Synthesis, crystal structure, Hirshfeld surface analysis, DFT, molecular docking and molecular dynamic simulation...

A novel drug to treat SARS-CoV-2 infections and hydroxyl chloroquine analogue, (E)-2,6-bis(4-chlorophenyl)-3-methyl-4-(2-(2,4,6-trichlorophenyl)hydrazono)piperidine (BCMTP) compound has been synthesized in one pot reaction. The novel compound BCMTP has been characterized by FT-IR, ¹H-NMR, ¹³C-NMR and single-crystal X-ray diffraction patterns. Crystal packing is stabilized by C8-H8A•••Cl10ⁱ, C41-H41•••Cl1ⁱⁱ and N1-H1A•••Cl6ⁱⁱⁱ intermolecular hydrogen bonds. From the geometrical parameters, it is observed that the piperidine ring adopts chair conformation. Hirshfeld surface analysis was carried out to quantify the interactions and an interaction energy analysis was done to study the interactions between pairs of molecules. The geometrical structure was optimized by density functional theory (DFT) method at B3LYP/6-31G (d, p) as the basic set. The smaller binding energy value provides the higher reactivity of BCMTP compound than hydroxyl chloroquine and was corrected by high electrophilic and low nucleophilic reactions. The stability and charge delocalization of the molecule were also considered by natural bond orbital (NBO) analysis. The HOMO-LUMO energies describe the charge transfer which takes place within the molecule. Molecular electrostatic potential has also been analysed. Molecular docking studies are implemented to analyse the binding energy of the BCMTP compound against standard drugs such as the crystal structure of ADP ribose phosphatase of NSP3 from SARS-CoV-2 in complex with MES and SARS-CoV-2 main protease with an unliganded active site (2019-nCoV, corona virus disease 2019, COVID-19) and found to be considered having better antiviral agents. Molecular dynamics simulation was performed for COVID-19 main protease (Mpro: 6WCF/6Y84) to understand the elements governing the inhibitory effect and the stability of interaction under dynamic conditions.