NMR Method for Simultaneous Host–Guest Binding Constant Measurement

An NMR-based relative
binding affinity measurement method has been
developed in which differences in the binding affinities of different
hosts toward a particular guest (ΔlogKass values) are measured in the same solution. As an advancement,
the method allows the simultaneous determination of several ΔlogKass values in a single run. As a proof of principle,
the method was used to measure binding affinity differences of a number
of indolocarbazole- and urea-based synthetic receptors toward acetate
ion in DMSO-d6/H2O (99.5%:0.5%
m/m). As a result, a binding affinity scale containing 33 receptors
and spanning 2.32 log units with excellent self-consistency (consistency
standard deviation = 0.01 log unit) was created. Together with the
very good agreement of the results with those obtained by UV–vis
spectrophotometry, this demonstrates the high accuracy of the method
and the fact that the NMR and UV–vis techniques can be used
interchangeably (in spite of the very different concentrations used
in these techniques). Additionally, it was found for symmetrical receptor
molecules from the same compound family that there is a correlation
between the acetate binding affinity of a receptor and the 15N chemical shift of the nitrogen atoms of its binding centers.