The synthesis and characterization of a new kind of tagged Ru-Pt bimetallic DNA binding agent

by Fang, Zhenglai

The goal of this project was to design a new kind of tagged supramolecular structural motif. These systems are modular in design and able to bind to DNA. The motif can be represented as TAG-LA-BL-BAS (TAG = NMR active phosphine ligand, LA = light absorber, BL = bridging ligand and BAS = bioactive site). The TAG provides a NMR probe for the characterization of supramolecular complexes as well as for the future investigation of the metal complex–DNA interaction process. In this project the phosphorous ligand PEt2Ph was selected as the TAG due its ability to provide an easy 31P NMR probe in the research. The LA represents the light absorber which could be photoexcited by photons of proper energy, here a RuII (tpy)(PEt2Ph)(BL) chromophore is used. The bridging ligands are those bidentate polyazine ligands that can connect two metal center together in a polymetallic system and have a low energy ?* orbital. The BAS represents the bioactive sites for binding to DNA, in this case the cis-PtII Cl2 moiety based on previous studies with cisplatin. The Ru-Pt bimetallic complexes [(tpy)Ru(PEt2Ph)(BL)PtCl2](PF6)2 (BL = bpm or dpp) and their precursors were designed, successfully synthesized and characterized. The synthesis followed a building block approach, allowing variation of the supramolecular system. The final bimetallic complexes were made without need for Al2O3 column chromatograph, important due to the presence of the labile PtII Cl2 center. ii The bimetallic complexes and all of their monometallic precursors were fully characterized by FAB MS, electrochemistry, electronic absorption and 31P NMR spectroscopy. The Ru-Pt bimetallic complex containing the bpm bridging ligand and its precursors were also characterized by 1H NMR. The FAB MS spectra of the complexes is characterized by the appearance of the parent ion peaks [M-PF6]+ and [M-2PF6]+. The cyclic voltammogram of all complexes show metal based oxidation(s) and ligand based reductions. The electronic absorption spectra of the complexes are characteristic of the lowest lying Ru?BL MLCT (metal to ligand charge transfer) transition with higher energy bridging and terminal ligand based ???* transitions. The electronic absorption data are consistent with the electrochemical data. The 31P NMR technique provides an efficient and easy characterization method for the complexes, showing the utility of this structural moiety. The DNA binding activity of the bimetallic complexes were studied by non-denaturing agarose gel electrophoresis and the results show that these tagged bimetallic complexes can bind to DNA through the cis-PtII Cl2 moiety. This binding has a more pronounced retardation effect on DNA migration than cis-[Pt(NH3)2Cl2] (cisplatin), but less than [Ru(bpy)2(dpq)PtCl2](CF3SO3)2. The DNA binding study establishes these bimetallic complexes with a NMR tag ligand, PEt2Ph, as a new kind of DNA binding agent. iii