Liquid-state NMR spectroscopy

The problems involved in quantitative analysis using NMR spectroscopy, have been discussed by several authors and it is evident that it still causes a lot of problems as especially pointed out by Hays55 in his excellent review on the subject. Thus in liquid state NMR spectroscopy the quantitative estimation of atoms and groups involves the use of normal analytical method. In the case of solid state NMR spectroscopy, however, the application of the cross-polarization technique results in signal enhancements and allows repetition rates faster than those allowed by the carbon C-13 Tl. Therefore, the distortion of relative spectral intensities must always be considered a possibility, and hence quantitative spectra will not always be obtained. 

In liquid-state NMR spectroscopy only the isotropic component of the chemical shift tensor is measurable. Upon ahgnment the situahon changes and the so-called zz-component of the chemical shift tensor includes anisotropic components. 

Microporous nanoparticles with ordered zeolitic structure such as Ti-Beta are used for incorporation into walls or deposition into pores of mesoporous materials to form the micro/mesoporous composite materials [1-3], Microporous particles need to be small enough to be successfully incorporated in the composite structure. This means that the zeolite synthesis has to be stopped as soon as the particles exhibit ordered zeolitic structure. To study the growth of Ti-Beta particles we used 29Si solid-state and liquid-state NMR spectroscopy combined with x-ray powder diffraction (XRPD) and high-resolution transmission electron microscopy (HRTEM). With these techniques we monitored zeolite formation from the initial precursor gel to the final Ti-Beta product. 

Liquid-state NMR spectroscopy (Davidson and Ripmeester, 1984) Yes Water mobility vs. time (mins) 15 psi Reorientation and diffusion... 

Biomolecular NMR spectroscopy is applicable to both liquid-and solid-state samples. Liquid-state NMR spectroscopy, in which molecules are dissolved in a variety of different solvents and studied at ambient temperatures, is a powerful tool to derive information on the stmcture of proteins and nucleic acids, as well as their complexes with each other and small molecules, ions, and solvents. Liquid-state NMR can be applied not only to native folded states of proteins, but also to intrinsically unstmctured proteins as well as proteins in their unfolded state and under nonphysiological conditions (i.e., in organic solvents). Figure 1 provides an overview on the number of protein structures determined by liquid-state NMR spectroscopy. 

In this review, we present the basic observables and tools in liquid-state NMR spectroscopy followed by examples of the application of NMR in chemical biology. We will focus on the application of NMR spectroscopy to study proteins in solution. 

The following discussion focuses exclusively on what is termed small molecules in the industry, namely compounds with a molecular mass on the order of 1000 Da or less. The study of proteins, polymers, and other such macromolecules by NMR warrants an entirely different approach that is beyond the scope of this book. Similarly, we will restrict our discussion to liquid-state NMR spectroscopy, since solid-state NMR techniques are discussed elsewhere in this book (see Chapter 3). 

To illustrate the power of PISA wheels and dipolar waves to determine the structure of helical peptides and proteins in uniaxiaUy oriented lipid bilayers. Fig. 6a-c show SIMPSON/SIMMOL-simulated PISEMA spectra of an ideal 18-residue a-helix with a tilt angle of 10°-30° relative to Bq. In these simulations, we have tried to mimic experimental conditions by including a random distribution of the principal components of the chemical shift tensor and the dipolar coupling. The chemical shift distribution is 6 ppm for each principal element and has been established as follows we obtained — 85000 N isotropic chemical shifts reported to the BioMagResBank and selected only the — 31000 located in helical secondary stractures to have a data set independent on secondary chemical shifts. The standard deviation on the N chemical shifts for these resonances was — 6 ppm. With the lack of other statistically reliable experimental methods to establish such results for the individual principal elements of the N CSA tensor, we assumed the above variation of 6 ppm for all three principal elements. The variation of the H- N dipolar coupling was estimated by investigating the structures for a small number of a-helical membrane proteins for which the structures were established by liquid-state NMR spectroscopy. These showed standard deviations... 

T. Vosegaard, A. Malmendal and N. C. Nielsen, The flexibility of SIMPSON and SIMMOL for numerical simulations in solid and liquid-state NMR spectroscopy. Chem. Monthly, 2002, 133, 1555-1574. 

The dipolar coupling allows one to obtain distance information that can be used to confirm signal assignment or to elucidate phase separation. Solid state NMR is then a powerful method for investigating molecular conformation and geometry in large molecular systems. The technique is able to provide information about protein structure of membrane, biomaterials and polymers that are not accessible with X-Ray or liquid state NMR spectroscopy. 

In the follo ving three experimental examples of such quantum mechanical exchange processes are discussed. The examples are taken from liquid state NMR spectroscopy, solid state NMR spectroscopy and INS. 

Slow Tunneling Determined by Liquid State NMR Spectroscopy... 

Kristiansen, S.M., Amelung, W. and Zech, W. (2001) Phosphorus forms as affected by abandoned anthills Formica polyctena Forster) in forest soils sequential extraction and liquid-state NMR spectroscopy. Zeitschrift fur Pflanz-enernahrung und Bodenkunde 1 64, 49-55. 

Dynamics in the p38a MAP kinase-SB203580 complex observed by liquid-state NMR spectroscopy. Angewandte Chemie - International Edition in English, 47, 3548-3551. 

Recent developments of DNP have shown great potential in solid-state and liquid-state NMR spectroscopy and in MRI. As promising as DNP is, the future development of hyperpolarization transition may require great improvement in the following aspects ... 

In this system, the adsorption of the stabilizer was characterized throroughly employing various spectroscopic techniques. Especially, H and C liquid state NMR spectroscopy proved as a useful probe for the surface chemistry of nanoparticles in concentrated dispersions, as species adsorbed to the surface can be identified, however the functional groups directly adjacent to the surface are motionally hindered, which results in spectral broadening [85], It is hence possible to assess the amount of surface-bound species, determine the functional groups binding to the particle surface, and qualitatively investigate the chemistry of both particle surface and bulk solution. In the zirconia case, it was detected that indeed only partially the initially bound benzyl alcohol solvent is replaced by the stabilizer... 

In liquid-state NMR spectroscopy, the anisotropic interactions cannot be seen directly due to the rapid tumbling of the molecule. In soHd-state NMR, an ingenious technique called MAS averages out anisotropic interactions, leaving behind mainly isotropic interactions. Unless specified, we will only consider MAS experiments in this contribution. Due to the periodic motions induced by MAS, the NMR interactions can be expended into a Fourier series in units of the rotor frequency, using zeroth-, first-, and second-order terms. Addressing the chemical shift interaction, we can write the Flamiltonian as... 

Steelink, C., R. L. Wershaw, K. A. Thom, and M. A. Wilson. 1990. Chapter 10 Application of liquid-state NMR spectroscopy to humic substances. In Humic Substances II In Search of Structure, ed. M. H. B. Hayes, R. L. Malcolm, P. MacCarthy, and R. S. Swift. 1st ed. Hohoken, NJ John Wiley Sons. 

It is the orientational dependence of the dipolar coupling that limits its role in liquid-state NMR spectroscopy. The reorientation time of a molecule in solution is... 

However, liquid-state NMR spectroscopy provides a clue telling us how the effects of the CSA can be eliminated. In liquids, molecules randomly and rapidly sample the ftill range of orientations, so that even a strongly asymmetric electron distribution will appear spherical when it is viewed on the NMR timescale. One can divide the chemical-shift Hamiltonian Hcs into an isotropic term and an anisotropic term. 

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