Characterization of sites of different thermodynamic affinities on the same metal center via isothermal titration calorimetry

We investigate the binding thermodynamics of a series of phosphorus ligands to a model compound, PdCl₂(solv)₂, where solv refers to a molecule of solvent, using isothermal titration calorimetry (ITC). ITC allows for the quantification of the equilibrium binding constant, the binding enthalpy, and the binding stoichiometry all in a single experiment. For systems in which two equivalents of ligand were able to bind to the Pd center, the binding sites on each Pd center in solution showed a different thermodynamic affinity for the same ligand. Changes in binding modes between different phosphorus ligands were due to steric bulk and poor electron-donating ability of such ligands. Our results demonstrate ligand binding was strongly enthalpy-driven due to solvent reorganization, which is the rearrangement of solvent molecules in the bulk solvent and the solvent molecules surrounding the solvated species.