NMRDOSY

NMRDOSY, or diffusion-ordered nuclear magnetic resonance spectroscopy, is a family of NMR experiments that separates signals in a spectrum according to the diffusion coefficients of molecules in solution. By encoding molecular diffusion with pulsed-field gradients, DOSY assigns each signal a diffusion coefficient, effectively grouping resonances by how rapidly species diffuse. This enables analysis of complex mixtures and the association of signals with individual components, even when chemical shifts overlap.

Principles and methods: Diffusion in liquids causes molecules to experience random Brownian motion, with a diffusion coefficient D that reflects size, shape, and interactions. In NMRDOSY, pulsed-field gradient sequences (such as PGSE or PGSTE) selectively attenuate signals based on D, following the Stejskal–Tanner relation I = I0 exp(-bD), where b depends on gradient strength and timing. By varying gradient strengths across many steps, the diffusion coefficients for all observable resonances can be extracted. Two-dimensional representations typically render the chemical shift along one axis and the diffusion coefficient along the other, producing the DOSY map.

Applications and limitations: DOSY is used to deconvolute mixtures, study aggregation and binding, and characterize polymers, biomolecules, metabolites, and materials where diffusion behavior informs molecular size and interactions. It helps distinguish species with overlapping peaks and can monitor binding equilibria. Limitations include convection artifacts, temperature and viscosity effects, long measurement times, and difficulty resolving many species with similar diffusion coefficients. Accurate analysis often requires careful sample preparation and data processing, with considerations for sample homogeneity and experimental stability.

Overview: DOSY has become a standard tool in chemical, biochemical, and material research for linking spectral information to molecular diffusion, providing a diffusion-principle dimension to traditional NMR spectra.