State Nuclear Magnetic Resonance Spectroscopy Research Articles

The influence of poly(allylamine hydrochloride) hydrogel crosslinking density on its thermal and phosphate binding properties

Sevelamer hydrochloride (SH) or Renagel® is an effective phosphate binder prescribed to prevent the absorption of phosphate in end stage renal disease (ESRD) patients. The relationship between SH structure and binding capacity and affinity is very important and can be used in characterising the sensitivity of the hydrogel to binding conditions. Thus, a series of hydrogels were prepared by varying the amount of crosslinker, whilst the other hydrogel components were kept constant. Variation of this parameter influenced the hydrogel structure as shown by swelling data, differential scanning calorimetry and solid state nuclear magnetic resonance spectroscopy. The hydrogels’ physical characteristics were found to correlate with the number of phosphate binding sites and affinity obtained from the Langmuir–Freundlich Isotherm (L–FI) and affinity distribution spectra (AD). The hydrogels formed using lower amounts of crosslinker showed a slight increase in binding capacity but with lower affinity. However, the influence of the pH of the binding media on the binding parameters of sevelamer hydrochloride was significant. This is the first report on the use of AD spectra generated from L-FI binding parameters in hydrogels, which demonstrates the sensitivity of the affinity and binding site numbers to changes in hydrogel physical properties and the pH of the binding media.

Quantitative analysis of the strength generating C-S-H-phase in concrete by IR-spectroscopy

The C-S-H-phase is the most important strength generating phase in concrete and other cementitious materials. The analysis of C-S-H is therefore an important instrument of innovations in the field of concrete and its durability and sustainability. The quantification and insights in C-S-H are hindered by the predominantly amorphous structure of C-S-H. Only the time consuming and expensive solid state nuclear magnetic resonance spectroscopy (NMR) gives a chance to get results, but is restricted to model substances. A new technique, based on the cheap and widespread infrared-spectroscopy (IR) was developed. The quantitative analysis is based on the silicon content in the different structural units of C-S-H and a calibration with natural and synthetic materials with known silicon content in these units. The technique allows to investigate specimens from real structures. Specimens with quartz or limestone aggregate can be analyzed directly. In other cases the aggregates must be separated, for example with heavy liquid separation. Tests with different mortars showed a good correspondence of measured and expected values of C-S-H concentration.

Structure Determination of Microtubules and Pili: Past, Present, and Future Directions.

Historically proteins that form highly polymeric and filamentous assemblies have been notoriously difficult to study using high resolution structural techniques. This has been due to several factors that include structural heterogeneity, their large molecular mass, and available yields. However, over the past decade we are now seeing a major shift towards atomic resolution insight and the study of more complex heterogenous samples and in situ/ex vivo examination of multi-subunit complexes. Although supported by developments in solid state nuclear magnetic resonance spectroscopy (ssNMR) and computational approaches, this has primarily been due to advances in cryogenic electron microscopy (cryo-EM). The study of eukaryotic microtubules and bacterial pili are good examples, and in this review, we will give an overview of the technical innovations that have enabled this transition and highlight the advancements that have been made for these two systems. Looking to the future we will also describe systems that remain difficult to study and where further technical breakthroughs are required.

Compartmentalized Polymeric Nanoparticles Deliver Vancomycin in a pH-Responsive Manner.

Vancomycin (VCM) is a last resort antibiotic in the treatment of severe Gram-positive infections. However, its administration is limited by several drawbacks such as: strong pH-dependent charge, tendency to aggregate, low bioavailability, and poor cellular uptake. These drawbacks were circumvented by engineering pH-responsive nanoparticles (NPs) capable to incorporate high VCM payload and deliver it specifically at slightly acidic pH corresponding to infection sites. Taking advantage of peculiar physicochemical properties of VCM, here we show how to incorporate VCM efficiently in biodegradable NPs made of poly(lactic-co-glycolic acid) and polylactic acid (co)polymers. The NPs were prepared by a simple and reproducible method, establishing strong electrostatic interactions between VCM and the (co)polymers’ end groups. VCM payloads reached up to 25 wt%. The drug loading mechanism was investigated by solid state nuclear magnetic resonance spectroscopy. The engineered NPs were characterized by a set of advanced physicochemical methods, which allowed examining their morphology, internal structures, and chemical composition on an individual NP basis. The compartmentalized structure of NPs was evidenced by cryogenic transmission electronic microscopy, whereas the chemical composition of the NPs’ top layers and core was obtained by electron microscopies associated with energy-dispersive X-ray spectroscopy. Noteworthy, atomic force microscopy coupled to infrared spectroscopy allowed mapping the drug location and gave semiquantitative information about the loadings of individual NPs. In addition, the NPs were stable upon storage and did not release the incorporated drug at neutral pH. Interestingly, a slight acidification of the medium induced a rapid VCM release. The compartmentalized NPs could find potential applications for controlled VCM release at an infected site with local acidic pH.

Dentin interaction with universal adhesive containing isopropanol solvent studied by solid-state NMR spectroscopy

ObjectiveThis study investigated the chemical and structural changes in the mineral phase and collagen of dentin during application of a mild universal adhesive. Particular attention was paid to the role of isopropanol and changes in water molecules. MethodsIn vitro application of the mild universal adhesive on dentin with two established etching modes (self-etch and etch-and-rinse) was studied using solid state nuclear magnetic resonance spectroscopy. ResultsIt was evidenced that the etch-and-rinse mode leads to a decrease of the inorganic apatite and a reorganization of the residual mineral phase with a low amount of adhesive phosphate monoesters calcium salt formed, compared to the self-etch mode. In contrast, the adhesive interacts very similarly to the level of dentin collagen in both protocols, with a strong decrease in the amount of the free water molecules induced by the presence of isopropanol as the adhesive solvent, but without significant changes in the initial collagen structure. For both modes, the adhesive acrylates monomers remain mobile and can infiltrate the collagen. SignificanceUnderstanding the molecular interactions between dentin and adhesive solutions is a major challenge for designing products that lead to the formation of ideal dentin resin hybrid layer. Notably, one point considered essential is the presence of unbound water which, over time, is associated with a hydrolytic degradation of the organic matrix. Isopropanol, as an adhesive solvent, leads to a decrease in the amount of the less stable water molecules while the water molecules strongly attached to the collagen are retained, thus preserving the collagen structure.

Solvent Effect in Imidazole-Based Poly(Ionic liquid) Membranes: Energy Storage and Sensing.

Polymerized ionic liquids (PILs) are interesting new materials in sustainable technologies for energy storage and for gas sensor devices, and they provide high ion conductivity as solid polymer electrolytes in batteries. We introduce here the effect of polar protic (aqueous) and polar aprotic (propylene carbonate, PC) electrolytes, with the same concentration of lithium bis(trifluoromethane) sulfonimide (LiTFSI) on hydrophobic PIL films. Cyclic voltammetry, scanning ionic conductance microscopy and square wave voltammetry were performed, revealing that the PIL films had better electroactivity in the aqueous electrolyte and three times higher ion conductivity was obtained from electrochemical impedance spectroscopy measurements. Their energy storage capability was investigated with chronopotentiometric measurements, and it revealed 1.6 times higher specific capacitance in the aqueous electrolyte as well as novel sensor properties regarding the applied solvents. The PIL films were characterized with scanning electron microscopy, energy dispersive X-ray, FTIR and solid state nuclear magnetic resonance spectroscopy.

Concerted effect of boron and porosity on shear thickening behavior of hybrid mesoporous silica dispersions

In the present work, the influence of porosity and boron on shear thickening behavior of hybrid mesoporous silica has been studied. Three different levels of boron modification were performed by varying the molar composition of boric acid viz., 1.5 mmol, 2.5 mmol, and 3.5 mmol in a co-condensation approach. The incorporation of boron in mesoporous silica network was confirmed by various techniques such as Fourier transform infra-red (FTIR), and 11B solid- state nuclear magnetic resonance (NMR) spectroscopy. The morphology and particle size were confirmed by using scanning and transmission electron microscopy. To evaluate the effect of boron and porosity on the shear thickening behavior, dispersions were prepared from mesoporous boron- modified silica (MSiB), control mesoporous silica (MSi), non-porous boron-modified silica (SiB), and control non-porous silica (Si) in polyethylene glycol. The shear thickening behavior was studied using steady shear rheology. The dispersion prepared from different loadings of synthesized MSiB containing 1.5 mmol boron showed more than 16 times increase in viscosity (657.7 Pa.s) compared to that of MSi (39.2 Pa.s) at a fairly low volume fraction (φ = 0.15) of silica. It is expected that the highly ordered mesoporous architecture of hybrid silica has improved the interaction between the particle and the dispersing medium through hydrogen bonding. The porous morphology of the hybrid mesoporous silica as well as the incorporation of boron in the silica network favors the formation of a frictional contact network, and a transition from continuous shear thickening (CST) to discontinuous shear thickening (DST) behavior was observed. Therefore, silica prepared via incorporation of boron as well as porosity can be material of interest in variety of applications, for example, soft body armors, sporting goods, and shear thickening electrolytes for high impact resistant batteries.

Measurement of local magnetic fields in actinide tetrafluorides.

Fluorine-19 magnetic shielding tensors have been measured in a series of actinide tetrafluorides (AnF4) by solid state nuclear magnetic resonance spectroscopy. Tetravalent actinide centers with 0-8 valence electrons can form tetrafluorides with the same monoclinic structure type, making these compounds an attractive choice for a systematic study of the variation in the electronic structure across the 5f row of the Periodic Table. Pronounced deviations from predictions based on localized valence electron models have been detected by these experiments, which suggests that this approach may be used as a quantitative probe of electronic correlations.

Inorganic-organic hybrid pigments based on carminic acid and clay minerals

Hybrid pigments based on carminic acid (CA) stabilized by clay minerals have been prepared. Three different pathways were used: CA@saponite; CA@Al-pillared saponite; and hydrogels of saponite-CA or montmorillonite-CA covered by polyorganosilane (POS). Pigments were characterized by a set of different techniques including X-Ray diffraction (XRD), transmission electron microscopy (TEM), infrared spectroscopy (FTIR), solid state nuclear magnetic resonance (NMR) and time-resolved fluorescence (TRF) spectroscopies. The color parameters, i.e., L*a*b*, were measured. In addition, the photostability of the samples under visible light was evaluated. The results showed that CA@PilSap presented a greater stability compared to CA@Saponite. The pigments obtained from hydrogels presented the greatest light stability due to the coverage with POS that acts as a protective layer.

Structural basis for the binding of the cancer targeting scorpion toxin, ClTx, to the vascular endothelia growth factor receptor neuropilin-1.

Chlorotoxin (ClTx) is a 36-residue disulfide-rich peptide isolated from the venom of the scorpion Leiurus quinquestriatus. This peptide has been shown to selectively bind to brain tumours (gliomas), however, with conflicting reports regarding its direct cellular target. Recently, the vascular endothelial growth factor receptor, neuropilin-1 (NRP1) has emerged as a potential target of the peptide. Here, we sought to characterize the details of the binding of ClTx to the b1-domain of NRP1 (NRP1-b1) using solution state nuclear magnetic resonance (NMR) spectroscopy. The 3D structure of the isotope labelled peptide was solved using multidimensional heteronuclear NMR spectroscopy to produce a well-resolved structural ensemble. The structure points to three putative protein-protein interaction interfaces, two basic patches (R14/K15/K23 and R25/K27/R36) and a hydrophobic patch (F6/T7/T8/H10). The NRP1-b1 binding interface of ClTx was elucidated using 15N chemical shift mapping and included the R25/K27/R36 region of the peptide. The thermodynamics of binding was determined using isothermal titration calorimetry (ITC). In both NMR and ITC measurements, the binding was shown to be competitive with a known NRP1-b1 inhibitor. Finally, combining all of this data we generate a model of the ClTx:NRP1-b1 complex. The data shows that the peptide binds to the same region of NRP1 that is used by the SARS-CoV-2 virus for cell entry, however, via a non-canonical binding mode. Our results provide evidence for a non-standard NRP1 binding motif, while also providing a basis for further engineering of ClTx to generate peptides with improved NRP1 binding for future biomedical applications.

Synergistic Combination of Calcium and Citrate in Mesoporous Nanoparticles Targets Pleural Tumors

Summary Conventional chemotherapy leads to severe adverse effects since it involves systemic administration of toxic drugs at high dosage. Unlike traditional chemotherapeutics, calcium phosphate and citrate have both been discussed as very promising anticancer agents and are not inherently toxic. Yet, their breakthrough has been hampered by the lack of an administration approach that overcomes the strict regulatory mechanisms of the cell. Here, we present a combinatorial administration of calcium, phosphate, and citrate as colloidal, amorphous nanoparticles (CPCs) that selectively kill cancer cells without involvement of inherently toxic drugs. The particles are toxic neither before endosomal release nor after their degradation. This highly selective toxicity allowed us to successfully treat two different aggressive pleural tumors in mice, reducing their size by about 40% and 70% after only two local applications. Safety assessment studies over 2 months show no signs of adverse effects except for slightly enhanced pleural thickening after eight applications.

Speciation transformation of Pb during palygorskite sorption-calcination process: Implications for Pb sequestration

In this work, palygorskite was used to immobilize Pb using a sorption-calcination method. The speciation transformation of Pb during the process was characterized using surface complexation modeling (SCM), X-ray photoelectron spectroscopy (XPS), powder X-ray diffraction (XRD), 27Al and 29Si solid state nuclear magnetic resonance (NMR) spectroscopy and field emission scanning electron microscopy (FESEM). Results showed that Pb was adsorbed at permanently charged sites in the form of outer-sphere surface complexes at pH < 6 and [Pb(II)] < 0.5 mM, whereas inner-sphere ≡SOPbOH complexes formed under alkaline conditions. At high [Pb(II)] (e.g., 2 mM), Pb3(CO3)2(OH)2 precipitate was observed. Since desorption experiments implied that sorbed Pb on palygorskite was labile, Pb-sorbed palygorskite was then heated at 200 and 800 °C, which suggested that thermal treatment effectively stabilized Pb(II), with no observable desorption after heating at 800 °C. Such stabilization is caused by the transformation of surface sorbed Pb(II) to Pb-containing enstatite based on XRD, SEM and solid state NMR characterizations. Overall, this study demonstrates a promising Pb stablization method in which Pb would be sorbed by palygorskite and sequestrated in the subsquent thermal treatment, leading to an effective immobilization of Pb.

Sol-gel synthesis and study of praseodymium substitution effects in yttrium aluminium garnet Y3-xPrxAl5O12

In this study, praseodymium substituted yttrium aluminium garnet (Y 3-x Pr x Al 5 O 12 ; YPrAG (0 ≤ x ≤ 3)) powders were synthesized by an aqueous sol-gel method and investigated. YPrAG samples were characterized by X-ray diffraction (XRD) analysis, solid state nuclear magnetic resonance (NMR) spectroscopy and scanning electron microscopy (SEM). Luminescence measurements of YPrAG samples were performed as well. It was demonstrated, that three phase regions exist depending on the substitutional level of Pr 3+ in Y 3-x Pr x Al 5 O 12 . The single-phase cubic garnets have formed up to x = 0.30. The mixture of garnet and trigonal perovskite (Y 1-x Pr x AlO 3 ) phase have formed when x is between 0.45 and 2.00. The perovskite phase was the main crystalline phase with further increasing amount of praseodymium, no garnet structure was observed. The amorphous impurity phases were detected by solid state NMR spectroscopy. Two broad and intense emission bands in the UV region peaked at 325 and 381 nm and several sharp emission bands in the visible region were determined by investigating the luminescence properties of the Y 3-x Pr x Al 5 O 12 mixed-metal oxides. • Y 3-x Pr x Al 5 O 12 specimens were synthesized using aqueous sol-gel synthesis method. • Monophasic garnets obtained at low substitution of yttrium by praseodymium. . • The region of coexisting phases have been evidently deduced by solid state NMR spectroscopy. . • The Pr 3+ emission in the range of 300–750 was observed in Y 3-x Pr x Al 5 O 12 garnets. • The decay times for the Y 3-x Pr x Al 5 O 12 garnets decreased with increasing Pr 3+ amount. .

Pharmaceutical Hydrates Analysis—Overview of Methods and Recent Advances

This review discusses a set of instrumental and computational methods that are used to characterize hydrated forms of APIs (active pharmaceutical ingredients). The focus has been put on highlighting advantages as well as on presenting some limitations of the selected analytical approaches. This has been performed in order to facilitate the choice of an appropriate method depending on the type of the structural feature that is to be analyzed, that is, degree of hydration, crystal structure and dynamics, and (de)hydration kinetics. The presented techniques include X-ray diffraction (single crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD)), spectroscopic (solid state nuclear magnetic resonance spectroscopy (ssNMR), Fourier-transformed infrared spectroscopy (FT-IR), Raman spectroscopy), thermal (differential scanning calorimetry (DSC), thermogravimetric analysis (TGA)), gravimetric (dynamic vapour sorption (DVS)), and computational (molecular mechanics (MM), Quantum Mechanics (QM), molecular dynamics (MD)) methods. Further, the successful applications of the presented methods in the studies of hydrated APIs as well as studies on the excipients’ influence on these processes have been described in many examples.

Palladium Catalysts Based on Porous Aromatic Frameworks, Modified with Ethanolamino-Groups, for Hydrogenation of Alkynes, Alkenes and Dienes

The current work describes an attempt to synthesize hybrid materials combining porous aromatic frameworks (PAFs) and dendrimers and use them to obtain novel highly active and selective palladium catalysts. PAFs are carbon porous materials with rigid aromatic structure and high stability, and the dendrimers are macromolecules which can effectively stabilize metal nanoparticles and tune their activity in catalytic reactions. Two porous aromatic frameworks, PAF-20 and PAF-30, are modified step-by-step with diethanolamine and hydroxyl groups at the ends of which are replaced by new diethanolamine molecules. Then, palladium nanoparticles are applied to the synthesized materials. Properties of the obtained materials and catalysts are investigated using X-ray photoelectron spectroscopy, transmission electron microscopy, solid state nuclear magnetic resonance spectroscopy, low temperature N2 adsorption and elemental analysis. The resulting catalysts are successfully applied as an efficient and recyclable catalyst for selective hydrogenation of alkynes to alkenes at very high (up to 90,000) substrate/Pd ratios.

Controls of nature: Secondary, tertiary, and quaternary structure of the enamel protein amelogenin in solution and on hydroxyapatite

Amelogenin, a protein critical to enamel formation, is presented as a model for understanding how the structure of biomineralization proteins orchestrate biomineral formation. Amelogenin is the predominant biomineralization protein in the early stages of enamel formation and contributes to the controlled formation of hydroxyapatite (HAP) enamel crystals. The resulting enamel mineral is one of the hardest tissues in the human body and one of the hardest biominerals in nature. Structural studies have been hindered by the lack of techniques to evaluate surface adsorbed proteins and by amelogenin’s disposition to self-assemble. Recent advancements in solution and solid state nuclear magnetic resonance (NMR) spectroscopy, atomic force microscopy (AFM), and recombinant isotope labeling strategies are now enabling detailed structural studies. These recent studies, coupled with insights from techniques such as CD and IR spectroscopy and computational methodologies, are contributing to important advancements in our structural understanding of amelogenesis. In this review we focus on recent advances in solution and solid state NMR spectroscopy and in situ AFM that reveal new insights into the secondary, tertiary, and quaternary structure of amelogenin by itself and in contact with HAP. These studies have increased our understanding of the interface between amelogenin and HAP and how amelogenin controls enamel formation.

Bis-3,5-Diamino-1,2,4-Triazolyl-1,2,4,5-Tetrazine: From Insensitive High Energy Density Materials to Small Molecule Organic Semiconductors

Besides the well-known pyrotechnic applications of insensitive high energy compounds such as s-tetrazine, they are promising materials for relevant applications (e.g., electrochemical energy storage, photocatalysis). Bis-3,5-diamino-1,2,4-triazolyl-1,2,4,5-tetrazine (BDTT) is a nitrogen-rich conjugated heterocyclic compound (nitrogen ≈ 71 wt %), inert to ignition and mechanical stimuli and thermally stable up to 370 °C. The solvent-free crystalline structure of this high energy density compound (named IEF-12 for IMDEA energy framework) is reported here for the first time using the high resolution powder X-ray diffraction (PXRD) and 1H, 13C, and 15N solid state nuclear magnetic resonance (NMR) spectroscopy. We demonstrate that IEF-12 has features of a small molecule organic semiconductor, namely, lamellar π-stacked crystal packing in the solid state, a low energy optical bandgap Egopt = 2.27 eV, and a relatively high value of dielectric constant εr = 4.86. Overall, we demonstrated on IEF-12 that insensitive high energy density materials (HEDM) may open an avenue for nonclassically structured organic semiconductors, paving the way for optoelectronic and photovoltaic applications.

Gallium and tin exchanged Y zeolites for glucose isomerisation and 5-hydroxymethyl furfural production

This study demonstrates the use of gallium and tin modified Y zeolites as catalysts for the conversion of glucose into fructose, mannose and 5-Hydroxymethyl furfural. These catalysts can be synthesised via a simple and scalable procedure that uses commercially available Y zeolite. The catalysts were characterised by various techniques including elemental analysis, electron microscopy, nitrogen physisorption, X-ray diffraction, X-ray photoelectron spectroscopy, ultraviolet-visible spectroscopy, solid state nuclear magnetic resonance spectroscopy and X-ray absorption near edge spectroscopy. It is found that tin containing Y zeolite generate a glucose conversion of 36 % and total product yield of 17 % in water. Meanwhile, gallium containing Y zeolite shows an HMF yield of 33 % when reactions were conducted in DMSO. The recyclability of tin and gallium containing Y zeolites were studied in DMSO and the activities of both materials were shown to remain stable. Furthermore, the spent catalysts can be regenerated via calcination in air.

A Simplified Method of Synthesis to Obtain Zwitterionic Cellulose under Mild Conditions with Active Ionic Moieties.

A simplified procedure to synthesize zwitterionic cellulose by means of N-protected aspartic anhydride under mild conditions was developed. The preparation of modified cellulose samples was carried out under heterogeneous, aqueous conditions by reacting NH4OH-activated cellulose with aspartic anhydrides N-protected with trifluoroacetyl (TFAc) and carbobenzyloxy (Cbz). Modified cellulose samples Cel-Asp-N-TFAc and Cel-Asp-N-Cbz were characterized by Fourier Transform Infrared (FTIR) and 13C solid state Nuclear Magnetic Resonance (NMR) spectroscopy. The functionalization degree of each cellulose sample was determined by the 13C NMR signal integration values corresponding to the cellulose C1 vs. the Cα of the aspartate residue and corroborated by elemental analysis. In agreement, both analytical methods averaged a grafting degree of 20% for Cel-Asp-N-TFAc and 16% for Cel-Asp-N-Cbz. Conveniently, Cel-Asp-N-TFAc was concomitantly partially N-deprotected (65%) as determined by the ninhydrin method. The zwitterion character of this sample was confirmed by a potentiometric titration curve and the availability of these amino acid residues on the cellulose was inspected by adsorption kinetics method with a 100 mg L−1 cotton blue dye solution. In addition, the synthesis reported in the present work involves environmentally related advantages over previous methodologies developed in our group concerning to zwitterionic cellulose preparation.

A Spectroscopic Marker for Structural Transitions Associated with Amyloid-β Aggregation.

An amyloid aggregate evolves through a series of intermediates that have different secondary structures and intra- and intermolecular contacts. The structural parameters of these intermediates are important determinants of their toxicity. For example, the early oligomeric species of the amyloid-β (Aβ) peptide have been implicated as the most cytotoxic species in Alzheimer's disease but are difficult to identify because of their dynamic and transitory nature. Conventional aggregation monitors such as the fluorescent dye thioflavin T report on only the overall transition of the soluble species to the final amyloid fibrillar aggregated state. Here, we show that the fluorescent dye bis(triphenylphosphonium) tetraphenylethene (TPE-TPP) identifies at least three distinct aggregation intermediates of Aβ. Some atomic-level features of these intermediates are known from solid state nuclear magnetic resonance spectroscopy. Hence, the TPE-TPP fluorescence data may be interpreted in terms of these Aβ structural transitions. Steady state fluorescence and lifetime characteristics of TPE-TPP distinguish between the small oligomeric species (emission wavelength maximum, λmax = 465 nm; average fluorescence lifetime, τFl measured at 420 nm = 3.58 ± 0.04 ns), the intermediate species (λmax = 452 nm; τFl = 3.00 ± 0.03 ns), and the fibrils (λmax = 406 nm; τFl = 5.19 ± 0.08 ns). Thus, TPE-TPP provides a ready diagnostic for differentiating between the various, including the toxic, Aβ aggregates and potentially can be utilized to screen for amyloid aggregation inhibitors.