Unveiling the effects of tautomerism, pH, and solvation on the UV/Vis spectrum of sulfapyridine: a joint theoretical and experimental study

Abstract Context Sulfapyridine (SPY) is a sulfonamide frequently detected as contaminant in aquatic environments, largely due to incomplete metabolism and its extensive use in livestock production and other anthropogenic activities. The spectroscopic properties of SPY are strongly influenced by prototropic tautomerism, pH conditions, and solvation effects. Herein, a joint theoretical–experimental study investigates the ultraviolet/visible (UV/Vis) electronic absorption spectra of SPY and its sulfonimide tautomer (TAUT) across different protonation states. Energetic analyses using a hybrid cluster-continuum (HCC) solvation approach reveal that TAUT forms predominate in aqueous solution. Hybrid solvation significantly lowers the tautomerization barriers (from 37.1 to 10.4 kcal.mol $$^{-1}$$ - 1 for neutral and from 35.4 to 8.6 kcal.mol $$^{-1}$$ - 1 for protonated forms), highlighting the catalytic role of the solvent. Theoretical data reproduce the main features of the experimental UV/Vis spectra, reinforcing that TAUT forms dominate in solution and exhibit characteristic absorption bands around 300 nm. These findings demonstrate that tautomeric equilibria and hybrid solvation are factors that strongly influence the spectroscopic properties of SPY in water and should be considered in studies involving sulfonamides, including biological interactions and photodegradation pathways. Methods Conformational analyses are carried out at the GFN2-xTB/GBSA level (CREST). Cluster structures from SOLVATOR, with posterior geometry optimizations and vibrational frequency calculations, are achieved at the GFN2-xTB/ALPB level in water (ORCA 6.0.1). DFT calculations are performed at the PBE-D3/cc-pVTZ/PCM level (Gaussian 09) for providing equilibrium geometries for the lowest-energy conformers. Improved single-point energies are retrieved from CAM-B3LYP-D3(BJ)/def2-QZVPP/SMD calculations, while TD-DFT data reached at the CAM-B3LYP/def2-TZVP/C-PCM level are employed for UV/Vis spectra simulation (ORCA 5.0.4).