐sphere chemical reduction gives the Lewis acid stabilized hyponitrite dianion trans ‐[LA‐O‐N=N‐O‐LA] 2− [LA=B(C 6 F 5 ) 3 ], which releases N 2 O upon acidification. Mechanistic and computational studies support initial reduction to the [RSNO‐B(C 6 F 5 ) 3 ] radical anion, which is susceptible to N−N coupling prior to loss of RSSR.