Synthesis, spectroscopic investigations, topological non-covalent interactions, chemical reactivity, molecular docking and molecular dynamic simulation on piperazine succinate - A potential antimicrobial compound

Abstract

Piperazine Succinate (PZSN) has been synthesized and extensively analyzed using various spectroscopic techniques, including FT-IR, FT-Raman and NMR spectra. In optimizing geometry, a comparison between the bond lengths of C2-H25 in PZSN (1.0999 Å) and SN (1.0938 Å) reveals an increase of 0.0061 Å in the C21-H25 bond length for PZSN. This elongation can be attributed to the significant C21-H25‧‧‧N2 intermolecular hydrogen bonding interaction. Natural bond orbital analysis of the molecule indicates a significant charge transfer between LP(1) N2 → σ* (C21-H25) leads to a substantial stabilization energy of 6.73 kcal/mol, providing strong evidence for the presence of intermolecular hydrogen bonding interactions. The strong band observed in the IR spectrum at 3510 cm−1, assigned to N2-H16 stretching mode, which clearly supports the formation of a hydrogen bond between succinate C=O and piperazine NH group. The complete vibrational assignments and the force constants has been reported for PZSN by using B3LYP/6–311++G** method. Molecular parameters, such as Frontier Molecular Orbital (FMO) energies, Fukui functions and Molecular Electrostatic Potential (MEP), have been calculated to gain insights into the stability and reactivity of the molecule. According to the QTAIM analysis, the presence of a strong non-bonded interaction is supported by the largest interaction energy observed at the C21-H25‧‧‧N2 bond critical point (BCP), which is 3.42 kcal/mol. Furthermore, Reduced Density Gradient (RDG) and Independent Gradient Model (IGM) approaches have been performed to disclose the attractive contacts like hydrogen bonds, repulsive and van der Waals interconnections. The molecule's drug-likeness has been assessed using Lipinski's rule and ADMET contour analysis indicated its potential for pharmaceutical applications. Molecular docking modeling have been conducted on antimicrobial proteins to explore the structure-activity relationship and antimicrobial testing confirmed the molecule's efficacy against microbial infections. Molecular dynamic simulations have been utilized to examine the stability of protein-ligand complex.