Furocoumarin photolysis: chemical and biological aspectsCaffieri, Sergio
doi: 10.1039/b107329jpmid: 12659510
Furocoumarins (psoralens) undergo photolysis when subjected to UVA radiation in solution. Several products are formed, depending on the molecular structure and experimental conditions. Some products are the result of anoxic mechanisms (cyclodimerisation, addition of solvent), others of oxic pathways, leading to oxidised products. The mechanisms thought to underlie photolysis are described and the possible biological relevance of the photoproducts and intermediates is discussed.
The use of 5-aminolaevulinic acid as a photosensitiser in photodynamic therapy and photodiagnosisKelty, Clive J.; Brown, Nicola J.; Reed, Malcolm W. R.; Ackroyd, Roger
doi: 10.1039/b201027ppmid: 12659511
Photodynamic therapy (PDT) is a treatment for cancer and pre-malignant conditions, which involves the administration of a photosensitising agent followed by exposure of the tissue to light. 5-Aminolaevulinic acid (ALA) is a naturally occurring compound in the haem biosynthetic pathway, which is metabolised to a photosensitive product, protoporphyrin IX (PpIX). The major advantage of ALA when compared to synthetic photosensitisers is the rapid metabolism, which significantly reduces the period of cutaneous photosensitivity. This review focuses on the development of ALA as a photosensitiser in photodynamic therapy and photodiagnosis, and the wide range of clinical applications in which ALA is now being used as a therapeutic modality.
Characterization of the cell death modes and the associated changes in cellular energy supply in response to AlPcS4-PDTPlaetzer, Kristjan; Kiesslich, Tobias; Krammer, Barbara; Hammerl, Peter
doi: 10.1039/b108816epmid: 12659513
Photodynamic therapy (PDT) can result in both types of cell death, apoptosis or necrosis. Several steps in the induction and execution of apoptosis depend on ATP and the intracellular ATP level has been shown to be one determinant in whether apoptosis or necrosis occurs. Therefore, photochemical damage of cellular targets involved in energy supply might play a crucial role in the mode of cell death being executed. The present study is aimed at the characterization of changes in cellular energy supply and the associated cell death modes in response to PDT. Using the human epidermoid carcinoma cell line A431 and aluminium(iii) phthalocyanine tetrasulfonate chloride (2.5 μM) as a photosensitizer, we studied the changes in mitochondrial function and intracellular ATP level after irradiation with different light doses. Employing assays for caspase-3 activation and nuclear fragmentation, 50of the cells were found to undergo apoptosis after irradiation between 2.5 to 3.5 J cm−2 while the remainder died by necrosis. At higher light doses (>6 J cm−2), neither caspase-3 activation nor nuclear fragmentation was observed and this suggests that these cells died exclusively by necrosis. Necrotic cell death was also associated with a rapid decline in mitochondrial activity and intracellular ATP. By contrast, with apoptosis the loss of mitochondrial function was delayed and the ATP level was maintained at near control levels for up to eight hours which was far beyond the onset of morphological changes. These data suggest that, depending on the light dose applied, both, necrosis as well as apoptosis can be induced with AlPcS4 mediated PDT and that photodamage in energy supplying cellular targets may influence the mode of cell death. Further, it is speculated that cells undergoing apoptosis in response to PDT might maintain a high ATP level long enough to complete the apoptotic program.
The involvement of cell cycle checkpoint-mutations in the mutagenesis induced in Drosophila by a longer wavelength light band of solar UVToyoshima, Megumi; Takinami, Syogo; Hieda, Kotaro; Furusawa, Yoshiya; Negishi, Tomoe
doi: 10.1039/b109556kpmid: 12659514
Solar ultraviolet radiation is considered to be injurious rather than necessary for most organisms living on the earth. It is reported that the risk of skin cancer in humans increases by the depletion of the ozone layer. We have examined the genotoxicity of solar ultraviolet, especially the longer wavelength light, using Drosophila. Recently, we have demonstrated that light of wavelength up to 340 nm is mutagenic on Drosophila larvae. Using an excision repair-deficient Drosophila strain (mus201), we have obtained results suggesting that the lesion caused in larvae by the 320 nm-light irradiation may be similar to the damage induced by irradiation at 310 nm, and that light of 330 and 340 nm may induce damage different from that induced by 310 and 320 nm-light. To examine the difference in DNA damage induced by light of a particular wavelength, we performed monochromatic irradiation on larvae of two Drosophila strains; one excision repair-deficient (mei-9) and another postreplication repair-deficient (mei-41). 310 and 320 nm-light was more mutagenic in the mei-9 strain than in mei-41, whereas 330 and 340 nm-light was more mutagenic in mei-41 than in mei-9. It is demonstrated that the mei-41 gene is a homologue of the human atm gene which is responsible for a cell cycle checkpoint. This result suggests that 310–320 nm-light induces DNA damage that is subject to nucleotide excision repair (NER) and that 330–360 nm-light causes damage to be recognized by the cell cycle checkpoint but it is not repairable by NER.
Laser flash photolysis study of the photochemistry of o-methylbenzilsWintgens, V.; Netto-Ferreira, J. C.; Scaiano, J. C.
doi: 10.1039/b108116kpmid: 12659515
The photochemistry of 2-methylbenzil (1) was investigated by steady state and laser flash photolysis techniques. Laser excitation of 1 in benzene leads to a transient, which shows absorption at 370 and 470 nm and is quenched by known triplet quenchers, whereas in methanol or acetonitrile a different transient absorption spectrum was observed. For the latter solvent the absorption bands are located at 350 and 410 nm when the spectrum is recorded 30 μs after the laser pulse. The kinetics associated with these two bands shows biexponential decay, from which lifetimes of 200 and >200 μs were determined. These transients were attributed to a mixture of two possible photoenols. Similar behavior was observed for 2,2′-dimethylbenzil (3), whereas 2,4,6-trimethylbenzil (4) did not show any detectable enol. Lamp irradiation of 1 in benzene leads to 2-hydroxy-2-phenylindan-1-one (2) as the major product, with a quantum yield of 0.09. Compound 3 also gives the corresponding hydroxyindanone as the main product (Φ = 0.25), whereas for 4 the cyclization product is formed in a very low quantum yield, i.e., <0.004. From these data two possible mechanisms were suggested to explain the formation of hydroxyindanones from methylbenzils, depending on the nature of the solvent.
An unusual energy transfer process from free-base porphyrin guests to a zinc porphyrin host in self-assembled systemsFlamigni, Lucia; Talarico, Anna Maria; Barigelletti, Francesco; Johnston, Martin R.
doi: 10.1039/b108635apmid: 12659516
The “V” shaped bis-porphyrinic host ZnH can complex the dipyridyl free-base porphyrin guests FBP and FBE with an association constant of 108 M−1. Complexation by ZnH of a reference photo-inactive guest, MN, occurs with a similar association constant and induces a perturbation in the luminescence properties of the host i.e. lower energy and decreased intensity and lifetime of the excited state localized on ZnH. A comparison of the effect of MN complexation by ZnH with those occurring in the complexes of FBP and FBE with ZnH, allowed us to establish the occurrence of an efficient energy transfer from each guest to the host ZnH. The rate constants are 2.5 × 1010 s−1 (ΔG0 = −0.2 eV) and 6.5 × 109 s−1 (ΔG0 = −0.13 eV) for FBE and FBP respectively. The results are consistent with a Förster type process with a very low orientation factor (κ2), even if a Dexter type mechanism with a weak intercomponent electronic interaction term (H), cannot be excluded.
Microcrystalline cellulose as a carrier for hydrophobic photosensitizers in waterZeug, André; Zimmermann, Jörg; Röder, Beate; Gabriela Lagorio, M.; San Román, Enrique
doi: 10.1039/b109592gpmid: 12659517
Samples of pheophorbide-a adsorbed on microcrystalline cellulose, which have been previously characterized in the solid state (M.G. Lagorio, E. San Roman, A. Zeug, J. Zimmermann and B. Röder, Phys. Chem. Chem. Phys., 2001, 3, 1524–1529), were washed with water, leading to stable suspensions of ultrafine particles (d < 2 μm) carrying photoactive, monomeric dye molecules. Detachment can be controlled through the particle size distribution. Suspensions are fluorescent and generate singlet molecular oxygen efficiently. A similar effect has been observed on washing samples containing hematoporphyrin IX adsorbed on the same support. Thus, using cellulose as a heterogeneous carrier, it is possible to introduce hydrophobic photosensitizers into the aqueous medium while avoiding aggregation, thus preserving their photophysical properties. At the same time, the spectroscopic properties of dyes attached to cellulose particles are compared with those in ethanol and ethanol–water mixtures and their differences are explained in terms of medium polarity and dye aggregation.
Mechanism of the photoinduced addition of methanol to the double bond of 2,2,4,6-tetramethyl- and 1,2,2,4,6-pentamethyl-1,2-dihydroquinolinesNekipelova, Tatiana D.
doi: 10.1039/b110113gpmid: 12659518
The mechanism of the photoinduced Markovnikov addition of methanol to the double bond of 2,2,4,6-tetramethyl-1,2-dihydroquinoline (1) and 1,2,2,4,6-pentamethyl-1,2-dihydroquinoline (2) was studied by the flash photolysis technique over a wide range of acetic acid and KOH concentrations. The successive formation of two transients was observed in neutral solutions in the case of compound 1. These transients have lifetimes on ms time-scales and absorption spectra with maxima at 420 and 480 nm for the first and the second transient, respectively. The decay rate constants of these transients (k1 and k2) were measured over the temperature range from 10 to 45 °C and the activation energies E1 ≈ 0 and E2 (31.4 ± 3.1) kJ mol−1 were determined. In MeOH acidified with acetic acid only the second transient (λmax = 480 nm) was observed, and it is proposed that this is due to a carbocation. The deuterium kinetic isotope effects determined in MeOD are 2 and 1.3 for k1 and k2, respectively, indicating that the first reaction is proton transfer proceeding via the A-SE2 mechanism and the second reaction is the nucleophilic addition of the solvent to the carbocation. In alkaline media, only the first transient (λmax = 420 nm) was observed with a lifetime of 250 ms at [KOH] > 2 × 10−3 mol dm−3. In the case of compound 2, the formation of a carbocation with λmax = 490 nm and a lifetime of several ms is observed within 10 ns of excitation in neutral, acidic, and alkaline solutions. The carbocation is quenched with KOH with a rate constant of 7 × 106 mol−1 dm3 s−1. The quantum yields of the reaction and of the fluorescence were measured and possible mechanisms discussed.
Photophysics and photochemistry of hydrophilic cyanine dyes in normal and reverse micellesTatikolov, Alexander S.; Costa, Sílvia M. B.
doi: 10.1039/b110450kpmid: 12659519
The photophysical and photochemical properties of the negatively charged hydrophilic cyanine dyes 1–3 were studied in isooctane/sodium bis(2-ethylhexyl) sulfosuccinate (AOT)/water and cyclohexane–hexanol/Triton X-100 (TX100)/water reverse micelles and in aqueous solutions in the presence of surfactants. In spite of the opposite total charges, 2 and its structural analog, cationic 3,3′-diethylthiacarbocyanine (DTC), show similar photophysical and photochemical behaviour in AOT reverse micelles. However, in normal micelles their photophysical properties are quite different: 2 exhibits unusual behaviour [a sharp increase in the fluorescence quantum yield (Φf) in the presence of both cationic and anionic micelles, but very small changes with neutral TX100], whereas the behaviour of DTC is normal. The Φf values of 1–3 in AOT reverse micelles suffer a steep drop when w0 increases from 0 to 10 (w0 = [H2O]/[AOT]) and remain essentially constant at higher w0, while in TX100 reverse micelles the Φf values undergo small variations with w0. A decrease in the photoisomerization quantum yield, and a rise in Φf, in S1→T intersystem crossing, in the back isomerization activation energy and in the preexponential factor were found for 12–3 in AOT reverse micelles with small w0. The unusual behaviour of 12–3 in micelles is attributed to the bipolar structure of the dyes.