L. Lespade

Theoretical Study of the Mechanism of Inhibition of Xanthine Oxydase by Flavonoids and Gallic Acid Derivatives

Xanthine oxidase is a flavoprotein enzyme which catalyzes the oxidative hydroxylation of purine substrates. Because of its availability, it has become a model for structural molybdoenzymes in general. The enzyme is a well-established target of drugs against gout and hyperuricemia and exists in two forms: oxidase and deshydrogenase. In some pathologies, its level increases in oxidase form, being the source of free radicals which can cause damage to surrounding tissues. It is important to understand the mechanisms of the enzyme inhibition to help in the search of new inhibitors. The main active center is a molybdopterin buried in a cavity. Theoretical calculations can be of some help for distinguishing the important aspects in the inhibition: attraction inside the cavity and anchorage. In this paper, the molybdopterin molecule geometry has been optimized by ab initio with the DFT method and the results have been shown to be very similar to the X-ray coordinates. In order to evaluate the attraction inside the cavity, the electrostatic potential between the charged molybdopterin molecule and two series of inhibitors, some flavonoids, and some gallic acid derivatives have been calculated using the multipolar development supplied by the Gaussian package. The good concordance between the electrostatic force and IC(50) indicates that the attraction is an important factor in the inhibition and must be taken into account in the designing of new drugs.

Theoretical investigation of the effect of sugar substitution on the antioxidant properties of flavonoids

Natural flavonoids are secondary phenolic plant metabolites known for their bioactivity as antioxidants. The evaluation of this property is generally done by the estimation of their direct free radical-scavenging activity as hydrogen or electron donating compounds. This paper reviews experimental results available in the literature for a selection of flavonoids and compares them with calculated quantities characteristic of the hydrogen or electron donation. For that purpose, bond dissociation energies, ionization potentials and electron transfer enthalpies are computed by using DFT methods and the ONIOM procedure implemented in the ab initio program Gaussian. This process has been chosen because it can be extended to the study of large molecules. When acid dissociation and interaction with the solvent are taken into account, the results present very good concordance with experimental results, enlightening the complexity of the processes involved in the classical assays which measure the ability of compounds to scavenge the (2,2′-azinobis-(3-ethylbenzthiazoline-6-sulfonic acid) diammonium salt) radical cation (ABTS +) or the 2,2-diphenyl-1-picryl-hydrazyl radical (DPPH·). This study demonstrates the good accuracy of theoretical calculations in obtaining the relative energies involved in free radical scavenging abilities and its capacity for predictive behaviour. It also highlights the necessity to take into account the pKa of the compounds and the solvent interaction. The ability of the method to calculate the antioxidant properties of larger molecules are tested on glycosylated flavonoids and the effects of sugar substitution on the antioxidant properties of flavonoids are investigated, pointing out the importance of the charges on the oxygen atoms.

Internal dynamics contributions to the CH stretching overtone spectra of gaseous monohydrogenated nitromethane NO2CHD2

The methyl CH‐stretching overtone spectra of gaseous monohydrogenated nitromethane NO2CHD2 have been recorded with conventional near infrared spectroscopy in the ΔvCH=1 to 4 regions and by intracavity laser photoacoustic spectroscopy in the ΔvCH=5 and 6 regions. They all exhibit a complex structure with, at ΔvCH=1 and 2, a characteristic asymmetric top vibration–rotation profile which vanishes as vibrational energy increases. These spectra have been analyzed with a theoretical model which takes into account in the adiabatic approximation the coupling between the anharmonic CH stretch described by a Morse potential and the quasifree internal rotation of the methyl group. All the parameters of this model (the zero point energy, the CH stretch frequency, the expansion coefficients of the dipole moment function) and their variation with the internal rotation coordinate have been determined from HF/6‐31G** ab initio calculations. This simple calculation, which contains no adjustable parameters, successfully de...

Internal dynamics contributions to the CH stretching overtone spectra of gaseous nitromethane NO2CH3

The methyl CH stretching overtone spectra of gaseous nitromethane NO2CH3 have been recorded with Fourier transform infrared conventional near infrared spectroscopy in the ΔvCH=1–4 regions and by intracavity laser photoacoustic spectroscopy in the ΔvCH=5 and 6 regions. They all exhibit a complex structure with, at ΔvCH=1 and 2, a characteristic asymmetric top vibration-rotation profile which vanishes as vibrational energy increases. In addition, in these two lower energy spectra, the perpendicular stretching vibrations exhibit a widely spaced fine structure profile resulting from a Coriolis coupling induced by the methyl internal rotation. These excited spectra have been analyzed with a theoretical model which takes into account, in the adiabatic approximation, the coupling of the anharmonic CH stretch vibrations, described by a Morse potential, with the quasi-free internal rotation of the methyl group and with isoenergetic combination states involving methyl bending modes. Till Δv=3, the theoretical treat...

CH-stretching overtone spectra of a fast rotating methyl group. I. Toluene C6D5CH3

The CH-stretching overtone spectra of the methyl group in gaseous toluene C6D5CH3 are recorded with conventional Fourier transform near infrared spectroscopy in the ΔvCH=1–4 regions and by intracavity laser photoacoustic spectroscopy in the ΔvCH=5 and 6 regions. All spectra exhibit a complex structure. They are analyzed with a theoretical model which takes into account, within the adiabatic approximation, the coupling of the anharmonic CH stretch vibrations, described by Morse potentials, with the quasifree internal rotation of the methyl group and with isoenergetic combination states involving the six angle deformation modes of the methyl group. Using uniquely determined canonical potential-energy and kinetic-energy matrices allows us to solve the problem of indeterminacy caused by the description of molecular vibrations in such redundant coordinates. A set of Fermi resonance parameters and their variation with the internal rotation coordinate are determined from the fitting of the ΔvCH=1–6 overtone spec...

Vibrational overtone spectroscopy and internal dynamics in gaseous nitromethane NO2CH2D

The CH-stretching overtone spectra of the methyl group in gaseous nitromethane NO2CH2D have been recorded with conventional Fourier transform near-infrared spectroscopy in the ΔvCH=1–4 regions and by intracavity laser photoacoustic spectroscopy in the ΔvCH=5 and 6 regions. All spectra exhibit a complex structure; they have been analyzed with a theoretical model which takes into account, within the adiabatic approximation, the coupling of the anharmonic CH stretch vibrations, described by Morse potentials, with the quasifree internal rotation of the methyl group and with isoenergetic combination states involving methyl bending modes. Most of the parameters of this model, and their variation with the internal rotation coordinate (θ), are identical to ones used to account for the overtone spectra of the monohydrogenated and perhydrogenated species. Fermi resonance phenomena, also modeled with θ dependent parameters, lead to only weak intramolecular vibrational energy redistribution. This simple calculation s...

CH-stretching overtone spectra of a fast rotating methyl group. II. Toluenes C6D5CH2D and C6D5CHD2

The CH-stretching overtone spectra of the methyl group in gaseous toluene C6D5CH2D and C6D5CHD2 are recorded with conventional Fourier transform near infrared spectroscopy in the Δv=1–4 regions and by intracavity laser photoacoustic spectroscopy in the Δv=5 and 6 regions. The spectra are analyzed with a theoretical model that takes into account, within the adiabatic approximation, the coupling of the anharmonic CH stretch with the quasifree internal rotation of the methyl group and with isoenergetic combination states involving methyl bending and rocking modes. A simultaneous successful reconstruction of the CH stretching overtone spectra of three isotopic derivatives of the methyl group of toluene is obtained with a single set of parameters from Δv=1–6 (18 spectra). The modifications caused by the partial deuteration of the rotating methyl group on its IVR mechanisms are analyzed. In both methyl deuterated compounds, the CH/CD interbond coupling induces a shift of the overtone spectra towards high freque...

Characterization of vibrational transition modes by use of normal forms

SummaryIn this paper we use the Birkhoff-Gustavson perturbation theory to analyze the vibrational modes of two linearly coupled Morse oscillators in the transition region from normal modes to local modes. Our study is based on: truncation of the Hamiltonian written in normal mode coordinates at the 4th order, transformation to normal form and analytical study; construction and use of the approximate integrals of motion of the exact Hamiltonian according to Birkhoff and Gustavson theory. By comparison with a previous analytical study, we demonstrate that perturbation theory, based either on local or normal modes can be used to accurately describe transition modes.

Calculation of displacement matrix elements for Morse oscillators

Displacement matrix elements of the Morse oscillators are widely used in physical and chemical computation. Many papers have been published about the analytical expressions of the displacement matrix elements. People still use an integration method rather than the analytical expressions to calculate the displacement matrix elements. Analytical expressions of the diagonal and off diagonal displacement matrix elements with intermediate variables are derived, where v, m and n are non-negative integers and n • 6. Calculation with these expressions is superior to that with numerical integration in precision, calculation speed and convenience.

Ab initio molecular dynamics of the reactivity of vitamin C toward hydroxyl and

Vitamin C is one of the most abundant exogenous antioxidants in the cell, and it is of the utmost importance to elucidate its mechanism of action against radicals. In this study, the reactivity of vitamin C toward OH and HO2/O2−\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}