A theoretical-electron-density databank using a model of real and virtual spherical atoms.

A database describing the electron density of common chemical groups using combinations of real and virtual spherical atoms is proposed, as an alternative to the multipolar atom modelling of the molecular charge density. Theoretical structure factors were computed from periodic density functional theory calculations on 38 crystal structures of small molecules and the charge density was subsequently refined using a density model based on real spherical atoms and additional dummy charges on the covalent bonds and on electron lone-pair sites. The electron-density parameters of real and dummy atoms present in a similar chemical environment were averaged on all the molecules studied to build a database of transferable spherical atoms. Compared with the now-popular databases of transferable multipolar parameters, the spherical charge modelling needs fewer parameters to describe the molecular electron density and can be more easily incorporated in molecular modelling software for the computation of electrostatic properties. The construction method of the database is described. In order to analyse to what extent this modelling method can be used to derive meaningful molecular properties, it has been applied to the urea molecule and to biotin/streptavidin, a protein/ligand complex.

Experimental and theoretical charge-density analysis of 1,4-bis(5-hexyl-2-thienyl)butane-1,4-dione: applications of a virtual-atom model.

The experimental and theoretical charge densities of 1,4-bis(5-hexyl-2-thienyl)butane-1,4-dione, a precursor in the synthesis of thiophene-based semiconductors and organic solar cells, are presented. A dummy bond charges spherical atom model is applied besides the multipolar atom model. The results show that the dummy bond charges model is accurate enough to calculate electrostatic-derived properties which are comparable with those obtained by the multipolar atom model. The refinement statistics and the residual electron density values are found to be intermediate between the independent atom and the multipolar formalisms.

Charge-density analysis using multipolar atom and spherical charge models: 2-methyl-1,3-cyclopentanedione, a compound displaying a resonance-assisted hydrogen bond.

The experimental charge-density distribution in 2-methyl-1,3-cyclopentanedione in the crystal state was analyzed by synchrotron X-ray diffraction data collection at 0.33 Šresolution. The molecule in the crystal is in the enol form. The experimental electron density was refined using the Hansen-Coppens multipolar model and an alternative modeling, based on spherical atoms and additional charges on the covalent bonds and electron lone-pair sites. The crystallographic refinements, charge-density distributions, molecular electrostatic potentials, dipole moments and intermolecular interaction energies obtained from the different charge-density models were compared. The experimental results are also compared with the theoretical charge densities using theoretical structure factors obtained from periodic quantum calculations at the B3LYP/6-31G** level. A strong intermolecular O-H···O hydrogen bond connects molecules along the [001] direction. The deformation density maps show the resonance within the O=C-C=C-OH fragment and merged lone pair lobes on the hydroxyl O atom. This resonance is further confirmed by the analysis of charges and topology of the electron density.

Experimental and theoretical charge density analysis of a bromoethyl sulfonium salt.

Bromoethyl sulfonium trifluoromethanesulfonate is a salt complex in which a sulfur atom makes three covalent bonds. This molecule has been proved to act as an efficient annulation reagent which results in formation of synthetically challenging and pharmaceutically important 4-, 5-, 6-, and 7-membered heterocycles in excellent yields. The charge density of the molecule was determined from both experimentally and theoretically derived diffraction data. The stereochemistry and electron density topology of the sulfonium group was analyzed. To understand the chemical reactivity of the molecule, the electrostatic potential difference between the two carbon atoms of the bromoethyl group was investigated. It has been considered that the hydrogen atoms on the carbon atom bound to sulfur are more acidic in character due to their vicinity with the triply covalently bonded positively charged sulfur atom. The electropositivity of the S-attached and Br-attached methylene groups are compared in the experimental and theoretical charge densities using topological atomic charges and electrostatic potential at the molecular surface.

A critical analysis of dipole-moment calculations as obtained from experimental and theoretical structure factors.

Three models of charge-density distribution - Hansen-Coppens multipolar, virtual atom and kappa - of different complexities, different numbers of refined parameters, and with variable levels of restraints, were tested against theoretical and high-resolution X-ray diffraction structure factors for 2-methyl-4-nitro-1-phenyl-1H-imidazole-5-carbonitrile. The influence of the model, refinement strategy, multipole level and treatment of the H atoms on the dipole moment was investigated. The dipole moment turned out to be very sensitive to the refinement strategy. Also, small changes in H-atom treatment can greatly influence the calculated magnitude and orientation of the dipole moment. The best results were obtained when H atoms were kept in positions determined by neutron diffraction and anisotropic displacement parameters (obtained by SHADE, in this case) were used. Also, constraints on kappa values of H atoms were found to be superior to the free refinement of these parameters. It is also shown that the over-parametrization of the multipolar model, although possibly leading to better residuals, in general gives worse dipole moments.