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.