Linkage Isomerization in Nitrosothiols (RSNOs): The X-ray Crystal Structure of an <i>S</i>-nitrosocysteine and DFT Analysis of its Metastable MS<sub>1</sub> and MS<sub>2</sub> Isomers

<p>Density functional theory calculations reveal that the previously unreported nitrosothiol MS<sub>1</sub> and MS<sub>2</sub> linkage isomers are metastable species with energies similar to those determined for other experimentally observed XNO linkage isomers.</p> <p>Nitrosation of protein cysteines to yield <i>S</i>-nitrosocysteine (cySNO) is an important component of nitric oxide biology. However, high-resolution structural data of cySNO in the absence of protein environment effects is lacking, as is information on cySNO linkage isomers. We report the ordered X-ray crystal structure of a cySNO compound. We employ density functional theory calculations to probe the ground-state and linkage isomers of cySNO, CH<sub>3</sub>SNO, and CF<sub>3</sub>SNO. The HOMO of CH<sub>3</sub>SNO contains an intramolecular CH···O interaction that helps rationalize the stability of the <i>cis</i> conformation; this interaction is absent in CF<sub>3</sub>SNO, which favors the <i>trans</i> conformation. We show that the isonitroso MS<sub>1</sub> (RSON) and side-on MS<sub>2</sub> (RS(η<sup>2</sup>-ON)) linkage isomers are metastable species, with MS<sub>1</sub> and MS<sub>2</sub> energies similar to those of other experimentally observed nitroso linkage isomers.</p>