Cleft‐Type Diamidinium Receptors for Dicarboxylate Binding in Protic Solvents

A series of potential cleft-type receptors for dicarboxylate substrates were prepared by attachment of two phenylamidinium ions to either naphthalene or 1,1′-binaphthalene scaffolds. Their synthesis (Schemes 1 – 4) involved the Pd0-catalyzed cross-coupling of aryl nitriles to the central scaffold, followed by transformation of the nitrile into amidinium groups using the Garigipati reaction. The 1,1′-binaphthalene derivative (±)-1 with phenylamidinium residues attached to the 6,6′-positions in the major groove was found to be a highly efficient receptor for dicarboxylate guests, such as glutarate and isophthalates, even in competing protic solvents such as CD3OD (Table 1). The van't Hoff analysis of variable-temperature 1H-NMR (VT-NMR) titrations (Table 2 and Fig. 3) and isothermal microcalorimetry (ITC; Table 3 and Fig. 4) revealed that complexation in MeOH is strongly entropically driven with an unfavorable enthalpic change, which partially compensates the entropic gain. These thermodynamic quantities are best explained by a particularly favorable solvation of the binding partners in the unbound state and the release of the MeOH molecules, which solvate the free ions into the bulk upon complexation. Receptor (±)-1 binds flexible glutarate and rigid isophthalates with similar association strength. This lack in response to guest preorganization and reduced guest selectivity is explained with the non-directionality of the coulombic charge-charge interactions in the complexes.