Cross-Peaks in Simple Two-Dimensional NMR Experiments from Chemical Exchange of Transverse Magnetisation.

Christopher A. Waudby,John Christodoulou,Tom Frenkiel

doi:10.1002/anie.201903245

Abstract

Two‐dimensional correlation measurements such as COSY, NOESY, HMQC, and HSQC experiments are central to small‐molecule and biomolecular NMR spectroscopy, and commonly form the basis of more complex experiments designed to study chemical exchange occurring during additional mixing periods. However, exchange occurring during chemical shift evolution periods can also influence the appearance of such spectra. While this is often exploited through one‐dimensional lineshape analysis (“dynamic NMR”), the analysis of exchange across multiple chemical shift evolution periods has received less attention. Here we report that chemical exchange‐induced cross‐peaks can arise in even the simplest two‐dimensional NMR experiments. These cross‐peaks can have highly distorted phases that contain rich information about the underlying exchange process. The quantitative analysis of such peaks, from a single 2D spectrum, can provide a highly accurate characterisation of underlying exchange processes.

Highlights

Two-dimensional correlation measurements such as COSY, NOESY, HMQC, and HSQC experiments are central to small-molecule and biomolecular NMR spectroscopy, and commonly form the basis of more complex experiments designed to study chemical exchange occurring during additional mixing periods
Exchange occurring during chemical shift evolution periods can influence the appearance of such spectra. While this is often exploited through one-dimensional lineshape analysis (“dynamic NMR”), the analysis of exchange across multiple chemical shift evolution periods has received less attention
By using radiofrequency pulses to perturb the magnetisation of systems in dynamic equilibrium, the associated chemical exchange processes can be characterised with high precision across a wide range of timescales

Summary

Introduction

Two-dimensional correlation measurements such as COSY, NOESY, HMQC, and HSQC experiments are central to small-molecule and biomolecular NMR spectroscopy, and commonly form the basis of more complex experiments designed to study chemical exchange occurring during additional mixing periods. In a long-standing approach termed lineshape analysis or “dynamic NMR”, onedimensional (1D) spectra may be fitted in a least-squares sense to solutions of the Bloch–McConnell or Liouville–von Neumann equations[7,8] that govern the evolution of magnetisation, in order to characterise the chemical exchange process.

Results

Conclusion