Identifier

etd-09252006-145513

Degree

Doctor of Philosophy (PhD)

Department

Chemistry

Document Type

Dissertation

Abstract

At elevated levels, homocysteine (Hcy) is a risk factor for cardiovascular diseases and Alzheimer’s disease. It’s also implicated in a number of other diseases such as neural tube defects, pregnancy complications, and renal failures. The monitoring of Hcy levels in plasma is of current concern. To date, the biochemical mechanism by which Hcy is involved in disease states is unclear. Herein, we describe highly selective colorimetric methods for the direct determination of Hcy. Inexpensive, commercially available materials are reported. The results show potential application for the detection of Hcy in human blood plasma. Additionally, new HPLC postcolumn detection methods for biological thiols are developed. The potential biomedical relevance of the chemical mechanisms involved in the detection of Hcy is discussed. In addition to the detection of bioactive amnino acids (such as Hcy and congeners), the detection of neutral sugars has been of great interest and ongoing for over a century. A big challenge remaining in this area is to achieve sensitive determination of specific saccharides at physiologically relevant pH. Inspired by calcium-dependent recognition of saccharides by C-type lectins, a water-soluble salophene-lanthanum complex was synthesized. It can be used in the detection of neutral sugars at physiological pH. Anionic sugar detection is also of importance to biomedical research. For instance, an increase or decrease in total sialic acid levels in biological fluids or tissues can indicate the occurrence of certain cancers. In the general procedure for the determination of sialic acid, a hydrolysis step is typically required to release bound sialic acid residues from the glycoconjugates. Two problems are often encountered in the hydrolysis: i) destruction of analytes; ii) incomplete release of sialic acid residues. New effective sensing agents for the determination of sialic acid are thus needed. A salophene-europium complex was synthesized and used in the selective detection of sialic acid-containing gangliosides under neutral conditions. Electrostatic interactions of Eu3+ with the carboxylate group of the sialic acid moiety as well as the secondary interactions of Eu3+ with proximal oligosaccharide hydroxyls play important roles in the signal transduction.

Date

2006

Document Availability at the Time of Submission

Release the entire work immediately for access worldwide.

Committee Chair

Robert M. Strongin

Included in

Chemistry Commons

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