A comparative computational study on molecular structure, NBO analysis, multiple interactions, chemical reactivity and first hyperpolarisability of imatinib mesylate polymorphs using DFT and QTAIM approach

Imatinib, a phenylaminopyrimidine compound is a therapeutic drug for treatment of chronic myelogeneous leukaemia and gastrointestinal stromal tumours. It is well known that imatinib mesylate (ImM) exists in two polymorphic forms α and β. In this work, a computational study on molecular properties of ImM polymorphs is presented using density functional theory, B3LYP functional and 6-311G(d,p) as basis set. Natural bond orbital analysis is carried out to investigate the various conjugative and hyperconjugative interactions within the molecule and their second-order stabilisation energy (E(2)). The local nucleophilic reactivity descriptors such as Fukui functions (), local softness () and electrophilicity indices () analyses are carried out to determine the reactive sites within the molecule. To determine strength and nature of intra- and intermolecular interactions, topological parameters as electron density (ED) (ρBCP), Laplacian of ED (▽2ρBCP) and total electron energy density (HBCP) at bond critical points have been analysed by ‘quantum theory of atoms in molecules’ in detail. The computed first hyperpolarisability (β0) for both forms of ImM molecule (10.927 and 10.354 × 10− 30 esu) suggests that the investigated molecule is an attractive object in future for non-linear optical properties. Molecular electrostatic potential surface of ImM has been mapped to predict the inhibitory activity and binding affinity with a panel of protein tyrosine kinases.