Contribution of high-energy conformations to NMR chemical shifts, a DFT-BOMD study.

This paper highlights the relevance of including the high-energy conformational states sampled by Born-Oppenheimer molecular dynamics (BOMD) in the calculation of time-averaged NMR chemical shifts. Our case study is the very flexible glycerol molecule that undergoes interconversion between conformers in a nonrandom way. Along the sequence of structures from one backbone conformer to another, transition states have been identified. The three (13)C NMR chemical shifts of the molecule were estimated by averaging their calculated values over a large set of BOMD snapshots. The simulation time needed to obtain a good agreement with the two signals present in the experimental spectrum is shown to be dependent on the atomic orbital basis set used for the dynamics, with a necessary longer trajectory for the most extended basis sets. The large structural deformations with respect to the optimized conformer geometries that occur along the dynamics are related to a kinetically driven conformer distribution. Calculated conformer type populations are in good agreement with experimental gas phase microwave results.

Structure, dynamics, and energetics of lysobisphosphatidic acid (LBPA) isomers.

Lysobisphosphatidic acid (LBPA), or bis(monoacylglycerol)phosphate, is a very interesting lipid, that is mainly found in late endosomes. It has several intriguing characteristics, which differ from those of other animal glycerophospholipids, that may be related to its specific functions, particularly in the metabolism of cholesterol. Its phosphodiester group is bonded at the sn-1 (sn-1') positions of the glycerols rather than at sn-3 (sn-3'); the position of the two fatty acid chains is still under debate but, increasingly, arguments favor the sn-2, sn-2' position in the native molecule, whereas isolation procedures or acidic conditions lead to the thermodynamically more stable sn-3, sn-3' structure. Because of these peculiar features, it can be expected that LBPA shape and interactions with membrane lipids and proteins are related to its structure at the molecular level. We applied quantum mechanical methods to study the structures and stabilities of the 2,2' and 3,3' LBPA isomers, using a step-by-step procedure from glycerol to precursors (in vitro syntheses) and to the final isoforms. The structures of the two positional LBPA isomers are substantially different, showing that the binding positions of the fatty acid chains on the glycerol backbone determine the shape of the LBPA molecule and thus, possibly, its functions. The 3,3' LBPA structures obtained are more stable with respect to the 2,2' form, as expected from experiment. If one argues that the in vivo synthesis starts from the present glycerol conformers and considering the most stable bis(glycero)phosphate structures, the 2,2' isoform should be the most probable isomer.

Density functional theory-based conformational analysis of a phospholipid molecule (dimyristoyl phosphatidylcholine).

The conformational space of the dimyristoyl phosphatidylcholine (DMPC) molecule has been studied using density functional theory (DFT), augmented with a damped empirical dispersion energy term (DFT-D). Fourteen ground-state isomers have been found with total energies within less than 1 kcal/mol. Despite differences in combinations of their torsion angles, all these conformers share a common geometric profile, which includes a balance of attractive, repulsive, and constraint forces between and within specific groups of atoms. The definition of this profile fits with most of the structural characteristics deduced from measured NMR properties of DMPC solutions. The calculated vibrational spectrum of the molecule is in good agreement with experimental data obtained for DMPC bilayers. These results support the idea that DMPC molecules preserve their individual molecular structures in the various assemblies.

Theoretical study of the structure and properties of Na-MOR and H-MOR zeolite models.

This work presents calculated structural parameters and energetic properties of Na- and H-mordenites (MORs) using cluster models with more than 400 atoms. These state of the art calculations were performed within the framework of density functional theory, using both the local density approximation and the generalized gradient approximation, employing all-electron basis sets. The most populated T3, T4, and T1 Al sites have been investigated using two different MOR models, each containing two isolated Al sites. A detailed analysis of the structures, three-dimensional contours of molecular electrostatic potential, binding energies of Na cations and protons, and BrØnsted O-H harmonic frequencies are presented. These properties are compared with available experimental results. The structural changes among Si/Al substitution as well as Na/H exchange are discussed.

The modelling of nucleophilic and electrophilic additions to organometallic complexes using molecular graphics techniques.

A new formalism has been developed in order to evaluate intermolecular interaction energies for inorganic and organometallic complexes in the framework of the extended Hückel method. In order to provide the shortest possible response time on an interactive computer graphics facility, this model should require the minimum amount of computer time, which explains why approximate procedures are used to evaluate electrostatic, charge transfer and exchange repulsion components. When applying this model to typical examples of electrophilic addition reactions to organometallic complexes, it is found that it is essential to take account of charge transfer interactions, the electrostatic component alone being not sufficient, even qualitatively, for a proper description of the reaction mechanism. The results, presented as color-coded dot molecular surfaces, show a very good agreement with experiment as to the site of attack, namely (i) on metal for the electrophilic attack on Fe(cp)2, Fe(CO)5 and X(cp)(CO)2, X = Co, Rh; (ii) on the cp ligand for the nucleophilic attack on Co(cp)2+ and Rh(cp)2+; (iii) on bz for the nucleophilic attack on Fe(cp)(bz)+. Finally, modellizations of the nucleophilic attack on a coordinated olefin and of the relation between structure and acidic properties of zeolites are presented and discussed.