Phototoxic effects of Hypericum extract in cultures of human keratinocytes compared with those of psoralen

Extracts of Hypericum perforatum (St. John's wort) are used in the treatment of depression. They contain the plant pigment hypericin and hypericin derivates. These compounds have light-dependent activities. In order to estimate the potential risk of phototoxic skin damage during antidepressive therapy, we investigated the phototoxic activity of hypericin extract using cultures of human keratinocytes and compared it with the effect of the well-known phototoxic agent psoralen. The absorbance spectrum of our Hypericum extract revealed maxima in the whole UV range and in parts of the visible range. We cultivated human keratinocytes in the presence of different Hypericum concentrations and irradiated the cells with 150 mJ/cm2 UVB, 1 J/cm2 UVA or 3 h with a white light of photon flux density 2.6 mumol m-2 s-1. The determination of the bromodeoxyuridine incorporation rate showed a concentration- and light-dependent decrease in DNA synthesis with high hypericin concentrations (> or = 50 micrograms/mL) combined with UVA or visible light radiation. In the case of UVB irradiation a clear phototoxic cell reaction was not detected. We found phototoxic effects even with 10 ng/mL psoralen using UVA with the same study design as in the case of the Hypericum extract. These results confirm the phototoxic activity of Hypericum extract on human keratinocytes. However, the blood levels that are to be expected during antidepressive therapy are presumably too low to induce phototoxic skin reactions.     

Approximate molecular orbital theory for inorganic molecules

As a first stage in the development of a suitable molecular orbital method for treating inorganic systems, we consider the possible integral approximations that may be made to reduce the complexity of the computation. The significance of invariance of the approximations to different transformations is discussed and the effect of various levels of neglect of differential overlap is analysed by the S-expansion technique. A method — the many-centre ZDO method — that is computationally feasible but contains more information than the widely used CNDO approximation is given particular consideration.

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Zusammenfassung Als erste Stufe in der Entwicklung einer geeigneten Molekular-orbital-Methode für die Behandlung anorganischer Systeme untersuchen wir mögliche IntegralnÄherungen, die geeignet sind, die Berechnungen zu vereinfachen. Die Bedeutung der Invarianz der NÄherungen unter verschiedenen Transformationen wird diskutiert und der Einflu\ verschiedener Stufen der VernachlÄssigung der differentiellen überlappung wird mit der S-Entwicklungstechnik analysiert. Einer Methode, der Vielzentren-ZDO-Methode, die rechnerisch gut durchführbar ist, aber mehr an Information enthÄlt als die meistens benutzte CNDO-NÄherung, wird besondere Beachtung geschenkt.

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Résumé Dans une première étape lors du développement d'une méthode d'orbitales moléculaires convenant aux systèmes inorganiques, nous envisageons les approximations possible pour les intégrales. On discute la signification de l'invariance des ces approximations par rapport à différentes transformations et l'on analyse par la technique du développement en S l'effet des différents niveaux d'approximation du recouvrement différentiel nul. On considère en particular une méthode — la méthode ZDO polycentrique-quis'avère réalisable numériquementtout en contenant plus d'information que l'approximation CNDO couramment utilisée.

     

DESTRUCTION OF PHOTOREACTIVATING ENZYME BY 365 nm RADIATION*

Abstract— Following the observation that in vivo photoreactivation of 365-nm-induced pyrimidine dimers could not be observed chemically, a study was made of the inactivation of photoreactivating enzyme activity by this near-ultraviolet wavelength. It was observed that: (1) Dimers induced in extracted bacterial DNA by 365 nm radiation are completely photoreactivable and are monomerized as an exponential function of the photoreactivation time. (2) Photoreactivability of 254-nm-induced damage in Escherichia coli B/r Hcr is progressively destroyed in vivo as a function of the dose of 365 nm radiation. (3) The ability of the yeast photoreactivating enzyme to monomerize dimers induced at 365 nm in bacterial DNA is destroyed in vitro as a function of the dose of 365 nm radiation, and at a rate comparable to killing of E. coli. These results are consistent with biological measurements which indicate that photoreactivability of ultraviolet (near and far) lethal damage is reduced by exposure of the bacteria to 365 nm radiation.     

1,1,3,3-Tetramethylguanidine-gallane, (Me2N)2CN(H).GaH3: an unusually strongly bound gallane adduct

The novel adduct 1,1,3,3-tetramethylguanidine-gallane, (Me2N)2CN(H).GaH3, has been prepared by the reaction of [(Me2N)2CNH2]+Cl- with LiGaH4 in Et2O solution. Its spectroscopic properties indicate a monomeric species with an unusually strong coordinate link between the imido function and GaH3, an inference confirmed by the crystal structure at 150 K which also reveals significant secondary interactions through non-classical N-H...H-Ga bridges. Despite the intrinsic strength of the Ga-N bond, however, vaporisation at ca. 310 K occurs with partial dissociation, and decomposition via more than one pathway proceeds at temperatures >330-350 K to give a variety of products, including the free base, Me2NH, H2, and a novel gallium-nitrogen compound composed of a Ga4N4 cubane-like core bridged on three edges by -N{C(NMe2)2}GaH2- units.     

Alloxazines and isoalloxazines. Mass spectrometric analysis of riboflavin and related compounds

The positive ion electron-impact mass spectra of a series of alloxazines, iso-alloxazines and some derivatives have been examined. The compounds employed were lumichrome (7,8-dimethylalloxazine), 1,3-dimethyllumichrome, lumiflavin (7,8,10-trimethyl-iso-alloxazine), 3-methyllumiflavin, riboflavin [7,8-dimethyl-10-(D-1′-ribityl)-iso-alloxazine], riboflavin tetraacetate, 3-methylriboflavin tetraacetate and riboflavin tetrapropionate. By using exact mass measurements, metastable ion defocusing and the mass/composition shifts occurring with derivatives, it has been possible to arrive at detailed interpretations of the mass spectra of all compounds. With lumichrome and lumiflavin, fragmentation commences by elimination of HNCO from the pyrimidine ring. With riboflavin and its derivatives the ribityl chain cleaves off first, followed by decomposition of the iso-alloxazine ring. Application of these methods and findings to the structural analysis of chemically interesting modified flavins is predicted to be rewarding.     

RAMAN- und infrarotspektrosktroskopische Untersuchungen an Alklyderivaten der Arsensäure. II. Die Schwingungsspektren einiger Alkanarsonsäuredialkylester

RAMAN and IR spectroscopic investigation of alkyl derivatives of arsenic acid. II. Vibrational spectra of some alkanearsonic acid dialkylesters RAMAN and IR spectra of CH₃AsO(OCH₃)₂, CH₃AsO(OC₂H₅)₂, C₂H₅AsO(OCH₃)₂, and C₂H₅AsO(OC₂H₅)₂, are communicated and discussed. Their skeleton CAsO(OC)₂ has very probably C_s symmetry.     

Photophysical and ab Initio Studies of Mononuclear Copper(I) Complexes

Described are the photophysical properties of the mononuclear copper(I) complexes CuL(4)(+) (L = pyridine (py), 4-methylpyridine, 4-phenylpyridine, or acetonitrile), Cu(lut)(3)(+) (lut = 2,6-lutidine), and Cu(lut)(2)(+). Each of these compounds as their solid PF(6)(-) salts display a relatively long-lived (>1 &mgr;s), visible range emission at both ambient temperature and at 77 K but not in fluid solutions. Also reported are the results for ab initio calculations at the restricted Hartree-Fock self-consistent field level to probe the natures of lower energy excited states of the hypothetical species CuL(n)()(+) (L = NH(3), CH(3)CN, or py; n = 1-4). These results point to an assignment of the lowest energy, luminactive excited states as being largely metal centered, d --> s in character for each of the above complexes with the possible exception of the CuL(4)(+) species where L is py or a substituted analogue. In the case of Cu(py)(4)(+) the ab initiocalculations indicate a metal-to-ligand charge transfer to be the lowest energy Franck-Condon state, although the similarities of emission band shapes, energies, and lifetimes among the various complexes suggest a common d --> s assignment.     

Direct immobilization of native yeast iso-1 cytochrome C on bare gold: fast electron relay to redox enzymes and zeptomole protein-film voltammetry

Cyclic voltammetry shows that yeast iso-1-cytochrome c (YCC), chemisorbed on a bare gold electrode via Cys102, exhibits fast, reversible interfacial electron transfer (k(0) = 1.8 x 10(3) s(-1)) and retains its native functionality. Vectorially immobilized YCC relays electrons to yeast cytochrome c peroxidase, and to both cytochrome cd(1) nitrite reductase (NIR) and nitric oxide reductase from Paracoccus denitrificans, thereby revealing the mechanistic properties of these enzymes. On a microelectrode, we measured nitrite turnover by approximately 80 zmol (49 000 molecules) of NIR, coadsorbed on 0.65 amol (390 000 molecules) of YCC.