Benzene Moiety Research Articles

Furobenzotropolones A, B and 3-Hydroxyepicoccone B with Antioxidative Activity from Mangrove Endophytic Fungus Epicoccum nigrum MLY-3.

Three new metabolites, furobenzotropolones A, B (1–2) with unusual benzene and dihydrofuran moieties and 3-hydroxyepicoccone B (3), together with seven known compounds (4–10) were obtained from the endophytic fungus Epicoccum nigrum MLY-3 isolated from the fresh leaf of mangrove plant Bruguiear gymnorrhiza collected from Zhuhai. Their structures were assigned by the analysis of UV, IR, NMR, and mass spectroscopic data. Compound 1 was further confirmed by single-crystal X-ray diffraction experiment using Cu Kα radiation. In antioxidant activities in vitro, compounds 2, 3, 5, and 8 showed promising DPPH· scavenging activity with IC50 values ranging from 14.7 to 29.3 µM. Compounds 2, 3, 5, 7, and 8 exhibited promising potent activity in scavenging ABTS· with IC50 values in the range of 18–29.2 µM, which was stronger than that of the positive control ascorbic acid (IC50 = 33.6 ± 0.8 µM).

Unraveling the Mechanism for Tuning the Fluorescence of Fluorescein Derivatives: The Role of the Conical Intersection and nπ* State.

Although a large number of fluorescein derivatives have been developed and applied in many different fields, the general mechanisms for tuning the fluorescence of fluorescein derivatives still remain uncovered. Herein, we found that the fluorescence quenching of neutral form of fluorescein derivatives in acidic medium resulted from a dark nπ* state, whereas the fluorescence of the anionic form of fluorescein derivatives in the gas phase and alkaline solutions was tuned by minimal energy conical intersection (MECI). The formation of MECI involved significant rotation of benzene ring and flip-flop motion of xanthene moiety, which would be restricted by intermolecular hydrogen bonding and lowering temperature. The energy barrier for reaching MECI depended on the substituents in the benzene moiety in accordance with experimentally observed substituent effects. These unprecedented mechanisms would lead to a recognition of fluorescein derivatives and could provide a correct and instructive design strategy for further developing new fluorescein derivatives.

Probing the Fate of Different Structures of Beta-Lactam Antibiotics: Hydrolysis, Mineral Capture, and Influence of Organic Matter

Beta-lactam antibiotics, which are used extensively in human and veterinary applications, are commonly detected in surface waters. To examine how the distinct structures of different generations of beta-lactam antibiotics can influence their persistence or degradation in environmental aqueous media, we examined the fate of two penams (amoxicillin and cloxacillin) and two cephems (cephalexin and ceftriaxone) at pH 5.0 and pH 7.0. By contrast to the lack of hydrolysis of the penam antibiotics at both pHs, we observed hydrolysis of cephalexin at pH 7.0 (t1/2 = 12 d) and ceftriaxone at pH 5.0 (t1/2 = 2.8 d). Using high-performance liquid chromatography coupled with a diode array detector or a high-resolution mass spectrometer, we were able to confirm thiotriazinone and 3-desacetyl cefotaxime as major hydrolysis products of ceftriaxone, and propose the hydrolytic cleavage of the benzene and cephem moieties from cephalexin. In addition, we studied the effects of smectite clay particles suspended in solutions without or with dissolved organic matter. The adsorption capacity of the clay was 4- to 9-fold higher at pH 7.0 than at pH 5.0. Subsequent X-ray diffraction analysis revealed that the antibiotic adsorption was not within the clay interlayer nanopores but occurred primarily on the external clay surfaces. The addition of dissolved organic matter interfered with the adsorption of a cephem antibiotic (ceftriaxone) on the clay, but the adsorption of a penam antibiotic (amoxicillin) remained unaffected. We employed molecular modeling simulations to probe the mechanisms of adsorption on the mineral surface. Our findings offer new insights on how the compound structures can dictate different fates of the beta-lactam class of antibiotics in environmental media.

Phthalocyanine, naphthalocyanine and their derivatives as corrosion inhibitors: A review

Phthalocyanine and naphthalocyanine are important classes of nitrogenous based five-membered heterocyclic compounds in which benzene and naphthalene moieties are fused with porphyrin structure, respectively. Because of the presence of four nitrogen atoms with free unshared electron pairs and various aromatic rings with extensively conjugated π-electrons, phthalocyanine, naphthalocyanine and their derivatives are assume to form strong chelating complexes with metallic atoms. Because of their this property these compounds act as excellent anticorrosive materials in aqueous as well as coating conditions for various metal/electrolyte systems. Present review article aims to collect the past and present advancements on phthalocyanine, naphthalocyanine and their derivatives as corrosion inhibitors. Though outcomes it can be seen that these compounds become effective by retarding both anodic and cathodic reactions and mostly behaving as mixed-type inhibitors. Adsorption of phthalocyanine, naphthalocyanine and their derivatives mostly followed the Langmuir adsorption isotherm.

The structure of a confiscated street drug: 6-Monoacetyl morphine hydrochloride trihydrate - C19H22NO4Cl·3H2O

Since street drugs are frequently and rapidly modified, in order to circumvent the current laws that make them illicit, it is necessary to fully identify them by single crystal X-ray diffraction; subsequently, ideal powder patterns are computed for rapid identification of additional confiscations, which are mostly available in powder form. Monoacetyl morphine is found in samples of heroin as a by-product of incomplete synthesis, or from degradation of diacetyl morphine caused by heat, humidity, or pH changes. It is formed by the hydrolysis of the acetyl function on the benzene moiety of the morphine ring, thereby inserting an OH moiety at that site. This compound, 6-monoacetyl morphine, is the primary and active metabolite of heroin, rapidly hydrolyzed in the user’s blood. Herein, we describe the structure of 6-monoacetyl morphine, IUPAC name: [(4R,4aR,7S,7aR,12bS)-9-hydroxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl] acetate (A), as the trihydrated hydrochloride, whose structure has not been described previously. Our crystals belong in space group P212121 with cell parameters of a = 6.9367(2), b = 13.0374(3), c = 21.9856(6) Å, V = 1988.30 (9) Å3; its composition is C19H22NO4Cl·3H2O, and Z = 4.0. A full sphere of data was collected at 100 K using CuKα radiation (λ = 1.54178 Å), yielding 3594 unique reflections measured and a final R-factor = 4.1%, with a Flack parameter = 0.05(1).

Enhanced recovery of acetophenone and 1‐phenylethanol from petrochemical effluent by highly porous starch-based hypercrosslinked polymers

It is highly desirable to design and fabricate porous bio-based adsorbent for efficient and selective recovery of acetophenone (AP) and 1-phenylethanol (PE) from the effluent of propylene oxide and styrene monomer co-production (PO/SM) process. Herein, using cassava starch as the starting material, starch-graft-styrene hypercrosslinked polymers (SSHCPs) were designed and synthesized facilely by starch-graft-styrene copolymerization and subsequent crosslinking via a Friedel-Crafts alkylation route. SSHCP-3 (knitted by 4,4′-bis-(chloromethyl)-1,1′-biphenyl) shows high BET surface area (818 m2·g−1), large pore volume, and high thermal stability, making it a highly efficient adsorbent for removal of aromatic pollutants from water. SSHCP-3 showed high uptake for AP (2.82 mmol·g−1) and selectivity (4.95) of AP over PE in binary-solute adsorption experiments. Spectral studies and theoretical calculation demonstrated that AP and PE uptake could occur at glucose units and benzene moiety via van der Waals interaction and π-π stacking interactions. SSHCP-3 also showed excellent adsorption efficiency of AP (93.6%) and PE (74.4%) in the wastewater discharged from PO/SM process. These results demonstrated that transforming styrene and starch to bio-based hypercrosslinked polymers provides an environmentally friendly and attractive strategy for recovery of AP and PE in practical application.

New benzimidazolequinones as trypanosomicidal agents

Herein, the design and synthesis of new 2-phenyl(pyridinyl)benzimidazolequinones and their 5-phenoxy derivatives as potential anti-Trypanosoma cruzi agents are described. The compounds were evaluated in vitro against the epimastigotes and trypomastigote forms of Trypanosoma cruzi. The replacing of a benzene moiety in the naphthoquinone system by an imidazole enhanced the trypanosomicidal activity against Trypanosoma cruzi. Three of the tested compounds (11a-c) showed potent trypanosomicidal activity and compound 11a, with IC50 of 0.65 μM on the trypomastigote form of T. cruzi, proved to be 15 times more active than nifurtimox. Additionally, molecular docking studies indicate that the quinone derivatives 11a-c could have a multitarget profile interacting preferentially with trypanothione reductase and Old Yellow Enzyme.

Efficient and stable inverted perovskite solar cells incorporating 4-Fluorobenzylammonium iodide

Improving the stability of high-performance perovskite solar cells (PVSCs) against humid air poses a substantial challenge for their future development. To address this issue, here we have incorporated a trace amount of 4-fluorobenzylammonium iodide into MAPbI3 based PVSCs, and significantly improved the efficiency and stability. Through spectroscopy measurements, space charge limited current analysis, etc., we find that the incorporation of 4-fluorobenzylammonium iodide can passivate defects, improve charge transport, and thus, increase the power conversion efficiency (PCE) from 18.1% to 19.1%. In the meanwhile, the fluorinated benzene moiety confers the hydrophobic character to the perovskite film and device, and enhances the device stability against moisture. This work should have implication toward stable and high-performance PVSCs for commercialization.

Fluorescence Probes for Imaging Basic Carboxypeptidase Activity in Living Cells with High Intracellular Retention.

Basic carboxypeptidases (basic CPs) cleave the C-terminal basic amino acid of peptides, and their activity is upregulated in some types of cancers. Therefore, detecting the activity of basic CPs in living cells would be important not only for studying the physiological functions of these enzymes but also for visualization of cancerous tissues. Here, we report two fluorescein diacetate (FDA)-based activatable fluorescence probes, named 5ArgAF-FDA and 5LysAF-FDA, in which the substrate amino acid arginine or lysine is conjugated to the benzene moiety via an azoformyl linker. In live-cell fluorescence imaging of CPM, one of the seven basic CPs, 5ArgAF-FDA showed a larger intracellular fluorescence increase than did 5LysAF-FDA within a few minutes. This increase was inhibited by coincubation with 2-mercaptomethyl-3-guanidinoethylthiopropanoic acid (MGTA), an inhibitor of basic CPs. When 5ArgAF-FDA was applied to a coculture of two breast cancer cell lines with different CPM activities, the fluorescence increase in individual cells was correlated with the expression level of CPM, suggesting that 5ArgAF-FDA has the ability to distinguish cell lines having different levels of CPM activity, owing to its high intracellular retention. We believe these probes will be useful for imaging cancers with upregulated basic CP activity.

Mitoapocynin, a mitochondria targeted derivative of apocynin induces mitochondrial ROS generation and apoptosis in multiple cell types including cardiac myoblasts: a potential constraint to its therapeutic use.

Mitoapocynin is a triphenylphosphonium conjugated derivative of apocynin that specifically locates to the mitochondria. It has been developed as a mitochondrially targeted therapeutic antioxidant. We attempted to attenuate the mitochondrial ROS induced in H9c2 cardiac myoblast cells treated with norepinephrine. Mitoapocynin was a poor quencher of total ROS as detected by the fluoroprobe DCFH-DA. Using mitochondrial superoxide specific probe MitoSoxRed, we found that 5-10µM mitoapocynin itself induces superoxide over and above that is generated by the norepinephrine treatment. A supposedly control molecule to mitoapocynin, the synthetic compound PhC11TPP, having the triphenylphosphonium group and a benzene moiety with C11 aliphatic chain spacer was also found to be a robust inducer of mitochondrial ROS. Subsequent assays with several cell lines viz., NIH3T3, HEK293, Neuro2A, MCF-7 and H9c2, showed that prolonged exposure to mitoapocynin induces cell death by apoptosis that can be partially prevented by the general antioxidant N-acetyl cysteine. Analyses of mitochondrial electron transport complexes by Blue Native Polyacrylamide gel electrophoresis showed that both mitoapocynin and PhC11TPP disrupt the mitochondrial Complex I and V, and in addition, PhC11TPP also damages the Complex IV. Our data thus highlights the limitations of the therapeutic use of mitoapocynin as an antioxidant.

The study on the inhibitory mechanism of JTZ-951 and its analogue against prolyl hydroxylase-2 to mediate the response to hypoxia in the process of sports

In the previous literatures, we found that the bioactivity of prolyl hydroxylase-2 (PHD-2) that can mediate the response to hypoxia in the process of sports was suppressed by JTZ-951 and its analogues. To investigate the interaction mechanism, the complexes of PHD-2 with its inhibitors were explored by using molecular docking, molecular dynamics simulation, and binding free energy decomposition calculation methods. The results of energy decomposition are consistent with available experimental results and suggest that the binding affinity of compound 14 located in the activity region of PHD-2 is more stable than those of compound 4 and compound 9. Due to the propyl benzene moiety of compound 14, compound 14 can exactly locate in the activity pocket of PHD-2 (residues of ASP-254, TYR-303, TYR-310, ILE-327, LEU-343, GLU-375, VAL-376 and ARG-411 are the binding sites in PHD-2-compound 14 complex) via the binding energy calculation between all residues of PHD-2 and inhibitors. In addition, compound 4 and 9 are far away from the activity core of PHD-1, resulting in the lower inhibitory activity. These results suggested that the propyl benzene group in compound 14 had a greater impact on the inhibitory activity. This work will improve the development of novel inhibitors targeting PHD-2.

Binding of azobenzene andp-diaminoazobenzene to the human voltage-gated sodium channel Nav1.4

The activity of voltage-gated ion channels can be controlled by the binding of photoswitches inside their internal cavity and subsequent light irradiation. We investigated the binding of azobenzene and p-diaminoazobenzene to the human Nav1.4 channel in the inactivated state by means of Gaussian accelerated molecular dynamics simulations and free-energy computations. Three stable binding pockets were identified for each of the two photoswitches. In all the cases, the binding is controlled by the balance between the favorable hydrophobic interactions of the ligands with the nonpolar residues of the protein and the unfavorable polar solvation energy. In addition, electrostatic interactions between the ligand and the polar aminoacids are also relevant for p-diaminoazobenzene due to the presence of the amino groups on the benzene moieties. These groups participate in hydrogen bonding in the most favorable binding pocket and in long-range electrostatic interactions in the other pockets. The thermodinamically preferred binding sites found for both photoswitches are close to the selectivity filter of the channel. Therefore, it is very likely that the binding of these ligands will induce alterations in the ion conduction through the channel.

Five naphthalene azo benzene ligands complexed with copper metals: An excellent in-situ catecholase catalyst

In order to mimic the function of catecholase activity, in situ copper (II) complexes of five ligands containing benzene and naphthalene moieties ponded by dazenyl groups: (E)-1-((2-methoxyphenyl)diazenyl)naphthalen-2-ol L1, (E)-1-((3-methoxyphenyl)diazenyl)naphthalen-2-ol L2, (E)-1- ((4-methoxyphenyl)diazenyl)naphthalen-2-ol L3, (E)-1-((2,4,6-tribromophenyl)diazenyl)naphthalen-2-ol L4, and (E)-1-((3-nitrophenyl)diazenyl)naphthalen-2-ol L5 were reported and examined, in combination with different copper salts, for their catecholase activities at ambient conditions. All complexes of tested ligands catalyze the studied reaction with the rate ranging from higher 25.1 µmol L−1 min−1 for the combination of two equivalents of ligand and one equivalent of metal in methanol, to weaker rate of 0.51 µmol L−1 min−1 for the combination of one equivalent of ligand and two equivalent of metal salt in methanol.

Meta-Non-flat substituents: a novel molecular design to improve aqueous solubility in small molecule drug discovery.

Aqueous solubility is a key requirement for small-molecule drug candidates. Here, we investigated the regioisomer-physicochemical property relationships of disubstituted benzenes. We found that meta-isomers bearing non-flat substituents tend to possess the lowest melting point and the highest thermodynamic aqueous solubility among the regioisomers. The examination of pharmaceutical compounds containing a disubstituted benzene moiety supported the idea that the introduction of a non-flat substituent at the meta position of a benzene substructure would be a promising approach for medicinal chemists aiming to improve the thermodynamic aqueous solubility of drug candidates, even though it might not be universally effective.

2-Сycloalkyl-(hetaryl-)-[1,2,4]triazol[1,5-с]quinazolines: synthesis, physical and chemical properties and antibacterial activity

In spite of the achievements in the chemistry of triazoloquinazolines, the synthetic possibilities of this class of compounds are not exhausted, some problems remain unresolved and require further study. 2-R-[1,2,4]triazolo[1,5-с]quinazolines are among them due to insufficiently explored but at the same time interesting in both chemical and biological aspects.
 Undoubtedly «pharmacophore» has the crucial role in the response of a biological action. It is contained in this heterocycle namely the substitute position 2.
 In view of the above, we attempted to modify triazolo[1,5-с]quinazoline by introducing a methyl group or halogens (fluorine, chlorine, bromine) into a benzene moiety and a triazole moiety of a cycloalkyl or heterocyclic substituent molecule.
 The aim of this work is to develop simple and affordable methods of the synthesis of new 2-cycloalkyl-(hetaryl-)-[1,2,4]triazolo[1,5-с]quinazolines, quinazolines, to study their physical and chemical properties and to conduct primary screening for antibacterial activity
 The antimicrobial activity of the synthesized chemical compounds was performed by the method of two-fold serial dilutions in Mueller–Hinton broth (for strains of Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853) and in Saburo broth (for Candida albicans ATCC 885–653). MIC (minimum inhibitory concentration), MBсC and MFсC (minimum bactericidal and fungicidal concentrations respectively) was determined.
 The optimal method of synthesis of 2-cycloalkyl-(hetaryl-)-[1,2,4]triazolo[1,5-с]quinazolines, which represent value as chemical reagents for further transformations and study of biological activity is substantiated and developed. The possibility of «one-pot» synthesis of the target compounds with 4-hydrazinoquinazolines and cycloalkylcarboxylic acids under conditions of activation of the carboxyl group N,N¢-carbonyldiimidazole is shown. Conducted microbiological screening of 2-cycloalkyl-(hetaryl-)-[1,2,4]triazolo[1,5-с]quinazolines revealed a number of promising compounds that inhibit the growth of St. aureus (МІС 25‒50 μg/ml) and C. albicans (25‒50 μg/ml).
 The optimal method of synthesis of 2-cycloalkyl-(hetaryl-)-[1,2,4]triazolo[1,5-с]quinazolin by cyclocondensation (3Н-quinazoline-4-ylidene)­hydrazides withcycloalkyl-(hetaryl)carboxylic acidsis substantiated and developed. The structure and individuality of the synthesized compounds were confirmed by elemental analysis, physicochemical methods (1H NMR-spectroscopy, HPLC/MS). The peculiarity of the 1H NMR spectra of this heterocycle is discussed, namely the significant paramagnetic shift of benzene protons and the characteristic weak-field single-proton singlet of the proton of position 5 of the heterocycle, which is a confirmation of recycling isomerization by Dimrot rearrangement. The structure-activity relationship is discussed and the study of the most active compounds for a wider range of strains and resistant strains of bacteria and fungi is recommended.

Benzene Linked Dipodal Naphthalene: Chemosensor with Colorimetric Enhancement and Fluorimetric Quenching for Fe3+ Ion and its Application in Live Cell Imaging

In this work, two naphthalene scaffolds dangling around a benzene moiety as a colorimetric and fluorimetric probe for Fe3+ in aqueous media have been reported. Recognition processes of Fe3+ were shown to be scarcely influenced by other coexisting metal ions. The probe exhibits a turn on colorimetric and a turn off fluorimetric detection of Fe3+ ions. The association constant for sensor 1–Fe3+ complex was found as Ka = 1.12 × 105 M–1 with the detection limit of 1.7 nM. The chemosensor has been utilized for bioimaging of E. coli cells.

Photoadduct of anthracenophane: Bi(anthracene-9,10-dimethylene)

The electronic structure of photoadduct (PA) of bi(anthracene-9,10-dimethylene) (anthracenophane; ACP) has been studied in the gas phase by UV photoelectron spectroscopy (UPS) and quantum chemical calculations. PA was obtained by photoisomerization of 9,10-anthracenophane induced by UV light from the He discharge lamp which is also used as an ionization radiation source for UPS. The electronic structure of PA was found to be very similar to the electronic structure of dianthracene (DA). Molecules of PA and DA both contain four non-conjugated benzene moieties with “butterfly” shaped molecular structures.

The role of surface chemistry of modified MWCNT on the development and characteristics of Pt supported catalysts

The performance and stability of electrocatalysts strongly depend on the physicochemical characteristics, such as the surface area, the crystalline structure, size and shape of the particles and the interactions with the support. Platinum (Pt) is one of the most versatile elements in catalysis, efficiently mediating a multitude of chemical reactions. Reducing the demand for expensive Pt is a major driving force in catalysis research. The objective of the present study is the development of electrocatalysts with innovative features and focuses on the synthesis and characterization of highly dispersed Pt supported catalysts using functionalized Multi-Wall Carbon Nanotubes (f-MWCNT) as the substrate. The choice of the substrate was based on the unique properties of carbon nanotubes that generate strong interest for their use in many nano-material devices in catalysis, batteries, optics, gas storage, electronics, sensors and others. Various chemical pathways were used to modify the sidewalls of MWCNT and introduce several covalently attached groups like pyridine, sulfonic acid, carboxyl, benzene or zwitterion type moieties. Using these substrates, deposition of Pt nanoparticles was realized by means of the polyol synthetic procedure. The parameters of the synthetic procedure differentiate the reduction/deposition mechanism. The surface chemistry and functionalities of the support and the diverse reaction conditions resulted in differentiations of the properties, not only in terms of quantitative deposition, but also with respect to platinum oxidation state, nanoparticle size and dispersion and overall catalyst morphology. The combined characterization techniques used shed light into the fundamental understanding of the support effect on the final properties, while metal-support interactions are intensely discussed.

Synthesis, Insecticidal Activities, and Structure-Activity Relationship of Phenylpyrazole Derivatives Containing a Fluoro-Substituted Benzene Moiety.

Fluorinated organic compounds represent a growing and important family of commercial chemicals. Introduction of fluorine into active ingredients has become an effective way to develop modern crop protection products. Given the particular properties of fluorine and high efficiency and selectivity of diamide insecticides, we designed and synthesized 27 anthranilic diamides analogues containing fluoro-sustituted phenylpyrazole. A preliminary bioassay indicated that most target compounds exhibited good biological activity against Mythimna separata and Plutella xylostella. Compound IIIf containing a 2,4,6-trifluoro-substituted benzene ring showed 43% insecticidal activity against M. separata at 0.1 mg L-1, while the control chlorantraniliprole was 36%. The activity of IIIe against P. xylostella at 10-5 mg L-1 was 94%, compared with that of the control being 70%. Thus, introduction of fluorine into diamide insecticides was useful for increasing activity. Insect electrophysiology studies showed that the calcium concentration in the nerve cells of third M. separata larvae was elevated by IIIf, which further confirmed that ryanodine receptor (RyR) was its potential target.

Application of Pleurotus ostreatus to efficient removal of selected antidepressants and immunosuppressant

Disposed pharmaceuticals constitute a significant threat to the environment due to the high consumption of drugs and inefficient treatment of wastewater. In this paper, we first described the efficient removal of a series of antidepressants and immunosuppressant from a cultivation medium carried out by white-rot fungus, Pleurotus ostreatus. We determined the removal efficiency of pharmaceuticals and the activity of fungal ligninolytic enzymes over time, as well as the toxicity of pre- and post-cultivation medium to Spirostomum ambiguum. We showed that P. ostreatus can remove from the model medium most of the pharmaceuticals studied, including clomipramine, mianserin, paroxetine, sertraline, and mycophenolic acid. Pharmaceuticals containing phenolic or benzene moieties, likewise in the natural monolignols, were removed in a high efficiency within a short time. The activity of the fungal ligninolytic enzymes, laccase, and lignin peroxidase, in the cultivation medium, was three times higher in the presence of the pharmaceuticals, which justifies their contribution to the degradation. The post-cultivation medium showed lower toxicity than pre-cultivation medium and toxic units were 7- and 2-fold lower for the sublethal and lethal response, respectively. Over twenty metabolites we detected resulted mostly from oxygenation or demethylation of parent pharmaceuticals. The biological treatment we developed using P. ostreatus-based system should be convenient and effective in mycoremediation of environmental wastewater polluted with emerging contaminants including monolignol-like antidepressants and immunosuppressant.