Carboxylate Binding by Indole-Based Guanidinium Receptors: Acylguanidinium Cations are Better than Aromatic Guanidinium Cations

The synthesis of three new indole-based guanidinium cations 3, 4, and 16, that feature two different types of anion binding sites, either an acylguanidium cation (3) or an aromatic guanidinium cation (4) or both (16), is presented. NMR binding studies with N-acetylalaninecarboxylate as substrate in dimethylsulfoxide (DMSO) show that the acylated guanidinium cation is a significantly better anion binding site than the aromatic cation by at least one order of magnitude. Therefore, in dication 16, which possesses both binding sites, stepwise formation of the 1:1 and the 1:2 complex is observed with similar affinities for each binding site to those determined for the monocations 3 and 4. However, a more detailed analysis using isothermal titration calorimetry (ITC) studies revealed that this apparent similarity in affinity is due to completely different thermodynamic reasons. For example, whereas substrate binding by the acylguanidinium cation in 3 is controlled by enthalpy, complex formation by the same binding site in dication 16 is driven by entropy. Simply looking at association constants or Delta G values can, therefore, be misleading. A thorough understanding of molecular recognition events requires closer inspection of Delta H and Delta S.