Self-assembled binuclear Cu(II)-serine tetrameric complex for chiral recognition and enantiomeric excess determination of cycloserine in the gas phase

摘要

The different physiological activities including pharmacology and toxicology of chiral drugs have been receiving more and more attention. Today, systematic studies of the biological activity of individual enantiomers are necessary for all listing new racemic drugs. D-cycloserine or d-4-amino-3-isoxazolidinone is a broad-spectrum antibiotic used as a chiral drug for the treatment of tuberculosis. In the current study, the chiral identification of cycloserine and quantification of its enantiomeric excess (ee) was achieved based on the competitive dissociation kinetics of Cu(II)-bound complexes. A novel binuclear Cu(II)-bound diastereomeric complex [(Cu(II))(2) (L/D-cycloserine) (Ser)(3)-3H](+) was formed and the complex structure which has an extraordinary self-assembled compact geometry with two Cu(II) ions bridged together tightly by three carboxylic acids from serines was revealed by both collision-induced dissociation tandem mass spectrometry and density functional theory calculations. The present work reporting binuclear Cu(II)-Ser tetrameric complex-based approach could contribute to the chiral recognition of other similar isoxazolidinone drugs, as well as the better understanding of metal ion complexation by Ser or Ser-containing ligands. (C) 2019 Elsevier B.V. All rights reserved.