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

Abstract

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···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(η²-ON)) linkage isomers are metastable species, with MS₁ and MS₂ energies similar to those of other experimentally observed nitroso linkage isomers.

GRAPHICAL ABSTRACT

Keywords:

• isonitroso
• linkage isomer
• thionitrite
• nitrosothiol
• structure elucidation

ACKNOWLEDGMENTS

We thank Dr. I. Novozhilova for assistance with some of the initial exploratory calculations, and the University of Oklahoma for the use of the OSCER supercomputing facilities.

Additional information

Funding

We are grateful to the National Science Foundation of China (grants NSFC-21271104 and NSFC-312000555 to JY) and the U.S. National Science Foundation (CHE-1213674 to GBRA) for funding of this work.