13 C dynamic nuclear polarization using isotopically enriched 4‐oxo‐TEMPO free radicals

Magnetic Reson in Chemistry

Parish

et al. 2017

Self Cite

Dynamic nuclear polarization (DNP) via the dissolution method has become one of the rapidly emerging techniques to alleviate the low signal sensitivity in nuclear magnetic resonance (NMR) spectroscopy and imaging. In this paper, we report on the development and C hyperpolarization efficiency of a homebuilt DNP system operating at 6.423 T and 1.4 K. The DNP hyperpolarizer system was assembled on a wide-bore superconducting magnet, equipped with a standard continuous-flow cryostat, and a 180 GHz microwave source with 120 mW power output and wide 4 GHz frequency tuning range. At 6.423 T and 1.4 K, solid-state C polarization P levels of 64% and 31% were achieved for 3 M [1- C] sodium acetate samples in 1 : 1 v/v glycerol:water glassing matrix doped with 15 mM trityl OX063 and 40 mM 4-oxo-TEMPO, respectively. Upon dissolution, which takes about 15 s to complete, liquid-state C NMR signal enhancements as high as 240 000-fold (P=21%) were recorded in a nearby high resolution C NMR spectrometer at 1 T and 297 K. Considering the relatively lower cost of our homebuilt DNP system and the relative simplicity of its design, the dissolution DNP setup reported here could be feasibly adapted for in vitro or in vivo hyperpolarized C NMR or magnetic resonance imaging at least in the pre-clinical setting. Copyright © 2017 John Wiley& Sons, Ltd.

Section: Resultsmentioning

confidence: 98%

Construction and ¹³C hyperpolarization efficiency of a 180 GHz dissolution dynamic nuclear polarization system

Kiswandhi

Magnetic Reson in Chemistry

Parish

et al. 2017

Self Cite

“…17,18,20,21,31,34,49 Trityl OX063, the stable organic radical used in this work, has a very narrow EPR linewidth that makes it ideal for polarizing low-γ nuclei such as 13 C. When using this free radical to polarize low-γ nuclei such as 13 C spins, DNP data at 3.35 T and temperatures close to 1 K have shown indications of thermal mixing (TM) as the predominant DNP mechanism. 24,[50][51][52][53] Other DNP data at similar conditions suggested that the mechanism could be a combination of the solid effect (SE) and cross effect (CE).…”

Section: Resultsmentioning

confidence: 99%

“…[25][26][27][28][29][30] Additionally, the DNP efficiency of these radicals may be increased through other means such as deuteration of the glassing matrix. [31][32][33] Meanwhile, the trityls, particularly OX063, which have some of the narrowest EPR linewidths among free radicals, were found to be excellent polarizing agents for low-γ nuclei like 13 C. 16,34 When using these radicals, DNP enhancements may be improved further by the addition of trace amounts of gadolinium. [34][35][36][37] Recently, it was found that the addition of holmium to a trityl-doped sample results in liquid state enhancement similar to that achieved by using gadolinium.…”

Section: Introductionmentioning

confidence: 99%

Influence of Dy3+ and Tb3+ doping on 13C dynamic nuclear polarization

The Journal of Chemical Physics

Parish

Kiswandhi

et al. 2017

Self Cite

Dynamic nuclear polarization (DNP) is a technique that uses a microwave-driven transfer of high spin alignment from electrons to nuclear spins. This is most effective at low temperature and high magnetic field, and with the invention of the dissolution method, the amplified nuclear magnetic resonance (NMR) signals in the frozen state in DNP can be harnessed in the liquid-state at physiologically acceptable temperature for in vitro and in vivo metabolic studies. A current optimization practice in dissolution DNP is to dope the sample with trace amounts of lanthanides such as Gd 3+ or Ho 3+ , which further improves the polarization. While Gd 3+ and Ho 3+ have been optimized for use in dissolution DNP, other lanthanides have not been exhaustively studied for use in 13 C DNP applications. In this work, two additional lanthanides with relatively high magnetic moments, Dy 3+ and Tb 3+ , were extensively optimized and tested as doping additives for 13 C DNP at 3.35 T and 1.2 K. We have found that both of these lanthanides are also beneficial additives, to a varying degree, for 13 C DNP. The optimal concentrations of Dy 3+ (1.5 mM) and Tb 3+ (0.25 mM) for 13 C DNP were found to be less than that of Gd 3+ (2 mM). W-band electron paramagnetic resonance shows that these enhancements due to Dy 3+ and Tb 3+ doping are accompanied by shortening of electron T 1 of trityl OX063 free radical. Furthermore, when dissolution was employed, Tb 3+ -doped samples were found to have similar liquid-state 13 C NMR signal enhancements compared to samples doped with Gd 3+ , and both Tb 3+ and Dy 3+ had a negligible liquid-state nuclear T 1 shortening effect which contrasts with the significant reduction in T 1 when using Gd 3+ . Our results show that Dy 3+ doping and Tb 3+ doping have a beneficial impact on 13 C DNP both in the solid and liquid states, and that Tb 3+ in particular could be used as a potential alternative to Gd 3+ in 13 C dissolution DNP experiments. Published by AIP Publishing.

“…14–19 Furthermore, certain sample preparation methods such as the addition of trace amounts of lanthanides in the DNP sample can significantly boost the DNP-enhanced NMR signals. 5,20–23 Previous studies have shown that 13 C enrichment 24 and deuteration 17,21,25 of the glassing matrix can expedite and also improve the DNP enhancement levels, respectively. All of these DNP sample optimization practices so far were additives or certain isotopic enrichment in the glassing matrix.…”

Section: Introductionmentioning

confidence: 99%

Influence of ¹³C Isotopic Labeling Location on Dynamic Nuclear Polarization of Acetate

Parish²,

Kiswandhi³

et al. 2017

J. Phys. Chem. A

Self Cite

Dynamic nuclear polarization (DNP) via the dissolution method has alleviated the insensitivity problem in liquid-state nuclear magnetic resonance (NMR) spectroscopy by amplifying the signals by several thousand-fold. This NMR signal amplification process emanates from the microwave-mediated transfer of high electron spin alignment to the nuclear spins at high magnetic field and cryogenic temperature. Since the interplay between the electrons and nuclei is crucial, the chemical composition of a DNP sample such as the type of free radical used, glassing solvents, or the nature of the target nuclei can significantly affect the NMR signal enhancement levels that can be attained with DNP. Herein, we have investigated the influence of 13C isotopic labeling location on the DNP of a model 13C compound, sodium acetate, at 3.35 T and 1.4 K using the narrow electron spin resonance (ESR) linewidth free radical trityl OX063. Our results show that the carboxyl 13C spins yielded about twice the polarization produced in methyl 13C spins. Deuteration of the methyl 13C group, while proven beneficial in the liquid-state, did not produce an improvement in the 13C polarization level at cryogenic conditions. In fact, a slight reduction of the solid-state 13C polarization was observed when 2H spins are present in the methyl group. Furthermore, our data reveal that there is a close correlation between the solid-state 13C T1 relaxation times of these samples and the relative 13C polarization levels. The overall results suggest the achievable solid-state polarization of 13C acetate is directly affected by the location of the 13C isotopic labeling via the possible interplay of nuclear relaxation leakage factor and cross-talks between nuclear Zeeman reservoirs in DNP.