DNA Interaction of Metallo-Organic Complexes Evaluated Through Binding-Strength and Cleavage Assays

Metals, like platinum, are utilized as chemotherapeutics due to their ability to inhibit cancer cell growth via DNA damage. Based on the success of platinum complexes, other transition metal-based complexes are of increasing interest for their potential biological applications. Organic schiff-base ligands were coordinated to a variety of copper(II) and nickel(II) salts, and the resulting complex structures were identified by x-ray crystallography. The ability of these complexes to interact with and cleave DNA was investigated. In particular, ethidium bromide displacement assays showed that the metal complexes evaluated competitively intercalate into calf-thymus DNA in a dose-dependent manner, with apparent binding constants within the range of 3.0 x 105 to 5.0 x 105. Gel electrophoresis studies demonstrated that the complexes cleave plasmid DNA to form both single and double-nicked fragments and that cleavage was concentration dependent. A summary of these techniques and how they were applied to evaluate the metal complex-DNA interactions will be presented and analyzed. Future studies will include continuations of these DNA interaction analyses with new sets of metallo-organic complexes synthesized from new ligands and varying metal salts.