Magnetic Resonance in Chemistry最新文献

The research team established a quantitative ¹H NMR method to determine the relative ethoxy content (EO%) in ethylcellulose using a CDCl₃/TFA-d solvent mixture. High-field NMR spectroscopy enabled direct measurement without the use of internal or external calibrants by integrating the methyl proton signals (δ 1.15 ppm) and the methylene/methine proton signals (δ 2.5–5.5 ppm), and using their equivalent ¹H numbers and corresponding mass fractions for calculations. The EO% was calculated as: EO% = $�\frac{�315�r�}{�486�-�614�r�}$ × 100, where r = $�\frac{I_A}{�I_A�+�I_B�}$ (I_A methyl ¹Hs integral; Iᴃ methylene/methine ¹Hs integral). Round robin multi-laboratory validation testing showed that the qNMR results deviated by less than 3% from the certificate of analysis (COA) values (44%–51%). The COA values, derived using the pharmacopeial gas chromatography-flame ionization detection (GC-FID) method, may be affected by factors related to incomplete derivatization and the volatility and instability of the product (iodoethane) and the inert internal reference standard (n-octane). Therefore, the qNMR method with its operational simplicity, reduced chemical hazards, and robust performance presents an alternative for quality control of pharmaceutical-grade ethylcellulose.

Epithelial splicing regulatory protein 2 (ESRP2) plays a pivotal role in alternative splicing regulation, particularly in maintaining epithelial cell identity and suppressing epithelial-to-mesenchymal transition (EMT). Despite its biological significance, the structural basis for its RNA-binding specificity remains poorly understood. In this study, we report the solution structure and RNA-binding properties of the RNA Recognition Motif (RRM3) of human ESRP2 using an integrative approach combining nuclear magnetic resonance (NMR) spectroscopy, ITC, molecular docking, and MD simulations. Our structural analysis revealed that ESRP2-RRM3 adopts a canonical RRM fold (βαββαβ), featuring a positively charged β-sheet surface conducive to RNA interaction. ITC assays demonstrated that RRM3 binds UG-rich RNA sequences with moderate affinity, and NMR titrations identified key interacting residues within the conserved RNP motifs, particularly F522 and R480. RNA docking and MD simulations further corroborated these interactions, revealing π–π stacking and hydrogen bonding at the protein-RNA interface. These findings represent the first atomic-level characterization of ESRP2's interaction with its RNA targets and provide mechanistic insight into how it may guide alternative splicing events in vivo. This work lays the groundwork for understanding the modular RNA recognition by ESRP2's multiple RRMs and its broader role in splicing regulation, development, and cancer suppression.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition often complicated by sepsis, leading to worse clinical outcomes. The role of biomarkers in distinguishing ARDS with and without sepsis remains unclear. This study aimed to evaluate the differences in serum metabolites between the two groups, comparing levels on Day 1 and Day 7 of intensive care unit (ICU) admission, and to assess the variation in outcomes via clinical characteristics. A cohort of n = 151 patients was included, with n = 91 providing serum samples on Day 1 and n = 60 on Day 7. Of the n = 91 patients on Day 1, n = 40 had ARDS with sepsis and n = 51 without sepsis, while on Day 7, n = 24 had ARDS with sepsis and n = 36 without. Serum samples were analyzed using ¹H NMR-based metabolomics to identify altered metabolites and perturbed pathways. In contrast, no significant differences were found between the patient groups with and without sepsis on either Day 1 or Day 7. Mortality rates were also similar in both groups, with a 50% survival rate on Day 7. No notable differences in the clinical data were observed. These findings suggest that ARDS, with and without sepsis, exhibits a similar metabolic profile, likely due to shared pathophysiological mechanisms. In light of these similarities, the findings indicate a unified approach to ARDS management that may improve the clinical outcomes across both groups.

Six sesquiterpene derivative compounds (1–6), including one new 7R-sydowic acid (1) and five known compounds (2–6) were isolated from the secondary metabolites of Aspergillus sydowii-HB. The structures were determined by NMR spectroscopy and ESI-MS analysis, and the configuration of compound 1 was confirmed through DP4⁺ calculation and NMR chemical shift. All the isolated compounds (1–6) were tested for their cytotoxic activities. The possible biosynthetic pathways for compounds (1–6) were also postulated.

G-protein–coupled receptors (GPCRs) are the largest and most heterogeneous group of cell membrane receptors dictating various physiological processes. GPCRs are the pivotal points for orchestrating almost every cellular response, making them the most sought-after drug targets. Although the GPCRs have extensively been studied, there are still many aspects that are yet to be understood. The GPCR structures have been characterised using various biophysical techniques like x-ray crystallography, cryo-EM and nuclear magnetic resonance (NMR) techniques. While the conventional techniques enabled a gross understanding of the GPCR structures, ligand interaction and conformational dynamics, the recent developments in NMR methods have unlocked new possibilities to better understand receptor bias, ligand-selectivity determination and ligand-binding characterisation in live cells. In this review, we have attempted to highlight how different NMR approaches can be utilised to add more details to the story of GPCRs.

Characterising drug-binding mechanisms, structural changes and dynamics at atomic resolution remains a challenge due to the dynamic and heterogeneous nature of surfactant supramolecular assemblies. In this context, nuclear magnetic resonance (NMR) is uniquely suited to overcome these complexities by offering precise information on binding, structure, dynamics and transport in native-like conditions. NMR spectroscopy, leveraging the nuclear Overhauser effect (NOE), spin-relaxometry and translational self-diffusometry, offers atomistic-level insights into drug–surfactant interactions. NOE measurements reveal spatial proximities between drug and surfactant molecules, while relaxometry captures local dynamics and facilitates the estimation of rotational correlation times for both free and bound drug species. Diffusometry probes global translational motion and geometric features, enabling quantification of the bound drug fraction (p_b) and partition coefficient (K), both of which are pertinent to pharmaceutical and chromatographic contexts. Together, these NMR approaches provide an integrated view of structure, dynamics and transport, which is critical for understanding the physicochemical behaviour of drug–surfactant systems. This mini-review summarizes key solution-state NMR techniques, supported by theoretical models and selected applications, for incisive characterisation of these interactions.

Determination of the correct 3D structure of regioisomers and other proton-deficient molecules such as the breitfussin analogue is a very challenging task. In the current work, we present the structural differentiation between the two regioisomeric forms of a spiro compound using anisotropic NMR data measured in graphene oxide derivatized cyclopentylamine liquid crystal. The constitution of the regioisomer was first derived from various 2D isotropic NMR data using CASE software, from which other possible regioisomer was generated. Finally, the correct 3D structure is obtained from the anisotropic NMR data, which is also further corroborated with DP4 and DP4+ analysis. We also investigated one proton-deficient breitfussin structural analogue. Finally, results obtained from the anisotropic NMR and DP4+ analysis were compared.

Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are chronic and complex autoimmune diseases with shared clinical features complicating differential disease diagnosis. Despite similarities, they exhibit distinct pathophysiological mechanisms and disease progression. This study is an attempt to investigate disease-specific metabolic alterations and identify potential biomarkers for differential diagnosis using a nuclear magnetic resonance (NMR)-based serum metabolomics approach. 1D ¹H Carr–Purcell–Meiboom–Gill (CPMG) NMR spectra were recorded, and a total of 35 serum metabolites were quantified using CHENOMX software across SSc, SLE, and healthy control (HC) groups. Multivariate and univariate statistical analyses revealed significant metabolic distinctions between the diseases. SLE is primarily characterized by disruptions in glycolysis, the tricarboxylic acid (TCA) cycle, and oxidative stress, indicating compromised energy metabolism and immune-mediated mitochondrial dysfunction. In contrast, SSc showed distinct perturbations in inositol and amino acid metabolism linked to fibrosis and endothelial dysfunction. Significantly elevated levels of acetate emerged as a key discriminatory metabolite in SSc patients, implying a shift towards enhanced fatty acid oxidation in SSc, potentially fueling fibrotic processes and contributing to the energy demands of chronic inflammation. Specific metabolic ratios (with acetate as the numerator) demonstrated high accuracy in distinguishing SSc from SLE and HC, highlighting their potential as diagnostic biomarkers; including multivariate and multiclass ROC, supported the diagnostic relevance of these markers. The study underscores the metabolic heterogeneity of SLE and SSc, offering new insights and a deeper understanding into their distinct pathological mechanisms and supporting the development of biomarker-based strategies for improved diagnosis, classification, and personalized therapeutic approaches.