Toward reliable modeling of S-nitrosothiol chemistry: Structure and properties of methyl thionitrite (CH3SNO), 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. As such, CH 3 SNO can provide insights into the intrinsic properties of the -SNO group in CysNO, in particular, its weak and labile S-N bond. Here, we report an ab initio computational investigation of the structure and properties of CH 3 SNO using a composite Feller-Peterson-Dixon (FPD) scheme based on the explicitly-correlated coupled cluster with single, double, and perturbative excitations calculations extrapolated to the complete basis set limit, CCSD(T)-F12/CBS, with a number of additive corrections for the effects of quadruple excitations, core-valence correlation, scalar-relativistic and spin-orbit effects, as well as harmonic zero-point vibrational energy (ZPE) with an anharmonicity correction. These calculations suggest that the S-N bond in CH 3 SNO is significantly elongated (1.814 Å), has low stretching frequency and dissociation energy values,

Computational Structural Biology of S-nitrosylation of Cancer Targets

“…This stabilization is even more pronounced when moving from gas phase to a polarizable aqueous environment by using an implicit solvent model, suggesting that the environment provided by the protein embedding might also offer a similar stabilization. This hypothesis is supported by investigations highlighting the effect of external electric fields on the RSNO electronic density, that can lead to its dramatic polarization ( 185 , 186 , 188 ). Noteworthy, the biologically relevant competition between the S -thiolation and the S -transnitrosylation processes might then be driven by the polarization of the -SNO by its surroundings.…”

“…Indeed, the complexity of the S-N bond nature might result from the combination of three different resonance structures: the neutral -S-N = O, the zwitterionic -S + = N-O − , and the RS − /NO + ion pair. Further investigations on the larger CH 3 SNO model confirmed this feature, yet it seems less pronounced for CH 3 SNO than HSNO ( 186 ). Unfortunately, no further evidences about RSNOs multi-reference character has been reported for larger models of RSNOs, the computational cost of such high-level calculations being prohibitive.…”

“…An interesting property of the -SNO moiety is the multi-reference character induced by the dramatic difference between its resonance structures (Figure 4) , as highlighted in several theoretical works published by Timerghazin's group ( 184 – 186 , 188 , 201 ). Indeed, the use of an external electric field (EEF) in QM calculations brought out the high polarizability of the–SNO moiety, with modulation between two minor resonance structures, which exhibit opposite charge distribution and reactivity.…”

“…Overall, several of these theoretical investigations highlighted the reliability and robustness of the B3P86 functional with large basis sets for the calculation of S-N bond energy dissociation, spectroscopic and structural properties of small RSNO ( 182 , 189 , 193 ). Likewise, the PBE0 functional with large basis sets has also been revealed as a good compromise between computational time and accuracy in describing RSNO properties ( 179 , 186 , 188 , 194 ). However, it is always strongly recommended to verify results obtained by DFT methods using more computationally demanding higher-level methods ( 186 ).…”

“…Likewise, the PBE0 functional with large basis sets has also been revealed as a good compromise between computational time and accuracy in describing RSNO properties ( 179 , 186 , 188 , 194 ). However, it is always strongly recommended to verify results obtained by DFT methods using more computationally demanding higher-level methods ( 186 ). Likewise, experimental data on RSNOs characteristics, mainly from NMR studies, have been reported and can validate values predicted by computational chemistry ( 44 , 195 – 197 ).…”