Diffusion weighted spectroscopy

Fatty acids are clearly larger in size and show markedly slower diffusion velocity than the small water (or creatine) molecules which have been examined so far by diffusion weighted NMR spectroscopy. However, assessment of diffusion properties of lipids could be a key step for further experimental studies of skeletal muscle lipid metabolism. Diffusion properties of FFA and triglycerides are likely different due to differences in molecular weight. In addition, effects of temperature, chemical surroundings, and the mobility of small lipid droplets in the cytosol may also lead to measurable differences in the diffusion characteristics. 

Z. Domingo, J. K. Bradley, K. Blamire, A. M. Brindle, P. Styles and B. Rajagopalan, Diffusion weighted imaging and magnetic resonance spectroscopy in a low flow ischaemia model due to endothelin induced vasospasm. NMR Biomed., 2000, 13, 154-162. 

Simpson, A. J. (2002). Determining the molecular weight, aggregation, structures and interactions of natural organic matter using diffusion ordered spectroscopy. Magn. Reson. Chem. 40, S72-S82. 

All the spectroscopic approaches applied for structural characterization of mixtures derive from methods originally developed for screening libraries for their biological activities. They include diffusion-ordered spectroscopy [15-18], relaxation-edited spectroscopy [19], isotope-filtered affinity NMR [20] and SAR-by-NMR [21]. These applications will be discussed in the last part of this chapter. As usually most of the components show very similar molecular weight, their spectroscopic parameters, such as relaxation rates or selfdiffusion coefficients, are not very different and application of these methodologies for chemical characterization is not straightforward. An exception is diffusion-edited spectroscopy, which can be a feasible way to analyze the structure of compounds within a mixture without the need of prior separation. This was the case for the analysis of a mixture of five esters (propyl acetate, butyl acetate, ethyl butyrate, isopropyl butyrate and butyl levulinate) [18]. By the combined use of diffusion-edited NMR and 2-D NMR methods such as Total Correlation Spectroscopy (TOCSY), it was possible to elucidate the structure of the components of this mixture. This strategy was called diffusion encoded spectroscopy DECODES. Another example of combination between diffusion-edited spectroscopy and traditional 2-D NMR experiment is the DOSY-NOESY experiment [22]. The use of these experiments have proven to be useful in the identification of compounds from small split and mix synthetic pools. 

Parsons MW, Li T, Barber PA et al. (2000). Combined (1)H MR spectroscopy and diffusion-weighted MRI improves the prediction of stroke outcome. Neurology 55 498-505... 

Murata T, Kimura H, Kado H, et al Neuronal damage in the interval form of CO poisoning determined by serial diffusion weighted magnetic resonance imaging plus lH-magnetic resonance spectroscopy. J Neurol Neurosurg Psychiatry 71 250-253, 2001... 

Kim, S.Y, et al., Neonatal hypoglycaemic encephalopathy diffusion-weighted imaging and proton MR spectroscopy. Pediatr Radiol, 2006. 36(2) p. 144-8. 

Diffusion-weighted magnetic resonance spectroscopy has been used by Xiao and Wu to study intramyocellular and extramyocellular lipids in vivo. These studies may provide new insights in the investigation of lipid metabolism in obesity and diabetes. 

More advanced techniques have been used effectively. Fogg has applied DOSY (diffusion-ordered spectroscopy)to separate the NMR signals for cyclic product and cyclic dimer in model RCM reactions such as that illustrated in Scheme 2.55. DOSY NMR resolves signals based on their diffusion coefficient one dimension of the resulting 2D spectra is the NMR spectrum, while the other is the diffusion coefficient (a time-bound parameter), which is related to molecular weight. Later, Sliwa showed that the same technique could be applied to discriminate between... 

DRIFT spectroscopy of microscopic amounts of dye mixtures extracted from small textile samples has been reported raw and pretreated data matrices were interpreted with the use of chemomet-rics (PCA, SIMCA, FC) [145]. DRIFTS can readily detect 200 ng quantities of pure, standard dyes. Bridge et al. [42] have qualitatively characterised acid dyes (Cl Acid Red 17, Red 18, Red 44, Red 88, Blue 45 and Yellow 17) applied to wool and nylon. Near-infrared diffuse reflectance spectroscopy was evaluated for its ability to analyse solid antioxidant blends [146]. These opaque materials do not transmit near-IR light. This fast method effectively predicts weight percentage composition with a precision comparable to the currently accepted HPLC method of analysis, and can identify blend types and contaminated materials. 

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