2,5-Disubstituted structures of 1,3,4-oxadiazole and 1,3,4-thiodiazole for anti-inflammatory potential: DFT approach for the structural aspects

• Published in: Journal of molecular structure 2024-12, Vol.1318, p.139263, Article 139263
• Main Authors: Veeramani, Vairaperumal, Ganesh, Pothapragada S．K．Prabhakar, Bharanidharan, Sarangapani, Muthuraja, Perumal, Govindasamy, Chandramohan, Rajamohan, Rajaram
• Format: Article
• Language: English
• Subjects: 1,3,4-oxadiazole; 1,3,4-thiodiazole; Anti-inflammatory; B3LYP/6–311++G (d,p); NLO property
• ISSN: 0022-2860
• DOI: 10.1016/j.molstruc.2024.139263

•[3 + 2] annulation method used for the synthesis of substituted 1,2,4-oxadiazole derivatives.•Utilized the environmentally friendly solvent PEG-400 for the synthesis.•The optimized geometrical parameters are obtained using the B3LYP/6–311++G (d,p).•A decrease in the energy gap and an increase in the NLO property of the molecules leads to good biological activity.•A promising anti-inflammatory and anti-diabetic activity, as evidenced by protein denaturation assay studies. We suggest a [3 + 2] annulation method that combines aromatic acid with acyl hydrazide using p-TSA, resulting in the formation of highly substituted 1,3,4-oxadiazole derivatives. These reactions take place efficiently under specific conditions: microwave irradiation, employing a metal-free environment, utilizing the environmentally friendly solvent PEG-400, and requiring only a short reaction time. Furthermore, employing similar conditions in the presence of Lawesson's reagent yields 1,3,4-thiadiazole derivatives. This method exhibits several notable characteristics, including atom and step economy, utilization of easily accessible raw materials, and simplicity in operation. From the DFT approach, the optimized geometrical parameters are obtained using the B3LYP/6–311++G (d,p) level of theory. There is a decrease in the energy gap and NLO property increases in nature and leads to more biological activity. Notably, there was a reduction in the energy gap, accompanied by an increase in the nonlinear optical property, and suggested the synthesized compounds exhibit heightened biological activity. Furthermore, these compounds demonstrate promising anti-inflammatory and anti-diabetic activity, as evidenced by protein denaturation assay studies. [Display omitted]