Relationship between Chemical Structure and Supramolecular Effective Molarity for Formation of Intramolecular H-Bonds

Effective molarity (EM) is a key parameter that determines the efficiency of a range of supramolecular phenomena from the folding of macromolecules to multivalent ligand binding. Coordination complexes formed between zinc porphyrins equipped H-bond donor sites and pyridine ligands equipped with H-bond acceptor sites have allowed systematic quantification of EM values for the formation of intramolecular H-bonds in 240 different systems. The results provide insights into the relationship of EM to supramolecular architecture, H-bond strength, and solvent. Previous studies on ligands equipped with phosphonate diester and ether H-bond acceptors were inconclusive, but the experiments described here on ligands equipped with phosphine oxide, amide, and ester H-bond acceptors resolve these ambiguities. Chemical double-mutant cycles were used to dissect the thermodynamic contributions of individual H-bond interactions to the overall stabilities of the complexes and hence determine the values of EM, which fall in th...