title: Antagonistic properties of a natural product-Bicuculline with the gamma-aminobutyric acid receptor: studied through electrostatic potential mapping, electronic and vibrational spectra using ab initio and density functional theory.
abstract: (+)-Bicuculline (hereinafter referred to as bicuculline), a phthalide isoquinoline alkaloid is of current interest as an antagonist of gamma-aminobutyric acid (GABA). Its inhibitor properties have been studied through molecular electrostatic potential (MEP) mapping of this molecule and GABA receptor. The hot site on the potential surface of bicuculline, which is also isosteric with GABA receptor, has been used to interpret the inhibitor property. A systematic quantum chemical study of the possible conformations, their relative stabilities, FT-Raman, FT-IR and UV-vis spectroscopic analysis of bicuculline has been reported. The optimized geometries, wavenumber and intensity of the vibrational bands of all the conformers of bicuculline have been calculated using ab initio Hartree-Fock (HF) and density functional theory (DFT) employing B3LYP functional and 6-311G(d,p) basis set. Mulliken atomic charges, HOMO-LUMO gap ΔE, ionization potential, dipole moments and total energy have also been obtained for the optimized geometries of both the molecules. TD-DFT method is used to calculate the electronic absorption parameters in gas phase as well as in solvent environment using integral equation formalism-polarizable continuum model (IEF-PCM) employing 6-31G basis set and the results thus obtained are compared with the UV absorption spectra. The combination of experimental and calculated results provides an insight into the structural and vibrational spectroscopic properties of bicuculline.
authors.affiliation: Department of Physics, University of Lucknow, Lucknow, Uttar Pradesh, India.
authors.forename: Anubha
authors.initials: A
authors.lastname: Srivastava
authors.forename: Poonam
authors.initials: P
authors.lastname: Tandon
authors.forename: Sudha
authors.initials: S
authors.lastname: Jain
authors.forename: B P
authors.initials: BP
authors.lastname: Asthana
mesh_terms: D001640:Bicuculline / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology; D004583:Electrons; D018756:GABA Antagonists / Q000494:pharmacology*; D008956:Models, Chemical; D008968:Molecular Conformation; D011789:Quantum Theory; D018079:Receptors, GABA / Q000737:chemistry / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D013059:Spectrum Analysis, Raman; D055672:Static Electricity; D013696:Temperature; D013816:Thermodynamics; D014732:Vibration; D014961:X-Ray Diffraction; D005680:gamma-Aminobutyric Acid / Q000737:chemistry
chemical_list: D001688:Biological Products; D018756:GABA Antagonists; D018079:Receptors, GABA; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline