Chemical structure and biological activity 



the structure of the compounds it follows that the active materials have a 

 greater tendency to go into an oil phase than the physiologically inactive 

 ones. Especially striking is the difference between chlorinated and un- 

 chlorinated phenylmaleimides. This points to the conclusion that one large 

 factor in the increased physiological effect of benzene chlorination is the 

 increased fat solubility that goes with this type of chlorination. 



HC- 

 HC- 



/ 



\ 



N — R 

 / 



Figure 4. Structures, water solubility, and physiological activity of maleimides. {After van Overbeek 

 et al., 1955.) 



The amino phosphine oxides 



While in the maleimides we can identify the reactive grouping in the 

 molecule, we do not know with what active site in the cell this grouping 

 reacts. In the amino phosphine oxides, on the other hand, we have a rare 

 example in which we can identify both the active grouping in the molecule 

 and the site in the cell with which it interacts. The structure of a reactive 

 amino phosphine oxide is shown in Figure 5. The reactive grouping in the 

 molecule is the amino phosphine oxide grouping, while the butyl radicals 

 serve to give the molecule the proper lipophilic characteristics. The reactive 

 site in the cell is the chloroplast, and more specifically chlorophyll molecules. 



When a benzene solution of chlorophyll is exposed to light, or exposed to 

 the action of other destructive agents such as acids, its colour will soon turn 

 from green to brown because the Mg atom is lost. The presence of equimolar 

 quantities of amino phosphine oxides will greatly retard this chlorophyll 

 degradation. Chromatographic studies have shown that chlorophyll and 

 amino phosphine oxides form a complex. Polar solvents such as alcohols 

 separate the components again. 



In the test tube all amino phosphine oxides of the type considered here 

 are capable of complexing with chlorophyll, whether the radicals on the P 

 atom are methyl, ethyl, propyl, allyl, butyl, or amyl. Biochemically speaking, 

 all these compounds are active, and if there were no penetration problem all 

 these materials should be equally active when applied to living cells. This is 

 not so. 



208 



