Antioxidant inhibition of porphyrin-induced cellular phototoxicity.

Porphyrins such as protoporphyrin IX (PP IX) and uroporphyrin I (UP I) can be phototoxic to human cells. To study the protective ability of antioxidants (beta-carotene, lycopene, ascorbic acid and alpha-tocopherol), against such porphyrin phototoxicity, membrane destruction experiments (Jurkat cells) and human cell cultures (fibroblasts) were performed. Both beta-carotene and lycopene and also the combination of beta-carotene, ascorbic acid and alpha-tocopherol offered cell protection against PP IX phototoxicity. Investigations of both cell membrane protection and of cell growth showed differences in terms of the protection afforded by the anti-oxidants. Thus, for PP IX, carotenoids alone, and in combination with ascorbic acid and alpha-tocopherol, showed higher protection factors in general than UP I. However, for membrane protection there was significant protection against UP I by the combination of beta-carotene, ascorbic acid and alpha-tocopherol but not by any of these anti-oxidants alone. The membrane protection against PP IX by beta-carotene, and especially lycopene, is significant presumably because of the high lipophilicity of all these molecules. However, the hydrophilic UP I will cause phototoxicity mainly via H(2)O(2), radical or singlet oxygen production in the aqueous phase, and these reactive species may be generated some distance from the cell membrane. This may lead to the little or no protection observed for UP I by the individual antioxidants. Nevertheless, a combination of beta-carotene, ascorbic acid and alpha-tocopherol offers membrane protection against the phototoxicity of both porphyrins. This is believed to occur as a result of synergistic processes. Our results suggest that the treatment of porphyria cutanea tarda and erythropoietic protoporphyria may be improved by the use of a combination of the antioxidants studied.     

Decomposition of cinnabarinic acid by hydrogen peroxide

The hydrogen peroxide-induced decomposition of cinnabarinic acid 2 has been examined. Two major compounds were found to arise from the decomposition; 3-hydroxyanthranilic acid 1 , and an isomeric mixture of two novel hemiketals.     

THE TRIPLET EXTINCTION COEFFICIENTS OF SOME BACTERIAL CAROTENOIDS

The extinction coefficients of the triplet states of the bacterial carotenoids, neurosporenc (Λ_max 489 nm). sphcroidene (Λ_max 510 nm). spheroidenone (Λ_max 550 nm) and spirilloxanthin (Λ_max 550 nm) in cyclohexane have been determined to be 27.4. 30.9. 6.06 and 9.20 × 10⁴ dm³ mol^?1 cm¹, respectively. These values were obtained by an energy transfer technique using a range of carotenoid concentrations. For the three that had been studied earlier, the extinctions now obtained are suhstantially higher than prcviously reported.     

SINGLET OXYGEN GENERATION BY FUROCOUMARIN TRIPLET STATES—I. LINEAR FUROCOUMARINS (PSORALENS)

Abstract— Triplet extinction coefficients and hence singlet → triplet intersystem crossing quantum yields have been measured in benzene for a number of linear furocoumarins including pseudopsoralen, 5, 8-dimethoxypsoralen, 4, 5', 8-trimethylpsoralen and 3-carbethoxypseudopsoralen. These triplet yields were then used in conjunction with the corresponding quantum yields of singlet oxygen formation, measured in oxygenated solution, to estimate the fractions of furocoumarin triplets which when quenched by ground state oxygen produce singlet excited oxygen, similar data being obtained for psoralen, 5-methoxypsoralen, 8-methoxypsoralen and 3-carbethoxypsoralen. The superoxide anion radical was not detected from these oxygen quenching reactions, nor was a contribution to the singlet oxygen yield found from furocoumarin excited singlet state quenching by oxygen. The fraction of furocoumarin-oxygen quenching interactions leading to singlet oxygen varied between 0.13 (for 5, 8-dimethoxypsoralen) and unity (for 3-carbethoxypsoralen), and thus needs to be taken into account, as well as the triplet quantum yields, in assessing photobiological processes involving singlet oxygen.     

WAVELENGTH DEPENDENCE OF THE INTERSYSTEM CROSSING EFFICIENCY FOR RETINAL ISOMERS

Abstract— The quantum efficiencies of intersystem crossing (_ISC) fur four isomers of retinal, the all- trans , 9- cis , 11- cis and 13- cis , have been measured using both 265 nm and 353 nm excitation. The values for the all- trans and 9- cis isomers are independent of the excitation wavelength but the values for the 11- cis and 13- cis isomers show a marked increase in the efficiency of ISC for 353 nm excitation compared with the 265 nm excitation.     

SOME PHOTOPHYSICAL PROPERTIES OF 3-CARBETHOXYPSORALEN, 8-METHOXYPSORALEN and 5-METHOXYPSORALEN TRIPLET STATES

Abstract Triplet absorption spectra, extinction coefficients (ɛ_T), decay rates ( K ₁), oxygen quenching rates (k_q) and intersystem crossing yields (φ_T) for 3-carbethoxypsoralen (3-CPs). 8-methoxypsoralcn (8-MOP) and 5-methoxypsoralen (5-MOP) in methanol are reported. For 8-MOP and 3-CPs corresponding values are also reported with water as the solvent. Some photophysical data are also reported for 5-MOP in water, but ɛ_T and φ_T were not obtained.
The phosphorescence spectra for these furocoumarin derivatives in ethanol at 77 K are reported together with the corresponding lowest triplet energy and lifetime. The values of the various photophysical properties obtained are compared with values reported by previous workers.     

PHOTOPHYSICAL PROPERTIES OF meso-TETRAPHENYLPORPHYRIN and SOME meso-TETRA(HYDROXYPHENYL)PORPHYRINS

Abstract— The o-, m-, and p-isomers of 5, 10, 15, 20- tetra(hydroxyphenyl)-porphyrin have been of recent interest as potential second-generation sensitisers in tumour phototherapy. Fluorescence spectroscopy, nanosecond laser flash photolysis and pulse radiolysis have been used to characterise the singlet and triplet excited states of tetraphenylporphyrin and the o, m-, and p-isomers of tetra(hydroxyphenyl)porphyrin. This has included evaluation of fluorescence yields and lifetimes, triplet spectra, lifetimes, oxygen quenching rate constants, extinction coefficients, and yields and singlet oxygen yields. Whilst the fluorescence quantum yields were low, the triplet yields were all 0.7 ± 10% and the singlet oxygen yields 0.6 ± 10%: all these parameters are in the ranges shown by other efficient porphyrin photosensitisers. The similar photophysical properties found for these compounds suggest that their differing tumour sensitising efficiencies are likely to be due to other factors.     

Well-defined [Rh(NHC)(OH)] complexes enabling the conjugate addition of arylboronic acids to α,β-unsaturated ketones

The synthesis and catalytic activity of three well-defined monomeric rhodium(I) hydroxide complexes bearing N-heterocyclic carbene (NHC) ligands are reported. [Rh(cod)(ICy)(OH)] promoted the 1,4-addition of arylboronic acids to cyclic enones, with TONs and TOFs of 100,000 and 6,600 h(-1), respectively, at 0.001 mol% catalyst loadings. Mechanistic studies permitted the isolation of a phenylrhodium intermediate.     

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.