Fig. 10. Hirshfeld surfaces “dnorm ”, “Shape index ” and “Curvedness ” of Chloroquine molecule.
The normalized contact distance (dnorm ) of the Chloroquin compound makes it possible to graphically illustrate the relative positioning of the neighboring atoms belonging to the molecule interacting together. This analysis type displays a surface with a color scheme (red, blue, white), where the red spots highlight the shortest intermolecular contacts which are attributed to C-H···N interactions. The blue areas indicate the most language intermolecular contacts in the structure and the white regions represent the contacts around the van der Waals separation. The latter corresponds respectively to the H···H, C···H and H···Cl interactions [81-84]. Concerning the two maps (3D) Shape index and Curvedness, indeed the two blue and red triangles located at the level of Chloroquin phenyl on the Shape index cartography and the large flat region delimited by a blue outline observed on the Curvedness graph suggest the presence of C-H… π interactions [83]. The percentages of the different contacts as well as the fingerprint plots of the main contacts existing in the chloroquin structure are illustrated respectively in Figs. 11 and 12. The hydrogen-hydrogen contacts (H … H) (Fig. 12a) occupy almost half of the entire Hirshfeld surface (44.6%) with a high concentration in the central region where de =di = 1.1Å. C… H / H… C (Fig. 12b) and H… Cl / Cl… H (Fig. 12c) contacts comprise respectively 29.8% and 10.2% of the entire Hirshfeld surface and represented by two symmetrical wings with de +di ~ 3 Å and 3.2 Å, the large percentage (29.8%) confirms the presence of the C-H… π interactions already mentioned in the three-dimensional graphs (Shape index and Curvedness). The nitrogen-hydrogen contacts (N… H / H… N) show on its 2D graph the presence of two narrow and symmetrical pointed points centered around a sumde + di ~ 2.2 Å, these contacts are responsible for the hydrogen bonds C-H… N. Based on the van der Waals rays of involved atoms in contacts (H: 1.09 Å, C: 1.70 Å, N: 1.55 Å, Cl: 1.75) Å and the de and di distances we carried out a comparative study to find out the nature of contacts, close or distant, this study is summarized in Table 7. We note from this table that only N… H / H… N contacts are considered close with a sum di +de less than the sum of van der Waals rays of involved atoms.
Table 7 Nature of main contacts existing in chloroquine molecule.