The Effect of Hindered Phenols on Mitochondrial Oxidative Phosphorylation.

Thyroxine is an ortho-para-hindered phenol and as such it has the structure necessary to form a relatively stable phenoxyl free radical. I f free radical stability is an important feature of its biological reactions, it is pertinent to determine whether there is any specificity rendered to the phenol by o-halogen or p-phenoxy substitution, In regard to the initial microsomal degradation reactions of thyroxine, neither the o-halogen nor p-phenoxy substituent is critical (1). Both may be replaced by other groups yielding a phenol still capable of displacing thyroxine from these reactions. The aim of this study has been to determine whether the feature of predictable free radical stability may be related to the capacity of thyroxine and related phenols to uncouple mitochondrial oxidative phosphorylation. Furthermore, since there is apparently such a ,relationship, the specificity of phenolic oand p-substitutions has been examined.