Stereoselective Formation of Ternary Copper(II) Complexes of (S)‐amino‐acid amides and (R)‐ or (S)‐amino acids in aqueous solution

Abstract

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].

Synthesis, Solution Thermodynamics, and X‐ray Study of CuII [12]Metallacrown‐4 with GABA Hydroxamic Acid: An Unprecedented Crystal Structure of a [12]MC‐4 with a γ‐Aminohydroxamate

“…The potentiometric apparatus for the automatic data acquisition was described previously. [32] A Hamilton combined glass electrode (P/N 238 000) was employed and was calibrated in terms of [H + ] concentration by titrating HCl solutions with KOH (pH = Àlog [H + ]), as reported previously. [32] The pK w value was 13.77(1).…”

“…[32] A Hamilton combined glass electrode (P/N 238 000) was employed and was calibrated in terms of [H + ] concentration by titrating HCl solutions with KOH (pH = Àlog [H + ]), as reported previously. [32] The pK w value was 13.77(1). The protonation constants of GABAha were determined by alkalimetric titration of four samples (4.7-7.1 10 À3 m).…”

“…0.2 m) were prepared by diluting concentrated Merck Titrisol ampoules and were standardized by using the usual procedure of this laboratory. [32] All solutions were prepared by using freshly boiled, doubly distilled water. The titrations were carried out in aqueous solution at T = 298.15 AE 0.1 K and I = 0.1 m (KCl) under a N 2 stream, using 25-cm 3 samples.…”

A Study on the Coordinative Versatility of the Zwitterionic S,N,S Ligand EtNHC(S)­Ph2P=NPPh2C(S)NEt in Its Anionic, Neutral and Cationic Forms – Determination of Absolute pKa Values in CH2Cl2 of RhI Complexes

“…0.2 ) were prepared by diluting concentrated Merck Titrisol ampoules and standardized with the reported procedures. [22] The titrant solution of HOTf (ca. 15 ϫ 10 -3 ) was prepared by dissolving pure triflic acid (15 µL) in CH 2 Cl 2 (10 mL) with the addition of reagent grade methanol (150 µL).…”

Copper(II) complexes ofN2-alkyl-(S)-amino acid amides as chiral selectors for dynamically coated chiral stationary phases in RP-HPLC

“…Moreover, we have shown that with bis(amino acid amidato)copper(II) complexes added to the eluent, ligand exchange is actually occurring in the chromatographic system, leading to formation of the ternary diastereomeric complexes and displacement of one ligand. However, we have also shown that the equilibria of ligand exchange occurring in the mobile phase are not sufficient to account for the o v e d discrimination process, 23 and that a series of partition equilibria of the different species occurring between the aqueous and the organic phase is involved. In order to favour the discrimination process occurring on the stationary phase, we modified the chiral selector slightly by introducing lipophilic chains in the amino acid amides so that they could be dynamically adsorbed on an octadecyl silica gel column.…”