Enantioselectivity-Evaluation of Chiral Copper(II) Complexes Coordinated by Novel Chiral Tetradentate Ligands for Free Amino Acids by Mass Spectrometry Coupled With the Isotopically Labeled Enantiomer Method.

Takashi Nakakoji,Hideya Kawasaki,Kaori Yoshino,Satoshi Shinoda,Motohiro Shizuma,Kazuki Izutsu,Hiroshi Tsukube,Hiroyuki Miyake,Daisuke Ono,Ryuichi Arakawa,Hirofumi Sato,Eiko Mieda

doi:10.3389/fchem.2020.598598

Abstract

A series of copper(II) complexes with chiral tetradentate ligands, N,N′-ethylene- bis(S-amino acid methyl amide or methyl ester) prepared from S-alanine, S-phenylalanine, S-valine or S-proline, was generated in methanol. The copper complexes provided three component complexes in the presence of a free chiral amino acid. The enantioselectivity for the amino acid was evaluated by electrospray ionization-mass spectrometry coupled with the deuterium-labeled enantiomer method and these copper complexes were found to exhibit high enantioselectivity for free amino acids having bulky side chains. This result suggests that steric interaction between the tetradentate ligand and free amino acid was a major factor in chiral recognition. The copper complex with a chiral tetradentate ligand prepared from S-proline showed opposite enantioselectivity to copper complexes consisting of tetradentate ligands prepared from other S-amino acids. The conformational difference of the tetradentate ligand in the copper complex was found to be significant for enantioselectivity.

Highlights

Chiral recognition is one of the essential and fundamental processes in living systems
It was clarified that the enantioselectivity for amino acids is controlled by the slight difference in the coordination form of the copper(II) complex with chiral tetradentate ligand, and the magnitude of the chiral discrimination ability depends on the steric interaction between the sidearms of the chiral tetradentate ligand and the side chain of the amino acid
Mass spectrometry coupled with the isotopically labeled enantiomer method can be applied to a method for determination of the enantiomeric excess of chiral guests by using an isotopically labeled/unlabeled enantiomer pair for the chiral host (Sawada et al., 1998; Shizuma et al., 2000)

Summary

Introduction

Chiral recognition is one of the essential and fundamental processes in living systems. Organometallics and metal complexes can play a special role to detect the chirality of amino acids (Severin et al, 1998; Chin et al, 1999). In ligand exchange chromatography using a stationary phase fixed with metal ion such as copper or nickel, enantiomers of chiral amino acids were separated by using a chiral selector as the mobile phase (Brückner et al, 1990). By reversed-phase chromatography, optical separation of chiral amino acids was achieved by using a mobile phase including a chiral selector and copper salts (Gil-Av et al, 1980). Detailed investigation of complexation of chiral metal complexes with amino acids leads to finding new designs for molecular recognition systems, which can spread to a wide range of fields such as organic, inorganic, analytical, and biological chemistries

Methods

Results

Conclusion