Molecular Probes for Biologically Important Molecules: A Study of Thiourea, Hydroxyl radical, Peroxynitrite and Hypochlorous acid

Numerous chemical species are important to the health of biological systems. Some species can be beneficial at low doses and harmful at high doses. Other species are highly reactive and trigger serious cell damage. Improved methods to detect the presence and activity of such species are needed. In this work, several biologically important species were studied using appropriate analytical techniques. Fluoride is an important species in human physiology. It strengthens teeth and gives protection against dental caries. However, elevated concentrations of fluoride in the body can lead to health problems such as dental and skeletal fluorosis. Reported fluoride sensors used fluorescence quenching methods in determining fluoride concentration. Our study explored synthesis and characterization of 1,8-bis(phenylthioureido) naphthalene (compound 1) as a fluoride sensing molecule. Compound 1 showed a remarkable 40 fold enhancement in fluorescence with 5 eq of fluoride addition. Compound 1 also showed possibility of visual colorimetric sensing with fluoride. Free radical mediated oxidations of biomolecules are responsible for different pathological conditions in the human body. Superoxide is generated in cells and tissues during oxidative burst. Moderately reactive superoxide is converted to peroxyl, alkoxyl and hydroxyl radicals by various enzymatic, chemical, and biochemical processes. Hydroxyl radical imparts rapid, non specific oxidative damage to biomolecules such as proteins and lipids. Superoxide also reacts with nitric oxide in cells to yield peroxynitrite, which is highly reactive and damages biomolecules. Both hydroxyl radical and peroxynitrite readily react with amino acids containing aromatic side chains. Low density lipoprotein (LDL) carries cholesterol in the human body. Elevated concentration of LDL is a potential risk factor for atherosclerosis. Previous research drew a strong correlation between oxidized low density lipoprotein (ox-LDL) and plaque formation in the arterial wall. More importantly, oxidative damage causes structural changes to the LDL protein (apo B-100) which might facilitate the uptake of LDL by macrophages. In this study LDL was exposed to various concentrations of hydroxyl radical peroxynitrite and hypochlorite. Thereafter oxidized amino acid residues in apo B-100 were mapped by LC-MS/MS methods. We found widely distributed oxidative modifications in the apo B-100 amino acid sequence.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Year

2010

Author dc:creator

• Chakraborty, Sourav

Contributors dc:contributor

• Tarr, Matthew A.
• Cole, Richard B.
• Cai, Yang

• fluoride
• fluorescence enhancement
• thiourea
• chromogenic sensing
• low density lipoproteins (LDL)
• Fenton Chemistry
• free radicals
• hydroxyl radical
• peroxynitrite
• hypochlorus acid
• surface mapping
• proteomics
• LC-MS/MS
• natural variants

Repository record dc:identifier

https://scholarworks.uno.edu/td/1132

OAI identifier oai:identifier

oai:scholarworks.uno.edu:td-2115