Alain Cartier

Determination of distributed polarizabilities to be used for peptide modeling

Abstract New sets of atomic hybrid parameters to be added to force fields for peptide modeling are presented. The approach used has been chosen as simple as possible to make their introduction into this kind of program easy. They are optimized to accurately reproduce the results obtained for polarizability and anisotropy from ab initio calculations on a series of model molecules and tested on a series of 30 molecules including some small peptides. Different empirical approaches to the calculation of molecular polarizabilities are exposed and their results compared. The most accurate approach gives mean polarizabilities which differ from the ab initio results by less than 10%.

An extended variational method for calculating molecular multipole polarizabilities

Abstract The improvement proposed by Shukla and Easa to the variational calculation of multipole polarizabilities of atoms has been applied to molecules. The convergence of the technique appears to be fair but the accuracy of the results is strongly dependent on the quality of the initial wavefunction. In the case of methane, the best values of the dipole—quadrupole and pure quadrupole polarizabilities are: (4πϵo)−1Ax,yz = 0.719 × 10−40 m4, (4πϵo)−1Cxx,xx = 1.562 × 10−50 m5, (4πϵo)−1 × Cxy,xy = 1.350 × 10−50 m5.

Mechanism of inhibition of rat liver bilirubin UDP‐glucuronosyltransferase by triphenylalkyl derivatives

A series of potent and competitive inhibitors of UDP‐glucuronosyltransferase derived from 7,7,7‐triphenylheptanoic acid has been synthesized in order to probe the active site of the isozyme involved in the glucuronidation of the endogenous toxic compound, bilirubin IXα. Like triphenylalkylcarboxylic acids, triphenyl alcohols were found to be very effective competitive inhibitors of the reaction (Ki 12 to 180 μM). Superimposition of the best inhibitors with bilirubin by computer modeling showed a marked spatial similarity, which accounts for the observed competitive‐type inhibition. The bulky triphenylmethyl moiety of the inhibitor superimposed well on the part of the bilirubin molecule containing three of the four pyrrole rings. In agreement, substitution of the triphenylmethyl moiety by planar structures such as fluorenyl or indenyl rings completely suppressed the inhibition. In addition, the weak inhibition exerted by the shortest carboxylic acids could be related to the higher acidity of these molecules. The inhibition potency depended on the acidity of the molecules; the more acidic, the less inhibitory, suggesting that the presence of a negative charge on the inhibitor molecule prevents bilirubin glucuronidation. Based on these results, a reaction mechanism for bilirubin glucuronidation is postulated.

Scaled semiempirical method for the calculation of vibrational spectra Molecular vibrational frequencies of monosaccharides and disaccharides by PM3 method

Abstract In this paper, we investigate the possibility of scaling, on a reference molecule, the force field computed by means of a semiempirical quantum chemical method, here PM3, and transferring the scaling factors to other parent molecules. The scaling, performed on α- d -glucose, allows good prediction of the vibrational spectra of β- d -glucose, α- d -galactose, α- d -mannose, methyl-α- d -glucopyranoside, methyl-α- d -mannopyranoside, cellobiose and gentiobiose within 20 cm −1 in the high and medium frequency range. Low frequency bands are less well reproduced, but they are also less widely used to characterize these molecules. The influence of the crystal field and intermolecular hydrogen bonds is discussed. The method can be extended to other chemical families.

A molecular orbital study of bonding and frequency shifts in free and solvated lithium thiocyanate aggregates

Abstract The MNDO method has been used to determine the stable structures of lithium thiocyanate aggregates. Two classes of aggregates have been found: (a) N-bonded (LiNCS) p (1

In vitro evaluation of glucuronidation of monohydroxylated aglycones related to quantum chemically-calculated parameters

/ p ⩽ 4) (i.e. linear LiNCS), the rhombic dimer, the triangular trimer and a cubane-like tetramer; (b) (LiSCN) p aggregates (1

Computational study of the addition of molecular oxygen to benzene

/ p ⩽ 3) with lithium bridges between S and C. The structures of class (a) are in agreement with those experimentally determined in solution; in this case unusual negative frequency shifts of ν(CN) due to μ 2 or gm 3 nitrogen coordination have been reproduced by our vibrational frequency calculations. IR intensity variations are also in qualitative agreement with experiment. The lithium solvation has been simulated by adding water molecules in the first solvation shell of Li in order to complete its coordination number to 4. This model gives a good account of aggregation energies in solution and of ν(CN) frequency variations.

Variational method for calculating molecular multipole polarizabilities using atom centered extended trial functions

Abstract Using monohydroxylated aglycones belonging to different chemical classes, we investigated the physicochemical criteria required to predict the elimination of these molecules which are substrates of UDP-glucuronosyltransferases. These enzymes possess a low specificity, particularly towards exogenous compounds. For this purpose, we determined the kinetic constants ( V max , K m , V K ) in non-treated and 3-methylcholanthrene-treated rat liver microsomes. QSAR studies were performed with the complete neglect of differential overlap assumption relating 15 theoretical descriptors characterizing the substrates. Principal component analysis shows the distributions, different before and after induction, of experimental values used as supplementary variables for V K , especially in the case of coumarinic compounds. The results described demonstrate the usefulness of QSAR analysis in glucuronidation in order to explain the observed variance in enzymatic activity and to determine the binding forces involved (steric and electronic).

Ab initio DFT investigations on structure of copper(I) bis-diazine complexes

Abstract The first step of the attack of the oxygen molecule, in its ground state, on the phenyl ring, in the gas phase, has been studied using SCF ab initio, BECKE3LYP DFT and AM1 and PM3 semiempirical calculations. This attack follows several stages: fixation of the oxygen molecule in the para position, then its dissociation followed by a two-step migration of hydrogen atoms, leading finally to hydroquinone. The potential curves obtained by DFT and SCF calculations are similar; the same stationary points are observed in both methods. However, the SCF energy barriers are overestimated by a factor greater than 30%. The semiempirical computations reproduce approximately some features of the non-empirical results.

Combined AM1/MM3 computations on organic systems: the Diels–Alder reaction as a test case

An improvement of the variational method for calculating the electronic multipole polarizabilities is proposed. This modification allows the computation of the polarizabilities at any point and the results are compatible with the relations existing for a change of origin. It is applied to H2, HF, CO and N2 by using SCF wavefunctions developed on a limited basis. The computed polarizabilities are systematically too large but this discrepancy is attributed to the fact that the ground state is too far from the exact wavefunction.