Catalytic, Theoretical, and Biological Investigations of Ternary Metal (II) Complexes Derived from L-Valine-Based Schiff Bases and Heterocyclic Bases

Abstract

A new series of ternary metal complexes, including Co(II), Ni(II), Cu(II), and Zn(II), were synthesized and characterized by elemental analysis and diverse spectroscopic methods. The complexes were synthesized from respective metal salts with Schiff's-base-containing amino acids, salicylaldehyde derivatives, and heterocyclic bases. The amino acids containing Schiff bases showed promising pharmacological properties upon complexation. Based on satisfactory elemental analyses and various spectroscopic techniques, these complexes revealed a distorted, square pyramidal geometry around metal ions. The molecular structures of the complexes were optimized by DFT calculations. Quantum calculations were performed with the density functional method for which the LACVP++ basis set was used to find the optimized molecular structure of the complexes. The metal complexes were subjected to an electrochemical investigation to determine the redox behavior and oxidation state of the metal ions. Furthermore, all complexes were utilized for catalytic assets of a multi-component Mannich reaction for the preparation of -amino carbonyl derivatives. The synthesized complexes were tested to determine their antibacterial activity against E. coli, K. pneumoniae, and S. aureus bacteria. To evaluate the cytotoxic effects of the Cu(II) complexes, lung cancer (A549), cervical cancer (HeLa), and breast cancer (MCF-7) cells compared to normal cells, cell lines such as human dermal fibroblasts (HDF) were used. Further, the docking study parameters were supported, for which it was observed that the metal complexes could be effective in anticancer applications.

Keywords: Cu(II) complexes; L-valine; antibacterial activity; binding interaction; ternary metal.

Scheme 1

Synthetic route of Co(II), Ni(II), Cu(II), and Zn(II) complexes with tridentate ligand (HL) and bidentate diamines (1,10-phenanthroline or 2,2′-bipyridyl).

Figure 1

UV spectra of (a) complexes 1a–1d and (b) complexes 1e–1h and (c) visible spectra of complexes 1a–1h in methanol.

Figure 1

UV spectra of (a) complexes 1a–1d and (b) complexes 1e–1h and (c) visible spectra of complexes 1a–1h in methanol.

Figure 2

TGA curve of [Cu(L)(bpy)] 1g complex.

Figure 3

X−band EPR spectrum of complex [Cu(L)(phen)] 1c and [Cu(L)(bpy)] 1g at room temperature.

Figure 4

Powdered X-ray patterns of (a) complexes 1a–1d and (b) complexes 1e–1h.

Figure 5

Cyclic voltammograms of metal(II) complexes 1a–h. (a) Reduction process at cathodic region. (b) Oxidation process at anodic region in DMF containing 0.1M of tetra(n−butyl)ammoniumperchlorate. The scan rate applied was 100 mVs⁻¹.

Scheme 2

Catalytic one-pot three-component Mannich reaction through multiple approaches.

Figure 6

Frontier molecular orbitals of investigated complexes, namely, (i) cobalt(II) complex 1a, (ii) nickel(II) complex 1b, (iii) copper(II) complex 1c, and (iv) zinc(II) complex 1d, using B3LYP/LACVP++ basis set.

Figure 7

Frontier molecular orbitals of investigated complexes, namely, (i) cobalt(II) complex 1e, (ii) nickel(II) complex 1f, (ii) copper(II) complex 1g, and (iv) zinc(II) complex 1h, using B3LYP/LACVP⁺⁺ basis set.

Figure 8

The 3D and 2D interactions of [Cu(L)(phen)] complex 1c located in hydrophobic sites of thymidylate synthase receptor.

Figure 9

Antibacterial activity of metal(II) complexes (1a–1h) tested against (a) Escherichia coli, (b) Klebsiella pneumonia, and (c) Staphylococcus aureus bacteria at different concentrations.

Figure 10

(a) In vitro anticancer activity of copper(II) complexes 1c and 1g against A549, HeLa, and MCF-7 cancer cell lines. (b) MTT-based antiproliferative photomicrographs of copper(II) complex 1c on MCF7 HeLa and A549 cancer cell lines after 24 h incubation under a phase contrast microscope. Arrows indicate (1) control cell, (2) condensed nuclei, (3) cell shrinkage, (4) membrane blebbing, (5) apoptotic bodies, (6) bubbling, and (7) echinoid spikes.

Figure 10

(a) In vitro anticancer activity of copper(II) complexes 1c and 1g against A549, HeLa, and MCF-7 cancer cell lines. (b) MTT-based antiproliferative photomicrographs of copper(II) complex 1c on MCF7 HeLa and A549 cancer cell lines after 24 h incubation under a phase contrast microscope. Arrows indicate (1) control cell, (2) condensed nuclei, (3) cell shrinkage, (4) membrane blebbing, (5) apoptotic bodies, (6) bubbling, and (7) echinoid spikes.