Self-Assembled Binuclear Cu(Ⅱ)-L-Histidine Complex in the Gas Phase for Chiral Differentiation of Naproxen
作者单位：State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation) and Shenzhen Key Laboratory of Food Biological Safety ControlShenzhen Research Institute of Hong Kong Polytechnic University School of Chemical Engineering and Energy TechnologyDongguan University of Technology Department of ChemistryCity University of Hong Kong State Key Laboratory of ChirosciencesFood Safety and Technology Research Centre and Department of Applied Biology and Chemical TechnologyThe Hong Kong Polytechnic University Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules (Yanbian University)Ministry of Education
会议名称：《2018年中国质谱学术大会（CMSC2018）》
会议日期：2018年
学科分类：1007[医学-药学(可授医学、理学学位)] 10[医学]
关 键 词：Collision-induced dissociation Ion-mobility spectrometry Collision cross section Density functional theory Molecular dynamics simulation
摘 要：Naproxen is one of the most consumed nonsteroidal anti-inflammatory drugs and marketed as Snaproxen as its R-enantiomer is hepatotoxic [1]. Developments of efficient and reliable methods for chiral differentiation and quantification of naproxen are thus essential [2]. In this work [3], we discovered a self-assembled binuclear Cu(II) diastereomeric complex ion in the gas phase, [(Cu IIL-His)2(S/R-naproxen)-3 H]+, that can be applied to effectively determine the absolute configuration of naproxen and quantify the enantiomeric excess of S/R-naproxen mixtures using collision-induced dissociation with a tandem mass spectrometer. The key candidate structure of this gas-phase diastereomeric complex ion has an unusual self-assembled, compact geometry with the two Cu(II) ions bridged closely together by the carboxylate groups of the two histidines, proposed using density functional theory, and supported by ion-mobility spectrometry and collision cross section modeling. The difference in dissociation efficiency of the two diastereomers is attributed to the σ-π interaction between the NH2 group of one histidine and the naphthyl ring of naproxen in the complex. The present report observes and characterizes the diastereomeric complexes of [(Cu IIL-His)2] with aromatic acid, which could contribute to the recognition of chiral aromatic acids, design of catalysts based on binuclear copper-bound complex, as well as the better understanding of metal-ion complexation by His or His-containing ligands.