Characterization of Pharmaceutical Cocrystals and Salts by Dynamic Nuclear Polarization-Enhanced Solid-State NMR Spectroscopy

Zhao, Li; Hanrahan, Michael P.; Chakravarty, Paroma; Dipasquale, Antonio G.; Sirois, Lauren Elizabeth; Nagapudi, Karthik; Lubach, Joseph W.; Rossini, Aaron J.

doi:10.1021/acs.cgd.8b00203

Title: Characterization of Pharmaceutical Cocrystals and Salts by Dynamic Nuclear Polarization-Enhanced Solid-State NMR Spectroscopy

Journal Article · Thu Feb 15 00:00:00 EST 2018 · Crystal Growth and Design

DOI:https://doi.org/10.1021/acs.cgd.8b00203· OSTI ID:1422770

Zhao, Li ^[1]; Hanrahan, Michael P. ^[1]; Chakravarty, Paroma ^[2]; Dipasquale, Antonio G. ^[2]; Sirois, Lauren Elizabeth ^[2]; Nagapudi, Karthik ^[2]; Lubach, Joseph W. ^[2]; Rossini, Aaron J. ^[1]

Iowa State Univ., Ames, IA (United States). Dept. of Chemistry; Ames Lab., Ames, IA (United States)
Genentech, Inc., San Francisco, CA (United States)

Multicomponent solids such as cocrystals have emerged as a way to control and engineer the stability, solubility and manufacturability of solid active pharmaceutical ingredients (APIs). Cocrystals are typically formed by solution- or solid-phase reactions of APIs with suitable cocrystal coformers, which are often weak acids. One key structural question about a given multicomponent solid is whether it should be classified as a salt, where the basic API is protonated by the acid, or as a cocrystal, where the API and coformer remain neutral and engage in hydrogen bonding interactions. It has previously been demonstrated that solid-state NMR spectroscopy is a powerful probe of structure in cocrystals and salts of APIs, however, the poor sensitivity of solid-state NMR spectroscopy usually restricts the types of experiments that can be performed. Here relayed dynamic nuclear polarization (DNP) was applied to reduce solid-state NMR experiments by one to two orders of magnitude for salts and cocrystals of a complex API. The large sensitivity gains from DNP facilitates rapid acquisition of natural isotopic abundance 13C and 15N solid-state NMR spectra. Critically, DNP enables double resonance 1H-15N solid-state NMR experiments such as 2D 1H-15N HETCOR, 1H-15N CP-build up, 15N{1H} J-resolved/attached proton tests, 1H-15N DIPSHIFT and 1H-15N PRESTO. The latter two experiments allow 1H-15N dipolar coupling constants and H-N bond lengths to be accurately measured, providing an unambiguous assignment of nitrogen protonation state and definitive classification of the multi-component solids as cocrystals or salts. In conclusion, these types of measurements should also be extremely useful in the context of polymorph discrimination, NMR crystallography structure determination and for probing hydrogen bonding in a variety of organic materials.

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Research Organization:: Ames Laboratory (AMES), Ames, IA (United States)

Sponsoring Organization:: USDOE; National Science Foundation (NSF)

Grant/Contract Number:: AC02-07CH11358; 1709972

OSTI ID:: 1422770

Report Number(s):: IS-J-9577

Journal Information:: Crystal Growth and Design, Vol. 18, Issue 4; ISSN 1528-7483

Publisher:: American Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 47 works

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References (114)

Crystal engineering of the composition of pharmaceutical phases. Do pharmaceutical co-crystals represent a new path to improved medicines? Almarsson, �rn; Zaworotko, Michael J. Chemical Communications, Issue 17 https://doi.org/10.1039/b402150a	journal	January 2004
Pharmaceutical Cocrystals: An Emerging Approach to Physical Property Enhancement Jones, William; Motherwell, W. D. Samuel; Trask, Andrew V. MRS Bulletin, Vol. 31, Issue 11 https://doi.org/10.1557/mrs2006.206	journal	November 2006
The Salt−Cocrystal Continuum: The Influence of Crystal Structure on Ionization State Childs, Scott L.; Stahly, G. Patrick; Park, Aeri Molecular Pharmaceutics, Vol. 4, Issue 3 https://doi.org/10.1021/mp0601345	journal	April 2007
Diversity in Single- and Multiple-Component Crystals. The Search for and Prevalence of Polymorphs and Cocrystals Stahly, G. Patrick Crystal Growth & Design, Vol. 7, Issue 6 https://doi.org/10.1021/cg060838j	journal	June 2007
Pharmaceutical Cocrystals and Their Physicochemical Properties Schultheiss, Nate; Newman, Ann Crystal Growth & Design, Vol. 9, Issue 6 https://doi.org/10.1021/cg900129f	journal	June 2009
Benefits of cocrystallisation in pharmaceutical materials science: an update Friščić, Tomislav; Jones, William Journal of Pharmacy and Pharmacology, Vol. 62, Issue 11 https://doi.org/10.1111/j.2042-7158.2010.01133.x	journal	October 2010
Preface: Engineering of pharmaceutical cocrystals, salts and polymorphs: Advances and Challenges Douroumis, Dennis; Nokhodchi, Ali Advanced Drug Delivery Reviews, Vol. 117 https://doi.org/10.1016/j.addr.2017.10.002	journal	August 2017
Exploring the salt–cocrystal continuum with solid-state NMR using natural-abundance samples: implications for crystal engineering Rajput, Lalit; Banik, Manas; Yarava, Jayasubba Reddy IUCrJ, Vol. 4, Issue 4 https://doi.org/10.1107/S205225251700687X	journal	June 2017
First O−H−N Hydrogen Bond with a Centered Proton Obtained by Thermally Induced Proton Migration Steiner, Thomas; Majerz, Irena; Wilson, Chick C. Angewandte Chemie International Edition, Vol. 40, Issue 14 https://doi.org/10.1002/1521-3773(20010716)40:14<2651::AID-ANIE2651>3.0.CO;2-2	journal	July 2001
Imaging proton migration from X-rays and neutrons Parkin, Andrew; Harte, Suzanne M.; Goeta, Andr�s E. New Journal of Chemistry, Vol. 28, Issue 6 https://doi.org/10.1039/b315515c	journal	January 2004
Screening for new pharmaceutical solid forms using mechanochemistry: A practical guide Hasa, Dritan; Jones, William Advanced Drug Delivery Reviews, Vol. 117 https://doi.org/10.1016/j.addr.2017.05.001	journal	August 2017
Determining Hydrogen Atom Positions for Hydrogen Bonded Interactions: A Distance-Dependent Neutron-Normalized Method Lusi, Matteo; Barbour, Leonard J. Crystal Growth & Design, Vol. 11, Issue 12 https://doi.org/10.1021/cg201087s	journal	December 2011
Accurate Hydrogen Positions in Organic Crystals: Assessing a Quantum-Chemical Aide Deringer, Volker L.; Hoepfner, Veronika; Dronskowski, Richard Crystal Growth & Design, Vol. 12, Issue 2 https://doi.org/10.1021/cg201505n	journal	January 2012
Characterization of Proton Transfer in Co-Crystals by X-ray Photoelectron Spectroscopy (XPS) Stevens, Joanna S.; Byard, Stephen J.; Schroeder, Sven L. M. Crystal Growth & Design, Vol. 10, Issue 3 https://doi.org/10.1021/cg901481q	journal	March 2010
Identification of Protonation State by XPS, Solid-State NMR, and DFT: Characterization of the Nature of a New Theophylline Complex by Experimental and Computational Methods Stevens, Joanna S.; Byard, Stephen J.; Muryn, Christopher A. The Journal of Physical Chemistry B, Vol. 114, Issue 44 https://doi.org/10.1021/jp106465u	journal	November 2010
Salt or Co-Crystal? Determination of Protonation State by X-Ray Photoelectron Spectroscopy (XPS) Stevens, Joanna S.; Byard, Stephen J.; Schroeder, Sven L. M. Journal of Pharmaceutical Sciences, Vol. 99, Issue 11 https://doi.org/10.1002/jps.22164	journal	November 2010
Pharmaceutical cocrystals, salts and polymorphs: Advanced characterization techniques Pindelska, Edyta; Sokal, Agnieszka; Kolodziejski, Waclaw Advanced Drug Delivery Reviews, Vol. 117 https://doi.org/10.1016/j.addr.2017.09.014	journal	August 2017
Solid-state NMR spectroscopy in pharmaceutical research and analysis Berendt, Robert T.; Sperger, Diana M.; Munson, Eric J. TrAC Trends in Analytical Chemistry, Vol. 25, Issue 10 https://doi.org/10.1016/j.trac.2006.07.006	journal	November 2006
NMR studies of organic polymorphs & solvates Harris, Robin K. The Analyst, Vol. 131, Issue 3 https://doi.org/10.1039/b516057j	journal	January 2006
Solid-State NMR Analysis of Organic Cocrystals and Complexes Vogt, Frederick G.; Clawson, Jacalyn S.; Strohmeier, Mark Crystal Growth & Design, Vol. 9, Issue 2 https://doi.org/10.1021/cg8007014	journal	December 2008
Evolution of solid-state NMR in pharmaceutical analysis Vogt, Frederick G. Future Medicinal Chemistry, Vol. 2, Issue 6 https://doi.org/10.4155/fmc.10.200	journal	June 2010
Solid-State Acid−Base Interactions in Complexes of Heterocyclic Bases with Dicarboxylic Acids: Crystallography, Hydrogen Bond Analysis, and ¹⁵ N NMR Spectroscopy Li, Z. Jane; Abramov, Yuriy; Bordner, Jon Journal of the American Chemical Society, Vol. 128, Issue 25 https://doi.org/10.1021/ja0541332	journal	June 2006
¹ H, ¹³ C, and ¹⁵ N Solid-State NMR Studies of Imidazole- and Morpholine-Based Model Compounds Possessing Halogen and Hydrogen Bonding Capabilities Bouchmella, Karim; Dutremez, Sylvain G.; Alonso, Bruno Crystal Growth & Design, Vol. 8, Issue 11 https://doi.org/10.1021/cg700975v	journal	September 2008
N?H bond stretching in histidine complexes: a solid-state NMR study Song, Xiang-jin; Rienstra, Chad M.; McDermott, Ann E. Magnetic Resonance in Chemistry, Vol. 39, Issue S1 https://doi.org/10.1002/mrc.956	journal	January 2001
Probing intermolecular interactions and nitrogen protonation in pharmaceuticals by novel 15N-edited and 2D 14N-1H solid-state NMR Tatton, Andrew S.; Pham, Tran N.; Vogt, Frederick G. CrystEngComm, Vol. 14, Issue 8 https://doi.org/10.1039/c2ce06547a	journal	January 2012
Improvement of the water solubility of tolfenamic acid by new multiple-component crystals produced by mechanochemical methods Gaglioti, K.; Chierotti, M. R.; Grifasi, F. CrystEngComm, Vol. 16, Issue 35 https://doi.org/10.1039/C4CE00549J	journal	January 2014
Investigation of Drug–Excipient Interactions in Lapatinib Amorphous Solid Dispersions Using Solid-State NMR Spectroscopy Song, Yang; Yang, Xinghao; Chen, Xin Molecular Pharmaceutics, Vol. 12, Issue 3 https://doi.org/10.1021/mp500692a	journal	January 2015
Role of the Strength of Drug–Polymer Interactions on the Molecular Mobility and Crystallization Inhibition in Ketoconazole Solid Dispersions Mistry, Pinal; Mohapatra, Sarat; Gopinath, Tata Molecular Pharmaceutics, Vol. 12, Issue 9 https://doi.org/10.1021/acs.molpharmaceut.5b00333	journal	July 2015
Acid–Base Interactions of Polystyrene Sulfonic Acid in Amorphous Solid Dispersions Using a Combined UV/FTIR/XPS/ssNMR Study Song, Yang; Zemlyanov, Dmitry; Chen, Xin Molecular Pharmaceutics, Vol. 13, Issue 2 https://doi.org/10.1021/acs.molpharmaceut.5b00708	journal	December 2015
Probing Hydrogen Bonding in Cocrystals and Amorphous Dispersions Using ¹⁴ N– ¹ H HMQC Solid-State NMR Tatton, Andrew S.; Pham, Tran N.; Vogt, Frederick G. Molecular Pharmaceutics, Vol. 10, Issue 3 https://doi.org/10.1021/mp300423r	journal	February 2013
Carbon-13 Spectral Editing in Solid-State NMR Using Heteronuclear Scalar Couplings Lesage, Anne; Steuernagel, Stefan; Emsley, Lyndon Journal of the American Chemical Society, Vol. 120, Issue 28 https://doi.org/10.1021/ja981019t	journal	July 1998
Heterosynthon mediated tailored synthesis of pharmaceutical complexes: a solid-state NMR approach Khan, Mujeeb; Enkelmann, Volker; Brunklaus, Gunther CrystEngComm, Vol. 13, Issue 9 https://doi.org/10.1039/c0ce00657b	journal	January 2011
Crystal Engineering of Pharmaceutical Co-crystals: “NMR Crystallography” of Niclosamide Co-crystals Luedeker, David; Gossmann, Rebecca; Langer, Klaus Crystal Growth & Design, Vol. 16, Issue 6 https://doi.org/10.1021/acs.cgd.5b01619	journal	April 2016
A ¹³ C solid-state NMR investigation of four cocrystals of caffeine and theophylline Vigilante, Nicolas J.; Mehta, Manish A. Acta Crystallographica Section C Structural Chemistry, Vol. 73, Issue 3 https://doi.org/10.1107/S2053229617000869	journal	February 2017
NMR crystallography of ezetimibe co-crystals Lüdeker, David; Brunklaus, Gunther Solid State Nuclear Magnetic Resonance, Vol. 65 https://doi.org/10.1016/j.ssnmr.2014.11.002	journal	February 2015
Measurement of NH Bond Lengths by Fast Magic-Angle Spinning Solid-State NMR Spectroscopy: A New Method for the Quantification of Hydrogen Bonds Zhao, Xin; Sudmeier, James L.; Bachovchin, William W. Journal of the American Chemical Society, Vol. 123, Issue 44 https://doi.org/10.1021/ja016328p	journal	November 2001
Investigation of an N��H hydrogen bond in a solid benzoxazine dimer by1H-15N NMR correlation techniques under fast magic-angle spinning Goward, Gillian R.; Schnell, Ingo; Brown, Steven P. Magnetic Resonance in Chemistry, Vol. 39, Issue S1 https://doi.org/10.1002/mrc.931	journal	January 2001
Multi-responsive cellulose nanocrystal–rhodamine conjugates: an advanced structure study by solid-state dynamic nuclear polarization (DNP) NMR Zhao, Li; Li, Wei; Plog, Andreas Phys. Chem. Chem. Phys., Vol. 16, Issue 47 https://doi.org/10.1039/C4CP04096A	journal	January 2014
Imidazole-Doped Cellulose as Membrane for Fuel Cells: Structural and Dynamic Insights from Solid-State NMR Zhao, Li; Smolarkiewicz, Iga; Limbach, Hans-Heinrich The Journal of Physical Chemistry C, Vol. 120, Issue 35 https://doi.org/10.1021/acs.jpcc.6b07049	journal	August 2016
¹⁵ N− ¹ H Bond Length Determination in Natural Abundance by Inverse Detection in Fast-MAS Solid-State NMR Spectroscopy Schnell, Ingo; Saalwächter, Kay Journal of the American Chemical Society, Vol. 124, Issue 37 https://doi.org/10.1021/ja026657x	journal	September 2002
Protonation, Tautomerization, and Rotameric Structure of Histidine: A Comprehensive Study by Magic-Angle-Spinning Solid-State NMR Li, Shenhui; Hong, Mei Journal of the American Chemical Society, Vol. 133, Issue 5 https://doi.org/10.1021/ja108943n	journal	February 2011
NMR Studies of Active-Site Properties of Human Carbonic Anhydrase II by Using ¹⁵ N-Labeled 4-Methylimidazole as a Local Probe and Histidine Hydrogen-Bond Correlations Shenderovich, Ilya G.; Lesnichin, Stepan B.; Tu, Chingkuang Chemistry - A European Journal, Vol. 21, Issue 7 https://doi.org/10.1002/chem.201404083	journal	December 2014
Dynamic nuclear polarization with a cyclotron resonance maser at 5 T Becerra, Lino R.; Gerfen, Gary J.; Temkin, Richard J. Physical Review Letters, Vol. 71, Issue 21 https://doi.org/10.1103/PhysRevLett.71.3561	journal	November 1993
Polarization-Enhanced NMR Spectroscopy of Biomolecules in Frozen Solution Hall, Dennis A.; Maus, Douglas C.; Gerfen, Gary J. Science, Vol. 276, Issue 5314 https://doi.org/10.1126/science.276.5314.930	journal	May 1997
Dynamic nuclear polarization at high magnetic fields Maly, Thorsten; Debelouchina, Galia T.; Bajaj, Vikram S. The Journal of Chemical Physics, Vol. 128, Issue 5 https://doi.org/10.1063/1.2833582	journal	February 2008
High Frequency Dynamic Nuclear Polarization Ni, Qing Zhe; Daviso, Eugenio; Can, Thach V. Accounts of Chemical Research, Vol. 46, Issue 9 https://doi.org/10.1021/ar300348n	journal	April 2013
Dynamic Nuclear Polarization of Amyloidogenic Peptide Nanocrystals: GNNQQNY, a Core Segment of the Yeast Prion Protein Sup35p van der Wel, Patrick C. A.; Hu, Kan-Nian; Lewandowski, Józef Journal of the American Chemical Society, Vol. 128, Issue 33 https://doi.org/10.1021/ja0626685	journal	August 2006
Dynamic Nuclear Polarization NMR Spectroscopy of Microcrystalline Solids Rossini, Aaron J.; Zagdoun, Alexandre; Hegner, Franziska Journal of the American Chemical Society, Vol. 134, Issue 40 https://doi.org/10.1021/ja308135r	journal	September 2012
Dynamic Nuclear Polarization Enhanced NMR Spectroscopy for Pharmaceutical Formulations Rossini, Aaron J.; Widdifield, Cory M.; Zagdoun, Alexandre Journal of the American Chemical Society, Vol. 136, Issue 6 https://doi.org/10.1021/ja4092038	journal	January 2014
Transportable hyperpolarized metabolites Ji, Xiao; Bornet, Aurélien; Vuichoud, Basile Nature Communications, Vol. 8, Issue 1 https://doi.org/10.1038/ncomms13975	journal	January 2017
DNP-enhanced solid-state NMR spectroscopy of active pharmaceutical ingredients Zhao, Li; Pinon, Arthur C.; Emsley, Lyndon Magnetic Resonance in Chemistry, Vol. 56, Issue 7 https://doi.org/10.1002/mrc.4688	journal	January 2018
Surface Enhanced NMR Spectroscopy by Dynamic Nuclear Polarization Lesage, Anne; Lelli, Moreno; Gajan, David Journal of the American Chemical Society, Vol. 132, Issue 44 https://doi.org/10.1021/ja104771z	journal	November 2010
Non-aqueous solvents for DNP surface enhanced NMR spectroscopy Zagdoun, Alexandre; Rossini, Aaron J.; Gajan, David Chem. Commun., Vol. 48, Issue 5 https://doi.org/10.1039/C1CC15242D	journal	January 2012
Rapid Natural-Abundance 2D ¹³ C- ¹³ C Correlation Spectroscopy Using Dynamic Nuclear Polarization Enhanced Solid-State NMR and Matrix-Free Sample Preparation Takahashi, Hiroki; Lee, Daniel; Dubois, Lionel Angewandte Chemie, Vol. 124, Issue 47 https://doi.org/10.1002/ange.201206102	journal	October 2012
Matrix-free dynamic nuclear polarization enables solid-state NMR 13C–13C correlation spectroscopy of proteins at natural isotopic abundance Takahashi, Hiroki; Hediger, Sabine; De Paëpe, Gaël Chemical Communications, Vol. 49, Issue 82 https://doi.org/10.1039/c3cc45195j	journal	January 2013
Quantitative Structural Constraints for Organic Powders at Natural Isotopic Abundance Using Dynamic Nuclear Polarization Solid-State NMR Spectroscopy Mollica, Giulia; Dekhil, Myriam; Ziarelli, Fabio Angewandte Chemie International Edition, Vol. 54, Issue 20 https://doi.org/10.1002/anie.201501172	journal	March 2015
Structure elucidation of a complex CO ₂ -based organic framework material by NMR crystallography Leclaire, Julien; Poisson, Guillaume; Ziarelli, Fabio Chemical Science, Vol. 7, Issue 7 https://doi.org/10.1039/C5SC03810C	journal	January 2016
A New Tool for NMR Crystallography: Complete ¹³ C/ ¹⁵ N Assignment of Organic Molecules at Natural Isotopic Abundance Using DNP-Enhanced Solid-State NMR Märker, Katharina; Pingret, Morgane; Mouesca, Jean-Marie Journal of the American Chemical Society, Vol. 137, Issue 43 https://doi.org/10.1021/jacs.5b09964	journal	October 2015
High-resolution NMR of hydrogen in organic solids by DNP enhanced natural abundance deuterium spectroscopy Rossini, Aaron J.; Schlagnitweit, Judith; Lesage, Anne Journal of Magnetic Resonance, Vol. 259 https://doi.org/10.1016/j.jmr.2015.08.020	journal	October 2015
Dynamic nuclear polarisation enhanced ¹⁴ N overtone MAS NMR spectroscopy Rossini, Aaron J.; Emsley, Lyndon; O'Dell, Luke A. Phys. Chem. Chem. Phys., Vol. 16, Issue 25 https://doi.org/10.1039/C4CP00590B	journal	January 2014
Dynamic Nuclear Polarization Enhanced Solid-State NMR Spectroscopy of Functionalized Metal-Organic Frameworks Rossini, Aaron J.; Zagdoun, Alexandre; Lelli, Moreno Angewandte Chemie International Edition, Vol. 51, Issue 1 https://doi.org/10.1002/anie.201106030	journal	November 2011
Dynamic Nuclear Polarization Enhanced Natural Abundance ¹⁷ O Spectroscopy Blanc, Frédéric; Sperrin, Luke; Jefferson, David A. Journal of the American Chemical Society, Vol. 135, Issue 8 https://doi.org/10.1021/ja4004377	journal	February 2013
Interfacial Ca2+ environments in nanocrystalline apatites revealed by dynamic nuclear polarization enhanced 43Ca NMR spectroscopy Lee, Daniel; Leroy, César; Crevant, Charlène Nature Communications, Vol. 8, Issue 1 https://doi.org/10.1038/ncomms14104	journal	January 2017
Dynamic Nuclear Polarization NMR of Low-γ Nuclei: Structural Insights into Hydrated Yttrium-Doped BaZrO ₃ Blanc, Frédéric; Sperrin, Luke; Lee, Daniel The Journal of Physical Chemistry Letters, Vol. 5, Issue 14 https://doi.org/10.1021/jz5007669	journal	June 2014
A novel class of phenol–pyridine co-crystals for second harmonic generation Huang, Kin-Shan; Britton, Doyle; late Margaret C. Etter, the Journal of Materials Chemistry, Vol. 7, Issue 5 https://doi.org/10.1039/a604311j	journal	January 1997
Towards Designing Proton-Transfer Systems—Direct Imaging of Proton Disorder in a Hydrogen-Bonded Carboxylic Acid Dimer by Variable-Temperature X-ray Diffraction Wilson, Chick C.; Goeta, Andres E. Angewandte Chemie International Edition, Vol. 43, Issue 16 https://doi.org/10.1002/anie.200352650	journal	April 2004
Tape and layer structures in cocrystals of some di- and tricarboxylic acids with 4,4′-bipyridines and isonicotinamide. From binary to ternary cocrystals Bhogala, Balakrishna R.; Basavoju, Srinivas; Nangia, Ashwini CrystEngComm, Vol. 7, Issue 90 https://doi.org/10.1039/b509162d	journal	January 2005
On the temperature dependence of H- U _iso in the riding hydrogen model Lübben, Jens; Volkmann, Christian; Grabowsky, Simon Acta Crystallographica Section A Foundations and Advances, Vol. 70, Issue 4 https://doi.org/10.1107/S2053273314010626	journal	May 2014
Polymorphs of Theophylline Characterized by DNP Enhanced Solid-State NMR Pinon, Arthur C.; Rossini, Aaron J.; Widdifield, Cory M. Molecular Pharmaceutics, Vol. 12, Issue 11 https://doi.org/10.1021/acs.molpharmaceut.5b00610	journal	October 2015
Large Molecular Weight Nitroxide Biradicals Providing Efficient Dynamic Nuclear Polarization at Temperatures up to 200 K Zagdoun, Alexandre; Casano, Gilles; Ouari, Olivier Journal of the American Chemical Society, Vol. 135, Issue 34 https://doi.org/10.1021/ja405813t	journal	August 2013
Proton‐enhanced NMR of dilute spins in solids Pines, A.; Gibby, M. G.; Waugh, J. S. The Journal of Chemical Physics, Vol. 59, Issue 2 https://doi.org/10.1063/1.1680061	journal	July 1973
Carbon-13 nuclear magnetic resonance of polymers spinning at the magic angle Schaefer, Jacob; Stejskal, E. O. Journal of the American Chemical Society, Vol. 98, Issue 4 https://doi.org/10.1021/ja00420a036	journal	February 1976
In Situ Characterization of Pharmaceutical Formulations by Dynamic Nuclear Polarization Enhanced MAS NMR Ni, Qing Zhe; Yang, Fengyuan; Can, Thach V. The Journal of Physical Chemistry B, Vol. 121, Issue 34 https://doi.org/10.1021/acs.jpcb.7b07213	journal	August 2017
Total suppression of sidebands in CPMAS C-13 NMR Dixon, W. T.; Schaefer, Jacob; Sefcik, M. D. Journal of Magnetic Resonance (1969), Vol. 49, Issue 2 https://doi.org/10.1016/0022-2364(82)90199-8	journal	September 1982
Spinning‐sideband‐free and spinning‐sideband‐only NMR spectra in spinning samples Dixon, W. Thomas The Journal of Chemical Physics, Vol. 77, Issue 4 https://doi.org/10.1063/1.444076	journal	August 1982
¹⁵N Chemical Shift Principal Values in Nitrogen Heterocycles Solum, Mark S.; Altmann, Karen L.; Strohmeier, Mark Journal of the American Chemical Society, Vol. 119, Issue 41 https://doi.org/10.1021/ja964135+	journal	October 1997
Direct spectral optimisation of proton–proton homonuclear dipolar decoupling in solid-state NMR Elena, Bénédicte; de Paëpe, Gaël; Emsley, Lyndon Chemical Physics Letters, Vol. 398, Issue 4-6 https://doi.org/10.1016/j.cplett.2004.09.122	journal	November 2004
Powder NMR crystallography of thymol Salager, Elodie; Stein, Robin S.; Pickard, Chris J. Physical Chemistry Chemical Physics, Vol. 11, Issue 15 https://doi.org/10.1039/b821018g	journal	January 2009
Powder Crystallography by Combined Crystal Structure Prediction and High-Resolution ¹ H Solid-State NMR Spectroscopy Salager, Elodie; Day, Graeme M.; Stein, Robin S. Journal of the American Chemical Society, Vol. 132, Issue 8 https://doi.org/10.1021/ja909449k	journal	March 2010
Powder crystallography of pharmaceutical materials by combined crystal structure prediction and solid-state 1H NMR spectroscopy Baias, Maria; Widdifield, Cory M.; Dumez, Jean-Nicolas Physical Chemistry Chemical Physics, Vol. 15, Issue 21 https://doi.org/10.1039/c3cp41095a	journal	January 2013
NMR Crystallography: Toward Chemical Shift-Driven Crystal Structure Determination of the β-Lactam Antibiotic Amoxicillin Trihydrate Santos, Sérgio M.; Rocha, João; Mafra, Luís Crystal Growth & Design, Vol. 13, Issue 6 https://doi.org/10.1021/cg4002785	journal	April 2013
Combining solid-state NMR spectroscopy with first-principles calculations – a guide to NMR crystallography Ashbrook, Sharon E.; McKay, David Chemical Communications, Vol. 52, Issue 45 https://doi.org/10.1039/C6CC02542K	journal	January 2016
Furosemide's one little hydrogen atom: NMR crystallography structure verification of powdered molecular organics Widdifield, Cory M.; Robson, Harry; Hodgkinson, Paul Chemical Communications, Vol. 52, Issue 40 https://doi.org/10.1039/C6CC02171A	journal	January 2016
Positional Variance in NMR Crystallography Hofstetter, Albert; Emsley, Lyndon Journal of the American Chemical Society, Vol. 139, Issue 7 https://doi.org/10.1021/jacs.6b12705	journal	February 2017
A Method for Measuring Heteronuclear ( ¹ H− ¹³ C) Distances in High Speed MAS NMR van Rossum, B. -J.; de Groot, C. P.; Ladizhansky, V. Journal of the American Chemical Society, Vol. 122, Issue 14 https://doi.org/10.1021/ja992714j	journal	March 2000
High‐resolution J ‐resolved NMR spectra of dilute spins in solids Terao, T.; Miura, H.; Saika, A. The Journal of Chemical Physics, Vol. 75, Issue 3 https://doi.org/10.1063/1.442194	journal	August 1981
Frequency-selective measurement of heteronuclear scalar couplings in solid-state NMR Trébosc, J.; Amoureux, J. P.; Delevoye, L. Solid State Sciences, Vol. 6, Issue 10 https://doi.org/10.1016/j.solidstatesciences.2004.04.019	journal	October 2004
Facile measurement of 1H–15N residual dipolar couplings in larger perdeuterated proteins Fitzkee, Nicholas C.; Bax, Ad Journal of Biomolecular NMR, Vol. 48, Issue 2 https://doi.org/10.1007/s10858-010-9441-9	journal	August 2010
Indirectly detected heteronuclear correlation solid-state NMR spectroscopy of naturally abundant 15N nuclei Althaus, Stacey M.; Mao, Kanmi; Stringer, John A. Solid State Nuclear Magnetic Resonance, Vol. 57-58 https://doi.org/10.1016/j.ssnmr.2013.11.001	journal	February 2014
High resolution solid state NMRspectroscopy in surface organometallic chemistry: access to molecular understanding of active sites of well-defined heterogeneous catalysts Blanc, Frédéric; Copéret, Christophe; Lesage, Anne Chem. Soc. Rev., Vol. 37, Issue 3 https://doi.org/10.1039/B612793M	journal	January 2008
Observation of a H-Agostic Bond in a Highly Active Rhenium–Alkylidene Olefin Metathesis Heterogeneous Catalyst by Two-Dimensional Solid-State NMR Spectroscopy Lesage, Anne; Emsley, Lyndon; Chabanas, Mathieu Angewandte Chemie International Edition, Vol. 41, Issue 23 https://doi.org/10.1002/1521-3773(20021202)41:23<4535::AID-ANIE4535>3.0.CO;2-O	journal	December 2002
Enhanced sensitivity in high-resolution 1H solid-state NMR spectroscopy with DUMBO dipolar decoupling under ultra-fast MAS Salager, Elodie; Stein, Robin S.; Steuernagel, Stefan Chemical Physics Letters, Vol. 469, Issue 4-6 https://doi.org/10.1016/j.cplett.2008.12.073	journal	February 2009
Coupling Amplification in 2D MAS NMR and Its Application to Torsion Angle Determination in Peptides Hong, Mei; Gross, John D.; Rienstra, Chad M. Journal of Magnetic Resonance, Vol. 129, Issue 1 https://doi.org/10.1006/jmre.1997.1242	journal	November 1997
Heteronuclear polarization transfer by symmetry-based recoupling sequences in solid-state NMR Zhao, Xin; Hoffbauer, Wilfried; Schmedt auf der Günne, Jörn Solid State Nuclear Magnetic Resonance, Vol. 26, Issue 2 https://doi.org/10.1016/j.ssnmr.2003.11.001	journal	September 2004
Neutron diffraction study of L-histidine hydrochloride monohydrate Fuess, H.; Hohlwein, D.; Mason, S. A. Acta Crystallographica Section B Structural Crystallography and Crystal Chemistry, Vol. 33, Issue 3 https://doi.org/10.1107/S0567740877004415	journal	March 1977
Nuclear Magnetic Resonance Saturation and Rotary Saturation in Solids Redfield, Alfred G. Physical Review, Vol. 98, Issue 6 https://doi.org/10.1103/PhysRev.98.1787	journal	June 1955
Nuclear-Magnetic-Resonance Line Narrowing by a Rotating rf Field Lee, Moses; Goldburg, Walter I. Physical Review, Vol. 140, Issue 4A https://doi.org/10.1103/PhysRev.140.A1261	journal	November 1965
Natural Abundance ¹⁷ O DNP Two-Dimensional and Surface-Enhanced NMR Spectroscopy Perras, Frédéric A.; Kobayashi, Takeshi; Pruski, Marek Journal of the American Chemical Society, Vol. 137, Issue 26 https://doi.org/10.1021/jacs.5b03905	journal	June 2015
Above-room-temperature ferroelectricity in a single-component molecular crystal Horiuchi, Sachio; Tokunaga, Yusuke; Giovannetti, Gianluca Nature, Vol. 463, Issue 7282, p. 789-792 https://doi.org/10.1038/nature08731	journal	February 2010
Solid-state dynamic nuclear polarization at 263 GHz: spectrometer design and experimental results Rosay, Melanie; Tometich, Leo; Pawsey, Shane Physical Chemistry Chemical Physics, Vol. 12, Issue 22 https://doi.org/10.1039/c003685b	journal	January 2010
NMR nomenclature. Nuclear spin properties and conventions for chemical shifts(IUPAC Recommendations 2001) Harris, Robin K.; Becker, Edwin D.; Cabral de Menezes, Sonia M. Pure and Applied Chemistry, Vol. 73, Issue 11 https://doi.org/10.1351/pac200173111795	journal	January 2001
Magic-angle spinning and polarization transfer in proton-enhanced NMR Stejskal, E. O.; Schaefer, Jacob; Waugh, J. S. Journal of Magnetic Resonance (1969), Vol. 28, Issue 1 https://doi.org/10.1016/0022-2364(77)90260-8	journal	October 1977
Variable-Amplitude Cross-Polarization MAS NMR Peersen, O. B.; Wu, X. L.; Kustanovich, I. Journal of Magnetic Resonance, Series A, Vol. 104, Issue 3 https://doi.org/10.1006/jmra.1993.1231	journal	October 1993
An Improved Broadband Decoupling Sequence for Liquid Crystals and Solids Fung, B. M.; Khitrin, A. K.; Ermolaev, Konstantin Journal of Magnetic Resonance, Vol. 142, Issue 1 https://doi.org/10.1006/jmre.1999.1896	journal	January 2000
Two-dimensional heteronuclear chemical shift correlation spectroscopy in rotating solids Roberts, James E.; Vega, Shimon; Griffin, Robert G. Journal of the American Chemical Society, Vol. 106, Issue 9 https://doi.org/10.1021/ja00321a003	journal	May 1984
SIMPSON: A General Simulation Program for Solid-State NMR Spectroscopy Bak, Mads; Rasmussen, Jimmy T.; Nielsen, Niels Chr Journal of Magnetic Resonance, Vol. 147, Issue 2 https://doi.org/10.1006/jmre.2000.2179	journal	December 2000
Optimal control in NMR spectroscopy: Numerical implementation in SIMPSON Tošner, Zdeněk; Vosegaard, Thomas; Kehlet, Cindie Journal of Magnetic Resonance, Vol. 197, Issue 2 https://doi.org/10.1016/j.jmr.2008.11.020	journal	April 2009
Computer-intensive simulation of solid-state NMR experiments using SIMPSON Tošner, Zdeněk; Andersen, Rasmus; Stevensson, Baltzar Journal of Magnetic Resonance, Vol. 246 https://doi.org/10.1016/j.jmr.2014.07.002	journal	September 2014
First principles methods using CASTEP Clark, Stewart J.; Segall, Matthew D.; Pickard, Chris J. Zeitschrift für Kristallographie - Crystalline Materials, Vol. 220, Issue 5/6 https://doi.org/10.1524/zkri.220.5.567.65075	journal	January 2005
Generalized Gradient Approximation Made Simple Perdew, John P.; Burke, Kieron; Ernzerhof, Matthias Physical Review Letters, Vol. 77, Issue 18, p. 3865-3868 https://doi.org/10.1103/PhysRevLett.77.3865	journal	October 1996
Calculation of NMR chemical shifts for extended systems using ultrasoft pseudopotentials Yates, Jonathan R.; Pickard, Chris J.; Mauri, Francesco Physical Review B, Vol. 76, Issue 2 https://doi.org/10.1103/PhysRevB.76.024401	journal	July 2007
Semiempirical GGA-type density functional constructed with a long-range dispersion correction Grimme, Stefan Journal of Computational Chemistry, Vol. 27, Issue 15, p. 1787-1799 https://doi.org/10.1002/jcc.20495	journal	January 2006
All-electron magnetic response with pseudopotentials: NMR chemical shifts Pickard, Chris J.; Mauri, Francesco Physical Review B, Vol. 63, Issue 24 https://doi.org/10.1103/PhysRevB.63.245101	journal	May 2001
Benchmark fragment-based ¹ H, ¹³ C, ¹⁵ N and ¹⁷ O chemical shift predictions in molecular crystals Hartman, Joshua D.; Kudla, Ryan A.; Day, Graeme M. Physical Chemistry Chemical Physics, Vol. 18, Issue 31 https://doi.org/10.1039/C6CP01831A	journal	January 2016

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Spectroscopic (FT-IR, FT-Raman, and ¹³ C SS-NMR) and quantum chemical investigations to provide structural insights into nitrofurantoin–4-hydroxybenzoic acid cocrystals Shukla, Anuradha; Khan, Eram; Alsirawan, MHD. Bashir New Journal of Chemistry, Vol. 43, Issue 18 https://doi.org/10.1039/c8nj05946b	journal	January 2019
¹⁹ F Magic Angle Spinning Dynamic Nuclear Polarization Enhanced NMR Spectroscopy Viger‐Gravel, Jasmine; Avalos, Claudia E.; Kubicki, Dominik J. Angewandte Chemie International Edition, Vol. 58, Issue 22 https://doi.org/10.1002/anie.201814416	journal	May 2019

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