N-Hydroxyethyl acrylamide as a functional eROP initiator for the preparation of nanoparticles under “greener” reaction conditions

Lentz, Joachim C.; Cavanagh, Robert; Moloney, Cara; Falcone Pin, Bruno; Kortsen, Kristoffer; Fowler, Harriet R.; Jacob, Philippa L.; Krumins, Eduards; Clark, Charlotte; Machado, Fabricio; Breitkreuz, Nicholas; Cale, Ben; Goddard, Amy R.; Hirst, Jonathan D.; Taresco, Vincenzo; Howdle, Steven M.

Abstract

N-Hydroxyethyl acrylamide was used as a functional initiator for the enzymatic ring-opening polymerisation of ϵ-caprolactone and δ-valerolactone. N-Hydroxyethyl acrylamide was found not to undergo self-reaction in the presence of Lipase B from Candida antarctica under the reaction conditions employed. By contrast, this is a major problem for 2-hydroxyethyl methacrylate and 2-hydroxyethyl acrylate which both show significant transesterification issues leading to unwanted branching and cross-linking. Surprisingly, N-hydroxyethyl acrylamide did not react fully during enzymatic ring-opening polymerisation. Computational docking studies helped us understand that the initiated polymer chains have a higher affinity for the enzyme active site than the initiator alone, leading to polymer propagation proceeding at a faster rate than polymer initiation leading to incomplete initiator consumption. Hydroxyl end group fidelity was confirmed by organocatalytic chain extension with lactide. N-Hydroxyethyl acrylamide initiated polycaprolactones were free-radical copolymerised with PEGMA to produce a small set of amphiphilic copolymers. The amphiphilic polymers were shown to self-assemble into nanoparticles, and to display low cytotoxicity in 2D in vitro experiments. To increase the green credentials of the synthetic strategies, all reactions were carried out in 2-methyl tetrahydrofuran, a solvent derived from renewable resources and an alternative for the more traditionally used fossil-based solvents tetrahydrofuran, dichloromethane, and toluene.

Citation

Lentz, J. C., Cavanagh, R., Moloney, C., Falcone Pin, B., Kortsen, K., Fowler, H. R., …Howdle, S. M. (2022). N-Hydroxyethyl acrylamide as a functional eROP initiator for the preparation of nanoparticles under “greener” reaction conditions. Polymer Chemistry, 13(42), 6032-6045. https://doi.org/10.1039/d2py00849a

• Journal Article Type: Article
• Acceptance Date: Oct 9, 2022
• Online Publication Date: Oct 10, 2022
• Publication Date: Nov 14, 2022
• Deposit Date: Oct 24, 2022
• Publicly Available Date: Oct 25, 2022
• Journal: Polymer Chemistry
• Print ISSN: 1759-9954
• Electronic ISSN: 1759-9962
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 13
• Issue: 42
• Pages: 6032-6045
• DOI: https://doi.org/10.1039/d2py00849a
• Keywords: Organic Chemistry, Polymers and Plastics, Biochemistry, Bioengineering
• Public URL: https://nottingham-repository.worktribe.com/output/12624584
• Publisher URL: https://pubs.rsc.org/en/content/articlelanding/2022/PY/D2PY00849A