Microcoil-NMR

FIGURE 4.5 Schematic design of a microcoil NMR probe. (From Rehbein, J. et al., Characterization of Bixin by LC-MS and LC-NMR, John Wiley Sons Ltd., 2387, 2007. With permission.)... 

Figure 7.3.1.8 Instrumental configuration for mass-limited characterization by microcoil NMR. The analyte is bracketed on both sides by plugs of an immiscible perfluorinated organic liquid and sealed with an optically curable glue to prevent dilution during the data-collection period...

As techniques for chemical analysis are used in continually smaller domains, experimental challenges for inherently insensitive methods such as NMR spectroscopy become increasingly severe. Among the various schemes to boost the intrinsic sensitivity of an NMR experiment, the development of small-volume RF probes has experienced a renaissance during the past decade. Commercial NMR probes now allow analyses of nanomole quantities in microliter volumes from natural product extracts and combinatorial chemical syntheses. Figure 7.3.1.9 illustrates the range of volumes that can be examined by NMR probes and accessories such as microsample tubes and inserts. With recently reported advances in sample preconcentration for microcoil NMR analysis [51], dilute microliter-volume samples can now be concentrated into nanoliter-volume... 

Although not at capillary level nor a physical separation, Johnson and He first introduced the combination of electrophoresis and NMR (E-NMR) to study electrophoretic mobilities and diffusion coefficients [27], Sweedier and coworkers described the first application of microcoil NMR probe as an on-line detector for CE [13,28], In 1998 Bayer, Albert, and co-workers reported the first CEC/NMR experiments which also included CE/NMR and capillary LC/ NMR results [29],... 

Figure 6 Instrumental schematic of CE with two-microcoil NMR detection showing the arrangement of the separation capillary, the two outlet capillaries, and the two NMR detection coils. (Reprinted with permission from Ref. 43. Copyright 2002 American Chemical Society.)...

Olson, D.L. Lacy, M.E. Sweedler, J.V. High resolution microcoil NMR for analysis of mass-limited, nanoliter samples. Anal. Chem. 1998, 70, 645-650. 

With this technique, the volume of the chromatographic peak is comparable with the volume of the microcoil NMR flow cell. 

New approaches to source novel compounds from untapped areas of biodiversity coupled with the technical advances in analytical techniques (such as microcoil NMR and linked LC-MS-NMR) have removed many of the difficulties when using natural products in screening campaigns. As the chemical space occupied by natural products is both more varied and more drug-like than that of combinatorial chemical collections, synthetic and biosynthetic methods are being developed to produce screening libraries of natural product-like compounds. A renaissance of drug discovery inspired by natural products can be predicted.2... 

R Subramanian, WP Kelley, PD Floyd, ZJ Tan, AG Webb, JV Sweedler. A microcoil NMR probe for coupling microscale HPLC with on-line NMR spectroscopy. Anal Chem 71 5335-5339, 1999. 

Peti W, Norcross J, Eldridge G, O Neil-Johnson M (2004) Biomolecular NMR using a microcoil NMR probe - new technique for the chemical shift assignment of aromatic side chains in proteins. J Am Chem Soc 126 5873-5878... 

Jayawickrama, D. A. and Sweedler, J. V., Dual microcoil NMR probe coupled to cychc CE for continuous separation and analyte isolation. Anal. Chem., 76, 4894, 2004. 

Strength and the sample concentration, po is the permeability of free space, Q is the quality factor of the coil, coo is the Larmor angular frequency, K is the volume of the coil, F is the noise figure of the preamplifier, k is Boltzmann s constant, is the probe (as opposed to sample) temperature, and A/is the bandwidth (in Hz) of the receiver. It can be seen that the concentration sensitivity 5c (SIN per pM concentration of analyte) is poor for microcoils. This is due to the fact that microcoil probes have very small observation volumes and therefore contain a very small amount of analyte. However, if the sample can be concentrated into a small volume, then the microcoil can more easily detect the signal. This high mass sensitivity 5m (SIN per pmol of analyte) is characteristic of microcoil NMR probes. In essence, the use of microcoil probes enhances the mass sensitivity 5m at the expense of the concentration sensitivity 5c. To better understand the relationship between sensitivity and coil diameter, a detailed analysis was reported by Peck et Their results showed that mass sensitivity increases monotonically with decreasing coil diameter within the 1mm to 50 pm range they studied. However, the concentration sensitivity decreases, and therefore there is a trade-off between Sc and 5m that depends on coil diameter. 

With the development of microcoil NMR techniques, it is now possible to couple NMR with some microseparation techniques, such as microbore L( 86,93,io3 capillary electrophoresis (CE), and capillary electrochro-matogrphy (CEC), where the inner diameters of the separation channels are in the range of 20 to 75 pm. After coupling these small separation channels with NMR microcoils whose diameters are in the same range, it is possible to achieve maximum mass sensitivity for NMR detec-... 

M. E. Lacey, A. G. Webb, J. V. Sweedler, On-line temperature monitoring in a capillary electrochromatography frit using microcoil NMR. Anal. Chem., 2002,... 

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