138 



L. J. MULLINS 



% of DDT 

 Rate 



140 



100 



60 



20 



!l 



i 



Br 



By OH" 

 By Enzyme 



.i .1 



CI H 



p,p' substituent 



CH 3 CH 3 



toxicity 



Fig. 7. The rate of transformation of DDT to DDE by alkali and by enzyme is 

 compared with rates for homologs of DDT differing only in their p-substituents. An 

 indication of the approximate toxicity of the substances to insects is given at the 

 bottom of the diagram (Sternberg et al. 1954). 



the type of substrate specificity as that of the receptor, e.g. the most toxic 

 compounds are the best substrates. While DDT shows an action superficially 

 similar to the application of acetylcholine to sensitive structures in mammals, 

 it is not an anticholinesterase (Hartley and Brown, 1955). 



One difficulty in this problem is the lack of any general understanding of the 

 mechanism of enzyme action; it is not intended here to do more than suggest a 

 mechanism applicable to this particular reaction. Attack on the 2-hydrogen of 

 DDT seems unlikely for the reasons mentioned previously. The same end prod- 

 uct, DDE, could be obtained by a removal of one of the CI atoms on the 1- 

 position of DDT; the hydrogen would then undergo a spontaneous release and 

 DDE would result. This reaction sequence would permit enzyme activity to be 

 independent of the p- substituent which is not precisely the case. It may be 

 argued that the nature of the p- substituent determines the extent of binding 

 of substrate to enzyme; this would explain the low reactivity when H is the p- 

 substituent but would fail to explain the poor reactivity of the p-iodo com- 

 pound. A comparison between Figs. 5 and 7 shows that enzyme action can be 

 correlated with "goodness of fit" or with the same parameters that were devel- 

 oped to explain the convulsant activity of DDT. 



In estimating the size of an interspace into which DDT would fit, the radius 

 of curvature of the cylindrical macromolecules was set by the points of tangency 

 of the two p-Cl atoms to the surface of the macromolecule. An identical radius 

 of curvature is defined by the p-Cl atom of one ring and an ethane-Cl on the 

 same side of the molecule. The cylinders so specified have a radius of 17.5 A 



