A spectroscopic tool for direct chemical structure determination in LC-MS

项目总结/摘要 拟议项目的总体目标是开发一种新的基于光谱的技术 这将允许对液体中迄今未知的分析物进行原位结构测定 色谱-质谱（LC-MS）框架。拟议的发展是建立在 现有的红外作用光谱方案的基础， 有限的方式在专门的研究实验室，并旨在使其广泛适用于 代谢组学研究，发现新的生物活性分子从天然来源和其他 目前使用LC-MS的情况。该项目的具体目标包括开发 获得质量选择的化合物的良好分辨的IR光谱所必需的方法和仪器 在LC-MS规定的短时间内对分析物进行明确的结构鉴定。 这需要大约两个数量级的数据采集速率的改进，这将 来自更快的波长调谐速率和增强的信噪比。取得这样 戏剧性的改进，该项目的一个主要组成部分涉及从使用 从低重复高脉冲功率激光器到高重复低脉冲功率激光器， IR光谱。这将需要对现有的实验装置进行彻底的重新设计， approach.此外，据我们所知，拟议的发展将涉及初审， 将调制技术和锁定检测应用于红外作用光谱。如果 如果成功，拟议的项目将导致大规模能力的显着增强， 光谱法，将其推入NMR的结构解析能力领域， 保持其高灵敏度、混合物耐受性和样品通过速率特性。为 例如，在天然产物研究中，绝大多数代谢物信号存在于 单个样品的质谱仍然是结构未知的，这是由于如此详细的 分析目前需要。同样，在新药开发中， 产生代谢物并需要完整的表征。拟议发展项目 将通过提供基于光谱的化学结构直接解决这些需求 在现有的和完善的LC-MS框架内的信息。

Project Summary/Abstract The overall goal of the proposed project is to develop a new spectroscopy-based technology that will allow for in situ structural determination of hitherto unknown analytes within the liquid chromatography-mass spectrometry (LC-MS) framework. The proposed development is built on the foundation of existing infrared action spectroscopy schemes that provide this capability in a limited manner within specialized research laboratories, and aims to make it broadly useful for metabolomic studies, the discovery of new bioactive molecules from natural sources and other instances where LC-MS is currently used. The specific aims of the project involve developing the methods and instrumentations necessary to obtain a well-resolved IR spectrum of a mass-selected analyte for unambiguous structural identification within the short timeframe dictated by LC-MS. This requires improvements in data acquisition rate of about two orders of magnitude, which will come from faster wavelength tuning rates and enhanced signal-to-noise ratio. To achieve such dramatic improvements, a major component of this project involves transitioning from using a low-repetition-high-pulse-power laser to a high-repetition-lower-pulse-power laser for acquiring the IR spectrum. This will necessitate a complete redesign of the existing experimental setup and approach. Moreover, the proposed developments will involve, to our knowledge, the first instance of applying modulation techniques and lock-in detection to infrared action spectroscopy. If successful, the proposed project will lead to dramatic enhancements in the capability of mass spectrometry, pushing it into the realms of NMR in terms of structural elucidation ability while retaining its high sensitivity, mixture tolerance, and sample throughput rate characteristics. For example, in natural products research the vast majority of the metabolite signals present in the mass spectra of a single sample remain structurally unknown due to the extreme cost such detailed analysis would currently entail. Similarly, in the development of new drugs, new unknown metabolites are generated and require complete characterization. The proposed developments would directly address these needs by providing spectroscopically based chemical structure information within the existing and well-developed LC-MS framework.