1,721,100 research outputs found

    New reaction pathways of dopamine under oxidative stress conditions: nonenzymatic iron-assisted conversion to norepinephrine and the neurotoxins 6-hydroxydopamine and 6,7-dihydroxyisoquinoline.

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    Aerial oxidation of dopamine at concentrations as low as 50 mu M in the presence of ferrous ions in phosphate buffer (pH 7.4) led in the early stages (6-8 h) to the formation of the quinone of the neurotoxin B-hydroxydopamine, 2, followed (24 h) by a complex product pattern comprising main components norepinephrine (5), 3,4-dihydroxybenzaldehyde (4), and the neurotoxic alkaloid 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (3). Product formation required the assistance of metal ions such as Mn(II), Zn(II), and iron, in either the ferrous or ferric form. Product yields were shown to vary linearly with iron and dopamine concentration in the early phases of the reaction (2 h). Biologically relevant antioxidants, like glutathione and ascorbate, and metal chelators, e.g., 2,2'-bipyridyl, inhibited dopamine conversion to products 2-5, but not substrate consumption, while hydroxyl radical scavengers such as DMSO and mannitol did not alter the course of the reaction. On the contrary, mannitol increased product yields, an effect seen for other monosaccharides. Catalase exhibited a significant inhibitory effect particularly on the formation of 3 and 4. By using O-18(2), evidence was obtained for incorporation of the label into the carbonyl oxygen of 4, but not into the hydroxyl group of 5. On the basis of these and other results, a complete mechanistic picture of the oxidation is drawn involving conversion of dopamine to the corresponding o-quinone and its quinonemethide tautomer with concomitant reduction of Oa to H2O2 Nucleophilic attack by H2O to the quinonemethide gives rise to 5, while H2O2 addition leads to benzaldehyde 4 via a beta-amino-hydroperoxide intermediate. This latter reaction path also gives formaldehyde which yields the isoquinoline 3 by Pictet-Spengler condensation with dopamine. The quinone 2 results from H2O2 attack at the 6-position of dopamine o-quinone in agreement with previous studies. These results provide an insight into new routes of nonenzymatic conversion of dopamine to its metabolite norepinephrine and neurotoxic species which may become operative under conditions relevant to neurodegeneration

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    A New Synthesis of 4H-1,4-Thiazines and Benzothiazines

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    Benzothiazines I [R1 = H, R2 = Me, Ph; R1 = Me, R2 = Ph; R1R2 = (CH2)4] and thiazines II [R1 = H, R2 = Me; R1R2 = (CH2)4] were prepd. in 23-59% yield by treatment of III or IV with p-MeC6H4SO3H in MePh at reflux for 30 min. III were prepd. in 13-81% yield by oxidn. of the resp. sulfide; unsym. 2-substituted dihydrobenzothiazoles gave a mixt. of 2 diastereoisomeric sulfoxides
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