Structure Activity Relationships of Dendritic Antioxidants

Reactive oxygen and nitrogen species, also known as free radicals, are by-products of normal metabolism. Inflammation, infection, lifestyle, and environmental factors also contribute to increasing free radical formation in the body. Excessive amounts of these species can cause oxidative damage to cells and induce the condition of oxidative stress, which can lead to pathogenesis of various human illnesses. Antioxidants neutralize harmful free radicals and prevent cells from oxidative cellular damage. There is substantial evidence showing the benefits of natural antioxidants like flavonoids, vitamins C and E in the prevention of various human diseases. However, many of these popular antioxidants in the presence of transition metal ions, such as iron and copper, generate large amounts of free radicals, resulting in cellular damage (pro-oxidant effect). This contradicting antioxidant and pro-oxidant behavior of the antioxidants is a significant concern in the use of antioxidants as preventative therapeutics. To overcome this antioxidant dilemma, we exploited a nanotechnology approach to design and synthesize antioxidants in dendritic architecture to separate the antioxidant properties from their undesirable pro-oxidant effects. These dendritic antioxidants displayed far superior free radical scavenging activities than naturally occurring antioxidants. Most importantly, they did not show pro-oxidant effects in the presence of physiological amounts of transition metals. In this presentation, synthesis of dendritic antioxidants, their protective effects on biomolecules (e.g. human low-density lipoproteins and DNA), and their structure–activity relationships will be reported.