Evaluation of phototoxic and photoallergic potentials of 13 compounds by different in vitro and in vivo methods

Phototoxic side effects of pharmaceutical and cosmetic products are of increasing concern for patients, dermatologists and the chemical industry. Moreover, the need of new chemicals and drugs puts pressure on pre-clinical test methods for side effects, especially interactive adverse-effects with UV-light. So, the predictive potential of different established test methods, which are used regularly in our departments in order to detect the phototoxic potential of chemicals, were analyzed. Namely the fibroblast 3T3 test, the photo hen's egg test, a guinea pig test for measuring acute photoreactions, and a modified Local Lymph Node Assay, the Integrated Model for the Differentiation of Skin Reactions. Various agents with different photoreactive potential were tested: quinolones like Bay y 3118, ciprofloxacin, enoxacin, lomefloxacin, moxifloxacin, ofloxacin, sparfloxacin, as well as promethazine, chlorpromazine, 8-methoxypsoralen and olaquindox serving as control. Special emphasis was taken to evaluate the capability of the employed test procedures to predict phototoxic side effects in patients. Following our results, both in vitro assays were useful tools to detect photoirritancy while the photoallergic potentials of tested compounds were exclusively detected by an in vivo assay. As long as no in vitro model for photoallergy is available, the UV-IMDS should be considered to evaluate photoallergic properties of a supposed photoreactive agent.     

The effect of inclusion inβ-cyclodextrin on the chemistry of peroxides: Reactions of radicals withβ-cyclodextrin

Studies by electron paramagnetic resonance (EPR), differential scanning calorimetry, thermogravimetric analysis, HPLC and NMR showed that radicals produced by thermolysis and photolysis of benzoyl peroxide,t-butyl peroxide and cumene hydroperoxide included in-cyclodextrin (-CD), undergo significant reaction with the-CD. The formation of-CD radicals was observed by EPR. Products formed by addition of radicals to-CD were also observed. Such host:guest radical reactions explain the reported stabilization of peroxides, found with-CD inclusion, as being primarily due to the interruption of chain reactions by trapping of the chain carriers. A small increase in activation barrier for cleavage of the included peroxide in-CD was also observed.     

Synthesis, structure and reactivity of new yttrium bis(dimethylsilyl)amido and bis(trimethylsilyl)methyl complexes of a tetradentate bis(phenoxide) ligand

The reactions of a bulky amino-methoxy bis(phenolate) ligand H₂L with Y(CH₂SiMe₃)₃(THF)₂ and Y[N(SiHMe₂)₂]₃(THF)₂ under mild condition leads to the selective formation of the thermally stable complexes [L]Y(CH₂SiMe₃)(THF) (1) and [L]Y[N(SiHMe₂)₂](THF) (2). The X-ray structures revealed very similar binding of the [ONOO] ligand core to the metal for both complexes, which feature an octahedral geometry involving coordination of the methoxy side-arm of the ligand and of a remaining THF molecule. ¹H-NMR spectroscopy indicates that the solid state structure of 1 and 2 is retained in hydrocarbon solutions with THF coordinated to yttrium. Alkyl complex 1 showed no activity in ethylene polymerization, presumably due to the presence of coordinated THF. The amido complex 2 catalyzed sluggishly the polymerization of methyl methacrylate to give isotactic-rich PMMA but is very active for the ring-opening polymerization of ε-caprolactone.     

η- and η-benzene coordination in [Ag(C6D6)3BF4]

The title complex with one η² and two η¹ deuterobenzene and one monodentate BF₄ ligands was isolated as a by-product in the reaction between [(dppe)RhCl]₂ and EtCl in C₆D₆, in the presence of AgBF₄ and its X-ray crystal structure determined.     

The infrared spectra (3500-140 cm−1) of the 2,2'-bipyridine, 2-aminomethylpyridine and ethylenediamine adducts and the sodium tris-compounds of cobalt(II), nickel(II) and zinc(II) acetylacetonates

Summary The M(acac)₂B and NaM(acac)₃ complexes (M = Coll, Ni^ll orZn^ll; acac=acetylacetonateanion; B=2,2=bipyridine, 2-aminomethylpyridine or ethylenediamine) have been prepared and their i.r. spectra determined over the 3500-140 cm^–1 range. Complete band assignments have been made on a comparative basis, with the effects of ligand substitution and metal ion substitution being considered. Bands in the i.r. spectra of the complexes which are associated with 2,2-bipyridine, 2-aminomethylpyridine and ethylenediamine arc in excellent agreement with values previously established for these ligand and metal-ligand vibrations, in related complexes. Band assignments for acetylacetonate anion and metal-acetylacetonate vibrations substantiate those made in certain of the previously published papers. The method of assignment adopted has allowed the complete assignment of bands in the i.r. spectra of the metal complexes.     

Bicyclo[3.2.1]amide-DNA: a chiral,nonchiroselective base-pairing system

The design, synthesis, and base-pairing properties of bicyclo[3.2.1]amide-DNA (bca-DNA), a novel phosphodiester-based DNA analogue, are reported. This analogue consists of a conformationally constrained backbone entity, which emulates a B-DNA geometry, to which the nucleo-bases were attached through an extended, acyclic amide linker. Homobasic adenine-containing bca decamers form duplexes with complementary oligonucleotides containing bca, DNA, RNA, and, surprisingly, also L-RNA backbones. UV and CD spectroscopic investigations revealed the duplexes with D- or L-complements to be of similar stability and enantiomorphic in structure. Bca oligonucleotides that contain all four bases form strictly antiparallel, left-handed complementary duplexes with themselves and with complementary DNA, but not with RNA. Base-mismatch discrimination is comparable to that of DNA, while the overall thermal stabilities of bca-oligonucleotide duplexes are inferior to those of DNA or RNA. A detailed molecular modeling study of left- and right-handed bca-DNA-containing duplexes showed only minor changes in the backbone structure and revealed a structural switch around the base-linker unit to be responsible for the generation of enantiomorphic duplex structures. The obtained data are discussed with respect to the structural and energetic role of the ribofuranose entities in DNA and RNA association.     

Photochemische Reaktionen 42. Mitteilung [1]. Photoisomerisierung von α, β-Epoxyketonen II Der sterische Verlauf der Umlagerung von 3-Oxo-4, 5-oxido-Steroiden

The photorearrangement previously described [3] of saturated and Δ¹-unsaturated 3-oxo-4,5-epoxy-10β-steroids to 3,5-dioxo-10(5 →4)-abeo compounds proceeds most likely via a radical 1,2-alkyl shift (Chart 1). The similar rearrangements of the related 10α-epoxyketone 10 and the 4-methyl-epoxyketones 13 , 15 , 16 , 20 and 21 to the corresponding 3,5-diketones occurred without epimerization at the migrating carbon atom (C-10) and the site of substitution (C-4) (Chart 3). The stereochemical control of the rearrangement is in agreement with the earlier proposed mechanism of a concerted alkyl radical shift in these alicyclic systems.     

Characterization of the nanomorphology of polymer-silica colloidal nanocomposites using electron spectroscopy imaging

The internal nanomorphologies of two types of vinyl polymer-silica colloidal nanocomposites were assessed using electron spectroscopy imaging (ESI). This technique enables the spatial location and concentration of the ultrafine silica sol within the nanocomposite particles to be determined. The ESI data confirmed that the ultrafine silica sol was distributed uniformly throughout the poly(4-vinylpyridine)/silica nanocomposite particles, which is consistent with the "currant bun" morphology previously used to describe this system. In contrast, the polystyrene/silica particles had a pronounced "core-shell" morphology, with the silica sol forming a well-defined monolayer surrounding the nanocomposite cores. Thus these ESI results provide direct verification of the two types of nanocomposite morphologies that were previously only inferred on the basis of X-ray photoelectron spectroscopy and aqueous electrophoresis studies. Moreover, ESI also allows the unambiguous identification of a minor population of polystyrene/silica nanocomposite particles that are not encapsulated by silica shells. The existence of this second morphology was hitherto unsuspected, but it is understandable given the conditions employed to synthesize these nanocomposites. It appears that ESI is a powerful technique for the characterization of colloidal nanocomposite particles.     

Untersuchungen an Metallkatalysatoren. XVII. Phasenaufbau,Dispersität und Dehydrieraktivität Molybdän- und wolframmodifizierter Palladiumkatalysatoren

Investigations on Metal Catalysts. XVII. Phase Structure, Dispersity, and Dehydrogenation Activity of Palladium Catalysts Modifided by Molybdenum and Tungsten Molybdenum and tungsten containing palladium catalysts were prepared by reduction of mixtures from Pd(NO₃)₂ with MoO₃ and WO₃, respectively, with hydrogen at 600°C and 800°C. The powders were characterized by means of several methods: Determination of the oxidation state for molybdenum and tungsten, X-ray measurements, N₂ adsorption, CO chemisorption, H₂ sorption, dehydrogenation of cyclohexane. The properties of the samples (heated at 600°C) are determined to a high degree by the co-existence of the palladium phase as well as the molybdenum and tungsten oxide, respectively, in the mean oxidation state +4. The after-reduction at 800°C leads to a great portion of metallic molybdenum and tungsten in the concerned catalysts. There are references that the treatment at 800°C in the presence of hydrogen causes for the Pd? Mo catalysts an increase of the palladium content in the surface of the crystallites.