Haixiao Qiu

Graduation Semester and Year

2013

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Chemistry

Department

Chemistry and Biochemistry

First Advisor

Daniel W Armstrong

Abstract

High performance liquid chromatography (HPLC) has proven to be the most widely applicable and versatile technique in separation science. Hydrophilic interaction liquid chromatography (HILIC) has attracted considerable interest and has become a viable option for the separation of polar compounds. Chirality is another major concern in the modern pharmaceutical industry for two reasons: 1). the majority of bio-organic molecules are chiral; 2). enantiomers of a racemic drug may often exhibit different biological activities, pharmacokinetics, and toxicities. The field of enantiomeric separations has reached a clear level of maturity after approximately 30 years of development. However, with the continued emphasis on stereochemistry in drug design and development, chiral separations are in ever increasing demand. The development of new, more effective methods is still challenging and demanding experimentally.This dissertation discusses new research in three areas: 1). Development and application of new HILIC stationary phases for the separation of polar organic compounds. Two types of new HILIC stationary phases have been successfully synthesized and evaluted. One is based on native cyclofructan 6 and another one is a zwitterionic stationary phase based on 3-P,P-diphenylphosphonium-propylsulfonate. Their performance and retention mechanisms in the HILIC mode will be discussed in this dissertation.2). Development and evaluation of new chiral stationary phases. R-naphthylethyl-carbamate cyclofructan 6 (RN-CF6) and dimethylphenyl-carbamate cyclofructan 7 (DMP-CF7) were successfully synthesized and provide enantioselectivity toward a broad range of chiral compounds. They were found to be the best aromatic-functionalized cyclofructan chiral stationary phases and provide enantiomeric separations complementary to the isopropyl-carbamate cyclofructan 6 based chiral stationary phase. This dissertation also describes method development of enantiomeric impurities quantification in chiral reagents. Three macrocyclic chiral stationary phases, including cyclodextrins, macrocyclic glycopeptides and cyclofructans, have been used to determine enantiomeric impurities in new chiral catalysts, auxiliaries and synthons used in asymmetric syntheses. It was found that many of the newer chiral reagents are highly enantiopure, probably due to continual improvements in asymmetric syntheses and purification in the manufacturing process. 3). Development and application of new stationary phases based on a resin substrate instead of silica gel. This dissertation describes methods for binding cyclofructan 6 to resin via "click" chemistry. It was found that these resin based stationary phases appear to have potential in HILIC separations (native cyclofructan 6 bonded to resin as stationary phases) and enantiomeric separations (isopropyl-carbamated cyclofructan 6 bonded to resin).

Disciplines

Chemistry | Physical Sciences and Mathematics

Comments

Degree granted by The University of Texas at Arlington

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