A New Hyaluronan Modified with β-Cyclodextrin on Hydroxymethyl Groups Forms a Dynamic Supramolecular Network

Molecules. 2019 Oct 25;24(21):3849. doi: 10.3390/molecules24213849.


A new hyaluronan derivative modified with β-cyclodextrin units (CD-HA) was prepared via the click reaction between propargylated hyaluronan and monoazido-cyclodextrin (CD) to achieve a degree of substitution of 4%. The modified hyaluronan was characterized by 1H-nuclear magnetic resonance spectroscopy (NMR) and size exclusion chromatography. Subsequent 1H-NMR and isothermal calorimetric titration experiments revealed that the CD units on CD-HA can form virtual 1:1, 1:2, and 1:3 complexes with one-, two-, and three-site adamantane-based guests, respectively. These results imply that the CD-HA chains used the multitopic guests to form a supramolecular cross-linked network. The free CD-HA polymer was readily restored by the addition of a competing macrocycle, which entrapped the cross-linking guests. Thus, we demonstrated that the new CD-HA polymer is a promising component for the construction of chemical stimuli-responsive supramolecular architectures.

Keywords: click reaction; cyclodextrin; host-guest systems; sodium hyaluronan; supramolecular network.

MeSH terms

  • Calorimetry
  • Click Chemistry
  • Hyaluronic Acid / chemical synthesis
  • Hyaluronic Acid / chemistry*
  • Magnetic Resonance Spectroscopy
  • Molecular Structure*
  • Polymers / chemical synthesis
  • Polymers / chemistry*
  • beta-Cyclodextrins / chemical synthesis
  • beta-Cyclodextrins / chemistry*


  • Polymers
  • beta-Cyclodextrins
  • Hyaluronic Acid
  • betadex