Oleate-modified hyaluronan: Controlling the number and distribution of side chains by varying the reaction conditions

Ondřej Štrympl; Jiří Vohlídal; Martina Hermannová; Mauricio Maldonado-Domínguez; Martina Brandejsová; Kateřina Kopecká; Vladimír Velebný; Gloria Huerta-Ángeles

doi:10.1016/j.carbpol.2021.118197

Oleate-modified hyaluronan: Controlling the number and distribution of side chains by varying the reaction conditions

Carbohydr Polym. 2021 Sep 1:267:118197. doi: 10.1016/j.carbpol.2021.118197. Epub 2021 May 14.

Authors

Ondřej Štrympl¹, Jiří Vohlídal², Martina Hermannová³, Mauricio Maldonado-Domínguez⁴, Martina Brandejsová³, Kateřina Kopecká³, Vladimír Velebný³, Gloria Huerta-Ángeles⁵

Affiliations

¹ Contipro a.s., Dolni Dobrouč 401, 561 02 Dolní Dobrouč, Czech Republic; Charles University, Faculty of Science, Department of Physical and Macromolecular Chemistry, Hlavova 2030/8, 128 40 Prague 2, Czech Republic.
² Charles University, Faculty of Science, Department of Physical and Macromolecular Chemistry, Hlavova 2030/8, 128 40 Prague 2, Czech Republic.
³ Contipro a.s., Dolni Dobrouč 401, 561 02 Dolní Dobrouč, Czech Republic.
⁴ Department of Computational Chemistry, J. Heyrovský Institute of Physical Chemistry, Czech Academy of Sciences, Prague, Dolejškova 2155/3, 182 23 Prague 8, Czech Republic.
⁵ Contipro a.s., Dolni Dobrouč 401, 561 02 Dolní Dobrouč, Czech Republic. Electronic address: huerta-angeles@contipro.com.

PMID: 34119164
DOI: 10.1016/j.carbpol.2021.118197

Abstract

In this work, low molecular weight hyaluronan was chemically modified by oleoyl moieties utilising mixed anhydrides methodology. The activation of oleic acid with benzoyl chloride in organic solvents miscible with water was followed by NMR spectroscopy. The product selectivity correlates with the solvent's Hildebrand solubility parameter. Furthermore, the effect of the solvent for the mixed anhydride formation was elucidated by density functional theory (DFT) and showed that the reactions are faster in acetonitrile or alcohols than in hexane. Furthermore, the solvent demonstrated to control the substituent distribution pattern along HA chain during esterification. An even distribution of substituents was observed in reactions performed in water mixed with ethers. The substituent distribution pattern clearly influenced the aggregation behaviour of amphiphilic HA, controlling the stability of the delivery system, while increasing the encapsulation capacity.

Keywords: Amphiphiles; Hyaluronan; Mixed anhydrides; Oleic acid (PubChem CID: 445639); Pyrene (PubChem CID: 31423); Self-assembly; Sodium hyaluronate (PubChem CID: 53447380); Solvent effect; Substituent distribution pattern.