Degradation and fate of 2,4-dinitroanisole (DNAN) and its intermediates treated with Mg/Cu bimetal: Surface examination with XAS, DFT, and LDI-MS.

A novel Mg-based bimetal reagent (Mg/Cu) was used as an enhanced reductive system to degrade insensitive munition 2,4-dinitroanisole (DNAN), a contaminant found in energetic-laden waste. Degradation of DNAN was significantly impacted by dissolved oxygen and studied in anoxic and oxic bimetal systems (i.e., purging with N2, air, or O2 gas). Degradation occurred through sequential nitroreduction: first one nitro group was reduced (ortho or para) to form short-lived intermediates 2-amino-4-nitroanisole or 4-amino-2-nitroanisole (2-ANAN or 4-ANAN), and then subsequent reduction of the other nitro group formed 2,4-diaminoanisole (DAAN). The nitro-amino intermediates demonstrated regioselective reduction in the ortho position to 2-ANAN; Regioselectivity was also impacted by the anoxic/oxic environment. Under O2-purging DNAN degradation rate was slightly enhanced, but most notably O2 significantly accelerated DAAN generation. DAAN also further degraded only in the oxygenated Mg/Cu system. Adsorption of DNAN byproducts to the reagent occurred regardless of anoxic/oxic condition, resulting in a partition of carbon mass between the adsorbed phase (27%-35%) and dissolved phase (59%-72%). Additional surface techniques were applied to investigate contaminant interaction with Cu. Density functional theory (DFT) calculations identified preferential adsorption structures for DNAN on Cu with binding through two O atoms of one or both nitro groups. X-ray absorption spectroscopy (XAS) measurements determined the oxidation state of catalytic metal Cu and formation of a Cu-O-N bond during treatment. Laser desorption ionization mass spectrometry (LDI-MS) measurements also identified intermediate 2-ANAN adsorbed to the bimetal surface.

The role of centrifugal partition chromatography in the removal of ß-asarone from Acorus calamus essential oil.

Β-asarone is a phenylpropane derivative present in the rhizomes of Acorus calamus, that was proved to exhibit toxic effects in humans. Because of its presence the whole plant that is commonly used in traditional medicine for its sedative, anti-inflammatory, neuroprotective and other properties has limited application nowadays. In the study, qualitative and quantitative analysis of a collection of nine essential oil (EO) samples of European and Asian origin was performed. The final content of ß-asarone in the tested samples ranged between 0.265 and 1.885 mg/mL. Having in mind a possible application of the EO as a biopesticide, this research aimed at the development of CPC-based purification protocol that could help remove ß-asarone from EO. It was proved that the biphasic solvent system composed of n-hexane/EtOAc/MeOH/water, 9:1:9:1 (v/v/v/v) was capable of the removal of the toxic constituent in the CPC chromatograph operated in the ascending elution mode with 2200 rpm and a flow rate of 5 mL/min. The chromatographic analysis that lasted only 144 min effectively separated ß-asarone (purity of 95.5%) and α-asarone (purity of 93.7%) directly from the crude Acorus calamus rhizome EO.

Effects of Cocrystallization on the Structure and Properties of Melt-Cast Explosive 2,4-Dinitroanisole: A Computational Study.

Melt-cast explosive 2,4-dinitroanisole (DNAN) crystal and its cocrystals DNAN/1,3-dinitrobenzene (DNB) and DNAN/2-nitroaniline (NA) were used to identify the effects of cocrystallization on the crystal structure, non-covalent interactions, and melting points of the DNAN crystal through density functional theory and molecular dynamics. The components DNB and NA with subtle structure variations between the nitro group and amino group can significantly affect the non-covalent interactions, especially the π-π stacking and H-bonds, which can lead to different crystal stacking styles. The melting points of the DNAN crystal are decreased through the cocrystallization, which expands the utilization of the DNAN-based melt cast explosives. Our study deciphers the effects caused by the cocrystallization on the structure and properties of melt cast explosives and may help to design and optimize novel melt-cast explosives.

Anti-oxidative and anti-hyperglycemic properties of Agastache foeniculum essential oil and oily fraction in hyperglycemia-stimulated and lipopolysaccharide-stimulated macrophage cells: In vitro and in silico studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Hyperglycemia (HG) and lipopolysaccharide (LPS) often promote superoxide accumulation, which may increase oxidative stress. Reducing superoxide production in hyperglycemia and the inflammatory condition is an emerging way to reduce protein and lipid oxidation and diabetes complication. AIM OF STUDY: To examine the effect of Agastache foeniculum essential oil (AFEO) and oil fraction (AFoil) on HG- and LPS-stimulated oxidative stress, the pathogenicity of AFEO and AFoil on oxidative stress was assessed. METHODS: The stimulatory effects of AFEO and AFoil on the activity and expression of NADH oxide (NOX), catalase (CAT), superoxide dismutase (SOD), and the expression of nuclear respiratory factor 2 (NRF2) and nuclear factor-kappa B (NF-kB) in the stimulated macrophage cell line, J774.A1, was studied. The interaction patterns of AFEO and AFoil components with NOX, SOD, CAT, NRF2, and NF-kB proteins were also deduced using molecular docking. RESULTS: Estragole was the main ingredient in AFEO (97%). Linolenic acid (32.10%), estragole (16.22%), palmitic acid (12.62%), linoleic acid (12.04%), and oleic acid (8.73%) were the major chemical components of the AFoil. NOX activation was stimulated in macrophage cells by HG and LPS. At 20 µg/mL, AFEO and AFoil decreased NOX activity while increased SOD and CAT activities in stimulated macrophages. AFoil with estragole and omega-3 fatty acids was better than AFEO with estragole in anti-hyperglycemic and anti-oxidative activity. According to molecular docking research, estragole, linoleic acid, and linolenic acid bind to different hydrophobic pockets of NOX, SOD, CAT, NFR2, and NF-kB using hydrogen bonds, van der Waals bonds, pi-alkyl, and pi-anion interactions, with different binding energies. CONCLUSION: AFEO and AFoil showed antioxidant and anti-diabetic activity. The mechanisms in lowering oxidative stress markers depended on down-regulating superoxide-producing enzymes and up-regulating superoxide-removing enzymes at gene and protein levels. The AFoil emulsion can be used to reduce the detrimental impacts of hyperglycemia and oxidative stress.

Variability of the Chemical Composition and Bioactivity between the Essential Oils Isolated from Male and Female Specimens of Hedyosmum racemosum (Ruiz & Pav.) G. Don.

Hedyosmum racemosum (Ruiz & Pav.) G. is a native species of Ecuador used in traditional medicine for treatment of rheumatism, bronchitis, cold, cough, asthma, bone pain, and stomach pain. In this study, fresh H. racemosum leaves of male and female specimens were collected and subjected to hydrodistillation for the extraction of the essential oil. The chemical composition of male and female essential oil was determined by gas chromatography-gas chromatography equipped with a flame ionization detector and coupled to a mass spectrometer using a non-polar and a polar chromatographic column. The antibacterial activity was assayed against five Gram-positive and two Gram-negative bacteria, and two dermatophytes fungi. The scavenging radical properties of the essential oil were evaluated by DPPH and ABTS assays. The chemical analysis allowed us to identify forty-three compounds that represent more than 98% of the total composition. In the non-polar and polar column, α-phellandrene was the principal constituent in male (28.24 and 25.90%) and female (26.47 and 23.90%) essential oil. Other main compounds were methyl chavicol, germacrene D, methyl eugenol, and α-pinene. Female essential oil presented a strong activity against Klebsiella pneumoniae (ATCC 9997) with an minimum inhibitory concentration (MIC) of 500 µg/mL and a scavenging capacity SC50 of 800 µg/mL.

Synthesis, antiepileptic effects, and structure-activity relationships of α-asarone derivatives: In vitro and in vivo neuroprotective effect of selected derivatives.

In the present study, we compared the antiepileptic effects of α-asarone derivatives to explore their structure-activity relationships using the PTZ-induced seizure model. Our research revealed that electron-donating methoxy groups in the 3,4,5-position on phenyl ring increased antiepileptic potency but the placement of other groups at different positions decreased activity. Besides, in allyl moiety, the optimal activity was reached with either an allyl or a 1-butenyl group in conjugation with the benzene ring. The compounds 5 and 19 exerted better neuroprotective effects against epilepsy in vitro (cell) and in vivo (mouse) models. This study provides valuable data for further exploration and application of these compounds as potential anti-seizure medicines.

In Vitro and In Vivo Pharmaco-Toxicological Characterization of 1-Cyclohexyl-x-methoxybenzene Derivatives in Mice: Comparison with Tramadol and PCP.

1-cyclohexyl-x-methoxybenzene is a novel psychoactive substance (NPS), first discovered in Europe in 2012 as unknown racemic mixture of its three stereoisomers: ortho, meta and para. Each of these has structural similarities with the analgesic tramadol and the dissociative anesthetic phencyclidine. In light of these structural analogies, and based on the fact that both tramadol and phencyclidine are substances that cause toxic effects in humans, the aim of this study was to investigate the in vitro and in vivo pharmacodynamic profile of these molecules, and to compare them with those caused by tramadol and phencyclidine. In vitro studies demonstrated that tramadol, ortho, meta and para were inactive at mu, kappa and delta opioid receptors. Systemic administration of the three stereoisomers impairs sensorimotor responses, modulates spontaneous motor activity, induces modest analgesia, and alters thermoregulation and cardiorespiratory responses in the mouse in some cases, with a similar profile to that of tramadol and phencyclidine. Naloxone partially prevents only the visual sensorimotor impairments caused by three stereoisomers, without preventing other effects. The present data show that 1-cyclohexyl-x-methoxybenzene derivatives cause pharmaco-toxicological effects by activating both opioid and non-opioid mechanisms and suggest that their use could potentially lead to abuse and bodily harm.

A computational approach to understand the role of metals and axial ligands in artificial heme enzyme catalyzed C-H insertion.

Engineered heme enzymes such as myoglobin and cytochrome P450s metalloproteins are gaining widespread importance due to their efficiency in catalyzing non-natural reactions. In a recent strategy, the naturally occurring Fe metal in the heme unit was replaced with non-native metals such as Ir, Rh, Co, Cu, etc., and axial ligands to generate artificial metalloenzymes. Determining the best metal-ligand for a chemical transformation is not a trivial task. Here we demonstrate how computational approaches can be used in deciding the best metal-ligand combination which would be highly beneficial in designing new enzymes as well as small molecule catalysts. We have used Density Functional Theory (DFT) to shed light on the enhanced reactivity of an Ir system with varying axial ligands. We look at the insertion of a carbene group generated from diazo precursors via N2 extrusion into a C-H bond. For both Ir(Me) and Fe systems, the first step, i.e., N2 extrusion is the rate determining step. Strikingly, neither the better ligand overlap with 5d orbitals on Ir nor the electrophilicity on the carbene centre play a significant role. A comparison of Fe and Ir systems reveals that a lower distortion in the Ir(Me)-porphyrin on moving from the reactant to the transition state renders it catalytically more active. We notice that for both metal porphyrins, the free energy barriers are affected by axial ligand substitution. Further, for Fe porphyrin, the axial ligand also changes the preferred spin state. We show that for the carbene insertion into the C-H bond, Fe porphyrin systems undergo a stepwise HAT (hydrogen atom transfer) instead of a concerted hydride transfer process. Importantly, we find that the substitution of the axial Me ligand on Ir to imidazole or chloride, or without an axial substitution changes the rate determining step of the reaction. Therefore, an optimum ligand that can balance the barriers for both steps of the catalytic cycle is essential. We subsequently used the QM cluster approach to delineate the protein environment's role and mutations in improving the catalytic activity of the Ir(Me) system.

Inhibitory Effect of Eugenol and trans-Anethole Alone and in Combination with Antifungal Medicines on Candida albicans Clinical Isolates.

One of the most common pathogens among yeasts is Candida albicans, which presents a serious health threat. The study aimed to check the antifungal properties of trans-anethole and eugenol with selected antifungal medicines (AMs) against C. albicans clinical isolates. The checkerboard method was used to tests of interactions between these compounds. Achieved results indicated that eugenol showed synergistic and additive activities with miconazole and econazole against investigated clinical isolates, respectively. Moreover, the combination - trans-anethole - miconazole also showed an additive effect against two clinical isolate. We tried to relate the results to changes in C. albicans cell sheaths under the influence of essential oils compounds (EOCs) performing the Fourier transform infrared spectra analysis to confirm the presence of particular chemical moieties in C. albicans cells. Nevertheless, no strong relationships was observed between synergistic and additive actions of used EOC-AMs combinations and chemical moieties in C. albicans cells.

A Solvent-free, Catalyst-free Formal [3+3] Cycloaddition Dearomatization Strategy: Towards New Fluorophores for Biomolecules Labelling.

A general, sustainable dearomatization reaction for nitrogen-containing heterocycles was developed. Under solvent free conditions and without catalyst, the biorenewable methyl coumalate (MC) reacted as an efficient C3 partner to convert nine types of basic aromatic rings into their pyrido[1,2-a] fused derivatives in good to excellent yields. The fluorescence properties of some of the products were harnessed to conjugate fluorescent tags to bovine serum albumin (BSA) and immunoglobulin G.

Use of alimentary film for selective sorption of haloanisoles from contaminated red wine.

Haloanisoles (HAs) are known to compromise wine quality because of their mouldy off-flavours. Up to now no treatment exists to eliminate the presence of these unpleasant volatiles in wine. This research aimed i) to assess the alimentary plastic film efficacy to remove or lessen HAs content in polluted wines; and ii) to evaluate its impact on wine quality. The film-treatment reduced significantly (p < 0,05) the 2,4,6-trichloroanisole (TCA) content of initial wine. This decrease became more noticeable as the contact time film-wine increased. Chromatic characteristics, phenolic and proanthocyanidin contents, and woody aroma profile did not change because of the film-treatment. A significant sorption of certain esters was observed, but as HAs were removed under detection thresholds, fruity perception of wines was improved. Globally, the alimentary plastic film was able to improve the organoleptic quality of wines contaminated with HAs, by reducing the cork taint and enhancing their overall fruity aroma.

Quantitative Analysis of ß-Asarone Derivatives in Acorus calamus and Herbal Food Products by HPLC-MS/MS.

α-Asarone and ß-asarone are reported as bioactive constituents of Acorus calamus. Phase I metabolism of asarone isomers results in a multiple spectrum of genotoxic metabolites. Thus, the question arises whether structural analogues of the known phase I metabolites also naturally occur in A. calamus-based food products. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for three product classes, herbal infusions, alcoholic beverages, and food supplements. High asarone contents were detected in herbal infusions (total mean 9.13 mg/kg, n = 8) and food supplements (total mean 14.52 mg/kg, n = 6); hence, these food products can highly contribute to human exposure to genotoxic asarone derivatives. Also, the occurrence of asarone oxidation products found in food and food supplements has to be taken under consideration because data on toxicity is limited so far.

High Performance Liquid Chromatography versus Stacking-Micellar Electrokinetic Chromatography for the Determination of Potentially Toxic Alkenylbenzenes in Food Flavouring Ingredients.

Alkenylbenzenes, including eugenol, methyleugenol, myristicin, safrole, and estragole, are potentially toxic phytochemicals, which are commonly found in foods. Occurrence data in foods depends on the quality of the analytical methodologies available. Here, we developed and compared modern reversed-phase high performance liquid chromatography (HPLC) and stacking-micellar electrokinetic chromatography (MEKC) methods for the determination of the above alkenylbenzenes in food flavouring ingredients. The analytical performance of HPLC was found better than the stacking-MEKC method. Compared to other HPLC methods found in the literature, our method was faster (total run time with conditioning of 15 min) and able to separate more alkenylbenzenes. In addition, the analytical methodology combining an optimized methanol extraction and proposed HPLC was then applied to actual food flavouring ingredients. This methodology should be applicable to actual food samples, and thus will be vital to future studies in the determination of alkenylbenzenes in food.

Iron (III)-mediated degradation of α-asarone and characterization of its major degradation products by UPLC-MS/MS and NMR.

α-Asarone, the main bioactive phytochemicals of Acorus species, is widely used in the treatment of respiratory disorders. The solution stability study of α-asarone was investigated in the presence of various metal ions. α-Asarone was found to be unstable in the presence of the metal ions Fe3+, Cu2+ and Al3+, in which the induction of Fe3+ was highly prone to the degradation of α-asarone. Thus, an iron (III)-mediated forced degradation study of α-asarone was carried out. One oxidative and four dimeric products were formed after the degradation of α-asarone. The complete mass fragmentation patterns for α-asarone and its degradation products (DPs) were established by UPLC-MS/MS in the positive ionization mode, and their structural confirmation was accomplished with 1H and 13C NMR. Then, the mechanistic pathways for the formation of all DPs were postulated. Finally, the oxidation degradation behavior and mechanism of α-asarone in the presence of oxidative stressors viz., hydrogen peroxide and azobisisobutyronitrile were explored.

Ultrasound-assisted preparation of anise extract nanoemulsion and its bioactivity against different pathogenic bacteria.

The present work aimed to characterize the nanoemulsion of anise seed extract and to compare its efficacy with the bulk extract against pathogenic bacteria. The anise seeds extract was prepared by cold solvent extraction method using ethanol. Nanoemulsion of anise extract was formulated using ultrasound assisted method and analyzed using high-performance liquid chromatography (HPLC), fourier transform infrared spectroscopy (FTIR) and UV-visible spectrophotometry. The antimicrobial activity of the nanoemulsion was tested against seven foodborne pathogenic bacterial species. Results showed that the extract contained anethole (37%), naringenin (21%), and taxifolin (13%) as the major phytochemical components. The average droplet size of the nanoemulsion droplets was measured by dynamic light scattering (DLS) and confirmed by transmission electron microscope to be about 400 nm. Anise extract nanoemulsion showed higher antimicrobial activity against most of the tested pathogens. Anise extract nanoemulsion performed better than bulk extract as an antimicrobial agent against some foodborne pathogenic bacteria.

Microdroplet Impact-Induced Spray Ionization Mass Spectrometry (MISI MS) for Online Reaction Monitoring and Bacteria Discrimination.

Microdroplet impact-induced spray ionization (MISI) is demonstrated involving the impact of microdroplets produced from a paper and their impact on another, leading to the ionization of analytes deposited on the latter. This cascaded process is more advantageous in comparison to standard spray ionization as it performs reactions and ionization simultaneously in the absence of high voltage directly applied on the sample. In MISI, we apply direct current (DC) potential only to the terminal paper, used as the primary ion source. Charge transfer due to microdroplet/ion deposition on the flowing analyte solution on the second surface generates secondary charged microdroplets from it carrying the analytes, which ionize and get detected by a mass spectrometer. In this way, up to three cascaded spray sources could be assembled in series. We show the detection of small molecules and proteins in such ionization events. MISI provides a method to understand chemical reactions by droplet impact. The C-C bond formation reactions catalyzed by palladium and alkali metal ion encapsulation using crown ether were studied as our model reactions. To demonstrate the application of our ion source in a bioanalytical context, we studied the noninvasive in situ discrimination of bacteria samples under ambient conditions.

Direct structural and mechanistic insights into fast bimolecular chemical reactions in solution through a coupled XAS/UV-Vis multivariate statistical analysis.

In this work, we obtain detailed mechanistic and structural information on bimolecular chemical reactions occurring in solution on the second to millisecond time scales through the combination of a statistical, multivariate and theoretical analysis of time-resolved coupled X-ray Absorption Spectroscopy (XAS) and UV-Vis data. We apply this innovative method to investigate the sulfoxidation of p-cyanothioanisole and p-methoxythioanisole by the nonheme FeIV oxo complex [N4Py·FeIV(O)]2+ (N4Py = N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine) in acetonitrile at room temperature. By employing statistical and multivariate techniques we determine the number of key chemical species involved along the reaction paths and derive spectral and concentration profiles for the reaction intermediates. From the quantitative analysis of the XAS spectra we obtain accurate structural information for all reaction intermediates and provide the first structural characterization in solution of complex [N4Py·FeIII(OH)]2+. The employed strategy is promising for the spectroscopic characterization of transient species formed in redox reactions.

Partitioning of Selected Anisole and Veratrole Derivatives between Water and Anionic Surfactant Micelles.

The UV absorption spectra of six structurally related derivatives of anisole and veratrole, i.e., anisaldehyde, (E)-anethole, estragole, veratraldehyde, methyleugenol and (E)-methylisoeugenol, were recorded at various concentrations of the anionic surfactants, either sodium lauryl sulfate (SLS) or sodium lauryl ether sulfate (SLES) at T = 298 K. In addition, conductivity and density measurements were made for the SLS and SLES solutions to determine the volumetric properties of the studied surfactants. Next, using the W. Al-Soufi, L. Pineiro and M. Novo model (APN model) including the pseudo-phase model for micellar solubilization, the values of micelle-water partition coefficients for each perfume-surfactant system were determined. In addition, the relations between the molecular structures of the solute and the head group of the surfactant and the value of the micelle-water partition coefficient as well as the octanol-water one were discussed.