Interrelationships between Conformational Dynamics and the Redox Chemistry of S-Nitrosothiols

An increasing number of biological roles are ascribed to S-nitrosothiol compounds. Their inherent instability in multicomponent solutions is recognized as forming the basis for their physiological effects, such as the release of nitric oxide or the posttranslational modification of protein cysteine residues. This reactivity also contributes to the lack of fundamental physical and spectroscopic data that have been reported. We have addressed this issue through characterization of the physical and spectroscopic properties of a group of commonly used S-nitrosothiols. The S-nitrosothiol Ph3CSNO, which is readily prepared by the biphasic nitrosation of Ph3CSH, is characterized by X-ray diffraction, vibrational spectroscopy, electrochemistry, and spectroelectrochemistry. Its behavior is contrasted with that of known S-nitrosothiols derived from glutathione and N-acetyl-d,l-penicillamine, which also are demonstrated to undergo facile electrochemical and chemical denitrosylation. The structure and vibrational data are contrasted with ab initio results calculated with density functional theory, B3LYP/6-311+G*, which indicates that electron transfer populates an orbital that is strongly ON−SR antibonding in character. The bond lengths observed for Ph3CSNO (N−O 1.18 Å, S−N 1.79 Å) indicate a formal nitrogen-to-oxygen double bond and sulfur−oxygen single bond. However, theoretical calculations show a measure of delocalization over the −CSNO framework. This is supported by experimental results that show low ν(NO) vibrational frequencies (1470−1515 cm-1) and a large ΔG ⧧ (10.7 kcal/mol) for syn−anti interconversion determined by variable-temperature 15N NMR. Together these results demonstrate an important new reactivity pattern for this biologically critical class of compounds.