Computational study of furosemide-piperazine (FS – PZ) and 2,3,5,6-tetramethylpyrazine (FS-TP) co-crystals

Abstract

• FS – TP shows the highest non-covalent interaction as compared to FS – PZ. • FS – TP co-crystal is more stable than the corresponding FS – PZ. • Stronger the intermolecular bonding is directly related to the stability of the corresponding co-crystals. • FS – TP shows better pharmacological activities as compared to the FS – TZ. Co-crystals are well-known for their applications in pharmaceutical chemistry. In this current manuscript, we have conducted a DFT analysis of two Co-Crystals of furosemide with piperazine (FS-PZ) and with 2,3,5,6-tetramethylpyrazine (FS-TP). The non-covalent interactions and structural, electronic, topological properties, and solvent effects are investigated in detail. The hyper-conjugative interactions and delocalization of charge are explored along with a molecular electrostatic potential map (MEP) and frontier molecular orbital (FMO) analysis. The Ab initio molecular dynamics studies showed that the co-crystals FS-TP is more stable than FS-PZ. Docking suggested that the co-crystals show biological activity and hence can be a good inhibitor against the absorption of inhibitors. Molecular dynamics (MD) simulations were carried out in three replicates to determine the stability and convergence of SARS-CoV-2 main protease (PDB ID: 6YB7) with FS-PZ and FS-TP co-crystals. We found that the structure of proteins was stable during simulation in ligand-bound conformations.