Chiral Recognition of Dicarboxylate Anions by Sapphyrin-Based Receptors

The synthesis and characterization of the open-chain and cyclic sapphyrin dimers 24 and 7, bearing various bisamide spacers is reported. This family of receptors was shown to display excellent recognition properties for various dicarboxylate anions, as judged from mass spectrometric analyses, U-tube aqueous I/CH2Cl2/aqueous II through-model-membrane transport experiments, and equilibrium binding studies. These latter were carried out in either methanol or dichloromethane using 1H or 2H NMR and visible spectroscopic titrations. The flexible, first-generation system 2, featuring a 1,3-bisamidopropane spacer was found to display a high affinity for dicarboxylate anions even in polar solvents, such as methanol. Within a range of substrates, this receptor showed a strong preference toward linear over bent, and aromatic over aliphatic dicarboxylate anions, a fact that is readily rationalized in terms of extra, stabilizing π−π, CH···π, or CH···N interactions. This latter CH···N hydrogen-binding motif was observed in the single crystal structure of the 1:1 complex formed between benzoate anion and the monoprotonated form of sapphyrin 1a. The second-generation, open-chain chiral sapphyrin dimers 3 and 4 (containing (1S,2S)-1,2-bisamidocyclohexane and (S)-2,2‘-bisamido-1,1‘-binaphthalene chiral auxiliaries, respectively) were found to form strong complexes with N-carbobenzyloxy-protected aspartate and glutamate anions (Ka values are on the order of 104−105 M-1 in 19:1 (v/v) dichloromethane−methanol), and displayed a preference for glutamate over aspartate, with receptor 4 showing a modest level of enantiomeric selectivity. The cyclic dimer 7 binds these anions less effectively, but displays excellent chiral discrimination between the d- and l-antipodal forms of N-carbobenzyloxy-protected glutamate anion.