Symmetry impact of 2,5-bis(cycloalkylsulfenyl)[1,3,4]thiadiazoles on their physicochemical properties, thermal behaviors, and bacterial activity

Regarding the importance of 1,3,4-thiadiazoles (TDs) due to versatile biological activity and for investigation of the symmetry impact on thermal behavior and antibacterial activity of 2,5-bis(cycloalkylsulfenyl)[1,3,4]thiadiazole (R₂TD), two new derivatives of symmetric and asymmetric R₂TD viz. 2,5-bis(cyclopentylsulfenyl)[1,3,4]thiadiazole (C5TD) and 2-cyclohexylsulfenyl-5-cyclopentylsulfenyl[1,3,4]thiadiazole (C6C5TD), were synthesized through the nucleophilic substitution reaction in greener conditions. The chemical structure of products was elucidated by the spectroscopic analysis. Interestingly, suitable crystals of C5TD could be isolated for single-crystal X-ray diffraction analysis from <i>n</i>-hexane after tedious work, whereas, the asymmetric derivative was a low viscous liquid. Then, the influence of symmetry on the thermal behavior of two new TD derivatives and C6TD was studied by TG-DTG and DSC. The thermal behavior of C5TD in a crystalline state is analyzed in detail for the first time. The pharmacokinetics and toxicology of three derivatives of R₂TD were evaluated by two prediction tools of SwissADME and T.E.S.T, respectively. Moreover, the <i>in vitro</i> antibacterial activity of the new TD derivative was evaluated against <i>S. aureus</i> and <i>E. coli</i> as gram-positive and gram-negative bacterial species and compared with the activities of chloromycetin and gentamicin as standard antibiotics by the broth microdilution method.