Investigating the binding properties of copper-based chemotherapeutics to ribonucleic acids

Metal-based therapeutics have been at the forefront of anticancer treatments beginning with the discovery of cisplatin; however, the lack of specificity to cancer cells with cisplatin treatment leads to severe unintended side-effects. The development of new copper-based metal complexes is of interest because copper is a micronutrient and is found in higher concentration in cancer cells than healthy cells, which may allow for specificity. Previous studies on Cu(II)-containing complexes have indicated that these types of species interact extensively with DNA but it is as of yet unknown if they interact with RNA. Here, an in-depth analysis of the interactions of Cu(II) complexes with RNA is presented. These studies include 1) measuring the binding affinity of the complex to tRNA through an ethidium bromide displacement assay, 2) assessing the induced changes in RNA secondary structure using circular dichroism (CD), and 3) determining if the complexes can cleave RNA using polyacrylamide gel electrophoresis (PAGE). Our data suggests that, like DNA, these copper complexes bind to RNA in a concentration dependent manner and cause changes in the RNA secondary structure. Further investigations into their ability to cleave RNA are underway. Overall, the RNA binding and reactivity of these Cu(II) complexes will be discussed and compared based on the structural differences between the set of complexes.