脂质结构的多样性赋予了其重要的生物学功能，明确脂质化合物的化学结构，对于揭示其在疾病的发生和发展过程中的分子作用机制和途径，具有重要的意义。目前结构脂质组学研究面临的最大难题，是对脂质异构体中的双键位置、双键的顺反异构和支链位置异构等信息进行准确的鉴定。质谱作为脂质组学最重要的研究手段之一，在脂质双键异构体的鉴定方面却面临着极大的挑战。这主要是因为在传统的脂质组学质谱分析中，所采用的碰撞诱导解离技术，无法使目标物在C=C键处断裂产生与其位置相关的特征离子。为了解决这个难题，研究者不断尝试开发不同的双键化学衍生方法。其中，紫外光化学反应衍生因为反应速度快、易产生特征离子，是目前的主流方法。然而，紫外光对健康存在潜在的危害，而且在复杂体系衍生时容易产生不可预知的副反应，增加生物样品分析的复杂性。因此，如果能够开发出温和的可见光激发双键衍生方法，将会具有重要的优势。
本课题组在可见光化学反应及其质谱分析和应用方面具有较好的研究基础（Angew. Chem. Int. Ed. 2016, 128, 9491），近期我们开发出了一种新型可见光诱导的C=O键和C=C键的[2+2]环加成反应，并将其用于脂质中双键的衍生和质谱分析，成功实现了复杂生物体系中脂质双键异构体的全面分析和精确鉴定。这一成果发表在化学预印本网站ChemRxiv和Chemical Science杂志上，详细内容参见X-mol的报道：https://www.x-mol.com/news/457177。论文链接：https://pubs.rsc.org/en/content/articlelanding/2020/sc/d0sc01149e
The diversity of lipid structures confers important biological functions, and clarifying the chemical structures of lipid compounds is of great importance to reveal their molecular mechanisms and pathways of action in the onset and progression of diseases. The biggest challenge of structural lipidomics research at present is the accurate identification of information on double bond positions, cis-trans isomerism of double bonds and branched position isomerism in lipid isomers. Mass spectrometry, as one of the most important research tools in lipidomics, has faced great challenges in the identification of lipid double bond isomers. This is mainly due to the fact that the collision-induced dissociation technique used in conventional lipidomics mass spectrometry analysis cannot cause the target to break at the C=C bond to produce characteristic ions associated with its position. To solve this challenge, researchers have continuously tried to develop different methods for the chemical derivatization of double bonds. Among them, UV chemical reaction derivatization is currently the mainstream method because of its fast reaction speed and easy generation of characteristic ions. However, UV light is potentially hazardous to health and is prone to unpredictable side reactions during derivatization of complex systems, increasing the complexity of biological sample analysis. Therefore, it would be an important advantage if a mild visible-light-excited double-bond derivatization method could be developed.
Our group has a good research foundation in visible-light-activated photochemical reactions and their mass spectrometric analysis and applications (Angew. Chem. Int. Ed. 2016, 128, 9491), and we have recently developed a novel visible light-induced [2+2] cycloaddition reaction of C=O and C=C bonds and used it for the derivatization and mass spectrometric analysis of double bonds in lipids, successfully achieving the comprehensive analysis and precise identification of lipid double bond isomers in complex biological systems. The results were published in ChemRxiv and Chemical Science journal. Please see: https://pubs.rsc.org/en/content/articlelanding/2020/sc/d0sc01149e
