Synthesis, Characterization, and Anti-Plasmodium falciparum Activity of a New Copper(II) Complex Containing 2-(Tert-Butoxy)-6-(1H-imidazol-1-yl)pyridine.

This work describes the synthesis, characterization, and preliminary evaluation of the anti-Plasmodium falciparum activity of a copper(II) coordination-complex derived from an imidazole-based ligand. This compound was characterized by Infrared, UV-Vis, Raman, high resolution mass spectrometry, fluorescence, Thermogravimetric analysis, and electrical conductivity allowing the elucidation of their structure and which was also confirmed by single-crystal X-ray diffraction. From the crystallographic analysis, it was found that the copper atom is situated in an octahedral environment, with both carboxylate ligands occupying equatorial positions and the ligands L located axially. Interestingly, the acetate ions act as bidentate ligands, but in an anisobidentate binding mode, where the oxygen atoms exhibit different bond distances to the metal center, resulting in asymmetric coordination. This phenomenon is attributed to strong hydrogen bonding within the crystal packing. Biological assays performed to test the complex revealed low hemocytotoxicity, with values ≤20% at concentrations above 500 µg/mL. When evaluated in vitro against Plasmodium falciparum (3D7 strain, chloroquine-sensitive), the complex exhibited significantly higher activity than the free ligand. These findings indicate that coordination to the metal center plays a substantial role in enhancing antiparasitic-activity, providing a solid foundation for future investigations aimed at elucidating the underlying mechanisms and advancing research on the anti-Plasmodium falciparum activity of metal complexes.