Prof. Derek Pratt

Professor Pratt will give the 2^nd Liebig-College seminar and lectures on 

(I) Hydrocarbon Autoxidation and its Inhibition: H-Atom Transfer with a Few Notable Exceptions

(II) Antioxidants, Oxidative Cell Death and Degenerative Disease: An Organic Chemists’ Perspective

Abstract:

(I)

The free radical mediated oxidation of hydrocarbons (autoxidation) is primarily responsible for the oxidative degradation of virtually all organic materials – from petroleum-derived products such as lubricants and polymers to fine chemicals and consumer products. The most important strategy in slowing this process is via the intervention of radical-trapping antioxidants, which are essential to life and generally included as additives to the aforementioned products. In this lecture, the mechanisms of hydrocarbon autoxidation and how it can be inhibited will be introduced. Select examples of my group’s efforts to study these processes, and elucidate key aspects of the mechanisms of the 4 most common classes of antioxidants (phenols, diarylamines, hindered amines and organosulfur compounds) will also be presented, along with the results of our efforts to use this knowledge to develop new compounds with significantly increased effectiveness.

(II)

Lipid autoxidation (peroxidation) has been implicated in virtually every degenerative disease and underpins a recently characterized form of oxidative cell death called ferroptosis. Yet, the hundreds of clinical trials intended to probe the potential of antioxidants for the treatment and/or prevention of disease have been disappointing at best. This apparent paradox will be introduced and our efforts to unravel it will be presented. In brief, we have recently developed chemical tools that can be deployed to rigorously quantify the reactivity of antioxidants and investigate the mechanisms that underlie their activity under physiological conditions. These methods, along with advances in chemical and cell biology that enable the specific initiation and monitoring of cellular lipid peroxidation, have enabled us to demonstrate very clearly that the vast majority of the most celebrated compounds (e.g. resveratrol from red wine, epigallocatechin gallate from green tea, allicin from garlic) simply aren’t very effective – and for simple chemical reasons. Moreover, we have identified the molecular characteristics that contribute to potent antioxidant activity under relevant conditions, which account for the potency of several recently-identified cytoprotective agents that are being advanced to the clinic to treat neurodegeneration and ischemia reperfusion injury, and enable the bottom-up design of new chemical entities for the prevention and/or treatment of degenerative disease.