Mentor: Dr. Sharon Burgmayer
In Dr. Sharon Burgmayer's research group, the investigation of the behavior of ruthenium complexes binding to DNA reaches a new phase this summer. These ruthenium complexes can potentially bind to DNA by intercalation, groove binding, surface binding, or other mechanisms. Viscosity measurements will provide definitive evidence to determine whether various ruthenium complexes intercalate DNA. Intercalating molecules are distinguished through viscosity, since insertion of a ligand among the DNA base pairs causes the DNA helix to lengthen. As a result, this elongation induces changes in the viscosity of DNA.
Viscosity measurements require the observant and careful timing of the flow of liquid through an Ostwald viscometer. If the data reveal a positive linear slope, then it is highly indicative of a complex that binds to DNA by intercalation. Previously, fluorescence and UV/Vis spectroscopic techniques have been used to study the binding mode. More than one method is needed to study the mode of binding primarily because much debate exists among chemists as to what experiment provides reliable proof of a binding mechanism.
The five ruthenium complexes being studied in these experiments are of the type [Ru(bpy) 2 L] 2+ , where bpy stands for bipyridine and L is a bidentate ligand formed from phenanthroline fused to dimethylalloxazine, pterin, diamino, alloxazine, or dipyridophenazine. Ethidium bromide, known to intercalate, and [Ru(bpy) 3 ] 2+ , a known groove binder, will be used as standards to which the other ruthenium complexes can be compared.
In these experiments, the mode of binding is a primary focus because such information can provide us with better insight as to how medicinal drugs bind to DNA, and how we may improve upon currently existing medicines that rely on such binding mechanisms for considerable effectiveness in the human body. Of all the known binding mechanisms, we strongly desire to find ligands that are able to intercalate because it is known that intercalation interrupts the capacity of DNA to replicate. This is especially desirable when replication is harmful, such as the production of cancer cells.