Photochemical Amplification of Signal for Structure Elucidation (PASSE): Improved Homonuclear Correlation Spectroscopy

The determination of molecular structure is a key step in any synthetic chemistry project, drug discovery campaign, or natural product identification. Nuclear magnetic resonance (NMR) spectroscopy is one of the most powerful and information rich analytical techniques available for the task, however, it is hampered by poor sensitivity. This low sensitivity is particularly acute for natural product and impurity identification, where limited sample material is available. A number of approached have been proposed to improve the sensitivity of NMR spectroscopy by increasing the population difference across the spin energy levels, including optical pumping of noble gases, dynamic nuclear polarisation and parahydrogen induced polarisation. These methods are capable of producing significant increases in signal under favourable conditions, however, their routine application in small molecule structure elucidation is limited due to the complex processes required for the generating of hyperpolarisation and the one-shot nature of several of the methods.

Photochemically induced dynamic nuclear polarisation (photoCIDNP) utilises a spin-state selective photochemical reaction between a suitable dye and the molecule of interest to produce nuclear spin polarisation via hyperfine modulations of a spin-correlated radical pair. This approach allows repetition of the experiment via multiple illuminations enabling both signal averaging and extension to multidimensional experiments. The only requirement is a suitable dye, e.g. a flavin, a high intensity illumination source and the formation of a spin-correlated radical pair. Recently, we have begun an EPSRC funded project (EP/P015735/1) to develop photoCIDNP as a sensitivity enhancement technique for small molecule structure elucidation, focusing on improvements in heteronuclear correlation experiments.

This project will focus on the development of a suit of homonuclear correlation experiments (i.e. 1H-1H corelations) applicable to structure elucidation, such as COSY, NOESY etc, including characterising the improvements in limit of detection and/or time saving available. These experiments form part of the routine package of spectroscopic experiments performed when undertaking the determination of an unknown structure. The project will have three distinct aims:

1. Develop photochemically enhanced variants of standard homonuclear correlation experiments. Modifications such as the combined COSY-NOESY experiment (termed COCONOESY) will also be explored in order to gain further information from a single experiment.
2. Incorporate state-of-the-art data collection strategies such as non-uniform sampling and ultrafast acquisition schemes. In combination with photochemical enhancement these techniques will greatly reduce the amount of time required to obtain the data, improving experimental throughput
3. Application of these homoPASSE experiments to structure elucidation and low concentration impurity identification

This project will utilise the second generation LED illumination setup currently under construction in the Day laboratory.

How to apply:
Please submit a formal application using our online application system at http://www.sussex.ac.uk/study/phd/apply, including a CV, degree transcripts and certificates, statement of interest (clearly stating supervisor’s name and the project title) and names of two academic referees. On the application system use Programme of Study – PhD Chemistry.

For enquiries about the application process contact Anna Izykowska ([Email Address Removed])
For enquiries about the project contact Dr Iain Day ([Email Address Removed])