title: FT-Raman, FT-IR, UV spectroscopic, NBO and DFT quantum chemical study on the molecular structure, vibrational and electronic transitions of clopidogrel hydrogen sulfate form 1: a comparison to form 2.
abstract: Clopidogrel hydrogen sulfate (+)-(S)-(2-chlorophenyl)-6,7-dihydrothieno[3,2-c]pyridine-5(4H)-acetate sulfate (1:1), is a selective adenosine diphosphate (ADP) receptor antagonist often used in the treatment of coronary artery, peripheral vascular and cerebrovascular diseases. In the present communication, a comparative study of two polymorphic forms (forms 1 and 2) of clopidogrel hydrogen sulfate (CLP) has been reported. There is difference in conformation and intermolecular hydrogen bonding pattern of two forms. These differences are nicely reflected in the vibrational spectra. The molecular structure, fundamental vibrational frequencies and intensity of the vibrational bands of CLP form 1 are interpreted with the aid of structure optimizations and normal mode analysis based on ab initio HF and DFT method employing 6-311++G(d,p) basis. Polymorphism in CLP have been studied using various characterization tools like FT-Raman, FT-IR spectroscopy and DSC in combination with the quantum chemical calculations. UV-vis spectroscopic studies along with HOMO-LUMO analysis of both polymorphs were performed. The solvent effect calculated by TD-DFT/IEF-PCM/6-31G model results complements with the experimental findings. Stability of the molecule arising from hyper conjugative interactions and charge delocalization has been analyzed using natural bond orbital (NBO) analysis.
authors.affiliation: Department of Physics, University of Lucknow, University Road, Lucknow, 226 007 Uttar Pradesh, India.
authors.forename: Anubha
authors.initials: A
authors.lastname: Srivastava
authors.forename: Rashmi
authors.initials: R
authors.lastname: Mishra
authors.forename: Poonam
authors.initials: P
authors.lastname: Tandon
authors.forename: A K
authors.initials: AK
authors.lastname: Bansal
mesh_terms: D000042:Absorption; D002152:Calorimetry, Differential Scanning; D000077144:Clopidogrel; D004583:Electrons; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation; D011789:Quantum Theory; D012997:Solvents / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman; D013816:Thermodynamics; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000737:chemistry; D014732:Vibration
chemical_list: D012997:Solvents; D000077144:Clopidogrel; D013988:Ticlopidine