Interrelationships between conformational dynamics and the redox chemistryof S-nitrosothiols

An increasing number of biological roles are ascribed to S-nitrosothiol com pounds. Their inherent instability in multicomponent solutions is recognize d 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 physi cal 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, w hich is readily prepared by the biphasic nitrosation of Ph3CSH, is characte rized by X-ray diffraction, vibrational spectroscopy, electrochemistry, and spectroelectrochemistry. Its behavior is contrasted with that of known S-n itrosothiols derived from glutathione and N-acetyl-D,L-penicillamine, which also are demonstrated to undergo facile electrochemical and chemical denit rosylation. The structure and vibrational data are contrasted with ab initi o results calculated with density functional theory, B3LYP/6-311+G*, which indicates that electron transfer populates an orbital that is strongly ON-S R antibonding in character. The bond lengths observed for Ph3CSNO (N-O 1.18 Angstrom, S-N 1.79 Angstrom) indicate a formal nitrogen-to-oxygen double b ond and sulfur-oxygen single bond. However, theoretical calculations show a measure of delocalization over the -CSNO framework. This is supported by e xperimental results that show low nu(NO) vibrational frequencies (1470-1515 cm(-1)) and a large Delta G double dagger (10.7 kcal/mol) for syn-anti int erconversion determined by variable-temperature N-15 NMR. Together these re sults demonstrate an important new reactivity pattern for this biologically critical class of compounds.