The chemistry blog The Curious Wavefunction recently described a good example of competition between enthalpy and entropy in biochemistry. The study involved inhibition of the enzyme acetylcholinesterase (AChE), which is critical to the transmission of nerve impulses across synapses.  Researchers found that both enantiomers of an inhibitor of AChE bound to the enzyme with the same affinity.  Because both the enzyme is enantiomerically pure, it would be expected that one inhibitor would bind more tightly than the other.

Although the exact manner in which the two enantiomers bind is different, the Gibbs free energy for each binding interaction is coincidentally similar. Experiments revealed that the enthalpy of binding was higher for the S- enantiomer (i.e. more exothermic). However, when the S- enantiomer binds it restricts the movement of functional groups on the enzyme.  Restricting the conformational possibilities of a molecule means less randomness, or higher entropy.  In contrast, the R-enantiomer of the inhibitor doesn’t bind as tightly, but it also doesn’t restrict the enzyme’s movement as much.  The result is that both enantiomers binding affinity is the same, because the equilibrium between unbound and bound inhibitor is determined by the Gibbs free energy, and not entropy or enthalpy alone. This is known as “entropy-enthalpy compensation”.