Chiral recognition of (18-crown-6)-tetracarboxylic acid as a chiral selector determined by NMR spectroscopy

It is shown that the chiral selector (+)-(18-crown-6)-2,3,11,12-tetracarbox ylic acid (18-C-6-TA) employed for resolution of alpha -amino acids in capi llary electrophoresis and in chiral HPLC can be used for resolution of alph a -amino acids and ester derivatives in NMR experiments. In a quest for the origin of chiral recognition of a-amino acids in the presence of 18-C-6-TA as a chiral selector, these interactions responsible for the differential affinities shown toward enantiomers are investigated by NMR spectroscopy. C hemical-shift differences of the corresponding H-1 and C-13 resonances of D - and L-phenylglycine (PG) or phenylglycine methyl ester (PG-ME) show that most chemical shifts in the presence of 18-C-6-TA moved in the same directi on (i.e., upfield or downfield) as compared with those of the free state. S ignificant reduction of the T-1-values is observed for the host-guest compl ex molecules, indicating that the mobility of the isomers is significantly reduced due to tight binding with 18-C-6-TA. NMR line broadening of the ana lyte upon complexation further supports this finding. The observed intermol ecular NOES of the alpha -proton and ortho phenyl protons of PG or PG-ME in the presence of 18-C-6-TA are used for generating structures for 18-C-6-TA /enantiomer complexes. Molecular dynamics calculations based on NOEs illust rate the essential features of the chiral recognition mechanism: 1) three NH . . .O hydrogen bonds in a tripod arrangement between polyether oxygens of 18-C-6-TA and the ammonium moiety of the enantiomer; 2) a hydrophobic in teraction between the polyether ring of 18-C-6-TA and the phenyl moiety of the enantiomer; 3) hydrogen bonding between the carboxylic acid of 18-C-6-T A and the carbonyl oxygen of the D-enantiomer.