benzofurans and 1-3-diphenylisobenzofuran

In this review we first provide an introductory description of the singlet fission phenomenon and then describe the ground and electronically excited states of the parent 1,3-diphenylisobenzofuran chromophore (1) and about a dozen of its derivatives. A discussion of singlet fission in thin polycrystalline layers of these materials follows. The highest quantum yield of triplet formation by singlet fission, 200% at 80 K, is found in one of the two known crystal modification of the parent. In the other modification and in many derivatives, excimer formation competes successfully and triplet yields are low. A description of solution photophysics of covalent dimers is described in the next section. Triplet yields are very low, but interesting phenomena are uncovered. One is an observation of a separated-charges (charge-transfer) intermediate in highly polar solvents. The other is an observation of excitation isomerism in both singlet and triplet states, where in one isomer the excitation is delocalized over both halves of the covalent dimer, whereas in the other it is localized on one of the halves. In the last section we present the operation of a simple device illustrating the use of triplets generated by singlet fission for charge separation.

Topics: Benzofurans; Electrons; Models, Chemical; Quantum Theory; Solvents

Topics: 9,10-Dimethyl-1,2-benzanthracene; Amines; Animals; Arachidonic Acid; Arachidonic Acids; Benzo(a)pyrene; Benzofurans; Benzopyrenes; Carcinogens; Dihydroxydihydrobenzopyrenes; Luminol; Nitrofurans; Oxidation-Reduction; Oxyphenbutazone; Phenylbutazone; Polycyclic Compounds; Prostaglandin-Endoperoxide Synthases; Prostaglandins

Sulphydryl oxidase, an enzyme isolated from milk, catalyses the de novo synthesis of disulphide bonds. Thiol groups in amino acids or their derivatives, peptides, and proteins are oxidized; molecular oxygen serves as the electron acceptor and undergoes a two-electron reduction to hydrogen peroxide. Michaelis constants vary considerably amongst various substrates; glutathione is a particularly good substrate. Inhibition studies and oxidation of 1,3-diphenylisobenzofuran suggest a mechanism involving an electron transfer to singlet O2 forming an enzyme-bound hydroperoxy group. Evidence for a direct interaction of the enzyme with horseradish peroxidase was also obtained. Although protein-folding appears to be thermodynamically favoured, rates of spontaneous acquisition of functional three-dimensional structures in disulphide-containing proteins have appeared disturbingly slow. In the presence of sulphydryl oxidase, functional structure is rapidly acquired by both reductively unfolded ribonuclease A and reductively denatured immobilized chymotrypsinogen A as judged by restoration of native fluorescence characteristics and biological activity. Preliminary data suggest that unlike thiol:protein-disulphide oxidoreductase, protein-disulphide isomerase, or GSSG/GSH redox systems, sulphydryl oxidase does not permit a 'reshuffling' of disulphide bonds.

Topics: Animals; Benzofurans; Catalysis; Cattle; Disulfides; Horseradish Peroxidase; Kinetics; Milk; Oxidoreductases; Protein Conformation

Mitochondria are crucial regulators of the intrinsic pathway of apoptosis. Herein, we report a photosensitizer-conjugated camptothecin (CPT)-based prodrug for combinative chemo-photodynamic treatment of solid tumors with cascade activations. Upon light irradiation, our prodrug can effectively target the mitochondria of cancer cells, generate singlet oxygen to increase the level of reactive oxygen species (ROS) and trigger ROS-responsive release of CPT, which synergistically induce mitochondrial damage and cause the apoptosis of cancer cells, therefore achieving high therapeutic efficacy for solid tumors and minimized adverse effects to normal tissues. Our prodrug holds great promise as a potent and inspiring means for cancer treatment.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Benzofurans; Camptothecin; Cell Line, Tumor; Drug Therapy, Combination; Humans; Mitochondria; Neoplasms; Photochemotherapy; Photosensitizing Agents; Prodrugs; Reactive Oxygen Species

A dual-functional nanosysterm is developed by means of Chlorin e6 (Ce6) as photosensitizer and 1,3-Diphenylisobenzofuran (DPBF) as fluorescent singlet oxygen (

Topics: Antineoplastic Agents; Benzofurans; Cell Survival; Chlorophyllides; Fluorescent Dyes; HeLa Cells; Humans; Light; Nanoparticles; Photochemotherapy; Photosensitizing Agents; Polymers; Porphyrins; Singlet Oxygen

Cancer is the second leading cause of death globally and is responsible, where about 1 in 6 deaths in the world. Therefore, there is a need to develop effective antitumor agents that are targeted only to the specific site of the tumor to improve the efficiency of cancer diagnosis and treatment and, consequently, limit the unwanted systemic side effects currently obtained by the use of chemotherapeutic agents. In this context, due to its unique physical and chemical properties of graphene oxide (GO), it has attracted interest in biomedicine for cancer therapy.. In this study, we report the in vivo application of nanocomposites based on Graphene Oxide (nc-GO) with surface modified with PEG-folic acid, Rhodamine B and Indocyanine Green. In addition to displaying red fluorescence spectra Rhodamine B as the fluorescent label), in vivo experiments were performed using nc-GO to apply Photodynamic Therapy (PDT) and Photothermal Therapy (PTT) in the treatment of Ehrlich tumors in mice using NIR light (808 nm 1.8 W/cm2).. This study based on fluorescence images was performed in the tumor in order to obtain the highest concentration of nc-GO in the tumor as a function of time (time after intraperitoneal injection). The time obtained was used for the efficient treatment of the tumor by PDT/PTT.. The current study shows an example of successful using nc-GO nanocomposites as a theranostic nanomedicine to perform simultaneously in vivo fluorescence diagnostic as well as combined PDT-PTT effects for cancer treatments.

Topics: Adsorption; Animals; Benzofurans; Carcinoma, Ehrlich Tumor; Graphite; Humans; Indocyanine Green; Male; Mice; Nanocomposites; Particle Size; Photochemotherapy; Photothermal Therapy; Rhodamines; Spectrometry, Fluorescence; Spectrum Analysis, Raman; Static Electricity; Theranostic Nanomedicine; Tumor Burden

In this study, a family of porphyrins based on 5,10,15,20-Tetrakis(4-ethylphenyl)porphyrin (

Topics: Benzofurans; Cell Survival; Inhibitory Concentration 50; Leishmania; Leishmania braziliensis; Light; Metalloporphyrins; Photochemotherapy; Photosensitizing Agents; Porphyrins; Singlet Oxygen

Combination of photodynamic therapy (PDT) and photothermal therapy (PTT) generally requires different components to build a composite irradiated with different excitation lights. One component photoactive agent for enhanced combination of PDT and PTT under the excitation of a single wavelength light source is more urgent in tumor phototherapy via adjusting spatial arrangement of photoactive units. Herein, porphyrin-based covalent organic framework nanoparticles (COF-366 NPs) were synthesized to control the orderly spatial arrangement of the photoactive building units and firstly used for antitumor therapy in vivo. COF-366 NPs provide the simultaneous therapy of PDT and PTT under a single wavelength light source with the monitoring of photoacoustic (PA) imaging, which makes the operation simpler and more convenient. COF-366 NPs had achieved good phototherapy effect even in the face of large tumors. The prepared multifunctional COF-366 NPs open up a new avenue to phototherapeutic materials and expand the application range of covalent organic framework.

Topics: Animals; Benzofurans; Cell Line, Tumor; Combined Modality Therapy; Female; Hemolysis; Magnetic Resonance Spectroscopy; Mice; Mice, Inbred BALB C; Mice, Nude; Nanoparticles; Neoplasm Transplantation; Neoplasms; Neoplasms, Experimental; Organic Chemicals; Photoacoustic Techniques; Phototherapy; Porphyrins; Rabbits; Reactive Oxygen Species

Conjugated polymer hybrid nanoparticles (NPs) loaded with both indocyanine green (ICG) and 1,3-diphenylisobenzofuran (DPBF) are described. The NPs are dually functional in that ICG acts as the photosensitizer, and DPBF as a probe for singlet oxygen (

Topics: Benzofurans; Fluorescence Resonance Energy Transfer; Hep G2 Cells; Humans; Indocyanine Green; Infrared Rays; Limit of Detection; Nanoparticles; Photochemotherapy; Photosensitizing Agents; Polylysine; Singlet Oxygen

meso-Naphthalene substituted BODIPY compounds were prepared in a facile one pot reaction. The naphthalene functionalization of BODIPY leads up to a 5-fold increase in the formation efficiency of excited triplet state and singlet oxygen in polar solvents. Steady state and time resolved fluorescence, laser flash photolysis, and quantum chemistry methods were used to reveal the mechanism. All measured data and quantum chemical results suggest that these systems can be viewed as electron donor-acceptor (D-A) pair (BODIPY acts as the acceptor), photoinduced charge transfer (PCT) or photoinduced electron transfer (PET) occurs upon photo excitation (D-A+hν→D

Topics: Benzofurans; Boron Compounds; Electrons; Light; Luminescence; Models, Molecular; Molecular Conformation; Naphthalenes; Oxidation-Reduction; Photolysis; Photosensitizing Agents; Quantum Theory; Singlet Oxygen; Solvents; Spectrometry, Fluorescence; Spectroscopy, Near-Infrared

1,3-Diphenylisobenzofuran (DPBF) has been developed as a selective probe for the detection and quantitative determination of hydrogen peroxide in samples containing different reactive nitrogen and oxygen species (RNOS). DPBF is a fluorescent probe which, for almost 20 years, was believed to react in a highly specific manner toward some reactive oxygen species (ROS) such as singlet oxygen and hydroxy, alkyloxy or alkylperoxy radicals. Under the action of these individuals DPBF has been rapidly transformed to 1,2-dibenzoylbenzene (DBB). In order to check if DPBF can act as a unique indicator of the total amount of different RNOS, as well as oxidative stress caused by an overproduction of these individuals, a series of experiments was carried out, in which DPBF reacted with peroxynitrite anion, superoxide anion, hydrogen peroxide, hypochlorite anion, and anions commonly present under biological conditions, namely nitrite and nitrate. In all cases, except for hydrogen peroxide, the product of the reaction is DBB. Only under the action of H

Topics: Benzofurans; Chromatography, High Pressure Liquid; Fluorescent Dyes; Hydrogen Peroxide; Limit of Detection; Reactive Nitrogen Species

The present investigation involved an attempt to develop a new reactive oxygen species (ROS) assay system for the photosafety assessment of chemicals using 1,3-diphenylisobenzofuran (DPBF), a fluorescent probe for monitoring ROS generation. The assay conditions of the fluorometric ROS (fROS) assay were optimized focusing on the solvent system, concentration of DPBF, fluorescent determination, screening run time and reproducibility. The photoreactivity of 21 phototoxic and 11 non-phototoxic compounds was assessed by fROS assay, and the obtained ROS data were compared with the results from a micellar ROS (mROS) assay and in vitro/in vivo phototoxicity information to confirm the predictive capacity of the fROS assay. In the optimized fROS assay, intra-day and inter-day precision levels (coefficient of variation) were found to be below 5%, and the Z'-factor for DPBF fluorescence quenching showed a large separation between positive and negative controls. Of all tested compounds, 3 false positive and 7 false negative predictions were observed in the fROS assay, and the negative predictivity for the fROS assay was found to be lower than that for the mROS assay. Although the fROS assay has some limitations, the procedures for it were highly simplified with a marked reduction in screening run time and one analytical sample for monitoring ROS generation from compounds. The fROS assay has the potential to become a new tool for photosafety assessment at an early stage of product development.

Topics: Benzofurans; Dermatitis, Phototoxic; Fluorescent Dyes; Fluorometry; Reactive Oxygen Species; Sunlight

We developed a two-step chemical bonding process using photosensitizer molecules to fabricate photofunctional nanolayer coatings on hematoporphyrin- (HP-) coated Ti substrates. In the first step, 3-aminopropyltriethoxysilane was covalently functionalized onto the surface of the Ti substrates to provide heterogeneous sites for immobilizing the HP molecules. Then, HP molecules with carboxyl groups were chemically attached to the amine-terminated nanolayer coatings via a carbodiimide coupling reaction. The microstructure and elemental and phase composition of the HP-coated Ti substrates were investigated using field-emission scanning electron microscopy and energy-dispersive X-ray spectrometry. The photophysical properties of the photofunctional nanolayer coatings were confirmed using reflectance ultraviolet-visible absorption and emission spectrophotometry. The singlet oxygen generation efficiency of the photofunctional nanolayer coatings was determined using the decomposition reaction of 1,3-diphenylisobenzofuran. The HP-coated Ti substrates exhibited good biocompatibility without any cytotoxicity, and these nanolayer coatings generated singlet oxygen, which can kill microorganisms using only visible light.

Topics: Animals; Bacteria; Benzofurans; Carbodiimides; Cell Line; Coated Materials, Biocompatible; Hematoporphyrins; Mice; Microscopy, Electron, Scanning; Nanotechnology; Photosensitizing Agents; Propylamines; Silanes; Singlet Oxygen; Spectrum Analysis; Surface Properties; Titanium

Challenges in photodynamic therapy (PDT) include development of efficient near infrared-sensitive photosensitizers (5,10,15,20-tetrakis(4-hydroxyphenyl)-21H,23H-porphine [PS]) and targeted delivery of PS to the tumor tissue. In this study, a dual functional dendrimer was synthesized for targeted PDT. For targeting, a poly(amidoamine) dendrimer (G4) was conjugated with a PS and a nitrilotriacetic acid (NTA) group. A peptide specific to human epidermal growth factor 2 was expressed in Escherichia coli with a His-tag and was specifically bound to the NTA group on the dendrimer. Reaction conditions were optimized to result in dendrimers with PS and the NTA at a fractional occupancy of 50% and 15%, respectively. The dendrimers were characterized by nuclear magnetic resonance, matrix-assisted laser desorption/ionization, absorbance, and fluorescence spectroscopy. Using PS fluorescence, cell uptake of these particles was confirmed by confocal microscopy and fluorescence-activated cell sorting. PS-dendrimers are more efficient than free PS in PDT-mediated cell death assays in HER2 positive cells, SK-OV-3. Similar effects were absent in HER2 negative cell line, MCF-7. Compared to free PS, the PS-dendrimers have shown significant tumor suppression in a xenograft animal tumor model. Conjugation of a PS with dendrimers and with a targeting agent has enhanced photodynamic therapeutic effects of the PS.

Topics: Animals; Benzofurans; Cell Line, Tumor; Dendrimers; Humans; Mice, Nude; Peptides; Photochemotherapy; Photosensitizing Agents; Proton Magnetic Resonance Spectroscopy; Singlet Oxygen; Spectrometry, Fluorescence; Spectrometry, Mass, Electrospray Ionization; Spectrophotometry, Ultraviolet; Static Electricity

Hybrid associates formed between peptide assemblies and fluorophores are attractive mainly because of their unique properties for biomedical applications. Recently, we demonstrated that the production of reactive oxygen species (ROS) by hypericin and their stability in excited states are enhanced upon conjugation with l,l-diphenylalanine microtubes (FF-MNTs). Although the detailed mechanisms responsible for improving the photophysical properties of ROS remain unclear, tentative hypotheses have suggested that the driving force is the growth of overall dipolar moments ascribed either to coupling between aligned H2O dipoles within the ordered structures or to the organization of hypericin molecules on peptide interfaces. To provide new insights on ROS activity in hypericin/FF-MNTs hybrids and further explore the role of water in this respect, we present results obtained from investigations on the behavior of these complexes organized into different crystalline arrangements. Specifically, we monitored and compared the photophysical performance of hypericin bound to FF-MNTs with peptides organized in both hexagonal (water-rich) and orthorhombic (water-free) symmetries. From a theoretical perspective, we present the results of new molecular dynamics simulations that highlight the distinct hypericin/peptide interaction at the interface of FF-MNTs for the different symmetries. As a conclusion, we propose that although water enhances photophysical properties, the organization induced by peptide structures and the availability of a hydrophobic environment surrounding the hypericin/peptide interface are paramount to optimizing ROS generation. The findings presented here provide useful basic research insights for designing peptide/fluorophore complexes with outstanding technological potential.

Topics: Anthracenes; Benzofurans; Hydrophobic and Hydrophilic Interactions; Kinetics; Molecular Dynamics Simulation; Oxidation-Reduction; Peptides; Perylene; Reactive Oxygen Species; Water; X-Ray Diffraction

The hydrophobicity of some photosensitizers can induce aggregation in biological systems, which consequently reduces photodynamic activity. The conjugation of photosensitizers with nanocarrier systems can potentially be used to overcome this problem. The objective of this study was to prepare and characterise hypericin-loaded solid lipid nanoparticles (Hy-SLN) for use in photodynamic therapy (PDT). SLN were prepared using the ultrasonication technique, and their physicochemical properties were characterised. The mean particle size was found to be 153 nm, with a low polydispersity index of 0.28. One of the major advantages of the SLN formulation is its high entrapment efficiency (EE%). Hy-SLN showed greater than 80% EE and a drug loading capacity of 5.22% (w/w). To determine the photodynamic efficiency of Hy before and after encapsulation in SLN, the rate constants for the photodecomposition of two (1)O2 trapping reagents, DPBF and AU, were determined. These rate constants exhibited an increase of 60% and 50% for each method, respectively, which is most likely due to an increase in the lifetime of the triplet state caused by the increase in solubility. Hy-SLN presented a 30% increase in cell uptake and a correlated improvement of 26% in cytotoxicity. Thus, all these advantages suggest that Hy-loaded SLN has potential for use in PDT.

Topics: Animals; Anthracenes; Benzofurans; Cell Line, Tumor; Cell Survival; Humans; Light; Lipids; Mice; Nanoparticles; Perylene; Photochemotherapy; Radiation-Sensitizing Agents; Singlet Oxygen; Uric Acid

In the present investigation, a Schiff base N'(1),N'(3)-bis[(Z)-(2-hydroxynapthyl)methylidene]benzene-1,3-dicarbodihydrazide (L1) and its Co(II), Ni(II) and Cu(II) complexes have been synthesized and characterized as novel photosensitizing agents for photodynamic therapy (PDT). The interaction of these complexes with calf thymus DNA (CT DNA) has been explored using absorption, thermal denaturation and viscometric studies. The experimental results revealed that Co(II) and Ni(II) complexes on binding to CT DNA imply a covalent mode, most possibly involving guanine N7 nitrogen of DNA, with an intrinsic binding constant Kb of 4.5×10(4)M(-1) and 4.2×10(4)M(-1), respectively. However, interestingly, the Cu(II) complex is involved in the surface binding to minor groove via phosphate backbone of DNA double helix with an intrinsic binding constant Kb of 5.7×10(4)M(-1). The Co(II), Ni(II) and Cu(II) complexes are active in cleaving supercoiled (SC) pUC19 DNA on photoexposure to UV-visible light of 365nm, through (1)O2 generation with quantum yields of 0.28, 0.25 and 0.30, respectively. Further, these complexes are cytotoxic in A549 lung cancer cells, showing an enhancement of cytotoxicity upon light irradiation.

Topics: Absorption; Animals; Antineoplastic Agents; Benzofurans; Cattle; Cell Death; Cell Line, Tumor; Coordination Complexes; DNA; DNA Cleavage; Electron Spin Resonance Spectroscopy; Electrophoresis, Agar Gel; Humans; Magnetic Resonance Spectroscopy; Models, Molecular; Nucleic Acid Denaturation; Photosensitizing Agents; Plasmids; Schiff Bases; Singlet Oxygen; Spectrophotometry, Infrared; Superoxides; Temperature; Thermodynamics; Ultraviolet Rays; Viscosity

Ultrafast broadband UV-visible transient absorption spectroscopy is used to characterize the photochemistry of α-terpinene, a 1,4-disubstituted-1,3-cyclohexadiene natural product. These results are compared with experiments probing the analogous ring-opening reaction of 7-dehydrocholesterol (DHC, provitamin D3) and the subsequent relaxation of previtamin D3. The major experimental results are as follows: (1) Like DHC, but unlike 1,3-cyclohexadiene, α-terpinene exhibits a broad excited state absorption (ESA) spectrum in the visible. The lifetime of the excited state is ca. 0.16 ps in 1-butanol and 0.12 ps in hexane. (2) The state responsible for the ESA is the initially excited state. Fluorescence from this state has a quantum yield of ~2 × 10(-5). The fluorescence quantum yield is an order of magnitude smaller, and the excited state lifetime is an order of magnitude shorter than that observed for DHC. (3) The initial gZg-triene photoproduct absorbs to the red, and the relaxed tZg-triene product absorbs to the blue of α-terpinene. The gZg→tZg reaction of the vibrationally hot photoproduct requires ca. 6.5 ps with no significant dependence on solvent polarity or viscosity. Thermalization occurs on a time scale of 2-4 ps depending on solvent, but shows no particular trends within the solvent series. (4) The conformational relaxation of previtamin D3 occurs on a similar time scale of ca. 5-8 ps with a modest dependence on the solvent viscosity.

Topics: Benzofurans; Crystallization; Cyclohexane Monoterpenes; Dehydrocholesterols; Electrons; Monoterpenes; Quantum Theory; Solvents; Spectrophotometry, Ultraviolet; Temperature

Reaction of 1,3-diphenylisobenzofuran (DPIBF) with 2-(iodoethynyl)(phenyl)-iodonium triflate at room temperature gave the expected Diels-Alder adduct, but using an excess of DFIBF (2 equiv.) and performing the reaction at 55 °C or heating at this temperature during the concentration stage, the initial orange solution or product mixture became dark brown and the products 1,2-phenylene-1,2-bis(phenylmethanone) and 2-(3-iodo-1,4-diphenylnaphthyl)(phenyl)iodonium triflate were obtained, which suggests an oxygen transfer between DPIBF and the initial adduct.

Topics: Benzofurans; Crystallography, X-Ray; Cycloaddition Reaction; Mesylates; Models, Molecular; Molecular Conformation; Naphthalenes; Oxidation-Reduction; Oxygen

Although a number of studies have focused on the higher ethyl pyruvate antioxidative activity than its sodium salt under various stress conditions, and the greater protective properties of the ester form have been suggested as the effect of better cell membrane penetration, the molecular mechanism has remained unclear. The aim of the present study was therefore to compare the antioxidative activities of sodium and ethyl pyruvate under in vitro conditions by using a liver homogenate as the model for cell membrane transport deletion. The potential effect of ethanol was also evaluated, and hypochlorous acid was used as an oxidant. Our data indicate the concentration-dependent scavenging potency of both sodium and ethyl pyruvate, with the ester having higher activity. This effect was not related to the presence of ethanol. Better protection of the liver homogenate by ethyl pyruvate was also apparent, despite the fact that cell membrane transport was omitted.

Topics: Animals; Benzofurans; Benzothiazoles; Biological Transport; Cell-Free System; Esters; Ethanol; Hypochlorous Acid; Liver; Models, Biological; Oxidation-Reduction; Oxidative Stress; Permeability; Pyruvates; Rats; Rats, Wistar; Sodium; Sulfonic Acids

Single crystal molecular structure and solution photophysical properties are reported for 1,3-diphenylisobenzofuran (1), of interest as a model compound in studies of singlet fission. For the ground state of 1 and of its radical cation (1(+*)) and anion (1(-*)), we report the UV-visible absorption spectra, and for neutral 1, also the magnetic circular dichroism (MCD) and the decomposition of the absorption spectrum into purely polarized components, deduced from fluorescence polarization. These results were used to identify a series of singlet excited states. For the first excited singlet and triplet states of 1, the transient visible absorption spectra, S(1) --> S(x) and sensitized T(1) --> T(x), and single exponential lifetimes, tau(F) = approximately 5.3 ns and tau(T) = approximately 200 micros, are reported. The spectra and lifetimes of S(1) --> S(0) fluorescence and sensitized T(1) --> T(x) absorption of 1 were obtained in a series of solvents, as was the fluorescence quantum yield, Phi(F) = 0.95-0.99. No phosphorescence has been detected. The first triplet excitation energy of solid 1 (11,400 cm(-1)) was obtained by electron energy loss spectroscopy, in agreement with previously reported solution values. The fluorescence excitation spectrum suggests an onset of a nonradiative channel at approximately 37,000 cm(-1). Excitation energies and relative transition intensities are in agreement with those of ab initio (CC2) calculations after an empirical 3000 cm(-1) adjustment of the initial state energy to correct differentially for a better quality description of the initial relative to the terminal state of an absorption transition. The interpretation of the MCD spectrum used the semiempirical PPP method, whose results for the S(0) --> S(x) spectrum require no empirical adjustment and are otherwise nearly identical with the CC2 results in all respects including the detailed nature of the electronic excitation. The ground state geometry of 1 was also calculated by the MP2, B3LYP, and CAS methods. The calculations provided a prediction of changes of molecular geometry upon excitation or ionization and permitted an interpretation of the spectra in terms of molecular orbitals involved. Computations suggest that 1 can exist as two nearly isoenergetic conformers of C(2) or C(s) symmetry. Linear dichroism measurements in stretched polyethylene provide evidence for their existence and show that they orient to different degrees, permitting a separation of their s

Topics: Benzofurans; Circular Dichroism; Crystallography, X-Ray; Electrons; Models, Molecular; Photochemistry; Quantum Theory; Spectrophotometry, Ultraviolet; Temperature

A novel catalytic exo/endo selectivity-controllable tandem heterocyclization/formal [4+3] cycloaddition was developed, which provides rapid, efficient and stereoselective access to highly fused polyheterocycles from readily available 2-(1-alkynyl)-2-alken-1-ones and 1,3-diphenylisobenzofuran under mild conditions.

Topics: Alkenes; Benzofurans; Catalysis; Cyclization; Heterocyclic Compounds; Molecular Structure; Polymers; Stereoisomerism

Topics: Bacteriophage M13; Benzofurans; Cell Line, Tumor; Drug Carriers; Drug Delivery Systems; Genetic Engineering; Humans; Liposomes; Microscopy, Electron, Transmission; Microscopy, Fluorescence; Nanostructures; Organometallic Compounds; Photosensitizing Agents

The synthesis, photophysical characterization, and determination of singlet oxygen quantum yields (Phi(Delta)) for a class of fluorene derivatives with potential application in two-photon photodynamic therapy (PDT) is reported. It has been demonstrated that these compounds possess the ability to generate singlet oxygen (1O2) upon excitation. A photochemical method, using 1,3-diphenylisobenzofuran (DPBF) as 1O2 chemical quencher, was employed to determine the singlet oxygen quantum yields (Phi(Delta)) of the fluorene-based photosensitizers in ethanol. Phi(Delta) values ranged from 0.35 to 0.75. These derivatives may have potential application as two-photon photosensitizers when pumped via two-photon excitation in the near-IR spectral region.

Topics: Benzofurans; Ethanol; Fluorenes; Molecular Structure; Oxidants; Photochemotherapy; Photosensitizing Agents; Quantum Theory; Singlet Oxygen; Solvents; Spectrophotometry

The quantum yield, Phi(Delta), of singlet oxygen generation under two-photon excitation has been determined for a fluorene derivative. A photochemical method was developed using 1,3-diphenylisobenzofuran (DPBF), a chemical quencher of 1O2, and 2-(9,9-didecyl-7-nitrofluoren-2-yl)benzothiazole (1) as a two-photon photosensitizer (PS). The photochemical kinetics of the quencher was measured by two different fluorescence methods. Fluorene 1 exhibited relatively high singlet oxygen quantum yield, Phi(Delta) approximately 0.4 +/- 0.1, and had a two-photon absorption cross-section of 28 +/- 5 GM. Thus, 1 may have potential for use as a two-photon PS in the near-IR spectral region for biomedical applications.

Topics: Benzofurans; Fluorenes; Kinetics; Molecular Structure; Photochemistry; Photons; Photosensitizing Agents; Quantum Theory; Singlet Oxygen; Spectrometry, Fluorescence

Photosensitisers based on the phenothiazinium chromophore have been reported to be bactericidal on illumination via a singlet oxygen-mediated mechanism. The current work reports on the immobilisation of the methylene blue analogue, new methylene blue, in polymer resins, and the preliminary development of photobactericidal materials. The resultant materials exhibited measurable levels of singlet oxygen and were photobactericidal against both Staphylococcus epidermidis and Escherichia coli. Such materials may be of use in surface disinfection/infection control in the healthcare milieu.

Topics: Anti-Bacterial Agents; Bacteria; Benzofurans; Disinfection; Escherichia coli; Methylene Blue; Phenothiazines; Photosensitizing Agents; Singlet Oxygen; Staphylococcus epidermidis; Surface Properties

1,3-Diphenylisobenzofuran afforded Diels-Alder cycloadducts 4a,b with n-butyl- and phenyl-substituted acetylenic sulfones 3a,b, respectively. The products underwent various types of rearrangements under pyrolytic, acid-catalyzed, and photochemical conditions. In the presence of acid, or upon heating in xylenes, they afforded the ketones 5a,b. In addition, the dehydration product 7a was produced from the pyrolysis of 4a, and the unexpected transposed ketone 6b was generated under acid-catalyzed or pyrolytic conditions from 4b via a postulated epoxide intermediate. The photolysis of 4a afforded ketone 5a as the sole isolated product, whereas 5b afforded oxepin 8b and indenyl phenyl ketone 9b. The formation of the latter two products can be rationalized by a series of pericyclic reactions. These include an intramolecular [2+2] cycloaddition, followed by a 1,3-dipolar cycloreversion, for the transformation of 4b to 8b and a series of electrocyclic and [1,3]sigmatropic reactions to convert 8b into 9b.

Topics: Acetylene; Benzofurans; Catalysis; Cyclization; Ketones; Molecular Structure; Stereoisomerism; Sulfones

Melatonin, a naturally occurring chemical mediator, although assigned a diverse range of functions, has attracted interest in recent years because of its ability to function as a free radical scavenger. Because of the implications of singlet oxygen in neurotoxicity, the objective of the study was to investigate the ability of melatonin to quench singlet oxygen generated using laser irradiation or lamp photolysis. The results show that melatonin produces radicals upon laser irradiation while the lamp photolysis studies show that melatonin is able to scavenge singlet oxygen produced by naphthalene. While melatonin is a free radical scavenger under biological conditions, it acts as a generator of singlet oxygen and or radicals (as PhiDelta is 1.41) when irradiated with laser light, implying that it has the potential to be used in photodynamic therapy in the destruction of tumors.

Topics: Benzofurans; Dimethyl Sulfoxide; Free Radical Scavengers; Humans; In Vitro Techniques; Kinetics; Lasers; Melatonin; Photochemistry; Photochemotherapy; Photolysis; Photosensitizing Agents; Singlet Oxygen

Recently, 4.4'-bis(1-p-carboxyphenyl-3-methyl-5-dydroxyl)-pyrazol (DRD156) has been developed as a new sensitive reagent that reacts specifically with singlet oxygen. The specificity of DRD156 for singlet oxygen in a biomimetic solution (micellar solution) and the effects of its coexistence with other reagent were examined with electron spin resonance (ESR). Singlet oxygen was generated using photosensitization reaction. The ESR spectrum of the radical derived from DRD156 after the reaction with singlet oxygen in phosphate buffered salines (PBS) was comprised of twenty-nine lines, whereas that in cetyltrimethylammonium bromide (CTAB) micelles was comprised of nine lines. Both 2,2,6,6-tetramethyl-4-piperidine (TMPD) and 1,3-diphenyl-isobenzofuran (DPBF) reduced the singlet oxygen-DRD156 signal intensity, and TMPD-mediated decrease in PBS (to 62%) was almost the same as that in CTAB micelle (to 65%). In contrast, DPBF reduced the DRD156 signal intensity more effectively in CTAB micelle (to 12%) than PBS (to 38%). These results indicate that the specificity of DRD156 for singlet oxygen is dependent on microenvironment.

Topics: Benzofurans; Cetrimonium; Cetrimonium Compounds; Electron Spin Resonance Spectroscopy; Hydrogen-Ion Concentration; Micelles; Models, Biological; Pyrazoles; Singlet Oxygen; Sodium Chloride; Spin Labels; Spin Trapping; Tetramethylphenylenediamine

From the roots of Rumex crispus, two known anthraquinones and a new one together with a new anthrone were isolated and the structures of compounds 1-4 were elucidated by spectroscopic means. The singlet oxygen generation capacity was tested with 1,3-diphenylisobenzofuran (DPBF) for compounds 1-4.

Topics: Algorithms; Anthracenes; Anthraquinones; Benzofurans; Chromatography, Thin Layer; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Oxygen; Photosensitizing Agents; Plant Roots; Plants, Medicinal; Polygonaceae; Spectrophotometry, Infrared; Spectroscopy, Fourier Transform Infrared; Turkey

Utilization of a fluorescence dye, 1,3-diphenylisobenzofuran (DPBF) as a detector of superoxide anion radical (O2*-) was examined. The fluorescence intensity of DPBF incorporated in phospholipid liposomes consisting of phosphatidylcholine (PC) and phosphatidylserine (PS) is effectively quenched by incubation with xanthine/xanthine oxidase system. On the other hand, xanthine or xanthine oxidase alone did not induce quenching of the DPBF fluorescence in the liposomes. Xanthine/xanthine oxidase-induced fluorescence quenching of DPBF-labeled liposomes was almost completely protected by the addition of superoxide dismutase (SOD, 1 U/ml), but not by heat-denatured SOD (10 min boiling) at the same concentration. On the other hand, catalase (1 U/ml), and hydroxyl radical and singlet oxygen scavengers (10 mM sodium benzoate, 300 mM mannitol, 1 mM tryptophan and 1 mM sodium azide) did not protect xanthine/xanthine oxidase-induced fluorescence quenching of DPBF-labeled liposomes. The concentration dependence profiles of xanthine oxidase on the DPBF fluorescence quenching and O2*- generation showed that there is a good correlation between these parameters. Under the present experimental conditions, approximately 7 microM H(2)O(2)/30 min were produced, but the addition of H(2)O(2) (1 mM) to DPBF-labeled liposomes did not quench the dye fluorescence in the liposomes. Temperature dependence profiles of the DPBF fluorescence quenching induced by xanthine/xanthine oxidase treatment and the excimer fluorescence formation of pyrene molecules embedded in the liposomal membrane suggested that the quenching efficiency of the DPBF fluorescence is largely dependent on their lipid dynamics. Based on these results, we proposed the possibility that DPBF fluorescence quenching method is able to be used as a simple method for detecting O2*- inside the membrane lipid layer and that DPBF fluorescence quenching by O2*- is controlled by the physical state of membrane lipids.

Topics: Benzofurans; Fluorescent Dyes; Free Radical Scavengers; Liposomes; Phospholipids; Reactive Oxygen Species; Superoxide Dismutase; Superoxides; Temperature; Xanthine Oxidase

The effect of magnesium lithospermate B purified from Salviae Miltiorrhizae Radix on the kinin-prostaglandin E2 system was investigated using kidney slices and isolated kidney microsomes. Magnesium lithospermate B markedly increased the amount of thiobarbituric acid-reactive substances produced by incubation of arachidonic acid in renal slices. Enhancement of arachidonic acid-mediated oxygenation of 1,3-diphenylisobenzofuran was also observed in renal microsomes from rats treated with magnesium lithospermate B, indicating an increase of prostaglandin biosynthesis. Furthermore, magnesium lithospermate B significantly increased the synthesis of prostaglandin E2 in renal slices, but the magnesium lithospermate B-mediated response was blunted with kinin antagonist. On the basis of the above results, it is apparent that magnesium lithospermate B exerts an influence on the prostaglandin system via kinin receptors.

Topics: Animals; Arachidonic Acid; Benzofurans; Bradykinin; Dinoprostone; Drugs, Chinese Herbal; Kidney; Male; Microsomes; Oxygen; Rats; Rats, Wistar; Receptors, Bradykinin; Thiobarbituric Acid Reactive Substances

A novel homogeneous immunoassay requiring only one incubation step, and applicable in principle to the determination of low- as well as high-molecular-weight substances, has been developed. The method is based on (a) photooxidation by singlet oxygen (1O2) of a fluorescent substrate (1,3-diphenylisobenzofuran, DPBF) embedded in unilamellar vesicles on the surface of which antibody to the analyte antigen is covalently attached (DPBF-immunoliposomes); (b) generation of singlet oxygen, upon illumination, by a chromophore (erythrosine) covalently attached to an antibody (Ab*) or antigen (Ag*); (c) formation of a "sandwich"- or "competition"-type complex whereupon the singlet oxygen-generating chromophore conjugate (Ab* or Ag*) and immunoliposome-embedded DPBF are brought into close proximity. Competition- and sandwich-type model assay systems for the detection of protein antigens and viruses were investigated. The detection range with protein antigens in competition- and sandwich-type assays was three (10(-10) - 10(-7) M) and two (10(-10) - 10(-8) M) orders of magnitude, respectively. With poliovirus using a sandwich-type assay, the detection range was 10(2) - 10(6) plaque-forming units per milliliter (pfu/ml).

Topics: Animals; Antibodies; Antigen-Antibody Reactions; Benzofurans; Erythrosine; Fluorescent Antibody Technique; Goats; Immunoglobulin G; Indicators and Reagents; Kinetics; Liposomes; Molecular Weight; Oxidation-Reduction; Oxygen; Photolysis; Rabbits; Singlet Oxygen

Fluorescence emission intensity of 1,3-diphenylisobenzofuran incorporated in polymorphonuclear granulocytes plasma membranes was investigated in basal conditions and during stimulation with different activators. Phorbol myristate acetate, known as the most effective "oxygen burst" inducer, produced a larger decrease in 1,3-diphenylisobenzofuran fluorescence intensity than 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet activating factor) and N-formyl-methionyl-leucyl-phenylalanine, known as weak stimulants of oxygen uptake. Diphenyl iodonium an inhibitor of leukocyte NADPH oxidase, and the singlet oxygen selective trap alpha-terpinene inhibited the quenching effect of phorbol myristate acetate on 1,3-diphenylisobenzofuran fluorescence. These data suggest formation of singlet oxygen in activated leukocytes and demonstrate that measurement of 1,3-diphenylisobenzofuran fluorescence intensity provides a new sensitive method of detection of neutrophils activation.

Topics: Benzofurans; Biphenyl Compounds; Cell Membrane; Cyclohexane Monoterpenes; Hydroxyl Radical; Monoterpenes; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Onium Compounds; Oxygen; Photochemistry; Platelet Activating Factor; Singlet Oxygen; Spectrometry, Fluorescence; Terpenes; Tetradecanoylphorbol Acetate

The oxidation of 1,3-diphenylisobenzofuran by singlet oxygen was investigated in methanol and in two different types of liposomes. It was found that at high concentrations of scavenger 1,3-diphenylisobenzofuran, e.g., > 100 microM in methanol, the 1:1 oxidation stoichiometry is lost and more than one scavenger molecule per molecule of singlet oxygen is consumed. In model membrane systems, where local scavenger concentrations are high due to compartmentalization, correct singlet oxygen quantum yields with 1,3-diphenylisobenzofuran are only determined if the increased oxidation is taken into account.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Benzofurans; Dimyristoylphosphatidylcholine; Free Radical Scavengers; Liposomes; Membranes, Artificial; Models, Biological; Oxidation-Reduction; Photochemistry; Quantum Theory; Reactive Oxygen Species; Rose Bengal; Solutions

Topics: Animals; Benzofurans; Free Radicals; Intracellular Membranes; Lipid Peroxidation; Microsomes; Oxidation-Reduction; Spectrometry, Fluorescence

Reperfusion of ischemic tissue is associated with the formation of hydroxyl radical (OH.). In this report, a novel mechanism for (OH.) generation from (1O2) is proposed based on the experimental evidence from the present study. A number of experiments were performed which conclusively demonstrated the formation of 1O2 from the reaction of lactic acid and hypohalite radical. Singlet oxygen attacks the unsaturated olefinic derivatives, which are also formed during reperfusion of ischemic tissue. The reaction between 1O2 and olefinic compounds produces hydroperoxides, which ultimately form OH. radical. The validity of the above mechanism of OH. radical formation is warranted from our experimental results.

Topics: Alkenes; Benzofurans; Chlorides; Cholesterol; Chromatography, High Pressure Liquid; Deuterium; Free Radicals; Hydrogen-Ion Concentration; Hydroxides; Hydroxyl Radical; Indicators and Reagents; Lactates; Lactic Acid; Myocardial Reperfusion Injury; Oxygen; Spectrometry, Fluorescence

As part of a wider programme to identify novel photosensitizers for photodynamic therapy, the ability of a number of phthalocyanine dyes, including some novel copper phthalocyanine derivatives with a range of water solubilities, to produce potentially cytotoxic species in solution was examined. The experiments were performed in dimethylformamide using 1,3-diphenylisobenzofuran (DPIBF) as the scavenger. The study revealed that all the dyes tested produced DPIBF photobleaching on illumination in vitro, but with widely different (greater than 12x) rates. The possible correlation of DPIBF photobleaching rates with a number of the dyes' properties is discussed.

Topics: Benzofurans; Coloring Agents; Indoles; Isoindoles; Kinetics; Photochemistry; Pigments, Biological; Platelet Aggregation Inhibitors; Radiation-Sensitizing Agents; Structure-Activity Relationship

The 5 microM hematoporphyrin-sensitized photooxidation of 1,3-diphenylisobenzofuran (DPBF) was studied in homogeneous ethanolic solutions and in aqueous dispersions of unilamellar liposomes of dipalmitoylphosphatidylcholine; both the porphyrin and DPBF are embedded in the phospholipid bilayer. The rate and quantum yield of DPBF photooxidation were found to increase upon increasing the substrate concentration and were higher in the liposome system, while they were unaffected by the fluidity of the phospholipid bilayer. Time-resolved spectroscopic measurements showed that the photooxidation of DPBF in ethanol solution proceeds by a type II O2(1 delta g)-involving mechanism. In the liposomal vesicles the high local concentration of hematoporphyrin (Hp) and DPBF in the phospholipid bilayer (ca 2000-fold higher than the stoichiometric concentration) enhances the probability of energy transfer from triplet Hp to DPBF with generation of triplet DPBF; hence O2 (1 delta g) formation can be promoted by both triplet Hp and triplet DPBF. A minor fraction of triplet DPBF quenchings appears to generate radical species which propagate DPBF damage by chain reaction.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Benzofurans; Ethanol; Hematoporphyrins; Liposomes; Oxidation-Reduction; Photochemistry

A fluorescence method for detecting singlet oxygen (1O2) in model membranes is proposed. 1O2 was generated by hydrogen peroxide/sodium hypochlorite system. 1,3-Diphenylisobenzofuran (DPBF), a specific 1O2 trap, dissolved in organic solvents gives a strong fluorescence spectrum when excited at 410 nm. A similar spectrum, with a maximum at 455 nm, is obtained when DPBF is incorporated in unilamellar dipalmitoylphosphatidylcholine liposomes. The intensity of fluorescence spectrum decreases when DPBF-labeled liposomes are exposed to singlet oxygen. This decrease is sensitive to 1O2 traps and quenchers like tryptophan and sodium azide, to lipid membrane fluidity and to the concentration of sodium hypochlorite and hydrogen peroxide.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Azides; Benzofurans; Fluorescent Dyes; Hydrogen Peroxide; Hypochlorous Acid; Liposomes; Membrane Fluidity; Oxygen; Singlet Oxygen; Sodium Azide; Spectrometry, Fluorescence; Tryptophan

The selective scavenging capacities of 19 important oxygen radical scavengers were determined by adding them individually to each of the four oxy radical standards, (superoxide, hydroxy, alkoxy and hydroperoxy, and singlet O2), calculating the percent chemiluminescence inhibited, and extrapolating O2 equivalents neutralized from baseline. The sensitivity (0.01 nm/ml) and selectivity of this method not only allows identification of individual oxygen free radical species but also quantitates the efficiency of free radical scavengers.

Topics: Benzofurans; Dimethyl Sulfoxide; Free Radicals; Glutathione Peroxidase; Hydrogen Peroxide; Luminescent Measurements; Luminol; Oxygen; Pyridazines; Superoxide Dismutase; Superoxides

Indirect methods for the detection of singlet oxygen in dye-sensitized photooxidation based on its interception by some singlet oxygen acceptors in aqueous and micellar solutions are discussed. Mechanistic aspects and some applications of a very sensitive method using p-nitrosodimethylaniline in the presence of imidazole (RNO + imidazole method) are also treated. The technique of competition kinetics with a singlet oxygen quencher N-3 which can serve for the determination of the role of singlet oxygen is discussed as well. Such competition with tryptophan and guanosine shows that these substrates react exclusively or predominantly via the singlet oxygen mechanism in the presence of hematoporphyrin as sensitizing dye.

Topics: Benzofurans; Coloring Agents; Free Radicals; Hematoporphyrins; Imidazoles; Kinetics; Micelles; Nitrogen Oxides; Nitroso Compounds; Oxygen; Photochemistry; Singlet Oxygen; Solutions; Water

Amplified chemiluminescence (CL) detects most sensitively biologically important reactive oxygen species (ROS) which are generated by phagocytes by the respiratory burst permitting the determination of cell activity in vitro. Different murine phagocyte populations were used in combination with various ROS-catabolizing enzymes and some of their inhibitors to determine the possible advantages of one of the two main presently used amplifiers, i.e. luminol and lucigenin. Lucigenin appeared to react mainly with the first of the generated ROS the superoxide anion radical (O-.2) and thus records cell activity via the respiratory burst much more reliable than luminol. The more commonly employed luminol reacts mainly with hydrogen peroxide (H2O2) and probably the singlet oxygen (1O2) which result in photon emission. However, it seems not to react with the hydroxyl radical (OH.). The dependence of luminol-amplified CL upon the generation of the chain reaction intermediate H2O2 and its three main catalysts catalase, myeloperoxidase and glutathione makes this reaction prone to different artifacts if cell activity is to be determined. Lucigenin-amplified CL offers great advantages to study cell activating or inhibiting properties of drugs and kinetics in vitro because of the biological relevance of O-.2 determination, its sensitivity, reproducibility and ease in handling.

Topics: Acridines; Amitrole; Animals; Azides; Benzofurans; Catalase; Cyanides; Ditiocarb; Exudates and Transudates; Female; Free Radicals; L-Lactate Dehydrogenase; Luminescent Measurements; Luminol; Mice; Mice, Inbred BALB C; Phagocytes; Pyridazines; Sodium Azide; Superoxide Dismutase; Time Factors; Zymosan

Monoclonal antibodies against prostaglandin H (PGH) synthase have been used to precipitate cyclooxygenase and peroxidase activities from detergent-solubilized preparations of ram seminal vesicle microsomes. Approximately 85% of the solubilized cyclooxygenase activity was precipitated using an excess of anti-PGH synthase antibody; under similar conditions, immunoprecipitation of 60% of the diphenylisobenzofuran peroxidase, 75% of the phenylbutazone peroxidase, and 50% of the epinephrine peroxidase activities occurred. In contrast, less than 10% of the cyclooxygenase or peroxidase activities could be precipitated with nonimmune, control antibody preparations. These data indicate that the hydroperoxidase activity of PGH synthase is the major peroxidase activity catalyzing the co-oxidation of xenobiotics in ram seminal vesicle microsomes.

Topics: Animals; Antibodies, Monoclonal; Antibody Specificity; Benzofurans; Epinephrine; Hydrogen Peroxide; Immunosorbent Techniques; Male; Microsomes; Oxidation-Reduction; Peroxidases; Phenylbutazone; Prostaglandin-Endoperoxide Synthases; Seminal Vesicles; Sheep; Staphylococcus aureus

A variety of prostaglandin synthetase inhibitors are cooxygenated during arachidonic acid peroxidation catalyzed by rat renal medulla prostaglandin synthetase or soybean lipoxygenase. Phenylbutazone, aminopyrine, 1,3-diphenylisobenzofuran, paracetamol, p-aminophenol, p-phenetidine and other o- and m-substituted aminophenol derivatives were cooxygenated, whereby prostaglandin synthetase inhibition was significantly weakened due to the formation of less inhibitory metabolites. In contrast, the inhibitory potency of diclofenac, indomethacin and phenacetin and its analogues remained unchanged during prostaglandin synthesis inhibition, because these compounds were no suitable cooxygenation substrates. Evidence is given that quinone imines may not be involved in the cooxidative metabolism of paracetamol and other aminophenols. As to the mechanisms of cooxygenation of suitable substrates dependent on their chemical structures either the arachidonic acid oxygenase or the subsequent hydroperoxidase reaction may trigger the oxygenation. 1,3-Diphenylisobenzofuran is metabolized during the formation of arachidonic acid hydroperoxides in contrast to paracetamol, which requires an additional peroxidase reaction to yield reactive metabolites.

Topics: Acetaminophen; Aminophenols; Aminopyrine; Animals; Arachidonic Acid; Arachidonic Acids; Benzofurans; Cyclooxygenase Inhibitors; Diclofenac; Indomethacin; Kidney Medulla; Lipoxygenase Inhibitors; Male; Peroxides; Phenacetin; Phenylbutazone; Rats; Rats, Inbred Strains

The microsomal fraction of sheep vesicular glands has been found to oxygenate 1,3-diphenylisobenzofuran, luminol, and the carcinogenic hydrocarbon benzopyrene when incubated with arachidonic acid. The oxygenations demonstrate an absolute dependence on enzyme and fatty acid and can be completely inhibited by indomethacin and 2,3-dimercaproptopanol, inhibitors of prostaglandin synthetase. The oxygenations can also be stimulated by the hydroperoxy endoperoxide, prostaglandin G2, and 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid. These latter reactions are not inhibited by indomethacin or dimercaptopropanol but do require the microsomal enzyme system. The involvement of superoxide anion in the transformations could not be demonstrated. The oxygenations occurring in the presence of arachidonic acid appear to arise via the interaction of a microsomal enzyme system with hydroperoxide intermediates of prostaglandin biosynthesis. The ability of various sulfur reagents (reduced glutathione, alpha-lipoic acid, methional) to inhibit co-oxygenation is probably related to their ability to stimulate the conversion of the intermediate to prostaglandins.

Topics: Animals; Benzofurans; Benzopyrenes; Kinetics; Luminol; Male; Microsomes; Mixed Function Oxygenases; Oxygen Consumption; Peroxides; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Seminal Vesicles; Sheep; Spectrometry, Fluorescence