Quantitative investigation of the nature of non-covalent interactions in 2-((benzo[d] [1,3] dioxol-5-ylmethyl)amino)-N-phenyl-2-thioxoacetamide : insights from crystallographic, DFT analysis, molecular docking, and molecular dynamics simulation

The aim of this work was to synthesise the novel compound 2-((benzo[d][1,3]dioxol-5-ylmethyl)amino)-N-phenyl-2-thioxoacetamide (P1) using the reflux method with ethanol as the solvent. The obtained product is characterised by single-crystal XRD analysis. All various contacts like intra and intermolecular found in P1 were determined by the X-ray diffraction technique performed on single crystals. On the other hand, the optimisation of P1 was accomplished by the DFT/ωB97XD method at the 6–311 + G(d, p) level. Furthermore, the electrostatic potential of the molecule (MEP), and global reactivity descriptors were analysed to gain a better understanding of the electronic properties and the active sites of P1. The Quantum Theory of Atoms in Molecules (QTAIM) and non-covalent interactions-based density of regional indicator (DORI) analyses were utilised to examine the intermolecular interaction energies and strength and nature of van der Waal's interactions. A computational analysis employing molecular docking simulations was conducted to explore the potential binding interactions between the synthesised compound P1 and the target proteins, specifically SARS-CoV-2 receptor protein (PDB ID: 6LU7) and breast cancer protein (PDB ID: 3HB5). In addition, molecular docking studies are validated by the molecular dynamics simulation studies.