Scaling analyses for hyperpolarization transfer across a spin-diffusion barrier and into bulk solid media

Prisco, Nathan A.; Pinon, Arthur C.; Emsley, Lyndon; Chmelka, Bradley F.

doi:10.1039/d0cp03195j

Cited by 50 publications

(94 citation statements)

References 64 publications

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“…The other used the same approach to simulate 13 C MAS-DNP build-up curves and gave a mechanistic account of how in this context polarization could efficiently be transferred from core to bulk spins ( 39 ). Last, a recent study used a model based on diffusion laws reminiscent of earlier works but in the context of MAS-DNP ( 29 ). This approach gave a phenomenological picture of the dependence of polarization transfer in the vicinity of the electron on the concentration of nuclear spins.…”

Section: Resultsmentioning

confidence: 99%

Direct observation of hyperpolarization breaking through the spin diffusion barrier

et al. 2021

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Dynamic nuclear polarization (DNP) is a widely used tool for overcoming the low intrinsic sensitivity of nuclear magnetic resonance spectroscopy and imaging. Its practical applicability is typically bounded, however, by the so-called “spin diffusion barrier,” which relates to the poor efficiency of polarization transfer from highly polarized nuclei close to paramagnetic centers to bulk nuclei. A quantitative assessment of this barrier has been hindered so far by the lack of general methods for studying nuclear polarization flow in the vicinity of paramagnetic centers. Here, we fill this gap and introduce a general set of experiments based on microwave gating that are readily implemented. We demonstrate the versatility of our approach in experiments conducted between 1.2 and 4.2 K in static mode and at 100 K under magic angle spinning (MAS)—conditions typical for dissolution DNP and MAS-DNP—and directly observe the marked dependence of polarization flow on temperature.

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Section: Resultsmentioning

confidence: 99%

Direct observation of hyperpolarization breaking through the spin diffusion barrier

et al. 2021

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“…This indicates that only a negligible fraction of the total histidine permeates the cells, and we can therefore assume that the histidine enhancement is the same as that of the solvent. 42 , 43 For the drug, two limiting cases can be considered: either the drug is buried in the cells, and therefore its enhancement is as low as the lowest measured enhancement for the cells (ε = 25 ± 4), or it is adsorbed on the cell surface, which is essentially in the same phase as the polarizing solution and shares the same enhancement as the solvent (ε = 244 ± 6). In the first case, this yields an amount of [ 15 N]CHIR-98014 per million cells, n CHIR , of 196 ± 112 pmol, while in the other case, n CHIR = 20 ± 9 pmol.…”

Section: Results and Discussionmentioning

confidence: 99%

In-Cell Quantification of Drugs by Magic-Angle Spinning Dynamic Nuclear Polarization NMR

et al. 2022

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The determination of intracellular drug concentrations can provide a better understanding of the drug function and efficacy. Ideally, this should be performed nondestructively, with no modification of either the drug or the target, and with the capability to detect low amounts of the molecule of interest, in many cases in the μM to nM range (pmol to fmol per million cells). Unfortunately, it is currently challenging to have an experimental technique that provides direct quantitative measurements of intracellular drug concentrations that simultaneously satisfies these requirements. Here, we show that magic-angle spinning dynamic nuclear polarization (MAS DNP) can be used to fulfill these requirements. We apply a quantitative 15 N MAS DNP approach in combination with 15 N labeling to quantify the intracellular amount of the drug [ 15 N]CHIR-98014, an activator of the Wingless and Int-1 signaling pathway, determining intracellular drug amounts in the range of tens to hundreds of picomoles per million cells. This is, to our knowledge, the first time that MAS DNP has been used to successfully estimate intracellular drug amounts.

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“…[8] As such, organic microcrystals (micrometer size in all dimensions), in particular bearing methyl groups, are challenging targets and useful for testing new PAs. [43,51]…”

Section: The Challenge Of Polarizing Large Protonated Microcrystals W...mentioning

confidence: 99%

Highly Efficient Polarizing Agents for MAS‐DNP of Proton‐Dense Molecular Solids

et al. 2022

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Efficiently hyperpolarizing proton‐dense molecular solids through dynamic nuclear polarization (DNP) solid‐state NMR is still an unmet challenge. Polarizing agents (PAs) developed so far do not perform well on proton‐rich systems, such as organic microcrystals and biomolecular assemblies. Herein we introduce a new PA, cAsymPol‐POK, and report outstanding hyperpolarization efficiency on 12.76 kDa U‐13C,15N‐labeled LecA protein and pharmaceutical drugs at high magnetic fields (up to 18.8 T) and fast magic angle spinning (MAS) frequencies (up to 40 kHz). The performance of cAsymPol‐POK is rationalized by MAS‐DNP simulations combined with electron paramagnetic resonance (EPR), density functional theory (DFT) and molecular dynamics (MD). This work shows that this new biradical is compatible with challenging biomolecular applications and unlocks the rapid acquisition of 13C–13C and 15N–13C correlations of pharmaceutical drugs at natural isotopic abundance, which are key experiments for structure determination.

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Scaling analyses for hyperpolarization transfer across a spin-diffusion barrier and into bulk solid media

Abstract: Quantitative scaling analyses based on mass and energy transport analogies enable rate-limiting processes to be established in hyperpolarization transfer phenomena.

Cited by 50 publications

References 64 publications

Direct observation of hyperpolarization breaking through the spin diffusion barrier

Direct observation of hyperpolarization breaking through the spin diffusion barrier

In-Cell Quantification of Drugs by Magic-Angle Spinning Dynamic Nuclear Polarization NMR

Highly Efficient Polarizing Agents for MAS‐DNP of Proton‐Dense Molecular Solids

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