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

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.