Type of Document	Dissertation
Author	Sunseri, James David
URN	etd-08192004-102232
Title	Synthetic Strategies to Improve Silica-Based Stationary Phases for Reversed-Phase Liquid Chromatography
Degree	Doctor of Philosophy
Department	Chemistry and Biochemistry, Department of
Advisory Committee	Advisor Name Title Dr. John G. Dorsey Committee Chair Dr. Albert E. Stiegman Committee Member Dr. Thomas J. Vickers Committee Member Dr. W. Ross Ellington Committee Member Dr. William T. Cooper Committee Member
Keywords	synthetic strategies liquid chromatography
Date of Defense	2003-12-01
Availability	unrestricted
Abstract Reversed-phase liquid chromatography (RPLC) is the most popular analytical technique for separating complex mixtures. The most common stationary phases used are octadecyldimethyl (C18) phases with silica as the solid support. Although silica is the most widely used support, it is not without problems. Silica-based stationary phases have been under investigation since they were first produced in the late 1970s, and studies still continue to try to improve the phases. Silica has a small pH range (3-8) where mixtures can be separated without degradation of the column performance. Above a pH of 8, silica supports dissolve and destroy the column. Below pH 3, the silicon-carbon bond is cleaved, and the column is destroyed. Also, the silica surface has 8 µmol/m2 of reactive silanols for covalent bonding with an alkylsilane. Unfortunately, due to steric hindrance, only about 45% of the silanols can be covalently bound. The remaining silanols left on the surface after derivatization are deleterious to the separation of basic solutes. This dissertation describes the investigation of improving silica-based stationary phases for reversed-phase liquid chromatography. This work focuses on the synthetic methods used to decrease silanol activity and increase pH stability through the removal of silanols or by increasing the bonding density of reversed-phase stationary phases. The use of dehydroxylation to remove silanols was investigated. Dehydroxylation is the removal of silanols to form stable siloxane bonds, which happens thermally above ~400ºC. The useful temperature range is from ~400- 800ºC. Above 800ºC, the silica surface sinters (melts) to reduce the surface area and becomes chromatographically useless. These phases were characterized using 29Si crosspolarization magic angle spinning solid-state NMR (29Si CP-MAS) and diffusereflectance infrared Fourier Transform Spectroscopy (DRIFTS), along with liquid chromatography. Dehydroxylation was shown to decrease silanol activity and increase pH stability. Using the traditional reaction scheme of monosilane coupling chemistry, four parameters of the reaction were investigated to improve the silica stationary phase. A solvent and base study were performed to increase the bonding density of C18 silica stationary phases. A number of different solvents and bases were used to study the effect on bonding density. It was found that solvents with high dielectric constants or halogenated solvents yielded higher bonding densities than other solvents, and 4- dimethylaminopyridine (4-DMAP) was the best base or acid scavenger. The reaction conditions or driving force were also studied to see the effect on bonding density. Monofunctional silane coupling chemistry was done under reflux and ultrasound driving forces. It was observed that ultrasound increases the bonding density of C18 chains to the silica surface in every case over reflux conditions. Lastly, the effect of the leaving group on trimethylsilanes was investigated to see the effect on the overall bonding density of a trimethylsilane to the silica surface. The results showed that the use of halogenated monofunctional silanes, yield higher bonding densities than any other leaving groups. The order of reactivity was iodine, bromine, and chlorine. The high reactivity of the bromo and iodo leaving groups counteracts the effects of steric hindrance seen when using chlorosilanes in the bonding reaction. This work lays the groundwork for longer chain bromo and iodo silanes to be attached to the silica surface. A new reaction scheme was investigated using a chlorination-methylation scheme. The silica surface was chlorinated with pure, dry thionyl chloride, and then reacted with methyllithium. Both steps of the reaction were done under vacuum using Schlenk techniques. The reaction with methyllithium forms covalent Si-CH3 bonds, which are very stable. The smaller CH3 ligands have less steric hindrance than the larger Si(CH3)3 ligands. The new “C1” phases were investigated using 29Si CP-MAS solid-state NMR and DRIFTS. Liquid chromatography was employed to check for silanol activity and pH stability. The silanol activity was greatly decreased, and the pH stability was greatly enhanced with no silica dissolution. Again, this study has laid the groundwork for longer chain alkyllithiums to be attached to the surface.
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