All Publications

  • Audiovisual augmentation for coil positioning in transcranial magnetic stimulation COMPUTER METHODS IN BIOMECHANICS AND BIOMEDICAL ENGINEERING-IMAGING AND VISUALIZATION Schutz, L., Weber, E., Niu, W., Daniel, B., McNab, J., Navab, N., Leuze, C. 2022
  • Assessing the Onset of Calcium Phosphate Nucleation by Hyperpolarized Real-Time NMR. Analytical chemistry Weber, E. M., Kress, T. n., Abergel, D. n., Sewsurn, S. n., Azaïs, T. n., Kurzbach, D. n. 2020


    We report an experimental approach for high-resolution real-time monitoring of transiently formed species occurring during the onset of precipitation of ionic solids from solution. This is made possible by real-time nuclear magnetic resonance (NMR) monitoring using dissolution dynamic nuclear polarization (D-DNP) to amplify signals of functional intermediates and is supported by turbidimetry, cryogenic electron microscopy, and solid-state NMR measurements. D-DNP can provide drastic signal improvements in NMR signal amplitudes, permitting dramatic reductions in acquisition times and thereby enabling us to probe fast interaction kinetics such as those underlying formation of prenucleation species (PNS) that precede solid-liquid phase separation. This experimental strategy allows for investigation of the formation of calcium phosphate (CaP)-based minerals by 31P NMR-a process of substantial industrial, geological, and biological interest. Thus far, many aspects of the mechanisms of CaP nucleation remain unclear due to the absence of experimental methods capable of accessing such processes on sufficiently short time scales. The approach reported here aims to address this by an improved characterization of the initial steps of CaP precipitation, permitting detection of PNS by NMR and determination of their formation rates, exchange dynamics, and sizes. Using D-DNP monitoring, we find that under our conditions (i) in the first 2 s after preparation of oversaturated calcium phosphate solutions, PNS with a hydrodynamic radius of Rh ≈ 1 nm is formed and (ii) following this rapid initial formation, the entire crystallization processes proceed on considerably longer time scales, requiring >20 s to form the final crystal phase.

    View details for DOI 10.1021/acs.analchem.0c00516

    View details for PubMedID 32378878

  • A DNP-hyperpolarized solid-state water NMR MASER: observation and qualitative analysis PHYSICAL CHEMISTRY CHEMICAL PHYSICS Weber, E. M., Kurzbach, D., Abergel, D. 2019; 21 (38): 21278–86


    We present observations of an NMR MASER (microwave amplification by stimulated emission of radiation) of hyperpolarized 1H nuclei by dynamic nuclear polarization (DNP) at 1.2 K and in a magnetic field of 6.7 T. The sustained maser pulses originate from the interplay between radiation damping (RD) due to the large 1H magnetization, and the remagnetization to a negative value by the DNP process. NMR signals lasting for several tens of seconds are thus observed on an ensemble of dipolar-coupled nuclear spins. Magnetization dynamics are analyzed in terms of the combined Bloch-Maxwell and Provotorov (BMP) equations for RD and DNP. Insight into the long time evolution of the magnetization is provided by a theoretical analysis of this nonlinear dynamical system, and by fitting the NMR signal to a simplified version of the BMP equations.

    View details for DOI 10.1039/c9cp03334c

    View details for Web of Science ID 000488835000006

    View details for PubMedID 31549135

  • Sample Ripening through Nanophase Separation Influences the Performance of Dynamic Nuclear Polarization ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Weber, E. M., Sicoli, G., Vezin, H., Frebourg, G., Abergel, D., Bodenhausen, G., Kurzbach, D. 2018; 57 (18): 5171–75


    Mixtures of water and glycerol provide popular matrices for low-temperature spectroscopy of vitrified samples. However, they involve counterintuitive physicochemical properties, such as spontaneous nanoscopic phase separations (NPS) in solutions that appear macroscopically homogeneous. We demonstrate that such phenomena can substantially influence the efficiency of dynamic nuclear polarization (DNP) by factors up to 20 % by causing fluctuations in local concentrations of polarization agents (radicals). Thus, a spontaneous NPS of water/glycerol mixtures that takes place on time scales on the order of 30-60 min results in a confinement of polarization agents in nanoscopic water-rich vesicles, which in return affects the DNP. Such effects were found for three common polarization agents, TEMPOL, AMUPol and Trityl.

    View details for DOI 10.1002/anie.201800493

    View details for Web of Science ID 000432382800066

    View details for PubMedID 29431894

  • Rates of Chemical Reactions Embedded in a Metabolic Network by Dissolution Dynamic Nuclear Polarisation NMR CHEMISTRY-A EUROPEAN JOURNAL Sadet, A., Weber, E. M., Jhajharia, A., Kurzbach, D., Bodenhausen, G., Miclet, E., Abergel, D. 2018; 24 (21): 5456–61


    The isomerisation of 6-phosphogluconolactones and their hydrolyses into 6-phosphogluconic acid form a non enzymatic side cycle of the pentose-phosphate pathway (PPP) in cells. Dissolution dynamic nuclear polarisation can be used for determining the kinetic rates of the involved transformations in real time. It is found that the hydrolysis of both lactones is significantly slower than the isomerisation process, thereby shedding new light onto this subtle chemical process.

    View details for DOI 10.1002/chem.201705520

    View details for Web of Science ID 000430169400009

    View details for PubMedID 29356139

  • Anisotropic longitudinal electronic relaxation affects DNP at cryogenic temperatures PHYSICAL CHEMISTRY CHEMICAL PHYSICS Weber, E. M., Vezin, H., Kempf, J. G., Bodenhausen, G., Abergel, D., Kurzbach, D. 2017; 19 (24): 16087–94


    We report the observation of anisotropic longitudinal electronic relaxation in nitroxide radicals under typical dynamic nuclear polarization conditions. This anisotropy affects the efficiency of dynamic nuclear polarization at cryogenic temperatures of 4 K and high magnetic fields of 6.7 T. Under our experimental conditions, the electron paramagnetic resonance spectrum of nitroxides such as TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl) is only partly averaged by electronic spectral diffusion, so that the relaxation times T1e(ω) vary across the spectrum. We demonstrate how the anisotropy of T1e(ω) can be taken into account in simple DNP models.

    View details for DOI 10.1039/c7cp03242k

    View details for Web of Science ID 000403965500051

    View details for PubMedID 28598474

  • Communication: Dissolution DNP reveals a long-lived deuterium spin state imbalance in methyl groups JOURNAL OF CHEMICAL PHYSICS Jhajharia, A., Weber, E. M., Kempf, J. G., Abergel, D., Bodenhausen, G., Kurzbach, D. 2017; 146 (4): 041101


    We report the generation and observation of long-lived spin states in deuterated methyl groups by dissolution DNP. These states are based on population imbalances between manifolds of spin states corresponding to irreducible representations of the C3v point group and feature strongly dampened quadrupolar relaxation. Their lifetime depends on the activation energies of methyl group rotation. With dissolution DNP, we can reduce the deuterium relaxation rate by a factor up to 20, thereby extending the experimentally available time window. The intrinsic limitation of NMR spectroscopy of quadrupolar spins by short relaxation times can thus be alleviated.

    View details for DOI 10.1063/1.4974358

    View details for Web of Science ID 000394520200002

    View details for PubMedID 28147551

  • Investigation of Intrinsically Disordered Proteins through Exchange with Hyperpolarized Water ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Kurzbach, D., Canet, E., Flamm, A. G., Jhajharia, A., Weber, E. M., Konrat, R., Bodenhausen, G. 2017; 56 (1): 389–92


    Hyperpolarized water can selectively enhance NMR signals of rapidly exchanging protons in osteopontin (OPN), a metastasis-associated intrinsically disordered protein (IDP), at near-physiological pH and temperature. The transfer of magnetization from hyperpolarized water is limited to solvent-exposed residues and therefore selectively enhances signals in 1 H-15 N correlation spectra. Binding to the polysaccharide heparin was found to induce the unfolding of preformed structural elements in OPN.

    View details for DOI 10.1002/anie.201608903

    View details for Web of Science ID 000394861200065

    View details for PubMedID 27918140

  • Dissolution dynamic nuclear polarization of deuterated molecules enhanced by cross-polarization JOURNAL OF CHEMICAL PHYSICS Kurzbach, D., Weber, E. M., Jhajharia, A., Cousin, S. F., Sadet, A., Marhabaie, S., Canet, E., Birlirakis, N., Milani, J., Jannin, S., Eshchenko, D., Hassan, A., Melzi, R., Luetolf, S., Sacher, M., Rossire, M., Kempf, J., Lohman, J. B., Weller, M., Bodenhausen, G., Abergel, D. 2016; 145 (19): 194203


    We present novel means to hyperpolarize deuterium nuclei in 13CD2 groups at cryogenic temperatures. The method is based on cross-polarization from 1H to 13C and does not require any radio-frequency fields applied to the deuterium nuclei. After rapid dissolution, a new class of long-lived spin states can be detected indirectly by 13C NMR in solution. These long-lived states result from a sextet-triplet imbalance (STI) that involves the two equivalent deuterons with spin I = 1. An STI has similar properties as a triplet-singlet imbalance that can occur in systems with two equivalent I = 12 spins. Although the lifetimes TSTI are shorter than T1(Cz), they can exceed the life-time T1(Dz) of deuterium Zeeman magnetization by a factor of more than 20.

    View details for DOI 10.1063/1.4967402

    View details for Web of Science ID 000388956900015

    View details for PubMedID 27875876

  • Cross-Correlated Relaxation of Dipolar Coupling and Chemical-Shift Anisotropy in Magic-Angle Spinning R-1 rho NMR Measurements: Application to Protein Backbone Dynamics Measurements JOURNAL OF PHYSICAL CHEMISTRY B Kurauskas, V., Weber, E., Hessel, A., Ayala, I., Marion, D., Schanda, P. 2016; 120 (34): 8905–13


    Transverse relaxation rate measurements in magic-angle spinning solid-state nuclear magnetic resonance provide information about molecular motions occurring on nanosecond-to-millisecond (ns-ms) time scales. The measurement of heteronuclear ((13)C, (15)N) relaxation rate constants in the presence of a spin-lock radiofrequency field (R1ρ relaxation) provides access to such motions, and an increasing number of studies involving R1ρ relaxation in proteins have been reported. However, two factors that influence the observed relaxation rate constants have so far been neglected, namely, (1) the role of CSA/dipolar cross-correlated relaxation (CCR) and (2) the impact of fast proton spin flips (i.e., proton spin diffusion and relaxation). We show that CSA/D CCR in R1ρ experiments is measurable and that the CCR rate constant depends on ns-ms motions; it can thus provide insight into dynamics. We find that proton spin diffusion attenuates this CCR due to its decoupling effect on the doublet components. For measurements of dynamics, the use of R1ρ rate constants has practical advantages over the use of CCR rates, and this article reveals factors that have so far been disregarded and which are important for accurate measurements and interpretation.

    View details for DOI 10.1021/acs.jpcb.6b06129

    View details for Web of Science ID 000382596700016

    View details for PubMedID 27500976

    View details for PubMedCentralID PMC5010779