Magnetic Resonance Spectroscopy Research Articles

Water Sorption on Isoreticular CPO-27-Type MOFs: From Discrete Sorption Sites to Water-Bridge-Mediated Pore Condensation

Pore engineering is commonly used to alter the properties of metal–organic frameworks. This is achieved by incorporating different linker molecules (L) into the structure, generating isoreticular frameworks. CPO-27, also named MOF-74, is a prototypical material for this approach, offering the potential to modify the size of its one-dimensional pore channels and the hydrophobicity of pore walls using various linker ligands during synthesis. Thermal activation of these materials yields accessible open metal sites (i.e., under-coordinated metal centers) at the pore walls, thus acting as strong primary binding sites for guest molecules, including water. We study the effect of the pore size and linker hydrophobicity within a series of Ni2+-based isoreticular frameworks (i.e., Ni2L, L = dhtp, dhip, dondc, bpp, bpm, tpp), analyzing their water sorption behavior and the water interactions in the confined pore space. For this purpose, we apply water vapor sorption analysis and Fourier transform infrared spectroscopy. In addition, defect degrees of all compounds are determined by thermogravimetric analysis and solution 1H nuclear magnetic resonance spectroscopy. We find that larger defect degrees affect the preferential sorption sites in Ni2dhtp, while no such indication is found for the other materials in our study. Instead, strong evidence is found for the formation of water bridges/chains between coordinating water molecules, as previously observed for hydrophobic porous carbons and mesoporous silica. This suggests similar sorption energies for additional water molecules in materials with larger pore sizes after saturation of the primary binding sites, resulting in more bulk-like water arrangements. Consequently, the sorption mechanism is driven by classical pore condensation through H-bonding anchor sites instead of sorption at discrete sites.

Simultaneous assessment of cerebral glucose and oxygen metabolism and perfusion in rats using interleaved deuterium (2H) and oxygen-17 (17O) MRS.

Cerebral glucose and oxygen metabolism and blood perfusion play key roles in neuroenergetics and oxidative phosphorylation to produce adenosine triphosphate (ATP) energy molecules in supporting cellular activity and brain function. Their impairments have been linked to numerous brain disorders. This study aimed to develop an in vivo magnetic resonance spectroscopy (MRS) method capable of simultaneously assessing and quantifying the major cerebral metabolic rates of glucose (CMRGlc) and oxygen (CMRO2) consumption, lactate formation (CMRLac), and tricarboxylic acid (TCA) cycle (VTCA); cerebral blood flow (CBF); and oxygen extraction fraction (OEF) via a single dynamic MRS measurement using an interleaved deuterium (2H) and oxygen-17 (17O) MRS approach. We introduced a single-loop multifrequency radio-frequency (RF) surface coil that can be used to acquire proton (1H) magnetic resonance imaging (MRI) or interleaved low-γ X-nuclei 2H and 17O MRS. By combining this RF coil with a modified MRS pulse sequence, 17O-isotope-labeled oxygen gas inhalation, and intravenous 2H-isotope-labeled glucose administration, we demonstrate for the first time the feasibility of simultaneously and quantitatively measuring six important physiological parameters, CMRGlc, CMRO2, CMRLac, VTCA, CBF, and OEF, in rat brains at 16.4T. The interleaved 2H-17O MRS technique should be readily adapted to image and study cerebral energy metabolism and perfusion in healthy and diseased brains.

Synthesis, Analytical Characterization, and Human CB1 Receptor Binding Studies of the Chloroindole Analogues of the Synthetic Cannabinoid MDMB-CHMICA

Synthetic cannabinoids (SCs) are one of the largest groups of new psychoactive substances (NPSs). However, the relationship between their chemical structure and the affinity to human CB1 receptors (hCB1), which mediates their psychotropic activity, is not well understood. Herein, the synthesis of the 2-, 4-, 5-, 6- and 7-chloroindole analogues of the synthetic cannabimimetic MDMB-CHMICA, along with their analytical characterization via ultraviolet–visible (UV/VIS), infrared (IR), nuclear magnetic resonance (NMR) spectroscopy, and mass spectrometry, is described. Furthermore, all five derivatives of MDMB-CHMICA were analyzed for their hCB1 binding affinities. Chlorination at position 4 and 5 of the indole core reduced the binding affinity compared to MDMB-CHMICA, while the test compounds chlorinated in positions 2, 6, and 7 largely retained their binding affinities relative to the non-chlorinated parent compound.

Integrated Carbon Dioxide Capture by Amines and Conversion to Methane on Single-Atom Nickel Catalysts.

Direct electrochemical reduction of carbon dioxide (CO2) capture species, i.e., carbamate and (bi)carbonate, can be promising for CO2 capture and conversion from point-source, where the energetically demanding stripping step is bypassed. Here, we describe a class of atomically dispersed nickel (Ni) catalysts electrodeposited on various electrode surfaces that are shown to directly convert captured CO2 to methane (CH4). A detailed study employing X-ray photoelectron spectroscopy (XPS) and electron microscopy (EM) indicate that highly dispersed Ni atoms are uniquely active for converting capture species to CH4, and the activity of single-atom Ni is confirmed using control experiments with a molecularly defined Ni phthalocyanine catalyst supported on carbon nanotubes. Comparing the kinetics of various capture solutions obtained from hydroxide, ammonia, primary, secondary, and tertiary amines provide evidence that carbamate, rather than (bi)carbonate and/or dissolved CO2, is primarily responsible for CH4 production. This conclusion is supported by 13C nuclear magnetic resonance (NMR) spectroscopy of capture solutions as well as control experiments comparing reaction selectivity with and without CO2 purging. These findings are understood with the help of density functional theory (DFT) calculations showing that single-atom nickel (Ni) dispersed on gold (Au) is active for the direct reduction of carbamate, producing CH4 as the primary product. This is the first example of direct electrochemical conversion of carbamate to CH4, and the mechanism of this process provides new insight on the potential for integrated capture and conversion of CO2 directly to hydrocarbons.

Sources of variation in the serum metabolome of female participants of the HUNT2 study.

The aim of this study was to explore the intricate relationship between serum metabolomics and lifestyle factors, shedding light on their impact on health in the context of breast cancer risk. Detailed metabolic profiles of 2283 female participants in the Trøndelag Health Study (HUNT study) were obtained through nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS).We show that lifestyle-related variables can explain up to 30% of the variance in individual metabolites. Age and obesity were the primary factors affecting the serum metabolic profile, both associated with increased levels of triglyceride-rich very low-density lipoproteins (VLDL) and intermediate-density lipoproteins (IDL), amino acids and glycolysis-related metabolites, and decreased levels of high-density lipoproteins (HDL). Moreover, factors like hormonal changes associated with menstruation and contraceptive use or education level influence the metabolite levels.Participants were clustered into three distinct clusters based on lifestyle-related factors, revealing metabolic similarities between obese and older individuals, despite diverse lifestyle factors, suggesting accelerated metabolic aging with obesity. Our results show that metabolic associations to cancer risk may partly be explained by modifiable lifestyle factors.

HRMAS NMR for Studying Solvent-Induced Mobility of Polymer Chains and Metallocene Migration Into Low-Density Polyethylene (LDPE).

HRMAS (high-resolution magic angle spinning) nuclear magnetic resonance (NMR) spectroscopy of low-density polyethylene (LDPE) affords 1H and 13C NMR spectra with superior resolution. For acquiring HRMAS NMR spectra, the polymer is first swollen with representative organic solvents. Then, the samples are measured with a conventional solid-state NMR spectrometer in the wideline mode or at the low spinning speed of 2 kHz. Anisotropic interactions like CSA (chemical shift anisotropy) and dipolar interactions are reduced due to the additional mobility of the polymer chains in the presence of the solvent within the polymer network. The combined effect of this mobility and MAS leads to signals with substantially reduced halfwidths as compared to classic MAS of the dry polymer. With HRMAS, all signals of the polymer become visible, and the spectra can be used for a quick and easy assessment of the polymer swelling behavior in diverse solvents. Being able to characterize polymers on the molecular level, and identifying the solvents that penetrate the polymer network best, enables the study of post-synthesis modifications of the polymers. It is demonstrated by paramagnetic HRMAS that the metallocene nickelocene (Cp2Ni) penetrates the LDPE network along with the solvent and is homogeneously dispersed in the polymer. SEM images prove that the structure of the polymer is not altered by the presence of a solvent and Cp2Ni. The impact of the paramagnetic Cp2Ni on the 1H signal halfwidth and T1 time of LDPE is studied. HRMAS allows a quick assessment of metal complexes regarding their ability to penetrate the LDPE network and therefore supports future studies of catalytic polymer degradation.

Surface Coordination Chemistry of Graphitic Carbon Nitride from Ag Molecular Probes.

Graphitic carbon nitride (g-C3N4) has gained significant attention for its catalytic properties,especiallyin the development of Single Atom Catalysts (SACs).However,the surface chemistry underlying the formation of these isolated metal sites remains poorly understood.In thisstudyweemploy Surface OrganoMetallic Chemistry (SOMC) together with advanced microscopic and spectroscopic techniquesfor an in-depth analysis of functionalizedg-C3N4materials, where tailored organosilver probe molecules are used to monitor surface processes and characterize resulting surface species. Amulti-technique approach-including high-angle annular dark-field scanning transmission electron microscopy(HAADF-STEM), X-ray absorption spectroscopy (XAS), and multinuclear solid-state Nuclear Magnetic Resonance spectroscopy (ssNMR),coupled with density functional theory (DFT) calculations- identifies three primary surface speciesin Ag-functionalized g-C3N4:bis-NHC-Ag+, dispersed Ag+sites, andphysisorbed molecular precursor.These findings highlight a dynamic grafting process and provide insights into the surface coordination chemistryof functionalizedg-C3N4materials.

A novel automated pipeline to assess MR spectroscopy quality control: Comparing current standards and manual assessment.

The absence of a consensus data quality control (DQC) process inhibits the widespread adoption of MR spectroscopy. Poor DQC can lead to unreliable clinical diagnosis and irreproducible research conclusions. Currently, manual visual assessment or the standard quantitative metrics of signal-to-noise, linewidth, and model fit are used as classifiers, but these measures may not be sufficient. To supplement standard metrics, this paper proposes a novel automated DQC pipeline named Visual Evaluative Control Technology Of Resonance Spectroscopy (VECTORS). Manual DQC ratings were conducted on 7180 spectra obtained from 110 young adults using short-echo chemical shift imaging at 3Tesla. Four reviewers conducted manual ratings on the presence of artifacts and location of metabolites. The ratings were labor intensive, taking over 180hours. VECTORS was developed to quantify their DQC criteria, detecting artifacts that present as duplicate peaks, vertical shifts, and glutamine+glutamate and myoinositol peak shapes. Run on the same data using a standard laptop, VECTORS only took 2hours. The manual ratings were not monotonic to the standard quantitative metrics. VECTORS correctly flagged spectra that the manual ratings missed. VECTORS accurately flagged an additional 126 poor DQ spectra that consensus cutoffs of the standard quantitative metrics deemed good DQ. Standard quantitative metrics may not account for all DQC artifacts as they are not monotonic to the manual ratings. However, manual ratings are labor intensive, subjective, and irreproducible. VECTORS addresses these issues and should be used in conjunction with standard quantitative metrics.

31P Nuclear Magnetic Resonance Spectroscopy for Monitoring Organic Reactions and Organic Compounds.

31P NMR spectroscopy is a consolidated tool for the characterization of organophosphorus compounds and, more recently, for reaction monitoring. The evolution of organic synthesis, mainly due to the combination of elaborated building blocks with enabling technologies, generated great challenges to understand and to optimize the synthetic methodologies. In this sense, 31P NMR experiments also became a routine technique for reaction monitoring, accessing products and side products yields, chiral recognition, kinetic data, intermediates, as well as basic organic parameters, such as acid-base and hydrogen-bonding. This review deals with these aspects demonstrating the essential role of the 31P NMR spectroscopy. The recent publications (the last ten years) will be explored, discussing the experiments of 31P NMR and the strategies accomplished to detect and/or quantify distinct organophosphorus molecules, approaching reaction mechanism, stability, stereochemistry, and the utility as a probe.

Composition and Biological Activity of Flavonoid-containing Fractions of an Extract from Gratiola officinalis L.

Gratiola officinalis L. (hedge hyssop), a medicinal plant of the Scrophulariaceae family, has diuretic, purgative, and vermifuge properties. It is used as a herbal tea to treat chronic gastroenteritis, renal colic, jaundice, and intestinal worms. Previously, we have found that an extract from G. officinalis is nontoxic and has antitumor, antioxidant, antimicrobial, antiinflammatory, anticachexic, and other properties. Our aims in this study were to separate the G. officinalis extract into individual fractions, to identify the most biologically active fractions, and to examine the chemical composition of these fractions and their biological activity toward A498 renal carcinoma cells. The G. officinalis extract was fractionated by reversed-phase high-performance liquid chromatography, and each fraction was tested for antitumor activity. The active fractions were characterized by UV-visible electron spectral analysis, circular dichroism analysis, Fourier transform infrared spectroscopy, high-performance liquid chromatography, electrospray ionization tandem mass spectrometry, and nuclear magnetic resonance spectroscopy. Two antitumor-active fractions of a flavonoid nature were isolated and chromatographically purified. On the basis of the nuclear magnetic resonance data, the aglycone fragment of the main component of one fraction was found to be structured as 2-(3,4-dimethoxyphenyl)-7-hydroxychroman-4-one, or 3',4'-dimethoxy-7- hydroxyflavanone. The antitumor effect of the most active fraction containing 7-O-glucoside of apigenin, glycoside 7,3'-di-O-luteolin and trace amounts of eupatilin against renal carcinoma A498 cells was manifested in its cytotoxic, cytostatic, apoptotic and autophagosomal activities. In addition, we found 3-(1-2)-glucoside of soyaspogenol B, which is a pentacyclic triterpenoid in the structure.

Role of Hydroxyl Groups in Zn-containing Nanosized MFI Zeolite for the Photocatalytic Oxidation of Methane.

The effective conversion of methane to a mixture of more valuable hydrocarbons and hydrogen under mild conditions is a significant scientific and practical challenge. Here, we synthesized Zn-containing nanosized MFI zeolite for direct oxidation of methane in the presence of H2O and air. The presence of the surface hydroxyl groups on nanosized MFI-type zeolite and their significant reduction in the Zn-containing nanosized MFI zeolite were confirmed with Infrared Fourier Transform (FTIR) spectroscopy. Incorporation of zinc atoms into the framework of nanosized MFI zeolite is revealed by Nuclear Magnetic Resonance, X-ray Diffraction and UV-Vis Spectroscopy. Unexpectedly, pure silica MFI zeolite exhibited the highest photocatalytic performance. Our findings demonstrated that large number of isolated silanol groups and silanol nests increase the formation of ⋅OH, and enhance the productivity of oxygenate compounds and C2H6, while the Zn incorporated into the zeolite framework or attached to the silanol nests of the nanosized zeolites are less efficient. A mechanism of photocatalytic methane oxidation is proposed. These findings provide insights into the development of active nanosized zeolite photocatalysts with an extended amount of surface hydroxyl groups that can play a key role in photocatalytic methane conversion.

Novel Photobase Generators Derived from Proazaphosphatrane–Aryl Borate for High‐Pressure Mercury Lamp Lithography

AbstractHerein, novel borate‐type photobase generators (PBGs) that generate a proazaphosphatrane known as Verkade's base (2,8,9‐triisobuthyl‐2,5,8,9‐tetraaza‐1‐phosphabicyclo[3.3.3]undecane (TTP)) were developed for photopatterning using a high‐pressure mercury lamp. Eight PBGs were synthesized, each featuring distinct borate substituents: phenyl, p‐fluorophenyl, p‐tolyl, p‐methoxyphenyl, m‐fluoro‐p‐methylphenyl, 4‐biphenyl, 2‐naphthyl, and 6‐methoxy‐2‐naphthyl. The relation between these substituents and their light absorption characteristics was analyzed via ultraviolet–visible spectroscopy and time‐dependent density functional theory calculations. The PBG with the 6‐methoxy‐2‐naphthylborate group (TTP–tetrakis[2‐(6‐methoxynaphthyl)]borate (TTP–TMNB)) demonstrated substantial light absorption near 365 nm (the i‐line of the high‐pressure mercury lamp), generating approximately 60 % of the corresponding TTP in deuterated tetrahydrofuran (THF) upon exposure to 650 mJ/cm2, as confirmed via 1H nuclear magnetic resonance spectroscopy. To evaluate its photolithographic potential, TTP–TMNB was mixed with epoxy resin (jER1001) and a poly(methacrylic acid)‐co‐poly(methyl methacrylate) copolymer (PMA1.6‐co‐PMMA100) in THF. The resulting mixture was spin‐coated onto a silicon wafer and irradiated with the i‐line through a photomask to create a negative‐tone image. The sensitivity and contrast of this photopolymer system were measured to be 45 mJ/cm2 and 1.0, respectively; moreover, a clear 10‐μm negative‐tone resolution was achieved.

Structural and Textural Characteristics of Municipal Solid Waste Incineration Bottom Ash Subjected to Periodic Seasoning

The objective of this study was to determine the structural and textural description of municipal solid waste incineration (MSWI) bottom ash that was subjected to a six-month seasoning process. Bottom ash samples, with a particle size fraction of 0.063–0.1 mm, were seasoned in a closed landfill and collected for laboratory analyses at monthly intervals. The research focused on determining the structural parameters, using methods such as nuclear magnetic resonance spectroscopy (1H NMR), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), ultraviolet-visible spectroscopy (UV-Vis), and the textural parameters, using low-pressure nitrogen adsorption (LPNA) at −196.15 °C. The analyses of the porous structure of the bottom ash samples revealed differences in texture of ASH 1 to ASH 6, specifically in the pore volume (micro- and mesopores), specific surface area, and pore size distribution. Changes in the structural and porous characteristics of the samples were attributed to the duration of the seasoning process. The results of the structural analysis of the bottom ash suggest its application in the concrete industry, potentially enhancing the long-term mechanical strength of concrete. The results of the textural analysis indicate the possible use of MSWI bottom ash in environmental applications, as the internal surface area could be further developed.

Bio-based sulfonated surfactants with high Ca2+ tolerance in detergent formulations

The use of calcium-resistant surfactants in household and industrial washing applications may simplify the formulation composition of laundry and therefore reduce costs. A series of bio-based surfactants, N-alkyl furfuryl methylamine sulfonates (AFMS), was developed from the biomass-derived furfural and aliphatic amines by a simple and effective method. The structure of these bio-based surfactants was characterized by gas chromatography–mass spectrometry, liquid chromatography–mass spectrometry and 1H nuclear magnetic resonance spectroscopy. These bio-based surfactants demonstrated low surface tension, high emulsification, and high decontamination efficiency. Meanwhile, the AFMS surfactants exhibited excellent calcium resistance, maintaining micelle stability in Ca2+up to 2.16 × 104 mg/L and the solution clarification in Ca2+up to 7.21 × 104 mg/L. Furthermore, the AFMS surfactants had a stable decontamination effect in hard water. The wetting ability, foaming ability, toxicity, and biodegradability parameters were also evaluated. Therefore, the AFMS surfactants synthesized in this work could be applied as a more efficient and promising bio-based surfactant candidate for application in household and industrial washing.

Rebalance the Inhibitory System in the Elderly Brain: Influence of Balance Learning on GABAergic Inhibition and Functional Connectivity

ABSTRACTAging involves complex processes that impact the structure, function, and metabolism of the human brain. Declines in both structural and functional integrity along with reduced local inhibitory tone in the motor areas, as indicated by reduced γ‐aminobutyric acid (GABA) levels, are often associated with compromised motor performance in elderly adults. Using multimodal neuroimaging techniques including magnetic resonance spectroscopy (MRS), diffusion magnetic resonance imaging (MRI), functional MRI as well as transcranial magnetic stimulation to assess short‐interval intracortical inhibition (SICI), this study explores whether these age‐related changes can be mitigated by motor learning. The investigation focused on the effects of long‐term balance learning (3 months) on intracortical inhibition, metabolism, structural, and functional connectivity in the cortical sensorimotor network among an elderly cohort. We found that after 3 months of balance learning, subjects significantly improved balance performance, upregulated sensorimotor cortical GABA levels and ventral sensorimotor network functional connectivity (VSN‐FC) compared to a passive control group. Furthermore, correlation analysis suggested a positive association between baseline VSN‐FC and balance performance, between baseline VSN‐FC and SICI, and between improvements in balance performance and upregulation in SICI in the training group, though these correlations did not survive the false discovery rate correction. These findings demonstrate that balance learning has the potential to counteract aging‐related decline in functional connectivity and cortical inhibition on the “tonic” (MRS) and “functional” (SICI) level and shed new light on the close interplay between the GABAergic system, functional connectivity, and behavior.

Plasma proteomic signatures of liver steatosis and fibrosis in people living with HIV: a cross-sectional study

Insights into the mechanisms driving metabolic dysfunction-associated steatotic liver disease (MASLD) in people living with HIV (PLHIV) remain limited. Plasma proteomics holds promise for biomarker discovery and the elucidation of biological mechanisms. We performed cross-sectional analyses on data from 1036 virally suppressed PLHIV using antiretroviral treatment (ART) from the Dutch multi-centre 2000HIV cohort. Participants underwent transient elastography to assess liver steatosis (controlled attenuation parameter (CAP)≥263dB/m) and -fibrosis (liver stiffness measurement (LSM)≥7.0kPa). Plasma protein concentrations (n=2367) (Olink® Explore Panel) were compared between PLHIV with vs. without liver steatosis and PLHIV with vs. without fibrosis. Enriched pathways (using GO, KEGG and Reactome libraries) and correlations with clinical characteristics wereassessed, and analyses were stratified by BMI category. In addition, concentrations of 242 proteins werecompared between individuals ("controls") with and without liver steatosis (ratio of methylene:methylene and water >5.6% on magnetic resonance spectroscopy) from a separate cohort (300-OB), all having a BMI >26kg/m2. Steatosis and fibrosis were associated with 67/2367 (2.2%) and 17/2367 (0.7%) differentially expressed proteins (DEP), respectively, enriched in mostly metabolic pathways. Immunoglobulin superfamily member 9 (IGSF9) was amongst the top DEP associated with both steatosis and fibrosis. Stratifying by BMI revealed 8/2367 DEP associated with steatosis in lean- and 12/2367 DEP in overweight/obese individuals, with two shared DEP (IGSF9 and GHR). Conversely, protein signatures of overweight/obese PLHIV (32/242 DEP) and overweight/obese HIV-uninfected individuals (32/242 DEP) exhibited substantial overlap with 16 shared DEP. Notably, DEP correlated with HIV characteristics in lean individuals but not in overweight/obese PLHIV. Lean and overweight/obese PLHIV exhibit distinct proteomic signatures associated with liver steatosis, with the former being more strongly correlated with HIV-specific factors and ART. In addition, we identified a protein, IGSF9, strongly related to liver fibrosis and steatosis across BMI categories. The 2000HIV study is funded by ViiV Healthcare.

Does concomitant diazepam and ethanol use modulate age-related cognitive decline in mice?

BackgroundConcomitant use of alcohol and benzodiazepines are described among elderly, raising concerns about their combined impact on memory. We aimed to evaluate the long-term impact of chronic diazepam use associated with ethanol intoxication on memory in aging mice. MethodsTwelve-month-old male C57BL6 mice were assigned into 4 groups: ethanol (OH), diazepam (DIA), diazepam + ethanol (DOH) and control (CTL). For 16 weeks, ethanol was available ad libitum and diazepam was mixed with food. Behavioral testing, performed during and after treatment cessation included working memory and visual recognition memory assessment. The second session was implemented with spatial reference learning and memory assessment in the Barnes maze test. In vivo magnetic resonance spectroscopy (MRS) acquisitions were performed to quantify hippocampal metabolites during and after cessation treatment. ResultsDuring treatment, visual recognition memory was significantly different between groups with the DIA group exhibiting the worst performance. MRS acquisition highlighted higher glutamate and choline levels in OH and DOH groups in comparison to CTL and DIA groups. After treatment wash-out, there was no difference between in the different memories evaluated. Only the learning phase of the spatial reference memory test differed significantly with worst performance in OH groups. Three months after treatment cessation, there was no remanent effect of diazepam + ethanol on hippocampal metabolites changes. ConclusionsWe did not evidence additive effect of ethanol and diazepam on memory and hippocampal metabolite levels. The disturbances observed during treatment were no remanent, highlighting the benefits of discontinuing these substances.

Regulation of Microlocalization of Antioxidants by Surfactant Micelles in Oil-in-Water Emulsions.

The mass transport effect of aqueous micelles on antioxidants and oxidation products in emulsions may alter the rate, degree, and pathway of lipid oxidation. In this study, the dynamic mass transport of oxidation products and endogenous tocopherol during storage at different micelle concentrations was monitored by UV-vis spectrophotometry and high-performance liquid chromatography. Furthermore, the microlocalization of tocopherol in micelles was investigated using 1H nuclear magnetic resonance and nuclear Overhauser effect spectroscopy, fluorescence measurements, and molecular dynamics simulation. It was demonstrated that high-concentration micelles enhanced the emulsion stability by promoting the mass transport of hydroperoxides and endogenous antioxidants. The enhancement of micelles was a superposition effect of concentration, interaction sites, and binding force between tocopherols and Tween 20 molecules. Tween 20 concentration-induced favorable changes of microlocalization of tocopherol and dynamic mass transport demonstrated a new integrated perspective to control lipid oxidation.

NMR coupled with multivariate data analysis for monitoring the degradation of a formulated therapeutic monoclonal antibody.

The function of a protein is directly coupled to its higher-order structure (HOS). Deviations in this critical quality attribute (CQA) may be linked to a decrease in the efficacy and/or safety of the final therapeutic product. High-resolution nuclear magnetic resonance (NMR) spectroscopy has been recently highlighted for protein HOS characterization, thanks to its ability to capture small changes at the molecular and structural levels (primary, secondary, tertiary and quaternary). The present study was carried out to demonstrate the ability of NMR (1D 1H and 2D 1H-13C experiments) coupled with multivariate data analysis (PCA and PLS regression) to monitor the degradation of a formulated mAb-like protein and for the simultaneous quantification of related CQAs, i.e., potency, purity and impurities (aggregates and fragments). The results indicate that this approach could be applied to mitigate product quality risks during development, manufacturing and stability studies of mAb therapeutics.

Bioassay-guided isolation and in Silico characterization of cytotoxic compounds from Hemimycale sp. Sponge targeting A549 lung cancer cells

Bioassay-guided fractionation approach led to identification of two novel compounds; (4-(hydroxymethyl)-3-methoxy-1H-pyrazol (1) and mycalene (2), alongside with four known metabolites; octadecane (3), hexatriacontane (4), 1-heneicosanol (5) and heptatriacontanoic acid (6) from the Red Sea marine sponge Hemimycale sp. The ethyl acetate fraction showed a noticeable cytotoxic activity against the lung cancer cell line (A549) with IC50 value of 75.54 µg/ mL. Structural elucidation was achieved using a combination of 1D and 2D nuclear magnetic resonance (NMR) spectroscopy and high-resolution electrospray ionization-mass spectrometry (HR-ESI-MS). To elucidate the potential mechanism of action behind the cytotoxic effects against lung cancer, a multi-faceted approach combining in silico network pharmacology, experimental validation, and molecular docking studies were employed. Both compounds, designated as 1 and 2, demonstrated significant binding affinities to predicted target proteins, with docking scores of -4.789 and − 4.421 kcal/mol, respectively. These results lay the groundwork for further investigation into the therapeutic potential of these novel compounds from Hemimycale sp. as promising candidates for lung cancer treatment.