An enthalpic component in cooperativity: The relationship between enthalpy, entropy, and noncovalent structure in weak associations

Attempts to quantify binding interactions of noncovalent complexes in aqueo us solution have been stymied by complications arising from enthalpy-entrop y compensation and cooperativity. We have extended work detailing the relat ionship between noncovalent structure and free energy of binding to include the roles of enthalpy and entropy of association. On the basis of van't Ho ff measurements of the dimerization of vancomycin type antibiotics, we demo nstrate that positive cooperativity manifests itself in a more favorable en thalpy of association and a partially compensating less favorable entropy o f association. Finally, we extend these results to rationalize thermodynami c observations in unrelated systems.