The Morris Research Group

Research in Nuclear Magnetic Resonance

 

DOSY

 

Diffusion-ordered spectroscopy (DOSY) seeks to separate the NMR signals of different species according to their diffusion coefficient. A series of spin echo spectra is measured with different pulsed field gradient strengths, and the signal decays are analysed to extract a set of diffusion coefficients with which to synthesise the diffusion domain of a DOSY spectrum. In 2D DOSY the initial diffusion-weighted spectra are one-dimensional; adding diffusion weighting to 2D experiments such as COSY, NOESY or HMQC gives 3D DOSY spectra. DOSY can be roughly subdivided into two areas: low resolution DOSY of simple mixtures of molecules with widely differing sizes and poorly resolved NMR spectra, and high resolution DOSY, of more complex mixtures which may contain molecules of very similar sizes but which give well-resolved NMR spectra. The difficulty of extracting clean diffusion parameters from overlapping signal decays sets strict limits on the diffusion resolution of low resolution DOSY, but in the high resolution case relatively small differences (of the order of 1%) in diffusion coefficient can be resolved. To identify such small differences reliably it is necessary that the systematic errors be reduced to an absolute minimum: the challenge of designing successful high resolution DOSY techniques is to combine experimental methods which minimise such errors with data analysis procedures which compensate as accurately as possible for the errors that remain.

Most recently we have been investigating the potential of pure shift methods, in which the efffects of scalar couplings are suppressed so that the multiplet structure normally encountered in proton NMR is collapsed, to provide a major improvement in the resolution of proton DOSY experiments (Chemical Communications designated this a "hot paper"). Other recent developments include a variety of uses of multivariate statistics to enhance the chemical information obtainable with DOSY, and the use of matrix-assisted DOSY methods to improve diffusion resolution, for example allowing the resolution of the NMR spectra of isomers.


Publications on DOSY

 

"Reaction Kinetics Studied Using Diffusion-Ordered Spectroscopy and Multi-Way Chemometrics".  M. Khajeh, A. Botana, M.A. Bernstein, M. Nilsson and G.A. Morris, submitted.

 

"T1-DOSY: Nuclear Magnetic Resonance Mixture Analysis Using Parallel Factor Analysis".  M. Nilsson, A. Botana and G.A. Morris, Anal. Chem. 81, 8119-8125 (2009). DOI: 10.1021/ac901321w

 

"Constant time gradient HSQC-iDOSY: practical aspects".  A.S. McLachlan, J. J. Richards, A.R.Bilia and G.A. Morris, Magn. Reson. Chem. 47, 1081-1085 (2009). DOI: 10.1002/mrc.2518

 

"Diffusion-Ordered Spectroscopy". G. A. Morris, in Encyclopedia of Magnetic Resonance, eds R. K. Harris and R. E. Wasylishen, John Wiley: Chichester. DOI: 10.1002/9780470034590.emrstm0119.pub2. Published 15th December 2009.

 

"Isomer Resolution by Micelle-Assisted Diffusion-Ordered Spectroscopy". R. Evans, S. Haiber, M. Nilsson and G.A. Morris, Anal. Chem. 81, 4548-4550 (2009), DOI: 10.1021/ac9005777

 

"Improving the Accuracy of Pulsed Field Gradient NMR Diffusion Experiments:  Correction for Gradient Non-Uniformity." M.A. Connell, P.J. Bowyer, P.A. Bone, A.L. Davis, A.G. Swanson, M. Nilsson and G.A. Morris, J. Magn. Reson. 198, 121-131 (2009), doi:10.1016/j.jmr.2009.01.025

 

"Diffusion NMR and trilinear analysis in the study of reaction kinetics." Mathias Nilsson, Maryam Khajeh, Adolfo Botana, Michael A. Bernstein, and Gareth A. Morris, Chem. Commun., 2009, 1252-1254. DOI:10.1039/B820813A.

 

"Novel artemisinin and curcumin micellar formulations: drug solubility studies by NMR spectroscopy." S. Lapenna, A.R. Bilia, G.A. Morris and M. Nilsson, J. Pharm. Sci. 98, 3666-3675 (2009). DOI 10.1002/jps.21685.

 

"Speedy Component Resolution (SCORE): an improved tool for processing DOSY data." M. Nilsson and G.A. Morris, Anal. Chem., 80, 3777-3782 (2008).  DOI: 10.1021/ac7025833

 

"Improved DECRA processing of DOSY data: correcting for non-uniform field gradients", M. Nilsson and G.A. Morris, Magn. Reson. in Chem., 45, 656-660 (2007). DOI: 10.1002/mrc.2023

 

"Residue-specific NH exchange rates studied by NMR diffusion experiments", T. Brand, E. J. Cabrita, G.A. Morris, R. GŸnther, H.-J. Hofmann, and S. Berger, J. Magn. Reson. 187, 97-104 (2007).

 

"Pure shift Proton DOSY: Diffusion-Ordered 1H Spectra without multiplet structure." M. Nilsson and G.A. Morris, Chem. Commun. 2007, 933-935 ("hot paper").

 

"Correction of systematic errors in CORE processing of DOSY data."  M. Nilsson and G.A. Morris, Magn. Reson. in Chem., 44, 655-660 (2006).

 

"Multiexponential fitting of diffusion-ordered NMR data:  practicalities and limitations." M. Nilsson, M.A. Connell, A.L. Davis and G.A. Morris, Anal. Chem. 78, 3040-3045 (2006).

 

"Improving Pulse Sequences for 3D DOSY:  Convection Compensation." M. Nilsson and G.A. Morris, J. Magn. Reson. 177, 203-211 (2005).

 

ÒImproving Pulse Sequences for 3D DOSY:  COSY-IDOSYÓ, Mathias Nilsson, Ana M. Gil, Ivonne Delgadillo and Gareth A. Morris, Chem. Commun. 2005, 1737-1739.

 

ÒImproving Pulse Sequences for 3D Diffusion-Ordered NMR Spectroscopy:  2DJ-IDOSYÓ, Mathias Nilsson, Ana M. Gil, Ivonne Delgadillo and Gareth A. Morris, Analyt. Chem. 76, 5418-5422 (2004); DOI: 10.1021/ac049174f.

 

Ò2D and 3D DOSY Methods for Studying Mixtures of Oligomeric DimethylsiloxanesÓ, Marc J. Stchedroff, Alan M. Kenwright, Gareth A. Morris, Mathias Nilsson and Robin K. Harris, Phys. Chem. Chem. Phys. 6, 3221-3227 (2004); DOI:10.1039/ B403960B ("hot paper").

 

ÒHigh Resolution NMR and Diffusion Ordered Spectroscopy of Port WineÓ, Mathias Nilsson, Iola F. Duarte, Cl‡udia Almeida, Ivonne Delgadillo, Brian J. Goodfellow, Ana M. Gil, and Gareth A. Morris, J. Agric. Food Chem. 52, 3736-3743 (2004).

 

ÒDiffusion Measurements on Concentrated Samples by NMR:  Avoiding Problems with Radiation DampingÓ, M.A. Connell, A.L. Davis, A.M. Kenwright and G. A. Morris, Anal. Bioanal. Chem. 378, 1568-1573 (2004).

 

"A One-Shot Sequence for High Resolution Diffusion Ordered Spectroscopy",  M.D. Pelta, G.A. Morris, M.J. Stchedroff and S.J. Hammond, Magn. Reson. Chem. 40, S147-S152 (2002).

 

Guest Editor's Foreword, Special Issue on ÒNMR and DiffusionÓ, G.A. Morris, Magn. Reson. Chem. 40, S2 (2002).

 

"A Diffusion-Ordered NMR Spectroscopy Study of the Solubilization of Artemisinin by Octanoyl-6-O-ascorbic Acid Micelles", A.R. Bilia, M.C. Bergonzi, F.F. Vincieri, P. Lo Nostro and G.A. Morris, J. Pharm. Sci. 91, 2265-2270 (2002).

 

"Diffusion-Ordered Spectroscopy", G.A. Morris, in Encyclopedia of Magnetic Resonance:  Supplementary Volume, ed. D.M. Grant and R.K. Harris, J. Wiley and Sons, Ltd., pp 35-44 (2002).

 

"Silicon-29 diffusion-ordered NMR spectroscopy (DOSY) as a tool for studying aqueous silicates", R.K. Harris, K.A. Kinnear, G.A. Morris , M.J. Stchedroff, A.A. Samadi-Maybodi and N. Azizi, Chem. Commun., 2001, 2422-2423.

 

"One-Dimensional DOSY".  N.M. Loening, J. Keeler and G.A. Morris, J. Magn. Reson., 153, 103-112 (2001).

 

ÒA novel nuclear magnetic resonance spectroscopy method for screening small soluble compound librariesÓ.  P. Hodge, P. Monvisade, G.A. Morris and I. Preece, Chem. Commun., 2001, 239-240.

 

"The acid-catalysed degradation of clarithromycin and erythromycin B:  a comparative study using NMR spectroscopy", M.N. Mordi, M.D. Pelta, V. Boote, G.A. Morris and J. Barber, J. Med.Chem., 43, 467-474 (2000).

 

Most recent revision 19th January 2010