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.

A series of eight stereoisomeric N-(tetrahydroxy bicyclo-[5.1.0]oct-2S*-yl)phthalimides were prepared in one to four steps from N-(bicyclo[5.1.0]octa-3,5-dien-2-yl)phthalimide (±)-7, which is readily available from cyclooctatetraene (62 % yield). The structural assignments of the stereoisomers were established by 1 H NMR spectral data as well as X-ray crystal structures for certain members. The outcomes of several epoxydiol hydrolyses, particularly ring contraction and enlargement, are of note. The isomeric phthalimides as well as the free amines did not exhibit β-glucosidase inhibitory activity at a concentration of less than 100 μM.