A Triazole–Thiophene‐Based Compound with Potential Nonlinear Optical Properties and β‐Lactamase Inhibitory Activity to Protect β‐Lactam Antibiotics

Abstract A novel compound, (5‐amino‐3‐(methylthio)‐1 H ‐1,2,4‐triazole‐1‐yl)(thiophen‐2‐yl)methanone (TAT), combining 1,2,4‐triazole and thiophene scaffolds, has been synthesized and characterized using crystallographic, spectroscopic, thermal, and computational methods. The crystalline packing of TAT is mainly controlled by hydrogen bonds, chalcogen bonds, C–H⋯π and π⋯π interactions, revealing the presence of R 6 6 (38), R 3 3 (17), and R 2 2 (8) fused rings. Hirshfeld surface analysis revealed a stable dimeric structure (DTAT), which was energetically favored by 70.16 kJ/mol, making it the basis for further analysis. Quantum chemical calculations indicated a small HOMO–LUMO gap and significant electronic delocalization in its dimeric structure. DTAT exhibited strong second‐order nonlinear optical (NLO) potential, with hyperpolarizability 4.4 times that of KDP and 15 times higher than that of urea. Dispersion energy was dominant in the monomer, while electrostatics defined the dimer. Molecular docking revealed the interactions of TAT with serine β‐lactamase, specifically targeting key residues and facilitating effective Zn 2 ⁺ binding, which suggests inhibitory potential. DTAT also demonstrated good interaction with metallo‐β‐lactamase, supporting its role in enhancing the activity of β‐lactam antibiotics. The bioavailability radar indicated favorable lipophilicity, polarity, and flexibility. Overall, DTAT is a promising candidate for NLO applications and β‐lactamase inhibition.