Low-field NMR Spectroscopy Research Articles

Dual stimuli-responsive polyurethane-based hydrogels as smart drug delivery carriers for the advanced treatment of chronic skin wounds

The design of multi-stimuli-responsive vehicles for the controlled and localized release of drugs is a challenging issue increasingly catching the attention of many research groups working on the advanced treatment of hard-to-close wounds. In this work, a thermo- and pH-responsive hydrogel (P-CHP407) was prepared from an ad hoc synthesized amphiphilic poly(ether urethane) (CHP407) exposing a significant amount of –COOH groups (8.8 ± 0.9 nmol/gpolymer). The exposure of acid moieties in P-CHP407 hydrogel led to slightly lower initial gelation temperature (12.1 °C vs. 14.6 °C, respectively) and gelation rate than CHP407 hydrogel, as rheologically assessed. Nanoscale hydrogel characterization by Low Field NMR (LF-NMR) spectroscopy suggested that the presence of carboxylic groups in P-CHP407 caused the formation of bigger micelles with a thicker hydrated shell than CHP407 hydrogels, as further proved by Dynamic Light Scattering analyses. In addition, P-CHP407 hydrogel showed improved capability to change its internal pH compared to CHP407 one when incubated with an alkaline buffer (pH 8) (e.g., pHchange_5min = 3.76 and 1.32, respectively). Moreover, LF-NMR characterization suggested a stronger alkaline-pH-induced interaction of water molecules with micelles exposing –COOH groups. Lastly, the hydrogels were found biocompatible according to ISO 10993 and able to load and release Ibuprofen: delivery kinetics of Ibuprofen was enhanced by P-CHP407 hydrogels at alkaline pH, suggesting their potential use as smart delivery systems in the treatment of chronic infected wounds.

Recent Low-field Time-domain NMR Spectroscopy and its Application on Analysis of Rubber Structural Change

Recent Low-field Time-domain NMR Spectroscopy and its Application on Analysis of Rubber Structural Change

Low-field benchtop NMR spectroscopy as a potential non-stationary tool for point-of-care urinary metabolite tracking in diabetic conditions

We describe the advantages and diagnostic/prognostic significance of low-field, near-portable benchtop NMR spectrometers for the multicomponent metabolomics analysis of targeted and untargeted urinary biomarkers (≥15) in type 2 diabetes patients. Implementation of these facilities at ‘point-of-care’ clinical sites may yield valuable advantages for the sequential monitoring of diabetic and prediabetic individuals.

Evaluation of low-field versus high-field proton NMR spectroscopy for quality control of cinnamon samples

The use of cinnamon as a spice for cooking or as a dietary supplement for its nutraceutical properties is widespread around the world. In this study, 28 samples, 14 cooking spices and 14 dietary supplements, were analysed using both high-field (400 MHz) and low-field (60 MHz) NMR. High-field NMR analysis was performed for profiling, quantitative analysis and classification of the samples between Ceylon cinnamon and cassia cinnamon. Then, the capabilities and limitations of low-field NMR for quality control of cinnamon were studied and discussed. At last, the chemometric treatment of low-field NMR spectra has proved to be an interesting way of predicting quantification of their contents in coumarin and (E)-cinnamaldehyde. For dietary supplements, this approach allowed to identify samples containing a higher quantity of hepatotoxic coumarin and thus presenting a potential risk to the health of consumers.

Active Roles of Water in Aqueous Assembly of Macromolecules

Aqueous self-assembly customarily focuses on the molecular interactions of assembling building blocks; the role of water is barely studied. The hydration of hydrophobic P+X- (P+: macromolecular phosphonium cation, X-: anion) is dependent on the ionic end groups, which is responsible for the consequent assembling behavior. The water interaction with the backbone was analyzed by FT-IR, and the dynamics were measured by low field-NMR spectroscopy. The combination of these two techniques reveals the effect of X- on hydration. When X- is I-, the ionic end group ordered water molecules that exerted a detectable long-range effect de-hydrating the backbone. The consequent hydrophobic interaction drove the aqueous assembly of P+I- into micelle-like aggregates with the ionic group exposed to water. In contrast, the ion pair with a hydrophobic anion of [BPh4]- was not able to hold water and did not deplete the hydration water. The hydrated backbone of P+[BPh4]- assembled into vesicles that were driven by hydration interactions. This elucidation at the molecular level is craved to progress aqueous supramolecular chemistry.

Application of low-field and medium-resolution 1H NMR spectroscopy combined with chemometric methods for automotive gasoline quality control

This work describes the application of low-field and medium-resolution 1H NMR (LF-1H NMR) combined with PLS and SVM multivariate regression techniques for fast prediction of five fundamental quality parameters of commercial Brazilian gasoline (specific gravity, distillation temperatures of 50 and 90 percent of recovered and olefinic and aromatic content). All these five parameters are of paramount importance to predict the fuel quality and the application of the developed PLS and SVM models showed prediction errors compared to the reference methodologies applied for these essays. Nevertheless, it is important to highlight that in a different way of the reference methodologies, such as distillation or chromatographic methods, the application of LF-1H NMR combined with PLS or SVM models enables the fast determination of those five parameters directly from a single LF-1H NMR spectrum, which is acquired without any sample pre-treatment nor dilution in deuterated solvents, and this whole process takes no more than 15 s.

A Rapid Screening Approach for Authentication of Olive Oil and Classification of Binary Blends of Olive Oils Using Low-Field Nuclear Magnetic Resonance Spectra and Support Vector Machine

Due to the quality differentiation and commercial concerns, rapid authentication and addressing the adulterants in olive oil is of great importance. The feasibility of identifying pure olive oil as well as classifying the binary blends of olive oils according to the adulterants in olive oils using low-field NMR spectroscopy and support vector machine (SVM) have been investigated. Based on the characterization of low-field NMR profiles of six types of vegetable oil and the binary blends of olive oils with three types of seeds oils (corn, soybean, and sunflower seed oils), SVM was employed to build the authentication and classification models. The result indicated that the difference of oils and the type of blends can be monitored by low-field NMR profiles. SVM classification models for identifying pure olive oils from blended ones were developed and an 84.92% classification accuracy was acquired when the adulteration ratio is above 10%. For the classification of binary blends of olive oils according to the seed oils, two SVM classification strategies have been developed and compared, and the SVM model with a suspected range of 10%–30% could provide an acceptable classification result. LF-NMR could be a novel screening method for the authentication of olive oil.

Low frequency magnetic field plus high pH promote the quality of pork myofibrillar protein gel: A novel study combined with low field NMR and Raman spectroscopy

This study investigated the combined effects of low frequency magnetic field (LF-MF) (3.8 mT) and pH (5–7) on pork myofibrillar protein (MP) gel quality. With LF-MF applying, the water ratio and migration rate both changed to varying extents. LF-MF modified secondary structure of MP by exposing tryptophan and tyrosine residues to participate in hydrogen bonding with water, as well changing α-helix and β-sheet to varying extents; LF-MF also drove molecular rearrangement and crosslinking. LF-MF brought gel larger and more ordered network to trap more water. And the water holding capacity of gels significantly increased by 2.50% and 2.47% when LF-MF involved at appropriate pH (pH 6.5 and 7.0). Collectively, our results support an optimum treatment (pH 6.5 or 7.0 with applying LF-MF) for the improvement in gel quality of pork MP, and the combination of physical and chemical treatments casts a new light into improving product quality during meat processing.

Online monitoring of enzymatic hydrolysis of marine by-products using benchtop nuclear magnetic resonance spectroscopy

Enzymatic hydrolysis is becoming a more commonly used method to create high value products from traditionally low value marine by-products. However, improvement to processing is hampered by a lack of ways to characterize the reaction in real time. Current methods of analysis rely on taking offline samples, deactivating the enzymes, and performing analysis on the products afterwards. Nuclear magnetic resonance benchtop spectroscopy was investigated as a method for online process monitoring of enzymatic hydrolysis. Online and offline NMR measurements were performed for enzymatic hydrolysis reactions on red cod, salmon and shrimp. Both the online and offline measurements were able to follow the reaction process and showed good agreement in their calculated reaction rate. Application of the methodology to several types of raw materials indicates the technique is robust with regards to sample type. Advantages and disadvantages of low-field versus high-field NMR spectroscopy are discussed as well as practical considerations needed in order to apply the method industrially.

Zein/Pectin Nanoparticle-Stabilized Sesame Oil Pickering Emulsions: Sustainable Bioactive Carriers and Healthy Alternatives to Sesame Paste

In this study, a kind of Pickering emulsion with a desirable interface architecture and sesame paste flavor was prepared using zein, apple pectin (AP), and sesame oil. Zein-AP composite nanoparticles (ZAPs) were first assembled via an anti-solvent procedure and electrostatic adsorption for stabilizing sesame-oil-in-water Pickering emulsions (ZASPEs). ZASPEs (volume fraction of oil φ = 0.7) exhibited excellent plasticity and viscoelasticity (indicated by low-field NMR spectroscopy and rheology). Confocal laser scanning microscopy (CLSM), demonstrated the anchoring of ZAPs at the oil–water interface, while cryo-SEM confirmed the three-dimensional microstructural network formed inside the emulsion. Compared to a commercial sesame paste, diluted ZASPEs (φ = 0.35) exhibited similar rheological and sensory properties, while ZASPEs (φ = 0.7) and diluted ZASPEs possessed greater smoothness and spreadability. Accordingly, the current ZASPEs as new additions to the existing Pickering emulsions not only function as bioactive carriers but also impart desirable flavor in food applications.

Change of C(2)-Hydrogen–Deuterium Exchange in Mixtures of EMIMAc

1-Ethyl-3-methylimidazolium acetate (EMIMAc) is an ionic liquid (IL) often investigated as a solvent, especially in the context of biopolymers and biomass pretreatment. A reduced solvent efficacy occurs upon the addition even of low amounts of water to EMIMAc. Molecular mechanisms have not yet been fully understood. It is expected that the functionality as hydrogen bond donor and acceptor is key for the solvent–solute interactions. In this work, we analyze the solvent efficacy of EMIMAc in terms of hydrogen–deuterium (H/D) exchange at the C(2)-position in mixtures with water or acetic acid added as proton donors. Low-field NMR spectroscopy and deuterated solvents are used for a time-resolved evaluation of H/D exchange reactions. The H/D exchange is also modeled to explore changes in the reaction kinetics as a function of the mixture composition. The significant difference in calculated rate constant values among the concentration regimes shows that the chosen model equations of a possible pseudo-first-order and second-order reaction mechanism including water dissociation do not cover all interaction phenomena that influence the exchange in the individual concentration ranges. However, the modeling also indicates that the investigated interaction of $$\hbox {EMIM}^+$$ and $$\hbox {Ac}^-$$ remains constant for concentrated IL mixtures containing $$70\, {\text{mol}}\%$$ of EMIMAc in water up to diluted mixtures as low as $$30\, {\text{mol}}\%$$ EMIMAc. This exemplifies the change between ions strongly associated in networks in concentrated mixtures suitable for biomass pretreatment and the much less associated anion–cation pairs in diluted mixtures which leads to the decreased efficiency of EMIMAc with increasing water content.

Differentiation of fentanyl analogues by low-field NMR spectroscopy

Forensic laboratories commonly receive new psychoactive substances such as fentanyl analogues and other synthetic opioids that are difficult to identify. Slight changes to chemical structures, e.g. shifting the position of functional groups such as methyl groups or halogens on the aromatic ring, may not be distinguished using traditional methods. NMR is a powerful tool used to elucidate distinctive structural information needed to differentiate regioisomers. However, the cost, size, and cryogen maintenance of superconducting NMR spectrometers can be impractical for some forensic laboratories. Recent studies have shown potential applications of low-field NMR as an alternative in forensic drug analysis. These benchtop, semi-portable instruments are less costly, have a smaller footprint, do not use cryogens, and require little maintenance. In this study, we show that 65 fentanyl and related substances, including various types of positional isomers, were readily differentiated using low-field (62 MHz) 1H NMR spectroscopy. In addition, the use of quantum mechanical spin system analysis was investigated for the purposes of translating experimentally observed high-field 1H spectra to lower field strengths. Spin system analysis of 600 MHz NMR spectra was conducted on a subset (15) of the reference materials analyzed. The results were used to calculate 62 MHz spectra for comparison purposes with the experimental spectra. This was successfully demonstrated, showing that field-strength independent 1H NMR spectral libraries are feasible and can facilitate reference material data dissemination across forensic drug laboratories.

Online low-field NMR spectroscopy for process control of an industrial lithiation reaction-automated data analysis.

Monitoring specific chemical properties is the key to chemical process control. Today, mainly optical online methods are applied, which require time- and cost-intensive calibration effort. NMR spectroscopy, with its advantage being a direct comparison method without need for calibration, has a high potential forenabling closed-loop process control while exhibiting short set-up times. Compact NMR instruments make NMR spectroscopy accessible in industrial and rough environments for process monitoring and advanced process control strategies. We present a fully automated data analysis approach which is completely based on physically motivated spectral models as first principles information (indirect hard modeling-IHM) and applied it to a given pharmaceutical lithiation reaction in the framework of the European Union's Horizon 2020 project CONSENS. Online low-field NMR (LF NMR) data was analyzed by IHM with low calibration effort, compared to a multivariate PLS-R (partial least squares regression) approach, and both validated using online high-field NMR (HF NMR) spectroscopy. Graphical abstract NMR sensor module for monitoring of the aromatic coupling of 1-fluoro-2-nitrobenzene (FNB) with aniline to 2-nitrodiphenylamine (NDPA) using lithium-bis(trimethylsilyl) amide (Li-HMDS) in continuous operation. Online 43.5 MHz low-field NMR (LF) was compared to 500 MHz high-field NMR spectroscopy (HF) as reference method.

Compact low-field NMR spectroscopy and chemometrics: A tool box for quality control of raw rubber

Styrene-butadiene rubber (SBR) is a major source material for the fabrication of elastomer products. Depending on its origin, differences are observed between SBR samples by tabletop NMR spectroscopy that relate to the constitution of the macromolecular chains. This study reports experimental results from the analysis of 108 SBR samples by low-field 1H and 13C NMR spectroscopy at 1 T in combination with partial least squares regression to develop a methodology for quality control of raw rubber. Partial least squares regression (PLS-R) models were developed for quantifying the individual monomer units present in SBR which are impossible to quantify directly because of peak overlap in a 1H NMR spectrum obtained at 1 T. The spectra revealed differences between samples from the same and different manufacturing batches of the same and different manufacturers in a qualitative and quantitative fashion. The range of samples included regular and oil-extended solution and emulsion polymerized SBR. Referring to high-field spectra acquired at 9.4 T the peaks in the low-field 13C NMR spectra could be assigned for determining the rubber microstructure, and the content of different repeat units could be quantified by partial least squares regression. Over 12 repeatable measurements the standard deviation in mass % was 0.03%, 0.06%, 0.05%, 0.33% and 0.37% for the contents of styrene, 1,2-butadiene, 1,4-butadiene, trans-1,4-butadiene and cis-1,4-butadiene units, respectively. Among 7 different sampling points in a delivery, the standard deviation was 0.51% for 1,2-butadiene, 0.88% for styrene, 0.56% for 1,4-butadiene unit, 0.42% for trans-1,4-butadiene and 0.68% for cis-1,4-butadiene units. The root-mean-square error of prediction (RMSEP) for styrene, 1,2-butadiene, 1,4-butadiene, and trans-1,4-butadiene was 0.15, 0.29, 0.29, and 0.28 with R2 values of 0.93, 0.92, 0.92, and 0.95, respectively, demonstrating the potential of low-field NMR spectroscopy with compact instruments for quality control of raw rubber when used in combination with effective data analysis procedures such as chemometrics.

Entrapped Styrene Butadiene Polymer Chains by Sol-Gel-Derived Silica Nanoparticles with Hierarchical Raspberry Structures.

A sol-gel transformation of liquid silica precursor to solid silica particles was carried out in a one-pot synthesis way, where a solution of styrene butadiene elastomer was present. The composites, thus produced, offered remarkable improvements of mechanical and dynamic mechanical performances compared to precipitated silica. The morphological analysis reveals that the alkoxy-based silica particles resemble a raspberry structure when the synthesis of the silica was carried out in the presence of polymer molecules and represent a much more open silica-network structure. However, in the absence of the polymer, the morphology of the silica particles is found to be different. It is envisaged that the special morphology of the in situ synthesized silica particles contributes to the superior reinforcement effects, which are associated with a strong silica-rubber interaction by rubber chains trapped inside the raspberry-like silica aggregates. Therefore, the interfaces are characterized in detail by low-field solid-state 1H NMR spectroscopy, 29Si solid-state NMR spectroscopy, and energy-dispersive X-ray spectroscopy. Low-field 1H NMR-based double-quantum experiments provide a quantitative information about the cross-link density of the silica-filled rubber composites and about the influence of silane coupling agent on the chemical cross-link density of the network and correlates well with equilibrium swelling measurements. The special microstructure of the alkoxy-based silica was found to be associated with the interaction between alkoxy-based silica and rubber chains as a consequence of particle growth in the presence of rubber chains.

Switching "on" and "off" the adhesion in stimuli-responsive elastomers.

The present work aims at the preparation of dry adhesives with switchable bonding properties by using the reversible nature of the [4πs+4πs] cycloaddition of anthracenes. Photo-responsive hydrogenated carboxylated nitrile butadiene rubber with photo-responsive pendant anthracene groups is prepared by one-pot synthesis. The formation of 3D networks relies on the photodimerization of the anthracene moieties upon UV exposure (λ > 300 nm). Controlled cleavage of the crosslink sites is achieved by either deep UV exposure (λ = 254 nm) or thermal dissociation at 70 °C. The kinetics of the optical and thermal cleavage routes are compared in thin films using UV-vis spectroscopy and their influence on the reversibility of the network is detailed. Going from thin films to free standing samples the modulation of the network structure and thermo-mechanical properties over repeated crosslinking and cleavage cycles are characterized by low-field NMR spectroscopy and dynamic mechanical analysis. The applicability of the stimuli-responsive networks as adhesives with reversible bonding properties is demonstrated. The results evidence that the reversibility of the crosslinking reaction enables a controlled switching "on" and "off" of adhesion properties. The recovery of the adhesion force amounts to 75 and 80% for photo- and thermal dissociation, respectively. Spatial control of adhesion properties is evidenced by adhesion force mapping experiments of photo-patterned films.

Online monitoring of the kinetic isotope effect in chemical reactions with 1H and 19F low-field NMR spectroscopy.

The kinetic isotope effect (KIE) describes the change in the rate of a chemical reaction by substituting one of the atoms in the reactants with one of its isotopes. Investigating the KIE and its temperature dependency in reactions renders information for reconstructing chemical processes and confirming the rate-determining step. However, conventional methods to study the KIE, e.g. by calorimetry, conductivity, titration, Raman spectroscopy etc., require calibration and sophisticated handling of the reaction calorimeter, and the data are obtained at irregular and sparse intervals. This current study employs a compact NMR system as an alternative means to determine the temperature dependency of the reaction rate and, thus, the KIE, as well as the activation energy, enthalpy, and entropy of each reaction. Here the neutral hydrolysis of acetic anhydride and ethyl trifluoroacetate was studied in H2O, D2O and H2O-D2O mixtures with 1H and 19F NMR spectroscopy. The activation energies for the hydrolysis of acetic anhydride with D2O and H2O were found to be 45 ± 2 kJ mol-1 and 40 ± 2 kJ mol-1, respectively. The activation energies of ethyl trifluoroacetate hydrolysis via19F NMR spectroscopy were determined to 46.7 ± 1 kJ mol-1 and 54.9 ± 1 kJ mol-1 for the reaction with H2O and D2O, respectively, and via1H NMR spectroscopy to 48 ± 3 kJ mol-1 and 55.8 ± 1 kJ mol-1. The differences in rate constants and activation energies for both reactions in H2O and D2O are due to the kinetic isotope effect, involving the breakage and formation of O-H and O-D bonds during the rate-determining step. The proton inventory studies were performed for both the reactions for determining the isotopic fractionation factors for the given transition states of the reactions which help to predict the reaction mechanisms of other similar reactions. The compact NMR system is a relevant and practical tool to unmask precise reaction pathways, by tracing the KIE in real time with densely sampled data, which are essential for obtaining accurate rate constants.

16-O-methylcafestol is present in ground roast Arabica coffees: Implications for authenticity testing

High-field and low-field proton NMR spectroscopy were used to analyse lipophilic extracts from ground roast coffees. Using a sample preparation method that produced concentrated extracts, a small marker peak at 3.16 ppm was observed in 30 Arabica coffees of assured origin. This signal has previously been believed absent from Arabicas, and has been used as a marker for detecting adulteration with robusta. Via 2D 600 MHz NMR and LC-MS, 16-O-methylcafestol and 16-O-methylkahweol were detected for the first time in Arabica roast coffee and shown to be responsible for the marker peak. Using low-field NMR, robusta in Arabica could be detected at levels of the order of 1–2% w/w. A surveillance study of retail purchased “100% Arabica” coffees found that 6 out of 60 samples displayed the 3.16 ppm marker signal to a degree commensurate with adulteration at levels of 3–30% w/w.

Precise control of agarose media pore structure by regulating cooling rate.

A porous structure is the key factor to successful chromatography separation. Agarose gel as one of the most popular porous media has been extensively used in chromatography separation. As the cooling process in the agarose gelation procedure can directly influence the pore structure, ten kinds of 4% agarose media with different cooling rates from 0.132 to 16.7°C/min were synthesized, and the pore structure was determined accurately by using low-field NMR spectroscopy. The curves of pore structure and cooling rate can be divided into two stages with the boundary of 6°C/min. In stage I, the pore structure met a power equation with the decrease of the cooling rate, and in stage II, the process reached a plateau. Confirmatory experiments proved that, by adjusting the cooling rate, a precise control of the pore structure of agarose media can be realized, furthermore, cooling rate optimization was an effective way to control the pore size of agarose media and can further tailor the pore structure for more effective separation of different proteins.

Characteristics of Xanthosoma sagittifolium roots during cooking, using physicochemical analysis, uniaxial compression, multispectral imaging and low field NMR spectroscopy.

To effectively promote the industrial utilization of cocoyam (Xanthosoma sagittifolium) roots for enhanced food sustainability and security, there is a need to study their molecular, mechanical and physicochemical properties in detail. The physicochemical and textural characteristics of the red and white varieties of cocoyam roots were thus analysed by low field nuclear magnetic resonance relaxometry, multispectral imaging, uniaxial compression testing, and relevant physicochemical analysis in the current study. Both varieties had similar dry matter content, as well as physical and mechanical properties. However, up to four fast-interacting water populations were observed in the roots, dependent on the root variety and their degree of gelatinization during cooking. Changes in the relaxation parameters indicated weak gelatinization of starch at approximately 80°C in both varieties. However, shorter relaxation times and a higher proportion of restricted water in the white variety indicated that this variety was slightly more sensitive towards gelatinization. A strong negative correlation existed between dry matter and all multispectral wavelengths>800nm, suggesting the potential use of that spectral region for rapid analysis of dry matter and water content of the roots. The small, but significant differences in the structural and gelatinization characteristics of the two varieties indicated that they may not be equally suited for further processing, e.g. to flours or starches. Processors thus need to choose their raw materials wisely dependent on the aimed product characteristics. However, the spectroscopic methods applied in the study were shown to be effective in assessing important quality attributes during cooking of the roots.