Journal ArticleDOI
Structural characterization of an anhydrous polymorph of paclitaxel by solid-state NMR
TLDR
The three-dimensional structure of a unique polymorph of the anticancer drug paclitaxel (Taxol) is established using solid state NMR (SSNMR) tensor and heteronuclear correlation data and is thus the first conformational characterization with Z' > 1 established solely by SSNMR.Abstract:
The three-dimensional structure of a unique polymorph of the anticancer drug paclitaxel (Taxol®) is established using solid state NMR (SSNMR) tensor (13C & 15N) and heteronuclear correlation (1H–13C) data. The polymorph has two molecules per asymmetric unit (Z′ = 2) and is thus the first conformational characterization with Z′ > 1 established solely by SSNMR. Experimental data are correlated with structure through a series of computational models that extensively sample all conformations. For each computational model, corresponding tensor values are computed to supply comparisons with experimental information which, in turn, establishes paclitaxel’s structure. Heteronuclear correlation data at thirteen key positions provide shift assignments to the asymmetric unit for each comparison. The two distinct molecules of the asymmetric unit possess nearly identical baccatin III moieties with matching conformations of the C10 acetyl moiety and, specifically, the torsion angle formed by C30–O–C10–C9. Additionally, both are found to exhibit an extended conformation of the phenylisoserine sidechain at C13 with notable differences in the dihedral angles centered around the rotation axes of O–C13, C2′–C1′ and C3′–C2′.read more
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Powder crystallography by combined crystal structure prediction and high-resolution 1H solid-state NMR spectroscopy.
TL;DR: A fast method for crystal structure determination using crystal structure prediction and solid-state (1)H NMR is presented, which does not need any prior knowledge except the chemical formula; resonance assignment is not necessary.
Journal ArticleDOI
Powder NMR crystallography of thymol
TL;DR: A protocol for the structure determination of powdered solids at natural abundance by NMR is presented and illustrated and yields a crystal structure for the powdered sample, which differs by an atomic root-mean-square-deviation from the single crystal X-ray diffraction structure with DFT-optimized proton positions.
Journal ArticleDOI
De novo determination of the crystal structure of a large drug molecule by crystal structure prediction-based powder NMR crystallography.
TL;DR: This is the first example of NMR crystal structure determination for a molecular compound of previously unknown structure, and at 422 g/mol this is the largest compound to which this method has been applied so far.
Journal ArticleDOI
Powder crystallography of pharmaceutical materials by combined crystal structure prediction and solid-state 1H NMR spectroscopy
Maria Baias,Cory M. Widdifield,Jean-Nicolas Dumez,Hugh P. G. Thompson,Timothy G. Cooper,Elodie Salager,Sirena Bassil,Robin S. Stein,Anne Lesage,Graeme M. Day,Lyndon Emsley +10 more
TL;DR: For cocaine, flutamide and flufenamic acid, it is found that the assigned (1)H isotropic chemical shifts provide sufficient discrimination to determine the correct structures from a set of predicted structures using the root-mean-square deviation between experimentally determined and calculated chemical shifts.
Journal ArticleDOI
Solid‐State NMR Studies of Pharmaceutical Systems
TL;DR: In this article, a review of high-and low-resolution solid-state nuclear magnetic resonance (SSNMR) applications to the study of pharmaceuticals is presented, where the most important aspects treated concern structural, dynamic, and morphological properties, and, in particular, identification, characterization, and quantitation of polymorphs and related forms, conformational and crystalline packing behavior, amorphous phase properties and stability, effects of drug processing, molecular motions, API•excipient and excipient•excipients chemical and physical interactions, and phase mixing in hetero...
References
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Accurate and simple analytic representation of the electron-gas correlation energy
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TL;DR: A simple analytic representation of the correlation energy for a uniform electron gas, as a function of density parameter and relative spin polarization \ensuremath{\zeta}, which confirms the practical accuracy of the VWN and PZ representations and eliminates some minor problems.
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Structure of a protein determined by solid-state magic-angle-spinning NMR spectroscopy
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TL;DR: The calculated global fold of the α-spectrin SH3 domain is based on 286 inter-residue 13C–13C and six 15N–15N restraints, all self-consistently obtained by solid-state MAS NMR, which should be widely applicable to small membrane proteins that can be expressed in bacteria.
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Design and use of questionnaires: a review of best practice applicable to surveys of health service staff and patients
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