Study Of The Interaction Of Native DNA And Nucleotides With Compounds Of Germanium

Nucleic acid is the essential genetic material, which plays an important role in the living activity. Since the complex cisplatin was clinically used in cancer chemotherapy in the late 1960s, metal complexes have attracted much attention as a new type of potential anticancer drugs involving DNA as the major biological target. In recent years a variety of studies have been carried out on the antitumor of the compounds organogermanium and shown that the organogermanium has the similar biomedical activity to the cisplatin, and now ,the compounds of organogermanium have been awarded as a new antitumor agent. But up to new, little is known about the mechanism of the antirumoural activity of organogermanium compounds, as for cisplatin and organotin ,DNA was proposed to be the target , and little work has been done on the interaction between organogermanium and DNA or its precursors.The purpose of this study is to elucidate if the organogermanium and inorganogermanium can interact with DNA using the UV spectrum and Fluorescence spectrum and the impact of pH, -PO32~, ion strength etc on the interaction. If it is true, next step is to investigate what kind of bonding mode occur between them by using IR, MS to study the interaction of the organogermanium with the nucleotides which can indirectly prove the possibility of the interaction. The results should be valuable in understanding the mechanism of the antitumor activity as well as laying the foundation for the rational design of more active organogermanium agents.The result shows that: the inorgnogermanium(GeO2), can not interact with DNA in a O.Olmol/L KNO3 solution, while the organogermanium(Et2GeCl2),can interact with DNA. The interaction of organogermanium with nucleotides is not soecific through the Fluorometric test using different fluorometric stains, EB and DAPI. The interaction between Et2GeCl2 and DNA is affected by pH and ion concentration in the solution. The change of the DNA caused by Et2GeCl2 is apparent when the ion strength is 0.01mol/L~0.1mol/L and the pH is 4.0-5.0. The test of KH2PO4 showes that there is another binding mode excluding the interaction mode with -PO32" between the interaction ofDNAandEt2GeC!2.The solid samples made from the diethylgermanium dichloride and AMP, CMP, GMP, IMP solution are investigated by infrared spectroscopy and mass spectrometry techniques. As demonstrated, diethylgermanium dichlorid can coordinate with nucleotides excluding CMP and exist different interaction site for different nucleotides. As for GMP there are three possible coordinate site, C6=O, N7 and -PO32" respectively; while there is only one site -PO32- to AMP and IMP.