Gradient vector field and properties of the experimental electrostatic potential: Application to ibuprofen drug molecule

Abstract

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.

Charge density and electrostatic potential analyses in paracetamol

“…found near O atoms and (3, +1) ring-critical point found in the center of the phenolic group. It was previously shown that the distances from the BCP and the connecting atoms can define the atomic covalent radii (Bouhmaida et al, 2002). It is worthy to note that other (3, +1) ring-critical points, not reported in Fig.…”

“…1992c; Bouhmaida et al, 2002). The flux of the gradient lines of the electrostatic potential rÈ(r) vanishes through atomic basin surfaces, where the atomic charge is zero (Bouhmaida et al, 2002). In an interatomic bond, the zero of the gradient of the electrostatic potential rÈ(r) defines a critical point (CP).…”

“…Displacement ellipsoids are drawn at the 50% probability level. 1992c; Bouhmaida et al, 2002). The flux of the gradient lines of the electrostatic potential rÈ(r) vanishes through atomic basin surfaces, where the atomic charge is zero (Bouhmaida et al, 2002).…”

“…In an interatomic bond, the zero of the gradient of the electrostatic potential rÈ(r) defines a critical point (CP). The distance from each atom of the bond to the critical point yields the atomic covalent radii (Bouhmaida et al, 2002;Novaković et al, 2007). Finally, the electrostatic interaction energy between molecules was estimated by the method developed in MOPRO and VMOPRO computer programs (Guillot et al, 2001;Jelsch et al, 2005).…”

“…We have previously characterized the electrostatic potential through its first derivative, i.e. the electric field and its critical points (Bouhmaida et al, 2002). All these calculations are based on the HansenCoppens multipolar atom model (Hansen & Coppens, 1978) which is widely used in the refinement of high-resolution diffraction data.…”