Controlled Synthesis and Inclusion Ability of a Hyaluronic Acid Derivative Bearing β-Cyclodextrin Molecules

Abstract

A new synthetic route to beta-cyclodextrin-linked hyaluronic acid (HA-CD) was developed. This was based on the preparation of a HA derivative selectively modified with adipic dihydrazide (HA-ADH) and a beta-cyclodextrin derivative possessing an aldehyde function on the primary face, followed by their coupling by a reductive amination-type reaction. The CD-polysaccharide was fully characterized in terms of chemical integrity and purity by high-resolution NMR spectroscopy. The complexation ability of the grafted CD was further demonstrated by isothermal titration calorimetry using sodium adamantane acetate (ADAc) and Ibuprofen as model guest molecules. The thermodynamic parameters for the complexation of these negatively charged guest molecules by the beta-CD grafted on negatively charged HA were shown to be largely influenced by the ionic strength of the aqueous medium.

Polymers Containing Covalently Bonded and Supramolecularly Attached Cyclodextrins as Side Groups

“…With the exception of the aCD monoaldehyde (12a), all of them are bCD derivatives. Preparation of monoCDs 11 [29] and 19 [30] involves extensive purification. In contrast, the procedure for mono deprotonation of a secondary hydroxyl group on C 2 on bCD with lithium hydride is quite simple and high yielding [31].…”

“…Likewise, the same authors coupled mono-6-[aminoethyl(4 0 -carboxybutanamide)]-bCD (14) to this polymer. This mild reaction was also applied for attachment of a bCD-monoaldehyde derivative (11) to adipic dihydrazide functionalized hyaluronic acid in a site-selective manner [29]. Also by reductive amination, Villalonga et al grafted 22b onto some polysaccharides, which were previously activated by periodate oxidation [53].…”

“…As model system, a mixture of two hyaluronic acid derivatives functionalized either with bCD or adamantly residues was chosen [29,65]. Above the overlap concentration it was found that these polymer systems generate parallel strands of contrarily derivatized polymers, denoted as railway complexes.…”

Amino–Acetone‐Bridged Cyclodextrins ― Artificial Alcohol Oxidases

“…The reductive amination approach has been used on cyclodextrins several times before for linking chitosan derivatives, [15] hyaluronic acid derivatives [16] and porphyrins [17] or for the N-glycosidation of 6-amino-6-deoxy-cyclodextrin with various 6-oxogalactosides [18] with reaction yields of 15-70 %.…”

Synthesis and characterization of a β-CD-alginate conjugate

“…The synthetic route was based on the activation of the hydroxyl groups of alginate with cyanogen bromide followed by coupling with 6-aminoa-cyclodextrin. We report here another strategy that was recently proposed for the synthesis of b-CD-linked hyaluronic acid [14]. This was based on the preparation of an alginate derivative selectively modified with adipic dihydrazide (alg-ADH) and a b-cyclodextrin derivative possessing an aldehyde function on the primary face, followed by their coupling by a reductive amination-type reaction.…”