摘要
酰胺键是一种广泛存在的重要化学键,既是构建蛋白质和多肽的核心,也是多种药物分子的活性中心。近年来,基于电化学的酰胺化反应以高选择性、环境友好等优势受到广泛关注,然而,受限于反应过程的复杂性以及缺乏适当的分析技术,其原位监测和机理研究却鲜有报道。本研究通过在纳升电喷雾喷针尖端集成金属工作电极的方式构建了一种新型耦合接口,实现了电化学与质谱的在线联用。基于该技术原位监测了以三苯基膦为缩合剂的芳伯胺酰胺化反应过程,并实现了其中多种关键中间体,特别是一些短寿命自由基中间体的鉴定。该电化学-质谱耦合接口具有延迟低、样品耗量小、制备简单等优点,有望成为电有机合成反应快速筛选和机理研究的重要工具。
Amide bond is a ubiquitous and crucial functional group that serves as the linchpin for constructing proteins,peptides,and is also the central site in numerous drug molecules.Consequently,it is crucial to investigate the strategies and mechanisms of amidation reactions.In recent years,the use of electrochemistry for amidation has gained significant attention due to its exceptional qualities such as increased selectivity and eco-friendliness.However,due to the complexities of the reaction processes and the scarcity of relevant analytical tools,the studys of in-situ monitoring and mechanistic investigations on these electrochemical amidation reactions are rare.In response to this challenge,a novel coupling device was designed in this study.The main component of the coupling device was a glass capillary tube with a metal cover.The metal coating on the tip's outer surface was connected to a high voltage power supply to drive the electrospray ionization process.Additionally,the metal coating inside the tip was also connected to the metal coating on the tip's outer surface and served as the working electrode for an electrochemical reaction.When high voltage was applied,both the electrospray process and the electrochemical reaction on the tip could be driven simultaneously.The substances produced by the electrochemical reaction in the capillary tip could be quickly transfered to spray droplets,ionized via desolvation process,and finally detected via mass spectrometry.Based on this technique,a series of aromatic primary amines amidation reactions were observed in situ while using triphenylphosphine as the condensing agent.Numerous important intermediates were also discovered during these reactions.Remarkably,this novel approach not only facilitated continuous real-time monitoring of these reactions but also empowered scientists to unambiguously identify an array of key intermediates,including the elusive short-lived free radical intermediates.The electrochemical-mass spectrometry coupling device has numerous advantages,including short analysis delays,the ethical use of sample resources,and uncomplicated,simple preparation processes.It's potential to revolutionize the field of electroorganic synthesis reactions.This cutting-edge technique is poised to become an invaluable tool for rapid screening and in-depth investigations into the complex mechanisms of driving amidation reactions.The coupling device represents an exciting improvement forward in the context of drug investigations,where precision and efficiency are critical.Additionally,as society places increasing emphasis on environmental sustainability and the demand for precise chemical processes intensifies,this breakthrough coupling device is expected to become a formidable instrument in investigating the mechanism of electrochemical reactions.
作者
羊雪
惠人杰
胡军
YANG Xue;HUI Ren-jie;HU Jun(School of Life Sciences and Health Engineering,Jiangnan University,Wuxi 214200,China)
出处
《质谱学报》
EI
CSCD
北大核心
2024年第1期131-140,I0004,共11页
Journal of Chinese Mass Spectrometry Society
基金
国家自然科学基金(22004071)
江苏省自然科学基金(BK20200668)
生命分析化学国家重点实验室开放基金(SKLACLS2313)。
关键词
酰胺化反应
自由基中间体
原位质谱
三苯基膦
amidation reactions
radical intermediate
in-situ mass spectrometry
triphenylphosphine