Friday, October 19, 2018

EPSRC Industrial CASE PhD Studentship “DNP-enhanced Solid-state NMR Studies of Pharmaceuticals” #DNPNMR

EPSRC Industrial CASE PhD Studentship “DNP-enhanced Solid-state NMR Studies of Pharmaceuticals”

Dr Jeremy Titman, School of Chemistry, University of Nottingham
Dr Tran N. Pham, GSK 

Solid-state nuclear magnetic resonance (NMR) is a powerful method for studying the molecular structure and dynamics of a broad range of systems from heterogeneous materials to biological molecules. In some situations solid-state NMR can suffer from low sensitivity, because of the small nuclear spin polarizations involved, so that long acquisition times or large sample volumes are required. However, weak NMR signals can be dramatically enhanced by dynamic nuclear polarization (DNP), which involves transfer of electron spin polarization from radicals implanted in the sample to nearby nuclei. The substantial enhancements (up to 300-fold) obtained with DNP make NMR studies of dilute species feasible for the first time and have already prompted exciting new NMR applications to interfaces, porous materials and microcrystalline substances.

The University of Nottingham has recently established a DNP-enhanced solid-state NMR Facility (unique in the UK) funded by a grant of £2.5 M from EPSRC. In this collaboration with GSK DNP-enhanced solid-state NMR will be used to study pharmaceutical formulations and drug delivery systems. These are challenging systems to study by solid-state NMR because of the often low concentration of the active pharmaceutical ingredient (API). However, the substantial signal enhancements obtained with DNP will allow natural abundance investigations of polymorphs or hydration states of APIs, of formulations involving amorphous APIs and of the interactions at the interfaces between APIs and excipients such as fillers, binders, lubricants and preservatives.

The PhD studentship is available immediately, and is fully funded for 4 years via a stipend covering PhD tuition fees (at the Home/EU rate) and a tax-free living allowance (£14,777 per annum). As part of the project the student will spend up to three months at the GSK Medicines Research Centre in Hertfordshire UK acquiring skills in formulation science and manufacturing samples.

The student will gain expertise in solid-state NMR spectroscopy, especially as applied to pharmaceutical formulations, as well as experience of DNP-enhanced methods. Transferable skills in computer programming, data analysis and scientific communication will also be acquired. In addition, the student will benefit from hands-on experience in industry, while pursuing a research project in an academic environment, and gain knowledge in the business of drug discovery and development.

Applications are invited from outstanding EU/UK students holding or expecting to gain a good undergraduate degree in Chemistry, Physics or a related subject. Prior experience in solid-state NMR is not essential. Note that the UK government has guaranteed EU eligibility for EPSRC funding for PhDs beginning before the end of the 2018-2019 academic year. Apply online at by 15th November 2018. For informal enquiries please contact:

The solid-state NMR group at Nottingham works on the design of new solid-state NMR experiments and their application to chemistry, energy research, nanotechnology and environmental science. The group has three solid-state NMR spectrometers, operating at 1H Larmor frequencies of 300, 600 and 800 MHz. A 600 MHz Dynamic Nuclear Polarization MAS NMR spectrometer was installed in Nottingham in November 2015. For more information about the solid-state NMR group see: The University of Nottingham is ranked in the top 100 universities in the world (QS World University Rankings).

Dr Jeremy J Titman
Associate Professor and Reader in Magnetic Resonance,
A43, School of Chemistry, University of Nottingham,
University Park, Nottingham, NG7 2RD, UK
Tel: +44 115 951 3560

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NMR web database:
Yoder, J. L., P. E. Magnelind, M. A. Espy, and M. T. Janicke. “Exploring the Limits of Overhauser Dynamic Nuclear Polarization (O-DNP) for Portable Magnetic Resonance Detection of Low γ Nuclei.” Applied Magnetic Resonance 49, no. 7 (July 2018): 707–24.

Nuclear magnetic resonance (NMR) spectroscopy in portable, permanent magnet-based spectrometers is primarily limited to nuclei with higher gyromagnetic ratio, γ, such as 1H, 19F, and 31P due to the limited field strength achievable in these systems. Overhauser effect dynamic nuclear polarization (O-DNP), which transfers polarization from an unpaired electron to a nucleus by saturating an electron paramagnetic resonance transition with an oscillating radio frequency magnetic field, B1e, can increase the polarization of low γ nuclei by hundreds or even thousands, enabling detection in a portable system. We have investigated the potential for O-DNP to enhance signals using (4-amino-2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO hereafter) as a source of unpaired electrons in a homebuilt ultra-low field (ULF) O-DNP-NMR spectrometer. We have found, in general, that larger concentrations of TEMPO are required for effective O-DNP with low γ nuclei, which has a number of important effects. Spin exchange effects cause the EPR lines to overlap and ultimately merge at high concentrations of TEMPO, fundamentally increasing the maximum possible enhancement, while the electron–electron dipolar interaction reduces both longitudinal and transverse relaxation times for the electrons, dramatically increasing the required B1e strength. The relationship between TEMPO concentration, B1e magnitude and O-DNP enhancement is quantified, and strategies for achieving these fields are discussed.

Wednesday, October 17, 2018

Structural Elucidation of Amorphous Photocatalytic Polymers from Dynamic Nuclear Polarization Enhanced Solid State NMR #DNPNMR

Brownbill, Nick J., Reiner Sebastian Sprick, Baltasar Bonillo, Shane Pawsey, Fabien Aussenac, Alistair J. Fielding, Andrew I. Cooper, and Frédéric Blanc. “Structural Elucidation of Amorphous Photocatalytic Polymers from Dynamic Nuclear Polarization Enhanced Solid State NMR.” Macromolecules 51, no. 8 (April 24, 2018): 3088–96. 

Dynamic nuclear polarization (DNP) solid-state nuclear magnetic resonance (NMR) offers a recent approach to dramatically enhance NMR signals and has enabled detailed structural information to be obtained in a series of amorphous photocatalytic copolymers of alternating pyrene and benzene monomer units, the structures of which cannot be reliably established by other spectroscopic or analytical techniques. Large 13C cross-polarization (CP) magic angle spinning (MAS) signal enhancements were obtained at high magnetic fields (9.4− 14.1 T) and low temperature (110−120 K), permitting the acquisition of a 13C INADEQUATE spectrum at natural abundance and facilitating complete spectral assignments, including when small amounts of specific monomers are present. The high 13C signal-to-noise ratios obtained are harnessed to record quantitative multiple contact CP NMR data, used to determine the polymers’ composition. This correlates well with the putative pyrene:benzene stoichiometry from the monomer feed ratio, enabling their structures to be understood.

Monday, October 15, 2018

Illuminating the dark metabolome to advance the molecular characterisation of biological systems #DNPNMR

This is a great review showcasing the capabilities of DNP-enhanced NMR spectroscopy for metabolomic studies.

Jones, Oliver A. H. “Illuminating the Dark Metabolome to Advance the Molecular Characterisation of Biological Systems.” Metabolomics 14, no. 8 (August 2018).

Background  The latest version of the Human Metabolome Database (v4.0) lists 114,100 individual entries. Typically, however, metabolomics studies identify only around 100 compounds and many features identified in mass spectra are listed only as ‘unknown compounds’. The lack of ability to detect all metabolites present, and fully identify all metabolites detected (the dark metabolome) means that, despite the great contribution of metabolomics to a range of areas in the last decade, a significant amount of useful information from publically funded studies is being lost or unused each year. This loss of data limits our potential gain in knowledge and understanding of important research areas such as cell biology, environmental pollution, plant science, food chemistry and health and biomedical research. Metabolomics therefore needs to develop new tools and methods for metabolite identification to advance as a field.

Monday, October 8, 2018

Resolving the Core and the Surface of CdSe Quantum Dots and Nanoplatelets Using Dynamic Nuclear Polarization Enhanced PASS–PIETA NMR Spectroscopy #DNPNMR

Piveteau, Laura, Ta-Chung Ong, Brennan J. Walder, Dmitry N. Dirin, Daniele Moscheni, Barbara Schneider, Janine Bär, et al. “Resolving the Core and the Surface of CdSe Quantum Dots and Nanoplatelets Using Dynamic Nuclear Polarization Enhanced PASS–PIETA NMR Spectroscopy.” ACS Central Science 4, no. 9 (September 26, 2018): 1113–25.

Understanding the surface of semiconductor nanocrystals (NCs) prepared using colloidal methods is a longstanding goal of paramount importance for all their potential optoelectronic applications, which remains unsolved largely because of the lack of site-specific physical techniques. Here, we show that multidimensional 113Cd dynamic nuclear polarization (DNP) enhanced NMR spectroscopy allows the resolution of signals originating from different atomic and magnetic surroundings in the NC cores and at the surfaces. This enables the determination of the structural perfection, and differentiation between the surface and core atoms in all major forms of size- and shape-engineered CdSe NCs: irregularly faceted quantum dots (QDs) and atomically flat nanoplatelets, including both dominant polymorphs (zinc-blende and wurtzite) and their epitaxial nanoheterostructures (CdSe/CdS core/shell quantum dots and CdSe/CdS core/crown nanoplatelets), as well as magic-sized CdSe clusters. Assignments of the NMR signals to specific crystal facets of oleate-terminated ZB structured CdSe NCs are proposed. Significantly, we discover far greater atomistic complexity of the surface structure and the species distribution in wurtzite as compared to zinc-blende CdSe QDs, despite an apparently identical optical quality of both QD polymorphs.

Friday, October 5, 2018

Probing the surface of γ-Al2O3 by oxygen-17 dynamic nuclear polarization enhanced solid-state NMR spectroscopy #DNPNMR

Li, Wenzheng, Qiang Wang, Jun Xu, Fabien Aussenac, Guodong Qi, Xingling Zhao, Pan Gao, Chao Wang, and Feng Deng. “Probing the Surface of γ-Al2O3 by Oxygen-17 Dynamic Nuclear Polarization Enhanced Solid-State NMR Spectroscopy.” Physical Chemistry Chemical Physics 20, no. 25 (June 27, 2018): 17218–25.

γ-Al2O3 is an important catalyst and catalyst support of industrial interest. Its acid/base characteristics are correlated to the surface structure, which has always been an issue of concern. In this work, the complex (sub-)surface oxygen species on surface-selectively labelled γ-Al2O3 were probed by 17O dynamic nuclear polarization surface-enhanced NMR spectroscopy (DNP-SENS). Direct 17O MAS and indirect 1H–17O cross-polarization (CP)/MAS DNP experiments enable observation of the (sub-)surface bare oxygen species and hydroxyl groups. In particular, a two-dimensional (2D) 17O 3QMAS DNP spectrum was for the first time achieved for γ-Al2O3, in which two O(Al)4 and one O(Al)3 bare oxygen species were identified. The 17O isotropic chemical shifts (δcs) vary from 56.7 to 81.0 ppm and the quadrupolar coupling constants (CQ) range from 0.6 to 2.5 MHz for the three oxygen species. The coordinatively unsaturated O(Al)3 species is characterized by a higher field chemical shift (56.7 ppm) and the largest CQ value (2.5 MHz) among these oxygen sites. 2D 1H → 17O HETCOR DNP experiments allow us to discriminate three bridging (Aln)-μ2-OH and two terminal (Aln)-μ1-OH hydroxyl groups. The structural features of the bare oxygen species and hydroxyl groups are similar for the γ-Al2O3 samples isotopically labelled by 17O2 gas or H217O. The results presented here show that the combination of surface-selective labelling and DNP-SENS is an effective approach for characterizing oxides with complex surface species.

Wednesday, October 3, 2018

Exploring Applications of Covalent Organic Frameworks: Homogeneous Reticulation of Radicals for Dynamic Nuclear Polarization #DNPNMR

Cao, Wei, Wei David Wang, Hai-Sen Xu, Ivan V. Sergeyev, Jochem Struppe, Xiaoling Wang, Frederic Mentink-Vigier, et al. “Exploring Applications of Covalent Organic Frameworks: Homogeneous Reticulation of Radicals for Dynamic Nuclear Polarization.” Journal of the American Chemical Society 140, no. 22 (June 6, 2018): 6969–77.

Rapid progress has been witnessed in the past decade in the fields of covalent organic frameworks (COFs) and dynamic nuclear polarization (DNP). In this contribution, we bridge these two fields by constructing radical-embedded COFs as promising DNP agents. Via polarization transfer from unpaired electrons to nuclei, DNP realizes significant enhancement of NMR signal intensities. One of the crucial issues in DNP is to screen for suitable radicals to act as efficient polarizing agents, the basic criteria for which are homogeneous distribution and fixed orientation of unpaired electrons. We therefore envisioned that the crystalline and porous structures of COFs, if evenly embedded with radicals, may work as a new “crystalline sponge” for DNP experiments. As a proof of concept, we constructed a series of proxyl-radical-embedded COFs (denoted as PR(x)-COFs) and successfully applied them to achieve substantial DNP enhancement. Benefiting from the bottom-up and multivariate synthetic strategies, proxyl radicals have been covalently reticulated, homogeneously distributed, and rigidly embedded into the crystalline and mesoporous frameworks with adjustable concentration (x%). Excellent performance of PR(x)-COFs has been observed for DNP 1H, 13C, and 15N solid-state NMR enhancements. This contribution not only realizes the direct construction of radical COFs from radical monomers, but also explores the new application of COFs as DNP polarizing agents. Given that many radical COFs can therefore be rationally designed and facilely constructed with well-defined composition, distribution, and pore size, we expect that our effort will pave the way for utilizing radical COFs as standard polarizing agents in DNP NMR experiments.

Monday, October 1, 2018

Bulk Nuclear Hyperpolarization of Inorganic Solids by Relay from the Surface #DNPNMR

Björgvinsdóttir, Snædís, Brennan J. Walder, Arthur C. Pinon, and Lyndon Emsley. “Bulk Nuclear Hyperpolarization of Inorganic Solids by Relay from the Surface.” Journal of the American Chemical Society 140, no. 25 (June 27, 2018): 7946–51.

NMR is a method of choice to determine structural and electronic features in inorganic materials, and has been widely used in the past, but its application is severely limited by its low relative sensitivity. We show how the bulk of proton-free inorganic solids can be hyperpolarized in a general strategy using impregnation dynamic nuclear polarization through homonuclear spin diffusion between low-g nuclei. This is achieved either through direct hyperpolarization or with a pulse-cooling cross-polarization method, transferring hyperpolarization from protons to heteronuclei at particle surfaces. We demonstrate a factor 50 gain in overall sensitivity for the 119Sn spectrum of powdered SnO2, corresponding to an acceleration of a factor >2500 in acquisition times. The method is also shown for 31P spectra of GaP, for 113Cd spectra of CdTe, and 29Si spectra of α-quartz.