Structural, Spectroscopic, and Docking Analysis of N,O-Donor Ligand Metal Complex Nanoparticles With Hypolipidemic Effects via Lipoprotein Lipase Activation in High-Fat Diet Mice

Abstract

New Cd(II), Zn(II), and Cu(II) chelates with cetirizine.2HCl (CETZ.2HCl) in incidence of 1,10 phenanthroline monohydrate (Phen.H₂O) were synthesized in search of new biologically active compounds. The ligands and their chelates were described by 1H NMR, FT-IR, elemental analysis, UV-vis spectrophotometry, thermal analyses, molar conductance, x-ray diffraction (XRD), and magnetic-susceptibility measurements. FT-IR demonstrated that CETZ.2HCl is bonded with metal ions, as a monodentate via carboxylate oxygen atom and Phen.H₂O chelated via two nitrogen atoms. The molar conductivity data showed that the complexes were nonelectrolytes, whereas XRD data supported that the compounds were crystalline. Density functional theory (DFT) was utilized to gain insight into the compounds' optimized design. The effects of CETZ.2HCl and the complexes on the activity of lipoprotein-(L)-lipase in mice were investigated. Unlike Cd(II) complex, all the other compounds exhibited significant increase in lipase activity, with reduction in triglycerides. Cu(II) and Zn(II) complexes showed robust hypolipidemic efficacy evidenced by lower levels of total cholesterol and low-density lipoprotein (LDL), concomitant with higher levels of high-density lipoprotein (HDL). Furthermore, Zn(II) complex was a safe alternative as it has a lower liver toxicity. Molecular docking demonstrated that Cu(II) and Zn(II) chelates exhibited greater affinities to lipase than the parent ligand. Finally, Cu(II) complex showed the highest antibacterial activity.

Keywords: density functional theory (DFT); hypolipidemic; lipoprotein lipase; metal complexes; spectroscopy.