Linkage Isomerization in Nitrosothiols (RSNOs): The X-ray Crystal Structure of an S-nitrosocysteine and DFT Analysis of its Metastable MS1 and MS2 Isomers

Density functional theory calculations reveal that the previously unreported nitrosothiol MS1 and MS2 linkage isomers are metastable species with energies similar to those determined for other experimentally observed XNO linkage isomers. Nitrosation of protein cysteines to yield S-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, CH3SNO, and CF3SNO. The HOMO of CH3SNO contains an intramolecular CH center dot center dot center dot O interaction that helps rationalize the stability of the cis conformation; this interaction is absent in CF3SNO, which favors the trans conformation. We show that the isonitroso MS1 (RSON) and side-on MS2 (RS(eta(2)-ON)) linkage isomers are metastable species, with MS1 and MS2 energies similar to those of other experimentally observed nitroso linkage isomers.