Untangling the diverse interior and multiple exterior guest interactions of a supramolecular host by the simultaneous analysis of complementary observables

The entropic and enthalpic driving forces forencapsulation versus sequential exterior guest binding to the [Ga4L6]12− supramolecular host in solution are very different,which significantly complicates the determination of these thermodynamic parameters. The simultaneous use of complementarytechniques, such as NMR, UV−vis, and isothermaltitration calorimetry, enables the disentanglement of such multiple host−guest interactions. Indeed, data collected by each technique measure different components of the host−guest equilibria and together provide a complete picture of thesolution thermodynamics. Unfortunately, commercially available programs do not allow for global analysis of different physical observables. We thus resorted to a novel procedurefor the simultaneous refinement of multiple parameters (ΔG°, ΔH°, and ΔS°) by treating different observables through aweighted nonlinear least-squares analysis of a constrained model. The refinement procedure is discussed for the multiple binding of the Et4N+ guest, but it is broadly applicable to the deconvolution of other intricate host−guest equilibria.