DFT and TD-DFT Study of Structural, Electronic and Spectroscopic Properties of Imatinib Using Gaussian

Abstract

Imatinib is a flexible, heteroaromatic tyrosine-kinase inhibitor whose clinical success and solid-state complexity make it a useful model for quantum-chemical investigation. This review summarizes how density functional theory (DFT) and time-dependent density functional theory (TD-DFT), particularly when implemented in Gaussian, can be applied to evaluate the structural, electronic and spectroscopic properties of imatinib and imatinib mesylate. The review covers molecular conformations, protonation states, polymorphism, geometry optimization, vibrational FT-IR/FT-Raman interpretation, frontier molecular orbitals, molecular electrostatic potential, natural bond orbital analysis, solvent effects, and TD-DFT simulation of UV–Vis transitions. The available literature shows that DFT is most informative when it is connected to experimental spectra, X-ray structures and realistic conformational/protonation models rather than a single isolated optimized structure. Recent crystal and computational studies also indicate that the extended and folded forms of imatinib are controlled by a delicate balance of intramolecular torsion, hydrogen bonding, π–π interactions, salt formation and receptor-environment effects. Therefore, a rigorous Gaussian-based study should include conformer screening, frequency validation, appropriate basis sets and functionals, solvent models such as PCM/SMD, and careful assignment of vibrational and electronic transitions.