Chitosan Hydrogels Based on the Diels-Alder Click Reaction: Rheological and Kinetic Study

Abstract

The Diels-Alder reaction is recognized to generate highly selective and regiospecific cycloadducts. In this study, we carried out a rheological and kinetic study of N-furfuryl chitosan hydrogels based on the Diels-Alder click reaction with different poly(ethylene)glycol-maleimide derivatives in dilute aqueous acidic solutions. It was possible to prepare clear and transparent hydrogels with excellent mechanical properties. Applying the Winter and Chambon criterion the gel times were estimated at different temperatures, and the activation energy was calculated. The higher the temperature of gelation, the higher the reaction rate. The crosslinking density and the elastic properties seem to be controlled by the diffusion of the polymer segments, rather than by the kinetics of the reaction. An increase in the concentration of any of the two functional groups is accompanied by a higher crosslinking density regardless maleimide:furan molar ratio. The hydrogel showed an improvement in their mechanical properties as the temperature increases up to 70 °C. Above that, there is a drop in G' values indicating that there is a process opposing to the Diels-Alder reaction, most likely the retro-Diels-Alder.

Keywords: Diels–Alder reaction; PEG-maleimide; chitosan; click chemistry; furan; rheology.

Scheme 1

Diels–Alder cycloaddition reaction between furan and maleimide derivatives.

Scheme 2

Diels–Alder reaction between N-furfuryl chitosan and PEG-maleimide compounds.

Figure 1

Evolution of storage modulus (G′), and loss modulus (G″) with time for the system N-furfuryl-chitosan (21% substitution degree) and PEG(mal)₂-7500. Polymer concentration: 1 wt.%, and R = 0.25. G′, closed symbols, and G″, open symbols. Only traces for ω = 1 rad·s⁻¹ are shown.

Figure 2

The loss tangent, tan(δ), as a function of the reaction time during the Diels–Alder click reaction between N-furfuryl chitosan (21% degree of substitution) and PEG(mal)₂-7500 at 50 °C. The tan(δ) curves at different frequencies crossover at the gel point (ω = 2.15, 4.64 and 10 rad·s⁻¹; red, green, and blue, respectively). Polymer concentration: 1 wt.%, and R = 0.25.

Figure 3

Arrhenius plot of the logarithm of the gelation time vs. reaction temperature according to Equation (5). Hydrogels formed between N-furfuryl chitosan (1%-w/w) and PEG(mal)₂-7500 with R = 0.25. All experimental parameters as specified in Figure 2.

Figure 4

Frequency sweeps of the system of N-furfuryl chitosan 1 wt.% (21% degree of substitution) in 2% acetic acid and PEG(mal)₂-7500 with R = 0.25 prepared at 50, 60, 70, 80, and 90 °C, as indicated in the figure. All the measurements were conducted at 25 °C and γ = 2.5%. G′, closed symbols, and G″, open symbols.

Figure 5

Mechanical spectra of N-furfuryl chitosan hydrogels based on the Diels–Alder click reaction varying the degree of polymerization and functionality of the PEG-maleimide compound, as indicated in the figure. Frequency sweeps were performed at 25 °C and γ = 2.5%, after gelation at 70 °C. N-furfuryl chitosan (21% degree of substitution) dissolved in 2% acetic acid. Polymer concentration: 1.0 and 1.8 wt.%, and R = 0.25 (red) and 0.5 (black), as indicated in the figure. G′, closed symbols, and G″, open symbols.

Figure 6

Mechanical spectra of N-furfuryl chitosan hydrogels based on the Diels–Alder click reaction after gelation at 70 °C. Frequency sweeps were performed at 25, 37, 50, 60, 70, 80, and 90 °C as indicated in the figure. The dependence of the storage modulus with angular frequency is magnified inside the figure. N-furfuryl chitosan 1-wt.% (21% degree of substitution) in 2% acetic acid, PEG(mal)₂-7500, R = 0.25, and γ = 2.5%. G′, closed symbols, and G″, open symbols.

Figure 7

Arrhenius plot of the logarithm of the storage modulus vs. temperature. All experimental parameters as specified in Figure 6.