Kai Wang

Mentor: Dr. Sharon Burgmayer

Abstract: Synthesis & Study of Polypyridyl Ruthenium Complexes on DNA Interaction & Photocleavage

Transition metal complexes are biologically important due to their interactions with DNA. One such group, Ruthenium tris-chelate complexes, are well studied DNA intercalators which have the same planar geometry as that of DNA base pairs. This structural similarity enables them to insert between the base pairs resulting in a structural distortion of DNA and disrupting replication. The ability of these intercalative compounds to prevent replication of DNA and proliferation of cells hold significant therapeutic developments in anti-cancer applications.

The Burgmayer Research lab has previously synthesized various Ruthenium (II)(bipyridine) and Ruthenium (II)(phenanthroline) compounds (Figure 1). Many inherent characteristic properties of the Ruthenium Polypyridyl complexes, such as their photochemical stability, redox and other photophysical properties, have guided techniques used to determine photocleavage ability. Gel electrophoresis was conducted in conjunction with UV exposure of DNA with the metal complex, viscosity titration tests as well as a range of pH tests were done on the bipyridine (bpy) compounds to determine the differing extent of DNA photocleavage.

The focus of the project at this stage is to define the effects of the phen complexes’ DNA photocleavage ability with respect to the behavior of their bpy analogs; much research has been conducted on the bpy complexes, so we hope to expand on the understanding of the phen variations. Studies done previously comparing select bpy and phen complexes showed that the phen compounds yielded higher photocleavage and was likely to have greater DNA intercalation. As such, additional pH studies will be tested to determine the validity of these earlier results. Furthermore, since these Ruthenium compounds have DNA replication inhibitory abilities, we hope to generate in vitro cell lines to develop the potential for these compounds as antineoplastic drugs. Finally, to refer to a more tangible element of our research, we hope to grow crystals to obtain a crystal structure of our Ruthenium complex intercalating DNA.

Fig 1

Figure 1.- Generic forms of the two Ruthenium complexes under study. Image on right is the [Ru(bpy)2L-pterine]2+ (blue), image on left is the phen analog (red), Ru(phen)2(L-pterine)]2+