Jacqueline Langlet

Theoretical study of the complexation of amphotericin B with sterols

The aim of this present work was the study of the intermolecular complexes between amphotericin B (AmB) and either cholesterol or ergosterol. In such complexes the intermolecular interaction energy mainly proceeds from both Van der Waals and H-bonding (via water molecules) forces. Our calculations have shown that the Van der Waals forces slightly favor the AmB-ergosterol complex. Several relative positions of the sterol with regard to AmB lead to energy minima: sterol may be either in contact with the AmB polar head or repelled towards the end of the macrolide ring. It appeared that the role played by some water molecules was to maintain the sterol close to the AmB polar head.

Theoretical study of the self-association of amphotericin B.

The aim of this present work is the study of self-association of amphotericin B (AmB) at a molecular levels, because of its importance in the toxicity of this antibiotic. Molecular mechanics calculations have been performed considering different conformations of the polar head of AmB, the two most stable ones we have determined (B and C) and the one issued from the X-ray data. Our calculations have shown that both head-to-head and head-to-tail stable dimers were found within an energy range between -30 and -40 kcal/mol, the very stable head-to-head dimer with the polar head within C conformation having an energy of -46.8 kcal/mol. We have shown that both electrostatic and Van der Waals terms contribute to the total interaction energy but their relative weight depends on the conformation of the polar head and on the head-to-head and head-to-tail structures involved in the dimer. Thus the electrostatic contribution does no particularly stabilize the head-to-tail dimer. Furthermore an explicit calculation of the dipole moment in the ground state of AmB has disproved the current assertion upon the greatest stabilization of head-to-tail dimers by electrostatic dipole-dipole interaction. Among all the dimers we have calculated, we have found a group denoted G1 with a geometrical structure consistent with absorption data, namely a blue-shift of the dimer main absorption band with regard to the monomer one. In this group G1 we have found two isoenergetic (-38.8 kcal/mol) very stable head-to-head and head-to-tail dimers. We have found that, as a rule, the self-association of AmB in dimers is more favourable than the complexation with the cholesterol and, in a less extent, with the ergosterol. It seems that these features could be also observed for some trimers, that we have roughly calculated.

Hydration and `inverse hydration' of platinum(II) complexes: an analysis using the density functionals PW91 and BLYP

Abstract The interaction between two platinum complexes and water was investigated using the DFT functionals PW91 and BLYP. Previous MP2 and HF calculations have shown that when a H 2 O molecule approaches Pt with its O atom, the interaction is governed by electrostatics and the MP2 and HF interaction energy curves nearly coincide, whereas for the approach with H pointing towards Pt, there is a significant dispersion component portrayed only by MP2 calculations. Here we show that both PW91 and BLYP satisfactorily reproduce the MP2 curves, PW91 slightly exaggerating and BLYP slightly underestimating the dispersion-induced energy minima. This result is discussed in view of the different behavior of the two exchange functionals at large density gradients.

Theoretical determination of structural parameters for s-triazine and some derivatives. Comparison between ab initio and semi-empirical calculations

Abstract The structures of s -triazine and some derivatives have been determined by ab initio computations with the 6-31 G and Dunning basis sets augmented by polarization functions. The effect of addition of the polarization functions as well as correlation effects, using a Moller-Plesset procedure, is analyzed. Comparison is made with experimental data and other calculations available from the literature. Basis set effects are evaluated. Moreover, a comparison is made with semi-empirical calculations using the AM1 method. Such semi-empirical methods are widely used for the study of compounds of biological or chemical interest and such a comparison provides an evaluation of the approximation involved in these methods.

Comparative theoretical study of the conformations of amphotericin methyl ester and amphotericin B polar heads in the presence of water

Amphotericin methyl ester (AmE) is an interesting derivative of amphotericin B (AmB) because of its enhancement of selectivity against the fungicells. Both AmB and AmE molecules differ by the structure of their polar heads. This work deals with a theoretical study of conformations of the polar head of AmE in the presence of hydration water molecules. The results will be compared with our previous work concerning AmB.

Theoretical study of the structure of the glutathione-hydrogen peroxide complex

SummaryTheoretical calculations have been performed in order to investigate the possibility of intermolecular hydrogen bonds between glutathione and hydrogen peroxide. Preliminary investigations of the conformations of GSH in water have been done in the framework of the SIBFA and CHARMm methods. We have proposed some privileged sites on the molecules of GSH for the formation of complexes with H2O and H2O2.