Experimental Binding Energies in Supramolecular Complexes

On the basis of many literature measurements, a critical overview is given on essential noncovalent interactions in synthetic supramolecular complexes, accompanied by analyses with selected proteins. The methods, which can be applied to derive binding increments for single noncovalent interactions, start with the evaluation of consistency and additivity with a sufficiently large number of different host–guest complexes by applying linear free energy relations. Other strategies involve the use of double mutant cycles, of molecular balances, of dynamic combinatorial libraries, and of crystal structures. Promises and limitations of these strategies are discussed. Most of the analyses stem from solution studies, but a few also from gas phase. The empirically derived interactions are then presented on the basis of selected complexes with respect to ion pairing, hydrogen bonding, electrostatic contributions, halogen bonding, π–π-stacking, dispersive forces, cation−π and anion−π interactions, and contributions from the hydrophobic effect. Cooperativity in host–guest complexes as well as in self-assembly, and entropy factors are briefly highlighted. Tables with typical values for single noncovalent free energies and polarity parameters are in the Supporting Information.