Bicyclic Aromatic Compounds Research Articles

In silico models for the screening of human transthyretin disruptors

The use of New Approach Methodologies (NAMs), such as Quantitative Structure-Activity Relationship (QSAR) models, is highly recommended by international regulations to speed up hazard and risk assessment of Endocrine Disruptors, which are known to be linked to a wide spectrum of severe diseases on humans and wildlife. A very sensitive target for these chemicals is the thyroid hormone system, which plays a key role in regulating metabolic and cognitive functions. Several chemicals have been demonstrated to compete with the thyroid hormone thyroxine (T4) for binding to human thyroid hormone distributor protein transthyretin (hTTR). In this work, we generated three new datasets composed by T4-hTTR competing potencies of more than 200 heterogeneous chemicals measured by three different in vitro assays. These datasets were used for the development of new regression QSAR models. The best models were thoroughly validated by internal and external validation procedures. The mechanistic interpretation of the selected molecular descriptors provided information on structural features which are relevant to characterise hTTR binders, such as the presence of hydroxylated and halogenated aromatic rings. PCA analysis was used to rank the studied chemicals according to their increasing T4-hTTR competing potency. Hydroxylated and halogenated bicyclic aromatic compounds are ranked as the strongest hTTR binders. The new QSARs are useful to screen potential Thyroid Hormone System-Disrupting Chemicals (THSDCs), and to support the identification of sustainable alternatives to hazardous chemicals.

Thymoquinone: A comprehensive review of its potential role as a monotherapy for metabolic syndrome.

Metabolic syndrome (MetS) is a widespread global epidemic that affects individuals across all age groups and presents a significant public health challenge. Comprising various cardio-metabolic risk factors, MetS contributes to morbidity and, when inadequately addressed, can lead to mortality. Current therapeutic approaches involve lifestyle changes and the prolonged use of pharmacological agents targeting the individual components of MetS, posing challenges related to cost, compliance with medications, and cumulative side effects. To overcome the challenges associated with these conventional treatments, herbal medicines and phytochemicals have been explored and proven to be holistic complements/alternatives in the management of MetS. Thymoquinone (TQ), a prominent bicyclic aromatic compound derived from Nigella sativa emerges as a promising candidate that has demonstrated beneficial effects in the treatment of the different components of MetS, with a good safety profile. For methodology, literature searches were conducted using PubMed and Google Scholar for relevant studies until December 2023. Using Boolean Operators, TQ and the individual components of MetS were queried against the databases. The retrieved articles were screened for eligibility. As a result, we provide a comprehensive overview of the anti-obesity, anti-dyslipidaemic, anti-hypertensive, and anti-diabetic effects of TQ including some underlying mechanisms of action such as modulating the expression of several metabolic target genes to promote metabolic health. The review advocates for a paradigm shift in MetS management, it contributes valuable insights into the multifaceted aspects of the application of TQ, fostering an understanding of its role in mitigating the global burden of MetS.

Synthesis and In Vitro Biocompatibility Studies of Novel Alkoxy 4,4-Difluoro-4-bora-3a,4a-diaza-s-indacenes.

BODIPYs are bicyclic aromatic compounds with unique spectroscopic, photophysical, and chemical properties. This study aimed to find BODIPYs with characteristics biocompatible with human cell lines for possible use as imaging agents. Six BODIPY derivatives were synthesised with groups linked to boron, fluorine, phenol, or catechol, resulting in compounds with different physicochemical characteristics. NMR, absorption, and emission spectroscopy and mass spectrometry were subsequently used to characterise them. Afterwards, the biocompatibility of these compounds was evaluated using MTT, SRB, and cellular uptake assays in A549 and H1299 cell lines. Furthermore, a haemolysis assay was performed on human blood cells. To summarise the main results, BODIPYs 1 to 4 showed considerable fluorescence. In contrast, BODIPYs 5 and 6 showed very weak fluorescence, which could be related to the presence of the catechol group and its quenching properties. Regarding biocompatibility, all compounds had metabolic activity and viability above 80% and 70%, respectively. BODIPYs 3 and 6 presented the most consistent data, demonstrating good uptake and, in general, haemolytic activity below 25%. In conclusion, the cytotoxic effects of the compounds were not considerable, and the presence of cyclic alkoxides in BODIPYs 3 and 6 may introduce exciting features that should be highlighted for dual imaging for BODIPY 3 due to its fluorescence or for radioactive labelling in the case of both BODIPYs.

In Silico Assessment of Naphthalene Interaction with Glutathione Reductase and Histological Changes in Naphthalene Exposed Rats Tissues

Naphthalene (NA), a bicyclic aromatic compound that is widely used in various commercial and industrial applications including lavatory scent disks and mothballs, is known to be readily absorbed into the systemic circulation following either inhalation or ingestion and may cause systemic toxicity. This study examined the histopathological changes in some tissues (lung, liver and kidney) of NA-exposed Wistar rats. Twenty-four rats (175-250 g) were randomly divided into six groups of four rats each. The rats in all groups were given food and water while in addition rats in the experimental groups were exposed to NA at 0.75 mg/m3 and 1.50 mg/m3 for 2 h and 4 h. Rats were sacrificed at 24 h after the last hour of NA exposure. The tissues were excised for histological examination. The effects of NA and some selected metabolites using the rat glutathione reductase homology model were examined via molecular docking and dynamic simulation. From this study, exposure of rats to NA resulted in hepatocyte necrosis at 0.75 mg/m3 for 2 h, dilation of the alveolar duct of the lung at 0.75 mg/m3 and severe epithelial hyperplasia and chronic infiltration of inflammatory cells in the lung at 1.50 mg/m3 for 4 h. Also, vascular congestion was observed in the kidneys at 0.75 mg/m3 for 2 h and 1.50 mg/m3 for 4 h. The in silico study revealed the NA metabolite toxic potential, and NA showed the lowest binding score (-5.40± 0.00 kcal/mol). Therefore, the study concludes that NA exposure irrespective of duration can lead to hepatic and alveolar damage in the absence of mechanisms that can ameliorate its toxic effects.

Facile and selective separation of anthraquinones by alizarin-modified iron oxide magnetic nanoparticles

Anthraquinones are widely distributed in higher plants and possess broad biological activities. The conventional separation procedures for isolating anthraquinones from the plant crude extracts require multiple extraction, concentration, and column chromatography steps. In this study, we synthesized three alizarin (AZ)-modified Fe3O4 nanoparticles (Fe3O4@AZ, Fe3O4@SiO2-AZ, and Fe3O4@SiO2-PEI-AZ) by thermal solubilization method. Fe3O4@SiO2-PEI-AZ showed strong magnetic responsiveness, high methanol/water dispersion, good recyclability, and high loading capacity for anthraquinones. To evaluate the feasibility of using Fe3O4@SiO2-PEI-AZ for separating various aromatic compounds, we employed molecular dynamics simulations to predict the adsorption/desorption effects of PEI-AZ for various aromatic compounds in different methanol concentrations. The results showed that the anthraquinones could be efficiently separated from the monocyclic and bicyclic aromatic compounds by adjusting the methanol/water ratio. The Fe3O4@SiO2-PEI-AZ nanoparticles were then used to separate the anthraquinones from the rhubarb extract. At 5% methanol, all the anthraquinones were adsorbed by the nanoparticles, thus allowing their separation from other components in the crude extract. Compared with the conventional separation methods, this adsorption method has the advantages of high adsorption specificity, simple operation, and solvent saving. This method sheds light on the future application of functionalized Fe3O4 magnetic nanoparticles to selectively separate desired components from complex plant and microbial crude extracts.

Recent Scenario for the Synthesis of Benzimidazole Moiety(2020–2022)

AbstractThe benzene ring is fused to the 4 and 5 positions of the imidazole ring in the bicyclic heterocyclic aromatic compound known as benzimidazole. Benzimidazole is an important heterocyclic scaffold exhibiting a wide range of biological and pharmacological properties and plays a crucial role in drug design. It is synthesized by a straightforward nucleophilic substitution reaction and condensation method between o‐phenylenediamine and a carbonyl compound under various conditions. In recent years benzimidazole have gained more attention in chemistry due to their biomedical importance. This study focuses on synthesis of benzimidazole derivatives by numerous homogeneous catalysts related from s‐ block, p‐ block, transition metal, inner transition metal and environmentally benign synthetic approaches, via heterogeneous catalyst in metal‐free conditions. Benzimidazole has several applications in pharmaceuticals, agrochemicals and fine chemicals. Its scaffolds are omnipresent in several bioactive natural products and pharmaceutically important compounds. This review highlights synthetic approaches and studies of benzimidazole reported from the year 2020 onwards.

Experimental and kinetic modeling study of α-methylnaphthalene laminar flame speeds

α-Methylnaphthalene (AMN) is the primary reference bicyclic aromatic compound of diesel, and it is commonly used as a component of diesel, kerosene and jet-fuel surrogates formulated to describe real fuel combustion kinetics. However, few experimental data on neat AMN combustion are available in the literature. This work provides the first measurements of laminar flame speed profiles of AMN/air mixtures at 1 bar varying the initial temperature from 425 to 484 K, and equivalence ratio (φ) between 0.8 and 1.35 paving the way for the kinetic study of AMN combustion chemistry at high temperatures (>1800 K). The experimental data obtained in a spherical reactor are compared with kinetic model simulations. Specifically, the AMN kinetics is implemented from its analogous monocyclic aromatic compound, i.e., toluene, through the analogy and rate rule approach. This method allows to develop kinetic mechanisms of large species from the kinetics of smaller ones characterized by analogous chemical features, namely the aromaticity and the methyl functionality in the case of toluene and AMN. In doing so, it is possible to overcome the need of high-level electronic structure calculations for the evaluation of rate constants, as their computational cost increases exponentially with the number of heavy atoms of the selected species. To assess the validity of this approach, ab initio calculations are performed to derive the rate constants of the H-atom abstraction reactions by H, OH and CH3 radicals from both toluene and AMN. The kinetic model obtained satisfactorily agrees with the measured laminar flame speed profiles. Sensitivity and flux analyses are performed to investigate similarities and differences between the main reaction channels of toluene and AMN combustion, with the former leading to ∼6 cm/s faster flame speed at almost identical conditions (P=1 bar, T∼425 K), as evidenced by both kinetic model simulations and experimental findings.

Benzimidazole based derivatives as anticancer agents: Structure activity relationship analysis for various targets

AbstractBenzimidazole, the benzo derivative of imidazole, is a class of bicyclic aromatic organic compound consisting of six‐membered benzene ring fused to five‐membered imidazole at 4‐ and 5‐positions of the imidazole ring. It is a vital pharmacophore of many biologically active heterocyclic compounds with a variety of pharmacological activities. Over the time, benzimidazole and its derivatives have evolved as vibrant heterocyclic systems due to their potency in a wide range of bioactive compounds like analgesics, antifungals, anti‐inflammatory, antihypertensives, proton pump inhibitors, anti‐HIV, antiviral, and so on. Multi‐drug resistance in cancer that led to the failure of many chemotherapeutic drugs is a major concern. Various approaches are being developed to overcome this problem. One of them is target based drug discovery, which is an effective method to develop a novel anticancer drug. To develop newer drugs, previously reported work needs to be studied. Keeping this in mind, last 5 years literature on benzimidazole used as anticancer agents has been reviewed and summarized in the paper herein. This review article along with the target of cancer also deal with structure activity relationship of various compounds having benzimidazole ring.

Synthesis of pH Dependent Pyrazole, Imidazole, and Isoindolone Dipyrrinone Fluorophores using a Claisen-Schmidt Condensation Approach

The Claisen-Schmidt condensation reaction is an important methodology for the generation of methine-bridged conjugated bicyclic aromatic compounds. Through utilizing a base-mediated variant of the aldol reaction, a range of fluorescent and/or biologically relevant molecules can be accessed through a generally inexpensive and operationally simple synthetic approach.

Synthesis of pH Dependent Pyrazole, Imidazole, and Isoindolone Dipyrrinone Fluorophores using a Claisen-Schmidt Condensation Approach.

Methine-bridged conjugated bicyclic aromatic compounds are common constituents of a range of biologically relevant molecules such as porphyrins, dipyrrinones, and pharmaceuticals. Additionally, restricted rotation of these systems often results in highly to moderately fluorescent systems as observed in 3H,5H-dipyrrolo[1,2-c:2',1'-f]pyrimidin-3-ones, xanthoglows, pyrroloindolizinedione analogs, BODIPY analogs, and the phenolic and imidazolinone ring systems of Green Fluorescent Protein (GFP). This manuscript describes an inexpensive and operationally simple method of performing a Claisen-Schmidt condensation to generate a series of fluorescent pH dependent pyrazole/imidazole/isoindolone dipyrrinone analogs. While the methodology illustrates the synthesis of dipyrrinone analogs, it can be translated to produce a wide range of conjugated bicyclic aromatic compounds. The Claisen-Schmidt condensation reaction utilized in this method is limited in scope to nucleophiles and electrophiles that are enolizable under basic conditions (nucleophile component) and non-enolizable aldehydes (electrophile component). Additionally, both the nucleophilic and electrophilic reactants must contain functional groups that will not inadvertently react with hydroxide. Despite these limitations, this methodology offers access to completely novel systems that can be employed as biological or molecular probes.

A new precursor for synthesis of nickel-tungsten sulfide aromatic hydrogenation catalyst

The unsupported NiWS-catalyst was obtained from the precursor [Ph3S]2Ni(WS4)2 in a hydrocarbon medium (in situ) for hydrogenation bicyclic aromatic compounds. The precursor [Ph3S]2Ni(WS4)2 and the catalyst prepared on its basis were studied by the X-ray diffraction and X-ray absorption methods, XPS and TEM. It was found that the new catalyst formed in situ contains tungsten sulfide and nickel sulfide nanophases. Tungsten sulfide, which has a layered structure, partially forms an insertion compound with nickel that enters between the WS2 layers and bonds covalently to sulfur. The proposed catalyst has proved to be active in the hydrodearomatization processes of model aromatic compounds (naphthalene, methylnaphthalenes) and exhibited the maximum selectivity with the formation of decalins compared to other earlier studied catalysts formed from other precursors in the reaction medium.

Cu(II)/Vasicine Promoted Intramolecular C-O Formation: Synthesis of Benzoxazoles in EtOH.

Benzoxazoles are valuable bicyclic aromatic compounds; the construction of benzoxazoles via C-O cross-coupling reactions has attracted more and more attention. The best condition of C-O bond formation from o-haloanilides was carried out, taking Cu(OTf)2 (5 mol%) and vasicine (10 mol%) as the catalysts in EtOH in the presence of K2CO3 (2 eq.) for 12 h at 90°C. A series of 2-substituted benzoxazoles have been prepared in high yields from 2-bromoanilides and 2- iodioanilides under mild conditions. We have developed an efficient Cu-vasicine catalytic system for intramolecular C-O bond formation. This strategy is applicable to the synthesis of a wide variety of 2-substituted benzoxazoles by intramolecular O-arylation of o-haloanilides.

Enzymatic C–H activation of aromatic compounds through CO2 fixation

The direct C-H carboxylation of aromatic compounds is an attractive route to the corresponding carboxylic acids, but remains challenging under mild conditions. It has been proposed that the first step in anaerobic microbial degradation of recalcitrant aromatic compounds is a UbiD-mediated carboxylation. In this study, we use the UbiD enzyme ferulic acid decarboxylase (Fdc) in combination with a carboxylic acid reductase to create aromatic degradation-inspired cascade reactions, leading to efficient functionalization of styrene through CO2 fixation. We reveal that rational structure-guided laboratory evolution can expand the substrate scope of Fdc, resulting in activity on a range of mono- and bicyclic aromatic compounds through a single mutation. Selected variants demonstrated 150-fold improvement in the conversion of coumarillic acid to benzofuran + CO2 and unlocked reactivity towards naphthoic acid. Our data demonstrate that UbiD-mediated C-H activation is a versatile tool for the transformation of aryl/alkene compounds and CO2 into commodity chemicals.

Актуальність проблеми визначення діоксинів і поліхлорованих біфенілів (ПХБ) у продуктах для дитячого харчування

The Aim of the Article. Analysis of the current state of the problem of the dioxins and polychlorinated biphenyls (PCBs) determination in baby food products and the development of sample preparation methods for determining these xenobiotics in food products for infants and young children. Dioxins form a group of structurally and chemically related chlorinated tricyclic oxygen-containing aromatic compounds (congeners), which includes 75 polychlorinated dibenzo-para-dioxins (PCDDs) and 135 polychlorinated dibenzofurans (PCDFs). The most toxic congeners of dioxins, in which chlorine atoms along with other positions are necessarily in 2,3,7,8 positions of benzene rings. Their total number is 17:7 PCDD congeners and 10 PCDF congeners. A group of polychlorinated biphenyls (PCBs) – chlorinated bicyclic aromatic compounds, which consists of 209 different congeners, 12 of which have a spatial and electronic structure and exhibit toxicological properties similar to dioxins, therefore, they are called dioxin-like PCBs (DL-PCBs). In addition, when monitoring food products as a marker, a group of 6 PCBs was selected that did not exhibit dioxin-like toxicity and therefore did not belong to dioxin-like PCBs (NDL-PCBs). Thus, of the total number of 419 PCDDs, PCDFs and PCBs, only 35 are toxicologically significant, therefore, these compounds are subject to control in baby food products. To control the content of the amount of dioxins, the amount of dioxins and DL-PCBs and the amount of NDL-PCBs in foods for infants and children from one to three years in Ukraine, the maximum levels of these compounds on the basis of the order of the Ministry of Health of Ukraine No. 368 of 05/13/2013 were harmonized with the maximum allowable levels in foods for infants and young children in accordance with Commission Regulation (EU) No. 1259/2011. Methods for the analysis of dioxins and PCBs. Two instrumental analysis methods are used to determine dioxins and dioxin-like PCBs in foods for baby food: 1) a combination of high-resolution (capillary) gas chromatography with high-resolution mass spectrometry (GC/MS); 2) a combination of GCHR with tandem mass spectroscopy (GC/MS/MS). High-resolution (capillary) gas chromatography is used to determine non-dioxin-like (marker) PCBs. The stage of sample preparation, including the stages of extraction and purification, is key in determining dioxins and PCBs. Conclusions. The stage of sample preparation using automatic devices (liquid extraction under pressure, an automated extract purification system) and chromatographic columns was developed to further determine the mass concentration of dioxins and PCBs in baby food products. The developed procedures using devices for the automatic extraction and purification of the obtained extracts from baby food samples will make it possible in the future to determine PCDDs/PCDFs, ortho-unsubstituted, mono-ortho-substituted and marker PCBs in one sample. Key Words: dioxins, polychlorinated biphenyls, baby food.

Versatile synthesis of cadalene and iso-cadalene from himachalene mixtures: Evidence and application of unprecedented rearrangements

From a mixture of α-, β- and γ-himachalenes extracted from waste wood of Atlas cedar (Cedrus atlantica), cadalene (1,6-dimethyl-4-isopropylnaphthalene) and iso-cadalene (1,6-dimethyl-3-isopropylnaphthalene) were produced in two steps with up to 71% ± 5% yield through the ar-himachalene intermediate using I2 and/or AlCl3 as reagents. The selectivity is shown to sharply depend on the operating conditions: while I2/AlCl3 in dichloromethane promotes the formation of cadalene, the formation of iso-cadalene is favored in the presence of AlCl3 in cyclohexane. The bicyclic aromatic compounds were thus obtained through unique rearrangements involving sequential CC bond cleavage/formation and hydride transfer processes. In the absence of AlCl3 or I2, dihydrocurcumene was also found to be formed with up to 70% selectivity. A tentative mechanism is proposed and discussed.

Geochemical characterization of aromatic hydrocarbons in light crude oil from Tazhong Uplift deep reservoirs, Tarim Basin, NW China

The aromatic compounds in the light crude oil samples from the deep Tazhong structural and the Central Uplift zones in the Tarim Basin, NW China, were investigated by gas chromatography-mass spectrometry (GC-MS). The results from the study showed the distribution of the aromatic hydrocarbon compounds in the order of monocyclic > bicyclic > tricyclic with Tazhong structural zone No. 1 showing relatively higher abundance of mono- and bicyclic aromatic compound when compared with the other structural zones. Based on the distribution of the isomers of naphthalenes in the oils and the equivalent reflectance caculated from them, the oils in the Tazhong structural zone No. 1 indicated wider range of maturity levels and are generally more mature than the other zones. The implication of this is that, the oils in the structural zone No. 1 reservoirs might have been filled with lately generated oils from older source rock.

Highly regioselective cobalt-catalyzed [2+2+2] cycloaddition of fluorine-containing internal alkynes to construct various fluoroalkylated benzene derivatives

Novel cobalt-catalyzed [2+2+2] cycloaddition using fluorine-containing alkynes was described. Cyclotrimerization of fluorinated alkynes under the influence of CoCl2(dppb) in acetonitrile at 80 °C for 3 h took place smoothly, affording the corresponding benzene derivatives in excellent yields with high regioselectivity. Additionally, intermolecular cycloaddition of fluorinated alkynes with non-fluorinated diynes also proceeded in the presence of a catalytic amount of CoCl2((S)-BINAP) and ZnI2 to give various bicyclic aromatic compounds in high yields.

Palladium-Catalyzed Ring-Opening Coupling of Cyclobutenols with Aryl Halides

A palladium(0)-catalyzed ring-opening cross-coupling reaction between tert-cyclobutenols and aryl halides produces γ-arylated β,γ-unsaturated ketones. In the case of aryl halides bearing functional groups at the ortho position, the resulting ring-opened ketones undergo intramolecular condensation to afford bicyclic aromatic compounds.

Separation and Purification of Indole in Model Coal Tar Fraction of 9 Compounds System

ABSTRACTSeparation and purification of indole present in model coal tar fraction was examined by the combination of extraction to separate indole from the crude model coal tar fraction, distillation to obtain high concentration of indole in the extract, and solute crystallization (SC) to obtain high-purity indole present in indole-enriched distillate. The model fraction was made up of four types of nitrogen heterocyclic compounds (quinoline, iso-quinoline, 4.66% indole, and quinaldine), three types of bicyclic aromatic compounds (1-methylnaphthalene, 2-methylnaphthalene, and dimethylnaphthalene), biphenyl, and phenyl ether. Aqueous solutions of formamide and n-hexane were used as the extraction solvent and the SC solvent, respectively. Through the combination of formamide extraction, distillation, and SC using n-hexane in this work, 99.5% indole was recovered. We confirmed that the combination examined by this work was one of the very useful combinations for the high-purity purification of indole present in the coal tar fraction.

Comparison of Methanol with Formamide on Separation of Nitrogen Heterocyclic Compounds from Model Coal Tar Fraction by Batch Cocurrent Multistage Equilibrium Extraction

The separation of nitrogen heterocyclic compounds (NHC) contained in a model coal tar fraction comprising four kinds of NHC [indole (In), quinoline (Q), iso-quinoline (iQ), quinaldine (Qu)], three kinds of bicyclic aromatic compound (BAC) [1-methylnaphthalene (1MN), 2-methylnaphthalene (2MN), dimethylnaphthalene (DMN) mixture with ten structural isomers (DMNs; regarded as one component)], biphenyl (Bp), and phenyl ether (Pe) was examined by batch cocurrent three stages equilibrium extraction. The model coal tar fraction used as a raw material in this work was prepared according to the components and compositions contained in coal tar fraction (distilled temperature ranges: 240–265°C). An aqueous solution of formamide and that of methanol were used as solvent, respectively. The distribution coefficient of the entire NHC (NHCs) summed four kinds of NHC was much larger than that of the entire BAC (BACs) summed three kinds of BAC, Bp, and Pe. Irrespective of solvent used in this work, the NHCs was recovered more than 90% through three stages of the equilibrium extraction. The selectivity of NHCs based on BACs obtained through the 3 stages equilibrium extraction using an aqueous solution of formamide was higher 3.6–8 times than that using an aqueous solution of methanol. Furthermore, we investigated the recovery process of NHCs contained in coal tar fraction using the formamide experimental results obtained from this work.