Affinity Capillary Electrophoresis Based On Cyclodextrins

Affinity capillary electrophoresis (ACE) is a new bioanalytical technique which combines unique selectivity of affinity interaction with high resolution of capillary electrophoresis (CE). Since its advent in early 90's, ACE has been extensively used to study molecular interactions involving drugs, enzymes, antibodies and nucleic acids. ACE is particularly suited for measuring the parameters that characterize molecular interactions, such as binding constants. The binding constants thus obtained can be used to elucidate the mode and strength of a given interaction, hence providing some valuable information for applications based on molecular recognition such as drug discovery and optimization. This thesis describes some applications of ACE to studies of inclusion complexation between cyclodextrin (CD) and several typical small molecules. Cyclodextrins and their derivatives (CDs) are used as host molecules and the small molecules as guests, respectively. Binding constants between them are determined by ACE and their interaction mechanisms are discussed thereof. Binding constants between (-CD and positional isomers of carboxylfluorescein (5-carboxylfluorescein and 6-carboxylfluorescein) are measured, which show that character of them is different. At the same time, effect of pH is discussed. Binding constants between (-CD and nicotinic acids(6-chloronicotinic acid, 6-hydroxylnicotinic acid and isonicotinic acid) are determined. Difference of their complexation with (-CD is analyzed. Optimum conditions of (-CD as additive to analyze nicotinic acid type compounds are presented. After method of determined binding constants of (-CD and neutral compounds in dual cyclodextrins systems by ACE is set up, binding constants of (-CD and naphthalene (1-naphthylamine, 1-naphthol and 2-naphthol) are measured. The cause of stronger complexation of 1-naphthol and (-CD is presented. Comparation of results with this method and document's shows that method proposed is reliable. Chiral compounds (propranolol, chlorpheniramine and verapamil) is separated by ACE. Binding constants of them and (-CD are determined in dual cyclodextrins systems. "Synergic effect" is observed when chlorpheniramine is separated in dual cyclodextrins systems. Optimum conditions for chiral separation of three chiral drugs are presented.