Revealing Ion Adsorption and Charging Mechanisms in Layered Metal-Organic Framework Supercapacitors with Solid-State Nuclear Magnetic Resonance.

Conductive layered metal-organic frameworks (MOFs) have demonstrated promising electrochemical performances as supercapacitor electrode materials. The well-defined chemical structures of these crystalline porous electrodes facilitate structure-performance studies; however, there is a fundamental lack in the molecular-level understanding of charge storage mechanisms in conductive layered MOFs. To address this, we employ solid-state nuclear magnetic resonance (NMR) spectroscopy to study ion adsorption in nickel 2,3,6,7,10,11-hexaiminotriphenylene, Ni3(HITP)2. In this system, we find that separate resonances can be observed for the MOF's in-pore and ex-pore ions. The chemical shift of in-pore electrolyte is found to be dominated by specific chemical interactions with the MOF functional groups, with this result supported by quantum mechanics/molecular mechanics (QM/MM) and density functional theory (DFT) calculations. Quantification of the electrolyte environments by NMR was also found to provide a proxy for electrochemical performance, which could facilitate the rapid screening of synthesized MOF samples. Finally, the charge storage mechanism was explored using a combination of ex-situ NMR and operando electrochemical quartz crystal microbalance (EQCM) experiments. These measurements revealed that cations are the dominant contributors to charge storage in Ni3(HITP)2, with anions contributing only a minor contribution to the charge storage. Overall, this work establishes the methods for studying MOF-electrolyte interactions via NMR spectroscopy. Understanding how these interactions influence the charging storage mechanism will aid the design of MOF-electrolyte combinations to optimize the performance of supercapacitors, as well as other electrochemical devices including electrocatalysts and sensors.

Frémy's Salt as a Low-Persistence Hyperpolarization Agent: Efficient Dynamic Nuclear Polarization Plus Rapid Radical Scavenging.

Nuclear magnetic resonance (NMR) spectroscopy is a key technique for molecular structure determination in solution. However, due to its low sensitivity, many efforts have been made to improve signal strengths and reduce the required substrate amounts. In this regard, dissolution dynamic nuclear polarization (DDNP) is a versatile approach as signal enhancements of over 10 000-fold are achievable. Samples are signal-enhanced ex situ by transferring electronic polarization from radicals to nuclear spins before dissolving and shuttling the boosted sample to an NMR spectrometer for detection. However, the applicability of DDNP suffers from one major drawback, namely, paramagnetic relaxation enhancements (PREs) that critically reduce relaxation times due to the codissolved radicals. PREs are the primary source of polarization losses canceling the signal improvements obtained by DNP. We solve this problem by using potassium nitrosodisulfonate (Frémy's salt) as polarization agent (PA), which provides high nuclear spin polarization and allows for rapid scavenging under mild reducing conditions. We demonstrate the potential of Frémy's salt, (i) showing that both 1H and 13C polarization of ∼30% can be achieved and (ii) describing a hybrid sample shuttling system (HySSS) that can be used with any DDNP/NMR combination to remove the PA before NMR detection. This gadget mixes the hyperpolarized solution with a radical scavenger and injects it into an NMR tube, providing, within a few seconds, quantitatively radical-free, highly polarized solutions. The cost efficiency and broad availability of Frémy's salt might facilitate the use of DDNP in many fields of research.

Conformational tuning of a DNA-bound transcription factor.

Transcription factors are involved in many cellular processes that take place remote from their cognate DNA sequences. The efficiencies of these activities are thus in principle counteracted by high binding affinities of the factors to their cognate DNAs. Models such as facilitated diffusion or dissociation address this apparent contradiction. We show that the MYC associated transcription factor X (MAX) undergoes nanoscale conformational fluctuations in the DNA-bound state, which is consistent with facilitated dissociation from or diffusion along DNA strands by transiently reducing binding energies. An integrative approach involving EPR, NMR, crystallographic and molecular dynamics analyses demonstrates that the N-terminal domain of MAX constantly opens and closes around a bound DNA ligand thereby dynamically tuning the binding epitope and the mode of interaction.

Assessing the Onset of Calcium Phosphate Nucleation by Hyperpolarized Real-Time NMR.

We report an experimental approach for high-resolution real-time monitoring of transiently formed species occurring during the onset of precipitation of ionic solids from solution. This is made possible by real-time nuclear magnetic resonance (NMR) monitoring using dissolution dynamic nuclear polarization (D-DNP) to amplify signals of functional intermediates and is supported by turbidimetry, cryogenic electron microscopy, and solid-state NMR measurements. D-DNP can provide drastic signal improvements in NMR signal amplitudes, permitting dramatic reductions in acquisition times and thereby enabling us to probe fast interaction kinetics such as those underlying formation of prenucleation species (PNS) that precede solid-liquid phase separation. This experimental strategy allows for investigation of the formation of calcium phosphate (CaP)-based minerals by 31P NMR-a process of substantial industrial, geological, and biological interest. Thus far, many aspects of the mechanisms of CaP nucleation remain unclear due to the absence of experimental methods capable of accessing such processes on sufficiently short time scales. The approach reported here aims to address this by an improved characterization of the initial steps of CaP precipitation, permitting detection of PNS by NMR and determination of their formation rates, exchange dynamics, and sizes. Using D-DNP monitoring, we find that under our conditions (i) in the first 2 s after preparation of oversaturated calcium phosphate solutions, PNS with a hydrodynamic radius of Rh ≈ 1 nm is formed and (ii) following this rapid initial formation, the entire crystallization processes proceed on considerably longer time scales, requiring >20 s to form the final crystal phase.

Relaxation of long-lived modes in NMR of deuterated methyl groups.

Long-lived imbalances of spin state populations can circumvent fast quadrupolar relaxation by reducing effective longitudinal relaxation rates by about an order of magnitude. This opens new avenues for the study of dynamic processes in deuterated molecules. Here we present an analysis of the relaxation properties of deuterated methyl groups CD3. The number of coupled equations that describe cross-relaxation between the 27 symmetry-adapted spin states of a D3 system can be reduced to only 2 non-trivial "lumped modes" by (i) taking the sums of the populations of all states that equilibrate rapidly within each irreducible representation of the symmetry group, and (ii) by combining populations that have similar relaxation rates although they belong to different irreducible representations. The quadrupolar relaxation rates of the spin state imbalances in CD3 groups are determined not by the correlation time of overall tumbling of the molecule, but by the frequency of jumps of methyl groups about their three-fold symmetry axis. We access these states via dissolution dynamic nuclear polarization (D-DNP), a method that allows one to populate the desired long-lived states at cryogenic temperatures and their subsequent detection at ambient temperatures after rapid dissolution. Experimental examples of DMSO-d6 and ethanol-d6 demonstrate that long-lived deuterium spin states are indeed accessible and that their lifetimes can be determined. Our analysis of the system via "lumped" modes allows us to visualize different possible spin-state populations of symmetry A, B, or E. Thus, we identify a long-lived spin state involving all three deuterons in a CD3 group as an A/E imbalance that can be populated through DNP at low temperatures.

Charge-Dependent Crossover in Aqueous Organic Redox Flow Batteries Revealed Using Online NMR Spectroscopy.

Aqueous organic redox-flow batteries (AORFBs) are promising candidates for low-cost grid-level energy storage. However, their wide-scale deployment is limited by crossover of redox-active material through the separator membrane, which causes capacity decay. Traditional membrane permeability measurements do not capture all contributions to crossover in working batteries, including migration and changes in ion size and charge. Here we present a new method for characterizing crossover in operating AORFBs using online 1H NMR spectroscopy. By the introduction of a separate pump to decouple NMR and battery flow rates, this method opens a route to quantitative time-resolved monitoring of redox-flow batteries under real operating conditions. In this proof-of-concept study of a 2,6-dihydroxyanthraquinone (2,6-DHAQ)/ferrocyanide model system, we observed a doubling of the 2,6-DHAQ crossover during battery charging, which we attribute to migration effects. This new membrane testing methodology will advance our understanding of crossover and accelerate the development of improved redox-flow batteries.

A novel sample handling system for dissolution dynamic nuclear polarization experiments.

We present a system for facilitated sample vitrification, melting, and transfer in dissolution dynamic nuclear polarization (DDNP) experiments. In DDNP, a sample is typically hyperpolarized at cryogenic temperatures before dissolution with hot solvent and transfer to a nuclear magnetic resonance (NMR) spectrometer for detection in the liquid state. The resulting signal enhancements can exceed 4 orders of magnitude. However, the sudden temperature jump from cryogenic temperatures close to 1 K to ambient conditions imposes a particular challenge. It is necessary to rapidly melt the sample to avoid a prohibitively fast decay of hyperpolarization. Here, we demonstrate a sample dissolution method that facilitates the temperature jump by eliminating the need to open the cryostat used to cool the sample. This is achieved by inserting the sample through an airlock in combination with a dedicated dissolution system that is inserted through the same airlock shortly before the melting event. The advantages are threefold: (1) the cryostat can be operated continuously at low temperatures. (2) The melting process is rapid as no pressurization steps of the cryostat are required. (3) Blockages of the dissolution system due to freezing of solvents during melting and transfer are minimized.

Incorporation of nanogels within calcite single crystals for the storage, protection and controlled release of active compounds.

Nanocarriers have tremendous potential for the encapsulation, storage and delivery of active compounds. However, current formulations often employ open structures that achieve efficient loading of active agents, but that suffer undesired leakage and instability of the payloads over time. Here, a straightforward strategy that overcomes these issues is presented, in which protein nanogels are encapsulated within single crystals of calcite (CaCO3). Demonstrating our approach with bovine serum albumin (BSA) nanogels loaded with (bio)active compounds, including doxorubicin (a chemotherapeutic drug) and lysozyme (an antibacterial enzyme), we show that these nanogels can be occluded within calcite host crystals at levels of up to 45 vol%. Encapsulated within the dense mineral, the active compounds are stable against harsh conditions such as high temperature and pH, and controlled release can be triggered by a simple reduction of the pH. Comparisons with analogous systems - amorphous calcium carbonate, mesoporous vaterite (CaCO3) polycrystals, and calcite crystals containing polymer vesicles - demonstrate the superior encapsulation performance of the nanogel/calcite system. This opens the door to encapsulating a broad range of existing nanocarrier systems within single crystal hosts for the efficient storage, transport and controlled release of various active guest species.

Mechanical adaptation of brachiopod shells via hydration-induced structural changes.

The function-optimized properties of biominerals arise from the hierarchical organization of primary building blocks. Alteration of properties in response to environmental stresses generally involves time-intensive processes of resorption and reprecipitation of mineral in the underlying organic scaffold. Here, we report that the load-bearing shells of the brachiopod Discinisca tenuis are an exception to this process. These shells can dynamically modulate their mechanical properties in response to a change in environment, switching from hard and stiff when dry to malleable when hydrated within minutes. Using ptychographic X-ray tomography, electron microscopy and spectroscopy, we describe their hierarchical structure and composition as a function of hydration to understand the structural motifs that generate this adaptability. Key is a complementary set of structural modifications, starting with the swelling of an organic matrix on the micron level via nanocrystal reorganization and ending in an intercalation process on the molecular level in response to hydration.

A Switch between Two Intrinsically Disordered Conformational Ensembles Modulates the Active Site of a Basic-Helix-Loop-Helix Transcription Factor.

We report a conformational switch between two distinct intrinsically disordered subensembles within the active site of a transcription factor. This switch highlights an evolutionary benefit conferred by the high plasticity of intrinsically disordered domains, namely, their potential to dynamically sample a heterogeneous conformational space housing multiple states with tailored properties. We focus on proto-oncogenic basic-helix-loop-helix (bHLH)-type transcription factors, as these play key roles in cell regulation and function. Despite intense research efforts, the understanding of structure-function relations of these transcription factors remains incomplete as they feature intrinsically disordered DNA-interaction domains that are difficult to characterize, theoretically as well as experimentally. Here we characterize the structural dynamics of the intrinsically disordered region DNA-binding site of the vital MYC-associated transcription factor X (MAX). Integrating nuclear magnetic resonance (NMR) measurements, molecular dynamics (MD) simulations, and electron paramagnetic resonance (EPR) measurements, we show that, in the absence of DNA, the binding site of the free MAX2 homodimer samples two intrinsically disordered conformational subensembles. These feature distinct structural properties: one subensemble consists of a set of highly flexible and spatially extended conformers, while the second features a set of "hinged" conformations. In this latter ensemble, the disordered N-terminal tails of MAX2 fold back along the dimer, forming transient long-range contacts with the HLH-region and thereby exposing the DNA binding site to the solvent. The features of these divergent substates suggest two mechanisms by which protein conformational dynamics in MAX2 might modulate DNA-complex formation: by enhanced initial recruitment of free DNA ligands, as a result of the wider conformational space sampled by the extended ensemble, and by direct exposure of the binding site and the corresponding strong electrostatic attractions presented while in the hinged conformations.

Long-Lived States in Hyperpolarized Deuterated Methyl Groups Reveal Weak Binding of Small Molecules to Proteins.

We introduce a method for the detection of weak interactions of small molecules such as metabolites or medicaments that contain deuterated methyl groups with proteins in solution. The technique relies on long-lived imbalances of spin state populations, which are generated by dissolution dynamic nuclear polarization (D-DNP) and feature lifetimes that depend on the frequency of internal rotation of deuterated methyl groups. We demonstrate the technique for interactions between deuterated dimethyl sulfoxide (DMSO- d6) and bovine serum albumin (BSA) or trypsin, where the methyl group rotation is slowed down upon protein binding, which causes a marked reduction in the lifetime of the population imbalances.

Event-related potentials reflect impaired face recognition in patients with congenital prosopagnosia.

Event-related brain potentials (ERPs) to faces have been shown to be altered in patients suffering from prosopagnosia. In this report we present ERP findings from two patients suffering from a congenital form of prosopagnosia, with other visual and cognitive functions being spared and without any structural abnormalities as assessed by anatomical brain imaging. Subjects were presented with photographs of faces and houses, and they had to respond to photographs of hands. Both patients did not show a difference in N170 amplitude to faces compared to houses, whereas there was a significant N170 difference of these two stimulus classes in healthy control subjects.

Developmental prosopagnosia: a review.

This article reviews the published literature on developmental prosopagnosia, a condition in which the ability to recognize other persons by facial information alone has never been acquired. Due to the very low incidence of this syndrome, case reports are sparse. We review the available data and suggest assessment strategies for patients suffering from developmental prosopagnosia. It is suggested that developmental prosopagnosia is not a unitary condition but rather consists of different subforms that can be dissociated on the grounds of functional impairments. On the basis of the available evidence, hypotheses about the aetiology of developmental prosopagnosia as well as about the selectivity of deficits related to face recognition are discussed.