Comparative Biological Reactivity of a Set of Mononuclear Copper(II) Complexes

Optimizing chemotherapeutics to maximize specificity and minimize adverse side effects has gained prominence in recent years. Specifically, the use of metallo-chemotherapeutics has been popularized. Research in synthesizing organic ligands which can be coordinated to transition metal salts have shown promising results in their ability to kill cancer cells. To this end, a set of dinuclear metal complexes containing organic schiff-base ligand frames had previously been synthesized and evaluated for their biological activity. Since, a set of four mono-nuclear species containing the same ligand frame have been synthesized and fully characterized by x-ray diffraction crystallography, UV-Vis, and infrared spectroscopy in order to confirm their nuclearity and structure. Three of the resulting species were evaluated for their biological activity through ethidium bromide competitive binding assays with both DNA and RNA, circular dichroism spectrophotometry, cancer cell viability assays, and DNA cleavage experiments. All three complexes demonstrated binding constants on the order of 10^5 and 10^4 with DNA and tRNA, respectively, and demonstrated dose-dependent intercalation with both DNA and tRNA. All three complexes also demonstrated DNA cleavage activity via an oxidative mechanism. Furthermore, the complexes showed toxicity in cancer cell lines with micromolar IC50 values. These results provide important insight into how both the nucleic acid interaction and cytotoxicity of the Cu(II) complexes being studied may influence their abilities to act as potential chemotherapeutics.