Mussel-inspired histidine-based transient network metal coordination hydrogels

Abstract

Transient network hydrogels cross-linked through histidine-divalent cation coordination bonds were studied by conventional rheologic methods using histidine-modified star poly(ethylene glycol) (PEG) polymers. These materials were inspired by the mussel, which is thought to use histidine-metal coordination bonds to impart self-healing properties in the mussel byssal thread. Hydrogel viscoelastic mechanical properties were studied as a function of metal, pH, concentration, and ionic strength. The equilibrium metal-binding constants were determined by dilute solution potentiometric titration of monofunctional histidine-modified methoxy-PEG and were found to be consistent with binding constants of small molecule analogs previously studied. pH-dependent speciation curves were then calculated using the equilibrium constants determined by potentiometric titration, providing insight into the pH dependence of histidine-metal ion coordination and guiding the design of metal coordination hydrogels. Gel relaxation dynamics were found to be uncorrelated with the equilibrium constants measured, but were correlated to the expected coordination bond dissociation rate constants.

Figure 1

Visual appearance of solutions of 4A-PEG-dHis (150 mg/mL) with Zn²⁺, Cu²⁺, Co²⁺, and Ni²⁺ at (a) 0.25× and (b) 0.5× metal relative to polymer endgroup.

Figure 2

Photographs of 4A-PEG-His gels with 0.5× divalent metal/ polymer endgroup. From left to right gels correspond to Zn²⁺ (clear), Cu²⁺ (blue), Co²⁺ (yellow), and Ni²⁺ (purple).

Figure 3

Rheological characterization of 4A-PEG-His coordination gels with 0.5× divalent metal/polymer end-group at pH 7 and (A) 10 °C, (B) 25 °C, and (C) 37 °C. Frequency sweep of gel with storage (G′) and loss (G″) moduli, reported as solid and open symbols, respectively.

Figure 4

Effect of concentration at pH 8 of 4A-PEG-His + 0.5×Ni²⁺ gels.

Figure 5

Effect of changing ionic strength for 4A-PEG-His + 0.5×Ni²⁺, 100 mg/mL, pH 8 gel.

Figure 6

Effect of pH on gel relaxation for 4A-PEG-His + 0.5×Ni²⁺, 100 mg/mL gel subjected to a 10 % step strain.

Figure 7

Potentiometric titration of mPEG-His with and without divalent metal added at 0.5× metal/polymer endgroup. Titrations were performed in 0.100 M KCl with 0.100 M KOH at 14.8 mg polymer/mL at 25 °C. KOH addition of 1× and 2× relative to polymer endgroup is marked. Every other data point was removed to increase plot clarity.

Figure 8

Ideal solution equilibrium predictions for pH-dependence of metal polymer equilibrium at ideal stoichiometric ratio of 2:1 histidine endgroup:metal for Zn²⁺, Cu²⁺, Co²⁺, and Ni²⁺. Curves were calculated based on equilibrium parameters reported in Table 1. Concentration of polymer endgroup is reflective of approximate concentration in gels (60 mM).

Scheme 1

Hypothesized cross-linking reaction

Chart 1

4A-PEG-dHis

Chart 2

4A-PEG-His

Chart 3

mPEG-His