Urea-Urease Reaction in Controlling Properties of Supramolecular Hydrogels: Pros and Cons

Abstract

Supramolecular hydrogels are useful in many areas such as cell culturing, catalysis, sensing, tissue engineering, drug delivery, environmental remediation and optoelectronics. The gels need specific properties for each application. The properties arise from a fibrous network that forms the matrix. A common method to prepare hydrogels is to use a pH change. Most methods result in a sudden pH jump and often lead to gels that are hard to reproduce and control. The urease-urea reaction can be used to control hydrogel properties by a uniform and controlled pH increase as well as to set up pH cycles. The reaction involves hydrolysis of urea by urease and production of ammonia which increases the pH. The rate of ammonia production can be controlled which can be used to prepare gels with differing properties. Herein, we show how the urease-urea reaction can be used for the construction of next generation functional materials.

Keywords: Institute and/or researcher Twitter usernames: @prof_djadams; dynamic gels; hydrogels; kinetic control; pH-responsiveness; urease-urea reaction.

Figure 1

Schematic representation of multilevel self‐assembly during gelation. The assembly kinetics can affect all levels of the assembly. Depending on the trigger, different nanoaggregates can be formed leading to different microstructures and gel properties.

Figure 2

(a) Schematic representation of possible energy landscapes during the self‐assembly of supramolecular materials. Gelation can be considered of as a kinetically trapped state, rather than the thermodynamic minimum. (b) The process of assembly may result in different pathways being followed.

Figure 3

(a) Different modes of hydrolysis of urea. (b) Structure‐based urease catalytic mechanism of the enzymatic hydrolysis of urea. Figure (b) is adapted with permission from Ref. [6]. Copyright © 2018 Elsevier.

Figure 4

(a) Bell‐shaped pH‐dependent urease activity with a maximum enzyme rate at pH 7. (b) Dependency of urea‐urease reaction on the pH of the medium. The initial pH value controls the enzyme activity and the rate of ammonia production. (c) Influence of the nature of acids on the pH‐time profile. (d) Influence of the initial urea concentration on the rate of pH change as well as on the final pH. Figure (a) is reproduced with permission from Ref. [20a]. Copyright © 2010, American Chemical Society. Figures (b) and (d) are adapted with permission from Ref. [20b]. Copyright © 2015 John Wiley and Sons. Figure (c) is adapted with permission from Ref. [14]. Copyright © 2019 The Royal Society of Chemistry.

Figure 5

Photographs of hydrogels of the Fmoc‐gelator formed by (a) NaOH and (b) urea‐urease reaction. Confocal microscopy images of the hydrogels from (c) NaOH and (d) urea‐urease reaction (scale bars represent 20 mm). Reproduced with permission from Ref. [14]. Copyright © 2019 The Royal Society of Chemistry.

Figure 6

Supramolecular polymerization through dynamic imine bond formation catalysed by urea‐urease reaction. An increase in viscosity indicates immobilization of solvent and gel formation. Reproduced with permission from Ref. [26]. Copyright © 2019, Springer Nature.

Figure 7

Schematic representation of possible energy landscapes during dynamic evolution of supramolecular gels.

Figure 8

Illustration of pH responsiveness of either a carboxylic acid‐terminated or an amine functionalized gelator along with transient hydrogel formation in presence of acid‐triggered (purple) and base‐triggered (red) pH cycles, respectively. These two compounds are chosen as model examples. For acid‐triggered pH cycle, initially a sudden pH drop occurs due to addition of acid. For base triggered pH cycles the pH decreases with time due to production of acids involving hydrolysis reaction at high pH. Since carboxylic acid and amine group display opposite ionization, for transient hydrogelation, the appropriateness of the pH‐cycle depends on the choice of gelator.

Figure 9

Chemical fuel‐controlled field‐responsive fluidic materials developed by Yang group. a) Photographs representing the time‐dependent non‐Newtonian behavior of fluid: i no shake‐gel before fuel addition, ii) transient shake‐gel behavior after fuel addition, iii) recovery of initial shake behavior after the energy dissipation with time. Adapted with permission from Ref. [33]. Copyright © 2020 John Wiley and Sons.

Figure 10

(a) Demonstration of the transient acidic pH flip involving a tri‐layered system. While esterase embedded gel layer (middle) catalyzed the hydrolysis of ethyl acetate to acetic acid, urease encapsulated gel layer (bottom) converted urea to NH₃ and CO₂. (b) Change of pH with time in the supernatant layer (top) involving the tri‐layered system described in (a). (c) Change of pH with time in the supernatant layer when both the enzymes were encapsulated in a single gel layer. Reproduced with permission from Ref. [35]. Copyright © 2020 John Wiley and Sons.

Figure 11

Demonstration of autonomous programming of homogeneous “molding and casting” of peptide hydrogel involving urease‐urea reaction. When an initially formed gel was extruded from the syringe, the extruded gel did not adapt to the shape of the container. With a gradual increase in pH, the gel changes from the initial distorted shape, producing a homogeneous solution inside the mold. With further time, regelation occurred, and a homogeneous gel was formed that conform to the shape of the mold.

Figure 12

Representation of kinetically controlled damage‐healing experiment of hydrogel. A transient acidic pH state was temporarily created that allowed recovery of the damage with red colouration. The transient healability of damaged hydrogels was temporally programmed by combining a fast acidic activator (acylhydrazone activation) with the slow enzymatic generation of a base (urea‐urease reaction). Adapted with permission from Ref. [39]. Copyright © 2020, American Chemical Society.