High-accuracy receptor-anion binding measurements – laying the foundation for anion sensor development

Studies of host-guest chemistry, in particular, binding of anions by synthetic receptors has become a prominent research topic at the Analytical chemistry research group at UT. This fundamental research prepares ground for developing sensor devices for fast and selective anion determination. Carboxylate anions are among the most interesting, because the carboxylate group is by far the most widespread anionic group in biological objects.

One of the challenges lies in the fact that it is not easy to design synthetic receptors that have very high binding affinity towards a given carboxylate anion and are insensitive towards all others. Thus, it is envisaged that rather than designing highly selective individual receptor molecules, it may be more practical to utilize a number of receptor molecules, having different affinities for different anions, as a receptor array. Applying chemometric tools to the responses (e.g. optical or potentiometric) from such arrays it is in principle possible to determine individual anions from mixtures.

At our group highly accurate methods anion-receptor binding constant (logK_ass) measurement have been developed recently, based on UV-Vis spectrophotometry (J. Org. Chem. 2013, 78, 7796−7808) and NMR spectrometry (J. Org. Chem. 2014, 79, 2501−2513). Applying these methods, the binding constants of small synthetic receptor molecules based on indolocarbazole, carbazole, indole, urea and some others, as well as their combinations were measured for small carboxylate anions of different basicity, hydrophilicity and steric demand: trimethylacetate, acetate, benzoate and lactate. As a result, four separate binding affinity scales (ladders) including thirty-eight receptors were obtained. The results are graphically depicted in the Figure on the left. The high accuracy of the measurement methods enables distinguishing between small changes in binding affinity. It can be seen that many “crossing” points between the lines (denoting switching of affinity orders) exist, which are the basis of designing useful receptor arrays. This work has recently been published (Chem. Eur. J. 2015, DOI: 10.1002/chem.201405858) and presented in the SupraChem 2015 conference (see the presentation).

Work is in progress to measure the binding constants between more anions and receptors with different molecular structures with the aim of compiling the most voluminous dataset available for predicting trends in anion-receptor binding as function of the structural features of the anions and the receptors.