APPLICATION OF A GENERALIZED ENTHALPY-ENTROPY RELATIONSHIP TO BINDINGCOOPERATIVITY AND WEAK ASSOCIATIONS IN SOLUTION

Enthalpy-entropy compensations are a consequence of weak associations where the binding enthalpy is much lower than typical covalent bond st rengths. The general form of an enthalpy-entropy curve is presented ba sed upon theoretical considerations and justified on the basis of expe rimental data for associations in the gas phase and for monatomic subl imation, The intrinsic curvature of the enthalpy vs. entropy plot prov ides the basis for a description of co-operativity and binding phenome na in solution. In the case of cooperativity, we divide the mutual aid ing of two interactions into two-distinct parts, one of which is entro pic in origin and related to the classical chelate enhancement of bind ing of Jencks; the other is an enthalpic benefit due to improved elect rostatic bonding. Since the experimental Gibbs energy for all weak ass ociations in solution is a consequence of competing solute-solvent, so lvent-solvent and solute-solute interactions, the summation of these i nteractions can be usefully described by a vector analysis using the e nthalpy-entropy curve. We illustrate the utility of this approach by p resenting a qualitative description of the various contributions to bi nding in the following examples: (i) one-point associations in non-pol ar solvents, (ii) entropy-driven association of two large discs involv ing the release of multiple solvent molecules and (iii) enthalpy drive n associations involving metal chelation by polyamines. By considering the curvature of the enthalpy-entropy plot for a given interaction, i n combination with the possibility of making or breaking multiple inte ractions on one template, net enthalpies and entropies of association in solution can be explored in an approximate manner.