Sponsor
Portland State University. Department of Chemistry
First Advisor
Robert M. Strongin
Date of Publication
Winter 3-20-2015
Document Type
Dissertation
Degree Name
Doctor of Philosophy (Ph.D.) in Chemistry
Department
Chemistry
Language
English
Subjects
Homocysteine -- Research, Cysteine, Fluorescent probes, Biochemical markers -- Diagnostic use, Photochemistry
DOI
10.15760/etd.2218
Physical Description
1 online resource (xii, 108 pages)
Abstract
Homocysteine is a natural occurring aminothiol. It is an intermediate product in the metabolism of methionine. Methionine is an essential amino acid required for protein synthesis. Metabolic irregularities disrupt homocysteine levels in plasma. Elevated homocysteine levels are directly linked to folate and cobalamin (vitamin B12) deficiencies, and are an independent risk factor for cardiovascular diseases. High homocysteine levels have also been associated with Alzheimer's, osteoporosis, renal failure, cancer, birth defects and pregnancy complications. The association of elevated homocysteine levels with cardiovascular disease and other diseases has generated great interest in the detection of homocysteine.
An optical method for the detection of homocysteine has been developed using fluorescein mono- and dialdehydes. Selectivity for homocysteine was achieved based on the characteristic differences between 5- and 6-membered ring heterocyclic amines formed upon the reaction with fluorescein mono- and dialdehydes. 6-membered ring homocysteine-derived thiazinane-4-carboxylic acids were found to be more basic than 5-membered cysteine-derived thiazolidine-4-carboxylic acids. Fluorescence enhancement in response to homocysteine was thus attained by tuning pH and excitation wavelengths. Furthermore, the design and synthesis of a more sensitive fluorophore, fluorescein tri aldehyde has been accomplished based on the aforementioned findings to enable the detection of homocysteine at physiological levels. Calculations of Mulliken charges revealed that the formation of thiazinanes results in modulation of the electron density on the fluorophore leading to higher fluorescence.
Rights
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Persistent Identifier
http://archives.pdx.edu/ds/psu/14612
Recommended Citation
Barve, Aabha, "Development of an Optical Method for the Detection of Homocysteine as a Disease Biomarker Using Fluorescein-Aldehydes" (2015). Dissertations and Theses. Paper 2221.
https://doi.org/10.15760/etd.2218