脂质作为六大营养素之一,与细胞膜构建、信号传导和能量代谢等多种生物学过程密切相关.然而,脂质分子结构多样性给分析带来了挑战.基于碰撞诱导解离(collision-induced dissociation,CID)的传统串联质谱(tandem mass spectrometry,MS/MS)技术仅可以鉴定分子种类和脂肪酰基链组成,难以分析C＝C位置、sn-位置、官能团取代及位置等精细结构.近年来,在多种结构层次上分辨脂质异构体的质谱方法迅速发展,其中,自由基的引入在脂质气相离子活化和引发化学反应等方面发挥着独特作用.本文综述了近10年来自由基化学结合串联质谱技术在脂质精细结构解析方面的应用进展,主要包括气相的自由基诱导解离(radical-induced dissociation,RID)和自由基参与反应的衍生化-串联质谱技术.
Research Progress of Free Radical Chemistry-Tandem Mass Spectrometry for Fine Structure Analysis of Lipids
As one of the six major nutrients,lipids play important roles in various bio-logical processes,including cell membrane construction,signal transduction,and energy metabolism.The diverse functions of lipids are intricately linked to the distinct struc-tures.More than 48 000 molecular lipid structures have been curated in the database which can be further categorized into 8 categories and more than one hundred lipid clas-ses and subclasses.The diverse structures of lipids pose challenges for their lipidomic analysis,especially the co-existence of isomers and isobar.Traditional tandem mass spectrometry(MS/MS)techniques based on collision-induced dissociation(CID)can provide the informations of molecular species and acyl chain composition of various types of lipids in a sensitive fashion.However,they typically fall short in providing detailed structural information,including C＝C positions,sn-positions,functional group substitutions and their locations on the fatty acyl chains.In recent years,mass spec-trometry methods capable of distinguishing lipid isomers at various structural levels have been developed,among which radical chemistry plays important role in both gas-phase ion activation and chemical derivatization.This article summarized the MS/MS tech-niques for lipid structural analysis at detailed structural levels via harnessing the power of both radical chemistry and tandem mass spectrometry in the past decade.Radical-induced dissociation(RID)refers to a group of gas-phase dissociation methods which can generate intrachain C—C cleavages in the fatty acyl chain and thus produce fragmen-tation patterns useful for identification of chain modification.Ultraviolet photodissocia-tion(UVPD)and CID triggered radical-directed dissociation,and electron impact excita-tion of ions from organics(EIEIO)are the major RID methods.By coupling RID with separation methods,such as reversed-phase liquid chromatography(RPLC),identifica-tion and quantitation of lipid isomers consisting of methyl branching,hydroxy group,and cyclopropane modification and their locations have been achieved.The two major derivatization methods utilizing radical chemistry for C＝C bond modification were discussed,including radical initiated epoxidation reactions and the Paternò-Büchi reaction.Furthermore,the future direction of combining radical chemistry and tandem mass spectrometry for deep lipidotyping was discussed,which included the coupling with advanced separation methods,integrated workflows for multi-level structure analy-sis,and development of automated annotation tools for data analysis.
fine structure of lipidsradical chemistrytandem mass spectrometryradical-induced dissociation
万方数据
维普
