CHAPTER 5 



QUINONES 



The quinones form a group of highly reactive and occasionally quite 

 specific metabolic inhibitors which present many interesting possibilities 

 for development as tools in enzyme research and as useful drugs in the con- 

 trol of disease. It is a heterogeneous group, embracing substances with 

 several distinct mechanisms of action, of which the reaction with SH 

 groups is only one. The quinones are possibly the most difficult inhibitors 

 to discuss because of this multiplicity of actions. The situation has recently 

 been made more complex with the demonstration of the participation of 

 various types of quinone in electron transport and oxidative phosphoryl- 

 ation, and the realization that exogeneous quinones may disturb these 

 processes by substituting for, displacing, or in other ways interfering with 

 these processes. It is for this reason that quinones are so frequently found 

 to stimulate cell metabolism and functions, the observed effect often rep- 

 resenting a balance between the stimulatory and inhibitory actions. The 

 quinones have long been known as potent inhibitors of the growth of micro- 

 organisms, and their abilities to induce nuclear and mitotic abnormalities 

 have been investigated more recently. Because of the many types of quinone, 

 natural and synthetic, they represent an ideal field in which to correlate 

 structure with action and in which to determine the effects of group substi- 

 tution or deletion. Many problems present themselves here for in no case 

 has a potent biological action of a quinone been correlated with a specific 

 mechanism, and it is likely that solution of these problems would provide 

 useful information on the processes of mitosis and growth. 



The simplest quinone and, at least with respect to reaction with SH 

 groups, the type substance of this class, p-benzoquinone, was first described 

 and synthesized by Woskresensky in 1838, but serious study of its effects on 

 biological material was delayed. It is true that Woskresensky remarked that 

 it was irritating to the eyes, while Wohler in 1844 confirmed this irritant 

 effect on mucous membranes. Nevertheless, Wohler and Frerichs (1848) 

 found that 0.5 g fed to a dog produced no observable effects and that no 

 quinone could be detected in the urine, posing the problem of its fate in 

 the body. Sporadic reports describing miscellaneous effects on animals ap- 



421 



