Tetrakis(phenylamidinium)-Substituted Resorcin[4]arene Receptors for the Complexation of Dicarboxylates and Phosphates in Protic Solvents

Three bowl-type cavitand receptors (1 – 3), consisting of a resorcin[4]arene core with four convergent phenylamidinium groups, were prepared in gram quantities by efficient synthetic routes (Schemes 1 and 2) for the recognition of organic anions in CD3OD and D2O. The key steps in the syntheses are the Suzuki cross-coupling reactions between the tetraiodo cavitands 12, 13, and 23, respectively, with the m-cyanophenylboronic ester 14 and subsequent conversion of the nitrile to amidinium groups by the Garigipati reaction. Compounds 1 and 2 displayed limited solubility in protic solvents, and evidence for stoichiometric host-guest association between 2 and AMP (28) could only be obtained by FAB-MS analysis of a complex precipitated from MeOH (Fig. 2). In contrast, receptor 3 with four triethyleneglycol monomethyl ether side chains was readily soluble in the protic environments, and complexation of isophthalates and nucleotides 25 – 37 was extensively studied by 1H-NMR titrations and Job's method of continuous variation. In CD3OD and pure D2O, isophthalates 25 and 26 formed stable 1 : 2 host-guest complexes (Table 1 and Fig. 3), whereas upon addition of borate (pH 9.2) or Tris/HCl buffer (pH 8.3) to the D2O solution, the tendency for higher-order complexation vanishes. Stable 1 : 1 complexes formed in the buffered solutions (Fig. 4) with 5-methoxyisophthalate being selectively bound over the 5-NO2 derivative. Complexation-induced upfield shifts of specific isophthalate 1H-NMR resonances (Fig. 5) suggest a preferred inclusion of the methoxyphenyl ring into the receptor cavity. Cavitand 3 forms stable 1 : 1 host-guest complexes with nucleotides in Tris/HCl-buffered D2O. Association constants increase strongly with increasing guest charge in the series cAMP<AMP