Synthesis, structure, DNA docking, pharmacokinetics/ADMET, Hirshfeld surface analysis, and antimicrobial studies on...

Biphenyl anchored pyrrolidine complexes [MLCl₂], [where M = Co (1), Ni (2), Cu (3) and Zn (4); L= 6-(2-(pyrrolidin-1-yl)ethyl)-6,7-dihydro-5H-dibenzo[c,e]azepine] were synthesized and characterized by elemental analysis, UV-Vis, FT-IR, ESI-MS, and NMR (in case of 4). Single crystal XRD revealed that all the complexes adopt distorted tetrahedral geometry. DFT calculations with their relative energies were compared with XRD structure. Absorption, oscillator strength, excitation energy, molecular orbital contributions were obtained from TDDFT calculation. The computed UV-Vis absorption data is comparable with experimental UV-Vis data. Molecular docking studies verified that all complexes strongly bind with DNA (PDB ID: 1BNA) through major groove interactions. The ligand and the complexes exhibit an elevated permeability of the blood-brain barrier and GI absorption, according to the SwissADME prediction criteria. The values of skin permeability (logKp) for the ligand and complexes 1-4 were determined to be -5.61, -5.27, -5.27, -5.30, and -5.31 cms^-1, respectively. All the complexes and the ligand were projected to function as a biological barrier, a transporter, and a substrate of P-glycoprotein (P-gp), which is responsible for the ADME of medications. Using Hirshfeld surface investigation, the intermolecular interactions within the crystal network were identified to support the prominent contribution from H∙∙∙∙∙H interactions, followed by Cl∙∙∙∙∙H and C∙∙∙∙∙H interactions, respectively. In the preliminary investigations, all the complexes displayed significant antibacterial properties against both Gram-positive and Gram-negative bacterial strains such as Staphylococcus aureus and Escherichia coli, respectively; those were obtained from human clinical isolates. Notably, the copper(II) complex, 3 showed better antibacterial activity in comparison to other complexes.