Molecular structure and vibrational spectroscopic analysis of an antiplatelet drug; clopidogrel hydrogen sulphate (form 2) - A combined experimental and quantum chemical approach

Clopidogrel hydrogen sulphate which belongs to a class of medicine called antiplatelet drugs. Chemically it is methyl (+)-(S)-alpha-(2-chlorophenyl)-4,5,6,7-tetrahydrothieno [3,2-c] pyridine-5-acetate hydrogen sulphate having the empirical formula C16H17CINO2S.HSO4 and molecular mass 321.82 g/mol. The present study is confined to vibrational spectroscopy of the polymorph identified as form 2 of the clopidogrel hydrogen sulphate. The vibrational analysis of clopidogrel hydrogen sulphate salt (form 2) considering separately the two counterions has been performed. We also report a theoretical and experimental study of the molecular conformation and vibrational dynamics of the independent moieties of the clopidogrel hydrogen sulphate salt. The equilibrium geometry, harmonic vibrational frequencies, infrared intensities and activities of Raman scattering were calculated by ab initio Hartree-Fock and density functional theory employing B3LYP with complete relaxation in the potential energy surface using 6-311++G(d,p) basis set. The calculated wavenumbers after a proper scaling show a very good agreement with the observed values. A complete vibrational assignment is provided for the observed Raman and infrared spectra of clopidogrel hydrogen sulphate form 2. (C) 2009 Elsevier B.V. All rights reserved.