General effects of binding site water exclusion on hydrogen bond based molecular recognition systems: a 'closed' binding site is less affected by environmental changes than an 'open' site

Diacid hosts with closed resting states bind less to water in chloroform than those with open binding sites. The intramolecular hydrogen bonds in the less reactive diacids are considerably stronger than in the easily hydrated diacids. The behavior of the closed diacid hosts makes them resistant to hydration attacks and facilitates binding through an induced-fit mechanism. Also, these closed diacid hosts exhibit less sensitivity to environmental changes regardless of the effects of similar changes on the enthalpy and entropy of open diacid hosts.