van't Hoff and calorimetric enthalpies from isothermal titration calorimetry: Are there significant discrepancies?

The enthalpy of a reaction is most often determined through one of two mean s; it can be determined directly using calorimetry or indirectly by measuri ng the temperature dependence of the equilibrium constant (i.e., the van't Hoff method). Recently, discrepancies have been noted between the enthalpy measured by calorimetry, DeltaH degrees (cal), and the enthalpy determined by the van't Hoff method, DeltaH degrees (nuH). This has been suggested to indicate that the binding reaction is more complex than the simple one-to-o ne binding model used to describe the data. To better understand possible d iscrepancies between DeltaH degrees (cal), and DeltaH degrees (nuH), we hav e undertaken both experimental studies using isothermal titration calorimet ry to measure the binding energetics of Ba2+ binding 18-crown-6 ether and 2 '-CMP binding RNase A, along with a simulation of a system involving a mole cule in conformational equilibrium coupled with binding. We find that when experimental setup and analysis are correctly performed, no statistically s ignificant discrepancies between DeltaH degrees (cal), and DeltaH degrees ( nuH) exist even for the linked system.