Enantiomeric NMR signal separation mechanism and prediction of separation behavior for a praseodymium (III) complex with (S,S)-ethylenediamine-N,N-disuccinate.

Abstract

Because choice of chiral nuclear magnetic resonance (NMR) shift reagents and concentration conditions have been made empirically by trials and errors for chiral NMR analyses, the prediction of NMR signal separation behavior is an urgent issue. In this study, the separation of enantiomeric and enantiotopic 1 H and 13 C NMR signals for α-amino acids and tartaric acid was performed by using the praseodymium(III) complex with (S,S)-ethylenediamine-N,N'-disuccinate ((S,S)-EDDS). All the present D-amino acids exhibited larger downfield shift of their α-protons and α-carbons compared with those for the corresponding L-amino acids in common. This regularity is applicable to absolute configurational assignment and determination of optical purity of amino acids. The chemical shifts of β-protons of d- and l-alanine fully bound with the Pr(III) ((S,S)-EDDS) complex (δb s) and the adduct formation constants of both enantiomers (Ks) were obtained by dependences of the observed downfield shifts of the β-protons on the total concentrations of the respective enantiomers in the presence of a constant concentration of the Pr(III) complex. The difference in the K values was found to be predominant determining factor for the enantiomeric signal separation. The chemical shifts of both enantiomers (δs) and the enantiomeric signal separations (Δδs) under given conditions could be calculated from the δb and K values. Furthermore, prediction of the signal separation behavior was enabled by using the calculated δ values and the signal broadening obtained by dependences of the half-height widths of the observed signals on the bound/free substrate concentration ratios for the respective enantiomers.