【作者】 龙朝阳；

【导师】 俞英；

【作者基本信息】 华南师范大学 ， 物理化学， 2002， 硕士

【摘要】 鉴于有些药物在生物体内发生转化，得电子还原后，可以与DNA发生作用，本文初步地探讨了这类药物的电学性质；用光度法研究了药物分子与DNA相互作用，从分子水平解释了抗癌、抗病毒药物的药理作用，同时为DNA提供了有效的检测方法。全文分为两个部分： 1．药物的电化学性质：研究了马兜铃酸A和甲硝唑的极谱伏安行为。在含有KCl、B-R缓冲液的底液中，马兜铃酸A和甲硝唑都产生一个良好的还原峰，还原峰电流与浓度呈良好线性关系，反应灵敏度高，大多数金属离子和常见中药不干扰测定，据此建立了这两种药物的极谱测定法，应用于实际样品测定，结果满意。运用多种电化学方法和技术研究了还原峰电流的性质，证实了这两种药物在汞电极上具有明显的吸附性。 2．药物与DNA的相互作用：药物与DNA相互作用的形式有多种，其中插入作用和静电结合较为普遍。以铜配合物为探针，用荧光光谱、摩尔比、粘度、MLCT减色效应、平衡常数以及荧光能量转移研究了配合物与鱼精子DNA的结合情况，证实了该配合物与DNA存在插入作用。实验发现配合物对DNA发生了能量转移，造成荧光量子产率比值(Φ_λ／Φ₃₂₀)的降低，从而解释了在不同激发光下，荧光发射峰在加入DNA后产生猝灭和增强两种绝然不同的现象。 基于盐酸巴马汀在加入DNA后荧光发生显著地增强，建立了一个DNA测定的新方法。本方法在生理条件的环境下，激发光和发射光的波长位移大，DNA的线性范围宽，灵敏度高，而且干扰小，操作简单，反应稳定。同时，通过对PMT与DNA作用的荧光光谱、粘度的测定、K₄[Fe（CN）₆]的猝灭研究、PMT与DNA作用的结合比的研究，认为PMT与DNA作用是以静电作用结合，而非插入形式结合。更多还原

【Abstract】 Based on the studying of the interaction of DNA with drugs, the pharmacological action of anticancer, antivirus have been explained at molecular lever and the novel method for DNA determining have been proposed. Since some drugs can accept electron when they are biologically reduced, then combine with DNA, the electrochemical action of these drugs were also primarily investigated. The two parts have been grouped into:1. The polarographic and voltammetric behavior of drugs: The polargraographic and voltammetric behavior of metronidazole and aristolochifc, A have been investigated by voltammetry, normal pulse polargraphy, osillopolarograph. In the base solution of B-R buffer solution containing KC1, a well-defined reduction peak of metronidazole and aristolochia A were obtained. The peak current directly proportioned to the concentration of metronidazole over the certain range, with sensitive detection limit and advanced correlation coefficient. The methods can be applied to the actual sample with satisfying result. The irreverisible adsorption characteristics of the peaks were proved by the experiments.2. The interaction of drugs with DNA: There are several interaction forms of drugs with DNA. However, the intercalation and hydrogen bonding are universal. Due to a new copper complex, the binding of the complex to fish sperm DNA was investigated by using fluorescence and absorption spectroscopy, continuous variation analysis, viscosity measurements, equilibrium binding and the salt dependence of the binding constant studies, fluorescence energy transfer experiments. The intercalation mode was proved to exist. Especially we found energy could transfer from bound ligand to DNA bases, which was provided additional evidence for the intercalation of copper complex into DNA and was used to explain the fluorescence spectroscopy.In addition, A novel fluorimetric method has been developed for rapid determination of DNA with palmatine hydrochloride (PMT) as a fluorescence probe, based on the fluorescence dramatical enhancement of PMT in the presence of DNA. The method is free from interference from a large number of foreign substances and is recommended for the determination of DNA in biological systems. All the reagents and reaction systems are stable and the procedure is easy to carry out. Moreover, Fluorescence, viscosity measurement, potassium ferrocyanide quenching studies have been used to characterize the interaction of PMT with fs DNA.更多还原