Kemp elimination in cationic micelles: designed enzyme‐like rates achieved through the addition of long‐chain bases

Abstract

The Kemp elimination is prototypical reaction used to study proton abstraction from carbon. Several hydrophobic systems are known to accelerate this reaction, including two classes of computationally-designed enzymes. However, it is unclear whether these computationally-designed enzymes establish specific interactions with their substrates, as natural enzymes do, or if most of the rate acceleration is due to the hydrophobicity of the substrate. We used a simple system composed of cationic micelles and a long chain base (such as lauryl phosphate or lauric acid) to measure the rate acceleration for the Kemp elimination. Remarkably, we found that this simple system can accelerate the reaction by 4 orders of magnitude, approaching the rates of more complex designed systems. Use of different substrates suggests that the reaction takes place at the interface between the micellar head and water (the Stern layer) with the long-chain base embedded in the micelle and the substrate in the aqueous solution. Thus, we suggest that significant rate accelerations can be achieved regardless of the precise positioning of substrates. Because natural enzymes use specific interactions to position their substrates, we propose that acceleration of the Kemp elimination is not a suitable benchmark for the success of the design process, and we suggest that more complex reactions should be used.

Serum Albumin in Health and Disease: Esterase, Antioxidant, Transporting and Signaling Properties

“…Kemp’s elimination, which is a prototypical reaction for the elimination of a proton from carbon, plays a certain role in the mechanism of albumin “promiscuity”. The reaction takes place in the Stern layer, at the interface between the micelle head or the surface of the protein and water, so that a significant acceleration of the reaction can be achieved regardless of the spatial arrangement of the substrate [ 92 , 93 ]. It should be noted that the reaction rate is reduced in protic solvents such as water compared to aprotic organic solvents.…”

Superior Proton‐Transfer Catalytic Promiscuity of Cytochrome c in Self‐Organized Media

“…Next, we studied the KE catalytic effect in cetyltrimethylammonium bromide (CTAB) containing cationic micellar system. Cationic micellar system is known to enhance KE catalytic effect as it enhances nucleophilicity of anions by decreasing their hydration [37–38] . In fact, under our experimental conditions, CTAB micelles independently exhibited strong KE catalytic activity after 0.5 mM concentration which saturates around 2 mM (Figure S9a).…”

Serum Albumin

“…The Kemp elimination is regarded to be a prototypical reaction used to study proton abstraction from carbon. The reaction takes place at the so-called Stern layer, the interface between a micellar head or protein surface and water, and a significant rate acceleration can be achieved regardless of the precise positioning of substrates [44,45]. It is interesting to note that the reaction rate is decreased in protic solvents such as water as compared with aprotic organic solvents, the electrostatic term of the hydrogen bonds being the main factor for the large inhibitory effect of water; the presence of an external electric field oriented in the direction of the charge transfer increases the reaction rate [46].…”