Aminochromes from catecholamines

More recent work has been aimed at establishing the existence of these and other intermediates. Since the formation of aminochromes from catecholamines occurs rapidly, detection of the intermediates is rather difficult and their isolation virtually impossible. As has been previously mentioned, the first step in the reaction appears to be a one electron oxidation to give the semiquinone (47) [66-68, 79], which is then oxidised to the open-chain quinone (12). The reaction stops at this stage in strongly acidic solution... 

It appears that the intermediates formed from different catecholamines are of different stability. The intermediate open-chain quinones derived from catecholamines with a primary amino group in the side chain do not appear to undergo intramolecular cyclization very readily and consequently would be able to take part in competing reactions this would account for the fact that in general it is difficult to obtain efficient conversions of such catecholamines (e.g. noradrenaline) into the corresponding aminochromes. This factor is important in catecholamine assay procedures (see Section V, E) and probably explains the wide variability in the apparent efficiency of the noradrenaline oxidation procedures used (as measured by the intensity of the fluorescence of the noradrenolutin obtained by the particular method). The fact that noradrenaline-quinone is relatively more stable than adrenaline-quinone accounts for the formation of entirely different types of fluorescent products from adrenaline and noradrenaline, respectively, in the Weil-Malherbe assay procedure for catecholamines (see Sections IV, H and V, E, 5). 

In summary, it would appear that the oxidation of a catecholamine probably first involves the formation of a semi-quinone radical (this can be brought about by an one-electron transfer, e.g. from Cu++ ions,14 or by photoactivation 1) which rapidly undergoes further oxidation (e.g. with atmospheric oxygen) to an intermediate open-chain quinone (such as adrenaline-quinone) and then cyclizes by an oxidative nucleophilic intramolecular substitution to the amino-chrome molecule. Whilst the initial formation of a leucoaminochrome by non-oxidative cyclization of the intermediate open-chain quinone in some cases cannot be entirely excluded at the moment (cf. Raper s original scheme for aminochrome formation72), the... 

Since certain aminochromes (e.g. dopachrome) are essential intermediates in the process of melanogenesis (see preceding section) and in view of the widespread distribution of melanitic pigments in both the plant and animal kingdoms, it would appear, that in this respect at least, aminochromes must presumably be formed in vivo from certain of the catecholamines. 

Assay procedures for dopamine which are superficially similar to the lutin procedure described above have been reported recently.266-268 The chemistry of the production of the fluorophore from dopamine is, however, somewhat different since the fluorophore is not a 5,6-dihydroxyindoxyl, it is incorrect to refer to the trihy-droxyindole fluorophore of dopamine (cf. ref. 252). Oxidation of the extracted catecholamine is usually carried out with iodine,266-268 presumably with the formation of 7-iodonorepinochrome. The aminochrome is subsequently rearranged to 5,6-dihydroxyindole (it is probable that deiodination accompanies the rearrangement in this case) by a solution of sodium sulfite in aqueous alkali the solution is acidified before measuring the fluorescence of the product (which is said to form relatively slowly and to be very stable).266-268 Irradiation of the reaction mixture with ultraviolet light accelerates the maximal development of fluorescence.266 Since acidification will produce sodium bisulfite in the reaction mixture, it is probable that the fluorophore is a 5,6-dihydroxyindole-sodium bisulfite addition complex. Complexes of this type are known to be both fluorescent and relatively stable in dilute acid solution.118 123,156 265 They also form relatively slowly.255... 

De Mol, N.J., Beijersbergen van Henegouwen, G.M.J., and Gerritsma, K.W. (1979) Photochemical decomposition of catecholamines. II. The extent of aminochrome formation from adrenaline, isoprenaline and noradrenaline induced by ultraviolet light, Photochem. Photobiol., 29, 479 -82. 

Borg [79] studied (a) the ceric sulphate oxidation of adrenaline, noradrenaline and DOPA in add solution (b) the ferricyanide oxidation of adrenaline and DOPA in alkaline solution and (c) the permanganate oxidation of adrenaline at neutral pH. Free radical intermediates, which were thought to be semiquinones formed in the first step of the oxidation, were detected in the reaction mixtures by means of e.p.r. spectroscopy. They were shown to have arisen before the aminochrome stage as the e.p.r. spectrum of oxidised adrenochrome was different from that observed in the initial stages of the oxidation of adrenaline. Thus the first stage in the oxidation of catecholamines involves the formation of a semiquinone [79]. 

It was concluded from the kinetic data that, as the potential became more positive, the catecholamine was oxidised to the open-chain quinone, which cyclised to the leucoaminochrome. The leuco compound, which is more easily oxidised than the original catecholamine was then oxidised to the aminochrome by some of the remaining uncyclised quinone, which was itself reduced back to the original catecholamine. On reversal of the scan, with the potential becoming more negative, the aminochrome was reduced back to the leucoaminochrome. Some of the latter compound then lost water to form the 5,6-dihydroxyindole (44), which was detected by its oxidation to the indole-5,6-dione (45) when the scan was again reversed (increasing potential) [106]. 

Galzigna has recently demonstrated the possibility of complex formation between acetylcholine and noradrenochrome [199, 200]. This led to the proposal of the short circuit theory to explain the onset of mental illness [200, 201]. According to this theory, if a central catecholamine were leaking from a synapse, in the absence of the enzyme system which normally destroys it, it could be oxidised to the aminochrome, which then forms a stable... 

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