The oxidation of 6-hydroxydopamine

Abstract

The oxidation of 6‐hydroxydopamine (I) with molecular oxygen or potassium ferricyanide in aqueous solution has been shown to lead mainly to the formation of the uncyclized quinone 2‐(β‐aminoethyl)‐5‐hydroxy‐p‐benzoquinone (VII). However this quinone cyclized slowly, presumably to norepinochrome (i.e. indoline‐5,6‐quinone, XII), since 5,6‐dihydroxyindole (II), known to be readily formed by rearrangement of norepinochrome (XII), can be isolated from these solutions. 5,6‐Dihydroxyindolines (cf. XIII) can also be isolated (as their acetyl derivatives) from the products obtained by the addition of reducing agents to solutions containing 6‐hydroxydopamine oxidation products. No evidence was found to suggest that the possible alternative cyclization of the quinone VII to the p‐quinonoid aminochrome 6‐hydroxyindoline‐4,7‐quinone (III) occurred to any significant extent.

Nuclear magnetic resonance studies of 6-hydroxydopamine and its interactions with mercapto-containing model compounds. Evaluation of possible mechanism for neurocytotoxicity

“…Such a process, of transferring aliphatic hydrogens to cyclic forms, should cause a marked effect on the NMR spectrum of 6-OHDA. However, inspection of spectra of oxidized 6-OHDA (at pH 7-8) for several hours revealed no significant change, implying, in agreement with previous observations (Powell & Heacock, 1972), that the cyclization process is very slow.…”

“…Cyclization. Intramolecular cyclization of oxidized 6-OHDA to form 5,6-dihydroxyindole may occur in aqueous solutions (Harley-Mason, 1953;Powell & Heacock, 1972). Such a process, of transferring aliphatic hydrogens to cyclic forms, should cause a marked effect on the NMR spectrum of 6-OHDA.…”

Ion trap tandem mass spectrometric evidence for the metabolism of 3,4-(methylenedioxy)methamphetamine to the potent neurotoxins 2,4,5-trihydroxymethamphetamine and 2,4,5-trihydroxyamphetamine

“…Upon further investigation we discovered that aqueous derivatization with methyl chloroformate provided a means of converting the highly reactive tri-HO-MA to a stable derivative that could be detected by GC-MS. The chemical ionization mass spectrum of the , , , -tetrakis-(methoxycarbonyl) derivative of tri-HO-MA showed an abundant protonated molecule at m/z 430 which was further characterized by CID to give a daughter ion mass spectrum that was identical to that of derivatized synthetic tri-HO-MA; the daughter ion mass spectrum contained the following ions [m/z (relative intensity)]: 431 (24), 430 (28), 399 (11), 398 (100), 354 (6), and 322 (13). The daughter ions at m/z 398, 354, and 322 can be rationalized by the loss of CH3OH, CH3OCOOH, and CH3OH plus CH3OCO-OH, respectively, from the protonated molecule.…”

Effects of Intraventricular Injections of 6-Hydroxydopamine on Plasma Lh and FSH in Male Rats

“…Alternatively, H202 produced by auto-oxidation of 6-OHDA has been considered the causative factor in neuronal degeneration (Heikkila & Cohen, 1972). Recent work has demon¬ strated that the open-chain quinone is the major initial product of oxidation of 6-OHDA and the zwitterionic form of this compound is the main chromophore in neutral pH solutions (Powell & Heacock, 1973). The slow rate of cyclization of the open-chain quinone probably indicates that this compound, rather than cyclized products, has the greatest physiological significance (Powell & Heacock, 1973).…”

“…Recent work has demon¬ strated that the open-chain quinone is the major initial product of oxidation of 6-OHDA and the zwitterionic form of this compound is the main chromophore in neutral pH solutions (Powell & Heacock, 1973). The slow rate of cyclization of the open-chain quinone probably indicates that this compound, rather than cyclized products, has the greatest physiological significance (Powell & Heacock, 1973). It must be pointed out that the selectivity and specificity of action of 6-OHDA (Bloom et al, 1969;Uretsky & Iversen, 1970;256 J. H. Kitchen et al Bréese & Traylor, 1970;Bartholini et al, 1971;Ungerstedt, 1971) has been questioned by Poirier, Langelier, Roberge, Boucher & Kitsikis (1972) …”