News & Updates

Efficient Cross-Effect Dynamic Nuclear Polarization without Depolarization in High-resolution MAS NMR

posted Oct 6, 2017, 8:51 AM by Daniel Lee   [ updated Oct 23, 2017, 12:27 AM ]

Efficient Cross-Effect Dynamic Nuclear Polarization without Depolarization in High-resolution MAS NMR. Dynamic nuclear polarization (DNP) has the potential to enhance the sensitivity of magic-angle spinning (MAS) NMR by many orders of magnitude and therefore to revolutionize atomic resolution structural analysis. Currently, the most widely used approach to DNP for studies of chemical, material, and biological systems involves the cross-effect (CE) mechanism, which relies on biradicals as polarizing agents. However, at high magnetic fields (≥ 5 T), the best biradicals used for CE MAS-DNP are still far from optimal, primarily because of the nuclear depolarization effects they induce. In the presence of bisnitroxide biradicals, magic-angle rotation results in a reverse CE that can deplete the initial proton Boltzmann polarization by more than a factor of 2. In this paper we show that these depolarization losses can be avoided by using a polarizing agent composed of a narrow-line trityl radical tethered to a broad-line TEMPO. Consequently, we show that a biocompatible trityl-nitroxide biradical, TEMTriPol-1, provides the highest MAS NMR sensitivity at ≥ 10 T, and its relative efficiency increases with the magnetic field strength. We use numerical simulations to explain the absence of depolarization for TEMTriPol-1 and its high efficiency, paving the way for the next generation of polarizing agents for DNP. We demonstrate the superior sensitivity enhancement using TEMTriPol-1 by recording the first solid-state 2D 13C-13C correlation spectrum at natural isotopic abundance at a magnetic field of 18.8 T.

Efficient 2D double-quantum solid-state NMR spectroscopy with large spectral widths

posted Aug 4, 2017, 1:30 AM by Daniel Lee   [ updated Oct 23, 2017, 12:40 AM ]

Efficient 2D double-quantum solid-state NMR spectroscopy with large spectral widths. 2D double-quantum single-quantum correlation spectra with arbitrary spectral widths can be recorded with SR26 and related supercycled recoupling sequences when applying Supercycle-Timing-Compensation (STiC) phase shifts. This concept widely extends the applicability of supercycled sequences, most importantly for obtaining long-range distance constraints for structure determination with solid-state NMR.

Book chapter: High-Field Solid-State NMR with Dynamic Nuclear Polarization

posted May 8, 2017, 2:15 AM by Daniel Lee

High-Field Solid-State NMR with Dynamic Nuclear Polarization. Microwave-induced dynamic nuclear polarization (DNP) can produce hyperpolarization of nuclear spins, leading to substantial signal enhancement in NMR. This chapter discusses the contemporary application of DNP for solid-state NMR spectroscopy at high magnetic fields. The main mechanisms and polarizing agents that enable this hyperpolarization are presented, along with more practical aspects such as the effect of decreasing sample temperature and analyzing the absolute sensitivity gain from these experiments. Examples of the exploitation of DNP for studies of biomolecules, biominerals, pharmaceuticals, self-assembled organic nanostructures, and mesoporous materials are given as is an outlook as to the future of this powerful technique.

Solvent signal suppression for high-resolution MAS-DNP

posted Mar 30, 2017, 3:05 AM by Daniel Lee

Solvent signal suppression for high-resolution MAS-DNP. Dynamic nuclear polarization (DNP) has become a powerful tool to substantially increase the sensitivity of high-field magic angle spinning (MAS) solid-state NMR experiments. The addition of dissolved hyperpolarizing agents usually results in the presence of solvent signals that can overlap and obscure those of interest from the analyte. Here, two methods are proposed to suppress DNP solvent signals: a Forced Echo Dephasing experiment (FEDex) and TRAnsfer of Populations in DOuble Resonance Echo Dephasing (TRAPDORED) NMR. These methods reintroduce a heteronuclear dipolar interaction that is specific to the solvent, thereby forcing a dephasing of recoupled solvent spins and leaving acquired NMR spectra free of associated resonance overlap with the analyte. The potency of these methods is demonstrated on sample types common to MAS-DNP experiments, namely a frozen solution (of L-proline) and a powdered solid (progesterone), both containing deuterated glycerol as a DNP solvent. The proposed methods are efficient, simple to implement, compatible with other NMR experiments, and extendable past spectral editing for just DNP solvents. The sensitivity gains from MAS-DNP in conjunction with FEDex or TRAPDORED then permits rapid and uninterrupted sample analysis.

Ernst award 2016 for Katharina Märker

posted Mar 30, 2017, 2:59 AM by Daniel Lee   [ updated Mar 30, 2017, 3:00 AM ]

Katharina Märker (PhD student) was awarded the Ernst Award during the Annual Meeting of the German Magnetic Resonance Discussion Group in Düsseldorf. At this occasion she had the opportunity to present her recently published work on NMR crystallography. The Ernst award was created in 1998 by the Magnetic Resonance Discussion Group of the German Chemical Society and is granted on the basis of a genuine work recently published as first author in an international scientific journal.

Interfacial Ca2+ environments in nanocrystalline apatites revealed by dynamic nuclear polarization enhanced 43Ca NMR spectroscopy

posted Jan 27, 2017, 3:26 AM by Daniel Lee   [ updated Mar 30, 2017, 4:47 AM ]

Interfacial Ca2+ environments in nanocrystalline apatites revealed by dynamic nuclear polarization enhanced 43Ca NMR spectroscopy. The interfaces within bones, teeth and other hybrid biomaterials are of paramount importance but remain particularly difficult to characterize at the molecular level because both sensitive and selective techniques are mandatory. Here, it is demonstrated that unprecedented insights into calcium environments, for example the differentiation of surface and core species of hydroxyapatite nanoparticles, can be obtained using solid-state NMR, when combined with dynamic nuclear polarization. Although calcium represents an ideal NMR target here (and de facto for a large variety of calcium-derived materials), its stable NMR-active isotope, calcium-43, is a highly unreceptive probe. Using the sensitivity gains from dynamic nuclear polarization, not only could calcium-43 NMR spectra be obtained easily, but natural isotopic abundance 2D correlation experiments could be recorded for calcium-43 in short experimental time. This opens perspectives for the detailed study of interfaces in nanostructured materials of the highest biological interest as well as calcium-based nanosystems in general.

Fast and accurate MAS–DNP simulations of large spin ensembles

posted Jan 26, 2017, 10:47 AM by Daniel Lee

Fast and accurate MAS–DNP simulations of large spin ensembles. A deeper understanding of parameters affecting Magic Angle Spinning Dynamic Nuclear Polarization (MAS–DNP), an emerging nuclear magnetic resonance hyperpolarization method, is crucial for the development of new polarizing agents and the successful implementation of the technique at higher magnetic fields (>10 T). Such progress is currently impeded by computational limitation which prevents the simulation of large spin ensembles (electron as well as nuclear spins) and to accurately describe the interplay between all the multiple key parameters at play. In this work, we present an alternative approach to existing cross-effect and solid-effect MAS–DNP codes that yields fast and accurate simulations. More specifically we describe the model, the associated Liouville-based formalism (Bloch-type derivation and/or Landau–Zener approximations) and the linear time algorithm that allows computing MAS–DNP mechanisms with unprecedented time savings. As a result, one can easily scan through multiple parameters and disentangle their mutual influences. In addition, the simulation code is able to handle multiple electrons and protons, which allows probing the effect of (hyper)polarizing agents concentration, as well as fully revealing the interplay between the polarizing agent structure and the hyperfine couplings, nuclear dipolar couplings, nuclear relaxation times, both in terms of depolarization effect, but also of polarization gain and buildup times.

Welcoming natural isotopic abundance in solid-state NMR: probing π-stacking and supramolecular structure of organic nanoassemblies using DNP

posted Nov 7, 2016, 1:38 PM by Daniel Lee   [ updated Nov 7, 2016, 1:41 PM ]

Welcoming natural isotopic abundance in solid-state NMR: probing p-stacking and supramolecular structure of organic nanoassemblies using DNP. The self-assembly of small organic molecules is an intriguing phenomenon, which provides nanoscale structures for applications in numerous fields from medicine to molecular electronics. Detailed knowledge of their structure, in particular on the supramolecular level, is a prerequisite for the rational design of improved self-assembled systems. In this work, we prove the feasibility of a novel concept of NMR-based 3D structure determination of such assemblies in the solid state. The key point of this concept is the deliberate use of samples that contain 13C at its natural isotopic abundance (NA, 1.1%), while exploiting magic-angle spinning dynamic nuclear polarization (MAS-DNP) to compensate for the reduced sensitivity. Since dipolar truncation effects are suppressed to a large extent in NA samples, unique and highly informative spectra can be recorded which are impossible to obtain on an isotopically labeled system. On the self-assembled cyclic diphenylalanine peptide, we demonstrate the detection of long-range internuclear distances up to ∼7 Å, allowing us to observe π-stacking through 13C–13C correlation spectra, providing a powerful tool for the analysis of one of the most important non-covalent interactions. Furthermore, experimental polarization transfer curves are in remarkable agreement with numerical simulations based on the crystallographic structure, and can be fully rationalized as the superposition of intra- and intermolecular contributions. This new approach to NMR crystallography provides access to rich and precise structural information, opening up a new avenue to de novo crystal structure determination by NMR.

Ultra-low temperature MAS-DNP

posted May 28, 2016, 4:13 AM by Daniel Lee

Ultra-low temperature MAS-DNP
Since the infancy of NMR spectroscopy, sensitivity and resolution have been the limiting factors of the technique. Regular essential developments on this front have led to the widely applicable, versatile, and powerful spectroscopy that we know today. However, the Holy Grail of ultimate sensitivity and resolution is not yet reached, and technical improvements are still ongoing. Hence, high-field dynamic nuclear polarization (DNP) making use of high-frequency, high-power microwave irradiation of electron spins has become very promising in combination with magic angle sample spinning (MAS) solid-state NMR experiments. This is because it leads to a transfer of the much larger polarization of these electron spins under suitable irradiation to surrounding nuclei, greatly increasing NMR sensitivity. Currently, this boom in MAS-DNP is mainly performed at minimum sample temperatures of about 100 K, using cold nitrogen gas to pneumatically spin and cool the sample. This Perspective deals with the desire to improve further the sensitivity and resolution by providing “ultra”-low temperatures for MAS-DNP, using cryogenic helium gas. Different designs on how this technological challenge has been overcome are described. It is shown that stable and fast spinning can be attained for sample temperatures down to 30 K using a large cryostat developed in our laboratory. Using this cryostat to cool a closed-loop of helium gas brings the additional advantage of sample spinning frequencies that can greatly surpass those achievable with nitrogen gas, due to the differing fluidic properties of these two gases. It is shown that using ultra-low temperatures for MAS-DNP results in substantial experimental sensitivity enhancements and according time-savings. Access to this temperature range is demonstrated to be both viable and highly pertinent.

A New Tool for NMR Crystallography: Complete 13C/15N Assignment of Organic Molecules at Natural Isotopic Abundance Using DNP-Enhanced Solid-State NMR

posted May 28, 2016, 4:11 AM by Daniel Lee

A New Tool for NMR Crystallography: Complete 13C/15N Assignment of Organic Molecules at Natural Isotopic Abundance Using DNP-Enhanced Solid-State NMR
NMR crystallography of organic molecules at natural isotopic abundance (NA) strongly relies on the comparison of assigned experimental and computed NMR chemical shifts. However, a broad applicability of this approach is often hampered by the still limited 1H resolution and/or difficulties in assigning 13C and 15N resonances without the use of structure-based chemical shift calculations. As shown here, such difficulties can be overcome by 13C–13C and for the first time 15N–13C correlation experiments, recorded with the help of dynamic nuclear polarization. We present the complete de novo 13C and 15N resonance assignment at NA of a self-assembled 2′-deoxyguanosine derivative presenting two different molecules in the asymmetric crystallographic unit cell. This de novo assignment method is exclusively based on aforementioned correlation spectra and is an important addition to the NMR crystallography approach, rendering firstly 1H assignment straightforward, and being secondly a prerequisite for distance measurements with solid-state NMR.

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