Structure, Stability, and Substituent Effects in Aromatic S-Nitrosothiols: The Crucial Effect of a Cascading Negative Hyperconjugation/Conjugation Interaction

Abstract

Aromatic S-nitrosothiols (RSNOs) are of significant interest as potential donors of nitric oxide and related biologically active molecules. Here, we address a number of poorly understood properties of these species via a detailed density functional theory and the natural bond orbital (NBO) investigation of the parent PhSNO molecule. We find that the characteristic perpendicular orientation of the -SNO group relative to the phenyl ring is determined by a combination of the steric factors and the donor-acceptor interactions including, in particular, a cascading orbital interaction involving electron delocalization from the oxygen lone pair to the σ-antibonding S-N orbital and then to the π*-aromatic orbitals, an unusual negative hyperconjugation/conjugation long-range delocalization pattern. These interactions, which are also responsible for the relative weakness of the S-N bond in PhSNO and the modulation of -SNO group properties in substituted aromatic RSNOs, can be interpreted as a resonance stabilization of the ionic resonance component RS(-)/NO(+) of the RSNO electronic structure by the aromatic ring, similar to the resonance stabilization of PhS(-) anion. These insights into the chemistry and structure-property relationships in aromatic RSNOs can provide an important theoretical foundation for rational design of new RSNOs for biomedical applications.

Toward reliable modeling of S-nitrosothiol chemistry: Structure and properties of methyl thionitrite (CH3SNO), an S-nitrosocysteine model

“…21,95,97,99 The antagonistic paradigm also provides a useful framework for designing novel RSNO reactions 97 as well as RSNOs with desired properties. 19,34,98 The accurate FPD data on the CH 3 SNO structure reported here are consistent with the antagonistic model. Compared to HSNO, the S-N bond is ~0.03 Å shorter (1.814 Å vs 1.842 Å in cis-CH 3 SNO and cis-HSNO, respectively) and 2.7 kcal/mol stronger (D 0 is 32.4 vs 29.7 in cis-CH 3 SNO and trans-HSNO), and the rotation barrier is ~3 kcal/mol higher (E 0 ≠ is 12.7 vs.…”

“…It elegantly accounts for the extreme malleability of the S-N bond in the presence of charged or neutral Lewis acids and bases, 20,96,97 provides chemically intuitive description of subtle substituent effects in RSNOs, 19,34,98 and explains the ability of RSNOs to engage in two competing reaction modes with the same molecule. 21,95,97,99 The antagonistic paradigm also provides a useful framework for designing novel RSNO reactions 97 as well as RSNOs with desired properties.…”

“…Although HSNO has been recently proposed to be an important biological RSNO in its own right, [31][32][33] accurate high-level computational-and also recently reported 30 experimental-data on HSNO may have only limited utility for understanding the chemistry of the most biologically abundant cysteine-based RSNOs, because the nature of substituent R may significantly affect the properties of the -SNO group. 19,34 The smallest aliphatic RSNO, methyl thionitrite CH 3 SNO, is a far better model of S-nitrosated cysteine sidechain, a primary aliphatic RSNO. As the prior computational investigations of HSNO have demonstrated, 25,26,28 the computed -SNO group properties show excruciatingly slow convergence with respect to the level of electron correlation treatment and the one-electron basis set size, necessitating using coupled cluster methods with electronic excitations up to quadruple level, and one-electron basis sets up to quintuple-(5Z) and sextuple-zeta (6Z) quality.…”

Research on the bonding properties of vitrified bonds with porous diamonds and the grinding performance of porous diamond abrasive tools

“…The C atom of the SP 2 hybrid orbital formed C=C, and the C=C had one σ bond and one π bond. The π bond tended to bond with electrons from other atoms, making the diamond surface electronegative [30][31][32]. Therefore, the electronegativity of the porous diamond surface was stronger than that of the ordinary diamond surface (Fig.…”

Conjugation and Hyperconjugation Effects: Comparative Studies Through Localized Molecular Orbitals Energy Decomposition Analysis (LMO-EDA) and Natural Bond Orbitals (NBO)

“…4 The most known hyperconjugative effect in the literature is the anomeric effect (negative hyperconjugation n→σ*) which is commonly observed in carbohydrates, and whose definition can be extended to structures with a C-X-C-Y pattern (where X = N, O or S and Y = Br, Cl, F, N, O or S), and the generalized prefix is added to the effect name. 5,6 These concepts are important to explain properties, stabilization and reactivities of chemical structures, 7,8,9 and primarily has its application in organic chemistry and natural products research.…”