Unprecedented External Electric Field Effects on S-Nitrosothiols: Possible Mechanism of Biological Regulation?

Reactions of S-nitrosothiols (RSNOs), ubiquitous carriers of nitric oxide NO and its physiological activity, are tightly regulated in biological systems, but the mechanisms of this regulation are not well understood. Here, we computationally demonstrate that RSNO properties can be dramatically altered by biologically accessible external electric fields (EEFs) by modulation of the two minor antagonistic resonance structures of RSNOs, which have opposite formal charge distributions and bonding patterns. As these resonance contributions relate to the two competing modes of RSNO reactivity with nucleophiles, via N- or S-atom directed nucleophilic attack, EEFs are predicted to be efficient in controlling biologically important RSNO reactions with thiols. For instance, EEF catalysis might be one of the mechanisms behind the high selectivity of protein trans-S-nitrosation reactions, or putative nitroxyl HNO formation via RSNO S-thiolation reactions.