232 ERNST FREESE 



All alkylating agents that prevent cell duplication have in common 

 their reactivity with nucloophilic, i.e., slightly negatively charged, groups 

 (Stacey et ai, 1958). The various chemical reactions by which alkyla- 

 tion can occur have been described, e.g., by Price (1958), and the rela- 

 tive reactivities, with respect to alkylation, of various chemical groups 



Al-Cl 



1. s Sulfur mustard: 



\ both alkyl groups halogenated, bifunctional; 



"^ ^^ only one alkyl group halogenated, monofunctional 



Al— CI 



2. CI — Al— N Nitrogen mustard: 



\ all tnree alKyl groups halogenated, trifunctional; 



two alkyl groups halogenated, bifunctional; 

 only one alkyl group halogenated, monofunctional 



O 



II 



3. Al— O— S— O— Al Dialkyl sulfates 



II 

 O 



o 



II 

 4 Al— O— S— Al Alkylalkane sulfonates 



II 

 O 



H H 



5. H— C-C — R Epoxides 



O 



H H 



6. HC — CH Ethyleneimines 



N 

 I 

 R 



H H 

 7 HC — CH /3 -Propiolactone 



I I 



o— c=o 



8. '*"N=N— R Diazo compounds 



9. R— O' Other reactive oxygens 



Fig. 12. Different t.vpes of most coinnionly used alkylating agents. 



have been compared by Ross (1958); most reactive are sulfhydryl and 

 thioester groups. When isolated DNA is treated in solution the reac- 

 tivity of alkylating agents depends on their charge, negatively charged 

 molecules, like chlorambucil, being least reactive. But when nucleopro- 

 teins are used (sperm heads) all alkylating agents can readily react with 

 phosphate groups and this reactivity compares well with their lethal 



