Applications Of Solid-state NMR Research Articles

Progress in development and application of solid-state NMR for solid acid catalysis

Solid acid catalysts have been widely used in petrochemical industry and their catalytic activities are normally dictated by their acidities. Unlike conventional acidity characterization techniques such as titration, infrared, or temperature-programmed desorption, detailed acid features of solid acids, such as type, distribution, concentration, and strength of acid sites may be attained by advanced methods involving pertinent probe molecules and state-of-the-art solid-state nuclear magnetic resonance (SSNMR) techniques, i.e. double resonance and two-dimensional correlation spectroscopies. In addition, in situ solid-state NMR method is capable of probing the guest/host properties of the reactant at the active centers of the catalysts as well as the intermediate species formed during conversion. It provides direct experimental evidence for exploring the mechanism of catalytic reaction. In this report, the fundamental theory and the recent developments in solid-state NMR are reviewed with specific focus on relevant applications in structure and acidity characterization of solid acid catalysts and catalytic mechanisms.

Modified lipid and protein dynamics in nanodiscs

For membrane protein studies, nanodiscs have been shown to hold great potential in terms of preparing soluble samples while maintaining a lipid environment. Here, we describe the differences in lipid order and protein dynamics in MSP1 nanodiscs compared to lamellar preparations by solid-state NMR. For DMPC, an increase of the dipolar C-H lipid acyl chain order parameters in nanodiscs is observed in both gel- and liquid crystalline phases. Incorporating proteorhodopsin in these nanodiscs resulted in a significantly longer rotating frame spin-lattice relaxation time for 13C leerzeichen and better cross polarisation efficiency due to restricted protein dynamics. A comparison of 13C–13C correlation spectra revealed no structural differences. The incorporation of proteorhodopsin into nanodiscs has been optimised with respect to detergent and to protein/scaffold protein/lipid stoichiometries. Its functional state was probed by time-resolved optical spectroscopy revealing only minor differences between lamellar and nanodisc preparations. Our observations show remarkable dynamic effects between membrane proteins, lipids and scaffold protein. The potential use of nanodiscs for solid-state NMR applications is discussed.

Application of single-pulse solid-state 1H-MAS NMR to probe the oxidation products in crosslinked polyethylene: A detailed spectral analysis procedure

A spectral analysis procedure for single-pulse 1H-MAS spectra acquired at 20 kHz MAS-rate is presented and thoroughly discussed and demonstrates that all relevant functional groups can be identified and quantified. In particular, the present technique finds special application in the analysis of oxidation products formed during ageing of cross-linked polymers, which are generally difficult or impossible to study by solution state NMR, since these polymers are mostly insoluble.The main objective and advantages of applying 1H-MAS solid-state NMR compared to liquid state 13C NMR are related to; 1) a much shorter experimental sampling time, on the order of a few minutes, 2) the bypass of sample preparation, as compared to traditional high-resolution liquid state 13C NMR which requires a high temperature (130 °C) preparation period of days, or even weeks and 3) the technique is non-destructive. Finally, the present technique gives a much easier access to quantitative information compared to solid-state 13C-CPMAS NMR.

Application of Solid-State NMR in Characterization of Bone Related Tissue Engineering

Solid-state NMR has the potential to contribute to the quality of monitoring of the in growth of synthetic biomaterials in bone related tissue engineering. Severe experimental difficulties arise from the morphological diversity of bone, from the coexistence, interrelationship and great complexity of its organic and inorganic components, and lastly, from the substantial sensitivity of bone samples to physical and chemical effects. High-resolution solid-state NMR gives us the opportunity to look specifically at selected magnetic nuclei in whole bone without any chemical pretreatment, thus avoiding interference with bone structure. Solid-state NMR spectroscopy is thus an excellent tool to obtain such high-resolution information on bone samples not subjected to any chemical pretreatment. This short review has thus discussed current application of solid-state NMR in characterization of bone related tissue engineering.

Editorial management of the Journal of Biomolecular NMR

A change at the helm, but staying on course. In 2011, the Journal of Biomolecular NMR completed its twentieth year of successful publication, during which time the journal has played an important role in advancing the use of NMR in molecular biology. Under the leadership of the founding Editor-in-Chief, Kurt Wuthrich, J. Biomol. NMR has seen good times in the early days as well as hard times when the impact factor dropped due to assessment glitches. Thanks to the efforts of Kurt, the journal has climbed back up the rankings and is now again in very good shape. I had always personally believed that Kurt Wuthrich would lead the journal forever, and as such, it came as a surprise when I received the message that he had decided to step down at the end of 2011. An even greater surprise was to follow, when the publisher approached me to take over from him; a hard act to follow. After much deliberation, I wholeheartedly agreed to accept the position. I have been Associate Editor for several years now and J. Biomol. NMR plays an important role in the area of science which is very dear to me. In my new capacity as Editor-in-Chief, I will do my utmost to maintain the high quality standards and together with a great team of Associate Editors, a supportive Editorial Advisory board and all the Journal’s contributors and readers, a successful future for the Journal of Biomolecular NMR is ensured. A change in Editorial structure also represents an opportunity to think about changes that could be made to improve the journal further. The first thing that we have decided to change is a switch to an online manuscript submission system. The current submission system has had the advantage of a personal interaction with the Associate Editors of the submitters’ choice, compared to the more anonymous submission to an online submission system. However, authors will still be able to direct their papers to their Editor of choice and will be able to track the progress of their papers through the peer-review process. The format of J. Biomol. NMR will not change and we will continue to publish all manuscripts online and in print. We will of course be keeping an eye on developments in the publishing world and given the increasing migration from print to electronic, we cannot exclude that at some time in the future J. Biomol. NMR will be published exclusively online. J. Biomol. NMR already has the online advantages of being able to publish large datasets and animations which can visualize the time course of coherences in pulse sequences or rotating structures. Together with the team of Associate Editors, I have also thought about new trends in our field of science and the opportunities that these may hold for the journal. For example, the number of papers on biological applications of solid state NMR has greatly increased in recent years and we will carefully follow this trend and where needed will adapt our scope and direction. J. Biomol. NMR will continue to publish regular papers, communications, structure notes and invited perspectives, and will also continue to produce special issues on a variety of topics. The special issues that have been published over the last few years have proved very popular. We are also thinking about new formats of publication that would make data concerning solution NMR more routinely usable for novices and users with a primary background in biology. G. Wagner (&) Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood, Avenue, Boston, MA 02115, USA e-mail: gerhard_wagner@hms.harvard.edu

Application of the solid state NMR to the study of the alcohol/alkane mixtures adsorption onto graphite

The mixing of molecules adsorbed from solution to different interfaces has both industrial and academic relevance and the mixing behaviour at the interface is a key to understanding for example, that the surface tension of a mixture of two surfactants is lower than either of the two pure materials and many other effects. In this paper, we report, for the first time, the application of Solid State NMR to the study of alkane/alcohol mixtures, in a range of relative size ratio between 0 and 0.35, adsorbed onto graphite at high, multilayer coverage. Moreover, this paper evaluated, for the first time, the utility of the combined used of 1H and 2H NMR for: (i) determining the surface composition and (ii) making a theoretical approach to the sorption isotherm. A variety of preferential adsorption behaviour is reported. Preferential adsorption of the longer molecule (decane vs. heptanol) from a mixture has been observed. However, if both components are of similar length, the alcohol is preferentially adsorbed (heptanol vs. octane and octanol vs. octane). Finally, a linear relation between the relative size ratio and the amount of alcohol at monolayer coverage is observed.

Solid-state magic-angle spinning NMR of membrane proteins and protein–ligand interactions

Structural biology is developing into a universal tool for visualizing biological processes in space and time at atomic resolution. The field has been built by established methodology like X-ray crystallography, electron microscopy and solution NMR and is now incorporating new techniques, such as small-angle X-ray scattering, electron tomography, magic-angle-spinning solid-state NMR and femtosecond X-ray protein nanocrystallography. These new techniques all seek to investigate non-crystalline, native-like biological material. Solid-state NMR is a relatively young technique that has just proven its capabilities for de novo structure determination of model proteins. Further developments promise great potential for investigations on functional biological systems such as membrane-integrated receptors and channels, and macromolecular complexes attached to cytoskeletal proteins. Here, we review the development and applications of solid-state NMR from the first proof-of-principle investigations to mature structure determination projects, including membrane proteins. We describe the development of the methodology by looking at examples in detail and provide an outlook towards future ‘big’ projects.

Solid state NMR study of hydrogen bonding, miscibility, and dynamics in multiphase polymer systems

The application of solid state NMR (SS NMR) to the study of multiphase polymer systems is growing rapidly. This article aims to provide an overview of the current state of development of this field, paying particular attention to the study of hydrogen bonding in hydrogen-bonded polymer materials through SS NMR investigations. The effection of hydrogen bonds on the miscibility, phase separation and dynamic behavior of selected systems will also be discussed, based on work during the last 10 to 15 years.

ChemInform Abstract: Operator‐Based Floquet Theory in Solid‐State NMR

AbstractReview: 92 refs.

Detection of low-level PTFE contamination: An application of solid-state NMR to structure elucidation in the pharmaceutical industry

We report a novel use of solid-state 19F nuclear magnetic resonance to detect and quantify polytetrafluoroethylene contamination from laboratory equipment, which due to low quantity (up to 1% w/w) and insolubility remained undetected by standard analytical techniques. Solid-state 19F NMR is shown to be highly sensitive to such fluoropolymers (detection limit 0.02% w/w), and is demonstrated as a useful analytical tool for structure elucidation of unknown solid materials.

ChemInform Abstract: Low-Temperature Solid-State NMR of Proteins

In surveying the literature of solid-state NMR it is striking that the ratio of reviews to original publications is unusually high. We believe that this reflects on the one hand the evident great potential of this technique for the study of chemical and biological systems, and on the other the formidable technical obstacles to be overcome in obtaining useful results. Despite some reluctance to worsen the review/publication ratio still further, we hope in this article to address, in particular, the community of potential users of solid-state NMR in biology, providing a survey of the area that highlights the practical problems and the means by which they may be tackled, and outlining the results obtained to date within the title field. It is not the intent to provide a comprehensive discussion of the physical hasis of solid-state NMR, which may readily he obtained from other sources,lb but a brief qualitative discussion is included to set the context. Likewise, some selected experimental techniques are described in section IV, but this is not intended to be a complete survey. Reviews of the technique of solid-state NMR can be found elsewhere.?,8 There are also prior reviews of the application of solid-state NMR to biological macromolecules>1° peptides, and proteins.12 In these introductory sections we have in mind in particular those who are quite familiar with NMR experiments in solution, and 90 we try to emphasize both the similarities and the differences between the two states.

Broadband heteronuclear dipolar recoupling without 1H decoupling in solid-state NMR using simple cross-polarization methods

Heteronuclear dipolar recoupling experiments without 1H decoupling based on simple cross polarization are introduced for applications in biological solid-state NMR. It is shown that standard or adiabatic variants of the cross-polarization experiment with irradiation on the low-γ (e.g., 13C, 15N) spins even at modest spinning frequencies enable efficient band-selective or broadband dipolar recoupling without the need for intense 1H decoupling. This facilitates experiments on expensive isotope-labelled protein samples for which sample heating by intense 1H decoupling may lead to sample detoriation. The principle is demonstrated numerically and experimentally on uniformly 13C, 15N-labelled samples of GB1 and fibrils of hIAPP (20–29) from the human islet amyloid labelled on the FGAIL part.

Applications of solid-state NMR to pharmaceutical polymorphism and related matters

Magic-angle spinning NMR is now making a significant contribution to our understanding of the structure of polymorphs and solvates of pharmaceutical significance. This personal review article discusses a range of applications, with particular emphasis on information about crystallography, for which NMR can address problems that cannot be readily solved by diffraction techniques (such as dynamic disorder and non-stoichiometric hydration). Unlike diffractograms, NMR spectra yield immediate chemical information. Moreover, heterogeneous samples can be investigated and amorphous content provides no significant barrier to studies. Furthermore, NMR can be an effective technique for quantitation (down to the level of ca. 1%). Additional strength is being derived from computation of chemical shifts in solids, using a code that takes account of the spatial repetition inherent in crystalline materials.

Comparative analysis of NMR chemical shift predictions for proteins in the solid phase

A comparative analysis of nuclear chemical shift predictions of proteins in the solid state by rapid algorithms trained on and verified with solution-state NMR assignments is presented. The precision of predictions by four dedicated computer programs (SHIFTS, PROSHIFTS, SHIFTX and SPARTA) was found to be close to values obtained for proteins in solution. Correlation coefficients depend on the NMR nucleus (N, C′, C α and C β) and on secondary structure (β-strand, random coil and α-helix), but also on the molecular environment (membrane-integral or not). The findings establish a quantitative basis for using chemical shift prediction programs for solid-state NMR applications. On the other hand, prediction inaccuracies identified for certain resonance kind, residue type, and molecular environment point to possible areas of methodological improvement.

Applications of Solid-State NMR to the Study of Organic/Inorganic Multicomponent Materials

The characterization of a variety of organic/inorganic multicomponent materials (OIMM) through solid-state NMR (SSNMR) spectroscopy will be reviewed. Many examples of applications to OIMM will be described, based on the observation of different nuclei and the use of various SSNMR methods, such as 1D and 2D techniques, measurements on relaxation and spin diffusion processes. OIMM are a very general category of systems differing, for example, by chemical nature and relative amount of organic and inorganic components, shape and size of the domains, and type of organic-inorganic interface. Some of the most investigated classes of OIMM are organically modified silicates, polymer/clay composites, polymer/inorganic filler systems, polymer electrolytes, stationary chromatographic phases, zeolites, and mesoporous silicas including small organic molecules. The aspects most efficiently investigated by SSNMR and discussed in this review include physical and/or chemical interactions occurring at the organic-inorganic interface, structural and dynamic behavior of the organic components, and dimensions and dispersion of organic and inorganic domains.

Solid-state NMR studies of weak interactions in supramolecular systems

The field of application of solid-state NMR to the study of supramolecular systems is growing rapidly, with many research groups involved in the development of techniques for the study of crystalline and amorphous phases. This Feature Article aims to provide an overview of the recent contributions of our research group to this field, paying particular attention to the study of the weak interactions such as hydrogen bonds in supramolecular systems through solid-state NMR investigations. The structure and dynamic behaviour of selected host-guest systems will be also discussed.

Resonator with reduced sample heating and increased homogeneity for solid-state NMR

In the application of solid-state NMR to many systems, the presence of radiofrequency (rf) electric fields inside classical solenoidal coils causes heating of lossy samples. In particular, this is critical for proteins in ionic buffers. Rf sample heating increases proportional to frequency which may result in the need to reduce the rf pulse power to prevent partial or total sample deterioration. In the present paper, we propose a multifrequency-tunable NMR resonator where the sample is electrically shielded from the NMR coil by a conductive sheet that increases the magneto-electric ratio. Expressions for the B 1 efficiency as function of magnetic and electric filling factors are derived that allow a direct comparison of different resonators. Rf efficiency, homogeneity, signal-to-noise, and rf sample heating are compared. NMR spectra at 700 MHz on ethylene glycol, glycine, and a model protein were acquired to compare the resonators under realistic experimental conditions.

Four-dimensional heteronuclear correlation experiments for chemical shift assignment of solid proteins

Chemical shift assignment is the first step in all established protocols for structure determination of uniformly labeled proteins by NMR. The explosive growth in recent years of magic-angle spinning (MAS) solid-state NMR (SSNMR) applications is largely attributable to improved methods for backbone and side-chain chemical shift correlation spectroscopy. However, the techniques developed so far have been applied primarily to proteins in the size range of 5-10 kDa, despite the fact that SSNMR has no inherent molecular weight limits. Rather, the degeneracy inherent to many 2D and 3D SSNMR spectra of larger proteins has prevented complete unambiguous chemical shift assignment. Here we demonstrate the implementation of 4D backbone chemical shift correlation experiments for assignment of solid proteins. The experiments greatly reduce spectral degeneracy at a modest cost in sensitivity, which is accurately described by theory. We consider several possible implementations and investigate the CANCOCX pulse sequence in detail. This experiment involves three cross polarization steps, from H to CA[i], CA[i] to N[i], and N[i] to C'[i-1], followed by a final homonuclear mixing period. With short homonuclear mixing times (<20 ms), backbone correlations are observed with high sensitivity; with longer mixing times (>200 ms), long-range correlations are revealed. For example, a single 4D experiment with 225 ms homonuclear mixing time reveals approximately 200 uniquely resolved medium and long-range correlations in the 56-residue protein GB1. In addition to experimental demonstrations in the 56-residue protein GB1, we present a theoretical analysis of anticipated improvements in resolution for much larger proteins and compare these results in detail with the experiments, finding good agreement between experiment and theory under conditions of stable instrumental performance.

Optimal control based NCO and NCA experiments for spectral assignment in biological solid-state NMR spectroscopy

We present novel pulse sequences for magic-angle-spinning solid-state NMR structural studies of 13C, 15N-isotope labeled proteins. The pulse sequences have been designed numerically using optimal control procedures and demonstrate superior performance relative to previous methods with respect to sensitivity, robustness to instrumental errors, and band-selective excitation profiles for typical biological solid-state NMR applications. Our study addresses specifically 15N to 13C coherence transfers being important elements in spectral assignment protocols for solid-state NMR structural characterization of uniformly 13C, 15N-labeled proteins. The pulse sequences are analyzed in detail and their robustness towards spin system and external experimental parameters are illustrated numerically for typical 15N– 13C spin systems under high-field solid-state NMR conditions. Experimentally the methods are demonstrated by 1D 15N → 13C coherence transfer experiments, as well as 2D and 3D 15N, 13C and 15N, 13C, 13C chemical shift correlation experiments on uniformly 13C, 15N-labeled ubiquitin.

Rational Design of Vector and Antibiotic Peptides Using Solid-State NMR

The application of 2H solid-state NMR in determining structure activity relationships and mechanism of action of membrane active peptides is discussed. The enhancement of the disruption of anionic lipids in the membrane by new lead compounds is shown to be a key determinant of both DNA vector and antimicrobial activity.