Magnetic Resonance Spectroscopy Methods Research Articles

IN VITRO CYTOTOXIC ACTIVITIES OF PLATINUM(II) COMPLEXES CONTAINING 1H-BENZO[d]IMIDAZOLE AND 1H-1,3-DIAZOLE DERIVATIVES

Objective: This study aimed to synthesize and evaluate the cytotoxic activities of four platinum(II) complexes with 2-substituted or nonsubstituted 1H-benzo[d]imidazole and 1H-1,3-diazole derivatives as carrier ligands (L1-L4), which may have potent cytotoxic activity and low side effects. Material and Method: K1-K4 complexes were synthesized by heating and mixing K2PtCl4 and the appropriate L1-L4. The chemical structures of K1-K4 were elucidated by Infrared and 1H Nuclear Magnetic Resonance spectroscopic methods. In vitro, cytotoxic effects of K1-K4 complexes against prostate (DU-145), endometrial adenocarcinoma (Ishikawa), and breast cancer (MCF-7) cell lines were tested by the MTT method. Result and Discussion: According to the IC50 values of the tested cell lines, K1 and K2 derivatives bearing unsubstituted 1H-benzo[d]imidazole (L1) and 1H-1,3-diazole (L2) were found to be the most effective compounds among these synthesized complexes.

Position-specific carbon stable isotope analysis of glyphosate: isotope fingerprinting of molecules within a mixture.

Glyphosate [N-(phosphonomethyl) glycine] is a widely used herbicide and a molecule of interest in the environmental sciences, due to its global use in agriculture and its potential impact on ecosystems. This study presents the first position-specific carbon isotope (13C/12C) analyses of glyphosates from multiple sources. In contrast to traditional isotope ratio mass spectrometry (IRMS), position-specific analysis provides 13C/12C ratios at individual carbon atom positions within a molecule, rather than an average carbon isotope ratio across a mixture or a specific compound. In this work, glyphosate in commercial herbicides was analyzed with only minimal purification, using a nuclear magnetic resonance (NMR) spectroscopy method that detects 1H nuclei with bonds to either 13C or 12C, and isolates the signals of interest from other signals in the mixture. Results demonstrate that glyphosate from different sources can have significantly different intramolecular 13C/12C distributions, which were found to be spread over a wide range, with δ13C Vienna Peedee Belemnite (VPDB) values of -28.7 to -57.9‰. In each glyphosate, the carbon with a bond to the phosphorus atom was found to be depleted in 13C compared to the carbon at the C2 position, by 4 to 10‰. Aminomethylphosphonic acid (AMPA) was analyzed for method validation; AMPA contains only a single carbon position, so the 13C/12C results provided by the NMR method could be directly compared with traditional isotope ratio mass spectrometry. The glyphosate mixtures were also analyzed by IRMS to obtain their average 13C/12C ratios, for comparison with our position-specific results. This comparison revealed that the IRMS results significantly disguise the intramolecular isotope distribution. Finally, we introduce a 31P NMR method that can provide a position-specific 13C/12C ratio for carbon positions with a C-P chemical bond, and the results obtained by 1H and 31P for C3 carbon agree with one another within their analytical uncertainty. These analytical tools for position-specific carbon isotope analysis permit the isotopic fingerprinting of target molecules within a mixture, with potential applications in a range of fields, including the environmental sciences and chemical forensics.

Update on chiral recognition mechanisms in separation science.

The stereospecific analysis of chiral molecules is an important issue in many scientific fields. In separation sciences, this is achieved via the formation of transient diastereomeric complexes between a chiral selector and the selectand enantiomers driven by molecular interactions including electrostatic, ion-dipole, dipole-dipole, van der Waals or π-π interactions as well as hydrogen or halogen bonds depending on the nature of selector and selectand. Nuclear magnetic resonance spectroscopy and molecular modeling methods are currently the most frequently applied techniques to understand the selector-selectand interactions at a molecular level and to draw conclusions on the chiral separation mechanism. The present short review summarizes some of the recent achievements for the understanding of the chiral recognition of the most important chiral selectors combining separation techniques with molecular modeling and/or spectroscopic techniques dating between 2020 and early 2024. The selectors include polysaccharide derivatives, cyclodextrins, macrocyclic glycopeptides, proteins, donor-acceptor type selectors, ion-exchangers, crown ethers, and molecular micelles. The application of chiral ionic liquids and chiral deep eutectic solvents, as well as further selectors, are also briefly addressed. A compilation of all published literature on chiral selectors has not been attempted.

Proton magnetic resonance spectroscopy in children with some neurological and mental disorders accompanied by mental and speech development delay: a prospective study

Proton magnetic resonance spectroscopy in children with some neurological and mental disorders accompanied by mental and speech development delay: a prospective study

Design, synthesis, and investigation of biological activities of new triazole derivatives with antifungal effect

Fungal infections pose a significant threat to both morbidity and mortality, especially in immunocompromised patients, notably those with conditions such as AIDS. In the last two decades, the incidence of such fungal infections has increased significantly, especially due to Candida species. The increasing incidence of life-threatening fungal infections has increased the need for new drugs to treat these infections. In this study, 10 novel oxadiazole-triazole hybrid compounds were synthesized. Analysis of the obtained compounds provided by 1H NMR (proton nuclear magnetic resonance), 13C NMR (carbon nuclear magnetic resonance) spectroscopic methods and HRMS (high resolution mass spectrometry) spectrometric method. The inhibition effects of the obtained compounds on the 14α-demethylase enzyme were investigated. Among the synthesized compounds, 4a (contains 4-methyl substituent), 4c (contains 4-cyano substituent), 4d (contains 4-nitro substituent), 4e (contains 4-fluoro substituent), 4 g (contains 4‑bromo substituent) and 4j (contains 3,4-dichloro substituent) coded compounds were useful against C. parapsilosis strain; Compounds 4c, 4f and 4 g also showed significant inhibitory effect against C. albicans strain. Within the scope of the study, the interactions of 14α-demethylase enzyme active site and our compound were elucidated by molecular modeling and molecular dynamics studies. Binding points were determined by docking studies for the selected compounds in enzyme active site. The strongest interaction with 14α-demethylase enzyme active sites was observed in 4c and 4 g coded compounds.

Neurometabolic activity in the thalamic and frontal cortex and cognitive functions in adolescents with generalized epileptic syndromes

The study aimed to analyse the mutual correlations between the metabolic activity of the brain evaluated by the magnetic resonance spectroscopy method (MRS) and intelligence and cognitive functions in adolescents with idiopathic generalised epilepsies (IGE). The focus of the study was placed on the activity of the thalamus and frontal cortex.Twenty newly diagnosed patients with juvenile absence epilepsy (JAE) and juvenile myoclonic epilepsy (JME) were included in the study. Adolescents underwent primary structural neuroimaging (1.5T) and advanced evaluation of the frontal cortex and thalamus by MRS. Concentrations of N-acetyl aspartate (NAA), creatine plus phosphocreatine (Cr) and choline (Cho) were measured and were expressed as ratios of NAA/Cr, NAA/Ch and NAA/Cr+Ch. Patients also completed a panel of IQ and cognitive tests (e.g., FePsy Battery – classification test, verbal fluency test, RAVLT memory test). The correlation between the level of metabolites and the results of intellectual and cognitive tests was examined.Strong correlations were found between IQ and some cognitive functions and metabolic ratios in the IGEs group. Overall the patients whose NAA/Cr, NAA/Ch, NAA/Cr+Ch ratios were lower, obtained worse results in IQ and in some of the neuropsychological tests.The metabolite activity in the thalamus and frontal cortex impacts the results of neuropsychological tests in the group of patients with IGE.

Abstract 5775: Structure and dynamics of the major PDGFR-β oncogene promoter G-quadruplex and insights into its cellular regulation

Abstract Overexpression of the receptor tyrosine kinase PDGFR-β promotes cancer growth and metastasis. PDGFR-β is a validated cancer target but PDGFR-β kinase inhibitors suffer from lack of selectivity and side effects. G-quadruplexes are an exciting class of non-B DNA secondary structures with functional importance. The G-quadruplex formed in the PDGFR-β promoter is a transcription repressor and targetable by small molecules. Therefore, the PDGFR-β promoter G-quadruplex is an attractive molecular target for anticancer drugs. Structural information of the PDGFR-β promoter G-quadruplex is crucial for understanding its cellular function and rational drug design. Herein, we used nuclear magnetic resonance (NMR) spectroscopy and biophysical methods to determine the structure and dynamics of the major G-quadruplex formed in the human PDGFR-β promoter. Unlike canonical G-quadruplexes formed by four runs of three continuous guanines (G), the major PDGFR-β G-quadruplex adopts a novel broken-strand structure where a two-G segment is continued by a non-adjacent guanine. The broken-strand G-quadruplex has a vacancy-G-tetrad (vG4) which is filled-in intramolecularly by a distal guanine. Interestingly, we discovered that the major PDGFR-β G-quadruplex is a novel mixture of two equilibrating broken-strand G-quadruplexes. Both structures adopt overall parallel-stranded folding with all 1-nt chain-reversal loops. However, a different 3’-filled-in guanine is delivered by a lateral loop, which forms structurally similar hairpin with a unique capping G-G base-pair. The formation of the equilibrating broken-strand G-quadruplexes and unique capping structures are both specific to the PDGFR-β promoter sequence. Intriguingly, the observed dynamic equilibrium between the two co-existing structures with different intramolecular fill-in guanines indicates a novel vG4 intermediate, which could be filled-in by cellular guanine metabolites such as cGMP. Therefore, our study provides critical insights into how the dynamics of the major PDGFR-β G-quadruplex lead to vG4 formation and potential regulation of gene transcription by cellular guanine metabolites. The determined molecular structures of the novel broken-strand G-quadruplexes provide a structural basis for rational design of small molecules to specifically target the major PDGFR-β promoter G-quadruplex for cancer therapeutics. Citation Format: Yichen Han, Jonathan Dickerhoff, Danzhou Yang. Structure and dynamics of the major PDGFR-β oncogene promoter G-quadruplex and insights into its cellular regulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5775.

The relationship between oxidative stress markers and 1H-Magnetic resonance spectroscopy findings in obsessive compulsive disorder

IntroductionThe purpose of this study was to examine N-acetyl aspartate (NAA)/creatine (Cr) and glutamate, glutamine, and gamma-aminobutyric acid complex (Glx)/Cr levels in patients with obsessive compulsive disorder (OCD) and healthy controls’ orbitofrontal cortex (OFC) and caudate nucleus (CN) by proton magnetic resonance spectroscopy (1H-MRS) method and to investigate their relationship with oxidative stress markers glutathione peroxidase (GPx) and superoxide dismutase (SOD). MethodsThis study included patients with OCD (n = 25) and healthy controls (n = 25) ranging in age from 18 to 65. We used the ELISA method to evaluate serum SOD and GPx levels. Levels of NAA/Cr and Glx/Cr in the orbitofrontal cortex and caudate nucleus were measured using the 1H-MRS method. ResultsOur study did not detect statistically significant differences in the orbitofrontal cortex Glx/Cr and NAA/Cr levels between the OCD patients and the control group. OCD patients exhibited a decrease in NAA/Cr levels, consistent with impaired neuronal integration, and an increase in Glx/Cr levels, consistent with hyperactivation, in the caudate nucleus compared to the control group. We observed a negative correlation between NAA/Cr levels in the caudate nucleus and the levels of SOD and GPx. ConclusionsOur study is the first to assess CN and OFC together in OCD patients using 3 T MR, investigating the relationship between neurometabolite concentrations and oxidative stress parameters. The negative correlation we observed between NAA/Cr levels and SOD and GPx in the caudate nucleus suggests that increased oxidative stress in this brain region in OCD patients may contribute to impaired neuronal integration and functionality.

New Strategy for the Synthesis of Some Valuable Chiral 1,3-Diols with High Enantiomeric Purity: New Organocatalyst, Asymmetric Aldol Reaction, and Reduction.

Chiral 1,3-diols are highly valuable molecules used in industries such as pharmaceuticals, cosmetics, and agriculture. Therefore, in this study, a new strategy was developed to synthesize enantiomerically pure (>99% ee) 1,3-diols. New chiral 1,3-diols (5a-5q) with high enantiomeric purity were synthesized from aldol products chiral 1,3-keto alcohols (4a-4q), which are aldol products with different structures. Chiral 1,3-keto alcohols (4a-4q) were synthesized by a new asymmetric aldol method in the first step. This method was developed using a new proline-derived organocatalyst (3g) and Cu(OTf)2 as an additive in DMSO-H2O for the first time. Almost >99% ee was obtained using our developed aldol procedure. In the second step, original chiral diols (5a-5q) of high enantiomeric purity were obtained by asymmetric reduction of chiral keto alcohols with chiral oxazaborolidine reagents. In this way, a two-step asymmetric reaction was developed for chiral 1,3-diol enantiomers with high enantiomeric purity. The structures of all the original chiral compounds obtained were elucidated by infrared and nuclear magnetic resonance spectroscopy, mass spectrometry, and elemental analysis methods. Their enantiomeric excesses were determined by the chiral high-performance liquid chromatography method. Both keto alcohols and their corresponding chiral diols synthesized can be used as chiral starting materials and chiral source materials or intermediates in the synthesis of many biologically active molecules, or they can be used as chiral ligands in asymmetric synthesis, serving as organocatalysts.

Novel biologically active paddlewheel-like palladium thiocyanate complex catalyzed cyanation of alkyl bromide utilizing Q-tube system: A green perspective

A novel paddlewheel-like complex of [Pd(SCN)2(3-Acpy)2], (1) was produced at ambient temperature by adding an aqueous solution of palladium chloride to an aqueous acetonitrile solution of 3-acetylpyridine (3-Acpy) and potassium thiocyanate. Elemental analysis, Fourier-transform infrared (FT-IR), ultraviolet–visible (UV–vis), and nuclear magnetic resonance (NMR) spectroscopic methods were used to characterize complex 1 comprehensively. Single crystal X-ray diffraction was used to analyze the crystal structure of complex 1. The palladium atom is bonded to two 3-Acpy ligands and two thiocyanates groups in trans mode giving square planer geometry in complex 1. The discrete units of paddlewheel-like complex 1 through hydrogen bonding extend to form a 3D supramolecular network structure. The synthesized and characterized new palladium complex 1 was utilized as a precatalyst for the cyanation of alkyl bromide using potassium ferrocyanide as a benign cyanide source reagent. The suggested catalytic test reaction under high-pressure conditions via a Q-tube system in green solvent cyclopentyl methyl ether introduced high yields and a short reaction time. Moreover, the cytotoxic activity of complex 1 was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against HePG-2 of liver cancer and MCF7 of breast cancer cell lines. According to the findings, complex 1 has significant strong activity against the cancer cell lines HePG-2 and MCF-7. Additionally, the luminescence spectra of complex 1 were investigated.

Preparation and characterization of the aflatoxin B1 purity certified reference material (GBW (E) 100599)

Aflatoxin B1 (AFB1), the most harmful mycotoxin, is widely distributed in many important foodstuffs, especially in peanuts, maize, and oil products. AFB1 certified reference material (CRM), essential for an accurate and reliable detection, is not easily obtained due to the difficulty of preparing high purity candidate. In this study, the high-purity AFB1 candidate was prepared by the preparative high performance liquid chromatography (Pre-HPLC) after high-yields of AFB1 on the maize medium by Aspergillus flavus. The structure of AFB1 was successively characterized by UV, IR, LC-TOF-MS/MS, 1H NMR, and 13C NMR. According to the principle of ISO 17034: 2016 and ISO guide 35: 2017, the purity of the candidate was accurately determined by the mass balance method (MB) and the quantitative nuclear magnetic resonance spectroscopy method (qNMR), while the homogeneity, long-term stability, short-term stability, and uncertainty were systematically studied by the MB method. Under the optimum conditions, the certified purity value for the AFB1 CRM was 99.53 % with an extended uncertainty of 0.56 % (k = 2, 95 % confidence interval), which was also sufficiently homogeneous and stable for 6 months at 4 °C and −20 °C. After approval by State Administration for Market Regulation, a new AFB1 purity CRM (GBW (E) 100599) was finally prepared. This is the first report for the preparation of a reliable AFB1 purity CRM, benefit for enhancing the accuracy, traceability, and comparability of measurements of AFB1 in various foodstuffs, and finally ensure the food quality and safety.

Effect of fertilizers and growth stimulants on the content of coumarin and its derivatives in the vegetative mass of melilot.

The paper presents the results of determining the content of coumarin and its derivatives in the melilot using nuclear magnetic resonance spectroscopy, including the study of the effect of fertilizers on the quantitative content of coumarin and its derivatives in the composition of the melilot treated by phases using the method of 1H and 13C nuclear magnetic resonance spectroscopy. Based on the results of the nuclear magnetic resonance spectroscopy, the possibility of qualitative and quantitative determination of the content of coumarin and its derivatives isolated from extracts of fertilized melilot was evaluated. The effect of eight preparations on the plant and its concentration in solution on the content of coumarin substances in the Altynbas yellow melilot variety was studied. It was shown that the preparations have a slight effect on the coumarin content in the melilot and, accordingly, on the quality of feed based on it. In the control variant (variant 9), the coumarin proton content was 9.85%, and the maximum coumarin proton content was observed in the variant where BioEnergy was used as fertilizer and amounted to 22.44%.

Experimental Studies of Schiff Base (E)-4-methoxy-2-(((2-phenoxyphenyl)imino)methyl) phenol Compound with Various Spectroscopic Methods

Schiff-based compounds, which represent an important class in the field of organic compounds, form the basis of this research article. This research article aims to investigate the synthesized compound (E)-4-methoxy-2-(((2-phenoxyphenyl) imino) methyl) phenol using experimental methods.FT-IR, UV-Vis, 13C and 1H Nuclear Magnetic Resonance (NMR) Spectroscopy and X-ray diffraction methods were used to elucidate the structural properties of the compound synthesized at the end of chemical processes. The structure solution was carried out from the data obtained as a result of X-ray analysis. According to these results, one of the two compounds in the asymmetric cell completed their formation in the enol-imine form and the other in the keto-amine form. This structural situation, which is rare in the literature, was supported and explained by FT-IR, 13C and 1H Nuclear Magnetic Resonance (NMR) spectroscopy studies.According to the results obtained as a result of UV-Vis spectroscopy, the structure revealed that the enol-imine form was dominant. The reasons for this situation were explained.

Study on the affinity sites of cadmium's binding to ligands by thermodynamics and nuclear magnetic resonance spectroscopy.

The affinity sites of cadmium (Cd(II)) when binding to cysteine (Cys) and glutathione (GSH) were studied via thermodynamics and nuclear magnetic resonance (NMR) spectroscopy methods. The results showed that the Cd(II) binding sites of Cys and GSH were -SH (exothermic), -NH2 (endothermic) and -COOH (endothermic). The thermodynamic behaviour of Cd(II) binding to Cys/GSH in boric acid and HEPES buffers differed, with the former being mainly endothermic and the latter mainly exothermic. It could be inferred that, in the boric acid system, the main binding site of Cd(II) with Cys and GSH is changed from -SH in HEPES to -COOH and -NH2 in boric acid. This was confirmed by the results of NMR experiments of Cd(II) with Cys/GSH. 1D 1H-NMR experiments showed that, after the combination of Cd(II) and Cys, the changes in the chemical shifts and peak strengths of protons near the -SH group for the reaction in HEPES were greater than when boric acid buffer was used. Changes in the chemical shift and peak strength of the -NH2 protons due to the binding of Cd(II) to GSH were evident in the boric acid buffer but not in HEPES. The screening of functional monomers is very important in the process of preparation of cadmium ion-imprinted materials. This research provides important theoretical and experimental guidance for the screening of functional monomers.

Methods for Cultivation of Bacteroides thetaiotaomicron and Analysis of Heme Metabolism by Mass Spectrometry and Spectroscopic Approaches.

Traditional studies of cellular metabolism have relied on the use of radioisotopes. These have clear disadvantages associated with safety and waste generation. Furthermore, detection of the labeled species by scintillation counting provides only a quantification of its presence or absence. The use of stable isotopes, by contrast, allows the application of powerful, orthogonal spectroscopic approaches such as nuclear magnetic resonance spectroscopy (NMR) and various mass spectrometric methods. Using stable isotope labeling to study heme metabolism requires integrating methods for (a) generating the heme in labeled forms, (b) cultivating and quantifying the organism of choice in chemically defined media, to which labeled compounds can be added, (c) recovering cellular components and/or spent growth media, and (d) analyzing these materials for the labeled species using spectroscopic and mass spectrometric methods. These methods are summarized here in the context of Bacteroides thetaiotaomicron, a generallynonpathogenic anaerobe and heme auxotroph.

New 5-Substituted SN38 Derivatives: A Stability Study and Interaction with Model Nicked DNA by NMR and Molecular Modeling Methods.

The new 5-substituted SN-38 derivatives, 5(R)-(N-pyrrolidinyl)methyl-7-ethyl-10-hydroxycamptothecin (1) and its diastereomer 5(S) (2), were investigated using a combination of nuclear magnetic resonance (NMR) spectroscopy and molecular modeling methods. The chemical stability, configuration stability, and propensity to aggregate as a function of concentration were determined using 1H NMR. The calculated self-association constants (Ka) were found to be 6.4 mM-1 and 2.9 mM-1 for 1 and 2, respectively. The NMR experiments were performed to elucidate the interaction of each diastereomer with a nicked decamer duplex, referred to as 3. The calculated binding constants were determined to be 76 mM-1 and 150 mM-1 for the 1-3 and 2-3 complexes, respectively. NMR studies revealed that the interaction between 1 or 2 and the nicked decamer duplex occurred at the site of the DNA strand break. To complement these findings, molecular modeling methods and calculation protocols were employed to establish the interaction mode and binding constants and to generate molecular models of the DNA/ligand complexes.

Synthesis, Characterization, and Single-Crystal X-ray Structures of Refractory Metal Compounds as Precursors for the Single-Source Chemical Vapor Deposition of Metal Nitrides.

The chemical vapor deposition of refractory metal nitrides requires volatile precursors and has previously been achieved by using metal complexes containing a variety of imide ligands. Recently, the 1,4-di-tert-butyl-1,3-diazabutadiene (DAD) adduct of bis(tert-butylimide)dichloridemolybdenum(VI) was shown to be an excellent precursor for the single-source CVD of Mo2N thin films. Leveraging the success of this work, we prepared chromium and tungsten compounds with the same framework. Additionally, the framework has been modified slightly to allow the isolation of mono(tert-butylimide)trichloride complexes of vanadium, niobium, tantalum, and molybdenum(V) to extend the search for new vapor-phase precursors. These compounds were all fully characterized using the standard methods of multinuclear magnetic resonance spectroscopy, combustion analysis, and single-crystal X-ray diffraction. Their thermal properties were determined by using thermogravimetric analysis and differential scanning colorimetry to assess their utility as vapor-phase precursors. Finally, preliminary deposition studies were carried out to investigate their potential as single-source CVD precursors.

Development and validation of a method for the simultaneous quantitative analysis of the active forms of vitamins B1, B2, and B6 using 31P qNMR

With increasing demand for active vitamins in functional foods and supplements, accurate quantification is crucial to ensure that quality and safety standards are met. This study presents the development of a phosphorous-31 quantitative nuclear magnetic resonance (31P qNMR) spectroscopy method for the simultaneous analysis of the active forms of vitamins B1, B2, and B6 in multivitamin supplements. The 31P NMR signals of the analytes and internal standard were effectively resolved and easily distinguishable. The method was validated in terms of specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), precision, accuracy, and stability. The curves for all three vitamins exhibited a high degree of linearity, with correlation coefficients (R2) exceeding 0.999. The LOD (0.04–0.07 mg mL−1) and the LOQ (0.14–0.24 mg mL−1) were adequate for analysis of multivitamin supplements, and the accuracy (99.2–102.0%) was excellent. The relative standard deviations for repeatability (1.06–1.89%) and intermediate precision (2.51–3.25%) were considered acceptable. The developed 31P qNMR method was successfully applied to commercial multivitamin supplements, demonstrating its practicality. Therefore, the 31P qNMR method is expected to be suitable for the simultaneous quantification of active vitamins B1, B2, and B6 and an effective analysis method for multivitamin preparations.

Structural Characterization and Cytotoxic Activity Evaluation of Ulvan Polysaccharides Extracted from the Green Algae Ulva papenfussii.

Ulvan, a sulfated heteropolysaccharide with structural and functional properties of interest for various uses, was extracted from the green seaweed Ulva papenfussii. U. papenfussii is an unexplored Ulva species found in the South China Sea along the central coast of Vietnam. Based on dry weight, the ulvan yield was ~15% (w/w) and the ulvan had a sulfate content of 13.4 wt%. The compositional constitution encompassed L-Rhamnose (Rhap), D-Xylose (Xylp), D-Glucuronic acid (GlcAp), L-Iduronic acid (IdoAp), D-Galactose (Galp), and D-Glucose (Glcp) with a molar ratio of 1:0.19:0.35:0.52:0.05:0.11, respectively. The structure of ulvan was determined using High-Performance Liquid Chromatography (HPLC), Fourier Transform Infrared Spectroscopy (FT-IR), and Nuclear Magnetic Resonance spectroscopy (NMR) methods. The results showed that the extracted ulvan comprised a mixture of two different structural forms, namely ("A3s") with the repeating disaccharide [→4)-β-D-GlcAp-(1→4)-α-L-Rhap 3S-(1→]n, and ("B3s") with the repeating disaccharide [→4)-α-L-IdoAp-(1→4)-α-L-Rhap 3S(1→]n. The relative abundance of A3s, and B3s was 1:1.5, respectively. The potential anticarcinogenic attributes of ulvan were evaluated against a trilogy of human cancer cell lineages. Concomitantly, Quantitative Structure-Activity Relationship (QSAR) modeling was also conducted to predict potential adverse reactions stemming from pharmacological interactions. The ulvan showed significant antitumor growth activity against hepatocellular carcinoma (IC50 ≈ 90 µg/mL), human breast cancer cells (IC50 ≈ 85 µg/mL), and cervical cancer cells (IC50 ≈ 67 µg/mL). The QSAR models demonstrated acceptable predictive power, and seven toxicity indications confirmed the safety of ulvan, warranting its candidacy for further in vivo testing and applications as a biologically active pharmaceutical source for human disease treatment.

Alginate supramolecular hydrogels based on viologen and cucurbit[8]uril: Host‐induced caveolae‐mediated endocytosis to white blood cancer cells

AbstractThe cellular uptake of drug carriers to the cytosol of a specific cell remains challenging, and a non‐classical supramolecular strategy is motivated. Here, we select a model host–guest complex in which a diamino‐viologen (1,1′‐bis(4‐aminophenyl)‐[4,4′‐bipyridine]−1,1′‐diium dichloride [VG]) fluorescent tag was engulfed by cucurbit[8]uril (CB8) and covalently linked to alginate polysaccharides (alginic acid [ALG]) as the modified drug vehicle. When adsorbed on the ALG surface, the encapsulation of VG was first confirmed utilizing Fourier transform infrared and nuclear magnetic resonance spectroscopic methods. Solid optical measurements (diffuse reflectance spectroscopy, photoluminescence, and time‐resolved photoluminescence) revealed emissive materials at around 650 nm and that CB8 enhanced the rigidity of the modified hydrogel. The molar composition of 2:1 for the complexation of VG to CB8 on the alginate surface and the thermal stabilities were also confirmed using thermogravimetric analysis and differential scanning calorimetry techniques. CB8 induced a dramatic decrease in the average size of the VGALG polysaccharides from 485 to 165 nm and a turnover in their charge from –19.8 to +14.4 mV. Flow cytometry with inhibitors of various endocytosis pathways was employed to track the cellular uptake across different blood cell types: human T‐cell leukemia 1301 and peripheral blood mononuclear cells. Noticeably, complexation of VG with the CB8 host on top of the sugar platform dramatically enhanced the internalization into 1301 cells (viz. from 1% to 99%) at a concentration of 1.8 mg/mL via caveolae‐mediated endocytosis because of the size reduction, turnover in the charge from negative to positive, and rigidity induction. These observations reveal a more profound understanding of the macrocyclic effects on drug delivery.