Chiral recognition of dicarboxylate anions by sapphyrin-based receptors

The synthesis and characterization of the open-chain and cyclic sapphyrin dimers 2-4 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 L/CH2Cl2/aqueous II through-model-membrane transport experiments, and equilibrium binding studies. These latter were carried out in either methanol or dichloromethane using H-1 or H-2 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 pi-pi, C-H ...pi, 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 la. 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 (K-a values are on the order of 10(4)-10(5) 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.