The Reaction of Singlet Oxygen with Adamantylideneadamantane Mediated by Rose Bengal

The photo-oxygenation of adamantylideneadamantane ( 1 ) on siliceous supports using admixed granules of ion-exchange resin fixed to methylene blue (MB) and rose bengal (RB) gave exclusively the corresponding dioxetane derivative 2 for the former sensitizer, while the latter gave 2 and traces of the epoxide 3. RB and the charge-transfer complex produced from N-ethylcarbazole and 2,4,5,6-tetranitrofluoren-9-one both reacted with chemically generated singlet oxygen to give superoxide radical anion. Trapping of the latter with 5,5-dimethyl-1-pyrroline 1-oxide gave an adduct exhibiting a characteristic ESR spectrum. The treatment of 1 in MeOH with 30% aqueous H₂O₂ for 22 h at 60° gave 3 in 100% yield. Repetition of this experiment in the presence of 2,6-di(tert-butyl)-p-cresol caused no significant change. These results indicate that singlet oxygen reacts with 1 , in the presence of RB, by two different processes. The first leads to dioxetane formation. The second process involves conversion of singlet oxygen by RB to superoxide radical anion which subsequently gives H₂O₂ so producing epoxide 3 from 1 .     

Photoinduced Electron‐Transfer Oxidation of Olefins with Molecular Oxygen Sensitized by Tetrasubstituted Dimethoxybenzenes: A Non‐Singlet‐Oxygen Mechanism

α‐Methylstyrene ( 1 ) was photo‐oxidized in the presence of a series of alkylated dimethoxybenzenes as sensitizers in an oxygen‐saturated MeCN solution to afford the cleaved ketone 2 , epoxide 3 , as well as a small amount of the ene product 4 in ca. 1 : 1 : 0.04 ratio. The relative rate of conversion was well‐correlated with the fluorescence quantum yield of sensitizers. Thus, a non‐singlet‐oxygen mechanism is proposed, in which an excited sensitizer is quenched by (ground‐state) molecular oxygen to produce a sensitizer radical cation and a superoxide ion (O), the former of which oxidizes the substrate, while the latter reacts with the resulting olefin radical cation ( 1 ^{+ .}) to give the major oxidation products. Photodurability of such electron‐donating sensitizers is dramatically improved by substituting four aromatic H‐atoms in 1,4‐dimethoxybenzene with Me or fused alkyl groups, which provides us with an environmentally friendly, clean method of photochemical functionalization with molecular oxygen, alternative to the ene reaction via singlet oxygenation.     

Reaction modes and mechanism in indolizine photooxygenation reactions

Photooxygenations of 1,2-, 1,3-, and 2,3-di- and 1,2,3-trisubstituted indolizines 1a-1f under different reaction conditions in methanol and acetonitrile have been investigated to establish the general reaction pattern and mechanism in indolizine photooxygenation in view of the influence of the ring substituents and substitution pattern. Photooxygenations of 1-acyl-2-phenylindolizines 1a and 1b and 1,3-dibenzoyl-2-phenylindolizine (1d) are self-sensitized, while those of 1-(p-nitrobenzoyl)-2-phenylindolizine (1c) and 2-phenyl-3-(p-chlorobenzoyl)indolizine (1e) need to be sensitized by rose bengal (RB) or methylene blue (MB). These reactions proceed via a singlet oxygen mechanism yet follow different pathways in methanol and in acetonitrile, with peroxidic zwitterion D (in methanol) and dioxetane E across the indolizine C2-C3 bond (in acetonitrile) as the intervening intermediates. Methanol trapping of the peroxidic zwitterion results in C3-N bond cleavage and pyrrole ring opening to give the corresponding (E)- and (Z)-3-(2-pyridinyl)-3-benzoylpropenoic acid methyl esters (2 and 3) and 4-(2-pyridinyl)-3-phenyl-5-aryl-5-hydroxyfuran-2-one (4) as products in methanol, while O-O bond homolysis of the dioxetane furnishes 3-(2-pyridinyl)-3-benzoyl-2-phenyloxirane-2-carboxaldehyde (6) and 1-(6-methyl-2-pyridinyl)-2-phenylethanedione (5) as products in acetonitrile. 3-Benzoyl-1-indolizinecarboxylic acid methyl ester (1f) is unreactive toward singlet oxygen; however, it could be photooxygenated under electron transfer conditions with 9,10-dicyanoanthracene (DCA) as a sensitizer. This reaction takes place by the combination of the indolizine cation radical with the superoxide anion radical (or molecular oxygen) to give the pyridine ring oxidized methyl 3-benzoyl-5-methoxy-8-hydroxy-1-indolizinecarboxylate (9f), dimethyl 2-(2-pyridinyl)fumarate (8f), and dimethyl 2-(2-pyridinyl)maleate (7f) as products.     

Photodynamic Crosslinking of Proteins. III. Kinetics of the FMN- and Rose Bengal-sensitized Photooxidation and Intermolecular Crosslinking of Model Tyrosine-containing N-(2-Hydroxypropyl)methacrylamide Copolymers

As part of a study on the role of Tyr residues in the photosensitized intermolecular crosslinking of proteins, we have surveyed the kinetics of the rose bengal- and flavin mononucleotide (FMN)-sensitized photooxidation and crosslinking of a water-soluble N-(2-hydroxypropyl)methacrylamide copolymer with attached 6-carbon side chains terminating in tyrosinamide groups (thus the -OH group of the Tyr is free, but both the amino and carboxyl groups are blocked, simulating the situation of a nonterminal Tyr in a protein). The intermolecular photodynamic crosslinking of the Tyr copolymer can result only from the formation of Tyr-Tyr (dityrosine) bonds, because the copolymer itself is not photooxidizable. Rose bengal, primarily a Type II (singlet oxygen) sensitizer, sensitized the rapid photooxidation of the Tyr residue in the Tyr copolymer only at high pH, where the Tyr phenolic group is ionized; crosslinking did not occur with rose bengal under any of the reaction conditions used. In contrast, FMN, which can sensitize by both Type I (free radical) and Type II processes, sensitized the photooxidation of the Tyr copolymer over the pH range 4-9.5. Also, significant photocrosslinking occurred, but only from pH 4 to 8, with a maximum rate at pH 6. Crosslinking required the presence of oxygen. Studies with inhibitors, D2O as solvent, catalase and superoxide dismutase indicated that the photooxidation and photocrosslinking of the Tyr copolymer with FMN at pH 6 were not mediated by singlet oxygen, superoxide or hydrogen peroxide. It appears that crosslinking involves the abstraction of an H atom from the Tyr phenolic group to give Tyr and FMN radicals. The Tyr radical in one Tyr copolymer can then react with a Tyr radical in another Tyr copolymer to give an intermolecular dityrosine crosslink.     

Electron Transfer‐Initiated Epoxidation and Isomerization Chain Reactions of β‐Caryophyllene

The abundant sesquiterpene β‐caryophyllene can be epoxidized by molecular oxygen in the absence of any catalyst. In polar aprotic solvents, the reaction proceeds smoothly with epoxide selectivities exceeding 70 %. A mechanistic study has been performed and the possible involvement of free radical, spin inversion, and electron transfer mechanisms is evaluated using experimental and computational methods. The experimental data—including a detailed reaction product analysis, studies on reaction parameters, solvent effects, additives and an electrochemical investigation—all support that the spontaneous epoxidation of β‐caryophyllene constitutes a rare case of unsensitized electron transfer from an olefin to triplet oxygen under mild conditions (80 °C, 1 bar O₂). As initiation of the oxygenation reaction, the formation of a caryophyllene‐derived radical cation via electron transfer is proposed. This radical cation reacts with triplet oxygen to a dioxetane via a chain mechanism with chain lengths exceeding 100 under optimized conditions. The dioxetane then acts as an in situ‐formed epoxidizing agent. Under nitrogen atmosphere, the presence of a one‐electron acceptor leads to the selective isomerization of β‐caryophyllene to isocaryophyllene. Observations indicate that this isomerization reaction is a novel and elegant synthetic pathway to isocaryophyllene.     

ANALYSIS OF THE MECHANISM OF PHOTODYNAMIC INDUCTION OF SYNTHESIS OF A POLYPEPTIDE IN ARTHROBACTER SP.

Synthesis of a 21000-dalton polypeptide is greatly stimulated in a species of Arthrobacter by the combined influence of light, oxygen and a sensitizing dye. The dye must enter the cells for the effect to occur. The extent of photoinduction was not enhanced in the presence of D₂O nor was it significantly inhibited by 10–20 mM azide or 1,4-diazabicyclo [2.2.2]octane. The phenazine dye neutral red was nearly as effective as methylene blue and rose bengal in sensitizing photoinduction, although neutral red was inactive as a sensitizer of the photooxidation of histidine or methionine, singlet oxygen-mediated reactions. Thus, generation of singlet oxygen does not seem to be a necessary step in the mechanism of induction. Neutral red had low activity as a sensitizer of the oxidation of sulfite, which proceeds by a radical mechanism. Considering also the known properties of phenazine compounds, the evidence supports the involvement of radical intermediates in the mechanism of photoinduction. Furthermore, the results suggest that the dyes must interact directly with an intracellular component, possibly DNA, for induction to occur.     

Reaction path calculations for the interaction of the ethylene radical cation with triplet oxygen

UMNDO reaction path calculations for trapping of the ethylene-cation radical with ground state oxygen suggest that formation of a dioxetane radical cation proceeds through the intermediacy of a peroxycation radical. The predicted enthalpy of activation (ΔH? = 13.8 kcal/mol) is consistent with rapid trapping of olefinic cation radicals by triplet oxygen at room temperature.     

Reaction mechanism of apocarotenoid oxygenase (ACO): a DFT study

The mechanism of the oxidative cleavage catalyzed by apocarotenoid oxygenase (ACO) was studied by using a quantum chemical (DFT: B3 LYP) method. Based on the available crystal structure, relatively large models of the unusual active-site region, in which a ferrous ion is coordinated by four histidines and no negatively charged ligand, were selected and used in the computational investigation of the reaction mechanism. The results suggest that binding of dioxygen to the ferrous ion in the active site promotes one-electron oxidation of carotenoid leading to a substrate radical cation and a Fe-bound superoxide radical. Recombination of the two radicals, which can be realized in at least two different ways, yields a reactive peroxo species that subsequently evolves into either a dioxetane or an epoxide intermediate. The former easily decays into the final aldehyde products, whereas the oxidation of the epoxide to the proper products of the reaction requires involvement of a water molecule. The calculated activation barriers favor the dioxetane mechanism, yet the mechanism involving the epoxide intermediate cannot be ruled out.     

Modification of pyridine-3-carboxamide (nicotinamide) by radical substitution

Pyridine-3-carboxamide ( 1 ) was reacted with alkyl radicals to give mono-, di-, and tri-alkylated products. The t-butyl radical gives only 6-t-butylpyridine-3-carboxamide ( 4a ). The reactivity decreases in the order of t-butyl, isopropyl, and ethyl radicals. The product 4a reacts further with the 2-phthalimidoethyl radical to give 2- and 4-substituted products 9 and 10 , which were transformed into tetrahydronaphthyridinone derivatives 11 and 12 .     

The invention of new radical chain reactions. Part VIII. Radical chemistry of thiohydroxamic esters; A new method for the generation of carbon radicals from carboxylic acids

The aliphatic and alicyclic esters of N-hydroxypyridine-2-thione are readily reduced by tributylstannane in a radical chain reaction to furnish nor-alkanes.¹ In the absence of the stannane a smooth decarboxylatlive rearrangement occurs to give 2-substituted thiopyridines.¹ The radicals present in this reaction provoke with $\text{t}$-butylthiol an efficient radical reaction with formation of nor-alkane and 2-pyridyl-$\text{t}$-butyl disulphide.¹Similarly these carbon radicals can be captured by halogen atom transfer to give noralkyl chlorides, bromides and iodides. 2 With oxygen in the presence of t-butylthiol the corresponding noralkyl hydroperoxides are formed in another radical chain reaction.³     

Mechanistic and kinetic aspects of photosensitization in the presence of oxygen

Determining whether the first step of photooxygenation is Type I or Type II is a necessary prerequisite in order to establish the mechanism of photodynamic action. But this distinction is not sufficient, because other processes, both consecutive and competitive, commonly participate in the overall mechanism. Thus, in both Type I and Type II reactions, the initial products are often peroxides that can break down and induce free radical reactions. These aspects of photosensitization are discussed and illustrated by sensitizer/substrate systems involving (1) only radical reactions (decatungstate/alkane) and (2) reactions of singlet oxygen occurring in competitive and consecutive processes and possibly followed by radical reactions (methylene blue/2'-deoxyguanosine). Two other previously investigated systems involving, respectively, a Type II interaction followed by radical processes (methylene blue/alkene) and Type II reactions, some of which being competitive or consecutive (rose bengal/alkene), are briefly reconsidered.     

Photoexcitation of aqueous suspensions of titanium dioxide nanoparticles: an electron spin resonance spin trapping study of potentially oxidative reactions

It is well‐established that exposure of aqueous suspensions of titanium dioxide (TiO₂) nanoparticles to ultraviolet A (UVA) light produces reactive oxygen species which leads to biological damage. However, there is disagreement in the literature as to the exact nature of these species and how they are formed. Using a number of different spin traps (i.e. PBN, POBN, DMPO, DEPMPO), we have shown that the primary damaging species produced on irradiation of an aqueous suspension of TiO₂ is the hydroxyl radical, which is formed at the valence band hole under both aerobic and hypoxic conditions. Hydroxyl radical production is enhanced by the presence of oxygen which probably reacts with the conduction band electrons or resultant Ti³⁺, inhibiting hole‐electron recombination, although we find no evidence of reaction of oxygen to form free superoxide radical anions or of the formation of any other radical at that site. The present results suggest that the resulting O₂ ^?? species may not be as labile as previously thought and may possibly undergo further reduction to the O ₂ ^2? dianion. Hydroxyl radicals formed at the surface of the TiO ₂ readily react with substrates containing an abstractable hydrogen to produce secondary radicals that, in biological systems, could lead to cell damage.     

The effect of 1,3-diphenylisobenzofuran on the photo-oxidative degradation of cis-1,4-polybutadiene

1,3-Diphenylisobenzofuran (DPBF) is easily photo-oxidized by two mechanisms viz free radical oxidation and singlet oxygen oxidation. The final products of DPBF oxidation by these two mechanisms are the same. Using light in the range 280–480 nm, DPBF is an effective sensitizer of photooxidative degradation of polybutadiene in the solid and in solution. In a system with methylene blue (MB) in methanol-benzene solution (0.5:9.5) where free radicals from MB and ¹O₂ are formed during irradiation with visible light, DPBF is oxidized by both ¹O₂ and free radical mechanisms. DPBF cannot stop free radical degradation of PB initiated by MB radicals in MB-methanol-benzene solution. These results show that the DPBF is an ineffective stabilizer for polydienes against ¹O₂ and free radical oxidation. It rather acts as a sensitizer for photo-oxidation of polydienes.     

9, 10-DICYANOANTHRACENE-SENSITIZED PHOTOOXYGENATION OF α,α'-DIMETHYLSTILBENES. MECHANISM AND KINETICS OF THE COMPETING SINGLET OXYGEN AND ELECTRON TRANSFER PHOTOOXYGENATION REACTIONS

Abstract— The 9, lodicyanoanthracene-sensitized photooxygenation of 2-methyl-2-butene and (+)-limonene proceeds via the singlet oxygen pathway in carbon tetrachloride as well as in acetonitrile, although the fluorescence of the sensitizer in acetonitrile is quenched by these olefins in an electron transfer quenching mechanism. The 9, 10-dicyanoanthracene-sensitized photooxygenation of cis- and trans-ä, ä′-dimethylstilbenes occurs exclusively via the singlet oxygen pathway in carbon tetrachloride; in acetonitrile, however, singlet oxygen and electron transfer photooxygenation reactions compete with one another. Addition of tetra-n-butyl ammonium bromide and increasing oxygen concentrations favor the formation of the singlet oxygen product, whereas addition of anisole, increasing substrate concentrations and decreasing oxygen concentrations favor the electron transfer photooxygenation products. In carbon tetrachloride, exciplexes of the sensitizer and the dimethylstilbenes are formed which give rise to cidrrans-isomerization of the substrates. In acetonitrile, neither exciplex formation nor cisltrans-isomerization are observed. A mechanism is proposed which allows us to calculate product distributions of the competing singlet oxygen/electron transfer photooxygenation reactions and thus to determine the efficiencies with which encounters between the singlet excited sensitizer and the substrates finally result in electron transfer photooxygenation products. Using (I) these efficiencies, (2) the β-value obtained from singlet oxygen photooxygenation sensitized by rose bengal, and (3) the appropriate k-values determined from fluorescence quenching of 9, 10-dicyanoanthracene in MeCN by oxygen and the stilbene, allows the calculation of the quantum yield of oxygen consumption by this stilbene. The quantum yield thus calculated is strictly proportional to the rate of oxygen consumption experimentally obtained; this result is considered as convincing evidence for the mechanism proposed.     

Reaction of zirconium alkoxides with tert-butyl hydroperoxide. Oxidative ability of the Zr(OBu-t)4-t-BuOOH system

Oxidation of the isopropoxy group in the Zr(i-PrO)₄·i-PrOH complex involves both direct reaction with tert-butyl hydroperoxide and intermediate formation of zirconium peroxy compound. Zirconium tetra-tert-butoxide reacts with tert-bytyl hydroperoxide to form metal-containing peroxide and trioxide. Decomposition of the latter leads to oxygen evolution and is accompanied by radical formation. The alkoxyl and peroxyl radicals formed were identified by ESR spectroscopy. The nature of the oxidant (oxygen, zirconium-containing peroxide and-trioxide) in the Zr(OBu-t)₄-t-BuOOH system is determined by the structure of the substrate molecule.     

Direct photooxidation and xanthene-sensitized oxidation of naphthols: quantum yields and mechanism

The photoinduced oxidation of 1-naphthol to 1,4-naphthoquinone and of 5-hydroxy-1-naphthol to 5-hydroxy-1,4-naphthoquinone was studied by steady-state and time-resolved techniques. The direct photooxidation of naphthols in methanol or water takes place by reaction of the naphoxyl radical ((?)ONaph) with the superoxide ion radical (O(2)(?-)), the latter of which results from the reaction of the solvated electron with oxygen after photoionization. The sensitized oxidation takes place by energy transfer from the xanthene triplet state to oxygen. From the two oxygen atoms, which are consumed, one is incorporated into the naphthol molecule giving naphthoquinone and the second gives rise to water. The effects of eosin, erythrosin, and rose bengal in aqueous solution, pH, and the oxygen and naphthol concentrations were studied. The quantum yield of the photosensitized transformation was determined, which increases with the naphthol concentration and is largest at pH > 10. The quantum yield of oxygen uptake is similar. The pathway involving singlet molecular oxygen is suggested to operate for the three sensitizers. The alternative pathway via electron transfer from the naphthol to the xanthene triplet state and subsequent reaction of (?)ONaph with O(2)(?-), the latter of which is formed by scavenging of the xanthene radical anion by oxygen, does also contribute.     

The mechanism of cooxidation of isobutyraldehyde and octene-2

The mechanism of isobutyraldehyde-octene-2 cooxidation at 20°C has been investigated. The ratio of cis to trans epoxides in the reaction products shows that, at aldehyde concentrations lower than 1.0M, the epoxide is formed mainly by a radical route. The difference in the ΔH of formation of cis and trans epoxides is around 0.8 kcal/mole at 20°. The isobutyraldehyde involved in the radical epoxidation chain has been found almost quantitatively to be isopropylhydroperoxide, which is formed through the decarboxylation of i-PrCO₂· radicals, addition of oxygen, and abstraction of hydrogen atoms from the aldehyde. A rate constant of about 14 M^?1 sec^?1 at 20° has been determined for the latter reaction. The chain length for the cooxdination reaction decreases from 75 to 20 as the isobutyraldehyde concentration goes from 1.0 to 0.3M. The termination step seems to involve mainly the interaction of two i-PrO₂ · radicals. The cooxidation of octene-2 with pivalaldehyde follows a similar mechanism, but the chain length is about ten times higher under the same experimental conditions.     

An application of spin trapping to radical polymerizations

Radical polymerizations and copolymerizations were carried out in the presence of phenyl tert-butyl nitrone(PBN) and tert-nitrosobutane (t-BuNO), and the structure of the spin adduct formed was investigated by ESR spectroscopy. PBN adducts gave the same ESR pattern, and the variation of the splitting constant was not large enough to warrant its use for the structure assignment. Therefore, the subsequent trapping experiments were performed with t-BuNO. The polymerization mixture of representative monomers showed esr patterns that are indicative of the propagating radical being trapped. These trapped radicals were not necessarily very stable and, in most cases, disappeared after long reaction periods. In the case of α-methyl substituted monomers, additional nine-line spectra were observed which were attributed to trapping of the radical species formed by hydrogen abstraction from the α-methyl group. The tert-butyl radical which was formed by decomposition of t-BuNo was probably responsible for the hydrogen abstraction. In the case of styrene, methyl acrylate, and methyl methacrylate, characteristic ESR patterns of the propagating radicals were observed with polymers which were prepared in the presence of t-BuNO and purified by reprecipitation. Simultaneous trapping of different propagating radicals was attempted in several copolymerization systems. However, this was generally unsuccessful, because of the large difference in reactivities of the propagating radical with t-BuNo.     

Photoactive Chitosan: A Step Toward a Green Strategy for Pollutant Degradation

This article is a highlight of the paper by Ferrari et al. in this issue of Photochemistry and Photobiology. It describes the innovative use of rose bengal‐conjugated chitosan as a reusable green catalyst that photo‐degrades phenolic compounds in aqueous media, and thereby has decontamination potential of polluted waters. Whether a next‐generation photoactive polymer that produces singlet oxygen is a solution to pollutant degradation can be argued. It is as yet unclear what polymeric sensitizer would be practical on a large scale. Nonetheless pursuing this goal is worthwhile.     

Probing the active site of trypsin with rose bengal: insights into the photodynamic inactivation of the enzyme

In this work the active site of trypsin has been probed with the dye rose bengal. The dye binds competitively to the enzyme, and it can be used as a probe of the active site of the enzyme. On the basis of the emission wavelength, the binding site of trypsin is relatively polar and is similar to that of acetone in its polarity. The triplet state of rose bengal is quenched by trypsin. This quenching may be caused by the tryptophan and tyrosine residues that are in the near vicinity of the trypsin active site. This quenching can compete with the formation of singlet oxygen from the excited triplet state of rose bengal. We demonstrate that the singlet oxygen involved in the photoinactivation of trypsin is produced by the free rose bengal in solution and the bound dye is incapable of producing singlet oxygen. This explains the lack of correlation between photoinactivation efficiency and sensitizer binding capability previously reported by Wade and Spikes.