Highly-branched Poly(N-isopropyl Acrylamide)

Abstract

Solutions of stimulus responsive polymers are desolvated at a lower critical solution temperature (LCST) from aqueous media. The temperature of this transition is modified by a number of key environmental variables such as ionic strength and pH. Thus, polymer systems that are responsive to temperature, pH and salt concentration are well-known. However, only a few examples of highly branched stimulus responsive polymers are available and until our work highly branched versions of the most studied responsive polymer, poly(N-isopropyl acrylamide, had not been reported. Here we review our work on highly branched (poly(N-isopropyl acrylamide)s (HB-PNIPAM). We describe their synthesis using self-condensing vinyl reversible addition fragmentation chain transfer (RAFT) polymerisations with polymerisable styrene dithionate esters. In some instances the residual end group from the RAFT process is useful but we also show how, following modification of the end groups to carboxylic acids, a wide range of other functionalities with uses in the life sciences can be produced. The LCST of HB-PNIPAM decreases as the degree of branching increases but we observed a strong dependence of the LCST on end group structure. Highly polar end groups, such as the RGD peptide, can reverse this trend so that the LCST increases with degree of branching as the concentration of end groups increases. HB-PNIPAMs with either polar end groups or containing hydrophilic monomer sequences form colloidal sub-micron particles above the LCST, rather than the usual flocs. These particles, with appropriate functionalisation, have been used by us to both purify recombinant proteins and to transfer human cells. An important aspect of the biological function of proteins is the conformational change that accompanies protein-protein binding. This refolding process is driven by binding and we have shown that a similar phase change can be induced in HB-PNIPAM by binding to bacteria. The hyperbranched architecture is a key aspect of the function of these materials because unlike linear architectures with pendant ligands the branched architecture allows the ligands to be available for binding both above and below the LCST.