Timerghazin Qadir K, Talipov Marat R
Department of Chemistry, Marquette University, P.O. Box 1881, Milwaukee, Wisconsin 53201-1881, United States.
J Phys Chem Lett. 2013 Mar 21;4(6):1034-8. doi: 10.1021/jz400354m. Epub 2013 Mar 15.
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.
S-亚硝基硫醇（RSNOs）是一氧化氮（NO）及其生理活性的普遍载体，其反应在生物系统中受到严格调控，但其调控机制尚未完全明确。在此，我们通过计算证明，生物可及的外部电场（EEFs）可通过调节RSNOs的两个次要拮抗共振结构，显著改变RSNO的性质，这两个共振结构具有相反的形式电荷分布和键合模式。由于这些共振贡献与RSNO与亲核试剂反应的两种竞争模式相关，即通过N原子或S原子定向亲核攻击，预计EEFs能够有效控制RSNO与硫醇的重要生物反应。例如，EEF催化可能是蛋白质转S-亚硝基化反应高选择性背后的机制之一，或者是通过RSNO S-硫醇化反应形成推定的硝酰基（HNO）的机制之一。
