嘧啶脲类化合物的合成及其除草活性

嘧啶脲类化合物的合成及其除草活性李斌林柄栋刘长令魏晓丽（化工部沈阳化工研究院沈阳１１００２１）关键词嘧啶异氰酸酯嘧啶脲合成除草剂４０年代开发的取代脲除草剂如敌草隆等已得到了广泛应用［１］，但由于用药量较大，已逐渐被磺酰脲类除草剂取代。在这类磺酰脲除草...     

PHOTOSENSITIZED DIMERIZATION OF URACIL

Abstract— The four isomeric dimers of uracil were isolated from photochemical reactions which were sensitized by acetone. Product analyses, made on the basis of the chemical properties of the compounds, showed that the h, h dimers predominate. Infrared and mass spectra for the dimers are here presented as well as nuclear magnetic resonance data. The syn h, h dimer has been found in two polymorphic forms.     

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.     

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 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.     

EFFECTIVE PHOTODYNAMIC ACTION BY RHODAMINE 123 LEADING TO PHOTOSENSITIZED KILLING OF CHINESE HAMSTER OVARY CELLS IN TISSUE CULTURE AND A PROPOSED MECHANISM

The effectiveness of rhodamine 123 (R123) as a photosensitizer of cell killing is relatively low and correlates with its inefficient production of singlet oxygen. The known selective retention of R123 in the mitochondria of epithelially derived carcinoma cells, however, is a selective feature that could lead to a more useful therapeutic ratio if photosensitizing effectiveness could be increased. Chinese hamster ovary (CHO) cells in tissue culture were therefore exposed to R123 shortly before and during illumination under conditions controlled for oxygen concentration and temperature. Effective photosensitization of cell killing, as judged by colony formation, was produced by 95% but not by 19% O₂ during illumination of cells at 5d?C or 37d?C, and this was additionally enhanced at the sublethal temperature of 42d?C. Two CHO cell lines were examined; one line, CHO-AA8, was proficient in the repair of DNA damage and the parent to the second line, CHO-EM9, that was deficient in the repair of DNA strand breaks. Cells of both lines incorporated R123 to a similar degree and were similarly photosensitized by the presence of igh oxygen concentration. Furthermore, plasma membrane damage as judged by teh exclusion of trypan blue was not observed immediately after illumination in the presence of R123, but was seen in the presence of meso-tetra-(4-sulfonatophenyl)-porphine (TPPS₄). The extent of damage to the plasma membrane by TPPS₄ was greater in the presence of 95% compared to 19% O₂ during illumination. Photodynamic action at the level of teh plasma membrane appears to contribute to photosensitization by TPPS₄ but not by R123 soon after exposure of cells to these sensitizers. It is hypothesized that photodynamic action by R123 is the primary mechanism causing the observed photosensitization of cell killing, and that mitochondria are teh site of photosensitized damage responsible for this killing.     

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.     

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.     

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.     

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.     

THERMAL REQUIREMENTS OF PHOTOSENSITIZED PYRIMIDINE DIMER SPLITTING

Abstract— A cis, syn -pyrimidine dimer (derived from thymine and orotate) covalently linked to 5-methoxyindole has been studied as a mechanistic model of photosensitized pyrimidine dimer splitting. In this dimer-indole, photoinitiated electron transfer to the dimer causes splitting in a manner that parallels the mechanism by which the DNA photolyases are thought to act. Dissolved in EPA (diethyl ether-isopentane-ethyl alcohol, 5: 5: 1, by vol) at room temperature, the dimer-indole exhibited indole fluorescence quenching and underwent splitting upon irradiation at 300 nm. In an EPA glass at 77 K, however, no splitting was detectable. To distinguish the effects of temperature and immobilization, photolysis experiments were performed on PMM [poly(methyl methacrylate)] films containing dimer-indole. In PMM at room temperature, dimer-indole underwent splitting when irradiated at 300 nm, which indicated that immobilization per se was not responsible for the failure of dimer-indole to split at low temperature. Furthermore, no splitting was observed when dimer-indole was irradiated in PMM at 77 K. These results imply that a step following photoinitiated, intramolecular electron transfer from indole to dimer has an insurmountable activation barrier at 77 K. The mechanistic implications for the photolyases are considered.     

INACTIVATION OF GRAM-NEGATIVE BACTERIA BY PHOTOSENSITIZED PORPHYRINS

Photosensitization of Escherichia coli and Pseudomonas aeruginosa cells by deuteroporphyrin (DP) is shown to be possible in the presence of the polycationic agent polymyxin nonapeptide (PMNP). Previous studies established complete resistance of Gram-negative bacteria to the photodynamic effects of porphyrins. The present results show that combined treatment of E. coli or P. aeruginosa cultures with DP and PMNP inhibit cell growth and viability. No antibacterial activity of PMNP alone could be demonstrated and cell viability remained unchanged. Spectroscopically, PMNP was found to bind DP, a mechanism which probably assists its penetration into the cell's membranes. Insertion of DP into the cells was monitored by the characteristic fluorescence band of bound DP at 622 nm. Binding times were 5-40 min and the extent of binding increased with decreasing the pH from 8.5 to 6.5. DP binding constants, as well as the concentrations of PMNP which were required for maximal effect on the various Gram-negative bacteria, were determined fluorometrically. By the treatment of DP, PMNP and light the growth of E. coli and P. aeruginosa cultures was stopped and the viability of the culture was dramatically reduced. Within 60 min of treatment the survival fraction of E. coli culture was 9 x 10(-6) and that of P. aeruginosa was 5.2 x 10(-4). Electron microscopy depicted ultrastructural alterations in the Gram-negative cells treated by DP and PMNP. The completion of cell division was inhibited and the chromosomal domain was altered markedly.     

PHOTOSENSITIZED INACTIVATION OF CHINESE HAMSTER CELLS BY PHTHALOCYANINES

Chloroaluminum phthalocyanine was found to sensitize cultured Chinese hamster cells upon exposure to white fluorescent light. Elimination of wavelengths below 370 nm did not reduce the effect significantly, indicating that the effective wavelengths were those absorbed by the Q band (600–700 nm) of phthalocyanine. The magnitude of the photosensitizing effect increased with the dye concentration and the time of its contact with the cells prior to light exposure. Although photosensitization was drastically reduced in the absence of oxygen, the lack of effect of glycerol and D₂0 during exposure suggests that neither hydroxyl radicals nor ¹O₂ are responsible for the cytotoxic response. The efficiency of the photosensitized induced cell killing did not vary with the position of the cells in the cell cycle, in contrast to exposure to X-rays. The improved spectral properties, the reported low toxicity and the selective retention by neoplasms, make phthalocyanines promising candidates for use in photodynamic therapy of cancer.     

含氧光敏引发体系的研究——Ⅵ.二苯酮/三乙胺体系引发光聚合过程中的再次引发效应

过去,作者曾发表了多种光敏引发体系引发烯类单体光聚合的工作,在研究2,2-二甲氧基苯乙酮在氧存在下引发甲基丙烯酸甲酯光聚合时,结合在聚合物链端的引发剂碎片具有光化学活性,在光聚合反应中产生高分子自由基,发生再次聚合,出现高分子量