Despite the enormous biological significance, the structure-stability relationship in S-Nitrosothiols (RSNOs) that govern their activity in vivo is not well understood We provide useful structural

There is currently great interest in S-nitrosothiols (RSNOs) because formation of protein-based RSNOsprotein S-nitrosationhas been recently recognized as a major pathway of the biological function of nitric oxide, NO. Despite the growing number of S-nitrosated proteins identified in vivo, enzymatic processes that control reactions of biological RSNOs are still not well understood. In this article, we use a range of models to computationally demonstrate that specific interactions of RSNOs with charged and polar residues in proteins can result in dramatic modification of RSNO structure, stability, and reactivity. This unprecedented sensitivity of the −SNO group toward interactions with charged species is related to their unusual electronic structure that can be elegantly expressed in terms of antagonistic resonance structures. We propose a ‘ligand effect map’ (LEM) approach as an efficient way to estimate the environment effects on the −SNO groups in proteins without performing electronic structure calculations. Furthermore, the calculated ¹⁵N NMR signatures of these specific interactions suggest that ¹⁵N NMR spectroscopy can be an effective technique to identify and study these interactions experimentally. Overall, the results of this study suggest that RSNO reactions in vivo should be tightly controlled by the protein environment via modulation of the RSNO electronic structure.

Structural properties and isomerisation of simple S-nitrosothiols: ab initio studies with a simplified treatment of correlation effects

Protein Control of S-Nitrosothiol Reactivity: Interplay of Antagonistic Resonance Structures B

Double, Rydberg, and charge transfer (CT) excitations have been great challenges for time-dependent density functional theory (TDDFT). Starting from an (N ± 2)-electron single-determinant reference, we investigate excitations for the N-electron system through the pairing matrix fluctuation, which contains information on two-electron addition/removal processes. We adopt the particle-particle random phase approximation (pp-RPA) and the particle-particle Tamm-Dancoff approximation (pp-TDA) to approximate the pairing matrix fluctuation and then determine excitation energies by the differences of two-electron addition/removal energies. This approach captures all types of interesting excitations: single and double excitations are described accurately, Rydberg excitations are in good agreement with experimental data and CT excitations display correct 1/R dependence. Furthermore, the pp-RPA and the pp-TDA have a computational cost similar to TDDFT and consequently are promising for practical calculations.

http://absimage.aps.org/image/MAR14/MWS_MAR14-2013-005856.pdf

Double, Rydberg and Charge Transfer Excitations from Pairing Matrix Fluctuation and Particle-Particle Random Phase Approximation

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 A, 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 $F_Z$.

/pdf/toward-reliable-modeling-of-s-nitrosothiol-chemistry-23ea7qhug2.pdf

Structural properties and isomerisation of simple S-nitrosothiols: ab initio studies with a simplified treatment of correlation effects

Citations

Protein Control of S-Nitrosothiol Reactivity: Interplay of Antagonistic Resonance Structures B

Double, Rydberg and Charge Transfer Excitations from Pairing Matrix Fluctuation and Particle-Particle Random Phase Approximation

References

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