Building steric hindrance into the product of a catalytic reaction improves turnover, report US scientists. 

Many chemists have tried to replicate the amazing catalytic abilities of enzymes by creating synthetic mimics. Often, however, the product acts as an inhibitor of the synthetic catalyst because it is not displaced quickly enough from the reactive site by the incoming reactants. 

Richard Hooley and Julius Rebek Jr. at the Scripps Research Institute, US, used a vase-like cavitand to catalyse Diels-Alder reactions between a diene and a selection of maleimides. Rebek describes the work in the short interview below. 

1. Could you explain the significance of your article to the non-specialist? 

Bio-inspired catalysis by supramolecular constructs is a field of great activity at this time. A number of reactions have been shown to be accelerated by enclosing the reactants in a defined space, but the lack of specificity of the receptors causes product inhibition to be a significant detriment to turnover. In this manuscript, we show the prevention of product inhibition by building additional steric hindrance into the product, abrogating its binding affinity for the receptor. Depending on the binding "handle" used for recognition, product inhibition can be reduced to zero. Additionally, the use of organized hydrogen bonding networks to activate bound substrate, common in enzymes, is underutilized in catalysis by supramolecular systems - most of the publications in this field rely on increased effective concentration to provide acceleration. 

The combination of substrate activation by an organized peptide-like network and the reduction of product inhibition should appeal to chemists in the supramolecular field, as well as those biological chemists interested in synthetic mimics of enzymatic behavior. 

2. Where do you see this work developing in the future? What challenges might there be? 

Our laboratory has been involved in the area of supramolecular catalysis for almost 20 years, and we have seen great strides made in this area. Still, the overall goal is synthetic receptors that match the reactive capabilities of enzymes. Overcoming product inhibition while maintaining strong binding affinity and substrate activation is a significant challenge, one that we aim to solve in the future.