Motivation

Biochemical processes in “Nature” are often associated with a chain of reactions occurring one after the other, or comprising of an intricate web of several corelated, yet distinguished series of reactions. The essential role of enzymes in selecting reactants from a pool of potential reactive species, for specific transformations cannot be neglected. Enzyme activities are generally modulated via the presence of stimulus such as change in pH, temperature, light. Besides, these reactions take place in aqueous media. Mimicking the ideal natural systems, we aimed to develop a catalyst system for organic transformations in aqueous medium. We also aimed for programming chemical reaction that can be switched 'ON/OFF'. Therefore, we chose an organocatalyst that can perform a chemical transformation in aqueous media (mimicking enzyme catalysis), and availability of the catalytic center for the substrates can be modulated on exposure to a stimulus. Throwing light to the wide variety of stimulus available; pH, temperature and light are most commonly being exploited in designing such switchable catalytic systems. Though such systems are quite efficient and give appreciable and desirable output in ‘nature-like’ conditions, yet using force as a stimulus in aqueous media is absent. Thus, we thought ultrasound in the form of stimulus could be intriguing. 

Design Strategy

Now, that we had the stimulus fixed, the next step was to find a suitable responsive material which can undergo reversible changes on exposure to the stimulus and most importantly maintain its structural and functional integrity in aqueous medium. An excellent choice is a bio-based polysaccharide, sodium alginate. It provides hydrogel material, on replacing the counter cations from monovalent sodium ions to any bivalent cation such as calcium ion. Preparation of alginate hydrogel by calcium ion cross-linking is completely non-invasive, intrinsic, has negligible toxicity, resulting a popular choice in biomedical applications. It grabbed our attention, as we came across an article by Mooney et. al. describing ultrasound-induced sustainable drug release. This raised our curiosity, that if catalytic species can be mingled with the alginate chains, it would be entrapped within the hydrogel matrix, which would be released in presence of ultrasound stimulus. Presence of reactants in close proximity of the catalytic center would allow their smooth transition to products (Catalysis ON). Once the ultrasound is ceased, the calcium ions will play its role and entrap the catalysts back within the matrix (Catalysis OFF).

Ultrasound induced Catalysis

We have selected imidazole as an organocatalyst and we have encapsulated it in calcium alginate beads. These beads were then exposed to ultrasonic vibrations, and the released imidazole molecules were tested for catalyzing hydrolysis reaction of an activated ester (para-nitrophenylacetate). It was observed that the entrapped catalysts on exposure to stimulus gave comparable reaction rates to that of the free catalytic species. Besides, we have applied the ultrasound stimulus during the progress of reaction. We observed that the reaction followed comparable reaction rate as the blank reaction in absence of the stimulus, whereas an increase in reaction rate was observed as soon as the stimulus is applied. This implied temporal control over the reaction by the application of ultrasound stimulus. However, as imidazole has a substantial solubility in water, the reaction could be observed in absence of the stimulus, which is presumably due to the diffusional escape of the catalyst from the alginate network. Progression could be observed. In order to regulate this uncontrolled catalytic activity, we realized the need of covalent functionalization of the catalytic moieties with the alginate chain. Towards this, we have used a simple carbodiimide activation strategy to functionalize imidazole with the alginate chain. Now, we observed that the catalysis rate in absence of the stimulus is comparable as blank reaction. Increase of reaction rate in presence of the stimulus confirmed the switching ‘ON’ the catalyst system towards chemical transformation in aqueous media. Likewise, two other substrates (para-nitrophenyl butyrate and di-nitrophenyl acetate) showed similar trends.

Switchable Catalysis

The next challenge was to check switching ‘OFF’ mode of the chemical reaction in absence of the stimulus. For this, an excess amount of calcium ions was taken in the medium having the hydrogel material consisting of catalyst systems. On allowing the ultrasound through the system, it switched “ON” the reaction and a quick increase in reaction rate was observed. On the other hand, ceasing the stimulus switches the system showed the 'OFF' state as the reaction rate was comparable as the blank condition. Additionally, we have monitored the reaction in absence of catalyst system, but in presence of ultrasound stimulus. No significant change in the rate of chemical reaction was observed. Next, we performed the reaction for multiple cycles just switching ‘ON’ the ultrasound stimulus and ceasing the stimulus as ‘OFF’ state. Thus, spatiotemporal control over a chemical reaction has achieved by just modulating the stimulus. The system would be further used in controlled formation of biological functional molecules under in-situ conditions.

A greater scientific outlook and related quantitative data can be found in our recent publication in Communication Materials (Click here).