# Synthesis, Characterization, and Preliminary In Vitro Anticancer Activity of Zinc Complexes Containing Amino Acid-Derived Imidazolium-Based Dicarboxylate Ligands

## TL;DR

This study creates zinc complexes with imidazolium ligands and tests their anticancer activity, finding some to be more selective than common chemotherapy drugs.

## Contribution

The paper introduces new zinc complexes with amino acid-derived ligands and evaluates their selective anticancer potential.

## Key findings

- The zinc complexes showed higher toxicity against cancer cells than non-cancerous cells.
- Complex 2c had a selectivity index similar to gemcitabine against melanoma cells.
- Compound 2a showed selective activity against lung cancer, while 2b was the most active but with low selectivity.

## Abstract

Coordination polymers containing zinc and imidazolium-based dicarboxylate ligands, [LR]−, were synthesized by reacting zinc acetate with HLR compounds, 1. The resulting complexes were characterized and structurally identified using single-crystal X-ray diffraction, revealing polymeric structures for the complexes [Zn(LR)2]n (R = Gly, 2a; βAla, 2b) and [Zn(LLeu)2(H2O)2]n (2c). In these structures, the [LR]− ligands adopt a bridging monodentate μ-κ1-O1,κ1-O3 coordination mode, resulting in distorted tetrahedral (2a, 2b) or octahedral (2c) geometries around the zinc center. When the synthesis was carried out in the presence of amino acids, mixed ligand complexes [Zn(LR)(aa)(H2O)]n (R = aa = Val, 2d, and R = aa = Ile, 2e) were formed. Complexes 2d–2e were also structurally characterized using single-crystal X-ray crystallography, revealing that the ligand [LR]− maintained the same coordination mode, while the zinc center adopted a five-coordinated geometry. The cytotoxic activity of complexes 2a–2e was evaluated against three cancer cell lines and one non-cancerous cell line. Remarkably, these complexes exhibited higher toxicity against cancer cells than against the non-cancerous cell line, and they showed greater selectivity than carboplatin, a commonly used chemotherapy drug. Although, in general, these complexes did not surpass the selectivity of gemcitabine, complex 2c stood out for exhibiting a selectivity index value similar to that of gemcitabine against melanoma cells. Among the series, compounds 2a–2c demonstrated the highest activity, with 2a being the only complex with some selective activity against lung cancer. Complex 2b was the most active, though with low selectivity, while complex 2c exhibited the highest selectivity for melanoma and bladder cancer (selectivity index of 3.0).