Kinetic Studies on Anthralin Photooxidation

Abstract

The photooxidation of the antipsoriatic drug anthralin (1,8-dihydroxy-9-anthrone) has been studied by several kinetic techniques, including direct observation of 1O2 (1 delta g) luminescence at 1.27 microns. The rate of deactivation of 1O2 increases at higher pH, demonstrating that the trihydroxyanthracene anion is the reactive species. Direct determination of the rate constant of 1O2 deactivation (kR + kQ) in deuterated buffer systems by luminescence quenching gave a value of 3.0 x 10(8) M-1 s-1 for the anion; the neutral anthrone is unreactive. The rate constant for the neutral anthrone in benzene-d6 is 2.8 x 10(4) M-1 s-1. Competition experiments with tetramethylethylene in acetonitrile gave a rate constant for reaction alone (kR) of 2.1 x 10(8) M-1 s-1 for the anion.

Singlet oxygen O2(1.DELTA.g) bimolecular processes. Solvent and compartmentalization effects

“…3 x 108 M-1 s-1, very close to that measured in acetonitrile. 256 Mesodiphenylhelianthrene (MDH) is the most reactive 02(x Ag) acceptor.259 kr values for this compound are very close to the diffusion-controlled limit in a variety of solvents (from cyclohexane to acetone). This implies that kr > fe_d.…”

Antipsoriatic Anthrones with Modulated Redox Properties. 3. 10-Thio-Substituted 1,8-Dihydroxy-9(10H)-anthracenones as Inhibitors of Keratinocyte Growth, 5-Lipoxygenase, and the Formation of 12(S)-HETE in Mouse Epidermis

“…However, there was no relationship found between stability and acidity of the compounds. The 10-thio derivatives were all more acidic than anthralin which had a p K a value of 9.5 …”

“…The 10-thio derivatives were all more acidic than anthralin which had a pK a value of 9.5. 55 The decomposition products of the 10-thio derivatives in the organic solvents detected by HPLC were the stable 1,8-dihydroxy-9,10-anthracenedione, which does not polymerize, and the corresponding thiols, whereas the dimer bianthrone and anthralin itself made no contribution to the overall degradation. Thus, a phenylthioether side chain at C-10 of anthralin greatly enhances its stability in both protic and aprotic solvents and also prevents the anthracenone molecule from being polymerized to anthralin-brown.…”

Current Status and Recent Developments in Anthracenone Antipsoriatics

“…The methylene moiety at C-10 has been recognized as a key site of the formation of superoxide radical, which in turn can dismutate to produce hydrogen peroxide, and in the presence of iron, the highly reactive hydroxyl radical [44]. Furthermore, especially in the presence of light and oxygen, anthralin is oxidized to the anthraquinone danthron [49]. In light of these findings it is unlikely that the anthralin molecule itself is responsible for the biological effects, and also the known oxidation products anthralin dimer and danthron are not effective against psoriasis.…”

“…the C-1 hydroxyl group associated with the C-9 carbonyl group, appear to be significant. On the other hand, the anthralin anion is highly reactive against singlet oxygen [49], and its rate of reaction with singlet oxygen is one magnitude or more larger than those of important potential targets for an oxidative attack. Therefore, the anthralin anion should be In light of the chemical instability of many anthracenones, side chains are usually introduced onto the anthracenone nucleus by a stepwise procedure via the anthracenedione.…”