药物分子与主体和生物分子相互作用的电化学方法研究
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摘要
研究药物与生物分子之间的相互作用，在医学、药学及生物学等领域具有重要的意义，药物只有通过与人体内的各种功能蛋白，DNA以及细胞膜等的相互作用作用才能够发挥它的药理药效作用。电化学方法研究相互作用已经有了大量的报道，但是主要集中在研究金属离子与生物分子之间的相互作用，本文将通过对有机药物分子电化学性质以及它与主体和生物分子作用后的电化学性质变化的比较研究，确定他们之间作用的大小，作用方式以及结合位点数等。
由于本研究的基本原理是基于电活性分子相互作用前后扩散系数变化来测定相互作用的，因而控制影响扩散系数的因素至关重要。针对各种主体和生物分子对溶液粘度的不同影响这一事实，本文首先建立了一个主体分子对溶液体系粘度没有影响或者它的影响可以忽略的研究主体分子与药物分子相互作用的实验模型，并且利用该实验模型研究了氯苯那敏与β-环糊精（β-CD）的相互作用。本文详细研究了氯苯那敏在悬汞电极上的电化学性质，并探讨了它在β-CD存在时的电化学性质变化，确定了利用电化学方法研究它们之间相互作用的可行性。实验假定了氯苯那敏与β-CD的结合比为1:1，测得它们之间的结合常数为2.83×102 。
蛋白质是一种高粘度的物质，针对这种情况，建立了在高粘度影响下研究蛋白质与药物分子相互作用的实验模型，并研究芦荟大黄素与牛血清白蛋白（BSA）的相互作用以及在模拟生理条件下对乙酰氨基酚与人血清白蛋白（HSA）和BSA的相互作用。实验首先详细讨论了血清白蛋白的电化学性质，发现在实验条件下，血清白蛋白不具有电活性。在芦荟大黄素电活性最强的条件下，芦荟大黄素与BSA作用形成一种非电活性的超分子，它们之间的结合比为1:1，结合常数K=2.39×104。由于药物药效的发挥是在人体进行的，因此在人体生理条件下，研究扑热息痛与BSA和HSA之间的相互作用发现，它们都形成2:1的结合，结合常数分别为：KBSA=2.99×109，KHSA=9.14×109，这说明了它们生物功能的相似性。
通过对药物与主体和生物分子相互作用的研究，建立了实验模型，为电化学方法相互作用研究提供了实验方法。
It is important for investigation of interaction between drug molecules with biomolecules in medicine, biology, pharmacy and so on. The function of drug is made through the interaction of drug molecules with biomolecules, such as protein, cell membrane or DNA. There are a lot of reports about the interaction of metal ion with biomolecules in electrochemistry. The characteristic of electroactive organic molecules on electrode and the interaction of it with host molecules and micromoclues is supplied in this thesis. The electrochemical data can be used to calculate the stoichiometry including of binding site, binding ratio, binding constant, and so on.
The basic principle exploring interaction between electroactive molecules and host molecules or biomolecules is the change of molecule diffuse coefficient with another action, therefore it is very important to consider some factors affecting the diffuse coefficient of electroactive molecules. Because the influence on the viscosity of a solution differs from biomolecule to biomolecule, a electrochemical method has been developed for the study of coordination equilibria in the solution whose viscosity is not affected by the added molecule. The electrochemical characterization on the interaction between chlorpheniramine and β-cyclodextrin is executed in the research. The electrochemical properties are discussed in detail at dropping-mercury electrode and the difference of electrochemical property of the solution with or without β-CD is studied as well. The feasibility on the interaction between chlorpheniramine andβ-Cyclodextrin is conformed. The binding ratio of chlorpheniramine and β-cyclodextrin is assumed as 1:1 and their binding constant is determined as 2.83×102.
When the proteins, such as bovine serum albumin(BSA), human serum albumin (HSA), are added in solution, the viscosity of the solution increases greatly. An emperimental mode investigating the interaction in the style of solution is put forward to study the interaction between aloe-emodin and BSA, between paracetamol and BSA and HSA respectively. The electrochemical property of serum albumin on the graphite electrode and the feasibility studing interaction of drug with it are discussed in detail. When aloe-emodin possesses the most electroactive in available solution condition, the bingding ratio of it with BSA is 1:1 and the bingding constant is K=2.39×104. The comparative research of interaction of paracetamol with BSA and HSA suggests the both of the binding ratio are 2:1 and the bingding constants are KBSA=2.99×109，
KHSA=9.14×109, which respectively proves HSA and BSA are similar in biologic function here.
In the work, some electrochemical models of the interaction between drug molecules with host molecules and biomolecules are constructed, which could provide some available methods for the interaction research.
由于本研究的基本原理是基于电活性分子相互作用前后扩散系数变化来测定相互作用的，因而控制影响扩散系数的因素至关重要。针对各种主体和生物分子对溶液粘度的不同影响这一事实，本文首先建立了一个主体分子对溶液体系粘度没有影响或者它的影响可以忽略的研究主体分子与药物分子相互作用的实验模型，并且利用该实验模型研究了氯苯那敏与β-环糊精（β-CD）的相互作用。本文详细研究了氯苯那敏在悬汞电极上的电化学性质，并探讨了它在β-CD存在时的电化学性质变化，确定了利用电化学方法研究它们之间相互作用的可行性。实验假定了氯苯那敏与β-CD的结合比为1:1，测得它们之间的结合常数为2.83×102 。
蛋白质是一种高粘度的物质，针对这种情况，建立了在高粘度影响下研究蛋白质与药物分子相互作用的实验模型，并研究芦荟大黄素与牛血清白蛋白（BSA）的相互作用以及在模拟生理条件下对乙酰氨基酚与人血清白蛋白（HSA）和BSA的相互作用。实验首先详细讨论了血清白蛋白的电化学性质，发现在实验条件下，血清白蛋白不具有电活性。在芦荟大黄素电活性最强的条件下，芦荟大黄素与BSA作用形成一种非电活性的超分子，它们之间的结合比为1:1，结合常数K=2.39×104。由于药物药效的发挥是在人体进行的，因此在人体生理条件下，研究扑热息痛与BSA和HSA之间的相互作用发现，它们都形成2:1的结合，结合常数分别为：KBSA=2.99×109，KHSA=9.14×109，这说明了它们生物功能的相似性。
通过对药物与主体和生物分子相互作用的研究，建立了实验模型，为电化学方法相互作用研究提供了实验方法。
It is important for investigation of interaction between drug molecules with biomolecules in medicine, biology, pharmacy and so on. The function of drug is made through the interaction of drug molecules with biomolecules, such as protein, cell membrane or DNA. There are a lot of reports about the interaction of metal ion with biomolecules in electrochemistry. The characteristic of electroactive organic molecules on electrode and the interaction of it with host molecules and micromoclues is supplied in this thesis. The electrochemical data can be used to calculate the stoichiometry including of binding site, binding ratio, binding constant, and so on.
The basic principle exploring interaction between electroactive molecules and host molecules or biomolecules is the change of molecule diffuse coefficient with another action, therefore it is very important to consider some factors affecting the diffuse coefficient of electroactive molecules. Because the influence on the viscosity of a solution differs from biomolecule to biomolecule, a electrochemical method has been developed for the study of coordination equilibria in the solution whose viscosity is not affected by the added molecule. The electrochemical characterization on the interaction between chlorpheniramine and β-cyclodextrin is executed in the research. The electrochemical properties are discussed in detail at dropping-mercury electrode and the difference of electrochemical property of the solution with or without β-CD is studied as well. The feasibility on the interaction between chlorpheniramine andβ-Cyclodextrin is conformed. The binding ratio of chlorpheniramine and β-cyclodextrin is assumed as 1:1 and their binding constant is determined as 2.83×102.
When the proteins, such as bovine serum albumin(BSA), human serum albumin (HSA), are added in solution, the viscosity of the solution increases greatly. An emperimental mode investigating the interaction in the style of solution is put forward to study the interaction between aloe-emodin and BSA, between paracetamol and BSA and HSA respectively. The electrochemical property of serum albumin on the graphite electrode and the feasibility studing interaction of drug with it are discussed in detail. When aloe-emodin possesses the most electroactive in available solution condition, the bingding ratio of it with BSA is 1:1 and the bingding constant is K=2.39×104. The comparative research of interaction of paracetamol with BSA and HSA suggests the both of the binding ratio are 2:1 and the bingding constants are KBSA=2.99×109，
KHSA=9.14×109, which respectively proves HSA and BSA are similar in biologic function here.
In the work, some electrochemical models of the interaction between drug molecules with host molecules and biomolecules are constructed, which could provide some available methods for the interaction research.
引文
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