Rotational spectrum, molecular structure and stereochemistry of the antitumor dithiolethione oltipraz

Sulfur-containing heterocycles play a prominent role in biomedical research because of their wide range of pharmacological activities. In this work we report on oltipraz, a synthetic 1,2-dithiole-3-thione derivative recognized for its chemo and hepatoprotective effects. The investigation has addressed the stereochemistry, molecular structure and intramolecular interactions of the title compound using a combination of chirped-pulsed Fourier transform microwave spectroscopy and quantum chemical calculations. The parent and three 34 S monosubstituted isotopologues were assigned in the rotational spectrum, confirming the presence of a single synclinal conformation in the gas phase. Density functional theory calculations (B3LYP-D3(BJ), ωB97X-D and B2PLYP-D3(BJ)) supplemented the experiment. The origin of the conformational preferences was further investigated using the Natural Bond Orbital (NBO) and Non-Covalent Interaction (NCI) analyses. Both approaches suggest a limited contribution of the N···S intramolecular interaction in stabilizing the observed molecular conformation.