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

• Published in: Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy Molecular and biomolecular spectroscopy, 2011-12, Vol.84 (1), p.144-155
• Main Authors: Srivastava, Anubha, Tandon, Poonam, Jain, Sudha, Asthana, B.P.
• Format: Article
• Language: English
• Subjects: (+)-Bicuculline; Ab initio and DFT calculations; Electronic spectra; FT-IR; FT-Raman; Molecular electrostatic potential; Vibrational analysis
• ISSN: 1386-1425
• DOI: 10.1016/j.saa.2011.09.022

FT-Raman, FT-IR and UV–vis spectra of a natural product bicuculline have been recorded and analyzed. The detailed interpretation of vibrational spectra of three conformers of bicuculline has been done in terms of potential energy distribution analysis. The assignments made at higher levels of theory, i.e., B3LYP/6-311G(d,p), gives reasonable deviations from the experimental values. A study on the electronic properties, such as HOMO and LUMO energies, were performed by time-dependent DFT (TD-DFT) approach using IEF-PCM model which demonstrated that charge transfer occurs within the molecule. Antagonistic property of bicuculline with the GABA receptor has been performed with the help of their molecular electrostatic potential mappings (MEPs). [Display omitted] ► FT-IR and FT-Raman spectra of bicuculline were recorded and compared with the theoretical results. ► The theoretical calculations were made using HF/DFT/B3LYP/6-311G(d,p) method. ► By using TD-DFT/6-31G method, electronic spectra for title compound have been predicted. ► The absorption spectrum has also been calculated in benzene environment using IEF-PCM model. ► Antagonistic property have been explained with the aid of molecular electrostatic potential mapping. (+)-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 Δ E, 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) employin