Most synthetic sensors are designed with covalent attachment between a receptor and a reporter moiety. In this report, we describe the current progress of our use of noncovalently attached indicators to signal binding of analytes. With these systems, analyte binding leads to indicator displacement from the binding cavity, which in turn yields an optical signal modulation. We include previous examples, the strategies involved in our development, and the advantages as well as disadvantages of this method. Finally, our latest research in this field is briefly presented.

[structure in text] The pK(a) values and the geometries of secondary and tertiary amines adjacent to boronic acids were determined using potentiometric and (11)B NMR titrations. The studies showed that the secondary ammonium ion has a pK(a) similar to that of the tertiary ammonium species, which leads to the formation of tetrahedral boron centers at pH values above approximately 5.5. Therefore, secondary amines as well as tertiary amines, when placed proximal to boron centers, can be used to create tetrahedral boronic acids at neutral pH for diol complexation.

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The thermodynamics of guanidinium and boronic acid interactions with carboxylates, alpha-hydroxycarboxylates, and diols were studied by determination of the binding constants of a variety of different guests to four different hosts (7-10). Each host contains a different combination of guanidinium groups and boronic acids. The guests included molecules with carboxylate and/or diol moieties, such as citrate, tartrate, and fructose, among others. The Gibbs free energies of binding were determined by UV/Vis absorption spectroscopy, by use of indicator displacement assays. The receptor based on three guanidinium groups (7) was selective for the tricarboxylate guest. The receptors that incorporated boronic acids (8-10) had higher affinities for guests that included alpha-hydroxycarboxylate and catechol moieties over guests containing only carboxylates or alkanediols. Isothermal titration calorimetry revealed the enthalpic and entropic contributions to the Gibbs free energies of binding. The binding of citrate and tartrate was investigated with hosts 7-10, for which all the binding events were exothermic, with positive entropy. Because of the selectivity of hosts 8-10, a simple boronic acid (14) was also investigated and determined to be selective for alpha-hydroxycarboxylates and catechols over amino acids and alkanediols. Further, the cooperativity of 8 and 9 in binding tartrate was also investigated, revealing little or no cooperativity with 8, but negative cooperativity with 9. A linear entropy/enthalpy compensation relationship for all the hosts 7-10, 14, and the carboxylate-/diol-containing guests was also obtained. This relationship indicates that increasing enthalpy of binding is offset by similar losses in entropy for molecular recognition involving guanidinium and boronic acid groups.