Time- and site-resolved kinetic NMR for real-time monitoring of off-equilibrium reactions by 2D spectrotemporal correlations

• Published in: Nature communications 2022-02, Vol.13 (1), p.833-833, Article 833
• Main Authors: Jaroszewicz, Michael J., Liu, Mengxiao, Kim, Jihyun, Zhang, Guannan, Kim, Yaewon, Hilty, Christian, Frydman, Lucio
• Format: Article
• Language: English
• Subjects: 140/131; 639/638/440/950; 639/766/930/878/1263; Chemical reactions; Continuous flow; Correlation; Equilibrium; Equilibrium conditions; Humanities and Social Sciences; Information processing; Monitoring; multidisciplinary; NMR; NMR spectroscopy; Nuclear magnetic resonance; Real time; Science; Science (multidisciplinary); Spectra; Spectroscopy; Spectrum analysis
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-28304-w

Nuclear magnetic resonance (NMR) spectroscopy provides detailed information about dynamic processes through line-shape changes, which are traditionally limited to equilibrium conditions. However, a wealth of information is available by studying chemical reactions under off-equilibrium conditions— e.g ., in states that arise upon mixing reactants that subsequently undergo chemical changes—and in monitoring the reactants and products in real time. Herein, we propose and demonstrate a time-resolved kinetic NMR experiment that combines rapid mixing techniques, continuous flow, and single-scan spectroscopic imaging methods, leading in unison to a 2D spectrotemporal NMR correlation that provides high-quality kinetic information of off-equilibrium chemical reactions. These kinetic 2D NMR spectra possess a high-resolution spectral dimension revealing the individual chemical sites, correlated with a time-independent, steady-state spatial axis that delivers information concerning temporal changes along the reaction coordinate. A comprehensive description of the kinetic, spectroscopic, and experimental features associated with these spectrotemporal NMR analyses is presented. Experimental demonstrations are carried out using an enzymatically catalyzed reaction leading to site- and time-resolved kinetic NMR data, that are in excellent agreement with control experiments and literature values. Time-resolved NMR spectra provide unique structural and dynamical information, but their measurement in systems undergoing chemical reactions is challenging. Here the authors, combining single-scan spectroscopic imaging, rapid mixing and continuous flow techniques, obtain chemically resolved snapshots of a reacting system throughout the reaction coordinate.