Reactive oxygen species (ROS) cause irreversible damage to biological macromolecules and act as signaling molecules in pro-inflammatory and proliferative pathways, leading to increasing interesting in small molecule antioxidants as models for putative therapeutics. This work builds on existing studies of the antioxidant gallic acid (GA) in the synthesis of antioxidant-conjugated polymers. Using radical polymerization of dimethylacrylamide (DMA) and glycine-functionalized hydroxyethyl methacrylate (Gly-HEMA) we present a post-polymerization synthetic pathway for the preparation of water-soluble p[(GA-Gly-HEMA)-co-DMA] (Scheme 1). This work is also extended to block copolymers comprised of hydrophobic p(styrene)- or p(methyl methacrylate)-b-p[(GA-Gly-HEMA)-co-DMA]. Characterization of p[(GA-Gly-HEMA)-co-DMA] consisted of both in vitro and in vivo techniques. p[(GA-Gly-HEMA)-co-DMA] exhibits radical scavenging activity both in vitro and in vivo. Using the ABTS radical-scavenging and ferric reducing ability of plasma (FRAP) assays, we determined that the p[(GA-Gly-HEMA)0.5-co-DMA0.5] conjugate, containing an antioxidant loading of 20.7 wt%, retained their antioxidant properties after coupling to the polymer. In vivo studies in RAW264.7 murine macrophages revealed that the GA-conjugate is non-toxic at concentrations up to 30 μM and that p[(Gly-HEMA)-co-DMA] polymers are taken up by macrophages in as little as 1 h. Finally, intracellular staining of the pro-inflammatory cytokine TNF-α showed that cells dosed with p[(GA-Gly-HEMA)0.5-co-DMA0.5] are resistant to lipopolysaccharide stimulation.

Antioxidant copolymers in biological applications

249th National Meeting (2015)

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