Periodic Reporting for period 3 - DINAMIX (Real-time diffusion NMR analysis of mixtures)
Okres sprawozdawczy: 2022-02-01 do 2023-07-31
Chemical samples often come as solution mixtures. While advanced analytical methods exist for samples at equilibrium, the information on components and their interactions that may be accessed for the frequent and important case of out-of-equilibrium mixtures is much more limited. This is an obstacle for the description, understanding and control of chemical reactions, with implications ranging from fundamental chemistry concepts to industrial plants. The DINAMIX project aims at providing new information on solution mixtures that evolve in time, through the development of fast analytical methods based on nuclear magnetic resonance spectroscopy (NMR).
NMR spectroscopy is a powerful tool for the analysis of mixtures. Extracting accurate chemical information from mixtures often requires the use of multidimensional NMR experiments. Diffusion-ordered NMR spectroscopy (DOSY) is a particularly useful 2D NMR experiment for mixture analysis, that provides virtual separation of a mixture’s components. However, 2D experiments are time consuming in their conventional implementation. This is a limitation for the analysis of samples that evolve in time. Ultrafast 2D NMR is a method that makes it possible to collect complete 2D data sets in less than one second. It has recently been shown that UF DOSY experiments are general, and are relevant analysis of out-of-equilibrium mixtures.
In the DINAMIX project, we are developing novel fast 2D NMR experiments, mainly -but not exclusively- based on diffusion NMR, for mixture analysis, and using these methods for reaction monitoring applications and for the sensitive detection of mixture’s components. This involves the design and implementation of more robust and accurate experiments, that are applicable in a variety of contexts, such as the analysis of flowing samples for online monitoring. It also involves the design and use of original algorithms and software for numerical simulation and signal processing. High-impact applications are targeted during the course of the project, including the use of fast 2D NMR for online monitoring of organic chemical reactions, and the rapid authentication of samples with hyperpolarised ultrafast 2D NMR.
NMR spectroscopy is a powerful tool for the analysis of mixtures. Extracting accurate chemical information from mixtures often requires the use of multidimensional NMR experiments. Diffusion-ordered NMR spectroscopy (DOSY) is a particularly useful 2D NMR experiment for mixture analysis, that provides virtual separation of a mixture’s components. However, 2D experiments are time consuming in their conventional implementation. This is a limitation for the analysis of samples that evolve in time. Ultrafast 2D NMR is a method that makes it possible to collect complete 2D data sets in less than one second. It has recently been shown that UF DOSY experiments are general, and are relevant analysis of out-of-equilibrium mixtures.
In the DINAMIX project, we are developing novel fast 2D NMR experiments, mainly -but not exclusively- based on diffusion NMR, for mixture analysis, and using these methods for reaction monitoring applications and for the sensitive detection of mixture’s components. This involves the design and implementation of more robust and accurate experiments, that are applicable in a variety of contexts, such as the analysis of flowing samples for online monitoring. It also involves the design and use of original algorithms and software for numerical simulation and signal processing. High-impact applications are targeted during the course of the project, including the use of fast 2D NMR for online monitoring of organic chemical reactions, and the rapid authentication of samples with hyperpolarised ultrafast 2D NMR.
During the first half of the project, we have implemented the actions that were planned in the DINAMIX project, and we also explored additional perspectives opened by the results that were obtained during the course of the project.
Specifically, we have worked on the following points, that have led to publications:
. The first comprehensive characterisation of the spatially encoded DOSY experiment, in its initial form. This work was essential to provide clear guidelines on how to best use the method, and also to characterise the limitations that need to be addressed;
. The development of an original multivariate processing algorithm for ultrafast diffusion NMR experiments. This algorithm provides a significantly improved separation of a mixture’s components, in cases where peak overlap in the mixture spectrum. This development required the development of a new class of radio-frequency pulses for spatial encoding;
. The development of novel UF 2D correlation experiments that can be used on a flowing sample. These are particularly important for online monitoring applications;
. A unified analytical and numerical description of the spatial encoding process, that covers the different types of spatially encoded, ultrafast 2D NMR experiments.
. The acquisition of 2D 1H-1H correlation experiments from mixtures of substrates hyperpolarised by D-DNP
We have also made progress on:
. The development of fast diffusion NMR methods that can be used in flow conditions, and that account for the effect of hardware non ideality such as non-uniform gradients
. The description of flow effects for spatially encoded NMR experiments
. The implementation of a user-friendly processing software package, to be distributed open source.
Specifically, we have worked on the following points, that have led to publications:
. The first comprehensive characterisation of the spatially encoded DOSY experiment, in its initial form. This work was essential to provide clear guidelines on how to best use the method, and also to characterise the limitations that need to be addressed;
. The development of an original multivariate processing algorithm for ultrafast diffusion NMR experiments. This algorithm provides a significantly improved separation of a mixture’s components, in cases where peak overlap in the mixture spectrum. This development required the development of a new class of radio-frequency pulses for spatial encoding;
. The development of novel UF 2D correlation experiments that can be used on a flowing sample. These are particularly important for online monitoring applications;
. A unified analytical and numerical description of the spatial encoding process, that covers the different types of spatially encoded, ultrafast 2D NMR experiments.
. The acquisition of 2D 1H-1H correlation experiments from mixtures of substrates hyperpolarised by D-DNP
We have also made progress on:
. The development of fast diffusion NMR methods that can be used in flow conditions, and that account for the effect of hardware non ideality such as non-uniform gradients
. The description of flow effects for spatially encoded NMR experiments
. The implementation of a user-friendly processing software package, to be distributed open source.
Until the end of the project, we expect to develop an extensive suite of fast 2D NMR experiments that provide detailed and useful information on reaction mixtures, and that are also compatible with the sensitive detection of components when used in combination with hyperpolarisation methods. This will be made available in open access. We also expect to apply this method in collaboration with research group in organic chemical synthesis.