COMPARISON OF HALOGENATED ACIDS 281 



The reversibility of the inhibitions should be tested since this will have 

 bearing on whether an alkylating mechanism is involved or not. 



Halogenated Substances Which May Alkylate SH Groups 



A general review of the alkylating agents has been presented by Ross 

 (1962) with the emphasis on compounds of possible use in cancer therapy. 

 Some of these are halogenated substances which are reactive by virtue of 

 the halogen atoms, but little is known of their effects on enzymes or me- 

 tabolism. In this final section we shall consider only a few compounds which 

 may be related in their actions to the haloacetates, and at least are often 

 potent metabolic inhibitors. These substances are all potent vesicants and 



Cl^x /^CO— CH3 <\ ,) — CO— CH2— CI 



Chloroaceto- Chloromethyl- 



phenone phenylketone 



/^CH,-Br <^^ /^CH 



/™ 



Br 



Benzyl Bromobenzyl 



bromide cyanide 



CI— CH2-CO-CH3 CI3C— NO2 Br— CN 



Chloroacetone Chloropicrin Bromocyanide 



lachrymators, properties which Bacq (1941) attempted to correlate with 

 inhibition of glycolysis. Fleckenstein et al. (1950), however, found them to 

 be more inhibitory to respiration than glycolysis, behaving in general as 

 the esters of bromoacetate, and classified them as cycle inhibitors. Fischer 

 (1944) found that papain is inhibited 80-90% within 15-30 min by 0.5 mM 

 chloropicrin, chloroacetone, and chloroacetophenone, all being somewhat 

 more potent than iodoacetamide. Several enzymes w^ere studied by Mack- 

 worth (1948) and some of the results are summarized in Table 1-46. She 

 further found that the enzymes can generally be protected from these 

 agents by cysteine or glutathione, indicating that reaction with SH groups 

 occurs readily. Although these substances react with SH groups, one cannot 

 yet attribute the inhibition of respiration or their vesicant action to this 



