Alkylating potential of N‐phenyl‐N‐nitrosourea

Alkylating agents are considered to be archetypical carcinogens. Since the decomposition of alkylnitrosoureas gives rise to alkyldiazonium ions without any need for metabolic activation, they offer an ideal series of compounds with which to examine the effect of variations in chemical structure on alkylating potential. Due to its instability N-phenyl-N-nitrosourea is easily hydrolyzed to a benzenediazonium ion. Since N-phenyl-N-nitrosourea shows a particular behavior when compared with other nitrosoureas, here its alkylating potential was studied. The nucleophile 4-(p-nitrobenzyl)pyridine (NBP), a trap for alkylating agents, was used as an alkylation substrate. Conclusions were drawn as follows: (i) the mechanism of the alkylation reaction of NBP by phenylnitrosourea is different from that caused by other nitrosoureas; (ii) the formation of the NBP–N-phenyl-N-nitrosourea adduct occurs about 20,000-fold slower than with N-methyl-N-nitrosourea, one of the most effective carcinogenic nitrosoureas; and, (iii) a correlation was found between the alkylating potential of nitrosoureas and their tumorigenicity.