Unraveling the S–S⋯π interactions in furan–disulfide heterodimers: insights from microwave spectroscopy and ab initio computations

Abstract

The non-covalent interactions between sulfur atoms and aromatic rings are critically important in maintaining the structural integrity, stability, and functionality of proteins and protein–ligand complexes. Nonetheless, the fundamental characteristics of the interaction between the S atom of a disulfide bond and an electron-rich aromatic ring (S–S⋯π) remain insufficiently characterized. Herein, we investigated the S–S⋯π interactions through an integrated approach combining conformer-specific high-resolution rotational spectroscopy and quantum chemical calculations. Experimentally, the predicted most stable isomer was detected for the furan⋯dimethyl disulfide (DMDS) heterodimer, showing the characteristic tunnelling splitting patterns attributed to the internal rotation of two methyl groups, while two isomers were observed for the furan⋯diethyl disulfide (DEDS) heterodimer. The observed isomers of the model heterodimers are primarily stabilized by the S–S⋯π interactions as well as the C–H⋯S, C–H⋯π, and C–H⋯O hydrogen bonds. The intermolecular interactions were comprehensively analyzed by using non-covalent interaction (NCI), natural bond orbital (NBO), and symmetry-adapted perturbation theory (SAPT) approaches. This study improves the understanding of sulfur–aromatic interactions, providing benchmark data for refining theoretical descriptions of disulfide–aromatic motifs.