Synthesis, X-Ray Structural Analysis and Computational Studies of a Novel Bis(2-Thienyl)Disulfide Derivative

Abstract

The reaction of ethyl 3-oxobutanoate, carbon disulfide, and chloroacetone in the presence of K₂CO₃ afforded a novel bis(2-thienyl)disulfide derivative (4). The structure of the synthesized compound was confirmed by spectral and X-ray analyses. Hirshfeld quantitative analysis of molecular packing showed that the H···H (40.8–42.1%), O···H (19.7–23.9%), S···H (11.1–13.8%), and C···H (11.9–12.1%) contacts were the most common intermolecular interactions in the crystal. Density functional theory (DFT) calculations were used to perform the charge population analysis and simulate the experimental NMR chemical shifts. Compound 4 was also evaluated in silico against dihydrofolate reductase to elucidate the binding mechanism and orientation around the active sites.

Keywords:

• Density functional calculations
• disulfide linkage
• Hirshfeld quantitative analysis
• molecular docking
• thiophene
• X-ray crystallography

Declaration of interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Additional information

Funding

The authors extend their appreciation to the Deanship of Scientific Research at King Khalid University for its funding of this prolific research group no. (R.G.P. 2/83/41).