Polymeric arsenicals as a platform for functional biomaterials

Arsenic exhibits diverse chemical reactivity depending upon its oxidation state. This distinctive reactivity has been largely overlooked in the field of polymer and biomaterials science, owing to concerns about the toxicity of arsenic. However, a recent clinical renaissance in the use of arsenicals suggests the possibility of broader acceptance and application. The aim of this work is to stimulate interest in and highlight the potential of polymeric arsenicals as a novel platform for functional and responsive biomaterials (Literature review discussed in Chapter 1). Cross-linking of polymers through pendent organic arsenic functional groups is demonstrated using three different chemistries: 1) reductive coupling forming arsine oligomers, As(I)n (Chapter 2) 2) forming arsenic-thiolate bonds with poly-thiol cross-linkers (Chapter 3) 3) polymerizing As(I) via the addition of acetylenes to form vinylene-acetylene bonds (Chapter 4). All three methods of cross-linking were able to cross-link thermally self-assembled NIPAm-PEG diblock copolymers with an arsenical acrylamide (AsAm) monomer incorporated in the NIPAm core. The first two were found to be responsive towards GSH and H2O2 under model physiological conditions. The stability of the particles can be finely tuned through varying the amounts of arsenic or varying the nature of the thiol-functional external cross-linker. The last form of cross-linking was found to be non-responsive towards the given stimuli however it enabled incorporation of further functionality to the nanoparticle, such as Rhodamine B, which helped determine the co-localization of the nanoparticle. Notably, in all three chemistries, the nanoparticles produced were not found to be toxic at 2 mg/ml by cell viability assays. Finally using the As(I)n cross-linking strategy, the formation of hydrogels (with DMA-AsAm copolymers made by FRP), was demonstrated which were responsive towards oxidation with H2O2. Synthesised hydrogels were responsive towards oxidation. 3D cell culturing of these gels were carried out by rehydration of dialyzed/lyophilized gels with trypsinized solution of cells. (Chapter 5). In addition to the investigation of polymeric arsenicals, synthesis of microscale multiblock copolymers are described (Appendix A). This enabled generation and characterisation of polymers at 2 μL scale, and procedure to synthesise Multi-block copolymers at 10 μL scale (DPn = 25, 5 blocks, 2 μL per block)