Europium(III)-N,N′-Ethylenebis( l -amino acid) Complexes as New Chiral NMR Lanthanide Shift Reagents for Unprotected α-Amino Acids in Neutral Aqueous Solution

Three N,N′-ethylenebis(l-amino acid) ligands have been obtained simultaneously with three α,α′-(1,4-piperazinediyl)bis[(S)-alkanoic acid] and four N,N′-ethylenedipeptide products, by reacting a mixture of l-histidine methyl ester and l-aspartic acid dimethyl ester with glyoxal in the presence of sodium cyanotrihydroborate in methanol. Europium(III) complexes with N,N′-ethylenebis(l-amino acid) ligands were useful as chiral NMR shift reagents for some unprotected natural α-amino acids as substrates in neutral aqueous solution, as characterized by large enantiomeric shift differences and unbroadened signal shapes on high-resolution NMR spectroscopy. In addition, the acid-dissociation constants of six bis(amino acid) ligands and the stability constant of the europium(III) complex with N,N′-ethylenedi(l-histidine) were obtained by potentiometric titration.