Nuclear Magnetic Resonance Spectroscopy Spectrometry Research Articles

Stratification of hypertension and SARS-CoV-2 infection by quantitative NMR spectroscopy of human blood serum

BackgroundDiagnostic approaches like the nuclear magnetic resonance spectroscopy (NMR) based quantification of metabolites, lipoproteins, and inflammation markers has helped to identify typical alterations in the blood serum of COVID-19 patients. However, confounders such as sex, and comorbidities, which strongly influence the metabolome, were often not considered. Therefore, the aim of this NMR study was to consider sex, as well as arterial hypertension (AHT), when investigating COVID-19-positive serum samples in a large age-and sex matched cohort.MethodsNMR serum data from 329 COVID-19 patients were compared with 305 healthy controls. 134 COVID-19 patients were affected by AHT. These were analyzed together with NMR data from 58 hypertensives without COVID-19. In addition to metabolite, lipoprotein, and glycoprotein data from NMR, common laboratory parameters were considered. Sex was considered in detail for all comparisons.ResultsHere, we show that several differences emerge from previous NMR COVID-19 studies when AHT is considered. Especially, the previously described triglyceride-rich lipoprotein profile is no longer observed in COVID-19 patients, nor an increase in ketone bodies. Further alterations are a decrease in glutamine, leucine, isoleucine, and lysine, citric acid, HDL-4 particles, and total cholesterol. Additionally, hypertensive COVID-19 patients show higher inflammatory NMR parameters than normotensive patients.ConclusionsWe present a more precise picture of COVID-19 blood serum parameters. Accordingly, considering sex and comorbidities should be included in future metabolomics studies for improved and refined patient stratification. Due to metabolic similarities with other viral infections, these results can be applied to other respiratory diseases in the future.

To Fluoresce or Not to Fluoresce: Investigation of Structural and Fluorescence Characteristics of CBI-Dopamine, CBI-Serotonin, and Their Structural Analogs.

Dopamine (DA) and serotonin (5-HT) are neurotransmitters that are vital for proper brain function and are implicated in a wide variety of diseases and disorders. Unfortunately, quantitative analysis of DA and 5-HT is difficult, as they are present at low concentrations in complex biological matrices. The fluorogenic reaction of napththalene-2,3-dicarboxaldehyde (NDA) with a primary amine in the presence of cyanide (CN) creates an N-substituted 1-cyanobenz[f]isoindole (CBI) derivative, whose fluorescence can be sensitively monitored in biological matrices. Given their biological importance, there are surprisingly few reports showing fluorescence of CBI-DA and no prior publications concerning CBI-5-HT. In this work, nuclear magnetic resonance spectroscopy (NMR) was employed to determine the atom connectivity of over 10 CBI-products, including CBI-DA and CBI-5-HT. NMR and fluorescence spectroscopy were applied to CBI-DA, CBI-5-HT, and select structural analogs to determine structural correlations with the observed lack of fluorescence. Experiments with CBI-DA and structural analogs indicated fluorescence was rapidly quenched due to both complexation with the historically employed buffer and oxidation in solution. Fluorescence of CBI-DA was recovered by modifying the derivatization background to prevent complexation and oxidation. In contrast, fluorescence characterization of CBI-5-HT and its structural analogs indicated that 5-HT was acting as a quencher of the CBI-ring. The addition of acid to protonate 5-HT was found to disrupt this interaction and enable the first reported fluorescence detection of CBI-5-HT. In the future, this work will be applied to detect DA and 5-HT in biological systems to gain insight into neurobiological disease states and disorders.

Molecular Dynamics Simulation of the Structure of BaF2-BaO-La2O3-B2O3 Glasses.

The structure of the BaF2-BaO-La2O3-B2O3 glasses was investigated using X-ray diffraction (XRD), nuclear magnetic resonance spectroscopy (NMR), and molecular dynamics (MD) simulation. The total correlation functions calculated from the prepared structural models using the MD simulation successfully reproduced the XRD measurements. In the structural models, the fraction of BO4 units increased with the increased fluorine (F) concentration. Furthermore, the introduced F atom is found to bond with Ba and La atoms but barely bonded with boron atoms, as confirmed through boron-11 and fluorine-19 NMR spectroscopy experiments. Furthermore, the structural models showed that an increase in F atoms increased the heterogeneity of the glass structure.

Polyesters of 14-Hydroxylated Taxoids Found for the First Time in <i>Taxus canadensis</i> Intact Plants

Taxane diterpenoids (taxoids) are found only in representatives of the Taxaceae family (different yew species); however, the unique structure and therapeutic properties of taxoids, which are in demand in medicine, have made these compounds one of the most studied secondary metabolites of higher plants. In this work, for the first time, a detailed study is performed into the structural diversity of polyesters of 14-hydroxylated taxoids in Taxus canadensis a yew species, for intact plants of which nonpolar 14-hydroxylated taxoids have not been previously described. At the first stage of the work, it was shown using chromato-mass spectrometry that polyesters of 14-hydroxylated taxoids (yunnanxan, taxuyunnanin C, sinenxan B, sinenxan C) are the dominant diterpenoid secondary metabolites in T. canadensis callus cell culture. Based on these results, as well as the similarity of the metabolism of cultivated in vitro plant cells and root cells in planta, it was suggested that polyesters of 14-hydroxylated taxoids will preferentially accumulate in the roots in intact T. canadensis plants. The validity of this hypothesis was confirmed using liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy (NMR). According to chromato-mass-spectrometric screening in T. canadensis needles, polyesters of 14-hydroxylated taxoids are actually found only in trace amounts, while they are one of the major (quantitatively) diterpenoids in the roots. One of the main 14-hydroxylated taxoids of T. canadensis roots, yunnanxan, was isolated preparatively and uniquely identified using NMR spectroscopy and high-resolution mass spectrometry. This work is the first report on the presence of polyesters of 14-hydroxylated taxoids in intact Canadian yew plants.

Stable Isotopomers of myo-Inositol Uncover a Complex MINPP1-Dependent Inositol Phosphate Network.

The water-soluble inositol phosphates (InsPs) represent a functionally diverse group of small-molecule messengers involved in a myriad of cellular processes. Despite their centrality, our understanding of human InsP metabolism is incomplete because the available analytical toolset to characterize and quantify InsPs in complex samples is limited. Here, we have synthesized and applied symmetrically and unsymmetrically 13C-labeled myo-inositol and inositol phosphates. These probes were utilized in combination with nuclear magnetic resonance spectroscopy (NMR) and capillary electrophoresis mass spectrometry (CE-MS) to investigate InsP metabolism in human cells. The labeling strategy provided detailed structural information via NMR-down to individual enantiomers-which overcomes a crucial blind spot in the analysis of InsPs. We uncovered a novel branch of InsP dephosphorylation in human cells which is dependent on MINPP1, a phytase-like enzyme contributing to cellular homeostasis. Detailed characterization of MINPP1 activity in vitro and in cells showcased the unique reactivity of this phosphatase. Our results demonstrate that metabolic labeling with stable isotopomers in conjunction with NMR spectroscopy and CE-MS constitutes a powerful tool to annotate InsP networks in a variety of biological contexts.

Synthesis of Ferrocene−Cyclodextrin, Anthracene−Cyclodextrin, and Pyrene−Cyclodextrin [2]Rotaxane Conjugates and Their Intercomponent Behavior as Observed in NMR Spectroscopy

AbstractFerrocene, anthracene, and pyrene‐terminated alkynylated moieties were reacted with azidized beta‐cyclodextrin derivatives to form supramolecular structures under various conditions. While initial experiments concerning mono‐azidized beta‐cyclodextrin proved difficult to isolate and have limited solubility, their reaction with peracetylated mono‐azidized beta‐cyclodextrin was more facile. Introduction and threading of the macrocycle, dibenzo‐24‐crown‐8 (DB24C8), allowed for [2]rotaxane synthesis. These compounds were characterized by infrared spectroscopy (IR), nuclear magnetic resonance spectroscopy (NMR), and mass spectrometry (MS). Among the compounds formed, the ferrocene‐capped species showed promising host‐guest inclusion complexation with the cyclodextrin cavity.

Comprehensive assessment of dissolved organic matter processing in the Amazon River and its major tributaries revealed by positive and negative electrospray mass spectrometry and NMR spectroscopy

Rivers are natural biogeochemical systems shaping the fates of dissolved organic matter (DOM) from leaving soils to reaching the oceans. This study focuses on Amazon basin DOM processing employing negative and positive electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI[±] FT-ICR MS) and nuclear magnetic resonance spectroscopy (NMR) to reveal effects of major processes on the compositional space and structural characteristics of black, white and clear water systems. These include non-conservative mixing at the confluences of (1) Solimões and the Negro River, (2) the Amazon River and the Madeira River, and (3) in-stream processing of Amazon River DOM between the Madeira River and the Tapajós River. The Negro River (black water) supplies more highly oxygenated and high molecular weight compounds, whereas the Solimões and Madeira Rivers (white water) contribute more CHNO and CHOS molecules to the Amazon River main stem. Aliphatic CHO and abundant CHNO compounds prevail in Tapajos River DOM (clear water), likely originating from primary production. Sorption onto particles and heterotrophic microbial degradation are probably the principal mechanisms for the observed changes in DOM composition in the Amazon River and its tributaries.

Microstructural Analysis of Poly(ethylene-co-propylene-co-1-butene) terpolymers by Multidimensional NMR Spectroscopy

Physical, rheological and optical properties of polymer depend on its molecular microstructure. Specifically, the monomer content and sequence distribution of polymer significantly affect the mechanical performance of the final product. To this base, Nuclear Magnetic Resonance Spectroscopy (NMR) has been introduced as a very powerful technique to study the microstructure of polymer. The purpose of this study was to develop a methodology to investigate the microstructure of poly(ethylene-co-propylene-co-butene) terpolymer by using multidimensional NMR spectroscopy, including pulsed-field-gradient (PFG) 1H-13C heteronuclear single quantum coherence (GHSQC), heteronuclear multiple bond coherence (gHMBC), and heteronuclear single quantum coherence-total correlation spectroscopy (GHSQC-TOCSY). The combination of 1D and 2D NMR experiments, permit the characterization of the complex structure of poly(ethylene-co-propylene-co-butene) terpolymer. The completed 13C NMR assignments provided in this work allow more accurate quantitative determination of the microstructure in these polymers.

Creatine Deficiency Syndromes: Comparison of Screening Methods and Characterization of Four Novel Intronic Variants

BackgroundCerebral creatine deficiency syndromes (CCDS) are disorders affecting creatine synthesis or transport. Several methods have been developed to measure creatine and guanidinoacetate (GAA) in different body fluids including methods based on gas chromatography-mass spectrometry (GC–MS) and High-pressure liquid chromatography mass spectrometry (HPLC-MS). The diagnosis of CCDS is then confirmed by sequencing of creatine biosynthesis genes guanidinoacetate methyltransferase (GAMT) and Arginine: glycine amidinotransferase (GATM) and creatine transporter gene solute carrier family 6 member 8 (SLC6A8) or by functional enzymatic assay. The aim of the current study was to find the most reliable and accurate screening method for CCDS by comparing methods using Nuclear Magnetic Resonance spectroscopy (NMR), GC–MS and HPLC-MS. Additionally, this study was performed to estimate the prevalence of CCDS in a cohort of Egyptian patients and potentially to discover novel variants. Subjects and methodsThe study was conducted on 150 subjects with clinical signs and symptoms consistent with CCDS. Metabolic profiling of urine samples was performed using three techniques: 1) GC–MS 2) Ultra high-pressure (or performance) liquid chromatography – Tandem Mass Spectrometry (UHPLC- MS/MS) and 3) NMR. ResultsThe linearity of peak areas for creatine and GAA by UHPLC-MS/MS and NMR covered and exceeded the ranges normally found in urine. The limit of quantification and the inter-day precision results for creatine and GAA were more robust by UHPLC-MS/MS than NMR. Ten cases were identified as being positive for CCDS by our analytical approaches and underwent next generation sequencing (NGS) for GAMT, GATM and SLC6A8 genes. NGS was performed and confirmed one patient with one likely Pathogenic variant in GAMT gene: (NC_000019.10:g.1401317C > G, NP_000147.1:p.Ala54Pro). Additionally, we describe four novel intronic variants in the GATM gene: c.1043-357del and c.1043-357_1043-356insT, and were predicted to activate cryptic acceptor site with potential alteration of splicing, c.979-227G > A was found to significantly alter the Exon Splice Enhancer (ESE) xon Splice Silencer (ESS) motifs ratio and c.1042 + 262del which was found to have no implications on splicing. ConclusionsBoth UHPLC-MS/MS and NMR spectroscopy are comparable to GC–MS in screening for CCDS. Nonetheless, the UHPLC-MS/MS method had better performance than NMR spectroscopy. Additionally, Sequencing of the full length of GATM, GAMT, and SLC6A8 genes is needed to identify intronic variants that could cause CCDS via affecting splice sites.

Battery Degradation and Lifetime – Studies within the Faraday Institution on NMC811/Graphite Full Cells

Lithium-ion batteries (LIBs) find use in a wide range of applications, each of which has its own design specifications and practical requirements. With regards to the role of LIBs in mitigating carbon emissions, and therefore climate change, it is desirable to support the rapidly growing adoption of electric vehicles and renewable grid-storage systems via development of higher energy density, lower cost, and improved rate capability. However, the design of energy-dense, low-cobalt, and/or high-rate cell chemistries is impeded by inherent trade-offs with cycling and calendar lifetimes. A key goal for the automotive and utilities industries is therefore to predict battery lifetime for new cell designs and chemistries at a very high level of confidence, for example through improved understanding of the physical and chemical processes that determine the state of health of battery systems.As part of the Faraday Institution, the UK’s independent institute for electrochemical energy storage technology, the Battery Degradation Project has built new understanding of the underlying physical and chemical processes that can lead to degradation in energy-dense NMC811/graphite lithium-ion cells as a model system. Led by the University of Cambridge (Clare Grey PI) in collaboration with eight UK universities, the research consortium is working closely with industry partners to create a new hub for lithium-ion battery research and to address key challenges and opportunities in the field. This presentation will give an overview of the research consortium’s diverse membership, key milestones, and technical progress.To date, the consortium has been applying a variety of analytical techniques to study degradation processes in NMC811/graphite cells. For example, electrochemical testing and operando solid-state 7Li nuclear magnetic resonance spectroscopy (NMR) were combined to monitor processes in both electrodes individually, including Li-ion mobility and its changes with temperature.1 The method is now being applied to understand how the dynamics are affected by long-term structural damage to the NMC811 material. A series of differential voltage analysis experiments have been paired with operando X-ray diffraction measurements to propose the mechanism behind a critical ‘turning point’ in NMC811/graphite cells, following which degradation accelerates significantly.2 New operando cell designs have been developed to measure changes in cell pressure,3 which are being paired with solution NMR spectroscopy,4 and differential electrochemical mass spectrometry to quantify electrolyte oxidation. The role and rate of transition-metal dissolution in cells under stressed cycling conditions, namely cycling at high temperature (60 °C) and high upper cut-off voltages (4.4, 4.6 V), has been investigated.5 Scanning transmission electron microscopy-energy dispersive X-ray spectroscopy (STEM-EDX) measurements were coupled with time-of-flight secondary-ion mass spectrometry (Tof-SIMS) to observe the Al-containing phases at NMC811 surfaces and grain boundaries.7 New spectroscopic methods are also being developed, including Kerr-gated Raman, which allows sensitive measurements of electrode materials and electrolytes with lower background signal than conventional Raman spectroscopy.6 Finally, X-ray computed tomography methods have been developed that enable operando imaging and spectroscopic mapping of heterogeneities at a sub-particle length scale and across large areas of electrodes, which are being applied to study the origins of microstructural defects, cracking, and redox activity during charging, cycling, or storage.8,9 Reference s: K. Märker, C. Xu, and C. P. Grey, J. Am. Chem. Soc., 142, 17447–17456 (2020). W. M. Dose, C. Xu, C. P. Grey, and M. F. L. De Volder, Cell Rep. Phys. Sci., 1, 100253 (2020). N. Ryall and N. Garcia-Araez, J. Electrochem. Soc., 167, 110511 (2020). B. L. D. Rinkel, D. S. Hall, I. Temprano, and C. P. Grey, J. Am. Chem. Soc., 142, 15058–15074 (2020). Z. Ruff, C. Xu, and C. P. Grey, J. Electrochem. Soc., 168, 060518 (2021). L. Cabo-Fernandez, A. R. Neale, F. Braga, I. V. Sazanovich, R. Kostecki, and L. J. Hardwick, Phys. Chem. Chem. Phys., 21, 23833–23842 (2019). J. Lee, H. Amari, M. Bahri, Z. Shen, C. Xu, Z. Ruff, C. P. Grey, O. Ersen, A. Aguadero, N. D. Browning, and B. L. Mehdi, Batter. Supercaps, 4, 1813–1820 (2021). T. M. M. Heenan, A. Wade, C. Tan, J. E. Parker, D. Matras, A. S. Leach, J. B. Robinson, A. Llewellyn, A. Dimitrijevic, R. Jervis, P. D. Quinn, D. J. L. Brett, and P. R. Shearing, Adv. Energy Mater., 10, 2002655 (2020). C. Tan, A. S. Leach, T. M. M. Heenan, H. Parks, R. Jervis, J. N. Weker, D. J. L. Brett, and P. R. Shearing, Cell Rep. Phys. Sci., 100647 (2021).

Abstract 2322: Multiplatform metabolomics studies of human cancers with NMR and mass spectrometry imaging

Abstract Unfortunately, at present, there is no single technique that possesses all the characteristics needed to be considered an ideal global metabolite profiling tool. Thus, the use of multiple analytical platforms, such as combining the strengths of Mass spectrometry (MS) and nuclear magnetic resonance spectroscopy (NMR), for metabolic profiling can maximize coverage and generate more global metabolomic profiles. In this study, we demonstrate the utilities of the combined NMR and MSI multiplatform in our metabolomics results on human prostate and lung cancers. Statistical data on the natural history of prostate cancer (PCa) show that >70% of patients diagnosed by PSA screening will likely experience indolent disease with little impact on well-being. For about 17% of newly PSA-diagnosed patients, however, aggressive PCa proliferation ensues, truncating life expectancy. At present, no reliable clinical test can differentiate between these two groups. Using HRMAS 1HNMR followed by quantitative histology, we showed statistically significant correlations between concentrations of Spm and the amount of histologically-benign epithelial (Hb Epi) prostatic cells and glands in human cancerous prostates. However, as above discussed that using HRMAS NMR alone we cannot prove that Spm was indeed generated or resided in the Hb Epi cells. Nevertheless, using MALDI MSI, we were able to locate Spm (m/z: 203.223 ± 0.001Da) onto Hb Epi, where spermine on the PCa lesions appeared below detection limits. From these maps, for the first time, we could visualize and confirm the differential localizations of Spm in prostates. This proof of Sym relationship to prostate pathologies and its proposed PCa inhibitory effects may support further studies that are critical in differentiating aggressive from indolent PCa for disease evaluations and patient personalized treatment strategies. To search for such screening metabolomics biomarkers in lung cancer, we used HRMAS NMR to analyze 93 pairs of human LuCa tissue and serum samples, and 29 healthy human sera. A number of potential metabolite candidates capable to differentiate LuCa characteristics were identified, including glutamate, lipids, alanine, glycerylphosphorylcholine, glutamine, phosphorylcholine, etc. This list can be further expanded by analyzing metabolite composition in the serum of cancer patients and control healthy subjects using LC-MS, which offers a dramatic increase in sensitivity compared to HRMAS NMR and, therefore, is better suited for the biomarker discovery. In addition to acquiring high-resolution mass data, the high data acquisition rate allows the fragment ion mass spectra (MS/MS) to be generated for the most abundant ionic species in each chromatographic peak. This feature allows specific classes of tumor-attenuated metabolites to be identified based on the presence of unique structurally diagnostic fragment ions in MS/MS spectra. Citation Format: Leo L. Cheng, Anya B. Zhong, Isabella H. Muti, Stephen J. Eyles, Richard W. Vachet, Sylwia A. Stopka, Kristen N. Sikora, Cedric E. Bobst, Jeffrey N. Agar, Mari A. Mino-Kenudson, Chin-Lee Wu, David C. Christiani, Igor A. Kaltashov, Nathalie Y. Agar. Multiplatform metabolomics studies of human cancers with NMR and mass spectrometry imaging [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2322.

Solution NMR Spectroscopy as a Tool to Study DNAzyme Structure and Function.

Catalytically active DNA oligomers (or DNAzymes) offer a broad spectrum of functions as well as applications. Although known for over two decades, the DNAzyme's mode-of-actions are still poorly understood, mainly due to lack of high-resolution structural insights. Due to their molecular size, structural flexibility, and dynamic interactions with metal-ion cofactors, solution nuclear magnetic resonance spectroscopy (NMR) can serve as optimal tool to obtain mechanistic insights of DNAzymes. In this respect, nearly all states of the DNAzyme and its substrate during the catalytic cycle are accessible. The instructions and protocols provided in the following may assist the initial steps of an NMR-based characterization of DNAzymes. To reduce the initial setup requirements and foster exciting new research projects, the discussed approaches focus on experiments that do not require cost-intensive isotope labeling strategies.

Composition and Corrosivity of Extracellular Polymeric Substances from the Hydrocarbon-Degrading Sulfate-Reducing Bacterium Desulfoglaeba alkanexedens ALDC.

Sulfate-reducing bacteria (SRB) often exist as cell aggregates and in biofilms surrounded by a matrix of extracellular polymeric substances (EPSs). The chemical composition of EPSs may facilitate hydrophobic substrate biodegradation and promote microbial influenced corrosion (MIC). Although EPSs from non-hydrocarbon-degrading SRB have been studied; the chemical composition of EPSs from hydrocarbon-degrading SRBs has not been reported. The isolated EPSs from the sulfate-reducing alkane-degrading bacterium Desulfoglaeba alkanexedens ALDC was characterized with scanning and fluorescent microscopy, nuclear magnetic resonance spectroscopy (NMR), and by colorimetric chemical assays. Specific fluorescent staining and 1H NMR spectroscopy revealed that the fundamental chemical structure of the EPS produced by D. alkanexedens is composed of pyranose polysaccharide and cyclopentanone in a 2:1 ratio. NMR analyses indicated that the pyranose ring structure is bonded by 1,4 connections with the cyclopentanone directly bonded to one pyranose ring. The presence of cyclopentanone presumably increases the hydrophobicity of the EPS that may facilitate the accessibility of hydrocarbon substrates to aggregating cells or cells in a biofilm. Weight loss and iron dissolution experiments demonstrated that the EPS did not contribute to the corrosivity of D. alkanexedens cells.

Nuclear Magnetic Resonance Spectroscopy in Clinical Metabolomics and Personalized Medicine: Current Challenges and Perspectives.

Personalized medicine is probably the most promising area being developed in modern medicine. This approach attempts to optimize the therapies and the patient care based on the individual patient characteristics. Its success highly depends on the way the characterization of the disease and its evolution, the patient’s classification, its follow-up and the treatment could be optimized. Thus, personalized medicine must combine innovative tools to measure, integrate and model data. Towards this goal, clinical metabolomics appears as ideally suited to obtain relevant information. Indeed, the metabolomics signature brings crucial insight to stratify patients according to their responses to a pathology and/or a treatment, to provide prognostic and diagnostic biomarkers, and to improve therapeutic outcomes. However, the translation of metabolomics from laboratory studies to clinical practice remains a subsequent challenge. Nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS) are the two key platforms for the measurement of the metabolome. NMR has several advantages and features that are essential in clinical metabolomics. Indeed, NMR spectroscopy is inherently very robust, reproducible, unbiased, quantitative, informative at the structural molecular level, requires little sample preparation and reduced data processing. NMR is also well adapted to the measurement of large cohorts, to multi-sites and to longitudinal studies. This review focus on the potential of NMR in the context of clinical metabolomics and personalized medicine. Starting with the current status of NMR-based metabolomics at the clinical level and highlighting its strengths, weaknesses and challenges, this article also explores how, far from the initial “opposition” or “competition”, NMR and MS have been integrated and have demonstrated a great complementarity, in terms of sample classification and biomarker identification. Finally, a perspective discussion provides insight into the current methodological developments that could significantly raise NMR as a more resolutive, sensitive and accessible tool for clinical applications and point-of-care diagnosis. Thanks to these advances, NMR has a strong potential to join the other analytical tools currently used in clinical settings.

Intrinsic anisotropy parameters of a series of lanthanoid complexes deliver new insights into the structure-magnetism relationship

Intrinsic anisotropy parameters of a series of lanthanoid complexes deliver new insights into the structure-magnetism relationship

Lorentzian peak sharpening and sparse blind source separation for NMR spectroscopy

In this paper, we introduce a preprocessing technique for blind source separation of nonnegative and overlapped data. For nuclear magnetic resonance spectroscopy (NMR), the classical method of Naanaa and Nuzillard (NN) requires the condition that source signals to be non-overlapping at certain locations, while they are allowed to overlap with each other elsewhere. NN’s method works well with data signals that possess stand-alone peaks (SAPs). The SAP does not hold completely for realistic NMR spectra, however. Violation of SAP often introduces errors or artifacts in the NN’s separation results. To address this issue, a preprocessing technique is developed here based on Lorentzian peak shapes and weighted peak sharpening. The idea is to superimpose the original peak signal with its weighted negative second-order derivative. The resulting sharpened (narrower and taller) peaks enable NN’s method to work with a more relaxed SAP condition, the so-called dominant peaks condition, and deliver improved results. To achieve an optimal sharpening while preserving the data nonnegativity, we prove the existence of an upper bound of the weight parameter and propose a selection criterion. Numerical experiments on NMR spectroscopy data show satisfactory performance of our proposed method.

Illustrating Elementary NMR Concepts through Simple Interactive Python Programs

Introducing elementary concepts of nuclear magnetic resonance spectroscopy (NMR) to a beginner can be challenging. Using an interactive graphical platform can greatly aid in demonstrating key concepts in such cases. This paper aims to bridge this gap in teaching basic NMR spectroscopy through simple standalone interactive Python programs or a Jupyter notebook, supplementing traditional theoretical approaches. These scripts allow the beginner with basic knowledge of quantum mechanics to grasp important concepts like precession, nutation, laboratory and rotating frames, on- and off-resonance RF-pulses through user input, and graphical and terminal output of results.

Rapid and accurate verification of drug identity, purity and quality by 1H-NMR using similarity calculations and differential NMR

The illegal trade in counterfeit and fake drugs is a worldwide multi-billion dollar industry, not only generating enormous economic losses, but health problems for the general population, through direct toxicity, treatment failure and the increased generation of antibiotic resistance. Techniques for high-throughput testing of suspect medicines are needed to face the challenges of the problem. In this study we show that with nuclear magnetic resonance spectroscopy (NMR) drug compliance can be verified in a few minutes, providing data on drug identity, purity and quality without the necessity to develop a specific methodology and using a direct extraction with deuterated solvent. The evaluation of the data is facilitated by similarity calculations and differential NMR spectroscopy. The viability and limitations of this method were assessed, with the application on five different drugs, namely sertraline hydrochloride, alprazolam, vitamin D3, enalapril maleate and paracetamol, in which the individual dosage quantity of the active ingredient ranged from 750 mg down to 0.25 mg. The appropriate sample weight, solvent and internal standard were determined for each drug and quantification was carried out by choosing the most adequate NMR signals for each compound and the internal standard. With the method the accuracy of the quantification is somewhat sacrificed for increased speed in the analysis, but the measurements offer excellent precision and offer the possibility of external calibration. Spectral similarity calculations and differential NMR spectroscopy were used to compare different generic brands and detect eventual undeclared constituents and contaminants. In one brand of alprazolam tablets the undeclared constituent tristearin was found, while in paracetamol tablets the contaminant para-aminophenol was found at a level above the allowed by the legislation. The applicability and limitations of the method are discussed.

NMR spectroscopy of electroceramics – Applications to lead-free perovskite oxides

Understanding about the local structure plays an increasing role for the discovery of structure-property relations in electroceramics. Despite that, characterization techniques dedicated to the local structure are still not widespread in the electroceramics community. Nuclear magnetic resonance spectroscopy (NMR) has the potential to close this gap, as particularly sensitive to minute distortions and well-suited for the structural analysis of partially disordered materials, such as solid-solutions. This review aims at an introduction of this technique tailored to the materials scientist. Following a brief description of the base concepts, its capabilities are demonstrated by a series of tangible examples from local structural questions pertinent to materials based on three classes of lead-free perovskites, namely BaTiO3, NaNbO3 and Na1/2Bi1/2TiO3. Beyond its application to lead-free perovskite oxides, the concepts illustrated here are of broad interest for further oxides and materials in general.

Increased usability, algorithmic improvements and incorporation of data mining for structure calculation of proteins with REDCRAFT software package

BackgroundTraditional approaches to elucidation of protein structures by Nuclear Magnetic Resonance spectroscopy (NMR) rely on distance restraints also known as Nuclear Overhauser effects (NOEs). The use of NOEs as the primary source of structure determination by NMR spectroscopy is time consuming and expensive. Residual Dipolar Couplings (RDCs) have become an alternate approach for structure calculation by NMR spectroscopy. In previous works, the software package REDCRAFT has been presented as a means of harnessing the information containing in RDCs for structure calculation of proteins. However, to meet its full potential, several improvements to REDCRAFT must be made.ResultsIn this work, we present improvements to REDCRAFT that include increased usability, better interoperability, and a more robust core algorithm. We have demonstrated the impact of the improved core algorithm in the successful folding of the protein 1A1Z with as high as ±4 Hz of added error. The REDCRAFT computed structure from the highly corrupted data exhibited less than 1.0 Å with respect to the X-ray structure. We have also demonstrated the interoperability of REDCRAFT in a few instances including with PDBMine to reduce the amount of required data in successful folding of proteins to unprecedented levels. Here we have demonstrated the successful folding of the protein 1D3Z (to within 2.4 Å of the X-ray structure) using only N-H RDCs from one alignment medium.ConclusionsThe additional GUI features of REDCRAFT combined with the NEF compliance have significantly increased the flexibility and usability of this software package. The improvements of the core algorithm have substantially improved the robustness of REDCRAFT in utilizing less experimental data both in quality and quantity.