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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.

Authors

Joachim C. Lentz

Cara Moloney

Kristoffer Kortsen

Harriet R. Fowler

Philippa L. Jacob

Eduards Krumins

Fabricio Machado

Nicholas Breitkreuz

Ben Cale

Amy R. Goddard



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