Solid-state NMR Investigations Research Articles

Solid-State 2H NMR Investigations of Viral Am2 Ion Channel Drugs

Solid-State 2H NMR Investigations of Viral Am2 Ion Channel Drugs

Mechanistic Investigation on Catalytic Deoxygenation of Phenol as a Model Compound of Biocrude Under Methane

A novel hydrogen-free approach is developed to effectively convert phenolic compounds into aromatics including benzene, toluene, ethylbenzene, and xylene (BTEX), a very important and widely used class of petrochemical intermediates, and naphthalene. High yield and selectivity of BTEX are achieved over Zn modified zeolite catalyst during phenol deoxygenation under a methane environment at 400 °C and 2 MPa. Methane can greatly enhance the liquid yield and selectivity of BTEX, but also improve the catalyst activity. Experimental analysis and mechanistic studies reveal that methane is incorporated into both the methyl group and aromatic ring. The embedding of methane into aromatic compounds is achieved via C-alkylation of phenyl ring, coaromatization with hydrocarbon radicals, and a ring-expansion/contraction mechanism. Liquid- and solid-state NMR investigations make evident the phenyl ring-opening in the reaction. Our mechanistic understanding of this process will provide valuable insights into the chemistry...

Solid-State NMR Investigations of Carbon Dioxide Gas in Metal-Organic Frameworks: Insights into Molecular Motion and Adsorptive Behavior.

Solid-state nuclear magnetic resonance (SSNMR) methods have been routinely used for the characterization of both the structure and the dynamics of metal organic frameworks (MOFs), a collection of porous media investigated for potential applications in carbon capture technologies, selective separation of small molecules, and catalysis. (1) The use and development of SSNMR techniques that enable the nondestructive characterization of the adsorbed behavior have become essential steps in bettering our understanding of MOFs and are often complementary to traditional methods of structural characterization. This Review aims to give a brief introduction to the relevant concepts of SSNMR and the methods employed when investigating the phenomenon of adsorbed carbon dioxide gas in MOFs. We summarize the published SSNMR literature on CO2 in MOFs, as well as highlight the best experimental practices when working with these complex systems.

Theoretical investigations into the variability of the 15N solid-state NMR parameters within an antimicrobial peptide ampullosporin A.

The solid-state NMR measurements play an indispensable role in studies of interactions between biological membranes and peptaibols, which are amphipathic oligopeptides with a high abundance of alpha-aminobutyric acid (Aib). The solid-state NMR investigations are important in establishing the molecular models of the pore forming and antimicrobial properties of peptaibols, but rely on certain simplifications. Some of the underlying assumptions concern the parameters describing the 15N NMR chemical shielding tensor (CST) of the amide nitrogens in Aib and in conventional amino acids. Here the density functional theory (DFT) based calculations were applied to the known crystal structure of one of peptaibols, Ampullosporin A, in order to explicitly describe the variation of the 15N NMR parameters within its backbone. Based on the DFT computational data it was possible to verify the validity of the assumptions previously made about the differences between Aib and other amino acids in the isotropic part of the CST. Also the trends in the magnitudes and orientations of the anisotropic components of the CST, as revealed by the DFT calculations of the full periodic structure of Ampullosporin A, were thoroughly analyzed, and may be employed in future studies of peptaibols.

Molecular Engineered Safer Organic Battery through the Incorporation of Flame Retarding Organophosphonate Moiety.

Here, we report the first electrochemical assessment of organophosphonate-based compound as a safe electrode material for lithium-ion batteries, which highlights the reversible redox activity and inherent flame retarding property. Dinickel 1,4-benzenediphosphonate delivers a high reversible capacity of 585 mA h g-1 with stable cycle performance. It expands the scope of organic batteries, which have been mainly dominated by the organic carbonyl family to date. The redox chemistry is elucidated by X-ray absorption spectroscopy and solid-state 31P NMR investigations. Differential scanning calorimetry profiles of the lithiated electrode material exhibit suppressed heat release, delayed onset temperature, and endothermic behavior in the elevated temperature zone.

Solid-State NMR Investigation of Drug-Excipient Interactions and Phase Behavior in Indomethacin-Eudragit E Amorphous Solid Dispersions.

To investigate the nature of drug-excipient interactions between indomethacin (IMC) and methacrylate copolymer Eudragit® E (EE) in the amorphous state, and evaluate the effects on formulation and stability of these amorphous systems. Amorphous solid dispersions containing IMC and EE were spray dried with drug loadings from 20% to 90%. PXRD was used to confirm the amorphous nature of the dispersions, and DSC was used to measure glass transition temperatures (Tg). 13C and 15N solid-state NMR was utilized to investigate changes in local structure and protonation state, while 1H T1 and T1ρ relaxation measurements were used to probe miscibility and phase behavior of the dispersions. Tg values for IMC-EE solid dispersions showed significant positive deviations from predicted values in the drug loading range of 40-90%, indicating a relatively strong drug-excipient interaction. 15N solid-state NMR exhibited a change in protonation state of the EE basic amine, with two distinct populations for the EE amine at -360.7ppm (unprotonated) and -344.4ppm (protonated). Additionally, 1H relaxation measurements showed phase separation at high drug load, indicating an amorphous ionic complex and free IMC-rich phase. PXRD data showed all ASDs up to 90% drug load remained physically stable after 2years. 15N solid-state NMR experiments show a change in protonation state of EE, indicating that an ionic complex indeed forms between IMC and EE in amorphous solid dispersions. Phase behavior was determined to exhibit nanoscale phase separation at high drug load between the amorphous ionic complex and excess free IMC.

Ammonia Treatment of 0.35Li2MnO3·0.65LiNi0.35Mn0.45Co0.20O2 Material: Insights from Solid-State NMR Analysis

Li-rich cathode materials of the formula xLi2MnO3·yLiNiaCobMncO2 (x + y = 1, a + b + c = 1) boast very high discharge capacity, ca. 250 mAh/g. Yet, they suffer capacity decrease and average voltage fade during cycling in Li-ion batteries that prohibit their commercialization. Treatment of the materials with NH3(g) at high temperatures produces improved electrodes with higher stability of capacity and average voltage. The present study follows the changes occurring in the materials upon treatment with ammonia gas, through 6Li and 7Li solid-state NMR investigations of the untreated and ammonia treated 0.35Li2MnO3·0.65LiNi0.35Mn0.45Co0.20O2 as well as its constituent phases, Li2MnO3 and LiNi0.4Co0.2Mn0.4O2. The NMR analysis demonstrates the biphasic nature of these materials. Furthermore, it shows that the Li2MnO3 component phase in the integrated material is the phase mostly being affected by the gas treatment. A thickening of a protective surface film in the integrated material, with the right exposure tim...

Solid-State 2H NMR Investigations of Viral M2 Ion Channel Drugs

Solid-State 2H NMR Investigations of Viral M2 Ion Channel Drugs

Free-Standing and Self-Crosslinkable Hybrid Films by Core-Shell Particle Design and Processing.

The utilization and preparation of functional hybrid films for optical sensing applications and membranes is of utmost importance. In this work, we report the convenient and scalable preparation of self-crosslinking particle-based films derived by directed self-assembly of alkoxysilane-based cross-linkers as part of a core-shell particle architecture. The synthesis of well-designed monodisperse core-shell particles by emulsion polymerization is the basic prerequisite for subsequent particle processing via the melt-shear organization technique. In more detail, the core particles consist of polystyrene (PS) or poly(methyl methacrylate) (PMMA), while the comparably soft particle shell consists of poly(ethyl acrylate) (PEA) and different alkoxysilane-based poly(methacrylate)s. For hybrid film formation and convenient self-cross-linking, different alkyl groups at the siloxane moieties were investigated in detail by solid-state Magic-Angle Spinning Nuclear Magnetic Resonance (MAS, NMR) spectroscopy revealing different crosslinking capabilities, which strongly influence the properties of the core or shell particle films with respect to transparency and iridescent reflection colors. Furthermore, solid-state NMR spectroscopy and investigation of the thermal properties by differential scanning calorimetry (DSC) measurements allow for insights into the cross-linking capabilities prior to and after synthesis, as well as after the thermally and pressure-induced processing steps. Subsequently, free-standing and self-crosslinked particle-based films featuring excellent particle order are obtained by application of the melt-shear organization technique, as shown by microscopy (TEM, SEM).

Solid-State NMR Investigation of Bio-chars Produced from Biomass Components and Whole Biomasses

Bio-char is a by-product from thermochemical treatment of biomass and has been identified as an energy condensed product with a comparable heating value as commercial coal. However, the combustion of such solid product as an energy resource is only a preliminary application. It is highly possible to convert bio-char, which always has a condensed aromatic and porous structure to various high-value products. The investigations of the structures and formation pathways for the bio-char are very important to any future applications. In this study, six different biomass components, including cellulose, lignin, and tannin, and three whole biomasses—pine wood, pine residue, and pine bark—have been used to produce bio-char at 400, 500, and 600 °C. Solid-state NMR and FT-IR have been employed in this study to characterize the structures for the bio-chars. The results indicated that the bio-chars produced from lignin contained some methoxyl groups, and the bio-chars produced from tannin contained significantly higher amount of phenolic hydroxyl groups. Compared to the bio-chars produced from pine wood and residue, the bio-chars produced from pine bark contained more aromatic C–O bonds, and aliphatic C–O and C–C bonds, which may be due to the significantly higher amount of lignin and tannin in the pine bark. However, the elevated amounts of aromatic C–O and aliphatic C–O and C–C bonds in the bio-chars from pine bark appeared to be completely decomposed at 600 °C.

NMR investigations unveil phase composition–property correlations in Sr0.55Na0.45SiO2.775 fast ion conductor

This paper reports results of 23Na and 29Si solid-state NMR investigations carried out on sodium strontium silicate ion conductor, Sr0.55Na0.45SiO2.775 and presents the first experimental evidence to show that different synthesis conditions induce multiple devitrified phases. Along with 1-dimensional NMR, 23Na MQMAS spectra have been used to identify the phases corresponding to polymorphs of Na2Si2O5, in addition to the crystalline SrSiO3 and the glass/amorphous Na2Si2O5 phases. The surprising observation of about an order of magnitude higher ionic conductivity achieved in devitrified samples is attributed to the growth of the crystalline δ-Na2Si2O5 phase within the amorphous Na2Si2O5 phase domains, identified using NMR. Together with XRD and conductivity measurement data, the study leads to the identification of the chemical phase composition and an understanding of the composition-property-structure correlation in this material. Present findings, while do not show any evidence of Na doping in the SrSiO3 phase confirming earlier reports, explain the large discrepancy in the conductivity reported in the literature.

Crystal Effects on Mesobilirubin: A Combined NMR Spectroscopic and Density Functional Theory Study.

We report solid-state NMR investigations of crystal effects in powdered mesobilirubin-IXα, an open-chain tetrapyrrole that is structurally related to bilirubin-IXα but hydrogenated at the 3- and 18-vinyl groups. 13 C and 15 N cross-polarization magic-angle spinning (CP/MAS) NMR experiments were performed on the compound at natural abundance. To facilitate the spectral analysis, density functional calculations were carried out at the B3LYP/6-311G(d,p) level of theory, using an enneameric cluster to simulate the solid. The 1 H, 13 C and 15 N chemical shift data calculated for the enneamer are in a good agreement with those observed in the experimental spectra, and the relative order of the calculated resonances was thus used to confirm the tentative assignments obtained mainly from the heteronuclear correlation spectra. The observed signal splittings of a small subset of the 13 C resonances in the peripheral regions of the two terminal rings provide evidence for microcrystalline heterogeneity of the powdered compound.

Combined Solid-State NMR and Computational Approach for Probing the CO2 Binding Sites in a Porous-Organic Polymer

We report on utilization of 1D and 2D 13C cross-polarization magic angle spinning (CPMAS) and MAS solid-state NMR spectroscopy in probing the binding sites and dynamical processes of 13C-enriched CO2 inside the pores of a pyridine-containing porous organic polymer (POP). Our findings from the spectroscopic measurements conducted on the evacuated sample and on the sample dosed with 800 mbar 13CO2 indicated preferential adsorption of the CO2 molecules at the vicinity of the basic binding sites within the POP, the pyridine rings. We further demonstrate the results of a computational study for probing the most favorable binding sites of CO2 inside a geometrically optimized model of the polymer in an attempt to better rationalize the experimental findings from 13C solid-state NMR investigations. Because of the amorphous nature of the studied POP, also being observed for a large number of emerging microporous solids, this combined approach can prove useful and versatile toward drawing a detailed picture of the ...

Expression, Functional Characterization, and Solid-State NMR Investigation of the G Protein-Coupled GHS Receptor in Bilayer Membranes

The expression, functional reconstitution and first NMR characterization of the human growth hormone secretagogue (GHS) receptor reconstituted into either DMPC or POPC membranes is described. The receptor was expressed in E. coli. refolded, and reconstituted into bilayer membranes. The molecule was characterized by 15N and 13C solid-state NMR spectroscopy in the absence and in the presence of its natural agonist ghrelin or an inverse agonist. Static 15N NMR spectra of the uniformly labeled receptor are indicative of axially symmetric rotational diffusion of the G protein-coupled receptor in the membrane. In addition, about 25% of the 15N sites undergo large amplitude motions giving rise to very narrow spectral components. For an initial quantitative assessment of the receptor mobility, 1H-13C dipolar coupling values, which are scaled by molecular motions, were determined quantitatively. From these values, average order parameters, reporting the motional amplitudes of the individual receptor segments can be derived. Average backbone order parameters were determined with values between 0.56 and 0.69, corresponding to average motional amplitudes of 40–50° of these segments. Differences between the receptor dynamics in DMPC or POPC membranes were within experimental error. Furthermore, agonist or inverse agonist binding only insignificantly influenced the average molecular dynamics of the receptor.

Solid-state MAS NMR investigations for pentavalent cation-replaced pollucite compounds with a negative thermal expansion coefficient

Pollucite compounds with an aluminosilicate structure, V-replaced pollucite, Cs0.7V0.1Al0.8Si2.1O6 (CVAS), P-replaced pollucite, Cs0.7P0.1Al0.8Si2.1O6 (CPAS), and Nb-replaced pollucite, Cs0.7Nb0.1Al0.8Si2.1O6 (CNbAS), were synthesized by a multistep heat treatment of 550–1200 °C. CVAS exhibited the superior thermal expansion with thermal expansion coefficients of 0.9 × 10−6 °C−1 (30–500 °C), −0.9 × 10−6 °C−1 (30–150 °C), and −0.4 × 10−6 °C−1 (30–100 °C). Solid-state 29Si MAS NMR spectroscopy clarified that the number of Si–O–Si bonds of tetrahedra in the framework of CVAS was larger than those of CPAS and CNbAS. The chemical shift for peaks of the 29Si MAS NMR spectrum of CVAS was larger than those of CPAS and CNbAS, suggesting that the bond angle of tetrahedra was enlarged by the V replacement. Solid-state 27Al MAS NMR spectroscopy implied that CVAS had a small amount of sixfold coordinated Al species, which resulted in an increase in the number of Si–O–Si bonds of tetrahedra of CVAS.

A 13C solid-state NMR investigation of four cocrystals of caffeine and theophylline.

We report an analysis of the 13C solid-state NMR chemical shift data in a series of four cocrystals involving two active pharmaceutical ingredient (API) mimics (caffeine and theophylline) and two diacid coformers (malonic acid and glutaric acid). Within this controlled set, we make comparisons of the isotropic chemical shifts and the principal values of the chemical shift tensor. The dispersion at 14.1 T (600 MHz 1H) shows crystallographic splittings in some of the resonances in the magic angle spinning spectra. By comparing the isotropic chemical shifts of individual C atoms across the four cocrystals, we are able to identify pronounced effects on the local electronic structure at some sites. We perform a similar analysis of the principal values of the chemical shift tensors for the anisotropic C atoms (most of the ring C atoms for the API mimics and the carbonyl C atoms of the diacid coformers) and link them to differences in the known crystal structures. We discuss the future prospects for extending this type of study to incorporate the full chemical shift tensor, including its orientation in the crystal frame of reference.

Solid-State NMR Investigations of Transmembrane Helix Interactions

Transmembrane proteins are vital to numerous biological processes, including signal transduction and ion conduction. In many cases, the behavior of potentially ionizable residues in the hydrophobic interior of the membrane is crucial to understanding protein function. We have employed a low-dynamic model α-helical transmembrane peptide, GWALP23 (acetyl-GGALWLALALALALALALWLAGA-amide) as a framework to investigate the possibility of (+/-) ion-pair interactions between arginine and glutamic acid side chains located on different and independent (separately diffusing) transmembrane helices, by 2H NMR spectroscopy. One peptide with an Arg residue, GWALP23-R14 (acetyl-GGALWLALALALARALALWLAGA-amide), and another with a Glu residue, GWALP23-E14 (acetyl-GGALWLALALALAEALALWLAGA-amide), were incorporated into DOPC bilayers together (1:67 peptide:lipid ratio). Past experiments have shown that GWALP23-R14 alone is well-aligned in DOPC bilayers, gives narrow resonances for 2H-labeled alanines and remains charged, even under alkaline pH conditions (JACS 2010, 132(16):5803). By contrast, 2H-Ala-labeled GWALP23-E14 exhibits much broader 2H NMR spectra. We now find that the spectra of labeled GWALP23-R14 become noticeably broadened and weakened, without changing the quadrupolar splittings, when even 16 mol% GWALP23-E14 is included with GWALP23-R14 in the DOPC bilayer samples. A control peptide, GWALP23, has little effect on GWALP23-R14 at 16 mol%, but spectral broadening and weakening occur with at 50 mol%. Conversely, the addition of GWALP-R14 (16 or 50 mol%), has no effect on the already broad spectra of labeled GWALP-E14 in DOPC bilayers. Preliminary results, therefore, suggest that while GWALP-E14 causes concentration-dependent effects on the spectra of GWALP-R14, the complex or possibly multi-state behavior of GWALP-E14 is not ‘rescued’ by the addition of GWALP-R14 in DOPC bilayers.

Dendritic polarizing agents for DNP SENS.

Dynamic Nuclear Polarization Surface Enhanced NMR Spectroscopy (DNP SENS) is an effective method to significantly improve solid-state NMR investigation of solid surfaces. The presence of unpaired electrons (polarizing agents) is crucial for DNP, but it has drawbacks such as leading to faster nuclear spin relaxation, or even reaction with the substrate under investigation. The latter can be a particular problem for heterogeneous catalysts. Here, we present a series of carbosilane-based dendritic polarizing agents, in which the bulky dendrimer can reduce the interaction between the solid surface and the free radical. We thereby preserve long nuclear T'2 of the surface species, and even successfully enhance a reactive heterogeneous metathesis catalyst.

Solid-state NMR and FTIR investigations of standard and nanotubular polyanilines

The standard emeraldine base (EB) form of polyaniline and the product obtained by the oxidative polymerization of aniline using a pH-stat method at a constant pH of 2.5 are investigated. The morphology of the pH-stat product was examined using scanning electron microscopy and transmission electron microscopy. The prevalence of self-assembled nanotubes in the pH-stat product is confirmed. The structural differences between the EB and pH-stat products are revealed by FTIR and solid-state NMR experiments. On the basis of these investigations, the presence and the role of the oligomeric material in the formation of nanotubes is confirmed.

Crystallization of a high-strength lithium disilicate glass-ceramic: An XRD and solid-state NMR investigation

The phase evolution of a high flexural strength lithium disilicate (Li2Si2O5: LS2) glass-ceramic in a complex SiO2–Li2O–Al2O3–MgO–P2O5–ZrO2 glass system has been investigated as a function of temperature using in situ and ex situ X-ray diffraction (XRD) and 31P and 29Si solid-state nuclear magnetic resonance (SSNMR) spectroscopy. In the base glass, lithium metasilicate (Li2SiO3: LS) crystallizes (at 525°C) before LS2 (at 675°C). 29Si NMR shows that LS is not only formed from the Q(2)glass species, but also by disproportionation of the Q(3)glass units. The XRD data demonstrate the formation of a minor phase of MgAl2Si4O12 from the reaction of SiO2 with minor components of Al2O3 and MgO. Diffraction peaks of Li3PO4 are firstly detected at 675°C, and they become evident at 750°C and above. The evolution of phosphorus species in the glass as a function of temperature has been revealed by 31P NMR spectroscopy. Two 29Si T1 relaxation components were observed in samples across all temperatures, suggesting the presence of glass-in-glass phase separation in the base glass. A plot of 29Si T1 relaxation measurements shows discontinuity at 750°C, indicating microstructural changes. A detailed crystallization mechanism of high-strength LS2 glass–ceramics is proposed.