INTERACTIONS AND PHOTOREACTIVITY OF 5-ALKOXYPSORALENS WITH THYMINE. A MODEL APPROACH

Abstract— In order to investigate the interactions and the photoreactions in solution between the thymine (thy) and the psoralen (Pso) rings, we have prepared model compounds Thy-(CH₂)_n-Pso in which two aromatic chromophores Thy and Pso are linked by flexible polymethylene chains of varying length (CH₂)_n. Two series of compounds were examined and compared as models for the two important drugs 5-methoxypsoralen and 8-methoxypsoralen. Results concerning the 5-alkoxypsoralen series are reported here. In water, these model molecules exhibit intramolecular ring-ring stacking interactions as indicated by hypochromism in the UV and by shielding of the protons in ¹H NMR spectroscopy. These interactions disappear in organic solvents. The photochemical properties of the models were examined in relation with their ground state interaction properties. Irradiation at 365 nm carried out at the usual concentrations (10^-2-10^-3 M) leads exclusively to a stereoselective dimerization involving the psoralen moieties of the models at the 3,4 double bonds. However, when operating at exceedingly low concentrations (2 × 10^-5 M ), the psoralen photodimerization is avoided and a highly regio and stereo-selective psoralen thymine photoaddition is observed involving the 3,4 double bond of psoralen leading to the cis adduct. The same reaction occurs for all models under study being independent of the length of the (CH₂)_n polymethylene linking chain, n = 2 to 6, 12 and of the solvent used. This is unambiguous proof for the highest intrinsic photoreactivity of the 3,4 vs the 4',5' double bond in 5-alkoxy psoralen.     

PHOTOCHEMICAL REACTIONS OF THYMINE WITH CARBOXYLIC ACIDS. A MODEL FOR NUCLEIC ACID-PROTEIN PHOTOCROSSLINKING

When nucleic acid bases are UV-irradiated in the presence of carboxylic acids or carboxylate anions new photoproducts are formed as compared to the bases irradiated in the absence of carboxylic acids. The behavior of thymine and thymidine has been examined in detail. At least four photoproducts are formed in the presence of propionic acid and three in the presence of butyric acid. None of them appears to be a cyclobutyl dimer. From the concentration dependence of the rate of photoproduct formation it is concluded that the reactive excited species is the first excited singlet state of thymine. When ¹⁴C-labelled thymine is irradiated in the presence of polyglutamic acid an important part of the radioactive material is covalently linked to the polymer. Photochemical reaction of thymine with glutamic (or aspartic) acid could thus induce crosslinks between proteins and nucleic acids. It is also shown that these photoproducts are stable under usual conditions of acidic hydrolysis of UV-irradiated DNA.     

PHOTOREACTIVITY OF 5-GERANOXYPSORALEN AND LACK OF PHOTOREACTION WITH DNA

5-Geranoxypsoralen, commonly called bergamottin, a major furocoumarin contained in bergamot oil, is reported in vitro as a highly photoreactive psoralen. In ethanol, it exhibits quite a high triplet state quantum yield (approximately 0.37). The triplet state is involved in subsequent photochemistry which depends on the initial concentration and on the presence of oxygen. In contrast to most psoralens, absorption and fluorescence data suggest that 5-geranoxypsoralen does not interact with DNA in the dark. No UVA-induced interstrand cross-links in DNA were shown.     

TRIPLET ELECTRONIC STRUCTURE AND PHOTOREACTIVITY OF 8-METHOXYPSORALEN*

Psoralen and its derivatives are implicated in a variety of photobiological processes including skin-sensitization in mammals, the experimental photochemotherapy of psoriasis, and photomutagenesis in bacteria. Although the various derivatives differ markedly in photoactivity, their excited triplet states as characterized by conventional luminescence spectroscopy are very similar and closely resemble that of the parent compound, coumarin, which is inactive as a skin sensitizer. Employing a more sensitive probe of triplet electronic structure, we have utilized optical detection of magnetic resonance to measure the zero-field splittings in the triplet state of several psoralens and find a striking variation among the derivatives. D*, taken as a composite measure of the dipole-dipole interaction of the unpaired electrons in the triplet state was found to be anomalously large, greater than 0.140 cm^-1, for the very active compounds, psoralen and 8-methoxypsoralen, while D*= 0.124cm^-1 for the inactive, though smaller, coumarin molecule. Although 8-hydroxypsoralen has a large D* value its inactivity as a skin-sensitizer may be explained by the dissociation of the hydroxyl proton. The resulting (excited) triplet state anion has D*= 0.120 cm^-1.     

INTRAMOLECULAR INTERACTIONS BETWEEN THYMINE AND PSORALEN INDUCED BY A POLYOXYETHYLENE CHAIN

Abstract— The electronic absorption, fluorescence emission and photoreaction quantum yields for thymine-psoralen (1), psoralen-psoralen (2) and thymine-thymine (3) linked by triethyleneoxide chains are determined in ethanol and in water. Compounds (1), (2) and (3) are able to complex Li⁺ cations, new and striking effects of which have been revealed in their fluorescence properties and photoreactivities. An important hypochromism effect is observed in the UV spectrum of compound (1) in contrast to compounds (2) and (3).     

SPECTROSCOPIC PROPERTIES AND PHOTOREACTIVITY WITH DNA OF NEW MONOFUNCTIONAL PYRIDOPSORALENS

Abstract— New psoralen derivatives have been synthesized in order to enhance their affinity towards DNA. The spectral properties (absorption, fluorescence emission, fluorescence quantum yield) and the photostability of pyrido[3,4-c]psoralen are first reported. The drastic changes observed in the solubility and in the fluorescence emission when these compounds are added to native DNA give evidence of the formation of non covalent dark complexes. Upon UV irradiation (365 nm) of the complexes, a photobinding occurs. Heat denaturation and renaturation experiments of modified DNA show that only monoadducts are formed. From the analysis of their fluorescence properties the involvement of the 4', 5' double bond is assumed. The monofunctional character has also been established for psoralens having a fused pyridine ring in the 4', 5' site. On the opposite, a fused tetrahydropyrido group in the 4', 5' site is inefficient to inactivate this reactive site.     

顺铂和反铂与红细胞膜糖蛋白的相互作用

用凝胶电泳法、荧光分光度法和圆二色谱研究顺铂和反铂与人红细胞膜糖蛋白的作用结果表明，顺铂在糖蛋白上的结合量明显高于反铂，顺铂对糖蛋白构象的影响也大于反铂，这提示顺铂的抗癌作用可能与膜糖蛋白的作用有关。     

RED LIGHT INTERACTIONS WITH BLUE AND ULTRAVIOLET LIGHT IN POLAROTROPISM OF GERMLINGS OF A FERN AND A LIVERWORT

Abstract— In polarotropism of the chloronema of the fern Dryopteris filix-mas (L.) Schott and of the germ tube of the liverwort Sphaerocarpos donnellii Aust. a phytochrome action in blue and u.v. was presumed[1, 2]. In the present paper this assumption was tested by simultaneously irradiating with red and blue, and red and near u.v. Red energy is given to shift the phytochrome photoequilibrium in favour of high P _fr/ P ^total concentrations. The data obtained by simultaneous irradiation are consistent with the predictions made under the assumption of a phytochrome involvement in the blue- and u.v.-mediated polarotropic response.     

DETECTION OF CYCLOBUTANE THYMINE DIMERS IN DNA OF HUMAN CELLS WITH MONOCLONAL ANTIBODIES RAISED AGAINST A THYMINE DIMER- CONTAINING TETRANUCLEOTIDE

Abstract— A hybrid cell line (hybridoma) has been isolated after fusion between mouse-plasmacytoma cells and spleen cells from mice immunized with a thymine dimer-containing tetranucleotide coupled to a carrier protein. Monoclonal antibodies produced by this hybridoma were characterized by testing the effect of various inhibitors in a competitive enzyme-linked immunosorbent assay (ELISA). The antibodies have a high specificity for thymine dimers in single-stranded DNA or poly(dT), but do not bind UV-irradiated d(TpC)₅. Less binding is observed with short thymine dimer-containing sequences. In vitro treatment of UV-irradiated DNA with photoreactivating enzyme in the presence of light, or with Micrococcus luteus UV-endonuclease results in disappearance of antigenicity. Antibody-binding to DNA isolated from UV-irradiated human fibroblasts (at 254 nm) is linear with dose. Removal of thymine dimers in these cells during a post-irradiation incubation, as detected with the antibodies, is fast initially but the rate rapidly decreases (about 50% residual dimers at 20 h after 10 J/m²). The induction of thymine dimers in human skin irradiated with low doses of UV-B, too, was demonstrated immunochemically, by ELISA as well as by quantitative immunofluorescence microscopy.     

甲醛、丙酮与三聚甲醛及其衍生物相互作用的理论研究

分子间相互作用的研究对于解释物质的性质,化学反应机理等具有重要意义。在理论上主要的研究方法有:一、将相互作用能分解成静电能、短程斥力、极化能、诱导能和色散能,分别计算这些能量,然后给出总的作用能;二、将相互作用的两个分子作为单个超分子,相互作用能为超分子能量和两个孤立分子能量之差,原则上,ab initio CI能够解决达一问题,但其应用因目前计算条件而受到限制。ab initio和CNDO等在计算作用能时须进行色散能校正。在实验上研究方法主要有分子束电共振谱(molecular beam electric resona-     

EXCITED STATE INTERACTIONS OF 7-AZAINDOLE WITH ALCOHOL AND WATER

Abstract— The fluorescence spectrum of 7-azaindole in alcohol is composed of two fluorescence bands. Effects of pH, temperature and solvent deuteration on the fluorescence spectra and quantum yields of 7-azaindole and other model compounds in ethanol and in water are reported. The long wavelength band arises from a tautomeric species formed in an adiabatic photoreaction involving double proton transfer between one molecule of 7-azaindole and one molecule of alcohol.
The fluorescence spectrum of 7-azaindole in water is composed of only one band, but the emission is weak and shows a large solvent isotope effect. The possibility of a double proton transfer reaction between 7-azaindole and water is discussed.     

PHOTOCHEMISTRY OF 4-THIOURIDINE AND THYMINE

Abstract— When thymine is irradiated in aqueous solution with monochromatic 334-nm UV radiation in the presence of 4-thiouridine a photoproduct of thymine is formed, as shown by thin-layer chromatography and autoradiography. The quantum yield for the formation of thymine photoproduct (θ=0.017) is greater than that for cytosine photoproduct formation (θ= 0.0015). The identity of the photoproduct is not known: one possibility is the formation of an adduct between the sensitizer and the base yielding a pyrimidine-pyrimidone type of photoproduct.     

PHOTOCHEMICAL EXCHANGE REACTIONS OF THYMINE, URACIL AND THEIR NUCLEOSIDES WITH SELECTED AMINO ACIDS

The photoinduced exchange reactions of thymine with lysine at basic pH, using 254 nm light, have been studied. Three products have been isolated, namely, 6-amino-2-(1-thyminyl)hexanoic acid ( Ia ), 2-amino-6-(1-thyminyl)hexanoic acid ( IIa ) and 1-amino-5-(1-thyminyl)pentane ( IIIa ). Compound IIIa was shown to be a secondary product, produced by photochemical decarboxylation of Ia . Photochemical reaction of thymine with glycine and alanine at basic pH led, respectively, to formation of 2-(1-thyminyl)acetic acid ( Ic ) and 2-(1-thyminyl)propionic acid ( Id ). Compounds Ic and Id underwent photolysis to produce the decarboxylated secondary products 1-methylthymine and 1-ethylthymine, respectively. Thymidine reacts photochemically with glycine and alanine to produce the same products.
Irradiation of DNA in the presence of lysine at basic pH led to the formation of the same products formed in the thymine-lysine system, namely Ia , IIa and IIIa .
Uracil was found to undergo analogous photochemical exchange reactions with lysine to form 6-amino-2-(1-uracilyl) hexanoic acid ( Ib ), and 2-amino-6-(1-uracilyl)hexanoic acid ( IIb ). Compound Ib was found to undergo photodecarboxylation to form 1-amino-5-(1-uracilyl)pentane ( IIIb ), analogous to the secondary photoreaction of Ia . Photoreaction of uracil with 1,5-diaminopentane (cadaverine) likewise led to formation of IIIb .     

REVERSIBLE PHOTOCYCLOADDITION OF A 4',5'-DIHYDROPSORALEN DERIVATIVE WITH THYMINE

The photocycloaddition reaction between a 4′,5′-dihydropsoralen derivative and thymine was studied in solution using a synthetic bichromophoric model 8 in which the two rings are associated by a tetramethylene chain. In water this model molecule exhibits intramolecular ring-ring stacking interactions as evidenced by UV and NMR spectroscopies. Irradiation at 365 nm at usual concentrations ( 5.10^?-⁴M) leads exclusively to a regio- and stereo-selective dimerization reaction involving the 3,4 double bonds of the psoralen moities. Extreme dilutions (ca 2.10^?-⁵M) were necessary to observe the intramolecular reaction which results in the exclusive formation of a 3,4 cb-anti adduct. This reaction is completely reversed by irradiation at 254 nm. These results are discussed with regard to the behavior of the homologous models in which the furan part of the psoralen ring is not hydrogenated, These latter compounds also lead exclusively to a 3,4 cis-anti adduct. It appears that saturation of the furan ring increases strongly the quantum yield of the photaddition at 365 nm (0.01 → 0.18) and that the triplet excited state of the 4′,5′-dihydropsoralen is involved in the photoaddition.     

THE THYMIDINE-PSORALEN PHOTOADDITION. A MODEL APPROACH

Abstract— In order to investigate the photoreactions between the thymidine and the psoralen chromophores and to devise a synthetic route to prepare thymidine-5-methoxypsoralen adducts, we have prepared and studied a compound in which thymidine is linked to a 5-methoxypsoralen derivative by a diester chain. Irradiation at 365 nm carried out at usual concentrations (10–³ M ) leads exclusively to one diastereoisomer of an intramolecular 3,4 cis-anti [2+2] adduct. No photodimerization is observed in these conditions. These results are compared to those obtained for models studied previously in which the thymine and the psoralen rings are linked by polymethylenic chains of varying length.     

PHOTOCHEMICAL INTERACTIONS OF CHLORPROMAZINE WITH PHOSPHOLIPIDS AND CHOLESTEROL IN ARTIFICIAL AND NATURAL MEMBRANES

Abstract— Dipalmitoylphosphatidyl-choline (DPPC) liposomes do not modify the nature of the photoproducts formed by UV irradiation of chlorpromazine. However, when cholesterol is added to DPPC liposomes, new photoproducts are formed which demonstrate the photoaddition of chlorpromazine to cholesterol. Similar results are obtained with phosphatidyl-serine and phosphatidyl-inositol. The reactivity of irradiated chlorpromazine towards lipidic components of myelin, taken as an example of biological membrane, is also demonstrated.     

高岭土基质与重金属的相互作用

The phase transformation of kaolin in the presence of 1%～5% vanadium had been investigated. The results indicated that vanadium mullite emerged at 660～700℃which was at least 400℃ lower than conventional mullite formation temperature, and a chemical reaction between kaolin and vanadium took place obviously. The reaction of vanadium mullite formation could be described as a process of low melting vanadium kaolin eutectic transition.In addition, the unit cell volume of vanadium mullite was found increased with the increment of vanadium content, which could be deduced that vanadium incorporated into mullites' framework and was therefore passivated. Furthermore, in comparison with hydro kaolin, modified kaolin—PAL and CLS reacted fast with vanadium to form more mullite and CLS could even reacted with nickel to form a rather stable compound of NiAl 10 O 16 , and therefore protected zeolite in cracking catalysts against the heavy metal poisoning effectively.     

表面活性剂与金属离子的相互作用

烷基硫酸盐(CnS)的抗盐能力很差,在其中引进氧乙烯基(Eo)以后,形成的烷基聚氧乙烯基醚硫酸盐(CnEnS)的抗盐能力明显增强。把CnEnS加到CnS中,形成混合表面活性剂的低温抗盐能力也将明显改善。Doscher、Schott等人认为,CnEnS中的Eo与高价金属阳离子形成了一种“复合物”,这使得CnEnS具有很强的抗盐能力。Chiu则没有发现这种“复合物”。显然,了解CnEmS的抗盐机理,对于该类表面活性剂的理论研究和实际应用,都有重要的意义。