Flow NMR unmixing of reaction components

Informazioni relative al progetto

UNMIX

ID dell’accordo di sovvenzione: 101124289

DOI

10.3030/101124289

Data della firma CE 15 Dicembre 2023

Data di avvio 1 Febbraio 2025

Data di completamento 31 Gennaio 2030

Finanziato da

• European Research Council (ERC)

Costo totale

€ 1 995 506,00

Contributo UE

€ 1 995 506,00

Coordinato da

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
France

Periodic Reporting for period 1 - UNMIX (Flow NMR unmixing of reaction components)

Periodo di rendicontazione: 2025-02-01 al 2027-07-31

Sintesi del contesto e degli obiettivi generali del progetto

Chemical reactions are the universal path to new molecules, and are of central importance in science. The description of reactions is largely obtained once they are completed, with a key role of nuclear magnetic resonance (NMR), through the structural information found in the spectra of purified products. Structural information is, however, elusive for ongoing reactions. While time-resolved NMR provides kinetics for known compounds, compound identification from a reaction mixture is not generally feasible today. Such identification would be transformative for the discovery, understanding and optimisation of reactions.
The UNMIX project aims at providing unprecedented levels of structural and quantitative information from ongoing reactions in experimentally relevant conditions. Its central, novel concept is the unmixing of compound-specific data by time-resolved diffusion NMR in continuous flow.
Diffusion NMR is a method with the potential to separate the spectra of mixture components. Until recently, diffusion NMR was limited to reactions performed in an NMR tube, a setup that often fails to replicate experimental conditions of interest. In contrast, emerging continuous-flow approaches give real-time monitoring in relevant conditions.
In 2022, the PI has shown the possibility to obtain high-quality diffusion NMR data for flowing samples. This opens the path to the UNMIX project, and its specific aims to:
1) develop novel accurate, fast, sensitive and flow-compatible diffusion NMR methods;
2) develop an original and broadly applicable data-analysis workflow to yield compound-specific 1D/2D spectra and concentration time curves from ongoing reactions;
3) address challenging applications such as the identification of intermediates in multi-step batch reactions, and reaction discovery with an autonomous flow reactor.
We expect these general methods will unravel transformative information on reactions and have broad impact in (bio)chemical science and engineering.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

Due to the passing of the PI in August 2025, only the first actions of Unmix were implemented during the first months of the project, before it was interrupted.

However, during this initial period, the PI performed the following actions:
1) detailed investigation of the state-of-the art on the main topic of the project, in particular on flow NMR methods for reaction monitoring;
2) purchase of a triple-axis gradient NMR probe operating at 400 MHz, crucial for the implementation of the project;
3) recruitement of a post-doctoral researcher (screening of international candidates, interviews and selection), for a start on September 1st 2025 (Post-doc 1 mention in the DoA);
4) recruitement of a Ph.D. student (screening of international candidates, interviews and selection), for a start on October 1st 2025 (Post-doc 1 mention in the DoA).

On item 1), the PI coordinated the writing of authoritative review article on flow NMR methods, together with a team of 4 international collaborators. This review was submitted to Nature Methods Primer, and it was submitted in July 2025. The PI's co-authors are now working on the revision of this manuscript, which will be published in 2026 with the PI as a posthumous author.

On item 2), the material has been purchased, delivered and installed in the host laboratory (CEISAM) and is running.

On items 3) and 4), the two persons were effectively hired and their contracts with the host institution had already been signed when the project was terminated. The host institution and host laboratory made sure that these contracts would be honoured, by funding these contracts on other research grants or CNRS's funding and by assigning research missions closely related to those initially assigned to these persons. The two recruited persons are now working in the same team (MIMM team at the CEISAM lab), on closely related topics (NMR methodologyu for complex mixture analysis). The CNRS is maintaining the contracts for the HR resources initially assigned to the UNMIX project. As the start dates for the employment contracts are set for 1 September 2025 and 1 October 2025, no HR costs for these recruitments are charged to the project; however, the individuals assigned will continue their work within the CEISAM laboratory teams. Only PI costs (JN DUMEZ) are charged.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

Due to the passing of the PI, no results can be reported, but a major authoritative review on the central topic of the project should be published in 2026, with the PI as posthumous co-author.