DOSY NMR as a tool for predicting optimal conditions for hydrogel formation: The case of a hyperbranched polyglycidol cross-linked with boronic acids

Abstract

This article demonstrates the utility of DOSY NMR for the determination of the optimal conditions for the efficient covalent, reversible cross-linking of macromolecules in water for hydrogel formation. The studied model system was hyperbranched polyglycidol (HbPGL) containing numerous diol groups in peripheral regions and two types of boronic acids, that is, B(OH) 4 § and benzene-1,4-boronic diacid, as crosslinking agents. Diffusion coefficient changes of a polymer in solution, under the influence of various concentrations of cross-linking agent and pH, which influences the equilibrium of the reaction between boronic acids and diols, were recorded.These data are consistent with the rheological properties, namely the G 0 max (x) of hydrogels prepared under analogous conditions, from more concentrated solutions of HbPGL. This approach appears to be promising as it facilitates avoiding the loss of a large amount of polymer that is necessary for the elaboration of appropriate conditions for network formation in aqueous media.

Poly(glyceryl glycerol): A multi‐functional hydrophilic polymer for labeling with boronic acids

“…Finally, we wanted to demonstrate the feasibility of the boronic ester formation for functionalization of PGG polymer conjugates under conditions relevant for biomedical applications. Recent studies suggest that there is no straightforward way to predict the optimum conditions for binding of a particular boronic acid derivative and a diol . The binding constant depends on the p K a of both reaction partners, the pH of the medium, as well as on structural and other factors, but it is often favored in alkaline solution.…”

“…Recent studies suggest that there is no straightforward way to predict the optimum conditions for binding of a particular boronic acid derivative and a diol. [43][44][45][46][47] The binding constant depends on the pK a of both reaction partners, the pH of the medium, as well as on structural and other factors, but it is often favored in alkaline solution. For most biomedical applications, however, the reaction needs to proceed in aqueous solution at neutral pH.…”

Temperature-Induced Changes in the Nanostructure of Hydrogels Based on Reversibly Cross-Linked Hyperbranched Polyglycidol with B(OH)4⊖ Ions

“…Dependence of Boronic Cross-Link Concentration on Temperature. The molar ratio of formed boronic diester to HbPGL macromolecules within the hydrogel at various temperatures was determined based on solid-state 11 B NMR spectra (see Figure 2 and SI, Figures S-4 and S-5).…”

“…10 Another example of a synthetic polymer which forms hydrogels in the presence of B(OH) 4 ⊖ ions is hyperbranched polyglycidol. 11 The presence of numerous 1,2-vicinal diol functional groups in the peripheral area of spherically shaped macromolecules of hyperbranched polyglycidol (HbPGL) facilitates the binding of individual macromolecules into a three-dimensional polymer network due to reactivity and good accessibility of reactive groups in the cross-linking reaction. Applications of branched polymers for hydrogel formation based on didiol−boronic diacid complexation have not been widely described yet.…”

“…⊖ ions, we applied solidstate 11 B nuclear magnetic resonance ( 11 B NMR) to evaluate the influence of temperature on the concentration of boronic diesters, which play the role of cross-links within the hydrogels, and the lifetime of these bonds on the basis of rheological measurements. Moreover, we investigated the nanostructure variation of hydrogels upon the changes in temperature based on positron annihilation lifetime spectroscopy (PALS) measurements.…”