Lewis Acid Coordination Redirects S-Nitrosothiol Reduction

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.