Solvent-controlled photodegradation pathways of a bioactive tetrazole-thiadiazole conjugate revealed by TDDFT, UV-Vis...

The photophysical and photochemical behaviour of 2-methyl-5-((1-phenyl-1H-tetrazol-5-yl)thio)-1,3,4-thiadiazole (MeTDZ-PhTTZ) was investigated through a combined computational and experimental approach. This heterocyclic compound, containing both tetrazole and 1,3,4-thiadiazole moieties of recognized medicinal relevance, has shown biological activity, but its excited-state properties and photodegradation pathways remain unexplored. Density functional theory and time-dependent density functional theory calculations were performed. Solvent effects of acetonitrile and ethanol were included through a polarizable continuum model. Theoretical calculations comprised the determination of UV-Vis absorption spectra, frontier molecular orbitals, HOMO-LUMO orbital energy gaps, and IR spectra of the singlet ground state, first singlet excited state, and first triplet excited state. Experimental UV-Vis and IR spectroscopy showed good agreement with the calculated spectra, supporting the proposed electronic transitions and excited-state behavior. Photolysis experiments revealed marked solvent-dependent photodegradation, demonstrating that the protic or aprotic nature of the solvent strongly influences the photochemical pathway. Based on computational results and literature precedents for tetrazole photochemistry, plausible degradation mechanisms involving nitrogen extrusion and formation of distinct photoproducts are proposed. LC-MS analysis provided experimental evidence for extensive formation of a major photoproduct in acetonitrile, whereas ethanol promoted a different and less extensive degradation profile. These results provide molecular-level insight into the excited-state properties, solvent effects, and photochemical reactivity of MeTDZ-PhTTZ, contributing to the understanding of heterocyclic systems of potential pharmaceutical and materials relevance.