Diphenylisobenzofuran Research Articles

Antioxidants suitable for use with chemiluminescence to identify oxyradical species

From a panel of 24 alleged antioxidants the most suitable antioxidants (AO) for use with chemiluminescence (CL) experiments were determined. Superoxide dismutase (SOD), using luminol as the chemiluminescence probe (Lum-CL), was inhibitory only towards O2•- and not HO• or 1O2. SOD was thus a suitable antioxidant for O2•-, as was tiron. Tiron had advantages, however, since SOD acted as a pro-oxidant in the presence of H2O2 or H2O2/HO• generators. The two most suitable antioxidants for 1O2 were diphenylisobenzofuran (DBF) and tryptophan, for both Lum and Lucigenin-CL (Luc-CL). Desferrioxamine, with both Lum and Luc-CL, was a very effective scavenger for HO•, but appeared to be an even more effective scavenger for 1O2. Cysteamine showed the best discrimination between IC50s when the two 1O2 generators NaOCl/H2O2 and NDPO2 were compared. Cysteamine was, therefore, the only scavenger that was appropriate for studies with hypochlorite. Melatonin, with Lum-CL, was found to be the most suitable scavenger for HO•. Mannitol, the classical AO for HO•, was not suitable when used with CL since it acted as a pro-oxidant. Some of the AOs revealed either calyx- or bell-shaped CL inhibition profiles and presumably, therefore, may act as both pro- or antioxidants at different concentrations. Antioxidants showing these kinds of dual activities should be used with caution in CL studies.

Trapping of 1,2-benzo-1,3,4-cycloheptatriene as evidence for a strained cyclic allene structure

8-bromo-6,7-dihydrobenzocycloheptene 16 and 9-bromo-6,7-benzocycloheptadiene 17 have been synthesized via a new and simple method, and their allene reactions were studied. Treatment of 16 with a base in the presence of DPIBF (diphenylisobenzofuran) gave the strained bicyclic allene 9, which underwent a cycloaddition reaction to yield 25 and 26. On the other hand, the reaction of the vinyl bromide 17 with a base, either in the presence or absence of DPIBF, resulted in the formation of 7 H-benzocycloheptadiene 21, rather than the alkyne 22.

Kinetics and Yield of Singlet Oxygen Photosensitized by Hypericin in Organic and Biological Media

The spectroscopy and photophysics of the photosensitizer hypericin when in homogeneous solutions and when bound to liposomes were studied. Hypericin was found to partition efficiently into DMPC liposomes, with a binding constant of 58 (mg lipid/mL)-1. In these liposomes the singlet oxygen production quantum yield was 0.43 +/- 0.09. To determine the deactivation constant of singlet oxygen in lipid bilayers for the first time, we calculated extrapolated values from its quenching by DMPC and lecithin in homogeneous solutions and obtained decay times of 36.4 and 12.2 microseconds, respectively. We also measured the quenching of singlet oxygen, sensitized by hypericin in DMPC liposomes, by NaN3, diphenyl isobenzofuran and H2O:D2O mixtures and explained the results on the basis of singlet oxygen diffusing rapidly out of the lipid bilayer into the aqueous medium. The observed temperature effect on the lifetime of singlet oxygen of about 50% over a 15 degrees C range in liposome suspension contrasts with a 3% change in a homogeneous solution in 1-nonanol and is explained by the temperature effect on the diffusion out of the liposome. A strong pH effect was observed, indicating that the deprotonated species formed above about pH 10 is a much weaker photosensitizer of singlet oxygen than the native, protonated species.

Kinetics and Yield of Singlet Oxygen Photosensitized by Hypericin in Organic and Biological Media

The spectroscopy and photophysics of the photosensitizer hypericin when in homogeneous solutions and when bound to liposomes were studied. Hypericin was found to partition efficiently into DMPC liposomes, with a binding constant of 58 (mg lipid/mL)−1. In these liposomes the singlet oxygen production quantum yield was 0.43 ± 0.09. To determine the deactivation constant of singlet oxygen in lipid bilayers for the first time, we calculated extrapolated values from its quenching by DMPC and lecithin in homogeneous solutions and obtained decay times of 36.4 and 12.2 μs, respectively. We also measured the quenching of singlet oxygen, sensitized by hypericin in DMPC liposomes, by NaN3, diphenyl isobenzofuran and H2,O: D2O mixtures and explained the results on the basis of singlet oxygen diffusing rapidly out of the lipid bilayer into the aqueous medium. The observed temperature effect on the lifetime of singlet oxygen of about 50% over a 15°C range in liposome suspension contrasts with a 3% change in a homogeneous solution in 1-nonanol and is explained by the temperature effect on the diffusion out of the liposome. A strong pH effect was observed, indicating that the deprotonated species formed above about pH 10 is a much weaker photosensitizer of singlet oxygen than the native, protonated species.

Photoprocesses of eosine and rose bengal ion pairs with cationic surfactant in non-polar solvent: application in photosensitization studies

The anionic dyes (D) eosine (Eo) and rose bengal (RB) form hydrophobic ion pairs (DS2) with cationic surfactants (S) which are soluble in non-polar solvents (Bilski et al., J. Phys. Chem., 95 (1991) 5784). The solubility of DS2 in non-polar solvents increases with increasing size of the surfactant cation. We have studied the photoproperties of ion pairs formed between RB or EO and the dimethyldioctadecylammonium cation (RBS2 and EoS2) in isooctane, CCI4, toluene and Ch2CI2. No significant concentration-dependent aggregation occurred in the dye solutions at room temperature. However, some features of initially formed “loose” aggregates developed in isooctane, CCl4 and toluene, which in CH2CI2 all DS2 spectra were characteristic of the monomeric dyes. DS2 showed a red shift in absorption/fluorescence and low-temperature phosphorescence which is characteristic of xanthene chromophores placed in an aprotic enviroment. The fluorescence intensity was also high in Ch2CI2 owing to its aproticity and the lack of aggregation. By contrast, aggregation lowered the fluorescence of the dyes in isooctane. Transient absorption measurements in degassed toluene indicated of a triplet state (λmax=630 nm for RB and 600 nm for Eo) which was self-quenched giving rise to transient absorbances at 380 and 460 nm, probably due to the formation of the dye radical anion and cation respectively. We found no evidence for photoredox reactions between the ion pair constituents, S+and D2-. In aerated solutions, strong 1O2 phosphorescence at 1268 nm was detected; we have compared the efficiency of 1O2 phosphorescence emission by the DS2 ion pair with that of tetraphenylporphine zinc complex. The quantum yield of photodepletion of 1,3- diphenylisobenzofuran (DPBF) sensitized by RBS2 (7 μM) in toluene was 0.89. The quantum yield of oxygen consumption during this reaction was 0.75; Eo was about three times less efficient as a sensitizer. The photostability of hydrophobic EoS2 and RBS2 ion pairs, as well as the photosensitization in non-polar solvents, are similar to those in H2O for both dyes. DS2 may be the photosensitizer of choice in some non-polar solvents.

Diphenylisobenzofuran (DPBF) follows the dynamics of ROO. to RO. and C-centered radicals in microsomal membranes.

Diphenylisobenzofuran (DPBF) follows the dynamics of ROO. to RO. and C-centered radicals in microsomal membranes.

Synthesis and chemistry of some tricyclic cyclopropenes. 3. Tricyclo[3.2.1.02,4]oct-2(4)-ene

The title compound cyclopropene 2 has been synthesized in situ from 2,4- dibromo or -diiodo tricyclo[3.2.1.0 2,4 ]octane via dehalogenation of tert-butyllithium in THF at -78 o C. The dihalides were formed in six steps starting with cyclopentadiene and (chloromethyl)maleic anhydride. In the presence of diphenylisobenzofuran (DPIBF) 2 forms a Diels-Alder adduct. Cyclopropene 2 and a previously synthesized cyclopropene were decomposed under these same conditions, only without DPIBF present, to give complex mixtures of products, some of which were characterized as tert-butyl adducts and dimers via the ene reaction of the cyclopropenes

Cutaneous photoprotection using a hydroxyl radical scavenger in photodynamic therapy

Photodynamic therapy (PDT) is emerging as an effective therapy for a variety of malignant diseases, including head and neck cancer. Prolonged cutaneous photosensitivity following therapy, however, remains the most significant side effect. The biochemical mechanism of this sensitivity, and indeed of the tumoricidal effect of PDT, is uncertain, but is believed to involve formation of singlet oxygen and possibly other oxygen-derived free radicals. This laboratory recently reported that a singlet oxygen scavenger, diphenylisobenzofuran (DPIBF), afforded cutaneous photoprotection to 67% of animals treated with PDT. Those results, the first from an in vivo study, supported the idea that singlet oxygen plays a significant role in PDT and its associated toxicity. They also, however, suggested that it is not the sole intermediate. The current study looks at the photoprotective effects of the hydroxyl radical scavenger dimethyl thiourea, alone and in conjunction with DPIBF. Our results strongly support a role for the hydroxyl radical in producing the cutaneous phototoxicity associated with PDT.

The reaction of cyclopropabenzene with 1,3-diphenylisobenzofuran: formal [4π + 2π] and [4π + 2σ] cycloadditions

Cyclopropabenzene reacts with diphenylisobenzofuran (DPIBF) to afford the formal endo and exo [4π + 2π] adducts 2 and 4. In addition, the unsymmetrical formal [4π + 2σ] adduct 3 is found. The reaction shows a temperature dependency. A mechanism for the formation of 2, 3, and 4 involving highly stabilized diradicals is offered.

Low Dose Measurements with Lyoluminescence Materials

The paper reports LL measurements for which the reader assembly has been improved in order to standardise the measurement procedures and to limit the uncertainties. Materials, like L-glutamine and N-acetyl-D-glucosamine, in addition to mannose and glucose, have been tested using sensitised solutions heated and kept at constant temperature during the read-out process. Mannose is rather insensitive even using sensitised solutions (minimum detectable dose: 0.1 Gy), while the detection limit for glucose and N-acetyl-D-glucosamine is of the order of 2 mGy using luminol as the sensitiser. The reproducibility is within ±10% for doses of the order of 50 mGy for glucose. Measurements with diphenylisobenzofuran (DPBF) have shown small amplification of the LL signal.

Low Dose Measurements with Lyoluminescence Materials

Abstract The paper reports LL measurements for which the reader assembly has been improved in order to standardise the measurement procedures and to limit the uncertainties. Materials, like L-glutamine and N-acetyl-D-glucosamine, in addition to mannose and glucose, have been tested using sensitised solutions heated and kept at constant temperature during the read-out process. Mannose is rather insensitive even using sensitised solutions (minimum detectable dose: 0.1 Gy), while the detection limit for glucose and N-acetyl-D-glucosamine is of the order of 2 mGy using luminol as the sensitiser. The reproducibility is within ±10% for doses of the order of 50 mGy for glucose. Measurements with diphenylisobenzofuran (DPBF) have shown small amplification of the LL signal.

Time-resolved determinations of deuterium isotope effects on O2(1.DELTA.g) lifetimes in solution

Results of experiments applying a time-resolved substrate bleaching method to studies of determination of the natural lifetime (tau/sub ..delta../) of the lowest excited state of molecular oxygen, O/sub 2/(/sup 1/..delta../sub g/) as a function of the solvent and its isotopic condition are described. Fully protiated and fully deuterated species of benzene, acetonitrile, acetone, and chloroform were used as solvents, and diphenylisobenzofuran (DPBF) or rubene (R) were used as monitoring substances (M) for directly monitoring the loss of optical absorbance of M owing to the elementary process O/sub 2/(/sup 1/..delta../sub g/) + M ..-->.. (k/sub m/) -M. Values of tau/sub ..delta..//sup D//tau/sub ..delta..//sup H/ obtained from these experiments do not resolve the discrepancy of previously reported values obtained by different workers. However, it is concluded that in solvents where large tau/sub ..delta../ values (approx. 1000 ..mu..s) are exhibited, direct luminescence measurements technique is to be preferred over indirect methods. Contrarily, for tau/sub ..delta../ values of less than approx. 200 ..mu..s, it is contended that use of the time-resolved substrate bleaching method following flash excitation gives very reliable results. (BLM)

The triplet state energies of rubrene and diphenylisobenzofuran

Until now controversies have arisen from the estimates of the triplet energies of rubrene (R) and diphenylisobenzofuran (DPBF), both of which are known reactants with singlet oxygen. To clarify the situation, flash kinetic spectroscopy was used to measure rates of energy transfer between these two molecules and other energy donor and energy acceptor molecules of known triplet energy. The lowest excited triplet state in R is nearly isoenergetic with the corresponding state in zinc phthalocyanine, and the energy value assignment is 9.2 ± 0.2 kilokaysers. Triplet—triplet annihilation is thermoneutral and is consistent with the lowest triplet state having approximately one-half the energy of the lowest excited singlet state. Based on the rates at which azulene and ferrocene quench the lowest excited triplet state of DPBF, the energy of this state can be assigned a value of 11.9 ± 0.1 kilokaysers.

The triplet state energies of rubrene and diphenylisobenzofuran

Until now controversies have arisen from the estimates of the triplet energies of rubrene (R) and diphenylisobenzofuran (DPBF), both of which are known reactants with singlet oxygen. To clarify the situation, flash kinetic spectroscopy was used to measure rates of energy transfer between these two molecules and other energy donor and energy acceptor molecules of known triplet energy. The lowest excited triplet state in R is nearly isoenergetic with the corresponding state in zinc phthalocyanine, and the energy value assignment is 9.2 ± 0.2 kilokaysers. Triplet—triplet annihilation is thermoneutral and is consistent with the lowest triplet state having approximately one-half the energy of the lowest excited singlet state. Based on the rates at which azulene and ferrocene quench the lowest excited triplet state of DPBF, the energy of this state can be assigned a value of 11.9 ± 0.1 kilokaysers.

Fatty acid induced drug and carcinogen metabolism in rat and human colonic mucosa: A possible link to the association of high dietary fat intake and colonic carcinogenesis

This study examined effects of fatty acids on the metabolism of 1,3 diphenylisobenzofuran (DPBF) and benzo(α) pyrene (BP) by rat or human colonic mucosal microsomes. Arachidonate, linoleate (25 μM) or their hydroperoxides increased oxidation of DPBF or BP 4 to 5-fold, whereas saturated fatty acids and NADPH had no effect. Studies of the influence of O 2 exclusion and indomethacin on DPBF and BP oxidation were consistent with the existence of both cyclooxygenase dependent and independent pathways for fatty acid stimulation of colonic microsomal drug oxidation. These results may have a bearing on the increased prevalence of colon cancer in populations with high fat intakes.

A pulse radiolysis study of the triplet sensitized production of singlet oxygen: determination of energy transfer efficiencies

The technique of pulse radiolysis has been used to produce aromatic and aromatic carbonyl triplet states in liquid benzene. The quenching of such triplets by O/sub 2/(/sup 3/SIGMA/sub g//sup -/) leads to the production of singlet oxygen (/sup 1/..delta../sub g/), the subsequent reactivity of which has been followed by time-resolved observation of the bleaching of diphenylisobenzofuran (DPBF). Measurement of quenching rate constants together with sensitizer triplet and DPBF bleaching yields has allowed the efficiency of the process for energy transfer to oxygen to be determined. This efficiency varies considerably from sensitizer to sensitizer and appears to be inversely related to the sensitizer intersystem crossing efficiency.

THE PHOTOSENSITIZED FORMATION AND REACTION OF SINGLET OXYGEN, O2*(1Δ), IN AQUEOUS MICELLAR SYSTEMS

Abstract— Oxygenated aqueous solutions of methylene blue containing dispersions of sodium dodecyl sulphate micelles with solubilised diphenyl isobenzofuran were irradiated with red light and the rate of loss of furan was followed over several min. The results are consistent with a mechanism in which singlet oxygen is produced by energy transfer from methylene blue triplet in the aqueous phase, and then diffuses to and penetrates the interior of the micelles where it reacts with the furan. The competition between this process and the natural decay of the excited oxygen has been examined and a β‐value of 9.7 times 10‐5M determined which is comparable to that for the same reaction in homogeneous solvents. A model of the system is proposed and its kinetic features discussed.