ABSTRACT

This chapter is concerned with the mode of action of synthetic monohydroxamates as antioxidants, in contrast to their iron chelating properties. A range of monohydroxamate compounds have been synthesized and their efficacies as free-radical scavenging agents have been investigated compared to the naturally occurring hexadentate trihydroxamate desferrioxamine and the bidentate dihydroxamate rhodotorulic acid. Several studies have demonstrated that desferrioxamine has an activity other than as a metal chelator through the activity of the trihydroxamate moiety as a hydrogen atom donor or electron donor to a variety of systems including activated horseradish peroxidase and activated cytochromes, ferryl myoglobin and ferryl hemoglobin, and the superoxide radical. Pretreatment of myoglobin with monohydroxamate and trihydroxamate hydrogen-donating compounds prior to activation with hydrogen peroxide substantially inhibits the development of the ferryl myoglobin. In a physiological system the monohydroxamates have been shown to ameliorate aspects of myocardial ischemia-reperfusion injury.