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.