Flow NMR unmixing of reaction components

Introduction

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.

Challenges in Reaction Monitoring

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.

Project Overview

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.

Methodology

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.

Recent Developments

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.

Expected Impact

We expect these general methods will unravel transformative information on reactions and have broad impact in (bio)chemical science and engineering.