News & Updates


The surface chemistry of a nanocellulose drug carrier unravelled by MAS-DNP

posted Mar 30, 2020, 7:29 AM by Daniel Lee

The surface chemistry of a nanocellulose drug carrier unravelled by MAS-DNP. Cellulose nanofibrils (CNF) are renewable bio-based materials with high specific area, which makes them ideal candidates for multiple emerging applications including for instance on-demand drug release. However, in-depth chemical and structural characterization of the CNF surface chemistry is still an open challenge, especially for low weight percentage of functionalization. This currently prevents the development of efficient, cost-effective and reproducible green synthetic routes and thus the widespread development of targeted and responsive drug-delivery CNF carriers. We show in this work how we use dynamic nuclear polarization (DNP) to overcome the sensitivity limitation of conventional solid-state NMR and gain insight into the surface chemistry of drug-functionalized TEMPO-oxidized cellulose nanofibrils. The DNP enhanced-NMR data can report unambiguously on the presence of trace amounts of TEMPO moieties and depolymerized cellulosic units in the starting material, as well as coupling agents on the CNFs surface (used in the heterogeneous reaction). This enables a precise estimation of the drug loading while differentiating adsorption from covalent bonding (∼1 wt% in our case) as opposed to other analytical techniques such as elemental analysis and conductometric titration that can neither detect the presence of coupling agents, nor differentiate unambiguously between adsorption and grafting. The approach, which does not rely on the use of 13C/15N enriched compounds, will be key to further develop efficient surface chemistry routes and has direct implication for the development of drug delivery applications both in terms of safety and dosage.

Disclosing Interfaces of ZnO Nanocrystals Using Dynamic Nuclear Polarization: Sol Gel versus Organometallic Approach

posted Sep 5, 2019, 1:43 AM by Daniel Lee   [ updated Mar 30, 2020, 7:32 AM ]

Disclosing Interfaces of ZnO Nanocrystals Using Dynamic Nuclear Polarization: Sol Gel versus Organometallic Approach. The unambiguous characterization of the coordination chemistry of nanocrystal surfaces that have been produced by a wet‐chemical synthesis presently remains a highly challenging issue. Here, zinc oxide nanocrystals (ZnO NCs) coated by monoanionic diphenyl phosphate (DPP) ligands were derived by a traditional sol‐gel process and a one‐pot self‐supporting organometallic (OSSOM) procedure, and advanced atomic‐scale characterization through dynamic nuclear polarization (DNP‐)enhanced solid‐state nuclear magnetic resonance (ssNMR) spectroscopy has notably enabled resolving their vastly different surface‐ligand interfaces. For the OSSOM‐derived NCs, DPP moieties form stable and strongly‐anchored µ2‐ and µ3‐bridging‐ligand pairs that are resistant to competitive ligand exchange processes. Contrastingly, the sol‐gel‐derived NCs contain a wide variety of coordination modes of DPP ligands and a ligand exchange process takes place between DPP ligands and glycerol molecules. This highlights the power of DNP‐enhanced ssNMR for detailed NC surface analysis and the superiority of the OSSOM approach for the preparation of high quality ZnO NCs.

Natural Isotopic Abundance 13C and 15N Multidimensional Solid-State NMR Enabled by Dynamic Nuclear Polarization

posted Sep 2, 2019, 2:16 AM by Daniel Lee

Natural Isotopic Abundance 13C and 15N Multidimensional Solid-State NMR Enabled by Dynamic Nuclear Polarization. Dynamic nuclear polarization (DNP) has made feasible solid-state NMR experiments that were previously thought impractical due to sensitivity limitations. One such class of experiments is the structural characterization of organic and biological samples at natural isotopic abundance (NA). Herein, we describe the many advantages of DNP-enabled ssNMR at NA, including the extraction of long-range distance constraints using dipolar recoupling pulse sequences without the deleterious effects of dipolar truncation. In addition to the theoretical underpinnings in the analysis of these types of experiments, numerous applications of DNP-enabled ssNMR at NA are discussed.

Detection of the Surface of Crystalline Y2O3 Using Direct 89Y Dynamic Nuclear Polarization

posted Sep 2, 2019, 2:13 AM by Daniel Lee

Detection of the Surface of Crystalline Y2O3 Using Direct 89Y Dynamic Nuclear Polarization. Nuclei with low gyromagnetic ratio (γ) present a serious sensitivity challenge for nulear magnetic resonance (NMR) spectroscopy. Recently, dynamic nuclear polarization (DNP) has shown great promise in overcoming this hurdle by indirect hyperpolarization (via 1H) of these low-γ nuclei. Here we show that at a magnetic field of 9.4 T and cryogenic temperature of about 110 K direct DNP of 89Y in a frozen solution of Y(NO3)3 can offer signal enhancements greater than 80 times using exogeneous trityl OX063 monoradical by satisfying the cross effect magic angle spinning (MAS) DNP mechanism. The large signal enhancement achieved permits 89Y NMR spectra of Y2O3 and Gd2O3-added Y2O3 materials to be obtained quickly (∼30 min), revealing a range of surface yttrium hydroxyl groups in addition to the two octahedral yttrium signals of the core. The results open up promises for the observation of low gyromagnetic ratio nuclei and the detection of corresponding surface and (sub-)surface sites.

Selective High-resolution DNP-enhanced NMR of Biomolecular Binding Sites

posted Feb 1, 2019, 10:06 AM by Daniel Lee   [ updated Sep 2, 2019, 2:09 AM ]

Selective High-resolution DNP-enhanced NMR of Biomolecular Binding Sites. Locating binding sites in biomolecular assemblies and solving their structures is of the utmost importance to unravel functional aspects of the system and provide experimental data that can be used for structure-based drug design. This often still remains a challenge, both in terms of selectivity and sensitivity for X-ray crystallography, cryo-electron microscopy and NMR. In this work, we introduce a novel method called Selective Dynamic Nuclear Polarization (Sel-DNP) that allows selectively highlighting and identifying residues present in the binding site. This powerful site-directed approach relies on the use of localized paramagnetic relaxation enhancement induced by a ligand-functionalized paramagnetic construct combined with difference spectroscopy to recover high-resolution and high-sensitivity information from binding sites. The identification of residues involved in the binding occurs using spectral fingerprints obtained from a set of high-resolution multidimensional spectra with varying selectivity. The methodology is demonstrated on the galactophilic lectin LecA, for which we report well-resolved DNP-enhanced spectra with linewidth between 0.5-1 ppm, which enable the de novo assignment of the binding interface residues, without using previous knowledge of the binding site location. Since this approach produces clean and resolved difference spectra containing a limited number of residues, resonance assignment can be performed without any limitation with respect to the size of the biomolecular system and only requires the production of one protein sample (e.g. 13C,15N labeled protein).

Sparsely Pillared Graphene Materials for High Performance Supercapacitors: Improving Ion Transport and Storage Capacity

posted Jan 17, 2019, 9:49 AM by Daniel Lee   [ updated Feb 7, 2019, 3:57 AM ]

Sparsely Pillared Graphene Materials for High Performance Supercapacitors: Improving Ion Transport and Storage Capacity. Graphene-based materials are extensively studied as promising candidates for supercapacitors (SCs) owing to the high surface area, electrical conductivity, and mechanical flexibility of graphene. Reduced graphene oxide (RGO), a close graphene-like material studied for SCs, offers limited specific capacitances (100 F.g-1) as the reduced graphene sheets partially restack through π-π interactions. This paper presents pillared graphene materials designed to minimize such graphitic restacking by cross-linking the graphene sheets with a bi-functional pillar molecule. Solid-state NMR, X-ray diffraction, and electrochemical analyses reveal that the synthesized materials possess covalently cross-linked graphene galleries that offer additional sites for ion sorption in SCs. Indeed, high specific capacitances in SCs are observed for the graphene materials synthesized with an optimized number of pillars. Specifically, the straight-forward synthesis of a graphene hydrogel containing pillared structures and an inter-connected porous network delivered a material with gravimetric capacitances two times greater than that of RGO (200 F.g-1 vs. 107 F.g-1) and volumetric capacitances that are nearly four times larger (210 F.cm-3 vs. 54 F.cm-3). Additionally, despite the presence of pillars inside the graphene galleries, the optimized materials show efficient ion transport characteristics. This work therefore brings perspectives for the next generation of high-performance SCs.

De novo prediction of cross-effect efficiency for magic angle spinning dynamic nuclear polarization

posted Jan 11, 2019, 5:27 AM by Daniel Lee   [ updated Feb 7, 2019, 3:57 AM ]

De novo prediction of cross-effect efficiency for magic angle spinning dynamic nuclear polarization. Magic angle spinning dynamic nuclear polarization (MAS-DNP) has become a key approach to boost the intrinsic low sensitivity of NMR in solids. This method relies on the use of both stable radicals as polarizing agents (PAs) and suitable high frequency microwave irradiation to hyperpolarize nuclei of interest. Relating PA chemical structure to DNP efficiency has been, and is still, a long-standing problem. The complexity of the polarization transfer mechanism has so far limited the impact of analytical derivation. However, recent numerical approaches have profoundly improved the basic understanding of the phenomenon and have now evolved to a point where they can be used to help design new PAs. In this work, the potential of advanced MAS-DNP simulations combined with DFT calculations and high-field EPR to qualitatively and quantitatively predict hyperpolarization efficiency of particular PAs is analyzed. This approach is demonstrated on AMUPol and TEKPol, two widely-used bis-nitroxide PAs. The results notably highlight how the PA structure and EPR characteristics affect the detailed shape of the DNP field profile. We also show that refined simulations of this profile using the orientation dependency of the electron spin-lattice relaxation times can be used to estimate the microwave B1 field experienced by the sample. Finally, we show how modelling the nuclear spin-lattice relaxation times of close and bulk nuclei as well as accounting for PA concentration allows the approximation of DNP enhancement factors and hyperpolarization build-up times.

Book chapter: MAS‐DNP Enhancements: Hyperpolarization, Depolarization, and Absolute Sensitivity

posted Jan 11, 2019, 5:24 AM by Daniel Lee   [ updated Feb 7, 2019, 3:59 AM ]

MAS‐DNP Enhancements: Hyperpolarization, Depolarization, and Absolute Sensitivity. Dynamic nuclear polarization at high magnetic fields has made significant progress over the last decades, and this hyperpolarizing technique is currently revolutionizing the impact of solid‐state NMR for the study of complex systems in chemistry, material science, and biology. In this article, we emphasize the importance and difficulty in quantifying sensitivity from DNP under magic‐angle spinning. To this end, we provide insight into the cross effect, the current main MAS‐DNP mechanism. This includes a description of the microwave‐induced hyperpolarization phenomenon but also of the reduction of the NMR signal prior to microwave irradiation for samples doped with polarizing agents (bleaching and depolarization effects). We highlight the importance of the nuclear hyperpolarization buildup time in the evaluation of MAS‐DNP efficiency. Finally, we discuss other experimental parameters affecting sensitivity in DNP‐enhanced spectra and propose a guideline for its proper characterization depending on the type of investigation.

Structural Fingerprinting of Protein Aggregates by Dynamic Nuclear Polarization-Enhanced Solid-State NMR at Natural Isotopic Abundance

posted Nov 9, 2018, 3:43 AM by Daniel Lee   [ updated Jan 11, 2019, 5:19 AM ]

Structural Fingerprinting of Protein Aggregates by Dynamic Nuclear Polarization-Enhanced Solid-State NMR at Natural Isotopic Abundance. A pathological hallmark of Huntington’s disease (HD) is the formation of neuronal protein deposits containing mutant huntingtin fragments with expanded polyglutamine (polyQ) domains. Prior studies have shown the strengths of solid-state NMR (ssNMR) to probe the atomic structure of such aggregates, but have required in vitro isotopic labeling. Herein, we present an approach for the structural fingerprinting of fibrils through ssNMR at natural isotopic abundance (NA). These methods will enable the spectroscopic fingerprinting of unlabeled (e.g., ex vivo) protein aggregates and the extraction of valuable new long-range 13C–13C distance constraints.

Computationally Assisted Design of Polarizing Agents for Dynamic Nuclear Polarization Enhanced NMR: The AsymPol Family

posted Nov 9, 2018, 3:32 AM by Daniel Lee

Computationally Assisted Design of Polarizing Agents for Dynamic Nuclear Polarization Enhanced NMR: The AsymPol Family. We introduce a new family of highly efficient polarizing agents for dynamic nuclear polarization (DNP)-enhanced nuclear magnetic resonance (NMR) applications, composed of asymmetric bis-nitroxides, in which a piperidine-based radical and a pyrrolinoxyl or a proxyl radical are linked together. The design of the AsymPol family was guided by the use of advanced simulations that allow computation of the impact of the radical structure on DNP efficiency. These simulations suggested the use of a relatively short linker with the intention to generate a sizable intramolecular electron dipolar coupling/J-exchange interaction, while avoiding parallel nitroxide orientations. The characteristics of AsymPol were further tuned, for instance with the addition of a conjugated carbon–carbon double bond in the 5-membered ring to improve the rigidity and provide a favorable relative orientation, the replacement of methyls by spirocyclohexanolyl groups to slow the electron spin relaxation, and the introduction of phosphate groups to yield highly water-soluble dopants. An in-depth experimental and theoretical study for two members of the family, AsymPol and AsymPolPOK, is presented here. We report substantial sensitivity gains at both 9.4 and 18.8 T. The robust efficiency of this new family is further demonstrated through high-resolution surface characterization of an important industrial catalyst using fast sample spinning at 18.8 T. This work highlights a new direction for polarizing agent design and the critical importance of computations in this process.


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