Chemical Biology of Free Radicals: Syntheses, Structures Reaction Dynamics and Thermochemistry

Free radicals are reactive species many of which are formed as undesirable side products of normal metabolism. They play significant roles in all the major chronic and fatal diseases, including rheumatoid arthritis, cataract formation, atherosclerosis and cancer. Although the involvement of many different radicals in pathological conditions is unquestionable, quantitative information about which radicals do what damage to biological targets such as membranes, proteins and DNA is still in its infancy.

The prevention or, at least, a reduction in radical-induced damage would be aided by a firmer knowledge of the reactivities and thermochemistries of the numerous radicals likely to formed in vivo, as well as by reactivity profiles for their potential targets. To this end, experimental and computational research is carried out on the kinetics, mechanisms and thermochemistries of both simple systems, e.g., hydrogen atom abstraction from phenols by specific radicals and the role of solvent effects on such reactions, and extremely complex systems, e.g., the oxidative cross-linking of proteins in the presence of glucose and fructose (the Maillard reaction or protein "browning").

In addition, compounds that may provide reproducible sources of bio-radicals under physiological conditions (water, 37 °C, pH 7.4) for rigidly controlled kinetic investigations are conceptualized and their syntheses attempted.

To date we have useful sources of peroxyl radicals bearing positive, negative and no electrostatic charge, of the superoxide radical anion and of phenonyl radicals. The reactions of those radicals with DNA and low density lipoproteins have been investigated.

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Institutes:

• NRC Steacie Institute for Molecular Sciences