Study On The New Separation Methods For Chiral Drugs And Proteins

Chiral drugs are a type of drugs that has the same chemical composition, physical properties and molecular structure, but different three-dimensional structures. Scientific research shows that the enantiomers have some differences in pharmacological and zoological effects on living beings. Proteins are natural chiral molecules, most of them are targeted of the drug. Thus, the separation of chiral drugs has very important significance. The purpose of this dissertation was mainly to develop simple, rapid, sensitive, reliable qualitative and quantitive methods for the separation and decetion of the chiral drugs and protein.This thesis is divided into three parts, including seven chapters. The first part is also chapter 1, presents the significance of the separation of chiral drugs. Meanwhile, the current chiral separation methods are described. And we also describe the capillary modified technology. The application of aptamers as chiral selectors in chiral detection and separation is also briefly overviewed. At the end of this chapter, the objectives and contents of this dissertation are introduced in brief.The second part of this thesis includes three chapters, which are chapter 2,3 and chapter 4. This part mainly focuses on the investigation of the application of aptamer as chiral selector on chiral drugs enantioseparation. Chapter 2 described a new method based on label-free aptamer-based partial filling technique for enantioseparation and determination of DL-tryptophan (Trp) with micellar electrokinetic chromatography. In chapter 3, a selective and sensitive method using capillary partial filling technique for the enantioseparation of ibuprofen by micellar electrokinetic chromatography with aptamer as chiral selector was developed. Field-amplified injection technique is also used to increase the detection sensitivity. In Chapter 4, a new simple method was fabricated for preparative separation of enantiomers based on functional nucleicacids modified gold nanoparticles. The aptamers are modified on the surface of gold nanoparticles through gold-thiol bond. In this method the simple centrifugation is used to enantioseparate DL-trp. The proposed approach has the potential to be extended to the preparative separation of a series of chiral compounds when the corresponding aptamer is used.The third part of this thesis mainly focuses on the fabrication and application of capillary electrophoresis (CE) with Poly[oligo(ethylene glycol) methyl ether methacrylate (POEGMA) modified capillary separation system. This part includes chapter 5,6 and 7. In chapter 5, a novel protein-resistant POEGMA films is in situ synthesis in capillary and it was applied on proteins separation. Chapter 6 described a new method for three cyanobacterial cyclicpeptide hepatotoxins separation and detection by using the POEGMA modified capillaries coupled with online sample stacking method-large-volume injection. And the established method has been successfully applied for the determination and separation of three cyanobacterial cyclicpeptide hepatotoxins in Min River. In chapter 7, a general enantioseparation method based on POEGMA modified capillaries was developed. The chiral selector BSA is modified on the POEGMA coated capillary through physical adsorption. The proposed method was successfully applied to enantioseparate DL-Trp in human serum.