In Silico Approach for the Evaluation of the Potential Antiviral Activity of Extra Virgin Olive Oil (EVOO) Bioactive Constituents Oleuropein and Oleocanthal on Spike Therapeutic Drug Target of SARS-CoV-2

Since there is an urgent need for novel treatments to combat the current coronavirus disease 2019 (COVID-19) pandemic, in silico molecular docking studies were implemented as an attempt to explore the ability of selected bioactive constituents of extra virgin olive oil (EVOO) to act as potent SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) antiviral compounds, aiming to explore their ability to interact with SARS-CoV-2 Spike key therapeutic target protein. Our results suggest that EVOO constituents display substantial capacity for binding and interfering with Spike (S) protein, both wild-type and mutant, via the receptor-binding domain (RBD) of Spike, or other binding targets such as angiotensin-converting enzyme 2 (ACE2) or the RBD-ACE2 protein complex, inhibiting the interaction of the virus with host cells. This in silico study provides useful insights for the understanding of the mechanism of action of the studied compounds at a molecular level. From the present study, it could be suggested that the studied active phytochemicals could potentially inhibit the Spike protein, contributing thus to the understanding of the role that they can play in future drug designing and the development of anti-COVID-19 therapeutics.     

Metabolite Fingerprinting Using 1H-NMR Spectroscopy and Chemometrics for Classification of Three Curcuma Species from Different Origins

Curcuma longa, Curcuma xanthorrhiza, and Curcuma manga have been widely used for herbal or traditional medicine purposes. It was reported that turmeric plants provided several biological activities such as antioxidant, anti-inflammatory, hepatoprotector, cardioprotector, and anticancer activities. Authentication of the Curcuma species is important to ensure its authenticity and to avoid adulteration practices. Plants from different origins will have different metabolite compositions because metabolites are affected by soil nutrition, climate, temperature, and humidity. ¹H-NMR spectroscopy, principal component analysis (PCA), and orthogonal projections to latent structures-discriminant analysis (OPLS-DA) were used for authentication of C. longa, C. xanthorrhiza, and C. manga from seven different origins in Indonesia. From the ¹H-NMR analysis it was obtained that 14 metabolites were responsible for generating classification model such as curcumin, demethoxycurcumin, alanine, methionine, threonine, lysine, alpha-glucose, beta-glucose, sucrose, alpha-fructose, beta-fructose, fumaric acid, tyrosine, and formate. Both PCA and OPLS-DA model demonstrated goodness of fit (R² value more than 0.8) and good predictivity (Q² value more than 0.45). All OPLS-DA models were validated by assessing the permutation test results with high value of original R² and Q². It can be concluded that metabolite fingerprinting using ¹H-NMR spectroscopy and chemometrics provide a powerful tool for authentication of herbal and medicinal plants.     

Determination of the stereochemistry of rotenoids by1H-NMR spectroscopy in C6D6

The application of¹H-NMR spectroscopy in C₆D₆ for the determination of configurations at C_12a and C_6a in rotenoids is discussed.

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Bestimmung der Stereochemie von Rotenoiden mittels¹H-NMR-Spektroskopie in C₆D₆

Zusammenfassung Es wird die Anwendung der¹H-NMR-Spektroskopie in C₆D₆ zur Bestimmung der Konfigurationen an C_12a und C_6a in Rotenoiden diskutiert.

     

Isotopic Traceability (13C and 18O) of Greek Olive Oil

In recent years, isotopic analysis has been proven a valuable tool for the determination of the origin of various materials. In this article, we studied the ¹⁸O and ¹³C isotopic values of 210 olive oil samples that were originated from different regions in Greece in order to verify how these values are affected by the climate regime. We observed that the δ¹⁸O isotopic values range from 19.2 ‰ to 25.2 ‰ and the δ¹³C values range from −32.7 ‰ to −28.3 ‰. These differences between the olive oils’ isotopic values depended on the regional temperature, the meteoric water, and the distance from the sea. Furthermore, we studied the ¹³C isotopic values of biophenolic extracts, and we observed that they have same capability to differentiate the geographic origin. Finally, we compared the isotopic values of Greek olive oils with samples from Italy, and we concluded that there is a great dependence of oxygen isotopes on the climatic characteristics of the different geographical areas.     

Tracing the origin of extra virgin olive oils by infrared spectroscopy and chemometrics: A case study

In this paper, the potential of coupling mid- and near-infrared spectroscopic fingerprinting techniques and chemometric classification methods for the traceability of extra virgin olive oil samples from the PDO Sabina was investigated. To this purpose, two different pattern recognition algorithm representative of the discriminant (PLS-DA) and modeling (SIMCA) approach to classification were employed. Results obtained after processing the spectroscopic data by PLS-DA evidenced a rather high classification accuracy, NIR providing better predictions than MIR (as evaluated both in cross-validation and on an external test set). SIMCA confirmed these results and showed how the category models for the class Sabina can be rather sensitive and highly specific. Lastly, as samples from two harvesting years (2009 and 2010) were investigated, it was possible to evidence that the different production year can have a relevant effect on the spectroscopic fingerprint. Notwithstanding this, it was still possible to build models that are transferable from one year to another with good accuracy.     

Polymerization of Bis(Pyridine)bis-(2,4,6-tribromophenoxo)copper(II) Complex (Py2Cu(TBrP)2) by Electrooxidation and Structural Characterization by 1H-NMR, 13C-NMR,and FTIR Spectroscopies

Abstract

Electroinitiated polymerization of bis(2,4,6-tribromophenoxo)- bis(pyridine)copper(II) complex was achieved in dimethylformamide-tetrabutylammonium tetrafluoroborate solvent-electrolyte couple under air or nitrogen at room temperature by constant potential electrolysis. Polymerization conditions were based on the peak potentials measured by cyclic voltammetry. The structural analyses of the polymers were done by ¹H-NMR, ¹³C-NMR, and FTIR spectral analyses along with molecular weight measurements by cryoscopy. The poly(dibromo phenylene oxide)s obtained only at oxidation potentials in either atmosphere were found to be highly linear, indicating mainly 1,4-catenation was taking place.     

Evaluation of molten inorganic salt hydrates as reaction medium for the derivatization of cellulose

Molten inorganic salt hydrates are highly efficient solvents forcellulose. The carboxymethylation of the polymer dissolved in this new group ofcellulose solvents was investigated. The homogeneous carboxymethylation ofcellulose in molten LiClO₄3H₂O using sodiummonochloroacetate in the presence of NaOH is possible. The formation of CMC wasconfirmed by FT- Raman spectroscopy. Structure analysis by means of HPLC afterchain degradation showed the formation of CMC with a DS of 2 after a shortreaction time of 4 h. The derivatives exhibit a statisticaldistribution of substituents along the polymer chain if prepared in moltenLiClO₄3H₂O as solvent. A substituent distributioninthe order C-6 > C-2 C-3 for anhydroglucose units (AGU) was concludedfrom ¹H-NMR measurements. The synthesis of CMC in the swellingmediumLiClxH₂O (2 x 5) yields polymers with astatistical distribution of functional groups along the chain. The watercontentof the salt melts has a dramatic influence on the DS_CMC.     

The Chemical Constituents from Fruits of Catalpa bignonioides Walt. and Their α-Glucosidase Inhibitory Activity and Insulin Secretion Effect

Catalpa pod has been used in traditional medicine for the treatment of diabetes mellitus in South America. Studies on the constituents of Catalpa species have shown that it is rich in iridoids. In the present study, three previously undescribed compounds (2–4), including two secoiridoid derivatives along with twelve known compounds, were isolated from the fruits of Catalpa bignonioides Walt. In addition, fully assigned ¹³C-NMR of 5,6-dihydroxy-7,4’-dimethoxyflavone-6-O-sophoroside (1) is reported for the first time in the present study. The structures of compounds were determined on the basis of extensive spectroscopic methods, including UV, IR, 1D, and 2D NMR, mass spectroscopy, and CD spectroscopic data. All the isolated compounds were evaluated for α-glucosidase inhibitory activity. Among the tested compounds, compounds 2, 3, and 9 exhibited significant inhibitory activity against α-glucosidase enzyme assay. Meanwhile, the effect of compounds 2, 3, and 9 on glucose-stimulated insulin secretion (GSIS) was measured using pancreatic β-cells. Compounds 2, 3, and 9 exhibited non-cytotoxicity-stimulated insulin secretion in INS-1 cells. The expression levels of proteins associated with β-cell function and insulin secretion such as phosphorylation of total insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3-kinase (PI3K), Akt, activated pancreatic duodenal homeobox-1 (PDX-1), and peroxisome proliferator-activated receptor-γ (PPAR-γ) were increased in INS-1 cells after treatment with compounds 2, 3, and 9. The findings of the present study could provide a scientific warrant for their application as a potential antidiabetic agent.     

Extra Virgin Olive Oil Secoiridoids Modulate the Metabolic Activity of Dacarbazine Pre-Treated and Treatment-Naive Melanoma Cells

Nowadays, many individuals, whether healthy or diagnosed with disease, tend to expose themselves to various easily accessible natural products in hopes of benefiting their health and well-being. Mediterranean populations have traditionally used olive oil not only in nutrition but also in cosmetics, including skincare. In this study, the phenolic profile—composed of twelve compounds altogether, including the secoiridoids oleocanthal (OCAL) and oleacein (OCEIN)—of extra virgin olive oil (EVOO) from autochthonous cultivars from Croatia was determined using ¹H qNMR spectroscopy and HPLC-DAD analysis, and its biological activity was investigated in melanoma cell lines. The EVOO with the highest OCEIN content had the strongest anti-cancer activity in A375 melanoma cells and the least toxic effect on the non-cancerous keratocyte cell line (HaCaT). On the other hand, pure OCAL was shown to be more effective and safer than pure OCEIN. Post-treatment with any of the EVOO phenolic extracts (EVOO-PEs) enhanced the anti-cancer effect of the anti-cancerous drug dacarbazine (DTIC) applied in pre-treatment, while they did not compromise the viability of non-cancerous cells. The metastatic melanoma A375M cell line was almost unresponsive to the EVOO-PEs themselves, as well as to pure OCEIN and OCAL. Our results demonstrate that olive oils and/or their compounds may have a potentially beneficial effect on melanoma treatment. However, their usage can be detrimental or futile, especially in healthy cells, due to inadequately applied concentrations/combinations or the presence of resistant cells.     

Metabolite Characterization and Correlations with Antioxidant and Wound Healing Properties of Oil Palm (Elaeis guineensis Jacq.) Leaflets via 1H-NMR-Based Metabolomics Approach

Oil palm (Elaeis guineensis Jacq.) leaflets (OPLs) are one of the major agricultural by-products generated from the massive cultivation of Malaysian palm oil. This biomass is also reported to be of potential value based on its health-improving effects. By employing proton nuclear magnetic resonance (¹H-NMR) spectroscopy combined with multivariate data analysis (MVDA), the metabolite profile of OPLs was characterized and correlated with their antioxidant and wound healing properties. Principal component analysis (PCA) classified four varieties of extracts, prepared using solvents ranging from polar to medium polarity, into three distinct clusters. Cumulatively, six flavonoids, eight organic acids, four carbohydrates, and an amine were identified from the solvent extracts. The more polar extracts, such as, the ethyl acetate-methanol, absolute methanol, and methanol-water, were richer in phytochemicals. Based on partial least square (PLS) analysis, the constituents in these extracts, such as (+)-catechin, (−)-epicatechin, orientin, isoorientin, vitexin, and isovitexin, were strongly correlated with the measured antioxidant activities, comprising ferric reducing antioxidant power (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and nitric oxide (NO) free radical scavenging activities, as well as with cell proliferation and migration activities. This study has provided crucial evidence on the importance of these natural antioxidant compounds on the wound healing properties of OPL.     

The modes of complexation of benzimidazole with aqueous β-cyclodextrin explored by phase solubility, potentiometric titration, 1H-NMR and molecular modeling studies

The results of rigorous modeling of phase solubility diagrams, pH solubility profiles and potentiometric titrations revealed the following for benzimidazole (BZ) and BZ/β-CD complexation in aqueous solution: (a) the pK _a value of BZ estimated at 5.66 ± 0.08 was reduced to 5.33 ± 0.06 in the presence of 15 mM β-CD at 25 °C, thus indicating inclusion complex formation; (b) BZ forms soluble 1:1 and 2:1 BZ/β-CD complexes with complex formation constants K ₁₁ = 104 ± 8 M⁻¹ and K ₂₁ = 16 ± 6 M⁻¹; (c) protonated BZ forms only 1:1 complex with K ₁₁ = 42 ± 12 M⁻¹; (d) ¹H-NMR studies in D₂O showed significant upfield chemical shift displacements for inner cavity β-CD protons indicating inclusion complex formation, while (e) Molecular modeling of BZ-β-CD interactions in water clearly indicated complete inclusion of one BZ molecule into the β-CD cavity.     

On the bromination of hypericin: The gymnochrome chromophores

Summary Stepwise electrophilic bromination of hypericin in pyridine as the solvent yields regioselectively 2,5-dibromohypericin, 2,5,9-tribromohypericin, and 2,5,9,12-tetrabromohypericin. The compounds were characterized by means of NMR-, UV-Vis-, and fluorescence-spectra, andpK _a andpK* _a measurements. These properties were compared with those of hypericin on the one hand and of the recently isolated gymnochromes on the other hand.

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Zur Bromierung des Hypericins: Die Gymnochrom-Chromophore

Zusammenfassung Schrittweise elektrophile Bromierung von Hypericin in Pyridin als Lösungsmittel liefert regioselektiv 2,5-Dibromhypericin, 2,5,9-Tribromhypericin und 2,5,9,12-Tetrabromhypericin. Diese Verbindungen wurden durch NMR-, UV-Vis- und Fluoreszenz-Spektrometrie sowie durchpK _a - undpk* _a -Messungen charakterisiert. Diese Eigenschaften wurden mit jenen des Hypericins und der kürzlich isolierten Gymnochrome verglichen.

     

On the chemistry of pyrrole pigments,XCI: Copper complexes of pyridinologous linear tri- and tetra-pyrroles as cyclopropanation catalysts

Summary In addition to two recently described pyridinologous linear tri- and tetrapyrroles a biisoquinologous system was prepared and its geometrical features derived by means of NMR measurements and force field calculations. The copper complexes of these three ligands were isolated and characterized, and then used as catalysts in the cyclopropanation of styrene. The results were found to be similar to those reported for a variety of catalysts in literature. Thus, it was demonstrated that these systems can be used in principle as catalysts.

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Zur Chemie von Pyrrolpigmenten, 91. Mitt.: Kupferkomplexe pyridinologer linearer Tri- und Tetrapyrrole als Katalysatoren für die Cyclopropanierung

Zusammenfassung Zusätzlich zu zwei jüngst beschriebenen linearen pyridinologen Tri- und Tetrapyrrolen wurde ein biisochinolylanaloges System dargestellt und seine Geometrie aus Kernresonanzmessungen und Kraftfeldrechnungen abgeleitet. Die Kupferkomplexe dieser drei Liganden wurden isoliert und charakterisiert und als Katalysatoren für die Cyclopropanierung von Styrol eingesetzt. Die Ergebnisse waren mit jenen aus der Literatur zahlreicher Komplexe vergleichbar. Damit konnte gezeigt werden, daß solche Systeme prinzipiell als Katalysatoren Verwendung finden können.

     

Study on the Mechanism of Ionic Liquids Improving the Extraction Efficiency of Essential Oil Based on Experimental Optimization and Density Functional Theory: The Fennel (Foeniculi fructus) Essential Oil Case

In this work, microwave-assisted ionic liquids treatment, followed by hydro-distillation (MILT-HD), as an efficient extraction technology, was used to extract essential oil. The purpose for this was to use multivariate analysis (MVA) models to investigate the effects of potential critical process parameters on the extraction efficiency of essential oil, and explore the mechanism of ionic liquids (ILs). According to the design of experiment (DoE), under optimal process conditions, the extraction efficiency of essential oil was dramatically enhanced, and had low energy demands. Since little is known regarding those mechanisms, according to the non-covalent interaction analysis, the underlying mechanism for ILs improving extraction efficiency was explored based on the density functional theory (DFT). The results showed that ILs could form intense non-covalent bond interaction with cellulose. It helped destroy the network hydrogen bond structure of cellulose in plant cells and caused the essential oils in the cells to be more easily exposed to the extraction solution, thereby accelerating extraction efficiency. Based on this work, it is conducive to understand the MILT-HD process better and gain knowledge of the mechanism of ILs.     

Synthesis of polyesters as binders for deinkable inks. VI. Structural analysis of the copolyesterification between o-phthalic anhydride,oleic acid,and trimethylolpropane in bulk at 160°C by high resolution 13C- and 1H nuclear magnetic resonance (13C- and 1H-NMR)

A detailed structural analysis of the copolyesterification in bulk without any external catalyst at 160°C between o-phthalic anhydride (P), oleic acid (O), and trimethylolpropane (T) with a mol ratio ([ COOH]/[ OH]) = 0.70 has been carried out by high resolution ¹³C nuclear magnetic resonance (¹³C-NMR) (DMSO-d₆ and CDCl₃ solutions), ¹H nuclear magnetic resonance (¹H-NMR) (CDCl₃ solution), and by volumetry. The use of CDCl₃ as NMR solvent has allow us to identify several signals that have been assigned to trimethylolpropane monoesters with different esterification degrees in the o-phthalate residue. Identically, we have detected signals assignable to monoesters at the chain ends in structures with different chain lengths. These monoesterified structures have been also confirmed by analyzing samples modified by the diazomethane addition. These modified samples have been also used to determine free acid groups as their methoxylic derivatives by ¹H-NMR in CDCl₃ solution. We have not observed any detectable signs of gelation nor products produced by secondary reactions. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35 : 3409–3429, 1997     

3-(1, 1-Dialkyl-2-hydroxyethyl)-5-hydroxyamino-5-triflouromethyl-Δ2-isoxazolines: The first representatives of β-dioximes existing in the cyclic form: The first representatives of β-dioximes existing in the cyclic form

It was demonstrated by X-ray diffraction analysis that the reaction of 3,3-dimethyl-6-trifluoromethyl-2,3-dihydro-4-pyrone with hydroxylamine afforded 5-hydroxyamino-3-(2-hydroxy-1,1-dimethylethyl)-5-trifluoromethyl-Δ²-isoxaline. Published inIzvestiya Akademic Nauk. Seriya Khimicheskaya. No. 11, pp. 1941–1944, November, 2000.     

Metabolite Profiling of “Green” Extracts of Cynara cardunculus subsp. scolymus,Cultivar “Carciofo di Paestum” PGI by 1H NMR and HRMS-Based Metabolomics

Globe artichoke (Cynara cardunculus L. var. scolymus L.), is a perennial plant widely cultivated in the Mediterranean area, known for its edible part named capitula or heads. Its functional properties are related to its high levels of polyphenolic compounds and inulin. “Carciofo di Paestum”, an Italian traditional cultivar, is a labeled PGI (Protected Geographical Indication) product of the Campania region, representing an important economic resource. So far, a few chemical investigations were performed on this cultivar, mainly focused on the analysis of methanol extracts. Due to the increasing use of food supplements, in this study, a comprehensive analysis of green extracts of “Carciofo di Paestum” PGI heads was performed. EtOH, EtOH: H₂O (80:20, 70:30, 60:40) extracts, as well as infusions and decoctions prepared according to Pharmacopeia XII were analyzed by LC-ESI/QExactive/MS/MS. A total of 17 compounds corresponding to caffeoylquinic acid derivatives, phenolics, flavonoids, and terpenoids were identified. The extracts were further submitted to NMR analysis to highlight the occurrence of primary metabolites. Both LCMS and NMR data were analyzed by Principal Component Analysis (PCA), showing significant differences among the extraction methods. Moreover, 5-caffeoylquinic acid and 1,5-dicaffeoylquinic acid were quantified in the extracts by LC-ESI/QTrap/MS/MS using the Multiple Reaction Monitoring (MRM) method. Furthermore, the phenolic content, antioxidant activity, and α-glucosidase inhibitory activity of C. cardunculus var. scolymus “Carciofo di Paestum” extracts were evaluated.     

The effect of polyether ligands on the solution structure of [Li]-α-(phenylthio)benzyllithium in tetrahydrofuran: A H,Li-HOESY NMR study

[⁶Li]-α-(phenylthio)benzyllithium 1-⁶Li was studied in THF/[D₈]THF solution (1:1) in the presence of several acyclic and cyclic polyether ligands by ¹H,⁶Li-HOESY, ¹H and ¹³C NMR spectroscopy. The question whether these ligands are bonded to lithium or not is important for physical–organic investigations as well as for studies of the ground state of (stereoselective) reactions of organolithium compounds in the presence of such ligands. Dimethoxyethane is not bonded to lithium under these conditions. The acyclic ethers diglyme and triglyme coordinate only weakly to the organolithium compound and form contact ion pairs (CIPs) at 25°C. At −80°C, CIPs are in equilibrium with separated ion pairs (SIPs). Very stable complexes of 1-⁶Li are obtained with crown ether ligands. Addition of 12-crown-4 and 15-crown-5, respectively, results in the exclusive formation of SIPs at 25°C and −80°C. With 18-crown-6, a CIP–SIP equilibrium is observed at 25°C which is shifted entirely to the SIP side at −80°C. Graphical analyses of the ¹H and ¹³C NMR spectra of the polyether complexes of 1-⁶Li revealed correlations between the chemical shifts of the para phenyl carbon C-5, the para phenyl proton H-5, the benzylic carbon C-1, and the proton–carbon coupling constant J(C-1,H-1) of 1-Li, which are useful probes for the charge distribution within the carbanionic moiety of 1-⁶Li in the respective complexes, and thus for the ion pair character as a function of the polyether complexation of lithium.