Harnessing the Combined Power of IR Spectroscopy and Mass Spectrometry: Development of a New Instrument for Process Analytical Technology

由于其国际领先的研发基地，英国化学制造业在包括药品和农用化学品在内的高价值产品方面保持着竞争优势。用于这些工业的新化学品最初是在研究实验室中小规模开发的，然后使用过程化学来确保在转移到商业化学品生产之前反应的产量最大化。对单个化学产品的任何特定工艺化学流的优化，都严重依赖于对可能降低所需化学产品收率的任何反应中间体和副产物的识别。传统的分析方法适用于所有的试验反应混合物，但存在开发更快、更敏感的技术以提供该领域阶跃变化的潜力。如果实现，这种使能技术有可能为化学制造业提供非常可观的竞争优势。此外，通过最大限度地生产利用化学品和尽量减少化学品浪费，实现最佳的“绿色”和可持续工业实践也很重要。质谱法是关键的分析技术之一，是快速、灵敏分析复杂混合物的理想选择。这使得它非常适合在过程化学中的应用，但迄今为止它的使用受到限制，因为它只能直接测量分子的质量。这并不能明确地定义分子的结构，因为具有相同质量的分子可以在分子内具有不同的原子排列，这种情况被称为异构化。这对于小分子鉴定来说是一个非常严重的问题，包括在过程化学中遇到的农用化学品和药品，因为同分异构体可以显示出截然不同的化学性质。在这里，我们提出了一种新的仪器，它将改变质谱的能力，通过将质谱与红外光谱结合在一个仪器中，严格识别未知分子，例如在过程化学中遇到的分子。新仪器将结合质谱的灵敏度和红外光谱的结构诊断技术，提供一种功能强大的新型台式分析设备。研究人员（Dessent和Fairlamb）将整合独特的专业知识，并与他们的工业合作伙伴（先正达，赛默飞世尔解决方案和光子解决方案）一起努力开发下一代结构测定技术，该技术可应用于过程分析技术，用于复杂反应混合物的敏感，实时分析，以识别产品，副产物和反应中间体的显著增强范围。通过与我们的工业合作伙伴先正达的合作，我们的建议将对农用化学品生产的优化产生直接影响，并随后对制药、化妆品和食品行业产生影响。从长远来看，我们设想与我们的合作伙伴赛默飞世尔解决方案公司合作，快速开发新仪器作为台式商业产品（TRL6/7），可广泛应用于研究实验室和工业环境。

The UK chemical manufacturing industry maintains a competitive advantage in high-value products including pharmaceuticals and agrochemicals due to its internationally leading research and development base. New chemicals for these industries are initially developed on a small scale in research laboratories, with process chemistry then being employed to ensure that the reaction is yield-maximized prior to its transfer into commercial chemical manufacture.The optimization of any particular process chemistry stream for an individual chemical product is critically dependent on the identification of any reaction intermediates and bi-products which can reduce the yield of the desired chemical product. Traditional analysis methods are applied to all trial reaction mixtures, but the potential exists to develop faster, more sensitive technologies to provide a step change in the field. If achieved, such an enabling technology has the potential to deliver very considerable competitive advantages to chemical manufacturing industries. Furthermore, it is also important for delivering the best "green" and sustainable industrial practice by maximizing the productive use of chemicals and minimizing chemical wastage.Mass spectrometry is one of the key analytical techniques and is ideal for fast, sensitive analysis of complex mixtures. This makes it ideally suited for application in process chemistry, but its use to date has been limited by the fact that it directly measures only a molecule's mass. This does not define the structure of the molecule unambiguously, since molecules with same mass can have different arrangements of the atoms within the molecule, a situation described as isomerization. This is a very serious problem for small molecule identification, including the agrochemicals and pharmaceuticals encountered in process chemistry, since isomers can display dramatically different chemical properties. Here, we propose a new instrument that will transform the ability of mass spectrometry to rigorously identify unknown molecules, such as those encountered in process chemistry, by combining mass spectrometry with IR spectroscopy in a single instrument. The new instrument will harness the combined sensitivity of mass spectrometry with the structural diagnostic technique of IR spectroscopy to deliver a powerful, new benchtop analytical device. The investigators (Dessent and Fairlamb) bring together unique expertise, and along with their Industrial Partners (Syngenta, Thermo Fisher Solutions, and Photonic Solutions) will work to unlock a next-generation structure determination technique, which can be applied in process analytical technology for sensitive, real-time analysis of complex reaction mixtures to identify a significantly enhanced range of products, side products and reaction intermediates. Through working with our industrial partner Syngenta, our proposal will have immediate impact on the optimization of agrochemical manufacture, with subsequent impact in the pharmaceutical, cosmetic and food product sectors. Longer term, we envisage working with our partner Thermo Fisher Solutions, to rapidly develop the new instrument as a benchtop commercial product (TRL6/7) that can be widely applied in research laboratories and industrial settings.