Toward Reliable Modeling of S-Nitrosothiol Chemistry: Structure and Properties of Methyl Thionitrite (CH$_3$SNO), an S-Nitrosocysteine Model

Abstract

Methyl thionitrite CH$_3$SNO is an important model of S-nitrosated cysteine aminoacid residue (CysNO), a ubiquitous biological S-nitrosothiol (RSNO) involved in numerous physiological processes. Here, we report accurate structure and properties of CH$_3$SNO using accurate ab initio Feller-Peterson-Dixon (FPD) approach. The FPD scheme included CCSD(T)-F12/CBS extrapolated values, as well as corrections for the quadruple coupled cluster excitations $\Delta$(Q), core-valence$\Delta$CV and scalar-relativistic $\Delta$SR effects. The FPD scheme for the energetic parameters also included harmonic zero-point vibrational energy (ZPE) corrected for anharmonicity. The S-N bond length in cis-CH$_3$SNO is calculated as 1.814 {\AA}, and its dissociation energy $D_0=32.4$ kcal/mol in the gas phase. The trans-CH$_3$SNO conformation is 1.2 kcal/mol less stable ($\Delta E_0$) compared to cis-CH$_3$SNO, with a sizeable cis-trans isomerization barrier $\Delta E_0^\ne = 12.7$ kcal/mol. The paradox of the unusually long and weak S-N bond, and hindered rotation along the S-N bond, was rationalized via the detailed analysis of the underlying electronic structure of the -SNO group using Natural Resonance Theory (NRT). After the benchmarking of the density functional theory (DFT) methods against the FPD reference, we recommend mPW2PLYP and mPW2PLYPD double hybrid functionals for calculation of the geometric properties, vibrational frequencies and isomerization barriers of S-nitrosothiols, and PBE0 (PBE0-GD3) hybrid functional for the S-N BDEs. The abovementioned DFT methods are capable of capturing the change in electronic structure and properties of the -SNO fragment, when the CH$_3$SNO molecule is exposed to the influence of physiologically feasible external electric field $F_Z$.