The electron density of monoclinic paracetamol was derived from high-resolution X-ray diffraction at 100 K. The HansenCoppens multipole model was used to refine the experimental electron density. The topologies of the electron density and the electrostatic potential were carefully analyzed. Numerical and analytical procedures were used to derive the charges integrated over the atomic basins. The highest charge magnitude (À1.2 e) was found for the N atom of the paracetamol molecule, which is in agreement with the observed nucleophilic attack occurring in the biological media. The electric field generated by the paracetamol molecule was used to calculate the atomic charges using the divergence theorem. This was simultaneously applied to estimate the total electrostatic force exerted on each atom of the molecule by using the Maxwell stress tensor. The interaction electrostatic energy of dimers of paracetamol in the crystal lattice was also estimated.

The present study focuses on the electric field features and related physical properties which can be derived from the topology of the experimental electrostatic potential. These properties were retrieved from the electron density multipole refinement of high-resolution x-ray data collected on a racemic crystal of ibuprofen drug. The electric field lines are depicted around the molecule revealing gradient vector zero flux atomic basins and critical points (CP’s) having a different significance than that brought out by the topology of the electron density. This method emphasizes a partioning of the molecular system mainly governed by the nuclear–electron interaction. The concept of Slater’s nuclear screening is here explored from the inspection of the gradient field zero flux surface separating the atoms in the molecule. Moreover, empirical parameters like covalent or atomic bond radii are accurately estimated from CP–atom distances in the molecular heteroatomic bonds. The local minima of the electrostatic potential are searched around the ibuprofen molecule in order to locate the binding sites for further molecular interactions with biological targets or with excipients in pharmaceutical preparations. Ibuprofen dipole moment is also estimated by a method based upon the fit to the experimental electrostatic potential values generated around the molecule.

We have synthesized and crystallized a cytosine-decavanadate compound, Na(3) [V(10)O(28)] (C(4)N(3)OH(5))(3)(C(4)N(3)OH(6))(3).10H(2)O, and its crystal structure has been determined from a single-crystal X-ray diffraction. A high resolution X-ray diffraction experiment at 210 K (in P1 space group phase) was carried out. The data were refined using a pseudo-atom multipole model to get the electron density and the electrostatic properties of the decavanadate-cytosine complex. Static deformation density maps and Atoms in Molecules (AIM) topological analysis were used for this purpose. To get insight into the reactivity of the decavanadate anion, we have determined the atomic net charges and the molecular electrostatic potential. Special attention was paid to the hydrogen bonding occurring in the solid state between the decavanadate anion and its environment. The comparison of the experimental electronic characteristics of the decavanadate anions to those found in literature reveals that this anion is a rigid entity conserving its intrinsic properties. This is of particular importance for the future investigations of the biological activities of the decavanadate anion.

Experimental electrostatic potential derived from X-ray diffraction data was used as a given physical property for the determination of atomic moments. The electrostatic potential is fitted against Buckingham moments expansion up to octupolar level. The estimation of the contribution of the aspherical part of the density to the electrostatic potential necessitates a judicious choice of the points grid around the system in order to get stability and reliability of the results. The net charges obtained by the fit to the electrostatic potential on a test crystal of the pseudo-peptide N-acetyl-c~,/3-dehydrophenylalanine methylamide are close to those derived from the electron-density refinements. The higher moments are related to the electron-density multipolar parameters.

No abstract

The present study is devoted to a general use of the Gauss law. This is applied to the atomic surfaces derived from the topological analysis of the electron density. The method proposed here is entirely numerical, robust and does not necessitate any specific parametrization of the atomic surfaces. We focus on two fundamental properties: the atomic charges and the electrostatic forces acting on atoms in molecules. Application is made on experimental electron densities modelized by the Hansen-Coppens model from which the electric field is derived for a heterogenic set of compounds: water molecule, NO(3) anion, bis-triazine molecule and MgO cluster. Charges and electrostatic forces are estimated by the atomic surface flux of the electric field and the Maxwell stress tensor, respectively. The charges obtained from the present method are in good agreement with those issued from the conventional volume integration. Both Feynman and Ehrenfest forces as well as the electrostatic potential at the nuclei (EPN) are here estimated from the experimental electron densities. The values found for the molecular compounds are presented and discussed in the scope of the mechanics of atomic interactions.

The electrostatic potential is a multicenter property that can be expressed as a sum of the contributions of electric moments located at each atomic site of a molecule. Independently of the model used to generate the electrostatic potential around the system, these atomic moments can be accurately obtained by the fit of this physical property outside the van der Waals envelop. However, the larger the system, the greater the number of parameters. In this study a way is proposed to reduce the number of centers in the representation of the electrostatic potential which becomes a sum of fragment contributions rather than atomic ones. A sample of six water molecules in different crystal environments was chosen to discuss the derived values of the electric moments referred to the molecular center of mass.

Busulfan electrostatic properties were used to quantify its chemical reactivity. This explains the difficulty to formulate busulfan into liposomes due to a strong polar character of the methylsulfonate terminal groups. The complexation with cyclodextrins deserves to be further investigated to allow the formulation of busulfan in nontoxic solvents.