Hypershifted spin spectroscopy with dynamic nuclear polarization at 1.4 K.

Dynamic nuclear polarization (DNP) enhances nuclear magnetic resonance (NMR) sensitivity by transferring polarization from unpaired electrons to nuclei, but nearby nuclear spins are difficult to detect or "hidden" due to strong electron-nuclear couplings that hypershift their NMR resonances. Here, we detect these hypershifted spins in a frozen glycerol-water mixture doped with TEMPOL at ~1.4 K using spin diffusion enhanced saturation transfer (SPIDEST), which indirectly reveals their spectrum.

Simultaneous Observation of the Anomerization and Reaction Rates of Enzymatic Dehydrogenation of Glucose-6-Phosphate by Dissolution DNP.

The hyperpolarization of biological samples using dissolution dynamic nuclear polarization (dDNP) has become an attractive method for the monitoring of fast chemical and enzymatic reactions using NMR by taking advantage of a large signal increase. This approach is actively developing but still needs key methodological breakthroughs to be used as an analytical method for the monitoring of complex networks of simultaneous metabolic pathways. In this article, we use the deceptively simple example of glucose-6-phosphate (G6P) oxidation reaction by the enzyme G6P dehydrogenase (G6PDH) to discuss some important methodological aspects of dDNP kinetic experiments, such as its robustness and its ability to provide repeatable results as well as the capacity of this time-resolved methodology to test kinetic models and hypotheses and to provide reliable parameter estimates.

Multimode Masers of Thermally Polarized Nuclear Spins in Solution NMR.

We present experimental single and multimode sustained ^{1}H NMR masers in solution on thermally polarized spins at room temperature and 9.4 T achieved through the electronic control of radiation feedback (radiation damping). Our observations illustrate the breakdown of the usual three-dimensional Maxwell-Bloch equations for radiation feedback and a simple toy model of few coupled classical moments is used to interpret these experiments.

Analysis of Velocity Autocorrelation Functions from Molecular Dynamics Simulations of a Small Peptide by the Generalized Langevin Equation with a Power-Law Kernel.

Internal motions play an essential role in the biological functions of proteins and have been the subject of numerous theoretical and spectroscopic studies. Such complex environments are associated with anomalous diffusion where, in contrast to the classical Brownian motion, the relevant correlation functions have power law decays with time. In this work, we investigate the presence of long memory stochastic processes through the analysis of atomic velocity autocorrelation functions.

Intrinsic Flexibility beyond the Highly Ordered DNA Tetrahedron: An Integrative Spectroscopic and Molecular Dynamics Approach.

Since the introduction of DNA-based architectures, in the past decade, DNA tetrahedrons have aroused great interest. Applications of such nanostructures require structural control, especially in the perspective of their possible functionalities. In this work, an integrated approach for structural characterization of a tetrahedron structure is proposed with a focus on the fundamental biophysical aspects driving the assembly process.

Quantitative analysis of cross-talk in partly deuterated samples of nuclear spins hyperpolarized by dynamic nuclear polarization (DNP) in the thermal mixing regime.

Dynamical nuclear polarization (DNP) is a powerful method that allows one to polarize virtually any spin-bearing nucleus by transferring electron polarization by microwave irradiation of the electron Zeeman transitions. Under certain conditions, the DNP process can be described in thermodynamical terms using the thermal mixing (TM) model. Different nuclear species can exchange energy indirectly through their interactions with the electron spins and reach a common spin temperature.

Dipolar field effects in a solid-state NMR maser pumped by dynamic nuclear polarization.

We report the observations and the analysis of a pulsed solid state sustained maser generated by proton spins hyperpolarized by Dynamic Nuclear Polarization (DNP) at cryogenic temperatures. Similar unconventional behaviour was observed recently [Weber , , 2019, , 21278-21286], with induction decays exhibiting multiple asymmetric maser pulses for short time (100 ms) and persistent for tens of second, when the spins are polarized negatively. We present new evidence of such DNP NMR masers, and shed light on previously observed but unexplained features of these masers through simulations of the non-linear spin dynamics using the Bloch-Maxwell-Provotrov (BMP) equations for radiation damping and DNP, and taking into account the (distant) dipolar field.

A Toolbox for Glutamine Use in Dissolution Dynamic Nuclear Polarization: from Enzymatic Reaction Monitoring to the Study of Cellular Metabolic Pathways and Imaging.

Glutamine is under scrutiny regarding its metabolic deregulation linked to energetic reprogramming in cancer cells. Many analytical techniques have been used to better understand the impact of the metabolism of amino acids on biological processes, however only a few are suited to work with complex samples. Here, we report the use of a general dissolution dynamic nuclear polarization (D-DNP) formulation using an unexpensive radical as a multipurpose tool to study glutamine, with insights from enzymatic modelling to complex metabolic networks and fast imaging.

Inversion of Hyperpolarized C NMR Signals through Cross-Correlated Cross-Relaxation in Dissolution DNP Experiments.

Dissolution dynamic nuclear polarization (DDNP) is a versatile tool to boost signal amplitudes in solution-state nuclear magnetic resonance (NMR) spectroscopy. For DDNP, nuclei are spin-hyperpolarized "" in a dedicated DNP device and then transferred to an NMR spectrometer for detection. Dramatic signal enhancements can be achieved, enabling shorter acquisition times, real-time monitoring of fast reactions, and reduced sample concentrations.

Spin relaxation: is there anything new under the Sun?

Spin relaxation has been at the core of many studies since the early days of nuclear magnetic resonance (NMR) and the underlying theory worked out by its founding fathers. This Bloch-Redfield-Abraham relaxation theory has been recently reinvestigated () in the perspective of Lindblad theory of quantum Markovian master equations in order to account for situations where the widely used semi-classical relaxation theory breaks down. In this article, we review the conventional approach of quantum mechanical theory of NMR relaxation and show that, under the usual assumptions, it is equivalent to the Lindblad formulation.

Effects of Microwave Gating on Nuclear Spin Echoes in Dynamic Nuclear Polarization.

Dipolar or quadrupolar echoes allow one to observe undistorted powder patterns, in contrast to simple Fourier transformations of free induction decays (FIDs). In this work, the buildup of proton polarization due to dynamic nuclear polarization (DNP) is monitored by observing echoes rather than FIDs. When the microwave irradiation is interrupted during the buildup of DNP, the electrons relax back to their Boltzmann distribution at high fields ( = 6.

Natural abundance oxygen-17 solid-state NMR of metal organic frameworks enhanced by dynamic nuclear polarization.

The 17O resonances of zirconium-oxo clusters that can be found in porous Zr carboxylate metal-organic frameworks (MOFs) have been investigated by magic-angle spinning (MAS) NMR spectroscopy enhanced by dynamic nuclear polarization (DNP). High-resolution 17O spectra at 0.037% natural abundance could be obtained in 48 hours, thanks to DNP enhancement of the 1H polarization by factors ε(1H) = Swith/Swithout = 28, followed by 1H → 17O cross-polarization, allowing a saving in experimental time by a factor of ca.

Assessing the Onset of Calcium Phosphate Nucleation by Hyperpolarized Real-Time NMR.

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.

A DNP-hyperpolarized solid-state water NMR MASER: observation and qualitative analysis.

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.

Transport of hyperpolarized samples in dissolution-DNP experiments.

Dissolution dynamic nuclear polarization (D-DNP) experiments rely on the transfer of a sample between two high-field magnets. During this transfer, samples might experience passage through regions where the stray fields of the magnets are very weak, can approach zero, and even change their sign. This can lead to unexpected spectral features in spin systems that undergo transitions from weak- to strong-coupling regimes and vice versa, much like in field cycling nuclear magnetic resonance experiments.

Stochastic modeling of macromolecules in solution. I. Relaxation processes.

A framework for the stochastic description of relaxation processes in flexible macromolecules, including dissipative effects, is introduced from an atomistic point of view. Projection-operator techniques are employed to obtain multidimensional Fokker-Planck operators governing the relaxation of internal coordinates and global degrees of freedom and depending upon parameters fully recoverable from classic force fields (energetics) and continuum models (friction tensors). A hierarchy of approaches of different complexity is proposed in this unified context, aimed primarily at the interpretation of magnetic resonance relaxation experiments.

Stochastic modeling of macromolecules in solution. II. Spectral densities.

In Paper I [Polimeno et al., J. Chem.

Targeting the Pentose Phosphate Pathway: Characterization of a New 6PGL Inhibitor.

Human African trypanosomiasis, or sleeping sickness, is a lethal disease caused by the protozoan parasite Trypanosoma brucei. However, although many efforts have been made to understand the biochemistry of this parasite, drug development has led to treatments that are of limited efficiency and of great toxicity. To develop new drugs, new targets must be identified, and among the several metabolic processes of trypanosomes that have been proposed as drug targets, carbohydrate metabolism (glycolysis and the pentose phosphate pathway (PPP)) appears as a promising one.

Relaxation of long-lived modes in NMR of deuterated methyl groups.

Long-lived imbalances of spin state populations can circumvent fast quadrupolar relaxation by reducing effective longitudinal relaxation rates by about an order of magnitude. This opens new avenues for the study of dynamic processes in deuterated molecules. Here we present an analysis of the relaxation properties of deuterated methyl groups CD.

Rates of Chemical Reactions Embedded in a Metabolic Network by Dissolution Dynamic Nuclear Polarisation NMR.

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.

Characterizing Thermal Mixing Dynamic Nuclear Polarization via Cross-Talk between Spin Reservoirs.

Dynamic nuclear polarization (DNP) embraces a family of methods to increase signal intensities in nuclear magnetic resonance (NMR) spectroscopy. Despite extensive theoretical work that allows one to distinguish at least five distinct mechanisms, it remains challenging to determine the relative weights of the processes that are responsible for DNP in state-of-the-art experiments operating with stable organic radicals like nitroxides at high magnetic fields and low temperatures. Specifically, determining experimental conditions where DNP involves thermal mixing, which denotes a spontaneous heat exchange between different spin reservoirs, remains challenging.

Single-Scan C Diffusion-Ordered NMR Spectroscopy of DNP-Hyperpolarised Substrates.

Diffusion-ordered NMR spectroscopy (DOSY) is a powerful approach for the analysis of molecular mixtures, yet its application range is limited by the relatively low sensitivity of NMR. We show here that spectrally resolved C DOSY data can be collected, in a single scan, for substrates hyperpolarised by dissolution dynamic nuclear polarisation (D-DNP), which provides signal enhancements of several orders of magnitude. For this we use a convection-compensation pulse scheme, which we also analyse by numerical simulation.