Quantitative analysis of deuterium using the isotopic effect on quaternary 13C NMR chemical shifts

Darwish, Tamim A.; Yepuri, Nageshwar R.; Holden, Peter J.; James, M. R.

doi:10.1016/j.aca.2016.05.003

Cited by 20 publications

(21 citation statements)

References 25 publications

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“…Spectra were referenced to residual deuterated solvent. 2 H and 13 C NMR with proton as well as proton and deuterium nuclei decoupled were recorded as detailed in a previous publication …”

Section: Methodsmentioning

confidence: 99%

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Apolipoprotein E Binding Drives Structural and Compositional Rearrangement of mRNA-Containing Lipid Nanoparticles

et al. 2021

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Emerging therapeutic treatments based on the production of proteins by delivering mRNA have become increasingly important in recent times. While lipid nanoparticles (LNPs) are approved vehicles for small interfering RNA delivery, there are still challenges to use this formulation for mRNA delivery. LNPs are typically a mixture of a cationic lipid, distearoylphosphatidylcholine (DSPC), cholesterol, and a PEG-lipid. The structural characterization of mRNA-containing LNPs (mRNA-LNPs) is crucial for a full understanding of the way in which they function, but this information alone is not enough to predict their fate upon entering the bloodstream. The biodistribution and cellular uptake of LNPs are affected by their surface composition as well as by the extracellular proteins present at the site of LNP administration, e.g., apolipoproteinE (ApoE). ApoE, being responsible for fat transport in the body, plays a key role in the LNP’s plasma circulation time. In this work, we use small-angle neutron scattering, together with selective lipid, cholesterol, and solvent deuteration, to elucidate the structure of the LNP and the distribution of the lipid components in the absence and the presence of ApoE. While DSPC and cholesterol are found to be enriched at the surface of the LNPs in buffer, binding of ApoE induces a redistribution of the lipids at the shell and the core, which also impacts the LNP internal structure, causing release of mRNA. The rearrangement of LNP components upon ApoE incubation is discussed in terms of potential relevance to LNP endosomal escape.

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“…Spectra were referenced to residual deuterated solvent. 2 H and 13 C NMR with proton as well as proton and deuterium nuclei decoupled were recorded as detailed in a previous publication …”

Section: Methodsmentioning

confidence: 99%

“…e ., 13 C { 1 H, 2 H}). The level of deuterium labeling at some specific sites in the molecule was calculated using 13 C { 1 H, 2 H} NMR according to the published method by Darwish et al . Detailed analysis and NMR and MS spectra of deuterated cholesterol (average 87% D) can be found in the SI.…”

Section: Methodsmentioning

confidence: 99%

Apolipoprotein E Binding Drives Structural and Compositional Rearrangement of mRNA-Containing Lipid Nanoparticles

et al. 2021

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“…In the case of irm‐ 2 H NMR, there is no need to take nOe account because of the quadrupolar nature of the 2 H nucleus; therefore,

T R = 5 . T_{1}^{max}

is sufficient because the target precision is 1%. Moreover, typical T 1 values for 2 H nuclei are shorter than for 13 C or 15 N, resulting in lower TR …”

Section: Principles Of Isotopic Nmr Analysismentioning

confidence: 99%

The new face of isotopic NMR at natural abundance

Jézéquel

Joubert

Giraudeau

et al. 2016

Magnetic Reson in Chemistry

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The most widely used method for isotope analysis at natural abundance is isotope ratio monitoring by Mass Spectrometry (irm-MS) which provides bulk isotopic composition in H, C, N, O or S. However, in the 1980s, the direct access to Site-specific Natural Isotope Fractionation by Nuclear Magnetic Resonance (SNIF-NMR ) was immediately recognized as a powerful technique to authenticate the origin of natural or synthetic products. The initial - and still most popular - application consisted in detecting the chaptalization of wines by irm- H NMR. The approach has been extended to a wide range of methodologies over the last decade, paving the way to a wide range of applications, not only in the field of authentication but also to study metabolism. In particular, the emerging irm- C NMR approach delivers direct access to position-specific C isotope content at natural abundance. After highlighting the application scope of irm-NMR ( H and C), this article describes the major improvements which made possible to reach the required accuracy of 1‰ (0.1%) in irm- C NMR. The last part of the manuscript summarizes the different steps to perform isotope analysis as a function of the sample properties (concentration, peak overlap) and the kind of targeted isotopic information (authentication, affiliation). Copyright © 2016 John Wiley & Sons, Ltd.

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“…The organic phase was dried over Na 2 SO 4 , filtered, and concentrated to provide the crude product mixture as an orange solid (6.1 g). This was adsorbed onto silica and purified by column chromatography (3:7–1:0 ethyl acetate/petroleum ether) to yield 4-hydroxybenzoic acid-d4 as a white-cream solid [1.6 g; overall 78% D by mass spectrometry (MS) and 13 C nuclear magnetic resonance (NMR) analysis; 58% D at the 2-position and 98% D at the 3-position by quantitative 13 C NMR analysis (Darwish et al , 2016); details of the NMR and MS spectra and deuteration analysis are provided in the online Supplementary Material].…”

Section: Methodsmentioning

confidence: 99%

Lattice response of the porous coordination framework Zn(hba) to guest adsorption

et al. 2017

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Analysis of in situ neutron powder diffraction data collected for the porous framework material Zn(hba) during gas adsorption reveals a two-stage response of the host lattice to increasing CO2 guest concentration, suggesting progressive occupation of multiple CO2 adsorption sites with different binding strengths. The response of the lattice to moderate CH4 guest concentrations is virtually indistinguishable from the response to CO2, demonstrating that the influence of host–guest interactions on the Zn(hba) framework is defined more strongly by the concentration than by the identity of the guests.

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Quantitative analysis of deuterium using the isotopic effect on quaternary 13C NMR chemical shifts

Cited by 20 publications

References 25 publications

Apolipoprotein E Binding Drives Structural and Compositional Rearrangement of mRNA-Containing Lipid Nanoparticles

Apolipoprotein E Binding Drives Structural and Compositional Rearrangement of mRNA-Containing Lipid Nanoparticles

The new face of isotopic NMR at natural abundance

Lattice response of the porous coordination framework Zn(hba) to guest adsorption

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