CHED 594

Interactions of Sn(IV) and Ti(IV) organometallic complexes with double-stranded DNA: ICP-AES and HPLC analysis

Shari U. Dunham and Katharine M. Davies. Department of Chemistry, Colby College, Waterville, ME 04901-8857,

In order to understand further the interactions that exist between specific organometallic complexes and DNA, reactions of double-stranded calf-thymus DNA with titanocene dichloride (Cp2TiCl2, Cp=C5H5), triphenyltin chloride (Ph3SnCl), diphenlytin dichloride (Ph2SnCl2), and triphenyltin acetate (Ph3SnOAc) were performed. The goal of this research is to establish how the fundamental structure and composition of these compounds determine the effectiveness of their DNA interactions. Each metal compound was incubated with DNA at several metal:DNA ratios and reactions were maintained at 37oC (pH 6-8). Multiple time points were taken of each reaction mixture and for each time point the modified DNA was isolated via ethanol precipitation. Modified DNA was then analyzed by ICP-AES (to determine the ratio of bound metal to phosphorous) and by HPLC separation of enzymatic digestions (to determine the relative percent area of each of the four bases in modified and control DNA). Preliminary data will be presented and DNA-binding trends will be discussed in view of a DNA-binding mechanism for these potential organometallic anticancer agents.