Real-time monitoring of chemical transformations by ultrafast 2D NMR spectroscopy

Maayan Gal, Mor Mishkovsky, Lucio Frydman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


An approach enabling the acquisition of 2D nuclear magnetic resonance (NMR) spectra within a single scan has been recently proposed. A promising application opened up by this "ultrafast" data acquisition format concerns the monitoring of chemical transformations as they happen, in real time. The present paper illustrates some of this potential with two examples: (i) following an H/D exchange process that occurs upon dissolving a protonated protein in D2O, and (ii) real-time in situ tracking of a transient Meisenheimer complex that forms upon rapidly mixing two organic reactants inside the NMR observation tube. The first of these measurements involved acquiring a train of 2D 1H-15N HSQC NMR spectra separated by ca. 4 s; following an initial dead time, this allowed us to monitor the kinetics of hydrogen exchange in ubiquitin at a site-resolved level. The second approach enabled us to observe, within ca. 2 s after the triggering of the reaction, a competition between thermodynamic and kinetic controls via changes in a series of 2D TOCSY patterns. The real-time dynamic experiments hereby introduced thus add to an increasing family of fast characterization techniques based on 2D NMR; their potential and limitations are briefly discussed.

Original languageEnglish
Pages (from-to)951-956
Number of pages6
JournalJournal of the American Chemical Society
Issue number3
StatePublished - 25 Jan 2006
Externally publishedYes


FundersFunder number
National Institute of General Medical SciencesR21GM072565


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