Synthesis, Structure and Biological Activity of Indole-Imidazole Complexes with ZnCl2: Can Coordination Enhance the Functionality of Bioactive Ligands?

Molecules. 2023 May 16;28(10):4132. doi: 10.3390/molecules28104132.

Abstract

The ability of the indole-imidazole hybrid ligands to coordinate with the Zn(II) ion and the resulting structures of this new class of coordination compounds were analyzed in order to determine their structural properties and biological functionalities. For this purpose, six novel Zn(II) complexes, [Zn(InIm)2Cl2] (1), [Zn(InMeIm)2Cl2] (2), [Zn(IniPrIm)2Cl2] (3), [Zn(InEtMeIm)2Cl2] (4), [Zn(InPhIm)2Cl2] (5) and [Zn2(InBzIm)2Cl2] (6) (where InIm is 3-((1H-imidazol-1-yl)methyl)-1H-indole), were synthesized by the reactions of ZnCl2 and the corresponding ligand in a 1:2 molar ratio in methanol solvent at an ambient temperature. The structural and spectral characterization of these complexes was performed using NMR, FT-IR and ESI-MS spectrometry and elemental analysis, and the crystal structures of 1-5 were determined using single-crystal X-ray diffraction. Complexes 1-5 form polar supramolecular aggregates by utilizing, for this purpose, the N-H(indole)∙∙∙Cl(chloride) intermolecular hydrogen bonds. The assemblies thus formed differ depending on the distinctive molecular shape, which can be either compact or extended. All complexes were screened for their hemolytic, cytoprotective, antifungal, and antibacterial activities. The results show that the cytoprotective activity of the indole/imidazole ligand significantly increases upon its complexation with ZnCl2 up to a value comparable with the standard antioxidant Trolox, while the response of its substituted analogues is diverse and less pronounced.

Keywords: Zn(II) complexes; antibacterial activity; fungicidal properties; human erythrocytes; indole derivatives; oxidative hemolysis.

MeSH terms

  • Coordination Complexes* / chemistry
  • Coordination Complexes* / pharmacology
  • Imidazoles
  • Indoles
  • Ligands
  • Spectroscopy, Fourier Transform Infrared
  • Zinc* / chemistry

Substances

  • Zinc
  • Ligands
  • Imidazoles
  • Indoles
  • Coordination Complexes

Grants and funding

This work was financially supported by the Research Subsidy at the Faculty of Chemistry of the Adam Mickiewicz University in Poznań, the Research Subsidy at the Faculty of Biology of the Adam Mickiewicz University in Poznań and by the ID-UB 054 grant number 054/12/SNŚ.0011.