Photochemistry of thioxanthones—IV. Spectroscopic and flash photolysis study on novel n-propoxy and methyl,n-propoxy derivatives

The spectroscopic properties of seven oil soluble n-propoxy and methyl, n-propoxy substituted thioxanthone structures have been examined in various solvents and the data compared to their photopolymerization efficiencies, photochemical stabilities and flash photolysis behaviours in solution. Absorption maxima, extinction coefficients, fluorescence and phosphorescence spectra and quantum yields have been measured. Generally, all the compounds exhibit low fluorescence and high phosphorescence quantum yields but the ratio is solvent dependent. These observations are consistent with the high photoreactivity of the molecules operating in the lowest excited triplet state which is nπ* in character. Photopolymerization rates of n-butyl methacrylate with N-diethylmethylamine co-initiator correlate with the absorption maxima and extinction coefficients of the thioxanthones and also the degree of quenching of their fluorescence by the amine, indicating the importance of electron transfer. In the absence of a tertiary amine, transient formation on micro-second flash photolysis in 2-propanol is associated with the ketyl radical formed by the lowest excited triplet state abstracting a hydrogen atom from the solvent. In the presence of a tertiary amine, both ketyl radical and radical anion (at longer wavelengths) are observed, the latter being formed via abstraction of an electron from the amine. This is confirmed by a flash photolysis study using amines of various ionization potentials where a correlation is observed with radical anion absorbance. A pH study confirms the identity of the transient species. Activation of the thioxanthone molecule in the 3 and 4 positions with a methyl group enhances initiator activity whereas substitution in the t-position deactivates the molecule through intra-molecular hydrogen atom abstraction.     

PHOTOCHEMISTRY OF MELANIN PRECURSORS: DOPA, 5-S-CYSTEINYLDOPA AND 2,5-S,S'-DICYSTEINYLDOPA

The photochemistries of the melanin precursors dopa, 5-S-cysteinyldopa (5-SCD) and 2.5-S,S'-dicysteinyldopa (2.5-SCD) were investigated by 265-nm laser flash photolysis. The quantum yield of hydrated electron following flash photolysis of dopa (9.1%) was half the yield of dopasemiquinone (19.6%), implying that dopasemiquinone is formed via two primary photochemical mechanisms: photionisation (giving e) or photohomolysis (giving H^˙). Dopasemiquinone rapidly disproportionates to form dopaquinone and re-form dopa. Dopaquinone in turn decays via a base-catalysed unimolecular cyclisation eventually to form dopachrome. Assignment of the transient species was confirmed by previous pulse radiolysis studies of the one-electron oxidation of dopa. In contrast, flash photolysis of the cysteinyldopas, 5-SCD and 2,5-SCD results in lower photoionisation quantum yields and the production of initial transient species whose absorption spectra were markedly different from their semiquinone absorption spectra previously determined pulse radiolytically. These observations indicate that the primary cysteinyldopa photochemical species is not such a semiquinone, but rather results from S-CH₂ bond photohomolysis. Absorption spectra and rate constants for the formation and decay of various transient species are reported.     

MECHANISTIC STUDIES OF THE PHOTOREACTION OF FLAVIN WITH N, N-DIMETHYLPROPARGYLAMINE

Abstract Both photoexcited free flavin and protein-bound flavin react with N, N-dimethylpropargyla-mine (DMPA) to yield dihydroflavin-adducts which are not reoxidizable by oxygen. The mechanism of the photoreaction was reinvestigated by flash photolysis and continuous illumination experiments. We suggest that a mechanism occurs in which a flavosemiquinone and a DMPA radical result in the first photoinduced reaction. The flavin-DMPA adducts are then formed by combinations of the two radicals.     

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.     

THE PHOTOREDUCTION OF FLAVINS BY AMINO ACIDS AND EDTA. A CONTINUOUS AND FLASH PHOTOLYSIS STUDY

Abstract— Primary and secondary photochemical processes in oxygen-free aqueous solution have been characterised for FMN alone and in the presence of EDTA and four amino acids using nanosecond and microsecond flash photolysis and continuous photolysis techniques. The relative contributions of oneelectron and two-electron (group or hydride transfer) reactions to the deactivation of the triplet has been determined by comparing the radical concentration (560 nm) with the bleaching of the ground state (446 nm). It was concluded that one-electron reactions (hydrogen atom or electron abstraction) are the major mode of reactivity of the flavin triplet state with all the suhstrates studied.
The nature of the reactions of the flavin semiquinone radical have been studied quantitatively by microsecond flash photolysis. These secondary reactions consist of either a 'back reaction' between the flavin and substrate radicals (tryptophan or glycyl-tyrosine) or the transfer of a second electron (or hydrogen atom) from the substrate radical to the flavin radical (EDTA, methionine and possibly cysteine) to form reduced flavin and oxidised substrate. From a comparison of the quantum yields of formation of reduced flavin using 'flash' and continuous irradiation, an additional pathway for the decay of the flavin radical is suggested to occur at low light intensities in the presence of glycyl-tyrosine or histidine.     

THE PHOTOLYSIS OF TRYPTOPHAN IN THE PRESENCE OF OXYGEN

Abstract— Quantum yields for the destruction of tryptophan by a single 500 J flash in aqueous solution have been determined over the pH range 1–13 in both air-equilibrated and nitrogen-saturated conditions. When these quantum yields are compared with the quantum yields for radical formation and photoejection of electrons, it is found that there is good agreement only for the nitrogen-saturated case. In air-equilibrated solutions of tryptophan, there is a large disparity between the measured degradation quantum yields and those for photoejection of electrons and radical formation. Oxygen, therefore, is playing a major role in the photochemical decomposition and it is proposed that the major reaction which occurs, under normal atmospheric conditions, is the reaction of the lowest triplet excited state of tryptophan with oxygen.
Preliminary photolysis-product distributions against pH are discussed, and indicate that a total of nine major products are formed in the presence of oxygen.     

SPECTROSCOPIC STUDIES OF CUTANEOUS PHOTOSENSITIZING AGENTS—IV. THE PHOTOLYSIS OF BENOXAPROFEN, AN ANTI-INFLAMMATORY DRUG WITH PHOTOTOXIC PROPERTIES

Abstract— Benoxaprofen [2-(4-chlorophenyl)-α-methyl-5-benzoxazole acetic acid] is an anti-inflammatory drug that causes acute phototoxicity in many patients. Photolysis studies in organic solvents (ethanol, benzene, dimethylsulfoxide) showed that benoxaprofen underwent both Type I and Type II reactions. Irradiation of an anerobic solution of benoxaprofen in ethanol resulted in hydrogen abstraction from the solvent to yield hydroxyethyl and ethoxyl radicals. In the presence of oxygen, superoxide, singlet oxygen and hydroxyethyl radicals were detected. Photolysis of benoxaprofen in air-saturated benzene or dimethylsulfoxide gave superoxide. However, under anerobic conditions the drug yielded a carbon-centered radical in benzene that could not be identified. These findings suggest that both oxygen-dependent and oxygen-independent processes may be important in the phototoxic reactions of benoxaprofen.     

Photoreactivity of the nonsteroidal anti-inflammatory 2-arylpropionic acids with photosensitizing side effects.

The photoreactivity of the nonsteroidal anti-inflammatory 2-arylpropionic acids benoxaprofen, carprofen, naproxen, ketoprofen, tiaprofenic acid, and suprofen is reviewed with special emphasis on fundamental photophysical and photochemical properties. The absorption and emission properties of the excited states of these drugs as well as their main photodegradation routes are summarized. The photochemical mechanisms are discussed on the basis of product studies and detection of short-lived intermediates by means of laser flash photolysis. After dealing with the unimolecular processes, attention is focused on the photosensitized reactions of key biomolecules, such as lipids, proteins or nucleic acids. Finally, a short section on the photobiological effects on simple biological models is also included. Although some earlier citations are included, the literature coverage is in general limited to the last decade.     

THE DEPENDENCE OF THE QUANTUM YIELD OF LIGAND PHOTODISSOCIATION FROM HAEM PROTEINS ON ULTRAFAST RECOMBINATION

Abstract— Measurements of relative photolysis yields in nanosecond flash photolysis studies of carbon monoxide and dioxygen complexes of haemoglobin and myoglobin are compared with published values of the quantum efficiency for photodissociation obtained from microsecond flash or continuous photolysis studies. It is shown that the differences in quantum yield between HbCO and MbCO and between Hb0₂ and Mb0₂ can be correlated with the different extent of ultrafast recombination observed in the nanosecond experiments. Furthermore, the temperature dependence of the quantum yield in the case of HbCO can be entirely attributed to the effect of temperature on the ultrafast recombination.     

Photophysical and photochemical processes of 9,10-dihydro-9-silaphenanthrene derivatives: photochemical formation and electronic structure of 9-silaphenanthrenes

Photophysical and photochemical processes of 9-methyl- and 9-phenyl-9,10-dihydro-9-silaphenanthrene derivatives have been studied at room temperature and 77 K in comparison with the carbon analogue, 9,10-dihydrophenanthrene. These 9,10-dihydro-9-silaphenanthrene derivatives show smaller fluorescence quantum yield and remarkably larger Stokes shifts than those of the carbon analogue. In contrast, their phosphorescence quantum yields are two times larger than those of the carbon analogue, although the absolute value is not so large (approximately 0.1). Reaction products and intermediates produced by the 266 nm light photolysis have been studied, and it has been confirmed that 9-methyl- and 9-phenyl-9-silaphenanthrenes have been photochemically formed in methylcyclohexane at 77 K, in addition to the formation of radical cations of 9,10-dihydro-9-silaphenanthrene derivatives and the carbon-centered radical: 9-hydro-9-silaphenanthrenyl radical.     

Photochemistry of carbonyl photoinitiators. Photopolymerisation,flash photolysis and spectroscopic study

The photochemistry of eight aromatic carbonyl based photopolymerisation initiators is examined and compared using u.v. absorption, phosphorescence, micro-second flash photolysis, steady-state photolysis and photopolymerisation rates for n-butyl methacrylate. In the latter case, conversion rates are significantly greater in the presence of a tertiary amine (diethylmethylamine). In both the presence and absence of the amine, the photofragmenting type initiators are more efficient than the hydrogen abstracting benzophenone. Benzil exhibits the most notable conversion rates from being the least efficient in the absence of the amine to the most efficient in its presence. There is no definite correlation between ε_max and phosphorescence quantum yields with photopolymerisation rates, although it is significant that overall the phosphorescence quantum yields are enhanced to varying extents by the tertiary amine. End-of-pulse transient absorption spectra between 300 and 380 nm (λ_{max at} ∼ 340 nm) for the photo-fragmenting initiators in 2-propanol are tentatively assigned to the benzoyl radical, whereas benzophenone gives the typical ketyl radical formed via hydrogen atom abstraction at ∼ 500 nm. In the former case, transient formation is reduced by up to 50% in the presence of the tertiary amine except for benzoin and Irgacure 184. In the case of benzophenone, ketyl radical formation is enhanced significantly. All transients are strongly quenched by oxygen indicating that the triplet state is directly involved in free radical formation. Transient formation from benzil appeared to be the least affected by oxygen and this effect may well account for its high efficiency during polymerisation. Addition of the hydrogen donors benzhydrol and a secondary amine (diethylamine) enhances ketyl radical formation in the case of benzophenone in 2-propanol, confirming the mechanism of hydrogen atom abstraction. In the cases of benzil and benzoin, transient formation is not affected indicating that photofragmentation is the primary step in free radical formation. A steady-state photolysis study in ethyl acetate in the absence and presence of the hydrogen atom donors appears to support this conclusion. The application of these results in terms of current mechanisms is discussed.     

水溶性二苯酮类光敏剂中的羟基对光谱和光聚合的影响

有许多公司和研究所在从事光聚合的研究.本文报导两种不同分子结构的水溶性光敏剂的紫外光谱、磷光光谱和在不同溶剂中的量子产率,比较它们在水溶性预聚体中的光聚合效应. 两种水溶性光敏剂为:     

Photochemistry of thioxanthones—III. Spectroscopic and flash photolysis study on hydroxy and methoxy derivatives

The spectroscopic properties of 9 oil soluble hydroxy and methoxy thioxanthone derivatives have been examined in various solvents and the data compared to their photopolymerization efficiency and flash photolysis behaviour in solution. Absorption maxima, extinction coefficients, fluorescence and phosphorescence spectra and quantum yields have been measured. Generally, most of the compounds exhibit low fluorescence and high phosphorescence quantum yields except 1-substituted derivatives where intra-molecular hydrogen bonding is involved. These observations are consistent with the high photoreactivity of the molecules occurring via the lowest excited triplet state. Photopolymerization rates of n-butyl methacrylate, using N-diethylmethylamine as co-initiator, correlate to some extent with the absorption maxima and extinction coefficients of the thioxanthones. Transient formation on micro-second flash photolysis is associated with the ketyl radical formed by the lowest excited triplet state of the thioxanthones abstracting a hydrogen atom from the solvent. In the presence of a tertiary amine, a new longer wavelength transient absorption is produced and is assigned to a radical-anion formed by the lowest excited triplet state of the thioxanthones abstracting an electron from the amine. A correlation was observed between the transient absorption due to the radical-anion and the ionisation potential of various amines. Flash photolysis studies in acid and base media confirmed the identity of the radical and radical-ion species. Intra-molecular hydrogen bonding in the α-position to the carbonyl group deactivates both the lowest excited singlet and triplet states of thioxanthone but has little effect on polymerization efficiency. The latter is associated with competition of the carbonyl group with the amine co-initiator for hydrogen bonding and consequent electron abstraction to give an active radical-anion. This is confirmed using micro-second flash photolysis.     

Electron Transfer Processes in the Reactivity of Nonsteroidal Anti-inflammatory Drugs in the Ground and Excited States

The nonsteroidal anti-inflammatory drugs (NSAID), naproxen, sulindac and indomethacin, were shown to donate electrons to nitro blue tetrazolium (NBT) when irradiated with UV light in deoxygenated aqueous buffer solution (pH 7.4, 30°C). The reaction was monitored spec-trophotometrically by the appearance of the diformazan reduction product from NBT. The electron transfer process facilitates the decomposition of the drugs. Naproxen in the presence of NBT is photodegraded principally to the alcohol (2-[1-hydroxyethyl]-6-methoxynaphthalene) at a rate approximately 20-fold faster than when irradiated alone in deoxygenated conditions. The photoproduct from naproxen also participates in the electron transfer to NBT but at a much slower rate than naproxen. Irradiation of sulindac or indomethacin in the presence of NBT caused the slow photoreduction of NBT to diformazan. In the absence of NBT, indomethacin and sulindac are essentially unreactive when irradiated in aqueous solution. The ability of a number of NSAID to act as electron donors in their ground state was studied by observing their oxidation by potassium peroxodisulfate in pH 7.0 phosphate buffer at 50°C. The HPLC analysis of the drug remaining showed that the 2-arylpropionic acid NSAID (naproxen, ibuprofen, ketoprofen and suprofen) reacted at a rate equivalent to the thermal decomposition of peroxodisulfate. The major products were the same as detected in the photooxidation of these drugs, resulting from decarboxylation and oxygen addition but also included a dimeric compound. On the other hand, the NSAID that do not contain the propionic acid substituent all reacted more slowly with peroxodisulfate, enabling specific reaction rate constants to be evaluated.     

FLASH PHOTOLYSIS OF RIBONUCLEASE A

Abstract— Flash photolysis spectra show that ultraviolet irradiation of RNase (Λ > 250 nm) at pH 11.5 generates the hydrated electron and a long-lived transient with absorption maxima at 390 nm and 410 nm, attributed to the phenoxyl type radical from tyrosyl residues. Comparison of the initial yields with flash photolysis spectra obtained from aqueous tyrosine and mixtures of the chromophoric amino acids indicates that 3–4 tyrosyl residues are photoionized in the primary act. This process is almost completely quenched at pH 1–9, even though the p -alanylphenoxyl radical is obtained with tyrosine over this pH range and the accompanying electron is observed at pH 7. The negative result is not altered by denaturation of RNase with 8 M urea or heating to 70°C, suggesting that a primary chain interaction is responsible for the suppression of tyrosyl residue photolysis. This mechanism is supported by flash photolysis spectra of small peptides, showing that the initial radical yield from tyrosylglycylglycine is strongly quenched compared to tyrosine when the phenolic group is protonated. Comparion of this work with published results on fluorescence and inactivation quantum yields indicates that photochemical electron ejection from RNase in alkaline solutions takes place in the dissociable residues and does not contribute to loss of enzymic activity.     

PHOTOPHYSICAL AND PHOTOSENSITIZING PROPERTIES OF 2-AMINO-4 PTERIDINONE: A NATURAL PIGMENT

Abstract— The characteristics of the fluorescence and phosphorescence emission of 2-amino-4 (3H) pteridinone (or pterin) in aqueous solutions are pH dependent. The room temperature fluorescence quantum yield is low and is maximum at pH = 10 (φ_F∼ 0.057). The 77K phosphorescence emission consists of two overlapping emissions originating from τ* triplet states. In agreement with low temperature results, the 353nm laser flash photolysis makes it possible to detect at pH 9.2, two transient triplet absorptions (τ₁∼ 0.3 μs and τ₂∼ 2.3 μs). The longer lived triplet is characterized by φ_TM∼ 0.20 and ∼ (550nm) = 2000 M ⁻¹ cm⁻¹. It reacts with the solvent forming the semireduced pterin with a quantum yield φ_R∼ 0.06. The photosensitizing properties of pterin have been studied by laser flash spectroscopy and steady state irradiations. Photoreactions implying singlet oxygen formation are shown to occur. Laser flash spectroscopy indicates that the pterin triplet is reduced by amino acids and nucleic acid bases. Corresponding bimolecular reaction rate constants have been measured.     

PHOTOLYSIS OF AMIODARONE, AN ANTIARRHYTHMIC DRUG

Abstract— The photochemical behaviour of amiodarone was examined in vitro in order to get more insight on the chemical reactions involved in the cutaneous phototoxicity processes . Irradiation at 300 nm of amiodarone degassed in ethanol solution leads to a photodehalogenation followed by a much slower α-cleavage reaction. Desethylamiodarone, the main metabolite of AD was found to undergo the same reaction as AD. Results of photosensitization and quenching experiments together with phosphorescence spectra indicated that the reaction proceeds via the triplet excited stateof amiodarone. Radical species formed during photolysis were identified by ESR spectroscopy. CH₃CHOH, HO₂ and an unidentified radical were detected using 5,5-dimethyl-1-pyrroline-1-oxide as spin trap. In aerated solutions, photosensitization of oxygen by amiodarone was demonstrated by adding singlet oxygen scavengers such as dimethylfuran and cholesterol. Overall, these results suggest that Type I and Type II mechanisms may take place in the phototoxicity of amiodarone and its metabolite.     

Characterization of the Transient Intermediates Generated from the Photoexcitation of Nabumetone: A Comparison with Naproxen

The photochemical and photophysical properties of nabumetone (4-[6-methoxy-2-naphthyl]-2-butanone) were examined employing conventional and time-resolved spectroscopic techniques. The naphthalene-like nabumetone triplet is formed with 29% efficiency in acetonitrile. Singlet oxygen formation was also detected in this solvent with a φ_A value of 0.19. A naphthalene-like radical cation absorption, formed via biphotonic processes, was also detected. The reactivity of both the triplet and radical cation of nabumetone toward different substrates was examined. The photochemical properties of nabumetone are compared with those of naproxen, a structurally related acidic nonsteroidal anti-inflammatory drug. For these two anti-inflammatory agents, a type II photosen-sitization process is most likely responsible for their phototoxicity.     

PHOTOCHEMICAL SENSITIZATION BY AZATHIOPRINE AND ITS METABOLITES—I. 6-MERCAPTOPURINE

Abstract— Azathioprine is used as an immunosuppressant for renal transplant recipients, but is frequently associated with severe skin cancer as a side effect. 6-Mercaptopurine, the primary metabolite of azathioprine. absorbs strongly in the UVA region and displays substantial photochemical reactivity. The primary photochemical processes in aqueous solution are triplet state formation and photoionization, as shown by flash photolysis. In oxygenated solution, singlet oxygen and superoxide are produced, and ground state 6MP appears to react with these species. Glutathione inhibits this reaction and is itself oxidized. In deoxygenated solution, reactions implicating the thiyl radical and hydrogen atom and electron transfer occur as shown by reaction with histidine and p-nitrosodimethylaniline. Nitro Blue Tetrazolium or acrylamide.     

Photolysis of ((3-(Trimethylsilyl)propoxy)phenyl)phenyliodonium salts in the presence of 1-naphthol and 1-methoxynaphthalene

Direct photolysis of ((3-trimethylsilylpropoxy)phenyl)phenyliodonium salts with different counteranions (Cl(-), SbF(6)(-), and B(C(6)F(5))(4)(-)) in methanol leads to products by both heterolytic and homolytic processes. In the presence of 1-naphthol and 1-methoxynaphthalene, products formed by a heterolytic reaction disappear, suggesting an electron-transfer process occurs between excited 1-naphthol/1-methoxynaphthalene and the iodonium salts. In the case of 1-methoxynaphthalene, three phenylated methoxynaphthalene isomers are produced. These are produced as radical coupling products from the phenyl radical and 1-methoxynaphthalene radical cation.