Modifying effects of cysteine and aromatic sulfhydryl and disulfide agents on the radiation-induced decomposition of thymidine

Steady-state γ radiolysis of oxygen-free aqueous solution of thymidine has been carried out in the presence of cysteine and five aromatic sulfydryl and disulfide agents. The common major mode of action of these compounds is their ability to scavenge water radiolysis species including OH^• radicals and solvated electrons. In addition, cysteine and the two compounds with a free SH group were found to act as hydrogen donor leading to an increase in the formation of the 5R and 5S diastereoisomers of 5,6-dihydrothymidine and 5-hydroxy-5,6-dihydrothymidine. Two sulfhydryl agents including cysteine were also found to chemically repair the radiation-induced osidic radicals through efficient hydrogen donation mechanisms. It should be noticed that hydrogen atom transfer to hydroxyl and electron thymidine adducts leads to the decomposition of the thymine moiety.     

Formation of 5-Hydroxy-5,6-Dihydrothymidine and cis-5,6-Dihydroxy-5,6-Dihydrothymidine in the Radiolysis of N2O-Saturated Aqueous Solutions of Thymidine, Thymidine 5"-Monophosphate, and DNA

The yields of formation of 5-hydroxy-5,6-dihydrothymidine and cis-5,6-dihydroxy-5,6-dihydrothymidine in the radiolysis of thymidine, thymidine 5"-monophosphate, and DNA in N₂O-saturated aqueous solutions were measured in order to study the mechanism of nucleic acid radiolysis. The above compounds were found to be main radiolysis products upon irradiation of thymidine and thymidine 5"-monophosphate. However, these compounds were formed in very low yields upon irradiation of DNA, and they amounted to less than 2% of the degradation yield of DNA thymine. The yield of the 5-hydroxythymidin-6-yl radical was evaluated by determining the amount of 5-hydroxy-5,6-dihydrothymidine formed in the radiolysis of the above compounds in the presence of cysteamine.     

Preparation,isomerisation et configuration absolue des “hydrates” de thymidine

The (+) and (?) cis-6-hydroxy-5,6-dihydrothymidines 4a and 5a have been prepared by mild reduction of (+) and (?) trans-5-bromo-6-hydroxy-5,6-dihydrothymidine 2a and 3a. The trans “hydrates” 6a and 7a have been prepared by warming 4a or 5a in alkaline aqueous solution at 60°C. The isomerization of 4a, 5a, 6a and 7a involved the opening of the pyrimidine ring at 1,6 position and subsequent keto-enolisation. The characterization of the configurations of “hydrates” is based on the specific formation of the enantiomeric forms of 6-hydroxy-5,6-dihydrothymine by radiation-induced degradation of 4a, 5a, 6a, 7a and 5,6-dihydrothymine 5S8b.     

Photoinduced reductive repair of thymine glycol: implications for excess electron transfer through DNA containing modified bases

Photoinduced reduction of thymine glycol in oligodeoxynucleotides was investigated using either a reduced form of flavin adenine dinucleotide (FADH(-)) as an intermolecular electron donor or covalently linked phenothiazine (PTZ) as an intramolecular electron donor. Intermolecular electron donation from photoexcited flavin (FADH(-)) to free thymidine glycol generated thymidine in high yield, along with a small amount of 6-hydroxy-5,6-dihydrothymidine. In the case of photoreduction of 4-mer long single-stranded oligodeoxynucleotides containing thymine glycol by *FADH(-), the restoration yield of thymine was varied depending on the sequence of oligodeoxynucleotides. Time-resolved spectroscopic study on the photoreduction by laser-excited N,N-dimethylaniline (DMA) suggested elimination of a hydroxyl ion from the radical anion of thymidine glycol with a rate constant of approximately 10(4) s(-1) generates 6-hydroxy-5,6-dihydrothymidine (6-HOT(*)) as a key intermediate, followed by further reduction of 6-HOT(*) to thymidine or 6-hydroxy-5,6-dihydrothymdine (6-HOT). On the other hand, an excess electron injected into double-stranded DNA containing thymine glycol was not trapped at the lesion but was further transported along the duplex. Considering redox properties of the nucleobases and PTZ, competitive excess electron trapping at pyrimidine bases (thymine, T and cytosine, C) which leads to protonation of the radical anion (T(-)(*), C(-)(*)) or rapid back electron transfer to the radical cation of PTZ (PTZ(+)(*)), is presumably faster than elimination of the hydroxyl ion from the radical anion of thymine glycol in DNA.     

Independent generation of the 5-hydroxy-5,6-dihydrothymidin-6-yl radical and its reactivity in dinucleoside monophosphates

Hydroxyl radical is a major reactive oxygen species produced by gamma-radiolysis of water or Fenton reaction. It attacks pyrimidine bases and gives the 5-hydroxy-5,6-dihydropyrimidin-6-yl radical as the major product. Here we report the synthesis of all four stereoisomers of 5-hydroxy-6-phenylthio-5,6-dihydrothymidine (T*), which, upon 254 nm UV irradiation, give rise to the 5-hydroxy-5,6-dihydrothymidin-6-yl radical (I). We also incorporated the photolabile radical precursors into dinucleoside monophosphates d(GT*) and d(TT*) and characterized major products resulting from the 254-nm irradiation of these dinucleoside monophosphates. Our results showed that, under anaerobic conditions, the most abundant product emanating from the 254-nm irradiation of d(GT*) and d(TT*) is an abasic site lesion. Products with the thymine portion being modified to thymine glycol and 5-hydroxy-5,6-dihydrothymine were also observed. In addition, we demonstrated that radical I can attack the C8 carbon atom of its 5' neighboring guanine and give rise to a novel cross-link lesion. Moreover, LC-MS/MS results showed that gamma-radiation of d(GT) under anaerobic condition yielded the same type of cross-link lesions.     

Annelation of perfluorinated heteroaromatic systems by 1,3-dicarbonyl derivatives

Reactions of various perfluorinated heteroaromatic substrates such as tetrafluoro-4-cyanopyridine, tetrafluoropyrazine and tetrafluoropyridazine with 1,3-dicarbonyl systems gave corresponding [5,6]-ring fused furo derivatives. Subsequent reactions of the [5,6] bicyclic scaffolds with nucleophiles gave some highly functionalised heteroaromatic systems.     

Phosphorylation of Tetrahydric Phenols with Trivalent Phosphorus Compounds. Synthesis of Tetraphosphites

The reactions of 1,1'-spirobi(5,6-dihydroxy-3,3-dimethylindane) and 1,2,4,5-tetrahydroxybenzene with 2-chloro-1,2,3-dioxaphosphorinanes of various structure were used to obtain tetraphosphorylated systems. Investigation of the chemical properties of the products was initiated. Basing on 1,1'-spirobi(3,3-dimethylindane-5,6-diyl) tetra(2,2-dimethylpropanediyl phosphite), a Pt(II) chelate was synthesized.     

辐射接枝法制备离子交换膜的研究现状

聚合物离子交换膜有多种制备方法，其中高分子材料辐射引发接枝功能性单体是一种文献中屡见报道且简单可行的方法．通过在不同聚合物基体上接枝各种类型的单体，可以改变接枝膜的电化学性能、物理化学等性能．丈中详细介绍了不同的高分子基材辐射接枝各类单体制备聚合物离子交换膜的研究现状．     

Blocking-Deblocking of the NH-Functionality of Uracil and its Derivatives

We have been interested in various 5,6-dihydrouracils and 5,6-dihydroorotic acid derivatives as possible inhibitors of dihydrouracil dehydrogenase, dihydroorotase, and dihydroorotate dehydrogenase.² The known methods for the synthesis of 5,6-dihydrouracils and 5,6-dihydroorotic acid derivatives are either a low yield cyclization process³ or a catalytic hydrogenation⁴ procedure which frequently led to the elimination of desired functionality⁵. In order to obviate these difficulties, we have recently developed⁶ a mild non-catalytic method for the reduction of 5,6-double bond of uracil and orotic acid derivatives. By using lithium tri-sec-butyl borohydride^7–8 we have been able to reduce N₁, N₃-dialkyl uracil and orotic acid derivatives to the corresponding 5,6-dihydrouracil and orotic acid derivatives as shown in scheme (1).     

Protonation behaviour of chiral tetradentate polypyridines derived from alpha-pinene

Detailed protonation experiments of the [5,6]-pinenebipyridine molecule and the unsubstituted [4,5]- and [5,6]-CHIRAGEN[0] ligands in various solvents indicate a variety of structures of the protonated species. UV-visible and NMR measurements (including (15)N chemical shifts) show the transition from trans to cis conformation of [5,6]-pinenebipyridine upon protonation. The [4,5]-CHIRAGEN[0] ligand, in which the protonation sites of the nitrogen atom donors are at opposite sides of the molecule, behave essentially like two independent bipyridine moieties; this behaviour was monitored by UV-visible, CD and NMR spectroscopy (including (15)N data). In the case of the [5,6]-CHIRAGEN[0], a pocket of donor atoms provides a chiral environment for two protons per ligand.     

Synthese von 5,6-Epimino-5,6-dihydro-β-jonon

Synthesis of 5,6-Ephnino-5,6-dihydro-β-ionone In order to synthesize the title compound 5 the 2-azidoalcohols 3 and 4 were treated with various nucleophilic phosphorus compounds. It was found that the course of the reaction depends strongly upon the kind of nucleophilic phosphorus derivative used.     

Effect of sovents on radiation-induced ionic graft polymerization

The influence of various solvents on radiation-induced cationic (grafting of vinyl-n-butyl ether onto polyethylene) and anionic (grafting of 2-methyl-5-vinylpyridine onto polyethylene) graft polymerization was studied. This ionic grafting was performed in thoroughly dried systems at room temperature. It was established that electron-acceptor solvents promote cationic grafting but that electron-donor solvents promote the anionic. A clear correlation between the donor number of solvents and grafting value by the anionic mechanism was shown. There was no correlation between dielectric constants and grafting values. The reaction orders, according to monomer concentration by 2-methyl-5-vinylpyridine grafting in various solvents, were equal to approximately 1.5 and 2 for the radical and anionic mechanisms, respectively. The effect of solvents on radiation-induced ionic graft polymerization is discussed. The results of this study indicate the correct choice of solvents for radiation-induced ionic grafting.     

Synthesis and bioactivity of secondary metabolites from marine sponges containing dibrominated indolic systems

Marine sponges. (e.g., Hyrtios sp., Dragmacidin sp., Aglophenia pleuma, Aplidium cyaneum, Aplidium meridianum.) produce bioactive secondary metabolites involved in their defence mechanisms. Recently it was demonstrated that several of those compounds show a large variety of biological activities against different human diseases with possible applications in medicinal chemistry and in pharmaceutical fields, especially related to the new drug development process. Researchers have focused their attention principally on secondary metabolites with anti-cancer and cytotoxic activities. A common target for these molecules is the cytoskeleton, which has a central role in cellular proliferation, motility, and profusion involved in the metastatic process associate with tumors. In particular, many substances containing brominated indolic rings such as 5,6-dibromotryptamine, 5,6-dibromo-N-methyltryptamine, 5,6-dibromo-N-methyltryptophan (dibromoabrine), 5,6-dibromo-N,N-dimethyltryptamine and 5,6-dibromo-L-hypaphorine isolated from different marine sources, have shown anti-cancer activity, as well as antibiotic and anti-inflammatory properties. Considering the structural correlation between endogenous monoamine serotonin with marine indolic alkaloids 5,6-dibromoabrine and 5,6-dibromotryptamine, a potential use of some dibrominated indolic metabolites in the treatment of depression-related pathologies has also been hypothesized. Due to the potential applications in the treatment of various diseases and the increasing demand of these compounds for biological assays and the difficult of their isolation from marine sources, we report in this review a series of recent syntheses of marine dibrominated indole-containing products.     

Radiation-Induced Conductivity of Polymer Composites Filled by Finely Divided Oxides

The radiation-induced conductivity of polymer composites based on polyisoprene rubber filled with finely divided oxides of various chemical natures was studied in the continuous irradiation mode. It was shown that the radiation conductivity is closely related to the molecular mobility of the rubber. It was found that a change in the character of thermal motion of fragments of rubber macromolecules, which is caused by interaction with the filler, could considerably enhance the radiation-induced conductivity of a polymer composite.     

A convenient entry to C2- and C3-substituted gulono-gamma-lactone derivatives from L-ascorbic acid

A convenient method to obtain unknown chiral C2- and C3-functionalized aldono-1,4-lactone derivatives starting from l-ascorbic acid, which would be valuable in the synthesis of derivatives of various pharmacologically active agents for structure-activity studies, is described. The practicality of this approach is demonstrated by the synthesis of a series of 5,6-O-isopropylidene-2-allyl-3-keto-l-galactono-gamma-lactone and 5,6-O-isopropylidene-3-allyl-2-keto-l-galactono-gamma-lactone derivatives using the thermal Claisen rearrangement of the corresponding 3-O- and 2-O-allyl derivatives of 5,6-O-isopropylidene-l-ascorbic acid, respectively, followed by stereospecific reduction to the corresponding alcohols. The synthetic steps are shown to be efficient, and enantiospecific, and they proceed with high yields.     

Synthesis of pyrido[1′,2′:1,2]imidazo[4,5-b]pyrazines from 2-amino-3-chloro-5,6-dicyanopyrazine with substituted pyridines

Novel synthesis of the title compounds by the cyclization between 2-amino-3-chloro-5,6-dicyanopyrazine and various substituted pyridines is described.     

Protonation Behaviour of Chiral Tetradentate Polypyridines Derived from α‐Pinene

Detailed protonation experiments of the [5,6]‐pinenebipyridine molecule and the unsubstituted [4,5]‐ and [5,6]‐CHIRAGEN[0] ligands in various solvents indicate a variety of structures of the protonated species. UV‐visible and NMR measurements (including ¹⁵N chemical shifts) show the transition from trans to cis conformation of [5,6]‐pinenebipyridine upon protonation. The [4,5]‐CHIRAGEN[0] ligand, in which the protonation sites of the nitrogen atom donors are at opposite sides of the molecule, behave essentially like two independent bipyridine moieties; this behaviour was monitored by UV‐visible, CD and NMR spectroscopy (including ¹⁵N data). In the case of the [5,6]‐CHIRAGEN[0], a pocket of donor atoms provides a chiral environment for two protons per ligand.     

An efficient de novo synthesis of partially reduced phenanthrenes through C-C insertion

An efficient and novel approach to the synthesis of highly congested 3-alkyl-, 4-alkyl-, 3-aryl-, 3,4-dialkyl-, 4-alkyl-3-aryl-, and 3,4-diaryl-9,10-dihydro-1-sec-aminophenanthrene-2-carbonitriles has been delineated through the base-catalyzed ring transformation of 5,6-dihydro-2-oxo-4-sec-amino-2H-benzo[h]chromene-3-carbonitrile by carbanion derived in situ from various ketones in moderate to good yields. 9,10-Dihydrophenanthrenes with and without substituent in the bay region are efficiently and regioselectively synthesized by using propanal and acetyltrimethylsilane as a source of carbanion. Even the synthesis of bisphenanthrenes has been achieved by the ring transformation of 5,6-dihydro-2-oxo-4-sec-amino-2H-benzo[h]chromene-3-carbonitrile by 2-acetylphenanthrene in moderate yield. Highly substituted 3-amino-1-sec-amino-5,6-dihydrophenanthrene-2,4-dicarbonitriles have also been prepared from the reaction of 2-oxobenzo[h]chromene and malononitrile.     

A substituent-controlled general approach to access arylated pyran-2-ones and pyrano[3,4-c]pyran-1,8-diones

2H-Pyran-2-ones are useful precursors for the synthesis of various aromatic and heterocyclic compounds. In this Letter, we describe substituent-controlled direct access to functionalized 4-(2-oxo-1,2-diarylethyl)-5,6-diaryl-pyran-2-ones by stirring a mixture of 3-cyano-5,6-diaryl-2H-pyran-2-ones and functionalized deoxybenzoins through an unusual decyanation reaction. Under similar reaction conditions, the reactions of 3-carbomethoxy-5,6-diaryl-2H-pyran-2-ones with either substituted acetophenones or deoxybenzoins led to the synthesis of pyrano[3,4-c]pyran-1,8-diones in excellent yields.     

5,6-Dimethylbenz[c]acridine functionalized in the 7-position

5,6-Dimethylbenz[c]acridines, functionalized in the 7-position by the carboxy, carbomethoxy, carboxamido, N-ethylcarboxamido, acetyl, cyano, chloro, methoxy or amino group are reported for the first time. Also various related 5,5-dimethyl-5,6-dihydrobenz[c]acridines including the 7-carbomethoxy, 6-hydroxy-7-carboxy, 6-bromo-7-carbomethoxy, 6-methoxy-7-carboxy, 6-methoxy-7-carbomethoxy, and 6-hydroxy-7-N-ethylcarboxamido derivatives which serve as precursors to the completely aromatized 5,6-dimethylbenz[c]acridines are also reported for the first time.