Synthesis, Structure, Supramolecular Assembly Inspection by Hirshfeld Surface Analysis, DFT Study and Molecular Docking Inspection of 4,5-Bis (2-Chlorophenyl) (1H,3H)-Dithione

Abstract

We studied the three-component condensation of 2-chloraldehyde, acetophenone, and thiourea in conjunction with HCl, resulting in the formation of a new compound: 4,5-bis(2-chlorophenyl)-8a-phenylhexahydropyrimido [4,5-d]pyrimidine-2,7(1H,3H)-dithione (CPPD). The compound's structure was affirmed via X-ray diffraction study. The asymmetric unit contained two molecules that were independent relative to crystallography and an ethanol solvent. The difference between independent molecules was explored by dihedral angles between similar rings in both molecular. The difference between molecules was further explored by molecular overlay plot. The supramolecular assembly was supported via diverse intermolecular interactions which were studied through the use of Hirshfeld surface analysis. Electronic structure computations were carried out at the omega b97xd/tzvp level. Natural bonding orbital (NBO), and FMO study reveal reactivity and charge transfer mechanisms within the compound. Furthermore, the nature of bonding in the present molecule is characterized through quantum theory of atoms in molecules (QTAIM), ELF, and LOL studies. Ab-initio molecular dynamic (AIMD) revealed the kinetic and thermodynamic stability at 300 K. The DFT results have excellent correlation with experimental data. The molecular docking and molecular dynamics simulation further revealed the compound to get deep access in the active pocket of type 2 anti-diabetes GLUT4 protein. This was validated by the stable dynamics as demonstrated by the uniform behavior of the root mean square deviation (RMSD) plot. The root mean square fluctuation (RMSF) also showed stable interactions with amino acids in the presence of the compound. Further, simulation trajectories on the basis of binding free energies indicate the significant role of van der Waals force in the formation of the intermolecular docked complex. This concluded the compound might be a potent structure for the development of anti-diabetic compounds.