Aimed at the simulation, design, and interpretation of advanced pulse experiments crossing the boundaries between nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR), including the rapidly emerging, hybrid discipline of pulsed dynamic nuclear polarisation (DNP), we present a host of novel features in the widely used SIMPSON software package addressing these aspects. Along with this come new features for advanced pulse sequence evaluation in terms of propagator splitting, high-order spin operator cross terms, and pulse phase transients. These fundamental new tools are introduced in a C++-based next generation of the SIMPSON software, which improves calculations speed in some aspects, is better prepared for further developments, and facilitates easier community contributions to the open-source software package.

We assessed the quantification of surface amino functional groups (FGs) for a large set of commercial and custom-made aminated silica nanoparticles (SiO2 NPs) with sizes of 20-100 nm, prepared with different sol-gel routes, different amounts of surface amino FGs, and different porosity with four methods providing different, yet connected measurands in a bilateral study of two laboratories, BAM and NRC, with the overall aim to develop standardizable measurements for surface FG quantification. Special emphasis was dedicated to traceable quantitative magnetic resonance spectroscopy (qNMR) performed with dissolved SiO2 NPs. For the cost efficient and automatable screening of the amount of surface amino FGs done in a first step of this study, the optical fluorescamine assay and a potentiometric titration method were utilized by one partner, i.e., BAM, yielding the amount of primary amino FGs accessible for the reaction with a dye precursor and the total amount of (de)protonatable FGs. These measurements, which give estimates of the minimum and maximum number of surface amino FGs, laid the basis for quantifying the amount of amino silane molecules with chemo-selective qNMR with stepwise fine-tuned workflows, involving centrifugation, drying, weighting, dissolution, measurement, and data evaluation steps jointly performed by BAM and NRC. Data comparability and relative standard deviations (RSDs) obtained by both labs were used as quality measures for method optimization and as prerequisites to identify method-inherent limitations to be later considered for standardized measurement protocols. Additionally, the nitrogen (N) to silicon (Si) ratio in the near-surface region of the SiO2 NPs was determined by both labs using X-ray photoelectron spectroscopy (XPS), a well established surface sensitive analytical method increasingly utilized for microparticles and nano-objects which is currently also in the focus of international standardization activities. Overall, our results underline the importance of multi-method characterization studies for quantifying FGs on NMs involving at least two expert laboratories for effectively identifying sources of uncertainty, validating analytical methods, and deriving NM structure-property relationships.

Chlorpromazine, a widely used antipsychotic medication formulated as a hydrochloride salt, has been a significant active pharmaceutical ingredient (API) for the treatment of schizophrenia for much of the last century. This work presents a comprehensive investigation into the nature of the structural disorder of chlorpromazine hydrochloride solvatomorphs using a combination of nuclear magnetic resonance (NMR) crystallography and molecular dynamics simulations. We focus on understanding the structural characteristics and stability of chlorpromazine hydrochloride and its hydrate, particularly the disorder in the dimethylaminopropyl side chain. This work provides a detailed analysis of the structural characteristics influencing this disorder, advancing the understanding of drug development and the design process for APIs that exhibit similar types of disorder.

Shared research facilities (SRFs) offer researchers cost-effective access to advanced analytical instrumentation that individual laboratories may find challenging to acquire or maintain. By centralizing resources, SRFs support a diverse user community including students, early-career scientists, senior principal investigators, and industrial collaborators, while providing expert technical support and ensuring efficient use of infrastructure and funding. These facilities not only drive research productivity and foster interdisciplinary collaboration, but also serve as centers for training the next generation of scientists. In this article, SRFs that offer solid-state nuclear magnetic resonance (NMR) capabilities are discussed, highlighting representative examples, their accessibility, governance models, technical operations, application areas, and data-sharing practices. Usage data reveal that solid-state NMR-based SRFs strongly align with high-priority research goals, contributing to impactful projects across chemistry, life sciences, and materials science, as reflected in publication outcomes. The article also emphasizes that the collaborative networks among SRFs enhance knowledge exchange and resource coordination. Such coordinated inter-facility partnerships are expected to address emerging challenges, ultimately supporting sustainable infrastructure that meets the evolving needs of the solid-state NMR community.

Surface functionalization is widely used to control the behavior of nanomaterials for a range of applications. However, methods to accurately quantify surface functional groups and coatings are not yet routinely applied to nanomaterial characterization. We have employed a combination of quantitative NMR (qNMR) and thermogravimetric analysis (TGA) to address this problem for commercial cerium, nickel, and iron oxide nanoparticles (NPs) that have been modified to add functional coatings with (3-aminopropyl)triethoxysilane (APTES), stearic acid, and polyvinylpyrrolidone (PVP). The qNMR method involves quantification of material that is released from the NPs and quantified in the supernatant after removal of NPs. Removal of aminopropylsilanes was accomplished by basic hydrolysis whereas PVP and stearic acid were removed by ligand exchange using sodium hexametaphosphate and pentadecafluorooctanoic acid, respectively. The method accuracy was confirmed by analysis of NPs with a known content of surface groups. Complementary TGA studies were carried out in both air and argon atmosphere with FT-IR of evolved gases in argon to confirm the identity of the functional groups. TGA measurements for some unfunctionalized samples show mass loss due to unidentified components which makes quantification of functional groups in surface-modified samples less reliable. XPS provides information on the presence of surface contaminants and the level of surface hydroxylation for selected samples. Despite the issues associated with accurate quantification using TGA, the TGA estimates agree reasonably well with the qNMR data for samples with high surface loading. This study highlights the issues in analysis of commercial nanomaterials and is an advance towards the development of generally applicable methods for quantifying surface functional groups.

We report the first “total synthesis” of 17O-labeled d-glucose and its solid-state 17O NMR characterization with unprecedented sensitivity and resolution.

Current processes to manufacture nanotubes at commercial scales are unfortunately imperfect and commonly generate undesirable byproducts. After manufacturing, purification is necessary and is a rate and cost determining step in advancing the development of commercial products based on nanotubes. Boron nitride nanotubes (BNNTs) produced without metal catalysts from high-temperature processes are known to contain a significant amount (e.g., 50 wt %) of various boron derivatives. Herein we report a simple yet efficient and scalable process to purify these types of BNNT materials at commercial scales, from a few grams to hundreds of grams, at purity over 85 wt % in a single step. The process relies on a vertically mounted flow tube reactor and scrubber system that can be operated under pure or diluted chlorine gas flow at temperatures up to 1100 degrees C. The main chemical reactions driving the purification are the conversion of boron and BN derivatives into BCl3 and HCl, which are removed as gaseous species, while pristine BNNTs are left behind. The preferential etching of impurities over pristine BNNTs shows the extreme chemical resistance of BNNTs in this harsh environment and opens up new applications for this nanomaterial. The process has been examined at various temperatures, up to 1050 degrees C, and the resulting materials display improved BNNT purity and quality across a range of imaging and spectroscopic assessments. The recommended temperature to optimize quality with yield is 950 degrees C, although higher quality material is obtained at a higher temperature.

Curcumin is known to exist in three polymorphs (forms I, II, and III) in the solid state. The most common polymorph of curcumin (form I) is monoclinic in the space group P2/n, whereas the other two uncommon forms are both orthorhombic with the space groups of Pca2(1) and Pbca for forms II and III, respectively. While crystal structures are known for all three polymorphs of curcumin, their solid-state NMR signatures are incomplete in the literature. In this study, we report a complete set of solid-state H-1, C-13, and O-17 NMR data for form III of curcumin. In addition, we discovered that form III of curcumin prepared by repeated drying from methanol is not stable, which undergoes slow structural transition to form II in the solid state over a period of days at room temperature. As a result, we were able to obtain new solid-state O-17 NMR data for form II of curcumin, which complements the existing solid-state H-1 and C-13 NMR data for this polymorph in the literature. We compare experimental NMR parameters with calculated values by the GIPAW DFT and dispersion corrected DFT-D2 methods. We found that while the computed C-13 chemical shifts are generally in excellent agreement with experimental values, the quality of the computed H-1 and O-17 NMR chemical shifts is less satisfactory. This may imply that it is necessary to include the nuclear quantum effects in future quantum chemical calculations to account for potential proton tunneling and dynamics.

Surface functionalization is a key factor for determining the performance of nanomaterials in a range of applications and their fate when released to the environment. Nevertheless, it is still relatively rare that surface groups or coatings are quantified using methods that have been carefully optimized and validated with a multi-method approach. We have quantified the surface groups on a set of commercial ZnO nanoparticles modified with three different reagents ((3-aminopropyl)-triethoxysilane, caprylsilane and stearic acid). This study used thermogravimetric analysis (TGA) with Fourier transform infrared spectroscopy (FT-IR) of evolved gases and quantitative solution 1H nuclear magnetic resonance (NMR) for quantification purposes with 13C-solid state NMR and X-ray photoelectron spectroscopy to confirm assignments. Unmodified materials from the same suppliers were examined to assess possible impurities and corrections. The results demonstrate that there are significant mass losses from the unmodified samples which are attributed to surface carbonates or residual materials from the synthetic procedure used. The surface modified materials show a characteristic loss of functional group between 300–600 °C as confirmed by analysis of FT-IR spectra and comparison to NMR data obtained after quantitative release/extraction of the functional group from the surface. The agreement between NMR and TGA estimates for surface loading is reasonably good for cases where the functional group accounts for a relatively large fraction of the sample mass (e.g., large groups or high loading). In other cases TGA does not have sufficient sensitivity for quantitative analysis, particularly when contaminants contribute to the TGA mass loss. X-ray photoelectron spectroscopy and solid state NMR for selected samples provide support for the assignment of both the functional groups and some impurities. The level of surface group loading varies significantly with supplier and even for different batches or sizes of nanoparticles from the same supplier. These results highlight the importance of developing reliable methods to detect and quantify surface functional groups and the importance of a multi-method approach.

Quantitative 1H nuclear magnetic resonance (qHNMR) with an appropriate internal standard is a well-established quantitation method for assigning purity to organic molecules. For accurate measurements, the premise of qHNMR relies on the careful selection of integrals, for both the analyte and the standard, in such a way that the selected integrals are free from interferences. The 13C-satellite signals of adjacent integrals, low-level impurities, and tautomer signals are among the common integral interferences that are typically encountered. One of the simplest ways to identify and avoid these interferences is to decouple the 13C-satellites. Two decoupling schemes were explored to illustrate the benefits of 13C-decoupling for qHNMR or qH{13C}NMR: GARP and bilevel adiabatic broadband decoupling. Unwanted sample heating and nuclear Overhauser effect (NOE) enhancements are the two main drawbacks of decoupling schemes. We show that with careful optimization of acquisition parameters and decoupling power, no excessive sample heating occurred during acquisition at 400 MHz. At 900 MHz, only bilevel adiabatic decoupling could be safely implemented. Furthermore, any undesirable NOE enhancements were completely avoided if acquisition was executed with an inverse-gated pulse sequence. We explored and confirmed the benefits of qH{13C}NMR through the quantitation of a diverse set of compounds, namely, small molecules (dimethyl terephthalate and zearalenone), a 13C-labeled compound (13C6-ochratoxin A), and an octapeptide (angiotensin II). Statistical comparisons confirmed that qH{13C}NMR produced comparable data to qHNMR. However, with qH{13C}NMR data providing added clarity about the presence of overlapping 13C-satellites, impurities, and tautomers, it has an edge over qHNMR for accurate measurements.

Surface chemistry is an important factor for quality control during production of nanomaterials and for controlling their behavior in applications and when released into the environment. Here we report a comparison of four methods for quantifying amine functional groups on silica nanoparticles (NPs). Two colorimetric assays are examined, ninhydrin and 4-nitrobenzaldehyde, which are convenient for routine analysis and report on reagent accessible amines. Results from the study of a range of commercial NPs with different sizes and surface loadings show that the assays account for 50-100% of the total amine content, as determined by dissolution of NPs under basic conditions and quantification by solution-state 1H NMR. To validate the surface quantification by the colorimetric assays, the NPs are modified with a trifluoromethylated benzaldehyde probe to enhance sensitivity for quantitative 19F solid state NMR and X-ray photoelectron spectroscopy (XPS). Good agreement between the assays and the determination from solid-state NMR is reinforced by elemental ratios from XPS, which indicate that in most cases the difference between total and accessible amine content reflects amines that are outside the depth probed by XPS. Overall the combined results serve to validate the relatively simple colorimetric assays and indicate that the reactions are efficient at quantifying surface amines, by contrast to some other covalent modifications that have been employed for functional group quantification.

Surface chemistry is an important factor for quality control during production of nanomaterials and for controlling their behavior in applications and when released into the environment. Here we report a comparison of four methods for quantifying amine functional groups on silica nanoparticles (NPs). Two colorimetric assays are examined, ninhydrin and 4-nitrobenzaldehyde, which are convenient for routine analysis and report on reagent accessible amines. Results from the study of a range of commercial NPs with different sizes and surface loadings show that the assays account for 50–100% of the total amine content, as determined by dissolution of NPs under basic conditions and quantification by solution-state H NMR. To validate the surface quantification by the colorimetric assays, the NPs are modified with a trifluoromethylated benzaldehyde probe to enhance sensitivity for quantitative F solid state NMR and X-ray photoelectron spectroscopy (XPS). Good agreement between the assays and the determination from solid-state NMR is reinforced by elemental ratios from XPS, which indicate that in most cases the difference between total and accessible amine content reflects amines that are outside the depth probed by XPS. Overall the combined results serve to validate the relatively simple colorimetric assays and indicate that the reactions are efficient at quantifying surface amines, by contrast to some other covalent modifications that have been employed for functional group quantification.

Thermogravimetric analysis (TGA) coupled with evolved gas analysis-FT-IR has been examined as a potential method to study the functional group content for surface modified silica nanoparticles. A comparison with a quantitative solution NMR method based on analysis of groups released after dissolution of the silica matrix is used to provide benchmark data for comparison and to assess the utility and limitations of TGA. This study focused primarily on commercially available silicas and tested whether it was possible to use a correction based on bare silica to account for the significant mass loss that occurs due to condensation of surface hydroxyl groups and loss of matrix-entrapped components at temperatures above ∼200 °C. Although this approach has been used successfully in the literature for in-house prepared samples, it was problematic for commercial silicas prepared by the Stöber method. For these materials the agreement between estimates from qNMR and TGA mass loss was poor in many cases. However much better agreement was observed for samples for which the mass loss above 200 °C is relatively low, such as non-porous silica, or samples for which the mass fraction of functional group is large (e.g., high molecule weight groups or multilayers). FT-IR was useful in identifying the likely structure of the components lost from the surface at various temperatures and in some cases provided evidence of contaminants in the sample. Nevertheless, in other cases correlation of thermograms and FT-IR with NMR data was necessary, particularly for samples where multi-step modification of the silica surface results in incomplete functionalization that gives a mixture of products. Overall the results indicate that TGA provides reliable results for silicas of low porosity or those for which the functional group accounts for a significant fraction of the total sample mass. It is also suitable as a supplementary or screening technique to indicate the presence of coatings or covalent surface modification, prior to applying other techniques or for routine analyses where sensitivity is not critical.

Although solution-state NMR is frequently used in metrologically-traceable quantification studies, this is not the case for solid-state NMR. However, solid-state NMR allows quantification of substances without the need of dissolution, providing a truly non-destructive approach, and extending metrologically-traceable quantitative NMR to sample classes that are difficult to characterize in solution. In this contribution we present a thorough and rigorous protocol for( 19)F quantitative solid-state NMR employing a certified reference material as external calibrant to provide metrological traceability to absolutely quantify the content of trifluoroacetic acid (TFA) in a peptide sample, typically the major impurity in synthetic peptides. The protocol includes determining the quantitative volume of the solid-state NMR sample holder (rotor), the ERETIC (electronic reference to access in vivo concentrations) method (Akoka et a1 1999 Anal. Chem. 71 2554) to compensate for variations in the sensitivity of the radio frequency resonant circuit when an external calibrant is used, and the EASY (elimination of artefacts in NMR spectroscopy) method (Jaeger and Hemmann 2014 Solid State Nucl. Magn. Reson. 57-58 22) to effectively suppress the F-19 NMR background signal from the probe head. We applied the protocol to quantify the amount of TFA in a candidate NRC certified reference material of the peptide angiotensin II. The results obtained by( 19)F quantitative solid-state NMR are in excellent agreement with those obtained by quantitative NMR in solution employing an internal calibrant.

19F nuclei are useful labels in solid-state NMR studies, since their chemical shift and tensor elements are very sensitive to the electrostatic and space-filling properties of their local environment. In this study we have exploited a fluorine substituent, strategically placed at the C-12-position of 11-cis retinal, the chromophore of visual rhodopsins. This label was used to explore the local environment of the chromophore in the ground state of bovine rhodopsin and its active photo-intermediate Meta II. In addition, the chemical shift and tensor elements of the chromophore in the free state in a membrane environment and the bound state in the protein were determined. Upon binding of the chromophore into rhodopsin and Meta II, the isotropic chemical shift changes in the opposite direction by +9.7 and -8.4 ppm, respectively. An unusually large isotropic shift difference of 35.9 ppm was observed between rhodopsin and Meta II. This partly originates in the light-triggered 11-cis to all-trans isomerization of the chromophore. The other part reflects the local conformational rearrangements in the chromophore and the binding pocket. These NMR data were correlated with the available X-ray structures of rhodopsin and Meta II using bond polarization theory. For this purpose hydrogen atoms have to be inserted and hereto a family of structures were derived that best correlated with the well-established 13C chemical shifts. Based upon these structures, a 12-F derivative was obtained that best corresponded with the experimentally determined 19F chemical shifts and tensor elements. The combined data indicate strong changes in the local environment of the C-12 position and a substantially different interaction pattern with the protein in Meta II as compared to rhodopsin.

Surface chemistry is a critical factor for determining the behavior of a nanomaterial after incorporation in composites, devices, and biomedical products, and is also important for nanotoxicology studies. We have developed an optimized protocol for dissolution of aminated silicas and determination of functional-group contents by quantitative 1H NMR (qNMR) analysis of the released amines. A number of variables were optimized for the dissolution protocol, including the base concentration, mass of silica, time, temperature, and method of sample agitation, in order to achieve adequate NMR signals for quantification. The protocol was tested using nanoparticles from a single commercial supplier with sizes ranging from 20 to 120 nm that were functionalized with 3-aminopropyl groups. Interestingly the batch-to-batch variability for some sizes of these aminated silicas was as high as 50%. Amine contents measured by a ninhydrin colorimetric assay were typically ∼20% lower than those measured by qNMR, consistent with measurement of only ninhydrin-reagent accessible amines. The dissolution-qNMR protocol was compatible with aminated silicas from other commercial suppliers, and in these cases, an even larger variability in surface coverage was observed. Silica nanoparticles with longer-chain amines and variable amine loadings were synthesized to demonstrate the ability to quantify amines with more complex structures and to assess the limit of quantification for the dissolution-qNMR method. Finally, the stability of the aminated nanoparticles was examined. Loss of 3-aminopropyl groups occurred in water at room temperature and was significantly more rapid at higher temperatures. Amine loss increased with increasing surface coverage and was slower for long-chain amines, consistent with studies of amine stability on planar silica. Overall, this work highlights the importance of developing methods for quantifying surface functionalization, particularly given the variability in surface coverage for commercial samples, and for ensuring that the amine group is stable under its usage conditions.

Curcumin, a compound derived from the herb turmeric, has gained considerable attention because of its purported pharmacological activity, but its poor water solubility and low bioavailability impedes its therapeutic potential. In addition to the frequently studied curcumin polymorph, referred to as form I, another polymorph with enhanced water solubility, referred to as form II, or red curcumin, has also been reported. We discuss experimental challenges in isolating the red curcumin polymorph. In the course of our studies, we were unable to obtain a third reported polymorph, form III. We redetermined crystal structures of forms I and II of curcumin and present C-13 and H-1 solid-state nuclear magnetic resonance (NMR) spectra for these two forms, as well as(13)C-H-1 two-dimensional heteronuclear correlation (HETCOR) data. The experimental H-1 and C-13 nuclear magnetic resonance (NMR) chemical shifts are compared with GIPAW density functional theory values computed using CASTEP. Our research illustrates the utility of NMR spectroscopy in characterization of polymorphism in bulk samples.