PHOTOSENSITIZED DIMERIZATION OF THYMINE

Abstract— In contrast with previous reports from other laboratories, four isomeric dimers were isolated from the photochemical reaction of thymine sensitized by either acetone or propiophenone. Product analyses, made by use of nuclear magnetic resonance spectroscopy, showed that the distribution of dimers is dependent on the character of the solvent medium. Mass spectra for all four dimers were obtained and are here presented.     

PHOTOCHEMISTRY OF URACIL. INTERSYSTEM CROSSING AND DIMERIZATION IN AQUEOUS SOLUTION

Abstract— Ultraviolet irradiation of ¹⁴C-uracil in aqueous solution results in the formation of hydrate and dimer photoproducts. The rate of dimerization increases with increasing uracil concentration, and decreases with increasing concentration of oxygen in solution. The kinetics are in agreement with a model previously proposed to account for the reactions, in which dimerization occurs by a reaction involving the triplet state of uracil, but hydration occurs from an excited singlet state. Oxygen reduces dimer formation by quenching the triplet. The quantum yield for intersystem crossing (ISC) to the triplet depends on the irradiation wavelength, increasing from 0.0014 at 280 nm to 0.016 at 230 nm. The ratio of rate constants for reaction of the triplet with oxygen and for dimerization is 1.1; the ratio of rate constants for triplet decay and for dimerization is 5.9 × 10^-5 M. The increase in ISC with photon energy suggests that ISC is favoured from excited vibrational levels. The quantum yield for hydration is about 0.002 at pH 4.5 for all wavelengths, but increases as the pH is decreased.     

INTERSYSTEM CROSSING AND DIMERIZATION IN AQUEOUS SOLUTIONS OF URACIL AND OROTIC ACID

Un analisis cinético de la fotoquímica en el u.v. de uracilo y ácido orótico muestra que el hidrato se forma a partir del estado singulete, mientras que el dímero lo hace a partir del estado triplete. El rendimiento cuantico de la formación del hidrato es independiente de la longitud de onda de irradiación, mientras que el rendimiento cuántico de la formación de triplete aumenta a longitudes de onda menores. Se presenta además una explicación para el aumento de “intersystem crossing” a altos niveles de excitación basada en la presen-cia de tautomeros.     

THE PHOTOADDITION OF NUCLEOPHILES TO URACIL

Abstract— Quantum yields for 254 nm ultraviolet photoaddition of the nucleophiles hydrazine, HCN, HSO₃^-, methyl amine, and BH₄^- to uracil have been measured; the quantum yields for hydrazine, HCN, and HSO₃^- additions are pH-dependent. The nucleophiles sulfide, azide, chloride, bromide, iodide, nitrite and thiocyanate failed to photo–add under similar conditions. These reactions are interpreted as 1,4-additions to the conjugated enone system of the anti-aromatic compound, uracil; as suggested by S. Y. Wang (Wang and Nnadi, 1968). The nuclear magnetic resonance (NMR) spectrum of the photohydrate of uracil-5-d-showed that the proton was added to the 5-position in a stereochemically random manner. The photoaddition of HSO₃^- takes place at much lower concentrations than required for the thermal addition of this anion and is also stereochemically random.     

THE PHOTOSENSITIZED OXIDATION OF SULPHIDES

Abstract— The rates of photosensitized oxidation of a number of sulphides were determined under standard conditions in 1, 1, 2,2-tetrachloroethane and in methanol. It was found that the ratio of the rates of reaction in the two solvents was not constant for different sulphides and that t -butyl sulphide does not react in methanol. It is inferred that the presence of an H atom in the α position is essential for reaction in polar solvents and an appropriate mechanism is suggested. The results indicate that reaction in chlorinated solvents may take place by a different mechanism which possibly involves H-abstraction by triplet sensitizer.     

PHOTOSENSITIZED CYCLODIMERIZATION OF 5-FLUOROURACIL

Abstract—The photosensitization by acetone or N-methyllutidone yields a C₄-cyclodimer from 5-fluorouracil in aqueous solution. with a quantum yield of 2 × 10^--³. The dimer isolated has been characterized by UV, IR. NMR, and mass spectra. The stereochemistry of the dimer has been determined to be anti head-to-tail configuration from the NMR spectral analysis.     

ACETONE-SENSITIZED DIMERIZATION OF CYTOSINE DERIVATIVES*

Abstract— Irradiation of cytosine derivatives in aqueous solution in the presence of acetone with light of wavelength > 290 nm results in the formation of cyclobutane-type dimers. A mixture of cis-syn, cis-anti and trans-anti isomers are formed, the trans-anti dimer being the major product. The trans-anti isomers have been isolated as crystalline products and are found to be fairly stable in the solid state. These dimeric products undergo deamination in neutral aqueous solution. In acidic solution monomerization is an important reaction whereas in alkaline solution ring opening is the major mode of degradation. The results of analysis of the photo-products are compared with those of sensitized irradiation of uracil and undine.     

PHOTOSENSITIZED SPLITTING OF PYRIMIDINE DIMERS

Abstract— The photosensitized monomerization of cis-syn and trans-syn cyclobutane-type thymine dimers, and the cis-syn thymine-uracil dimer, using anthraquinone derivatives as sensitizers, is described.     

PHOTOSENSITIZED DEGRADATION OF C-PHYCOCYANIN*

Abstract— –Irradiation with visible light in the presence of allylthiourea causes the transformation of phycocyanin into a ‘purple’ chromoprotein absorbing maximally at 565 and 605 nm. This reaction is irreversible, and not affected by the presence of oxygen. The product is homogeneous on electrophoresis, ultracentrifugation and chromatography, and has a molecular weight one third that of the starting material. Although apparently physically homogeneous, the action spectrum for fluorescence suggests that the ‘purple’ compound may consist of two two chromophores associated with protein moieties that are indistinguishable.     

烯烃光敏顺反异构化反应

烯烃光顺反异构化是一个重要的基元有机光化学反应.本文从垂直中间态理论和势能面的角度对烯烃光敏顺反异构化反应机理进行了综述,并介绍了这些理论在异构体激发三重态能量的确定和敏化剂筛选中的应用.     

MECHANISMS OF THE PHOTOSENSITIZED OXIDATION OF TYRAMINE

Abstract— …According to the criteria of enhancement in D₂O and inhibition by sodium azide, the oxidation of tyramine photosensitized by methylene blue is largely a singlet oxygen or Type II process. Its quantum yield approximates 0.3 in D₂O at pH 10. There is a less efficient reaction not quenched by azide, which is assigned to a dye-substrate or Type I process. It gives rise to products with distinct bands at 320 and 285nm. Products of the Type I reaction are further oxidized by singlet oxygen and thereby compete with tyramine for this reagent. Kinetic parameters were estimated by computer simulation of the dependence of quantum yield on extent of reaction. The rate constant for reaction of O₂ (¹Δ_g) with tyramine was estimated to be 2.8 × 10⁸ M ^-1 s ^-1± 20% at pH 10. The reaction was also sensitized by hypericin in what appears to be a Type II process.     

PHOTOCHEMICAL ADDITION OF GLUTATHIONE TO URACIL AND THYMINE

Abstract —Irradiation (Λ > 240 nm) of thymine in aqueous solution in the presence of glutathione produces primarily 5-S-glutathione-5, 6-dihydropyrimidine and 5- S, S -glutathione-5, 6-dihydro-pyrimidine. These adducts are obtained in better yields when the irradiations (Λ > 280 nm) are carried out in the presence of triplet-state sensitizers. Reduction of 5- S, S -glutathione-5, 6-dihydropyrimidine with zinc dust in acetic acid yields the corresponding 5, 6-dihydropyrimidine. When thymine-glutathione adducts are heated in 6 N HCl for 2h, 5- S -cysteine-5, 6-dihydrothymine and 5- S, S -cysteine-5, 6-dihydrothymine are formed. Under these conditions, uracil-glutathione adducts are less stable and are converted to products other than uracil-cysteine adducts.     

PHOTOCYCLOADDITION OF ACETONE TO URACIL AND CYTOSINE

Abstract— Ultraviolet irradiation (Λ > 280 nm) of uracil in aqueous acetone (1:1) produces cyclobutane uracil dimer and uracil-acetone addition product. The addition product is identified as an oxetane. The same product is also obtained from cytosine irradiated under the same conditions. The cytosine-acetone oxetane apparently undergoes deamination readily. Irradiation (Λ= 265 nm) of the oxetane in aqueous solution produces acetone and uracil with a quantum efficiency of 0–16.     

PHOTOSENSITIZED DEGRADATION OF DNA BY DAUNOMYCIN

Abstract Visible irradiation of DNA-daunomycin solutions resulted in a decrease of viscosity of the DNA and an increase of the rate of denaturation of DNA in formaldehyde. These changes are consistent with the induction of single-strand breaks in the DNA, some of which pair to cause fragmentation of the DNA. The DNA damage increases with drug: nucleotide ratio up to 0.2 and is diminished beyond that range. The damage also increases with ionic strength up to 0.6 M and is diminished above that value. These results suggest that the non-intercalated form of the drug is involved in the photosensitization process. Radicals that are produced accompanying the degradation have been trapped by 5,5-dimeth-yl-l-pyrroline-1-oxide and identified as hydroxyl radicals from their ESR spectrum. The DNA photosensitized damage is completely inhibited when hydroxyl radicals are removed by the spin-trap, suggesting a direct role for the hydroxyl radicals in the DNA photosensitized degradation process. The implications of the photosensitized DNA damage and the production of hydroxyl radicals in this process are discussed with respect to the medical uses and chemotherapeutic role of daunomycin.     

KINETICS OF THE ULTRAVIOLET-INDUCED DIMERIZATION OF THYMINE IN FROZEN SOLUTIONS*

Abstract— It is known that thymine forms dimers when aqueous solutions are irradiated with ultraviolet light while in the frozen state, but does not form dimers when solutions are irradiated in the liquid state. The eutectic point of aqueous thymine solutions was found to be. —0.02°C. Since the irradiation of frozen solutions is always carried out at lower temperatures, the dimerization must be occurring in the solid state. Activation energies and quantum yields for dimer formation were determined by irradiating 1–mm layers of thymine solution at —5°C to — 707deg;C for various lengths of time. As expected, the activation energy was zero. After measuring the amount of radiation scattered by samples of ice, the extreme values for the quantum yield were found to be 0.73 and 4.08. The lower limit assumed that all the scattered light was absorbed by thymine; the upper limit assumed that none was absorbed. Since the theoretical maximum quantum yield is 2, the best estimate of the quantum yield is considered to be between 1 and 2.     

PHOTOSENSITIZED LYSIS OF LIPOSOMES BY HEMATOPORPHYRIN DERIVATIVE

The spectral properties and efficiency for photosensitizing the lysis of phosphatidylcholine liposomes have been measured for the components of hematoporphyrin derivative (Hpd) after alkaline hydrolysis and fractionation by polyacrylamidc gel chromatography. Two major and two minor Hpd fractions have been identified whose spectral properties correlate with the anoxic sensitizing efficiency and the oxygen enhancement ratio (OER). The fastest moving fraction, which is the putative biologically active component, comprised one-third of the starting material and had OER = 2.7. Liposome lysis by this fraction was inhibited in the presence of human serum albumin at concentration ratios comparable to those employed for photoradiation therapy. The present results show that Hpd can act as an oxic and anoxic photosensitizer of a model biomembrane and suggest that separation from serum proteins is required for in vivo photosensitization.