Explanation Of Enantioseparation Of Amino Acid Derivatives In Gas Chromatography And The Mechanism Of Supermolecular Compounds Of Cyclodextrins And Chloamphenicol

Since theβ-cyclodextrin (β-CD) was came out in 1903, cyclodextrin chemistry has made tremendous strides on the aspects of preparation, property and application. Cyclodextrin has been widely used in medical, food, environmental protection and analytical chemistry, especially in the field of supramolecular chemistry that was in the frontier of Chemistry. As an important supermolecular host because of the special structure, cyclodextrin is attracting more and more attention. Cyclodextrins are a class of cyclic oligosaccharide molecules normally comprised of six (α-CD), seven (β-CD) or eight (γ-CD),α-1,4 linked D-glucopyranose unite, in which the interior surface of the cavity is hydrophobic and the external surface is hydrophilic. This work includes two part:1. Explanation of enantioseparation of amino acid derivatives in Gas Chromatography.2. The property and mechanism of supermolecular compounds of cyclodextrins and chloramphenicol in aqueous solution and solid state.1. Enantioseparation techniques are urgently needed not only to separate mixtures of chiral drugs and their optically active metabolites, but also for the quality control of enantiomerically pure drugs and in the development of asymmetric synthesis. Gas chromatographic (GC) enantioseparation is a simple, exact and effective method, so it is one of the most suitable techniques for the purpose. Various types of cyclodextrins and their modified cyclodextrins have been successfully investigated as CSPs in GC, and these compounds exhibit very broad enantioselectivity for a variety of chiral compounds in GC. However, enantioseparation mechanisms on cyclodextrin CSPs are not clear, and a simple and reasonable mechanism is still lack so far. Herewith, we proposed a more effective and simple method, so-called molecular dynamic simulation (MD), to study the chiral recognition mechanisms on cyclodextrin CSPs.Using this method, we successfully investigated the recognition mechanisms of some compounds separated on the cyclodextrin CSPs.In this paper, permethylatedβ-cyclodextrin (PM-β-CD), cyclodextrin derivative, is one of the most versatile inclusion-type selectors as the Chiral Stationary Phase in the Gas Chromatography (GC). Using molecular dynamics simulation method, molecular recognition mechanisms of amino acid derivatives suah as N-trifluoroacetyl ethyl esters were successfully investigated, and the results obtained from MD were consistent with those from experiment.(1) Using Autodock and MD methods, chiral recognition mechanisms of amino acid derivatives N-TFA-AAA-OEt with PM-β-CD and MUPM-β-CD were investigated. From the molecular simulations, we can reproduce the elution order of the enantiomers in GC, the MD results revealed that the preferred binding site for all investigated enantiomers is the interior of modified cyclodextrins; From the molecular modeling, it is found that according to the different selector/analyte complexes there are different dominating forces responsible for enantioselective binding; From the molecular modeling, it is also observed that due to the induced-fit interaction, the conformations of PM-P-CDs or MUPM-P-CDs were changed during the binding processes, and their conformation changes were different between a pair of enantiomers of the same racemates, thus resulting in the stereoselectivity.(2) For the competitive binding of L-or D-enantiomers to PM-P-CD, with the systems containing 10 D-or 10 L-enantiomers and one PM-P-CD molecule, the interaction energy of enantiomers with PM-P-CD was simulated. The frequency of enantiomers appearing around a certain distance from the center of mass of PM-p-CD was investigated. This work demonstrated that, by studying the interaction energy, distance between the centers of mass (COM) of the guest and of the host molecules and enantiomer appearing frequency, the enantioseparation of the amino acid derivatives in gas chromatography can be explained, and the simulated elution orders of the enantiomers are in accordance with the experimental data.2. Chloramphenicol (CAP) with poor aqueous solubility was used as a model drug in this paper. Firstly, the solubility and the respective affecting factors were investigated and a solid CAP complex with hydroxypropyl-β-cyclodextrin (HP-β-CD) having greater aqueous solubility than natural cyclodextrins (β-CD) was prepared. Then, Using MD methods, inclusion complex mechanisms of CAP withβ-CD and HP-β-CD were investigated.In the study of the complexation of CAP withβ-CD and HP-β-CD, the host-guest molecular interactions, complexing molar ratio and complex steric conformation were studied by lots of methods such as UV absorption spectroscopy, IR absorption spectroscopy and phase-solubility method. The results indicated that a 1:1 molar ratio soluble CAP complex withβ-CD and HP-β-CD could form in aqueous solution, and the HP-β-CD was better. Furthermore, formations of inclusion complexes between CAP withβ-CD and HP-β-CD have been investigated by MD methods in system of aqueous,10% ethanol solution and 20% ethanol solution. The comparison between experiment results and simulation results showed that it was feasible and authentic for MD simulation.