Solvent‑Polarity Effects on the Electronic Structure and Vibrational Spectra of Talazoparib: A PCM‑DFT and QTAIM Study

• Comprehensive DFT modeling reveals solvent-dependent stabilization of Talazoparib. • Polar solvents enhance thermodynamic stability and modulate electronic reactivity descriptors. • Vibrational analyses indicate solvent-induced frequency shifts relevant to formulation design. • MEP and QTAIM analyses localize reactive sites and intramolecular interactions across solvents. • Findings provide computational insights to guide solvent-specific drug development strategies. We use density functional theory at the B3LYP/6-311+G(d,p) level with the polarizable continuum model to examine how solvent polarity modulates Talazoparib’s electronic structure and vibrational spectra. Geometry optimizations in polar protic (water, methanol), polar aprotic (acetonitrile, DMSO), and nonpolar (n-hexane) media enabled evaluation of frontier orbital energies, chemical potential, global hardness/softness, atomic charges, dipole moments, electronic energies, and solvation stabilization. Solvation energies ranged from –10.5 kcal·mol⁻¹ in n-hexane to –28.3 kcal·mol⁻¹ in water, with dipole moments increasing by up to 1.2 D in polar media. Vibrational analyses reveal solvent-induced red shifts of up to 15 cm⁻¹ in carbonyl and aromatic stretching modes, reflecting weakened bond force constants and enhanced solute–solvent interactions, particularly hydrogen bonding in polar media. Molecular electrostatic potential mapping and QTAIM topological analysis elucidate reactive sites and intramolecular hydrogen bonding. A HOMO–LUMO gap decrease from 5.42 eV (n-hexane) to 4.87 eV (water) underscores solvent impact. These findings offer quantitative guidance for solvent-tailored formulations and analogue design.