Synthesis, Characterization, and Preliminary In Vitro Anticancer Activity of Zinc Complexes Containing Amino...

Coordination polymers containing zinc and imidazolium-based dicarboxylate ligands, [L^R]^-, were synthesized by reacting zinc acetate with HL^R compounds, 1. The resulting complexes were characterized and structurally identified using single-crystal X-ray diffraction, revealing polymeric structures for the complexes [Zn(L^R)₂]_n (R = Gly, 2a; βAla, 2b) and [Zn(L^Leu)₂(H₂O)₂]_n (2c). In these structures, the [L^R]^- 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(L^R)(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 [L^R]^- 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).