含5-氟脲嘧啶的聚硅氧烷的合成

5-氟脲嘧啶与α、ω双二乙胺基聚二取代基硅氧烷反应 可得含5-氟脲嘧啶的缩聚物。并以红外、核磁对缩聚物进行了研究。在室温将所得缩聚物在不同pH介质中,进行水解,以266.5nm处紫外吸收光度,定量测定所释放出来5-氟脲嘧啶。当缩聚物n值增大时,水解速度减慢,1、3结构则比2、4结构缩聚物为快。     

含5-氟脲嘧啶齐聚物的合成

<正> 5-氟脲嘧啶是用于治疗肺癌、肾癌、乳癌、结肠癌等癌变的药物。虽然5-氟脲嘧啶具有上述疗效,但在临床应用时,尚存在恶心,呕吐,腹泻,白细胞、血小板下降等副作用。更为严重的缺点,是既对肿瘤细胞有活性,同时也作用于正常细胞,为克服此缺点,将抗癌药物与低分子化合物结合,诸如激素、磺胺,这些是已知能集聚在一定组织内药物,但利用此法,迄今也很少获得成效。     

SYNTHESIS OF OLIGOMERS CONTAINING 5-FLUOROURACIL

The condensation oligomers of 5-fluorouracil were prepared by reaction of 2,4-bis-(trimethyl-silyloxy)-5-fluoropyrimidine) with various dicarboxylic chlorides, e.g.The structures of obtained oligomers were characterized by IR and the oligomers were then hydrolyzed in acid, alkaline and neutral media at room temperature respectively. The amount of 5-fluorouracil released was quantitated by measuring its UV absorbance at 265.5nm. However in the case of oligomers containing phenylene moiety, 5-fluorouracil was not detected when the hydrolysis was conducted in acid or neutral medium, while in the case of oligomers containing methylene moiety, hydrolysis proceeded easily in acid, alkaline and neutral media.     

THE SYNTHESIS OF GLYCOSIDES OF 1-ETHOXYMETHYL-5-FLUOROURACIL

ABSTRACT

Three N-glycosides 3(A–C) of 1-ethoxymethyl-5-fluorouracil were synthesized by the reaction of 2 with α-bromoacetylglucose 1(A–C) under phase transfer catalysis. The compounds 3(A–C) were treated by ammonia to obtain three new compounds 4(A′–C′). Their structures were confirmed by elementary analysis, IR, ¹H NMR.     

侧链含5-氟尿嘧啶甲壳胺的合成及其抗肿瘤活性的研究

本文报道了以不同分子量的甲壳胺为载体,制备了侧链含5-氟尿嘧啶的一系列高分子载体药物;通过定氮分析测定了H_2N-基的反应率;由IR、UV和~(13)C-NMR确定了载体药物的结构;模拟生理条件考查了在不同pH的缓冲溶液中5-氟脲嘧啶或其衍生物的水解释放率。体外初步实验结果表明,具有Ⅰ和Ⅱ结构的载体药物对艾氏腹水癌细胞有较强的杀伤作用。     

5-氟尿嘧啶短肽的合成及其抗肿瘤活性研究

5-氟尿嘧啶乙酸对-硝基苯酯和5-氟尿嘧啶丙酸对-硝基苯酯分别与三种二肽反应,制备了五个5-氟尿嘧啶二肽(4 a-e)。以5-氟尿嘧啶的氨基酸对-硝基苯酯(2 a-c)分别和三种二肽反应,制得四个5-氟尿嘧啶三肽(5 a-d)。产物经元素分析、NMR、IR和UV鉴定。初步动物试验表明:5-氟尿嘧啶丙酰甘-苯丙二肽,5-氟尿嘧啶乙酰甘-甘-苯丙三肽和5-氟尿嘧啶乙酰缬-亮-甘三肽对小白鼠移植性艾氏腹水癌有一定的抑制作用。     

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.     

铜(Ⅱ)5-氟尿嘧啶的多核配合物的合成及磁学性质表征

本文合成了两种新的铜(Ⅱ)5—氟尿密嘧啶配合物,[Cu(fuH)(Ac)(OH)](1)和[Cu_3O(fuH)_2(Ac)(OH)_3](2),进行了元素分析和红外光谱测定。从80-300K变温磁化率的数据表明,1和2均服从Curie-Weiss定律,θ值分别为-92K和-94K,证示在1和2分子内部均存在着反铁磁偶合作用。出1的室温多晶EPR谱测得g‖=2.30,g⊥=2.08和|A‖|=16.8mT,表明铜(Ⅱ)的几何构型为畸变四方形,其单电子主要集居于d_(x~2-y~2)轨道。同时对1和2的可能结构及反铁磁偶合作用机制进行了讨论。     

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.     

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.     

高分子药物研究——Ⅱ.主链含5-氟脲嘧啶聚酯的合成

本文报道主链含5-氟脲嘧啶聚酯的合成及抗动物肿瘤初步试验。将5-氟脲嘧啶在二甲基甲酰胺中与无水碳酸钾作用,所生成的5-氟脲嘧啶钾盐随即与双氯乙酸二醇酯进行共缩聚,得到了6种主链含5-氟脲嘧啶的聚酯。同时还合成了三种新的双氯代乙酸二醇酯单体。     

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.     

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.     

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.