Enzyme Catalysis Illustrated

A tenet of enzyme catalysis is that the catalyst should bind the transition state more strongly than the ground state. Although the principle is widely applied, particularly with catalytic antibodies, chemists have lacked a simple, well-characterized model to illustrate this seminal system. Jay S. Siegel at China’s Tianjin University, J. Fraser Stoddart of Northwestern University, and colleagues report in Nature Chemistrythat they’ve designed a representative reaction that depicts a catalytic conformational change (2014, DOI: 10.1038/nchem.1842). The team studied the inversion of corannulene, a bowl-shaped hexacyclic aromatic hydrocarbon that has an energy barrier to inversion of 11.5 kcal/mol. That energy barrier can be lowered to about 7.9 kcal/mol by a catalyst that stabilizes the planar intermediate state. The catalyst, known as ExBox⁴⁺, is a cyclic macromolecule made from two extended bipyridinium units that selectively bind planar polycyclic aromatics. When complexed inside ExBox⁴⁺, the energy barrier for bowl-flipping lowers because of the catalyst’s increased affinity for the flat transition state of corannulene. The corannulene bowl-to-bowl inversion process—like an umbrella flipping inside out—happens 10 times as fast with ExBox⁴⁺ than without it. “The dependence of this example on shapes, rather than on the intricate mechanistic details of a more complicated organic reaction, gives it a visual simplicity that every chemist can understand,” writes Boston College’s Lawrence T. Scott in an accompanying perspective.