Thermodynamic analysis of receptors based on guanidinium/boronic acid groups for the complexation of carboxylates, alpha-hydroxycarboxylates, and diols: driving force for binding and cooperativity.

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.

Energetics of phosphate binding to ammonium and guanidinium containing metallo-receptors in water.

The design and synthesis of receptors containing a Cu(II) binding site with appended ammonium groups (1) and guanidinium groups (2), along with thermodynamics analyses of anion binding, are reported. Both receptors 1 and 2 show high affinities (10(4) M(-1)) and selectivities for phosphate over other anions in 98:2 water:methanol at biological pH. The binding of the host-guest pairs is proposed to proceed through ion-pairing interactions between the charged functional groups on both the host and the guest. The affinities and selectivities for oxyanions were determined using UV/vis titration techniques. Additionally, thermodynamic investigations indicate that the 1:phosphate complex is primarily entropy driven, while the 2:phosphate complex displays both favorable enthalpy and entropy changes. The thermodynamic data for binding provide a picture of the roles of the host, guest, counterions, and solvent. The difference in the entropy and enthalpy driving forces for the ammonium and guanidinium containing hosts are postulated to derive primarily from differences in the solvation shell of these two groups.

Studies into the thermodynamic origin of negative cooperativity in ion-pairing molecular recognition.

The association of synthetic receptors to target guests often proceeds through the cooperative action of multiple binding forces. An investigation into the thermodynamic origin of cooperativity in ion-pairing host-guest binding in water is described. The binding affinities of 1,2,3,4-butanetetracarboxylate, tricarballate, glutarate, and acetate to a C(3)(v) symmetric metallo-host (1) are characterized in terms of the binding constants (K(a)) and the thermodynamic parameters deltaG degrees, deltaH degrees, and deltaS degrees, as determined by isothermal titration calorimetry (ITC). These values are used to determine the individual contributions of the binding interaction to the overall binding. Several ways to view the combination of the individual binding events that make up the whole are analyzed, all of which lead to the conclusion of negative cooperativity. Combined, the data were used to evaluate the thermodynamic origin of negative cooperativity for this series of guests, revealing that entropy is the largest contributing factor. An interpretation of this result focuses upon differences in the number of water molecules displaced upon binding.

Determination of inorganic phosphate in serum and saliva using a synthetic receptor.

[structure: see text] A C(3)(v) symmetric synthetic receptor (1) was employed in an indicator-displacement assay to determine the phosphate concentrations in both horse serum and human saliva at biological pH. The determination of the phosphate concentrations in the serum and saliva using the colorimetric assay were 1.6 and 5.1 mM, respectively. These results further accentuate the usefulness of synthetic receptors in truly practical applications.

C3v symmetric receptors show high selectivity and high affinity for phosphate.

The binding of phosphate to tripodal metalloreceptors 1 and 2 is reported. Receptors 1 and 2 are C3v symmetric, designed to complement three sides of a tetrahedron. The receptors derive from tripodal ligands that are preorganized through binding to a central Cu(II) atom. These metalloreceptors demonstrate high selectivity and affinity for the molecular recognition of phosphate in aqueous media at neutral pH. The binding of phosphate and other anions to the cavities of receptors 1 and 2 was monitored by UV/vis titration techniques. Binding algorithms were used to determine the affinity of phosphate to 1 and 2 with association values (Ka) of 2.5 x 104 and 1.5 x 104 M-1, respectively.