NMR Method for Simultaneous Host–Guest Binding Constant Measurement

Abstract

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 (ΔlogK(ass) values) are measured in the same solution. As an advancement, the method allows the simultaneous determination of several ΔlogK(ass) 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 (15)N chemical shift of the nitrogen atoms of its binding centers.

Towards the Discrimination of Carboxylates by Hydrogen‐Bond Donor Anion Receptors

“…The binding constant measurements are based on the relative measurement method recently introduced by our group and applied both for UV/Vis14 and NMR spectroscopy15 as techniques. The NMR version of this method enables the unprecedented ability to differentiate between very close binding constants, that is, log K ass differences of 0.05 are detectable.…”

1‐(Methylamino)anthracene – An Accessible Building Block for Photoresponsive Compounds

“…Since the receptors are equipped with just two hydrogenbond donors, the measurements were carried in acetonitrile, which is a noncompetitive solvent (Figure 4). [22][23][24][25] Results are presented in Table 1. [21] Association constants (K a ) of receptor 10 were determined by direct 1 H NMR titrations.…”

Determination of pKa values of fluorocompounds in water using 19F NMR

“…Another is the high resolving power of NMR leading to the possibility of simultaneously monitoring several processes in the same solution. This has been successfully used for simultaneous measurement of several relative binding constants in the same solution using 1 H NMR . Because in relative measurements a number of error‐causing effects (eg, pH measurement in the case of p K a ) cancel either partially of fully, it is expected that highly reliable results can be obtained.…”