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Regioselective chitosan end-group activation: the triskelion approach

Vincent Pickenhahn, M. Grange, Gregory De Crescenzo, Marc Lavertu and Michael Buschmann

Article (2017)

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Cite this document: Pickenhahn, V., Grange, M., De Crescenzo, G., Lavertu, M. & Buschmann, M. (2017). Regioselective chitosan end-group activation: the triskelion approach. RSC Advances, 7(30), p. 18628-18638. doi:10.1039/c7ra01348e
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Chitosan (CS) end-group conjugation methods are rarely reported in the literature, mainly since the CS terminal aldehyde moiety produced by nitrous acid depolymerization is only present in trace amounts in its reactive form. In a previous study, our group proposed an intermolecular thioacetylation process that allowed terminal conjugation of thiol-reactive species to chitosan with 50% efficiency. However, this reaction is incompatible with acid-labile substituents and the conversion efficiency of CS end-groups could be limited by the size of the thiol-reactive species engaged in the reaction, mainly by steric hindrance since two substituents are required to obtain the stabilized thioacetal derivative. In the present study, we developed a novel CS end-group thioacetylation approach relying on a new regioselective linker that bears three thiol moieties. This trivalent linker, referred to as triskelion here, was specifically designed for activation of the CS 2,5-anhydro-D-mannose (M-Unit) end-group and consists of a thiolhook for efficient aldehyde conjugation through an intramolecular reaction and a thiol-tail that remains available for subsequent end-group functionalization with any thiol-reactive species. The chemical synthesis of this linker provided the desired material with high yields over three steps. The in situ intramolecular thioacetylation process between the triskelion linker and 2,5-anhydro-D-mannose (M-Unit, monomeric) was assessed by semi-quantitative LC-MS studies, revealing that the corresponding intramolecular thioacetal largely predominated (similar to 90%). This regioselective derivatization was also performed onto M-Unit CS aldehydes and the desired CS-b-triskelion conjugates were obtained with functionalization degrees over 85%, as confirmed by NMR spectroscopy (H-1 and DOSY). As a final assessment of the CS-b-triskelion thiol-tail reactivity, these conjugates were successfully engaged with thiol-reactive magnetic beads into disulfide bond displacement with 50% efficiency. The proposed CS terminal activation with the triskelion linker opens new perspectives for biomedical applications, especially brush-like surface modifications and other copolymer formation through disulfide linkages or Michael-type additions.

Open Access document in PolyPublie
Subjects: 1800 Génie chimique > 1800 Génie chimique
1900 Génie biomédical > 1900 Génie biomédical
Department: Département de génie chimique
Institut de génie biomédical
Research Center: Non applicable
Funders: CRSNG/NSERC, ANRis Pharmaceuticals
Date Deposited: 06 Dec 2018 12:59
Last Modified: 08 Apr 2021 10:43
PolyPublie URL: https://publications.polymtl.ca/3540/
Document issued by the official publisher
Journal Title: RSC Advances (vol. 7, no. 30)
Publisher: The Royal Society of Chemistry
Official URL: https://doi.org/10.1039/c7ra01348e


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