We demonstrate that natural isotopic abundance 2D heteronuclear correlation (HETCOR) solid-state NMR spectra can be used to significantly reduce or eliminate the broadening of 1 H and 13 C solid-state NMR spectra of organic solids due to anisotropic bulk magnetic susceptibility (ABMS). ABMS often manifests in solids with aromatic groups, such as active pharmaceutical ingredients (APIs), and inhomogeneously broadens the NMR peaks of all nuclei in the sample. Inhomogeneous peaks with full widths at half maximum (FWHM) of ∼1 ppm typically result from ABMS broadening and the low spectral resolution impedes the analysis of solid-state NMR spectra. ABMS broadening of solid-state NMR spectra has previously been eliminated using 2D multiple-quantum correlation experiments, or by performing NMR experiments on diluted materials or single crystals. However, these experiments are often infeasible due to their poor sensitivity and/or provide limited gains in resolution. 2D 1 H– 13 C HETCOR experiments have previously been applied to reduce susceptibility broadening in paramagnetic solids and we show that this strategy can significantly reduce ABMS broadening in diamagnetic organic solids. Comparisons of 1D solid-state NMR spectra and 1 H and 13 C solid-state NMR spectra obtained from 2D 1 H– 13 C HETCOR NMR spectra show that the HETCOR spectrum directly increases resolution by a factor of 1.5 to 8. The direct gain in resolution is determined by the ratio of the inhomogeneous 13 C/ 1 H linewidth to the homogeneous 1 H linewidth, with the former depending on the magnitude of the ABMS broadening and the strength of the applied field and the latter on the efficiency of homonuclear decoupling. The direct gains in resolution obtained using the 2D HETCOR experiments are better than that obtained by dilution. For solids with long proton longitudinal relaxation times, dynamic nuclear polarization (DNP) was applied to enhance sensitivity and enable the acquisition of 2D 1 H– 13 C HETCOR NMR spectra. 2D 1 H– 13 C HETCOR experiments were applied to resolve and partially assign the NMR signals of the form I and form II polymorphs of aspirin in a sample containing both forms. These findings have important implications for ultra-high field NMR experiments, optimization of decoupling schemes and assessment of the fundamental limits on the resolution of solid-state NMR spectra.
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Understanding Soap Formation in Paint Films by 207Pb, 119Sn, and 13C Solid-State NMR
The formation of lead carboxylates (lead soaps) has been identified as the cause of deterioration of hundreds of oil paintings. Soaps form when heavy metal-containing pigments, for example lead white and lead-tin yellow, react with saturated fatty acids in the oil medium. Understanding the mechanism of the reactions requires chemical information, which can be obtained with solid-state 207Pb, 119Sn and 13C NMR spectroscopy. Using the chemical-shift tensors determined by solid-state NMR we can gain structural insights on the coordination environment of the lead carboxylates and identify and quantify components in a paint film mixture. We have examined the spectroscopy of lead-containing pigments, lead carboxylates, and model paint films that were subjected to accelerated aging. We have also begun to investigate the dynamics of soap formation by 13C NMR spectroscopy. The NMR methods applied to the model paint systems could also be applied to other lead-containing materials.
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- NSF-PAR ID:
- 10012667
- Date Published:
- Journal Name:
- Materials science and technology
- ISSN:
- 1743-2847
- Page Range / eLocation ID:
- 2161 - 2168
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Heavy metal carboxylate or soap formation is a widespread deterioration problem affecting oil paintings and other works of art bearing oil‐based media. Lead soaps are prevalent in traditional oil paintings because lead white was the white pigment most frequently chosen by old masters for the paints and in some cases for the ground preparations, until the development of other white pigments from approximately the middle of the 18th century on, and because of the wide use of lead‐tin yellow. In the latter part of the 19th century, lead white began to be replaced by zinc white. The factors that influence soap formation have been the focus of intense study starting in the late 1990s. Since 2014, nuclear magnetic resonance (NMR) studies have contributed a unique perspective on the issue by providing chemical, structural, and dynamic information about the species involved in the process, as well as the effects of environmental conditions such as relative humidity and temperature on the kinetics of the reaction(s). In this review, we explore recent insights into soap formation gained through solid‐state NMR and single‐sided NMR techniques.
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Abstract In oriented‐sample (OS) solid‐state NMR of membrane proteins, the angular‐dependent dipolar couplings and chemical shifts provide a direct input for structure calculations. However, so far only1H–15N dipolar couplings and15N chemical shifts have been routinely assessed in oriented15N‐labeled samples. The main obstacle for extending this technique to membrane proteins of arbitrary topology has remained in the lack of additional experimental restraints. We have developed a new experimental triple‐resonance NMR technique, which was applied to uniformly doubly (15N,13C)‐labeled Pf1 coat protein in magnetically aligned DMPC/DHPC bicelles. The previously inaccessible1Hα–13Cαdipolar couplings have been measured, which make it possible to determine the torsion angles between the peptide planes without assuming α‐helical structure a priori. The fitting of three angular restraints per peptide plane and filtering by Rosetta scoring functions has yielded a consensus α‐helical transmembrane structure for Pf1 protein.
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Abstract In oriented‐sample (OS) solid‐state NMR of membrane proteins, the angular‐dependent dipolar couplings and chemical shifts provide a direct input for structure calculations. However, so far only1H–15N dipolar couplings and15N chemical shifts have been routinely assessed in oriented15N‐labeled samples. The main obstacle for extending this technique to membrane proteins of arbitrary topology has remained in the lack of additional experimental restraints. We have developed a new experimental triple‐resonance NMR technique, which was applied to uniformly doubly (15N,13C)‐labeled Pf1 coat protein in magnetically aligned DMPC/DHPC bicelles. The previously inaccessible1Hα–13Cαdipolar couplings have been measured, which make it possible to determine the torsion angles between the peptide planes without assuming α‐helical structure a priori. The fitting of three angular restraints per peptide plane and filtering by Rosetta scoring functions has yielded a consensus α‐helical transmembrane structure for Pf1 protein.
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Abstract A combined enzymatic and chemical synthesis of a 2′‐
O ‐cyanoethoxymethyl (CEM) protected [1′,6‐13C2, 5‐2H]‐uridine phosphoramidite is described herein. This is the first report of an atom‐specific nucleobase and ribose labeled 2′‐O ‐CEM protected ribonucleoside phosphoramidite. Importantly, the CEM 2′‐OH protecting group permits the efficient solid‐phase synthesis of large (>60 nucleotides) RNAs with good yield and purity. The new isotope‐labeled phosphoramidite can therefore be applied to nuclear magnetic resonance (NMR) spectroscopy studies. Specifically, the [1′,6‐13C2, 5‐2H]‐uridine phosphoramidite can be used to make position‐specifically labeled RNAs for NMR analysis without complications from resonance overlap and scalar and dipolar couplings. © 2022 Wiley Periodicals LLC.Basic Protocol 1 : Synthesis of the ribonucleoside6 Basic Protocol 2 : Synthesis of the ribonucleoside phosphoramidite11
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