Charge density and electrostatic potential analyses in paracetamol

Abstract

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.

d-Orbital orientation in a dimer cobalt complex: link to magnetic properties?

“…The critical-point properties of the organic part (C-C bonds, phenyl ring etc., see supplementary materials) are in very good agreement with the values found in other recent electron-density studies (see, for example, Bouhmaida et al, 2009;Scheins et al, 2009).…”

Single crystal XRD, vibrational and quantum chemical calculation of pharmaceutical drug paracetamol: A new synthesis form

“…Other H atoms, which are participating in the hydrogen bonding interactions, were located from different fourier map and refined isotropically. The re-determined structure matches well with the reported Form I polymorph of the PAR [25].…”

The generalized invariom database (GID)

“…Further studies are under way. Other properties, which are currently under critical study, include the electrostatic interaction energy (Abramov et al, 2000a,b;Li et al, 2002Li et al, , 2006Volkov, Koritsá nszky & Coppens, 2004;Spackman, 2007;Bouhmaida et al, 2009) and the molecular dipole moment (Spackman, 1992;Spackman et al, 2007;Poulain-Paul et al, 2012;). An open question is whether the approximations set in the HansenCoppens multipole model (frozen core, order of the expansion l max ¼ 4, m-independent radial functions) permit an accuracy to be reached that is high enough to obtain these properties from a reciprocal-space fit to structure factors in a reliable manner (Bąk et al, 2011;Jarzembska & Dominiak, 2012), and how modifications in the pseudoatom description can improve the situation.…”