Studies Of The Interaction Among Cu(phen)₂～(2+) Complex, Purine Drugs And DNA

Based on nuclease activities of Cu(phen)₂²⁺ complex, its interaction studies with some drugs used in clinic containing purine groups including 6-Mercaptopurine (6-MP), 6-Thiolguanine(6-TG), 6-Hypoxanthhine(6-HX), Adenine(A) and 2,5-Dime-rcapto-1,3,4- thiadiazole (DMcT) have important scientific meaning for researching novel anticancer drugs. The main purpose of this article is to study the interaction among Cu(phen)₂²⁺ complex, purine drugs and DNA using electrochemical methods(cyclic voltammetry, differential pulse voltammetry, rotating disk electrode measurements, ac impedance and its data fitting), spectral techniques, viscosity measurements and agarose gel electrophoresis technique.In chapter 1, the structure of DNA and the interaction mechanisms of anticancer drugs with DNA are first described. At the same time, the used methods of the interaction between anticancer drugs and DNA are also summarized. With these described above as basis, the purposes of this article are suggested.In chapter 2, all chemicals, instruments, experimental methods used in this article are briefly described.In chapter 3, the interaction of Cu(phen)₂²⁺complex with 6-MP has been studied using electrochemical methods(cyclic voltammetry, differential pulse voltammetry, rotating disk electrode measurements, ac impedance and its data fitting), electronic absorption spectroscopy, potential titration. The results show that the interaction of Cu(phen)₂²⁺ with 6-MP is proved to exist under diffusion control or electrochemicalcontrol. The cyclic voltammograms exhibit a couple of redox peaks and the electrochemical impedance spectra for Cu(phen)22+ on the platinum disk electrode show two obvious capacitance arches in the absence or presence of 6-MP. However, peak potentials shift negatively, peak currents decrease significantly, the charge transfer resistance and the adsorption resistance are increased in the presence of 6-MP compared with that in the absence of 6-MP. On the other hand, with the addition of the rotating rate, the values of the charge transfer resistance and the adsorption resistance show a decrease, double-layer capacitance and adsorption capacitance indicate the enhanced and reduced tendencies in the absence or presence of 6-MP, respectively. At the same time, electronic absorption spectroscopy of Cu(phen)2 +complex is regularly changed in the presence of 6-MP, the maximal absorption peak from absorption spectra is red-shift and the intensity is weakened. And the binding constant of Cu(phen)22+complex with 6-MP is 3.41 X 103 L · mol"1. In the same condition, the interactions of Cu(phen)22+complex with the other compounds including 6-TG, 6-HX, A and DMcT have been studied by electrochemical methods and electronic absorption spectroscopy. The results show that the interaction of 6-HX with -OH group and A containing -NH2 group with Cu(phen)22+complex is weak, but the interaction of 6-TG and DMcT containing -SH group is strong as that of 6-MP.In chapter 4, the interaction between Cu(phen)22+complex and calf thymus DNA has been investigated using electrochemical methods(cyclic voltammetry, differential pulse voltammetry), electronic absorption spectroscopy, ethidium bromide(EB) fluorescene spectroscopy, viscosity measurement and agarose gel electrophoresis technique. The experimental results show that peak potentials for the interaction product of Cu(phen)22+ complex with 6-MP shift positively, peak currents decrease significantly in the presence of DNA. With the increasing of DNA, peak currents indicate a corresponding decrease. At the same time, the interaction products of Cu(phen)22+complex with 6-MP can quench remarkably the emission of EB-DNA system, the maximal absorption peak from absorption spectra shows a red-shift andthe intensity is weakened. All experimental results indicate that their interaction product has an enhanced action with calf thymus DNA compared with that in the absence of 6-MP and the part intercalation is proved to exist. More importantly, 6-MP is shown to have an enhanced pBR322...