Isolation and Characterization of Two Furan-side Photoadducts of 7-Methylpyrido[3,4-c] Psoralen to the Sugar Moiety of 2-Deoxyadenosine†

Abstract. The UVA-mediated photoreaction of the monofunctional 7-methylpyrido[3,4-c]psoralen (MePyPs) with 2′-deoxy-adenosine was investigated in the dry state. Two main 7-methylpyrido[3,4-c]psoralen monoadducts to 2′-deoxy-adenosine were isolated by HPLC and characterized by soft ionization mass spectrometry (fast atom bombardment) and extensive ¹H NMR analyses including correlation spectroscopy, total correlation spectroscopy and nuclear Overhauser effect measurements. The two unusual photoadducts exhibit a covalent bond between the C-4′ of the furan moiety of the psoralen on one hand and either the C-l' or the C-4′ of the furanose ring of the purine nucleoside on the other hand. The furan-side monoadducts appear to be specific for both 2′-deoxy-adenosine and MePyPs. They are likely to result from the recombination of the 4′,5′-dihydrofuran-4′-yl radical of MePyPs with 2′-deoxyadenosyl carbon-centered sugar radicals at either the 1′ or the 5′ position.     

Approximate D4d symmetry of the cation site in hexahydrated trichlorides of rare earths and actinides

Many spectroscopic and magnetic properties of the monoclinic hexahydrated chlorides of rare earths have been shown to approximate those of a uniaxial crystal. We explain this approximate symmetry by the shape of the coordination polyhedron of the rare-earth ions which is approximately that of a square antiprism of D_4d symmetry, with an inverse eightfold axis. The directions of this axis and of the spectroscopically or magnetically determined axes agree well. The absence of M_J mixing for some levels, as observed in the Zeeman effect, can be explained by an eightfold axis. As a first approximation, we propose a study of the magnetic ions using a D_4d crystal field hamiltonian with the limited set of even parameters B₀², B₀⁴ and B₀⁶; polarization and intensity spectral data, Zeeman effect, electron paramagnetic resonance and susceptibility measurements can be interpreted in this symmetry. Such remarks also apply to actinide hexahydrated chlorides.     

Microscopic examination of chitosan-polyphosphate beads with entrapped spores of the biocontrol agent, Streptomyces melanosporofaciens EF-76.

Spores of the biocontrol agent, Streptomyces melanosporofaciens EF-76, were entrapped by complex coacervation in beads composed of a macromolecular complex (MC) of chitosan and polyphosphate. A proportion of spores entrapped in beads survived the entrapment procedure as shown by treating spores from chitosan beads with a dye allowing the differentiation of live and dead cells. The spore-loaded chitosan beads could be digested by a chitosanase, suggesting that, once introduced in soil, the beads would be degraded to release the biocontrol agent. Spore-loaded beads were examined by optical and scanning electron microscopy because the release of the biological agent depends on the spore distribution in the chitosan beads. The microscopic examination revealed that the beads had a porous surface and contained a network of inner microfibrils. Spores were entrapped in both the chitosan microfibrils and the bead lacuna.     

Ligand K-edge X-ray absorption spectroscopy of [Fe4S4]1+,2+,3+ clusters: changes in bonding and electronic relaxation upon redox

Sulfur K-edge X-ray absorption spectroscopy (XAS) is reported for [Fe(4)S(4)](1+,2+,3+) clusters. The results are quantitatively and qualitatively compared with DFT calculations. The change in covalency upon redox in both the [Fe(4)S(4)](1+/2+) (ferredoxin) and the [Fe(4)S(4)](2+/3+) (HiPIP) couple are much larger than that expected from just the change in number of 3d holes. Moreover, the change in the HiPIP couple is higher than that of the ferredoxin couple. These changes in electronic structure are analyzed using DFT calculations in terms of contributions from the nature of the redox active molecular orbital (RAMO) and electronic relaxation. The results indicate that the RAMO of HiPIP has 50% ligand character, and hence, the HiPIP redox couple involves limited electronic relaxation. Alternatively, the RAMO of the ferredoxin couple is metal-based, and the ferredoxin redox couple involves extensive electronic relaxation. The contributions of these RAMO differences to ET processes in the different proteins are discussed.     

Reductive photocyclization of benzo[b]furans and their analogs

The UV irradiation of substituted 2,3-diphenylbenzo[b]furans and of 2,3-diphenyl-5-t-butylfuran in n-propylamine gives 1,4-dihydro derivatives of the corresponding aromatic cyclized compounds. This reaction does not involve a photoreduction. It can be concluded from deuterium labelling experiments that H atoms of the alkyl chain of n-propylamine are incorporated in the product. When the solvent is not an unhindered primary amine, only totally aromatic photocyclized products are obtained. It is proposed that hydrogens eliminated during formation of the isolated compounds are released in a reductive form and not as radicals. This is supported by the fact that acenaphthylene is reduced when irradiated in n-propylamine together with 2,3-diphenylbenzo[b]furan under conditions which do not promote, photoreduction. This seems to be a general finding in that the irradiation of stilbene in n-propylamine to acenaphthylene is the same as that of 2,3-diphenylbenzo[b]furan.     

First total synthesis of fumaridine

The first total synthesis of the alkaloid fumaridine 1a is reported. The key step is the assemblage of the arylmethylene isoindolinone 2a (E) by Horner reaction between the phosphorylated isoindolinone 3a and the suitably substituted benzaldehyde 4. N-Lactam deprotection and concomitant E→Z isomerization complete the synthesis of the title compound.     

A new synthesis of (+)- and (-)-cherylline

A new and concise synthesis of enantiopure antipodes of alkaloid cherylline has been devised. The synthetic strategy relies upon the reduction of a diversely and polyprotected diarylenamine bearing a chiral auxiliary. Separation of diastereopure intermediates, concomitant deprotections and intramolecular reductive amination complete the synthesis of the natural (S)-enantiomer and of the unnatural (R)-configured antipode.     

A role of melanin-concentrating hormone producing neurons in the central regulation of paradoxical sleep

Background

Peptidergic neurons containing the melanin-concentrating hormone (MCH) and the hypocretins (or orexins) are intermingled in the zona incerta, perifornical nucleus and lateral hypothalamic area. Both types of neurons have been implicated in the integrated regulation of energy homeostasis and body weight. Hypocretin neurons have also been involved in sleep-wake regulation and narcolepsy. We therefore sought to determine whether hypocretin and MCH neurons express Fos in association with enhanced paradoxical sleep (PS or REM sleep) during the rebound following PS deprivation. Next, we compared the effect of MCH and NaCl intracerebroventricular (ICV) administrations on sleep stage quantities to further determine whether MCH neurons play an active role in PS regulation.

Results

Here we show that the MCH but not the hypocretin neurons are strongly active during PS, evidenced through combined hypocretin, MCH, and Fos immunostainings in three groups of rats (PS Control, PS Deprived and PS Recovery rats). Further, we show that ICV administration of MCH induces a dose-dependant increase in PS (up to 200%) and slow wave sleep (up to 70%) quantities.

Conclusion

These results indicate that MCH is a powerful hypnogenic factor. MCH neurons might play a key role in the state of PS via their widespread projections in the central nervous system.