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., Jacob, P. L., Krumins, E., Clark, C., Machado, F., Breitkreuz, N., Cale, B., Goddard, A. R., Hirst, J. D., Taresco, V., & 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