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

Abstract

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<ADP<ATP (Table 2). Association strength is strongly reduced in the presence of high salt (NaCl) concentration (Table 3). Receptor 3 shows a slight preference for the complexation of AMP (Fig. 7) and analogs dAMP or ε‐AMP (Table 4) over nucleotides containing G (guanine), C (cytosine), T (thymine), or U (uracil) as bases. According to the 1H‐NMR analysis, only the nucleobase adenine and derivatives thereof possess the necessary stereoelectronic complementarity for inclusion into the bowl‐type cavity. The major forces stabilizing the complexes of 3 with isophthalates and nucleotides result from ion pairing and ionic H‐bonding between the charged groups of host and guest, and from the desolvation of these groups upon complexation. Apolar interactions and hydrophobic desolvation do not seem to make a large contribution to the measured binding free enthalpies.

Dual-Oriented Solid-Phase Molecular Imprinting: Toward Selective Artificial Receptors for Recognition of Nucleotides in Water

“…1,2 Like guanidine, 32 amidine groups are superbases with pK a of ∼12 in water 33 and can form strong stoichiometric electrostatic interactions with carboxylates 34 and phosphates. 35 Recently, we have synthesized a benzamidine-based monomer ((4-acrylamidophenyl)(amino)methaniminium acetate (AB)) (Figure 3), which forms a 1:1 AB-carboxylate template complex with a high association constant (K a > 900 M −1 ), 34 in CD 3 OD/ D 2 O (4/1), as determined by 1 H NMR spectroscopy. 25,36 The resulting MIPs displayed high specificity and selectivity for their target molecules in aqueous conditions.…”

Molecular Recognition in Water Using Macrocyclic Synthetic Receptors

“…The tetra-cationic cavitand 84 4+ was used for the binding of carboxylate anions in water . Isophthalates, such as 85 2– (Figure ), formed 1:1 and 2:1 guest/host complexes with receptor 84 4+ in pure D 2 O ( K a ( 85 2– ⊂ 84 4+ ) = 8.6 × 10 4 M –1 and K a ( 85 2– ⊂ 84 4+ ⇌ [ 85 2 ] 4– ⊂ 84 4+ ) = 7.7 × 10 3 M –1 ).…”

“…Diederich et al elaborated the aromatic cavity of the resorcin [4]arene scaffold by functionalizing the resorcinol units at their para-position with phenyl substituents, 230 84 (Figure 39). In addition, the authors used ethylene chains to bridge the resorcinol OHs of the receptor's scaffold.…”

Room Temperature Hydrolysis of Benzamidines and Benzamidiniums in Weakly Basic Water

“…Benzamidinium groups have also proven useful in supramolecular chemistry, both in the context of host–guest chemistry and in self-assembly. Early studies by Nocera, Gale, , and Diederich , demonstrated that strong interactions were possible between the benzamidinium group and carboxylates in solution (including in polar organic solvents and water), and these and similar interactions have subsequently been used to prepare a range of self-assembled structures. Notably, Crego-Calama’s group pioneered the development of capsules based on benzamidinium···carboxylate and benzamidinium···sulfonate interactions, , and Yashima has developed a range of structures including catenanes, helices, and capsules assembled via benzamidinium···carboxylate hydrogen bonds. − More recently, our group − and the groups of Ben and Comotti , have demonstrated that benzamidinium groups can be used to form hydrogen bonded frameworks with carboxylate and sulfonate anions.…”