Incorporating adaptive and dynamic behavior in a catalytic system is the foremost prerequisite to gain nature-like complex functionality in a synthetic chemical network. Herein, we report a self-assembled modular catalytic system based on the multivalent interaction between a cationic gold nanoparticle surface and nucleotides. It is shown that the catalytic preference and activity of the nanoparticle can be directed in a controllable manner toward either hydrazone formation or a proton transfer reaction only by creating a differential local microenvironment around the nanoparticle surface, simply by changing or converting the multivalent scaffold around it. The temporal control of the system in governing the reaction preference and catalytic activity will enable designing a system of higher complexity with a preprogrammed reaction networking property.

Evolutionarily elderly proteins commonly feature greater catalytic promiscuity. Cytochrome c is among the first set of proteins in evolution to have known prospects in electron transport and peroxidative properties. Here, we report that cyt c is also a proficient proton‐transfer catalyst and enhances the Kemp elimination (KE; model reaction to show proton transfer catalytic property) by ∼750‐fold on self‐organized systems like micelles and vesicles. The self‐organized systems mimic the mitochondrial environment in vitro for cyt c. Using an array of biophysical and biochemical mutational assays, both acid–base and redox mechanistic pathways have been explored. The histidine moiety close to hemin group (His18) is mainly responsible for proton abstraction to promote the concerted E2 pathway for KE catalysis when cyt c is in its oxidized form; this has also been confirmed by a H18A mutant of cyt c. However, the redox pathway is predominant under reducing conditions in the presence of dithiothreitol over the pH range 6–7.4. Interestingly, we found almost 750‐fold enhanced KE catalysis by cyt c compared to aqueous buffer. Overall, in addition to providing mechanistic insights, the data reveal an unprecedented catalytic property of cyt c that could be of high importance in an evolutionary perspective considering its role in delineating the phylogenic tree and also towards generating programmable designer biocatalysts.

Understanding the fundamental facts behind dynamicity of catalytic processes has been a longstanding quest across disciplines. Herein, we report self-assembly of catalytically active gold nanorods that can be regulated by tuning its reactivity towards a proton transfer reaction at different pH. Unlike substrate-induced templating and cooperativity, the enhanced aggregation rate is due to alteration of catalytic surface charge only during reactivity as negatively charged transition state of reactant (5-nitrobenzisoxazole) is formed on positively charged nanorod while undergoing a concerted E2-pathway. Herein, enhanced diffusivity during catalytic processes might also act as an additional contributing factor. Furthermore, we have also shown that nanosized hydrophobic cavities of clustered nanorods can also efficiently accelerate the rate of an aromatic nucleophilic substitution reaction, which also demonstrates a catalytic phenomenon that can lead to cascading of other reactions where substrates and products of the starting reactions are not directly involved.

The evolutionary drive towards specificity has developed individual enzymes for specific reactions; however, some ancient proteins/enzymes display promiscuous substrate specificity, which is central theme of the image. We have shown that cytochrome c, one of the oldest members of the protein family, known for electron transport and peroxidative properties in lipid membranes, is also capable of performing proton transfer, but only in membrane‐mimetic media. We discovered that His18, close to the hemin group, is mainly responsible for proton abstraction. This result is not only important in evolutionary perspectives, but also exemplifies the differential behavior of biomolecules in response to their surroundings. More information can be found in the full paper by S. Maiti et al.