422 5. QUINONES 



peared: e. g., the work of Brieger (1880) on rabbits, of Gibbs and Hare 

 (1890) on dogs, of Schulz (1892) and Baglioni (1905) on frogs, and of Da- 

 nilewski (1895) on various invertebrates. Much of this early work is well 

 summarized by Ellinger (1923). Certain actions on the nervous system, 

 the heart, and the blood were made evident by this work, but the results 

 were not of sufficient interest to stimulate further more intensive study. 

 Meanwhile some pertinent chemical reactions of the quinones were noted, 

 especially the combination with amines and the important observations by 

 Wiirster (1887, 1888) that quinones react with amino acids to give colored 

 products, and by Troeger and Eggert (1896) that reactions with thiols 

 often occur readily. 



The first significant study of the biological effects of the quinones was 

 made by Thalhimer and Palmer (1911) in Virginia. They showed p-henzo- 

 quinone to be a very potent bactericidal substance with a phenol coeffi- 

 cient of 160 against Salmonella typhosa. Early workers had indeed ob- 

 served that protein solutions do not spoil in the presence of quinones and 

 concluded that they must be disinfectants, and several had reported that 

 polyhydroxy phenols often show an increased antibacterial activity under 

 conditions favorable for oxidation, a fact soon postulated by Cooper (1913) 

 as due to the formation of quinones. Morgan and Cooper (1924) made 

 some fundamental comparisons of various quinones with respect to their 

 antibacterial actions, but found the presence of biological fluids to depress 

 the activity markedly and concluded that the quinones would be worth- 

 less as practical disinfectants. With this proclamation further work stopped 

 and not a single paper was published on this subject until the observa- 

 tions of Raistrick in the early 1940's that several fungal quinones are 

 bacteriostatic. The interest in penicillin and the possibility of the use of 

 some of the fungal quinones as antibiotics led to an intensive period of 

 research culminating in the isolation and synthesis of numerous highly 

 active compounds, and a survey of their actions on metabolic systems. One 

 of the most thorough studies was that of Fieser and his associates during 

 the war on many 2-hydroxy-3-alkyl-l,4-naphthoquinones active against 

 the malarial parasite. 



Knowledge of the actions of the quinones on enzymes and metabolic 

 systems is fairly recent despite the fact that it was known for a very long 

 time that proteins, especially those of wool, are readily reacted, and that 

 the mechanism of the antibacterial action had actually been attributed 

 to an inhibition of enzymes by Cooper (1913). Several observations between 

 1912 and 1928 showed that quinones can often act as hydrogen acceptors 

 in tissues and can function in electron trasport in connection with certain 

 enzymes, e. g., xanthine oxidase (Dixon, 1926), but the first definite 

 instance of inhibition was the demonstration by Harvey (1929) that bac- 

 terial luminescence is very sensitive to several quinones. The initial work 



