Amino acid-based squaramides for anion recognition

Abstract

Eight receptors 1–8 comprising an L-lysine scaffold modified at N- and C-termini with aliphatic alkyl chains and N,N0-alkyl amides, respectively, and bearing squaramide moieties on the amino acid side chain were synthesised by a combination of solid- and solution-phase chemistries and shown to complex various anions in 0.5%H2Oin dimethyl sulfoxide-d6 solution. All of the receptors were found to bind SO22 4 ; Cl2, AcO2 and BzO2 via hydrogen-bond or acid–base interactions with the squaramide protons; however, 1 was found to bind to SO22 4 via hydrogen bonds formed between the anion and both the squaramide and amideNHmoieties. Moreover, modification of both the N- and C-termini of the amino acids with different alkyl substituents had a negligible effect on their anion-binding properties while simultaneously conferring lipophilicities in a range that is optimal for molecules to behave as ‘drug-like’ systems as defined by Lipinski’s rule of five. The results of this study demonstrate the versatility of such amino acid receptors as building blocks in the field of anion recognition.