Optimized triazine-mediated amidation for efficient and controlled functionalization of hyaluronic acid

Tina Borke; Françoise M Winnik; Heikki Tenhu; Sami Hietala

doi:10.1016/j.carbpol.2014.04.012

Optimized triazine-mediated amidation for efficient and controlled functionalization of hyaluronic acid

Carbohydr Polym. 2015 Feb 13:116:42-50. doi: 10.1016/j.carbpol.2014.04.012. Epub 2014 Apr 19.

Authors

Tina Borke¹, Françoise M Winnik², Heikki Tenhu³, Sami Hietala⁴

Affiliations

¹ Laboratory of Polymer Chemistry, Department of Chemistry, P.O. Box 55, 00014 University of Helsinki, Finland. Electronic address: tina.borke@helsinki.fi.
² Laboratory of Polymer Chemistry, Department of Chemistry, P.O. Box 55, 00014 University of Helsinki, Finland; Faculty of Pharmacy and Department of Chemistry, Universite de Montreal, CP 6128 Succursale Centre Ville, Montreal, QC H3C 3J7, Canada; World Premier International (WPI) Research Center Initiative, International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan. Electronic address: francoise.winnik@umontreal.ca.
³ Laboratory of Polymer Chemistry, Department of Chemistry, P.O. Box 55, 00014 University of Helsinki, Finland. Electronic address: heikki.tenhu@helsinki.fi.
⁴ Laboratory of Polymer Chemistry, Department of Chemistry, P.O. Box 55, 00014 University of Helsinki, Finland. Electronic address: sami.hietala@helsinki.fi.

PMID: 25458271
DOI: 10.1016/j.carbpol.2014.04.012

Abstract

Triazine-based coupling agents have the potential to replace carbodiimides in the functionalization of hyaluronic acid (HA) giving derivatives with high degrees of substitution (DS) under mild conditions with excellent efficiency. Kinetics of the triazine-mediated amidation of HA in aqueous solution were investigated to understand the reaction mechanism and the role of the amine reagent. The DS decreased with increasing basicity of the amine. The water soluble coupling agent was stable under the reaction conditions (t1/2=10 days) in the absence of amines. The activation of HA proceeded quantitatively. The stoichiometry of amine was the limiting factor in the substitution. Functional HA derivatives with DS up to 55% were obtained by the triazine-mediated amidation. They were used successfully to prepare well-defined HA conjugates via the maleimide-thiol and the azide-alkyne "click" reactions.

Keywords: Azide-alkyne; Carbodiimide; Click reaction; Hyaluronic acid; Maleimide-thiol; Triazine.

Publication types

Research Support, Non-U.S. Gov't