THE CHEMISTRY OF SYNTHETIC RECEPTORS AND FUNCTIONAL GROUP ARRAYS .19. 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

A general interpretative scheme for the effects of water on hydrogen bond based molecular recognition of neutral substrates in chloroform is presented. Diacid 1a is shown to exist in wet or dry CDCl3 in the intramolecular hydrogen bonded state. In comparison, diacids 2a and 3a are less tightly closed. As expected, the more tightly closed host binds more weakly to 2-aminopyrimidine in dry CDCl3. A valuable feature of this self-enclosed host is that it is far less susceptible to hydration than the more easily opened hosts. Thus there is very little effect on the enthalpy and entropy changes associated with binding when water is introduced into the CDCl3. This insensitivity of the binding site to limited environmental changes contrasts markedly with the behavior of hosts 2a and 3a. Thermodynamic measurements of binding for these latter hosts are quite sensitive to small amounts of water in the CDCl3. It is suggested that the susceptibility of a host-guest system to environmental changes is variable and can be characteristic of induced-fit binding.