Study of polymorphism in imatinib mesylate: a quantum chemical approach using electronic and vibrational spectra

Imatinib mesylate, 4-(4-methyl-piperazin-1-ylmethyl)-N-u[4-methyl-3-(4-pyridin-3-yl)pyrimidine-2-ylamino)phenyl]benzamide methanesulfonate is a therapeutic drug that is approved for the treatment of chronic myelogeneous leukemia (CML) and gastrointestinal stromal tumors (GIST). It is known that imatinib mesylate exists in two polymorphic forms α and β. However, β-form is more stable than the α-form. In this work, we present a detailed vibrational spectroscopic investigation of β-form by using FT-IR and FT-Raman spectra. These data are supported by quantum mechanical calculations using DFT employing 6-311G(d,p) basis set, which allow us to characterize completely the vibrational spectra of this compound. The FT-IR spectrum of α-form has also been discussed. The importance of hydrogen-bond formation in the molecular packing arrangements of both forms has been examined with the vibrational shifts observed due to polymorphic changes. The red shift of the NH stretching bands in the infrared spectrum from the computed wavenumber indicates the weakening of the NH bond. The UV-vis spectroscopic studies along with the HOMO-LUMO analysis of both polymorphs (α and β) were performed and their chemical activity has been discussed. The TD-DFT method was used to calculate the electronic absorption spectra in the gas phase as well as in the solvent environment using IEF-PCM model and 6-31G basis set. Finally, the results obtained complements to the experimental findings.