Design And Preparation Of Functional β-Cyclodextrin Derivatives And Their Molecular Recognition

Cyclodextrins,as functional supermolecular host compound,have attracted more and more attention in simulation design of artificial hosts for their good biocompatibility and modifiable molecular structure.As the largest scale industrial production of cyclodextrins,β-CD has been winning more and more applications and developments for its low price and high performance.However,the inherent defects of naturalβ-CD restrict its practical applications.For instance,the lacks of chromophores and auxochromes would limit the UV-Fluorescence analysis application ofβ-CD in supramolecular chemistry(Host-Guest interaction).In addition,β-cyclodextrin is lack of effective functional point of enzymes.To increase its Pattern Recognization(PR) ability for an enzyme simulation,theβ-cyclodextrin should be modified to become functionalβ-cyclodextrin derivatives by introducing certain functional groups.Moreover,poor water-solubility also restricts the application ofβ-CD.In order to expending its application,it is necessary to modifyβ-cyclodextrin properly.The main content of the paper showed as follows:1 Series of hydroxylalkyl-β-cyclodextrin supermolecular host compounds:their preparation and application in molecular recognitionA new water-soluble cyclodextrin derivative 6-O-(2-hydroxyibutyl)-β-cyclodextrin (6-HB-β-CD) was prepared.A serie of supermolecular host compounds 6-O-(2-hydroxylpropyl)-β-cyclodextrin(6-HP-β-CD),2-O-(2-hydroxylbutyl)-β-cycl odextrin(2-HB-β-CD),2-O-(2-hydroxylpropyl)-β-cyclodextrin(2-HP-β-CD) were also prepared for the purpose of detecting the rules of host-guest interaction.Ultraviolet-visible spectrophotometer was employed to detect the host-guest inclusion phenomena and circulardichroism spectrophotometer was employed to detect the possible structure of host-guest complex.The combination of the two methods could analysis the structure of host-guest complex.And this method is very helpful in understanding the vital process and in the development of new catalytic system.Methyl orange,methyl blue,methyl violet,which have correlated molecular structure were used as the guest probes.The series of cyclodextrin derivatives,which have homologous substituent group on different sides ofβ-cyclodextrin were used as the host compounds.It found that there were several factors affecting the interaction of host-guest,such as size/shape matching,hydrophilic property,hydrophobic property,the steric hindrance.2 Betainyl-β-cyclodextrins:preparation and their application in capillary electrophoresis.Two methods were employed to link the betaine substituent toβ-cyclodextrin with the entire inner-salt structure by stable covalent bonds.One method was that the betaine substituent linked toβ-cyclodextrin directly(mono-6-deoxy-betainyl-β-cyclodextrin) with the intermediate mono-6-O-p-toluenesulfnyl-β-cyclodextrin.The other method was that the betaine was converted to pro-betaine compound and the betaine substituent was linked toβ-cyclodextrin with ether bonds by a "synthesis-deprotection one pot" method(6-O-(2-hydroxyl-3-betainylpropyl)-β-cyclodextrin,6-HBP-β-CD).Two kinds of water-soluble cationicβ-cyclodextrin derivatives 2-O-(hydroxyl propyltriethylammonia)-β-cyclodextrin(2-O-HPTEA-β-CD),6-O-(hydroxypropyl triethylammonia)-β-cyclodextrin(6-O-HPTEA-β-CD) were prepared with the intention of producing useful functional models with enhanced performances characteristics.The molecular recognition ability ofβ-CD,2-HP-β-CD,2-HB-β-CD, 6-HB-β-CD,mono-6-deoxy-betainyl-β-cyclodextrin,6-HBP-β-CD,2-O-HPTEA -β-CD,6-O-HPTEA-β-CD was carried out by the separate results of the cappilary electrophoresis.The substituents on the secondary side ofβ-cyclodextrin could enlarge the cavity ofβ-cyclodextrin and accommodate guest molecules with enough space.This could enhance the molecular recognition ability of host compounds. HB-β-CDs with neutral substituents had little selectivity about neutral drugs and acidic drugs in our experiment conditions for there were no charge on hosts or guests.2-O-HPTEA-β-CD,6-O-HPTEA-β-CD had better separate ability about neutral drugs and acidic drugs for they could form inclusion compounds with charge which were propitious to electromigration in capillary electrophoresis.Mono-6-deoxy-betainyl-β-cyclodextrin had poor molecular recognition ability for the betainyl group could cover the cavity of the cyclodextrin derivative because of short distance between betainyl group and cyclodextrin.6-HBP-β-CD could avoid the direct interaction of the betainyl group and the cavity of 6-HBP-β-CD for the chain between betainyl groups with parent cyclodextrin was long enough,pH 2.5 was found to be the most suitable pH for 6-HBP-β-CD about the drug enantiomers.When pH increased,electrovalent interaction of the betainyl group was stable and 6-HBP-β-CD had no selectivity to the drugs.When pH decreased,electrovalent interaction of the betainyl group could be broken and the carboxylate group turned to be carboxyl group, which resulted in a decreased enantioselectivity of 6-HBP-β-CD to the drugs. 6-HBP-β-CD had no selectivity about neutral drugs and acidic drugs for neutral drugs and acidic drugs had no charge under the pH.3 Amphiphilic cyclodextrin derivative 2-O-(hydroxylpropyl-N,N-dimethyl-N-do decylammonio)-β-cyclodextrin:preparation and characterizationA new water-soluble amphiphilic cyclodextrin derivative 2-O-(hydroxyl propyl-N,N-dimethyl-N-dodecylammonio)-β-cyclodextrin(2-HPDMDA-β-CD) was prepared.A useful method was employed to synthesize N,N-dimethylalkylamine with a long phobic chain.An efficient phase-transfer catalyst isopropyl alcohol was employed to resolve the problem of the low yield of 2-HPDMDA-β-CD in aqueous phase.2-HPDMDA-β-CD was found to be a fine surfactant with a smaller critical micelle concentration(cmc)(1.21mM) value than that of dodecyltrimethylammonium chloride.The cmc of 2-HPDMDA-β-CD was relatively stable between 15℃and 35℃.20℃was the temperature at which the highest effectiveness of 2-HPDMA-C12-CD was observed. The results of steady-state fluorescence measurement suggested that 2-HPDMDA-β-CD could perhaps be used as a fine host compound with two functional spaces:one is micelles and the other is the cyclodextrin cavity.The degree of ionization,α,of the micelle suggested that most of 2-HPDMDA-β-CD existed in aqueous solution as cationic ions.This could attributed to that the cross-sectional area of the hydrophilic head was larger than that of N(CH₃)₃⁺ and could accommodate antiparticle Cl^- with enough space.The results of dynamic light scattering and transmission electron microscopy measurement showed that two major aggregates existed in the solution.The aggregates with a smaller size(hydrodynamic radius(R_h) of 2.4 nm) were independent of concentration,which may be attributed to the R_h of a monomer or oligomer of 2-HPDMDA-β-CD.The aggregate with a larger size shows relatively strong concentration dependence.4 Series of amphiphilic cationic cyclodextrin derivatives:preparation and additive effect about their microstructureN,N-dimethyltetrodecylamine,N,N-dimethylhexadecylamine,N,N-dimethyl octadecylamine was prepared with alkyl p-toluenesulfonate which had high reactivity. Then,series of amphiphilic cationic cyclodextrin derivatives 2-o-(hydroxypropyl-N, N-dimethyl-N-dodecylammonio)-β-cyclodextrin(2-HPDMDA-β-CD),2-o-(hydroxyl propyl-N,N-dimethyl-N-tetrodecylammonio)-β-cyclodextrin(2-HPDMTA-β-CD), 2-o-(hydroxypropyl-N,N-dimethyl-N-Hexadecylammonio)-β-cyclodextrin(2-HPDM HA-β-CD),2-o-(hydroxypropyl-N,N-dimethyl-N-octadecyl ammonio)-β-cyciodextrin (2-HPDMOA-β-CD) were prepared for the first time.Dynamic light scattering and transmission electron microscopy were employed to observe the aggregation of above series of the amphiphilic cyclodextrin derivatives in aqueous solution.The additive effect,such as NaCl,ethanol,sodium salicylate, 1-adamantanecarboxylic acid about the aggregation was also observed.The aggregation form of the amphiphilic cationic cyclodextrin dereivatives in aqueous solution related to the length of the hydrophobic alkyl chain.The hydrophobic ability of alkyl chains would enhance when the alkyl chain prolonged, and the hydrophile-lipophile balance number(HLB) of the amphiphilic cyclodextrin derivatives would decrease.Then,the aggregation stability of a monomer or oligomer would decrease and disappear in aqueous solution.When NaCl was the additive,counterion Cl^- could combine to the hydrophilic head and decrease the amount of the water of hydration on the hydrophilic head.This could result in that the volume of the hydrophilic head in water became small and the stability of a monomer or oligomer of 2-HPDMDA-β-CD aggregation would decrease. Counterion Cl^- could also decrease the electrovalent repulsion of the hydrophilic head and the long alkyl chains aggregated easily to form large aggregation.Ethanol could enter the hydrophobic parts of the aggregation and decrease the hydrophobic interaction.This could make a monomer or oligomer of 2-HPDMDA-β-CD aggregation stable in aqueous solution.The amount of ethanol in the hydrophobic parts of the aggregation would decrease when the hydrophobic ability of the long alkyl chain enhanced.Ethanol in aqueous solution would compete with the water of hydration on the hydrophilic head and decrease the volume of the hydrophilic head.This could result in the formation of large aggregation with large hydrodynamic radius.The amount of ethanol in aqueous solution could also increase when the ethanol concentration increased.This could also result in the formation of large aggregation.Sodium salicylate could not enter into the hydrophobic parts of the aggregation for its better solubility in water.Sodium salicylate could enter into the cavity of the amphiphilic cyclodextrin derivative to form inclusion compounds with electrovalent interaction and decrease the electrovalent repulsion of the hydrophilic head.This could make the aggregation of the amphiphilic cyclodextrin derivatives stable in water. However,sodium salicylate could not effect the aggregation of the amphiphilic cyclodextrin derivatives when the hydrophilic property of the long alkyl chain enhanced to a certain extent.1-adamantanecarboxylic acid could enter into the cavity of the amphiphilic cylcodextrin dereivativs and form stable inclusion compounds with simple surfactant structure when 1-adamantanecarboxylic acid added into the aqueous solution.This resulted in that there were three kinds of aggregations in the aqueous solution.When the concentration of 1-adamantanecarboxylic acid increased,the concentration of inclusion compounds with simple surfactant structure increased and the hydrodynamic radius of aggregations increased,1-adamantanecarboxylic acid began to enter into the hydrophobic parts of the aggregation when its concentration was larger than 1mM. This could change the structure of the hydrophobic parts of the aggregation and decrease the hydrodynamic radius of the aggregations.