DFT investigation of 2-(2,2-difluoroethoxy)-N-(5,8-dimethoxy[1,2,4]triazolo[1,5-c]pyrimidin-2-yl)-6-(trifluoromethyl)benzenesulfonamide (DTPB): Electronic structure, nonlinear optical response and bioactivity insights

The molecular structure of 2-(2,2-difluoroethoxy)-N-(5,8-dimethoxy-[1,2,4]triazolo[1,5- c ]pyrimidin-2-yl)-6-(trifluoromethyl)benzenesulfonamide (DTPB), which incorporates biologically relevant triazolopyrimidine and sulfonamide groups, has not yet been comprehensively investigated using theoretical approaches. This work presents the first integrated computational assessment of DTPB, providing a detailed correlation between its structural, electronic, spectroscopic, intermolecular, and molecular recognition characteristics. Density functional theory calculations performed at the B3LYP/6-311G(d,p) level confirmed a well- defined geometry for DTPB. The computed HOMO–LUMO energy gap of 4.61–4.89 eV indicates moderate molecular stability together with favourable intramolecular charge-transfer behaviour. The electronic distribution evaluated using Mulliken population analysis, molecular electrostatic potential (MEP), electron localization function (ELF), and localized orbital locator (LOL) identifies the oxygen- and nitrogen-containing regions as the principal reactive sites. Furthermore, reduced density gradient (RDG) and non-covalent interaction (NCI) analyses reveal that hydrogen-bonding and van der Waals interactions contribute substantially to the stabilization of the molecular structure. The estimated first-order hyperpolarizability (β = 1.5 × 10 −30 esu) is approximately eleven times greater than that of urea (0.13 × 10 −30 esu), highlighting the strong nonlinear optical (NLO) response and efficient charge-transfer characteristics of DTPB. Graph-theoretical evaluation further demonstrates the structural complexity of the molecule, with the calculated topological indices (M₁ = 170, M₂ = 201, and HM = 878). Pharmacokinetic assessment using the BOILED-Egg model predicts poor gastrointestinal absorption together with negligible blood–brain barrier permeability. Molecular docking investigations produced moderate binding affinities toward the protein targets 1 N10, 6OAN, and 1YHY, indicating that DTPB could provide a useful starting scaffold for future ligand optimization, although experimental studies are necessary to validate its predicted biological activity.