Flow NMR spectroscopy

Important progress in terms of higher throughput in ADME/PK work was realized recently by wider use of liquid chromatography/mass spectrometry (LC/MS), which has now become a standard analytical tool [26]. Flow NMR spectroscopy has become a routine method to resolve and identify mixtures of compounds and has found applications in drug metabolism and toxicology studies [27]. 

Table 1.1 Variation of residence time and line broadening as a function of detection cell volume and flow rate in continuous-flow NMR spectroscopy.

B. J. Stockman, Flow NMR Spectroscopy in Drug Discovery , p. 269 A. Williams, Recent Advances in NMR Prediction and Automated Structure Elucidation Software , p. 298... 

Flow NMR spectroscopy allows investigations of reaction processes nearly in real time and under process conditions in a wide temperature and pressure range. Modem multipulse and PFG NMR experiments can be used, which increase the quahty of the data and reduce the experiment time. Typical commercial NMR probe flow cells have an active volume of 60-120[i.l and a total volume of about 120-240 ]tl, which is significantly smaller than that of about 600 ]tl of conventional 5 mm tubes, and a small fraction of the total reactant volume. 

R. E. Collins, Flow of Fluids through Porous Materials, Reinhold, New York, 1961. C. Dyhowski and R. L. Lichter, eds., NMR Spectroscopy Techniques, Marcel Dekker,... 

NMR spectroscopy finds a number of applications in chemical kinetics. One of these is its application as an analytical tool for slow reactions. In this method the integrated area of a reactant, intermediate, or product is determined intermittently as the reaction progresses. Such determinations are straightforward and will not concern us further, except to note that the use of an internal standard improves the accuracy. With flow mixing, one may examine even more rapid reactions. This is simply overflow application of the stopped-flow method. 

A study on the effectiveness of the E-plastomers as impact modifiers for iPP was carried out in relation to the traditional modifier EPDM. In this study, the flow properties of the E-plastomer-iPP and EPDM-PP blends were also evaluated. The blends were analyzed by solid-state 13C-nuclear magnetic resonance (NMR) spectroscopy, microscopy (SEM), and DSC. The results showed that E-plastomer-PP and EPDM-PP blends present a similar crystallization behavior, which resulted in a similar mechanical performance of the blends. However, the E-plastomer-PP blend presents lower torque values than the EPDM-PP blend, which indicates a better processibility when E-plastomer is used as an impact modifier for iPP. 

Although limited by sensitivity, chemical reaction monitoring via less sensitive nuclei (such as 13C) has also been reported. In 1987 Albert et al. monitored the electrochemical reaction of 2,4,6-tri-t-butylphenol by continuous flow 13C NMR [4]. More recently, Hunger and Horvath studied the conversion of vapor propan-2-ol (13C labeled) on zeolites using 1H and 13C in situ magic angle spinning (MAS) NMR spectroscopy under continuous-flow conditions [15]. 

In order to illustrate the potential applications of rheo-NMR five examples have been chosen. The first example deals with wormlike micelles [22] in which NMR velocim-etry is used to profile anomalous deformational flow and deuterium NMR spectroscopy is used to determine micellar ordering in the flow. The second example concerns flow in a soft glassy material comprising a solution of intermittently jammed star polymers [23], a system in which flow fluctuations are apparent. The third... 

Fig. 5.3.10 (A) Polarization obtained contin- lasers (squares). (B) Actual intensities as uous-flow hp-xenon experiment as a function of measured by 129Xe NMR spectroscopy at xenon partial pressure for two different laser 110.69 MHz using 29-W laser power (triangles) powers, i.e., one 30-W diode array laser (tri- and full laser power (squares). Adapted from angles) and two combined 30-W diode array Ref. [16].

Hyphenation of chromatographic separation techniques (SFC, HPLC, SEC) with NMR spectroscopy as a universal detector is one of the most powerful and time-saving new methods for separation and structural elucidation of unknown compounds and molecular compositions of mixtures [171]. Most of the routinely used NMR flow-cells have detection volumes between 40... 

Systems have been developed by some of the major spectrometer manufacturers to deal specifically with this type of application. These systems are designed with automation very much a priority. Typically, an integrated robot adds a predetermined volume of solvent to each of the wells and then injects the resultant solution into a flow line that transfers it into the spectrometer s probe, which is of course fitted with a flow cell. Spectroscopy can then be performed without the time constraints of the HPLC-NMR system and the sample returned to the well on the plate where it came from, or into a fresh one if required. 

Fitzpatrick, S. M., Hetherington, H. P, Behar, K. L. etal. The flux from glucose to glutamate in the rat brain in vivo as determined by H-observed, 13C-edited NMR spectroscopy. /. Cereb. Blood Flow Metab. 2 170-179,1990. 

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