CHEMISTRY OF SINGLET OXYGEN—XXVI. PHOTOOXYGENATION OF PHENOLSy†

Abstract— The aerobic dye-sensitized photooxygenation of monohydric phenols proceeds by way of singlet oxygen under the conditions studied. Various phenols give different proportions of reaction with and quenching of singlet oxygen. Para-substituted 2,6-di-t-butylphenols show a linear correlation between the log of the total rate of singlet oxygen removal and their halfwave oxidation potentials; the same correlation is given for certain phenol methyl ethers. A Hammett plot using s?⁺ gives ρ - 1.72 ± 0.12, consistent with development of some charge in the quenching step. Reaction of photo-chemically generated singlet oxygen with 2,4,6-triphenylphenol gives 2,4,6-triphenylphenoxy radical as an intermediate in singlet oxygen quenching, although no overall reaction occurs. Kinetic analysis indicates that the radical is derived exclusively from the interaction of 2,4,6-triphenylphenol with singlet oxygen. A charge-transfer mechanism for quenching of singlet oxygen by phenols is proposed.     

QUENCHING OF SINGLET OXYGEN BY SENSITIZER IN DYE-SENSITIZED PHOTOOXYGENATION*

Abstract— A general method for the determination of the extent of the singlet oxygen (¹O₂) quenching by sensitizer in the dye-sensitized photooxygenation of olefins is used in the case of rose bengal (RB) in methanol and oil-soluble chlorophyll (M) in benzene with 2-methyl-2-pentene and tetramethylethylene as acceptors. Unlike RB, M which contains only a low percentage of pure chlorophyll (Chi), quenches ¹O₂. It is shown that this very cheap mixture can be used for kinetic studies and that the chemical quenching of ¹O₂ by M is very weak with respect to the physical quenching. The upper limit for the rate constants of physical and chemical quenching of ¹O₂ by Chi is estimated.     

PHOTOOXYGENATION OF BIPHENYL AND ITS DERIVATIVES via PHOTOINDUCED ELECTRON TRANSFER: EFFECT OF Mg(CIO4)2 ON PHOTOOXYGENATION

The 9,10-dicyanoanthracene (DCA)-sensitized photooxygenation of biphenyl derivatives in the presence of Mg(CIO₄)₂ in acetonitrile produces benzoic acid and its derivatives in high yields. In the absence of Mg(CIO₄)₂, the rates for the consumption of biphenyl derivatives decrease by a factor of 0.5-0.8, compared with those in the presence of Mg(CIO₄)₂. In these cases, however, both biphenyls and DCA are oxygenated to give benzoic acids and anthraquinone, respectively, indicating that the addition of Mg(CIO₄)₂ retards the photooxygenation of DCA. With 4-methylbiphenyl, the photooxygenation proceeds efficiently without added Mg(CIO₄)₂, and benzene rings and methyl groups are competitively oxygenated to give benzoic acid, 4-methylbenzoic acid, 4-phenylbenzoic acid, and 4-phenylbenzaldehyde. The addition of Mg(CIO₄)₂ facilitates the oxidation of benzene rings, giving benzoic acid and 4-methylbenzoic acid as major products. These photooxygenations are initiated by a one-electron transfer from biphenyls to the excited singlet DCA and proceed via the radical cations of biphenyls and the radical anion of DCA.     

PHOTOOXYGENATION OF MAGNESIUM meso-TETRAPHENYLPORPHYRIN*

Abstract— On unsensitized photooxygenation magnesium meso -tetraphenylporphyrin underwent oxidative ring cleavage yielding a bilitriene derivative as the sole product. Kinetic studies by quenching technique using singlet-oxygen quenchers, ß-carotene and α-tocopherol, and by substrate direct disappearance technique (Foote and Ching) indicated that only singlet-oxygen process is involved in the photooxygenation, and that the rate of total consumption of singlet oxygen ( k _Q+ k _R) is 1.0 ± 0.4 times 10⁸ M ^-1s^-1.     

LUMIFLAVIN-SENSITIZED PHOTOOXYGENATION OF INDOLE

Abstract— The lumiflavin-sensitized photooxygenation of indole in aqueous solutions has been investigated by means of steady light photolysis and flash photolysis. The semiquinone of lumiflavin and the half-oxidized radical of indole were formed by the reaction between triplet lumiflavin and indole (3.7 times 10⁹ M ^-1 s^-1). The semiquinone anion radical of lumiflavin reacted with oxygen to form superoxide radical. The triplet state of lumiflavin also reacted with oxygen forming singlet oxygen, ¹O₂. But the reaction between ¹O₂ and indole (7 times 10⁷ M^_l s^_1; estimated from steady light photolysis using Rose Bengal as a sensitizer) was far less efficient than the reaction between indole and triplet lumiflavin. The quantum yield of the lumiflavin-sensitized photooxygenation of dilute indole via radical processes was much higher than that via ¹O₂ processes, though appreciable ¹O₂ was formed.     

CHEMISTRY OF SINGLET OXYGEN—48. ISOLATION and STRUCTURE OF THE PRIMARY PRODUCT OF PHOTOOXYGENATION OF 3,5-DI-t-BUTYL CATECHOL

The dye-sensitized photooxygenation of t -butyl substituted catechols has been investigated. The primary product from 3,5-di- t -butyl catechol has been isolated and shown to be a hydroperoxydienone by single crystal X-ray diffraction. The absence of sensitizer effects and the faster reaction rate in polar solvents suggest that the reaction proceeds with singlet oxygen as the primary oxygenating species. Charge-transfer or full electron-transfer from the catechol to singlet oxygen is probably involved. Substituent effects are in agreement with this mechanism. The products from thermal breakdown of the hydroperoxydienone are inconsistent with a Baeyer-Villiger mechanism.     

SENSITIZED PHOTOOXYGENATION: CHANGE FROM TYPE I (RADICAL) TO TYPE II (SINGLET OXYGEN) MECHANISM

Abstract— As we have shown in previous papers, thionine-sensitized photooxygenation reactions follow a Type I (radical) mechanism. We now demonstrate that, by an appropriate choice of the acceptor and its concentration (solvent: pyridine) or by working in a rigid matrix (ethyl cellulose), the reaction can be switched to a Type II (singlet oxygen) mechanism. The system studied in the present investigation, thionine and 9,10-dimethylanthracene, represents to a certain extent an intermediate type. Photooxygenation at low DMA-concentration occurs according to a Type II mechanism as verified by the method of competitive photooxygenation, while in oxygen-free solutions, the sensitizer is partially photoreduced by the acceptor, which is typical for Type I systems. Whereas the photooxygenation of allylthiourea (ATU) with thionine as sensitizer takes place via radicals at high ATU concentrations, a change to the singlet oxygen mechanism could be observed at low ATU concentrations in pyridine solution.     

A study of sensitized photooxygenation of 3,4-dihydro-2H-pyran

The photooxygenation of 3,4-dihydro-2H-pyran sensitized by cyanoanthracenes (9,10-dicyanoanthracene and 9-cyanoanthracene) in different solvents (CH₃CN, CH₃Cl_2,C₆H₆ and CCl₄) has been studied in this paper. The products, product distribution as well as solvent isotope effect are the same as those in the reaction of singlet oxygen. Fluorescence quenching, exciplex formation and free energy change also reveal that electron transfer occurs between sensitizer-excited singlet state and substrate and then singlet oxygen is formed subsequently as the reactive intermediate in the process.     

Immobilized Organic Photosensitizers with Versatile Reactivity for Various Visible‐Light Applications

Various photosensitizers were grafted by conventional peptide coupling methods to functionalized silica with several macroscopic shapes (powders, films) or embedded in highly transparent and microporous silica xerogel monoliths. Owing to the transparency and free‐standing shape of the monoliths, the transient species arising from irradiation of the PSs could be analyzed and were not strikingly different from those observed in solutions. The observed reactivity for either liquid–solid (α‐terpinene oxygenation vs dehydrogenation) or gas–solid (dimethylsulfide, DMS, solvent‐free oxidation) reactions was consistent with the properties of the excited states of the PSs under consideration. Immobilized anthraquinone‐derived materials preferentially react in both cases by electron transfer from the substrate to the triplet state of the sensitizer, in spite of an efficient singlet oxygen production. The recently developed 9,14‐dicyanobenzo[b]triphenylene‐3‐carboxylic acid, DBTP‐COOH, efficiently reacts via energy transfer to yield singlet oxygen from its triplet state. It was shown to perform better than 9,10‐dicyanoanthracene and rose bengal for DMS oxidation and α‐terpinene photooxygenation to ascaridole, respectively. Thus, by a proper choice of the organic immobilized photocatalyst, it is possible to develop efficient and reusable materials, activated under visible light, for various applications and to tune the reaction pathway, opening the way to green oxidation processes.     

Azide/oxygen photocatalysis with homogeneous and heterogeneous photocatalysts for 1,2-aminohydroxylation of acyclic/cyclic alkenes and Michael acceptors

Homogeneous as well as heterogeneous photocatalysts that are able to oxidize the azide anion with low competitive singlet oxygen quantum yields are used to generate azidyl radicals. These radicals add to electron-rich as well as electron-poor (Michael acceptors) alkenes, and carbon radicals are formed regioselectively. Trapping with triplet oxygen (type I photooxygenation) is diffusion controlled, and the initially formed peroxy radicals are reduced with regeneration of the photocatalyst. Fluorescence quenching studies reveal rapid photoinduced electron transfer in the first catalysis step. The lack of rearrangement products in the bicyclic terpene series (pinenes, limonene) accounts for rapid subsequent oxygen trapping and back electron transfer steps. The 1,2-azidohydroperoxidation enables synthesis of 1,2-azidoalcohols and 1,2-aminoalcohols by different reduction protocols. Substrate modification and combination of type II photooxygenation with electron transfer photocatalysis allows the synthesis of 1-amino-2,3-diols and 2-amino-1,3-diols.     

THE PHOTO-OXIDATION OF N, N-DIETHYLHYDROXYLAMINE BY ROSE BENGAL IN ACETONITRILE AND WATER

The Rose Bengal photosensitized oxidation of N,N-diethylhydroxylamine has been investigated in water and acetonitrile using the techniques of oxygen uptake, singlet oxygen phosphorescence and electron spin resonance. In both solvents H₂O₂ is the major oxidation product and diethylnitroxide is an intermediate. In water, superoxide dismutase decreases oxygen uptake suggesting involvement of superoxide anions in the oxidation process. Results indicate that in water the photo-oxidation proceeds mainly by a Type I(electron transfer) mechanism, while in acetonitrile a Type II(energy transfer) mechanism has been confirmed (Encinas et al., 1987, J. Chem. Soc. Perkin Trans. II,1125–1127).     

SENSITIZED PHOTOOXYGENATION REACTIONS AND THE ROLE OF SINGLET OXYGEN†,‡

Abstract— In this paper we discuss various theoretical and experimental aspects of the role of singlet oxygen in sensitized photooxygenation reactions. New spectroscopic observations on the photosensitized production of singlet oxygen molecules are presented. The various factors which control the generation and reactions of singlet oxygen molecules are considered in detail. A relatively simple theoretical procedure is developed to predict the relative reactivities of ¹σ, ¹δ and ³σ oxygen toward various organic acceptors, and is used to discuss the chemical and photochemical properties of some of the oxygenation products. Finally, the properties of dioxetanes are examined in connection with the role which they may play in chemi- and bioluminescence. While we have said rather little about photodynamic reactions per se , the results presented in this paper strongly support the suggestion that many of the observed photodynamic effects could be due to reactions of singlet oxygen. Clearly a careful reexamination of various photodynamic effects at the molecular level to establish whether or not reactions of singlet oxygen are involved is now in order.     

PHOTOOXYGENATION OF METHYL LINOLEATE SENSITIZED BY PORPHYRINS AND DYES IN ACETONITRILE SOLUTION AND AQUEOUS EMULSION SYSTEMS

Photooxygenation reaction of an unsaturated fatty acid ester, methyl linoleate (methyl 9- cis. 12- cis -octadecadienoate, ML-H), sensitized by porphyrins and several types of dyes has been studied in aqueous emulsion and acetonitrile solution under air at 40°C. The oxygen (O₂) uptake proceeded slowly in the absence of sensitizers upon irradiation of an aqueous emulsion and an acetonitrile solution of ML-H (20 m M ) at ℷ_ex > 290 nm (11.4 and 6.1 μmol h^-1, respectively). The rate of O₂ uptake was enhanced by a catalytic amount (0.1 m M ) of porphyrins and dyes; hematoporphyrin (HP), zinc tetrakis(N-methyl-4-pyridiniumyi)porphyrin (ZnTMPyP), methylene blue (MB), rose bengal (RB), acridine orange (AO), and acriflavine (AF). In both systems, the sensitized photooxidation of ML-H by O₂ proceeded equimolarly to produce isomeric mixture of C9 and C13 hydroperoxides having the trans,cis and trans,trans conjugated diene configurations, independent of the types of the sensitizers used. The yield ratio of trans,trans/ trans,cis products in the MB-sensitized photooxygenation in acetonitrile and aqueous emulsion were almost equal (0.32 and 0.35. respectively). The sensitizing activity of the sensitizers, as measured by the quantum yield of O₂ uptake, increased in the order: MB (≃ 0) < ZnTMPyP < RB < HP < AF < AO in the aqueous emulsion and AO < AF < HP < RB = MB in the acetonitrile solution. The order in homogeneous acetonitrile solution was interpreted by the sensitizing ability of the dyes to produce singlet oxygen, while that in heterogeneous aqueous emulsion was correlated to the lipophilicity of dyes as well as the singlet-oxygen-producing ability.     

PHOTOOXYGENATION OF CAFFEINE SENSITIZED BY HYPOCRELLIN B

The photooxygenation of caffeine sensitized by Hypocrellin B in alcohol solvents hasbeen investigated in this paper. The products have been isolated and identified. The mainproduct is 8--alkoxyl substituted caffeine derivatives. Deuterium. oxygen partial pressure andNaN_3-quenching experiments indicate that the reaction proceeds on singlet oxygen mechanism.     

SINGLET OXYGEN INDUCED MUTAGENESIS OF BENZO[α]PYRENE DERIVATIVES

Singlet oxygen activates the mutagenicity of several benzo[a]pyrene (BP) derivatives in the absence of mammalian metabolic action. This has been demonstrated using a separated-surface-sensitizer system for generating chemically pure singlet oxygen, eliminating most of the complications that arise with singlet oxygen generation by conventional photosensitization. Salmonella typhimurium bacteria were exposed to singlet oxygen in the presence of certain BP derivatives and the mutation frequency determined with an azaguanine forward mutation assay. The mutation frequency was increased by exposure to singlet oxygen compared to light-only controls for those BP derivatives that were saturated at either the 7,8 or 9,10 positions but not both. The increase in mutation frequency depends on both the concentration of BP derivative and on the dose of singlet oxygen. Mutation frequency was also significantly increased when bacteria were treated with a solution of trans-7,8-dihydrodiol-BP that had been separately exposed to singlet oxygen, unequivocally demonstrating that the mutagenicity is due to the formation of a product of BP derivative oxidation by singlet oxygen and that this product has a lifetime at least on the order of minutes in acetonitrile. The requirement for singlet oxygen rather than some other form of reactive oxygen was confirmed by determination of the gas phase lifetime of the intermediate responsible for activating mutagenicity. This was performed by measuring the dependence of the mutation frequency on the distance separating the sensitizer from the target. This gives a value of 88 +/- 35 ms, which is in excellent agreement with the mean value of 89 ms calculated from previous independent determinations of the gas phase lifetime of singlet oxygen reported in the literature.     

SENSITIZED PHOTOOXYGENATION ACCORDING TO TYPE I MECHANISM (RADICAL MECHANISM) — PART III. EXPERIMENTS WITH CONTINUOUS ILLUMINATION

Abstract— The photochemical reaction in the system thionine (sensitizer), allylthiourea (ATU, acceptor), and oxygen was studied with continuous illumination. In oxygen-free aqueous solution thionine is photoreduced to leucothionine. With oxygen, however, a photooxygenation of the acceptor takes place. At the same time the quantum yield of the bleaching reaction of thionine decreases markedly in comparison with that of the oxygen-free solution. At about 100 sec after the beginning of illumination, the overall quantum yield of the bleaching reaction diminishes further because the leucothionine formed during the reaction now becomes transformed into thionine. The quantum yields do not change significantly over the range of oxygen concentrations studied (initial concentration 1 × 10^-5 to 5 × 10^-5 M ). In addition they are independent of the light intensity. The influence of the pH and the acceptor concentration were also investigated.
The sensitizer is not only bleached reductively, but is also partly destroyed by oxidation. The results are in agreement with the reaction scheme elucidated by flash photolysis measurements.
In accordance with this reaction scheme, the primary reaction (a) of the reductive bleaching of the sensitizer, (b) of the photooxygenation of the acceptor and (c) of the oxidative destruction of the sensitizer, is identical in all cases. This process is the redox reaction between the sensitizer triplet and the acceptor, where a semithionine and an ATU-radical are formed. The reaction represents an example of a Type I photooxygenation according to the notation of Gollnick.     

REACTIVITY OF SINGLET OXYGEN TOWARD AMINO ACIDS AND PEPTIDES

Quenching of singlet oxygen (¹O₂) in D₂O-ethanol by the amino acids tryptophan, tyrosine, histidine, methionine, cysteine and their derivatives was measured by exciting the sensitizers rose bengal or meso-tetra (N-methyl-4-pyridyl)porphyrin tetratosylate in the presence of oxygen and the above quenchers in solution. In our polar solvent, containing 75% D₂O on a molar basis it was found that (1) substitution of the aromatic ring in indole, phenol and imidazole by the electron-donating methyl group increases the total (i.e. nonreactive and reactive) quenching rate constant by a factor of five to eight. Free or blocked amino and carboxyl groups removed by two methylene groups from the ring counteract the above increase in the rate constant. The reactive quenching of singlet oxygen, which leads to oxidative destruction of the aromatic ring, correlates with the above substitution effects. It has been proposed that the quenching process takes place by formation of an exciplex between ¹O₂ and the quencher. Thus our results indicate that the better an electron donor the amino acid residue is the more pronounced is the charge transfer contribution in the exciplex formed with ¹O₂ and the more likely it is to lead to charge separation and hence to a chemical reaction. (2) Oligopeptides in solution or peptide bonds linked to the amino acid residue have only a minor effect on singlet oxygen. It can therefore be expected that the polypeptide chains per se in the protein network will not interact significantly with the single oxygen molecules present. The quenching of the latter should, to a first approximation, depend only on the presence of the above reactive amino acid residues and to their accessibility to ¹O₂ as well as on the effective dielectric constant within the protein structure.     

Alpha-methylstilbene and the duality of mechanism in the quenching of stilbene triplets by molecular oxygen

Spin-exchange quenching of alpha-methylstilbene triplets by molecular oxygen and by the free radical di-tert-butyl nitroxide is shown to favor the cis isomer more than does natural decay. The effect of the two quenching events is an identical 7% decrease in the fraction of perpendicular triplets that decay to the trans isomer. The conclusion that relaxed stilbene triplets reside in a shallow minimum corresponding to a geometry in which the two benzyl moieties are orthogonal was based on the observation that their quenching by O2 does not alter the trans/cis photostationary ratio. Our results with alpha-methylstilbene confirm the hypothesis that in the case of stilbene spin exchange quenching by O2 at the twisted geometry favors the cis isomer but occurs in competition with excitation transfer from transoid triplets that leads to the trans isomer and to singlet oxygen. The opposite effects of the two oxygen quenching paths on stilbene isomer composition cancel accidentally leading to an overall insensitivity of benzophenone-sensitized photostationary states to the presence of oxygen. Quenching rate constants derived on the basis of this cancellation are close to diffusion-controlled and predict singlet O2 quantum yields of 0.08 and 0.13 in the presence of air and under an O2 atmosphere, in good agreement with experimental measurements.     

Fiber-optic Singlet Oxygen [1O2 (1Δg)] Generator Device Serving as a Point Selective Sterilizer

Traditionally, Type II heterogeneous photo-oxidations produce singlet oxygen via external irradiation of a sensitizer and external supply of ground-state oxygen. A potential improvement is reported here. A hollow-core fiber-optic device was developed with an “internal” supply of light and flowing oxygen, and a porous photosensitizer-end capped configuration. Singlet oxygen was delivered through the fiber tip. The singlet oxygen steady-state concentration in the immediate vicinity of the probe tip was ca 20 f m by N-benzoyl- dl -methionine trapping. The device is portable and the singlet oxygen-generating tip is maneuverable, which opened the door to simple disinfectant studies. Complete Escherichia coli inactivation was observed in 2 h when the singlet oxygen sensitizing probe tip was immersed in 0.1 mL aqueous samples of 0.1–4.4 × 10⁷ cells. Photobleaching of the probe tip occurred after ca 12 h of use, requiring baking and sensitizer reloading steps for reuse.     

Synthesis and Photooxygenation of Linear and Angular Furocoumarin Derivatives as a Hydroxyl Radical Source: Psoralen,Pseudopsoralen, Isopseudopsoralen,and Allopsoralen

Synthesis of linear and angular furocoumarins with new skeleton structure of potential photobiological feature interest was carried out through Williamson reaction of hydroxycoumarins with 3‐chloro‐2‐butanone followed by cyclization with polyphosphoric acid or by heating in a strongly alkaline solution. The photooxygenation reactions of synthesized furocoumarins were performed in chloroform and in the presence of tetraphenylporphyrin as singlet oxygen sensitizer (¹O₂). The photooxygenation reactions afforded the photocleaved product through [2 + 2] cycloaddition and the photooxygenated products through ene reaction and [4 + 2] cycloaddition. The photoproducts were isolated and fully characterized by spectral analyses.