Design and synthesis of 2,5-di(pyridin-4-yl)-1,3,4-oxadiazole: structural elucidation, DFT insights, and preliminary in silico biological evaluation.

A multidisciplinary experimental and computational investigation of 2,5-di(pyridin-4-yl)-1,3,4-oxadiazole (compound 4) is reported. The compound was synthesized and characterized using FTIR, NMR, ESI-MS, and single-crystal X-ray diffraction, confirming its molecular structure and crystallographic features. To explore its possible pharmacological relevance, SwissTargetPrediction, molecular docking, molecular dynamics simulations, ADME/toxicity prediction, and DFT calculations were performed. SwissTargetPrediction suggested possible interactions with several protein classes, while molecular docking indicated favorable predicted binding poses of compound 4 within selected protein targets, particularly MurA and JAK2. Molecular dynamics simulations over 50 ns supported the preliminary stability of the corresponding protein-ligand complexes under the applied simulation conditions. ADME predictions suggested acceptable rule-based drug-likeness parameters, including predicted gastrointestinal absorption and blood-brain barrier permeability. However, in silico toxicity assessment also indicated potential safety alerts, including hepatotoxicity, neurotoxicity, and carcinogenicity risks, which require experimental verification. DFT calculations at the B3LYP/6-311G level, together with NBO, MEP, and Hirshfeld-related analyses, provided additional insight into the electronic distribution, charge-transfer behavior, and intermolecular interaction features of compound 4. Overall, the combined experimental and computational results identify compound 4 as a structurally confirmed oxadiazole scaffold with computationally suggested interactions toward selected biologically relevant targets. Nevertheless, its predicted biological properties should be considered preliminary and require further in vitro and in vivo validation.