Structural-Dependent N,O-Donor Imine-Appended Cu(II)/Zn(II) Complexes: Synthesis, Spectral, and in Vitro Pharmacological Assessment.

Abstract

Four mononuclear bioefficient imine-based coordination complexes, [(L1)2Cu], [(L1)2Zn], [(L2)Cu(H2O)], and [(L2)Zn(H2O)], were synthesized using ligands [L1 = 2-(((3-hydroxynaphthalen-2-yl)methylene)amino)-2-methylpropane-1,3-diol and L2 = 4-(1-((1,3-dihydroxy-2-methylpropan-2-yl)imino)ethyl)benzene-1,3-diol]. The formation of the complexes was ascertained by elemental analysis, Fourier transform infrared, 1H NMR, 13C NMR, electrospray ionization–mass spectroscopy, electron paramagnetic resonance, and thermogravimetric analysis. The comparative binding propensity profiles of the above-synthesized complexes with the DNA/human serum albumin (HSA) were investigated via UV absorption, fluorescence, and Förster resonance energy-transfer studies. On the basis of extended conjugation and planarity, L1 complexes exhibited superior bioactivity with greater calculated DNA binding constant values, (Kb) 2.9444 × 103[(L1)2Cu] and 2.2693 × 103[(L1)2Zn], as compared to L2 complexes, 1.793 × 103[(L2)Cu(H2O)] and 9.801 × 102[(L2)Zn(H2O)]. The competitive displacement assay of complexes was performed by means of fluorogenic dyes (EtBr and Hoechst), which corroborates the occurrence of minor groove binding because of the enhanced displacement activity with Hoechst 33258. The minor groove binding of the [(L1)2Cu] complex is further confirmed by the molecular docking study. Moreover, the HSA study demonstrated effective static quenching of complexes with substantial Ksv values. The [(L1)2Cu] complex was found to have pronounced cleavage efficiency as evaluated from sodium dodecyl sulfate polyacrylamide gel electrophoresis electrophoresis. Furthermore, in vitro antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl and superoxide radicals further proclaimed the remarkable bioefficiency of compounds, which make them promising as active chemotherapeutic agents.