Formation constants of ternary complexes of Cu" with (S)-amino-acid amides (phenylalaninamide, proiinamide, and tryptophanamide) and (R)-or (S)-amino acids (valine, phenylalanine, proline, and tryptophan) were determined potentiometrically at 25" and I = 0 . 1~ (KC1). Significant stereoselectivity was found for the systems (S)-tryptophanamide/proline, (S)-prolinamide/tryptophan, and (S)-phenylalaninamide/proline, the diastereoisomeric complexes with 'homochiral' ( S S ) being more stable than with 'heterochiral' ( S R ) ligands. The stereoselectivity observed may be explained on the basis of repulsive interactions between the ligand side-chain residues. The present data on the stability of mixed complexes in solution allow to draw some conclusions on the mechanism of chiral discrimination of amino acids in HPLC (reversed-phase) using Cu" complexes of (S)-amino-acid amides as selectors for ligand-exchange chromatography (LEC).1. Introduction. -Several investigations on mixed complexes of transition-metal ions with amino acids or dipeptides and different ligands are reported in the literature both in solution and in the solid state because of their significance as models for metal-ionassisted biological processes [ 13 [2]. The stabilities of these complexes were often explained on the basis of noncovalent interactions such as hydrophobic effects, aromatic ring stacking, H-bonding, or electrostatic ligand-ligand interactions [3].Stereoselectivity in mixed complexes of Cu" with a -amino acids has received little attention [4], and it appears to be essentially restricted to systems in which phenylalanine [5] [6], proline [7] [8], tryptophan [5-71, tyrosine [8] [9], and histidine [5] [6] are mutually involved, the effect being negligible, whenever one or both amino acids are aliphatic. Significant enantioselective effects were reported for Cu" complexes of N-alkylated valine and proline [lo], or histidine [5] with amino acids, although some data are not reliable (low precision) [lo]. N-carboxymethyl derivatives of (S)-Val, Ser, Ileu, Ala, Asp, Glu are enantioselective towards (R)/(S)-Val, Thr, and Leu [ 1 I].