Elsevier

Polymer

Volume 49, Issue 17, 11 August 2008, Pages 3744-3750
Polymer

Equilibrium swelling behavior of thermally responsive metal affinity hydrogels, Part II: Solution effects

https://doi.org/10.1016/j.polymer.2008.06.036Get rights and content

Abstract

In a previous study the effect of compositional variations on the equilibrium swelling of co-polymer hydrogels designed and synthesized from N-isopropylacrylamide (NIPAAm) and vinyl iminodiacetic acid (VIDA) monomers was investigated [Iyer G, Tillekeratne LMV, Coleman MR, Nadarajah A. Polymer, in this issue, doi:10.1016/j.polymer.2008.06.037]. The gels have both thermally responsive swelling and metal affinity properties and the effect of solution conditions on the equilibrium swelling of copper chelated and unchelated gels is studied here. In contrast to their sharp phase transition behavior in DI water, buffer solutions unexpectedly caused swelling of both gels to be the same and lose the sharp phase transition. Imidazole solutions had the expected phase transition behavior with increasing swelling and loss of phase transition of the unchelated gels which were partially reversed by copper chelation. Other small non-binding molecules, such as phenol, had minimal effects on the swelling behavior. Chicken egg white lysozyme solutions caused both gels to have reduced but equal equilibrium swelling and lose their sharp phase transition. These solution effects are explained in terms of salting in/salting out phenomena, the polarization of amide groups in VIDA, the solution pH and protein adsorption on hydrogel surfaces.

Introduction

In a previous study we described our efforts to develop N–isopropylacrylamide (NIPAAm)-based hydrogels incorporating the metal affinity ligand vinyl iminodiacetic acid (VIDA) groups employing a molecular design approach [1], [2] The temperature induced phase transition behavior of these hydrogels was shown to be quite sensitive to the composition of NIPAAm, VIDA and crosslinker. Some combinations of these groups produced sharp phase transition behaviors similar to pure NIPAAm gels, while others resulted in more linear changes in swelling with temperature and the lack of a complete collapse even at high temperatures. These effects allowed us to propose a phase transition phase diagram for these gels [2].

The phase transition behavior of NIPAAm-based hydrogels is also quite sensitive to the solution conditions, such as solute concentrations and pH [3], [4], [5], [6]. Pure NIPAAm hydrogels in fact have a salt concentration induced phase transition behavior in addition to a temperature induced one [7]. Such effects are of importance for the affinity hydrogels being developed here as pH and salt and/or buffer concentration are employed in metal affinity binding for the binding and release of target molecules. The concentration of the target molecules themselves can have an effect. Given the complexity of the composition effects on the phase transition behavior of these gels, a similar complexity is likely in the effects of solution conditions.

As discussed in the previous study the compositional effects on the phase transition behavior is largely driven by the balance between the hydrophobic and hydrophilic groups in the VIDA incorporated co-polymer hydrogel [2]. Temperature induced swelling and collapse of the gel are driven by pentagonal clathrate water structures around hydrophobic groups [7], [8], [9], [10], [11], [12], [13], [14], [15]. Hydrophilic groups instead contribute to swelling by binding to water molecules through hydrogen bonds which are less sensitive to temperature changes. When considering solution effects on these hydrogels other factors have to be considered as well. In ionic gels the addition of salt diminishes the osmotic pressure inside the gel and reduces its swelling [16]. The molecular processes giving rise to the osmotic pressure are also responsible for a more subtle effect known as the “salting out” phenomenon. This is the process by which the salt ions bind water molecules reducing the amount of free water available to form hydrogen-bonded networks [7], [17]. As the salt concentration is increased this causes gel collapse to occur at lower temperatures for NIPAAm-based hydrogels. At low salt concentrations yet another effect is the “salting in” phenomenon where salt ions provide electrostatic shielding through counter-ions for charged groups [18], [19]. This allows other nearby groups to become ionized increasing the swelling of the gel as a result.

In this work we study the effect of buffer concentration, pH and target molecule on the temperature induced swelling and phase transition behavior of the metal affinity gels developed here. There have been very few studies of the effect of non-binding small molecule on the temperature induced phase transition behavior of affinity hydrogels [20], [21], and none on the effect of binding small molecules and the effect of the size of the binding molecule. These studies will be done here for the VIDA co-polymer hydrogel. Based on these studies we will examine the effect of these conditions on the phase transition phase diagram proposed earlier for these gels. Such an understanding of these effects is needed to further improve the molecular design approach, so as to ensure that the gels retain their phase transition behavior under various environmental conditions.

Section snippets

Experimental

The syntheses of NIPAAm, NIPAAm–VIDA and copper chelated NIPAAm–VIDA (Cu-NIPAAm–VIDA) were described in detail in the first part of this study [2]. In brief, gels of 0.5 mm thickness were prepared by free radical polymerization of NIPAAm with co-monomer N-(6-(acrylamido)hexanoyl)-iminodiacetic acid sodium salt (VIDA) [1] and crosslinker N,N-methylenebisacrylamide (MBAAm) using photoinitiator riboflavin, in the proportions shown in Table 1. The gels synthesized were cut into discs of 1.6 cm

Effect of buffer concentration

The equilibrium swelling of the gels as a function of temperature was studied in a pH 7 sodium phosphate buffer, which is a commonly used medium for chromatographic separations and biological applications. The salt effects of the buffer on pure NIPAAm and on unchelated and copper chelated VIDA–NIPAAm co-polymer gels are shown in Fig. 1(a). The first observation is that the pure NIPAAm hydrogels are largely unaffected by the buffer retaining the phase transition behavior. There is a small

Conclusions

The swelling of chelated and unchelated NIPAAm–VIDA gels behave in some unexpected ways in the presence of solutions with different solutes. Sodium phosphate buffer solutions cause both gels to have the same swelling behavior with loss of sharp phase transition and lack of complete gel collapse even at 80 °C. The change in the phase transition behavior is most likely due to the salting in effect on the carboxylic acid groups in VIDA. The same swelling of the two gels is likely due to a

Acknowledgements

This research was supported by a research grant from the USDA and by the Department of Chemical and Environmental Engineering, University of Toledo. Douglas Sturtz and Jonathan Frantz of the USDA assisted with the induction coupled plasma analysis of the gels samples.

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