Novel Helical Metallocryptand for Size-Selective Recognition of Amino Acid Derivatives with Aliphatic Side Chains

The novel tris(salen)-type metallocryptand, LNi₃, was designed and synthesized. Its crystallographic analysis revealed the presence as a helical enantiomeric pair, right-handed (P) and left-handed (M) forms, rather than the meso form, which was energetically supported by density functional theory (DFT) calculations. This LNi₃ host was capable of recognizing amino acid derivatives by several non-covalent interactions, showing a selectivity to those bearing an aliphatic side chain. Its shape-persistent nature of the cryptand facilitated the size-based discrimination, which was clearly demonstrated by ¹H NMR spectroscopic titration studies. Recognition of some of the guests caused the emergence of CD signals, indicating the biased P/M helix inversion equilibrium of LNi₃. Three aliphatic side-chain guests, Val, Ile, and Leu, caused an M-favored shifting, while two π-containing side-chain guests, Arg and Trp, showed a preference to the P form. This metallocryptand, LNi₃, overcomes the limitation in recognition of less polar amino acids having an alkyl side chain and provides future applications in molecular recognition, biochemical sensing, and enantiomeric sensing.