High-throughput NMR

Figure 8.2.2 (a) Schematic of the four-coil probehead introduced in Reference [12]. The four individual solenoidal coils are represented by an inductance (L), series resistance (R), and inter-turn capacitance (Q. The entire circuit was impedance-matched to 50 it at a frequency of 300 MHz by using the variable capacitors Ct and Cm. (b) Photograph of the four-coil assembly. Reprinted from MacNamara, E., Hou. T., Fisher, G., Wilhams, S. and Raftery, D., Multiplex Sample NMR an approach to high-throughput NMR using a parallel coil probe , Anal. Chem. Acta, 397, 9-16, copyright (1999), with permission of Elsevier Science... 

Dalvit, C., et al., High-throughput NMR-based screening with competition binding experiments. J Am Chem Soc, 2002,124, 7702-7709. 

The major bottleneck created by these high-throughput NMR techniques is in the analysis of the vast amount of data that is generated. A number of commercial packages are now available that use chemical shift/structure databases to aid in the interpretation of the spectra. However, fully automated spectral analysis systems are still under development. 

E. MacNamara, T. Hon, G. Eisher, S. Williams, and D. Raftery, Multiplex sample NMR An approach to high-throughput NMR using a parahel coh probe. Anal. Chim. Acta 397 (1999), 9-16. 

Dalvit C, Flocco M, Knapp S, Mostardini M, Perego R, Stockman BJ, Veronesi M, and Varasi M. High-Throughput NMR-Based Screening with Competition Binding Experiments./Am Chem Soc2002 124 7702-7709. 

This remains a non-trivial issue and represents one of the practical aspects in which sol-id-phase chemistry frequently poses a greater challenge than the corresponding solution-phase chemistry. High-throughput NMR spectroscopy and liquid chromatography-mass spectrometry (LC-MS) are now common place among the armamentarium of the synthetic chemist. 

Not all NMR data sets should be collected using a high-throughput NMR probe, because damping the probe s tuning response sacrifices... 

Mercier KA, Powers R (2005) Determining the optimal size of small molecule mixtures for high throughput NMR screening. J Biomol NMR 31(3) 243-258... 

HIGH-THROUGHPUT NMR TECHNIQUES FOR COMBINATORIAL CHEMICAL LIBRARY ANALYSIS... 

Recent developments in high-throughput NMR indicate that, with further development, parallel NMR techniques will play an important role in high-throughput chemical analysis and drug screening. 

While the authors demonstrated this approach with four parallel coils and line widths of 2 to 3 Hz per sample, the maximum number of parallel detection coils and the ultimate achievable resolution of this approach have yet to be determined. An issue that will limit very high numbers of parallel coils is the fact that the S/N varies as 1/Vij in this coil configuration, where n is the number of parallel coils. One can compensate by increasing the size of the coil volume, essentually trading some mass sensitivity for improved concentration sensitivity. Alternatively, the use of multiple resonant drcuits - or even switched coils can potentially overcome this limitation. The design of multicoil high-throughput NMR probes is currently an active area of research. 

Future applications of biocatalysis will be related to discovery of novel activities and substrate relationships (21). As mentioned earlier in this paper, high throughput NMR spectroscopy provides a mechanism to discover such new enzymatic activities and chemistry. To date, this technology has been applied to substrate bioconversions. However, the application can be extended to the discovery of biocatalysis applications to polymer science. 

R. E. Hopson and W. Peti, Microcoil NMR Spectroscopy A Novel Tool for Biological High Throughput NMR Spectroscopy , in Methods in Molecular Biology (Totowa, NJ, United States), eds. B. Kobe, M. Guss and T. H. Huber, Humana Press Inc., 2008, vol. 426, Structural Proteomics, p. 447. 

T. Hou and D. Raftery, High-Throughput NMR Techniques for Combinatorial Chemical Library Analysis , Chem.Anal., 2004,163,139... 

Radical Polymerization , Chinese J.Polym.Sci., 2004,22,99 R 482 J.R. Quine, T.A. Cross, M.S. Chapman and R. Bertram, Mathematical Aspects of Protein Structure Determination with NMR Orientational Restraints , B.Math.Biol., 2004,66,1705 R 483 D. Raftery, High-Throughput NMR Spectroscopy , Anal.Bio-anal.Chem., 2004,378,1403... 

R 630 T. Kohno, High Throughput NMR Analyses of Protein Three-Dimensional Structures , Seikagaku, 2004,76,1443... 

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