The late, great Linus Pauling, twice Nobel laureate (chemistry and peace) and advocate of mega doses of vitamin C for beating disease and extending life (he died at the ripe old age of 93) was one of the most influential scientists of the 20th century.
He worked out how nature’s catalysts, proteins known as enzymes, speed up biochemical reactions. They bind to the transition states of a substrate molecule and so lower the energy of the highest energy point on a reaction pathway, which means that the reaction can proceed at much greater speed, often millions of times faster than the uncatalyzed reaction in fact.
Chemists have borrowed this in the design of organic catalysts and in making artificial enzymes, for their non-biological reactions. It is not a
complete description of catalytic behavior of enzymes of course, for that you might turn to Nanda and Koder in Nature Chemistry.
However, in a new paper from Simon and Goodman, they reveal a simple system which is common in both enzymic catalysis and organocatalysis, that does not conform to this simple idea of transition state binding. The reaction of carbonyls with a nucleophile to form an oxyanion can be catalyzed by hydrogen bonding, they explain, and there are many examples of this type of process using enzymes and using organocatalysts. The enzymes, however, do not use the arrangement of hydrogen bonds that binds the transition state best.
Enzymes do not bind to transition states; they bind to minimize the energy difference between the ground state and the transition state.
“This has implications for the design of both artificial enzymes and organocatalysts,” says Goodman.
Simon, L., & Goodman, J. (2009). Enzyme Catalysis by Hydrogen Bonds: The Balance between Transition State Binding and Substrate Binding in Oxyanion Holes The Journal of Organic Chemistry DOI: 10.1021/jo901503d
This post adapted from materials provided by Dr Goodman.