Biologically relevant free radical reactions.
|Title:||Biologically relevant free radical reactions.|
|Abstract:||The work described in this thesis is concerned with gaining insight into chemical processes which may be toxic in the biological model systems studied. The aim was to gain a detailed mechanistic understanding through the model systems which may aid in the understanding of how certain chemical processes may be implicated in terms of biological systems. One of the studies undertaken involved determining if an applied magnetic field can affect the kinetics and population of free radicals in a DNA environment. Previous studies have shown that when radical-pairs are produced in a cage-like environment such as a micelle, that the rate of escape versus that of recombination is significantly altered when a magnetic field is applied. Our aim was to determine if DNA can act as a cage as well as the other half of the radical-pair through laser photolysis of a radical source which is associated with the DNA. Another aspect of the same study was to ascertain if the effects an applied field may have on the kinetics and population of radical results in enhanced radical-induced damage to DNA. In view of the ongoing controversy regarding the possible health effects of high magnetic fields this research could provide some mechanistic insight. Another area of research was concerned with how a sequence of chemical reactions ultimately leading to the generation of peroxyl radicals is specific to the use of a laser as the source of radiation. Time-resolved work with various molecules and product studies resulted in the elucidation of a provisional mechanism for the laser-specific generation of this reactive oxygen species. In view of the ever-increasing use of lasers for various medical and cosmetic procedures, the possibility of laser-induced production of reactive species such as peroxyl radicals is an area worth looking into. The final research area covered in this thesis involved the study of a physical sunscreening agent, specifically titanium dioxide, and its possible phototoxicity. In this case the model system was either an amino acid or a functioning enzyme in solution. Both time-resolved studies with amino acids and steady-state photolyses with enzymes were performed. After steady-state irradiation, the enzyme samples were assayed for activity to determine if the combination of titanium dioxide and UVA light affect the enzymatic activity in any way, indicating that some sort of photo-initiated damage had been done. The results clearly showed that while the extent of the deactivation of the two enzymes studied was quite different, both were clearly damaged significantly by the reactive oxygen species created upon UVA photolysis of TiO2. UVA alone caused no impairment to the activity in the case of chymotrypsin and a smaIl effect on horseradish peroxidase activity due to its absorption characteristics. As titanium dioxide is a common ingredient in commercially available sunscreens, knowledge regarding any possible phototoxic reactions is quite valuable.|
|Collection||Thèses, 1910 - 2010 // Theses, 1910 - 2010|