Category Archives: Perdeuteration

Deuteration of Hyperpolarized 13 C-Labeled Zymonic Acid Enables Sensitivity-Enhanced Dynamic MRI of pH

Hundshammer, C., et al., Deuteration of Hyperpolarized 13 C-Labeled Zymonic Acid Enables Sensitivity-Enhanced Dynamic MRI of pH. ChemPhysChem, 2017. 18(18): p. 2422-2425.

https://www.ncbi.nlm.nih.gov/pubmed/28719100

Aberrant pH is characteristic of many pathologies such as ischemia, inflammation or cancer. Therefore, a non-invasive and spatially resolved pH determination is valuable for disease diagnosis, characterization of response to treatment and the design of pH-sensitive drug-delivery systems. We recently introduced hyperpolarized [1,5-13 C2 ]zymonic acid (ZA) as a novel MRI probe of extracellular pH utilizing dissolution dynamic polarization (DNP) for a more than 10000-fold signal enhancement of the MRI signal. Here we present a strategy to enhance the sensitivity of this approach by deuteration of ZA yielding [1,5-13 C2 , 3,6,6,6-D4 ]zymonic acid (ZAd ), which prolongs the liquid state spin lattice relaxation time (T1 ) by up to 39 % in vitro. Measurements with ZA and ZAd on subcutaneous MAT B III adenocarcinoma in rats show that deuteration increases the signal-to-noise ratio (SNR) by up to 46 % in vivo. Furthermore, we demonstrate a proof of concept for real-time imaging of dynamic pH changes in vitro using ZAd , potentially allowing for the characterization of rapid acidification/basification processes in vivo.

Heteronuclear DNP of protons and deuterons with TEMPOL #DNPNMR

Kaminker, I., et al., Heteronuclear DNP of protons and deuterons with TEMPOL. Phys Chem Chem Phys, 2016. 18(16): p. 11017-41.

https://www.ncbi.nlm.nih.gov/pubmed/27047995

Dynamic nuclear polarization (DNP) experiments on samples with several types of magnetic nuclei sometimes exhibit “cross-talk” between the nuclei, such as different nuclei having DNP spectra with similar shapes and enhancements. In this work we demonstrate that while at 20 K the DNP spectra of (1)H and (2)H nuclei, in a sample composed of 50% v/v (1)H2O/DMSO-d6 and containing 40 mM TEMPOL, are different and can be analyzed using the indirect cross effect (iCE) model, at 6 K the DNP spectra of both (1)H and (2)H nuclei become identical. In addition we experimentally demonstrate that there exists an efficient polarization exchange between the two nuclear pools at this temperature. Both of these results are hallmark predictions of the thermal mixing (TM) formalism. However, the origin of these observations cannot, in our case, be explained using the standard TM formalism, as in our sample the electron reservoir cannot be described by a single non-Zeeman spin temperature, which is a prerequisite of TM. This conclusion follows from the analysis of the electron electron double resonance (ELDOR) experiments on our sample and is similar to the previously published results. Consequently, another mechanism must be used in order to explain these “cross-talk” effects. The heteronuclear cross effect (hnCE) DNP mechanism, previously introduced based on the simulations of the spin evolution in small model systems, results in “cross-talk” effects between two types of nuclei that are similar to the experimental ones seen in this work. In particular we show that the hnCE mechanism exhibits polarization transfer between the nuclei and that there exists a clear relationship between the steady state polarizations of the two types of nuclei which may, in the future, be correlated with the phenomenon observed in the two types of bulk nuclear signals in samples during DNP experiments. It is suggested that the hnCE electrons are a possible source for the process that equalizes the bulk enhancements of the (1)H and (2)H nuclei and are responsible for the observed cross-talk effects.

Effects of biradical deuteration on the performance of DNP: towards better performing polarizing agents

Perras, F.A., et al., Effects of biradical deuteration on the performance of DNP: towards better performing polarizing agents. Phys Chem Chem Phys, 2016. 18(1): p. 65-9.

http://www.ncbi.nlm.nih.gov/pubmed/26619055

We study the effects of the deuteration of biradical polarizing agents on the efficiency of dynamic nuclear polarization (DNP) via the cross-effect. To this end, we synthesized a series of bTbK and TOTAPol biradicals with systematically increased deuterium substitution. The deuteration increases the radicals’ relaxation time, thus contributing to a higher saturation factor and larger DNP enhancement, and reduces the pool of protons within the so-called spin diffusion barrier. Notably, we report that full or partial deuteration leads to improved DNP enhancement factors in standard samples, but also slows down the build-up of hyperpolarization. Improvements in DNP enhancements factors of up to 70% and time savings of up to 38% are obtained upon full deuteration. It is foreseen that this approach may be applied to other DNP polarizing agents thus enabling further sensitivity improvements.

Ultra-high resolution in MAS solid-state NMR of perdeuterated proteins: Implications for structure and dynamics

This article is not directly related to DNP-enhanced NMR spectroscopy. However, since deuteration of the sample material plays an important role in DNP spectroscopy, this article could be of great interest to researchers in the field.

Bernd, R., Ultra-high resolution in MAS solid-state NMR of perdeuterated proteins: Implications for structure and dynamics. J. Magn. Reson., 2012. 216(0): p. 1-12.

http://dx.doi.org/10.1016/j.jmr.2011.12.017

High resolution proton spectra are obtained in MAS solid-state NMR in case samples are prepared using perdeuterated protein and D2O in the recrystallization buffer. Deuteration reduces drastically 1H, 1H dipolar interactions and allows to obtain amide proton line widths on the order of 20 Hz. Similarly, high-resolution proton spectra of aliphatic groups can be obtained if specifically labeled precursors for biosynthesis of methyl containing side chains are used, or if limited amounts of H2O in the bacterial growth medium is employed. This review summarizes recent spectroscopic developments to access structure and dynamics of biomacromolecules in the solid-state, and shows a number of applications to amyloid fibrils and membrane proteins.

Ultra-high resolution in MAS solid-state NMR of perdeuterated proteins: Implications for structure and dynamics

This article is not directly related to DNP-enhanced NMR spectroscopy. However, since deuteration of the sample material plays an important role in DNP spectroscopy, this article could be of great interest to researchers in the field.

Bernd, R., Ultra-high resolution in MAS solid-state NMR of perdeuterated proteins: Implications for structure and dynamics. J. Magn. Reson., 2012. 216(0): p. 1-12.

http://dx.doi.org/10.1016/j.jmr.2011.12.017

High resolution proton spectra are obtained in MAS solid-state NMR in case samples are prepared using perdeuterated protein and D2O in the recrystallization buffer. Deuteration reduces drastically 1H, 1H dipolar interactions and allows to obtain amide proton line widths on the order of 20 Hz. Similarly, high-resolution proton spectra of aliphatic groups can be obtained if specifically labeled precursors for biosynthesis of methyl containing side chains are used, or if limited amounts of H2O in the bacterial growth medium is employed. This review summarizes recent spectroscopic developments to access structure and dynamics of biomacromolecules in the solid-state, and shows a number of applications to amyloid fibrils and membrane proteins.

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