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.