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

Lead Research Organisation: University of York
Department Name: Chemistry

Abstract

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.

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