How do you design a complex polymer?

High throughput (HTP) screening has proved to be a powerful tool in the design of molecules and materials where the exact properties are difficult to predict from first principles. HTP techniques have been often applied to small molecules (as in small molecule drug design) but rarely to polymers due to the lack of appropriate synthetic methods.

Our group has introduced a number of novel techniques for the removal of oxygen in controlled radical polymerisation reactions. This, in combination with automated synthesis, machine learning and advances in computational chemistry is unlocking a whole range of complex problems in biomaterials design.

Degassing can be performed either using a photocatalyst, or using the enzyme glucose oxidase. Both processes are able to scrub oxygen (even at very low concentrations of enzyme/catalyst) faster than diffusion from the surface can occur. We have applied this work to low volume polymer synthesis and to enable a polymerisation based amplification of enzymatic signal for biosensing.

Our seminal papers:

  • Li et al.; A High Throughput Approach for Designing Polymers That Mimic the TRAIL Protein; Nano Letters, 2022,

  • Li et al.; A Dual Wavelength Polymerization and Bioconjugation Strategy for High Throughput Synthesis of Multivalent Ligands; J. Am. Chem. Soc, 2019, 141, p19823

  • Gormley AJ; An oxygen tolerant PET-RAFT polymerisation for screening structure-activity relationships; Angewandte Chemie Int. Ed., 2018, 57, p1557

  • Chapman R, et al; Combinatorial low-volume synthesis of well-defined polymers by enzyme degassing, Angewandte Chemie Int. Ed., 2016, 128, p4576

  • Chapman R et al.; Highly controlled open vessel RAFT polymerizations by enzyme degassing. Macromolecules, 2014, 47, p8541

  • Yeow et al.; Oxygen tolerant polymerisations for ultralow volumes, Polymer Chemistry, 2017, 8, p5012

Some other important contributions from our lab:

Controlled polyolefins via radical polymerisation: In 2017 we developed a new set of reactions to prepare homo- and block- polyolefins, including polypropylene and polybutylene, by post-polymerisation modification of RAFT polymers. This represented the first and only route to truly well-defined block polyolefins using a controlled radical polymerisation.

  • Chapman R, et al., Controlled poly(olefin)s via decarboxylation of poly(acrylic acid), Polymer Chemistry, 2017, 8, 6636-6643.

Peptide and protein delivery: There are relatively few convenient methods for delivering small hydrophilic peptides to cells. In 2017, we introduced a novel nanogel made by emulsion polymerisation, which was very efficient at delivering small charged molecules. We have now adapted these nanoparticles for the delivery of therapeutic peptides. See for example:

  • Rahimi M, et al.; Polymer mediated transport of the Hsp90 inhibitor LB76, a polar cyclic peptide, produces an Hsp90 cellular phenotype, Chemical Communications, 2019, 55, 4515-4518

  • Farazi S, et al.; Real time monitoring of peptide delivery in vitro using high payload pH responsive nanogels, Polymer Chemistry, 2020, 11, 425-432

Stabilisation of enzymes within polymer nanoparticles: We have developed an approach that uses polyion complexes to assemble a crosslinked shell around a range of enzymes, which stabilises them against aggressive environments. Because each enzyme is individually wrapped we have excellent control over the properties of the polymer wrapping.

  • Chapman R, Stenzel MH; All wrapped up: Stabilisation of enzymes within single enzyme nanoparticles, J. Am. Chem. Soc., 2019, 141(7), 2754–2769.

  • Wang Y, et al.; Polyion Complex-Templated Synthesis of Cross-Linked Single-Enzyme Nanoparticles, Macromolecules, 2020, 5487-5496

Peptide directed self-assembly of polymeric nanoparticles: During my PhD I developed a range of (alt D,L) cyclic peptides to drive the assembly of polymers into poylmeric nanotubes. These can be used as artificial membranes and ion channels. See for example:

  • Chapman R, et al.; Design and properties of functional nanotubes from the self-assembly of cyclic peptide templates. Chemical Society Reviews, 2012, 41, 6023.

  • Chapman R, et. al; Multi-shell Soft Nanotubes from Cyclic Peptide Templates. Advanced Materials, 2013, 25, 1170.