Thanks to the team developments in fast multi-dimensional NMR, this recent research axis has been initiated in 2015 and is aiming at monitoring complex (bio)chemical transformations in real time. Reacting media are complex, out-of-equilibrium mixtures that require tailored pulse sequences compatible with flow analysis. Such methods are developed both at high field and on benchtop spectrometers.
At high-field, a unique experimental setting associating a flow tube with a micro-imaging equipment has recently been installed.
Two benchtop spectrometers are also equipped with a flow system. Targeted applications include the monitoring and control of chemical flow syntheses through a self-optimizing reactor, in collaboration with the CORAIL team. The monitoring of bioprocesses such as microalgae cultivations and enzymatically induced food processes is also explored.
17. Benchtop NMR for flow chemistry and bioprocess monitoring
Current team members: Dylan Bouillaud, Benoît Charrier, Jonathan Farjon*, Patrick Giraudeau*
Benchtop NMR spectrometer dedicated to reaction monitoring and its implementation in an intelligent flow chemistry setting.
NMR is ideally suited for the online, real-time monitoring of (bio)chemical processes, but it can be limited by size, cost and accessibility considerations that make high-field NMR incompatible with the environment where the targeted processes take place, such as fume hoods or production sites. In this context, we are exploring the potential of benchtop NMR for the online monitoring and control of such processes. In order to circumvent the limitations inherent to low magnetic field (low sensitivity and resolution), we are adapting pulse sequences akin to those developed at high field, thanks to state-of-the-art benchtop spectrometers equipped with a gradient coil and including pulse sequence programming capabilities.
In particular, we have implemented solvent suppression and ultrafast 2D NMR pulse sequences suited to flow measurements. In collaboration with synthetic chemistry groups, we explore their potential for the online monitoring of catalytic reactions, and we use such experiments as an online detector in flow chemistry settings, including intelligent flow experiments where the NMR data are analyzed automatically in real time to optimize the reaction. We are also exploring the potential of benchtop NMR for the monitoring of bioprocesses.
Key References:
B. Gouilleux, B. Charrier, E. Danieli, J.-N. Dumez, S. Akoka, F.-X. Felpin, M. Rodriguez-Zubiri, P. Giraudeau, Real-time reaction monitoring by ultrafast 2D NMR on a benchtop spectrometer, Analyst, 140, 7854 (2015)
B. Gouilleux, B. Charrier, S. Akoka, F.-X. Felpin, M. Rodriguez-Zubiri, P. Giraudeau, Ultrafast 2D NMR on a benchtop spectrometer: Applications and perspectives, Trends Anal. Chem. 83, 65 (2016)
B. Gouilleux, S. Akoka, P. Giraudeau, Gradient-based solvent suppression methods on a benchtop spectrometer, Magn. Reson. Chem. 55, 91 (2017)
B. Picard, B. Gouilleux, T. Lebleu, J. Maddaluno, I. Chataigner, M. Penhoat, F.X. Felpin, P. Giraudeau, J. Legros, Oxidative Neutralization of Mustard-Gas Simulants in an On-Board Flow Device with In-Line NMR Monitoring, Angew. Chem. Int. Ed. 56, 7568 (2017)
D. Bouillaud, J. Farjon, O. Gonçalves, P. Giraudeau, Benchtop NMR for the monitoring of bioprocesses, Magn. Reson. Chem. in press (2019)
Supported by: Région Pays de la Loire (Paris scientifiques RésoNantes and AMER-METAL), CNRS (Projet interdisciplinarité RMN-(ME)2-TAL and Projet Emergence ARES-TATION)
