Europium(III)-N,N '-ethylenebis(L-amino acid) complexes as new chiral NMR lanthanide shift reagents for unprotected alpha-amino acids in neutral aqueous solution

Three N,N'-ethylenebis(L-amino acid) ligands have been obtained simultaneou sly with three alpha,alpha'-(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 presenc e of sodium cyanotrihydroborate in methanol. Europium(III) complexes with N ,N'-ethylenebis(L-amino acid) ligands were useful as chiral NMR shift reage nts for some unprotected natural alpha -amino acids as substrates in neutra l aqueous solution, as characterized by large enantiomeric shift difference s and unbroadened signal shapes on high-resolution NMR spectroscopy. In add ition, the acid-dissociation constants of six bis(amino acid) ligands and t he stability constant of the europium(III) complex with N,N'-ethylenedi(L-h istidine) were obtained by potentiometric titration.