Quantum chemical and experimental studies on polymorphism of antiviral drug Lamivudine

Lamivudine, is chemically known as [4-amino-1-[(2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-1,2-dihydropyrimidin-2-one], is an anti-HIV agent belonging to the class of the non-nucleoside inhibitors of the HIV-1 virus reverse transcriptase. Spectral characteristics of Lamivudine have been studied by methods of FTIR, NMR and quantum chemistry. The FTIR and spectra of Lamivudine was recorded in the regions 4000–400 cm-1. The thermal stability of Lamivudine was studied by the thermogravimetric analysis (TGA). The isotropic 13C-nuclear magnetic shielding constants of this compound were calculated by employing the direct implementation of the gauge including-atomic-orbital (GIAO) method at the HF and B3LYP density functional theory using 6-31G(d,p) basis set. The optimized molecular geometry, bond orders, harmonic vibrational spectrum of anhydrous and hydrated Lamivudine were calculated by restricted Hartree Fock and density functional B3LYP method with the 6-31G(d,p) basis set using Gaussian 03W program.

Polymorphism of HIV drug Lamivudine has been studied along with its structure in this article using a complete vibrational analysis performed by combining the experimental and theoretical information using ab initio and density functional theory based on scaled quantum chemical approach..Figure optionsDownload as PowerPoint slideHighlights
► FT-IR and thermogravimetric analysis of Lamivudine in the solid state were recorded and analyzed.
► The optimized geometry and vibrational spectrum was computed using ab initio HF and DFT methods.
► The complete vibrational assignment and spectroscopic analysis have been carried out.
► Total atomic charges on the various atoms of molecule were obtained by Mulliken population analysis.
► The 13C NMR chemical shift data assignment for Lamivudine have also been reported.