Theoretical and experimental investigations into structural, electronic, molecular and biological properties of 4-(3-chlorophenyl)-1-(3-chloropropyl) piperazin-1-ium chloride

Abstract

A convenient and facile synthesis of 4-(3-chlorophenyl)-1-(3-chloropropyl)piperazin-1-ium chloride is accomplished by stirring 1-(3-Chlorophenyl)piperazine hydrochloride with 3-chloropropanal by reductive amination in ethanol. The resulting compound was characterized using spectral data analysis augmented by X-ray. Single crystal analysis depicted that the synthesized compound crystallizes in monoclinic crystal system with P 21/c point group. The structural and electronic properties of the title compound have been calculated at DFT/B3LYP/6-311G (d,p) level of theory. Theoretically obtained parameters were well compared to the experimentally obtained results, showing excellent agreement. Molecular electrostatic potential surface, frontier orbital analysis and vibrational analysis were also carried out. HOMO-LUMO energy gap was calculated which allowed the calculation of relative properties like chemical hardness, chemical inertness, chemical potential, nucleophilicity and electrophilicity index of the synthesized products. Pass prediction was carried out which revealed that the target compound can be active against Prostate specific membrane protein, bearing Pa value of 0.411. Based on Pass, molecular docking studies of compound was carried out against Prostate specific membrane protein. The title compound depicted a binding free energy of −6.3 kcal/mol and is seen to be involved in key bonding interactions which include both alkyl and mixed pi-alkyl hydrophobic interactions: Alkyl hydrophobic interactions: (LEU 259; 4.64 Å, LEU 261; 3.79 Å), mixed Pi/alkyl hydrophobic interactions: (HIS 552; 4.96 Å, HIS 553; 4.64, 5.31 Å LEU; 3.45 Å) respectively with Prostate specific membrane protein. Target compound was screened for their cytotoxic potential with various cancer cell lines being most effective against prostate. In short, this study reveals the synthesis of a 4-(3-Chlorophenyl)-1-(3-chloropropyl)piperazin-1-ium chloride and exposes its structural, electronic and biological properties, paving way for further research in the field of drug development.