Advances in free radical oxidation: Mechanistic studies, fluorescent probe design and radically different antioxidants

Abstract

Organic matter may contain predominantly paired electrons, but much of it was, at some point, shaped by reactions involving unpaired electrons, i.e., radicals. Free radicals are involved in many reactions including combustion, petroleum reforming, polymer and industrial synthesis, and oxidation reactions. This last class of radical reactions is the central theme of this thesis. Oxidation of organic matter, including our own bodies and plastic, is accelerated by the presence of radicals and oxygen. This often undesired reaction can be limited by antioxidants that trap radicals and effectively stop oxidation. Here, we report a new class of antioxidants based on dimers of persistent carbon-centered radicals. The dimers reversibly dissociate to form radicals, which we studied using Variable-Temperature UV-Visible and Electron Paramagnetic Resonance spectroscopies. Unlike most, these carbon-centered radicals do not react with oxygen (k<5x103M-1s-1). They do, however, efficiently trap peroxyl radicals (k>108M -1s-1). Using oxygen uptake kinetics, we measured rate constants between the reaction of dimers and peroxyl radicals (kinh) that were higher than many commercial antioxidants such as b&barbelow;utylated h&barbelow;ydroxyt&barbelow;oluene (BHT) and CIBA's Irganox HP-136. The antioxidant activity of dimers remarkably increases with temperature as more dimers dissociate to the active antioxidant form. In the absence of antioxidants, radical-induced oxidation of polyunsaturated lipids and cholesterol generates electrophilic oxidation products. Of these, the formation of ketones has eluded a satisfactory explanation for many decades. We propose that alphaC-H abstraction from hydroperoxides, the major primary oxidation products, generates ketones and hydroxyl radicals (HO·) in a long overlooked path to these intermediates. The HO· was trapped by benzene to yield phenol and the mechanism was further investigated using computational chemistry. The final sections describe the development and application of 7-mercapto-4-methylcoumarin (C-SH) as a prefluorescent probe to detect electrophilic lipid oxidation products. For this, we performed the first photophysical study of C-SH and related coumarin-derivatives. It was found that alkylation of C-SH generally increases the fluorescence quantum yield while substitution by an electron withdrawing group renders C-SH non-fluorescent. We successfully employed the increase in fluorescence upon alkylation of C-SH to quantify lipid oxidation electrophiles such as 4-hydroxynonenal.