Thiophene detoxication

In humans, the bioactivation of tienilic acid as its reactive intermediate depends on cytochrome P-450 2C9. This isoform is one of the major forms of cytochrome P-450 in the human liver. It has recently been demonstrated that in the presence of cytochrome P-450 thiophene is oxidized in vivo to yield thiophene sulfoxide (Fig. 32.12). This unusual function is a very electrophilic species capable of reacting with thiol group nucleophiles such as glutathione (detoxication) or proteins. This interaction with free proteins that contain thiol groups may give rise to an adduct and the potential associated toxicity. 

The conversion of thiophene into a shielded derivative (Maxted, 14) thus involves the application of a two-stage process consisting of a preliminary hydrogenation step (which, in practice, may be of very short duration, e.g. 2-3 minutes) followed by the addition of a small quantity of an oxidizing detoxicant. The course of the detoxication is therefore ... 

The principal difficulty in detoxication by a single hydrogenation-oxidation treatment lies in the effective limitation of the hydrogenation stage to the thiophene originally adsorbed on the catalyst. Amounts of... 

Fig. 4. Detoxication of thiophene contained ae a catalyst poison in impure benzene.

The detoxication of condensed thiophenes was also studied (Maxted and Walker, 16) in connection with the possible detoxication of naphthalene prior to its hydrogenation. The nature and relative abundance of the sulfur-containing poisons which are present in coal-tar naphthalene... 

As with thiophene, several repetitions of the alternate short hydrogenation and oxidation were in general necessary before complete detoxication... 

Very similar results were obtained with the thiophthenes. Detoxication of all these condensed thiophenes can also be obtained by using the revivable filter-column method. 

Complete detoxication was easily obtained and it was found that, if the preliminary hydrogenation period was extended to 15 minutes, there was no necessity to repeat the hydrogenation-oxidation treatment as in the work with thiophene. 

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