Quantification of the effect of conformational restriction on supramolecular effective molarities

The association constants for a family of 96 closely related zinc porphyrin–pyridine ligand complexes have been measured in two different solvents, toluene and 1,1,2,2-tetrachloroethane (TCE). The zinc porphyrin receptors are equipped with phenol side arms, which can form intramolecular H-bonds with ester or amide side arms on the pyridine ligands. These association constants were used to construct 64 chemical double mutant cycles, which measure the free energy contributions of intramolecular H-bonding interactions to the overall stability of the complexes. Measurement of association constants for the corresponding intermolecular H-bonding interactions allowed determination of the effective molarities (EM) for the intramolecular interactions. Comparison of ligands that feature amide H-bond acceptors and ester H-bonds at identical sites on the ligand framework show that the values of EM are practically identical. Similarly, the values of EM are practically identical in toluene and in TCE. However, comparison of two ligand series that differ by one degree of torsional freedom shows that the values of EM for the flexible ligands are an order of magnitude lower than for the corresponding rigid ligands. This observation holds for a range of different supramolecular architectures with different degrees of receptor–ligand complementarity and suggests that in general the cost of freezing a rotor in supramolecular complexes is of the order of 5 kJ/mol.