Accurate Method To Quantify Binding in Supramolecular Chemistry

An approach for accurate and comparable measurement of host–guest binding affinities is introduced whereby differences in binding strength (ΔlogK_ass values) are measured between two host molecules toward a particular guest under identical solvent conditions. Measuring differences instead of absolute values enables obtaining highly accurate results, because many of the uncertainty sources (the solvation/association state of the guest in solution, deviations in solvent composition, etc.) cancel out. As a proof of concept, this method was applied to the measurement of the binding strength of 28 synthetic anion receptors toward acetate in acetonitrile containing 0.5% water. The receptors included differently substituted indolocarbazoles, ureas, thioureas, and some others. Possible deprotonation of more acidic receptors of each compound class by acetate was checked by measuring their acidities (ΔpK_a values) relative to acetic acid in the same solvent. A self-consistent (consistency standard deviation 0.04 log units) binding affinity scale ranging for around 2.7 log units was constructed from the results. Absolute logK_ass values were found by anchoring the scale to the absolute logK_ass values of two receptor molecules, determined independently by direct measurements. This new approach is expected to find use in accurate quantification of a wide range of binding processes relevant to supramolecular chemistry.