Resolving Structures of Paramagnetic Systems in Chemistry and Materials Science by Solid-State NMR: The Revolving Power of Ultra-Fast MAS.

Ultra-fast magic-angle spinning (100+kHz) has revolutionized solid-state NMR of biomolecular systems but has so far failed to gain ground for the analysis of paramagnetic organic and inorganic powders, despite the potential rewards from substantially improved spectral resolution. The principal blockages are that the smaller fast-spinning rotors present significant barriers for sample preparation, particularly for air/moisture-sensitive systems, and are associated with low sensitivity from the reduced sample volumes. Here, we demonstrate that the sensitivity penalty is less severe than expected for highly paramagnetic solids and is more than offset by the associated improved resolution.

Hydrophilic interaction liquid chromatography: An efficient tool for assessing thorium interaction with phosphorylated biomimetic peptides.

In the field of nuclear toxicology, the knowledge of the interaction of actinides (An) with biomolecules is of prime concern in order to elucidate their toxicity mechanism and to further develop selective decorporating agents. In this work, we demonstrated the great potential of hydrophilic interaction liquid chromatography (HILIC) to separate polar thorium (Th) biomimetic peptide complexes, as a key starting point to tackle these challenges. Th was used as plutonium (Pu) analogue and pS16 and pS1368 as synthetic di- and tetra-phosphorylated peptides capable of mimicking the interaction sites of these An in osteopontin (OPN), a hyperphosphorylated protein.

Delving into theoretical and computational considerations for accurate calculation of chemical shifts in paramagnetic transition metal systems using quantum chemical methods.

The chemical shielding tensor for a paramagnetic system has been derived from the macroscopically observed magnetization using the perturbation theory. An approach to calculate the paramagnetic chemical shifts in transition metal systems based on the spin-only magnetic susceptibility directly evaluated from the Hilbert space of the electronic Zeeman Hamiltonian has been discussed. Computationally, several advantages are associated with this approach: (a) it includes the state-specific paramagnetic Curie (first-order) and Van Vleck (second-order) contributions of the paramagnetic ion to the paramagnetic chemical shifts; (b) thus it avoids the system-specific modeling and evaluating effectively in terms of the electron paramagnetic resonance (EPR) spin Hamiltonian parameters of the magnetic moment of the paramagnetic ion formulated previously; (c) it can be utilized both in the point-dipole (PD) approximation (in the long-range) and with the quantum chemical (QC) method based the hyperfine tensors (in the short-range).

Geometry and electronic structure of Yb(III)[CH(SiMe)] from EPR and solid-state NMR augmented by computations.

Characterization of paramagnetic compounds, in particular regarding the detailed conformation and electronic structure, remains a challenge, and - still today it often relies solely on the use of X-ray crystallography, thus limiting the access to electronic structure information. This is particularly true for lanthanide elements that are often associated with peculiar structural and electronic features in relation to their partially filled f-shell. Here, we develop a methodology based on the combined use of state-of-the-art magnetic resonance spectroscopies (EPR and solid-state NMR) and computational approaches as well as magnetic susceptibility measurements to determine the electronic structure and geometry of a paramagnetic Yb(III) alkyl complex, Yb(III)[CH(SiMe)], a prototypical example, which contains notable structural features according to X-ray crystallography.

Structure Determination and Refinement of Paramagnetic Materials by Solid-State NMR.

Paramagnetism in solid-state materials has long been considered an additional challenge for structural investigations by using solid-state nuclear magnetic resonance spectroscopy (ssNMR). The strong interactions between unpaired electrons and the surrounding atomic nuclei, on the one hand, are complex to describe, and on the other hand can cause fast decaying signals and extremely broad resonances. However, significant progress has been made over the recent years in developing both theoretical models to understand and calculate the frequency shifts due to paramagnetism and also more sophisticated experimental protocols for obtaining high-resolution ssNMR spectra.

Determining the selectivity of a tetra-phosphorylated biomimetic peptide towards uranium in the presence of competing cations through the simultaneous coupling of HILIC to ESI-MS and ICP-MS.

A cyclic tetra-phosphorylated biomimetic peptide (pS1368) has been proposed as a promising starting structure to design a decorporating agent of uranyl (UO) due to its affinity being similar to that of osteopontin (OPN), a target UO protein in vivo. The determination of this peptide's selectivity towards UO in the presence of competing endogenous elements is also crucial to validate this hypothesis. In this context, the selectivity of pS1368 towards UO in the presence of Ca, Cu and Zn was determined by applying the simultaneous coupling of hydrophilic interaction chromatography (HILIC) to electrospray ionization (ESI-MS) and inductively coupled plasma (ICP-MS) mass spectrometry.

Determination of the affinity of biomimetic peptides for uranium through the simultaneous coupling of HILIC to ESI-MS and ICP-MS.

Several proteins have been identified in the past decades as targets of uranyl (UO) in vivo. However, the molecular interactions responsible for this affinity are still poorly known which requires the identification of the UO coordination sites in these proteins. Biomimetic peptides are efficient chemical tools to characterize these sites.

Probing the electronic structure and hydride occupancy in barium titanium oxyhydride through DFT-assisted solid-state NMR.

Perovskite-type oxhydrides such as BaTiOH exhibit mixed hydride ion and electron conduction and are an attractive class of materials for developing energy storage devices. However, the underlying mechanism of electric conductivity and its relation to the composition of the material remains unclear. Here we report detailed insights into the hydride local environment, the electronic structure and hydride conduction dynamics of barium titanium oxyhydride.

Synthesis of Tertiary Amines through Extrusive Alkylation of Carbamates.

Basic amines are key elements of many biologically active natural products and pharmaceuticals. Given their inherent reactivity, it is often necessary to protect basic amines during target-directed synthesis, which results in wasteful protection/deprotection sequences. We report a step-economical approach enabling the protection of secondary amines as carbamates prior to their conversion to tertiary amines via the formal extrusion of CO.

Half-integer-spin quadrupolar nuclei in magic-angle spinning paramagnetic NMR: The case of NaMnO.

A combination of solid-state NMR methods for the extraction of Na shift and quadrupolar parameters in the as-synthesized, structurally complex NaMnO Na-ion cathode material, under magic-angle spinning (MAS) is presented. We show that the integration of the Magic-Angle Turning experiment with Rotor-Assisted Population transfer (RAPT) can be used both to identify shifts and to extract a range of magnitudes for their quadrupolar couplings. We also demonstrate the applicability of the two-dimensional one pulse (TOP) based double-sheared Satellite Transition Magic-Angle Spinning (TOP-STMAS) showing how it can yield a spectrum with separated shift and second-order quadrupolar anisotropies, which in turn can be used to analyze a quadrupolar lineshape free of anisotropic bulk magnetic susceptibility (ABMS) induced shift dispersion and determine both isotropic shift and quadrupolar products.

H-Detected Biomolecular NMR under Fast Magic-Angle Spinning.

Since the first pioneering studies on small deuterated peptides dating more than 20 years ago, H detection has evolved into the most efficient approach for investigation of biomolecular structure, dynamics, and interactions by solid-state NMR. The development of faster and faster magic-angle spinning (MAS) rates (up to 150 kHz today) at ultrahigh magnetic fields has triggered a real revolution in the field. This new spinning regime reduces the H-H dipolar couplings, so that a direct detection of H signals, for long impossible without proton dilution, has become possible at high resolution.

Proton-detected fast-magic-angle spinning NMR of paramagnetic inorganic solids.

Fast (60 kHz) magic angle spinning solid-state NMR allows very sensitive proton detection in highly paramagnetic organometallic powders. We showcase this technique with the complete assignment of H and C resonances in a high-spin Fe(ii) polymerisation catalyst with less than 2 mg of sample at natural abundance.

Multi-attribute Raman spectroscopy (MARS) for monitoring product quality attributes in formulated monoclonal antibody therapeutics.

Rapid release of biopharmaceutical products enables a more efficient drug manufacturing process. Multi-attribute methods that target several product quality attributes (PQAs) at one time are an essential pillar of the rapid-release strategy. The novel, high-throughput, and nondestructive multi-attribute Raman spectroscopy (MARS) method combines Raman spectroscopy, design of experiments, and multivariate data analysis (MVDA).

Separation of quadrupolar and paramagnetic shift interactions in high-resolution nuclear magnetic resonance of spinning powders.

Separation and correlation of the shift anisotropy and the first-order quadrupolar interaction of spin I = 1 nuclei under magic-angle spinning (MAS) are achieved by the phase-adjusted spinning sideband (PASS) nuclear magnetic resonance (NMR) experiment. Compared to methods for static samples, this approach has the benefit of higher sensitivity and resolution. Moreover, the PASS experiment has the advantage over previous MAS sequences in the ability to completely separate the shift anisotropy and first-order quadrupolar interactions.

Co-Designing Health Service Evaluation Tools That Foreground First Nation Worldviews for Better Mental Health and Wellbeing Outcomes.

It is critical that health service evaluation frameworks include Aboriginal people and their cultural worldviews from design to implementation. During a large participatory action research study, Elders, service leaders and Aboriginal and non-Aboriginal researchers co-designed evaluation tools to test the efficacy of a previously co-designed engagement framework. Through a series of co-design workshops, tools were built using innovative collaborative processes that foregrounded Aboriginal worldviews.

Crystal and electronic facet analysis of ultrafine NiP particles by solid-state NMR nanocrystallography.

Structural and morphological control of crystalline nanoparticles is crucial in the field of heterogeneous catalysis and the development of "reaction specific" catalysts. To achieve this, colloidal chemistry methods are combined with ab initio calculations in order to define the reaction parameters, which drive chemical reactions to the desired crystal nucleation and growth path. Key in this procedure is the experimental verification of the predicted crystal facets and their corresponding electronic structure, which in case of nanostructured materials becomes extremely difficult.

Separation of multiphosphorylated cyclopeptides and their positional isomers by hydrophilic interaction liquid chromatography (HILIC) coupled to electrospray ionization mass spectrometry (ESI-MS).

Peptides are efficient models used in different fields such as toxicology to study the interactions of several contaminants at the molecular scale, requiring the development of bio-analytical strategies. In this context, Hydrophilic interaction liquid chromatography (HILIC) coupled to electrospray ionization mass spectrometry (ESI-MS) was used to separate synthetic multiphosphorylated cyclopeptides and their positional isomers at physiological pH. We assessed (i) the selectivity of eleven HILIC columns, from different manufacturers and packed with diverse polar sorbents, and (ii) the effect of mobile phase composition on the separation selectivity.

Cascaded processing enables continuous upstream processing with E. coli BL21(DE3).

In many industrial sectors continuous processing is already the golden standard to maximize productivity. However, when working with living cells, subpopulation formation causes instabilities in long-term cultivations. In cascaded continuous cultivation, biomass formation and recombinant protein expression can be spatially separated.

Indium(III) in the "Periodic Table" of Di(2-pyridyl) Ketone: An Unprecedented Transformation of the Ligand and Solid-State In NMR Spectroscopy as a Valuable Structural Tool.

Reactions of di(2-pyridyl) ketone, (py)CO, with indium(III) halides in CHNO have been studied, and a new transformation of the ligand has been revealed. In the presence of In, the C═O bond of (py)CO is subjected to nucleophilic attack by the carbanion :CHNO, yielding the dinuclear complexes [InX{(py)C(CHNO)(O)}] (X = Cl, ; X = Br, ; X = I, ) in moderate to good yields. The alkoxo oxygens of the two η:η:η-(py)C(CHNO)(O) ligands doubly bridge the In centers and create a {In(μ-OR)} core.

A method to calculate the NMR spectra of paramagnetic species using thermalized electronic relaxation.

For paramagnetic species, it has been long understood that the hyperfine interaction between the unpaired electrons and the nucleus results in a nuclear magnetic resonance (NMR) peak that is shifted by a paramagnetic shift, rather than split by the coupling, due to an averaging of the electronic magnetic moment caused by electronic relaxation that is fast in comparison to the hyperfine coupling constant. However, although this feature of paramagnetic NMR has formed the basis of all theories of the paramagnetic shift, the precise theory and mechanism of the electronic relaxation required to predict this result has never been discussed, nor has the assertion been tested. In this paper, we show that the standard semi-classical Redfield theory of relaxation fails to predict a paramagnetic shift, as does any attempt to correct for the semi-classical theory using modifications such as the inhomogeneous master equation or Levitt-di Bari thermalization.

Frequency-swept adiabatic pulses for broadband solid-state MAS NMR.

We present a complete description of frequency-swept adiabatic pulses applied to isolated spin-1/2 nuclei with a shift anisotropy in solid materials under magic-angle spinning. Our theoretical framework unifies the existing descriptions of adiabatic pulses in the high-power regime, where the radiofrequency (RF) amplitude is greater than twice the spinning frequency, and the low-power regime, where the RF power is less than the spinning frequency, and so links the short high-powered adiabatic pulse (SHAP) and single-sideband-selective adiabatic pulses (SAP) schemes used in paramagnetic solid-state NMR. We also identify a hitherto unidentified third regime intermediate between the low- and high-power regimes, and separated from them by rotary resonance conditions.

Low-power synchronous helical pulse sequences for large anisotropic interactions in MAS NMR: Double-quantum excitation of N.

We develop a theoretical framework for a class of pulse sequences in the nuclear magnetic resonance (NMR) of rotating solids, which are applicable to nuclear spins with anisotropic interactions substantially larger than the spinning frequency, under conditions where the radiofrequency amplitude is smaller than or comparable to the spinning frequency. The treatment is based on average Hamiltonian theory and allows us to derive pulse sequences with well-defined relationships between the pulse parameters and spinning frequency for exciting specific coherences without the need for any detailed calculations. This framework is applied to the excitation of double-quantum spectra of N and is used both to evaluate the existing low-power pulse schemes and to predict the new ones, which we present here.

Picometer Resolution Structure of the Coordination Sphere in the Metal-Binding Site in a Metalloprotein by NMR.

Most of our understanding of chemistry derives from atomic-level structures obtained with single-crystal X-ray diffraction. Metal centers in X-ray structures of small organometallic or coordination complexes are often extremely well-defined, with errors in the positions on the order of 10-10 Å. Determining the metal coordination geometry to high accuracy is essential for understanding metal center reactivity, as even small structural changes can dramatically alter the metal activity.