Studies on chemical carcinogens and mutagens. XXXIX. Effects of silicon and germanium substitutions on physicochemical properties and cytotoxicity of N-alkyl-N-nitrosoureas.

Abstract

N-Trialkylsilymethyl- and N-trialkylgermylmethyl-N-nitrosoureas, which are analogues of N-neopentyl-N-nitrosourea, were synthesized and tested for cytotoxicity to leukemia L1210 cells. Rates, activation energies, and entropies of activation of the hydrolytic activation of these derivatives were determined. The chemoselectivity and partition properties were also determined in terms of the Swain-Scott's substrate constant and logk', respectively. In aqueous media, all the Si- and Ge-containing nitrosoureas examined underwent hydrolysis accompanied by the ready cleavage of the Si-C or Ge-C bond to give methanol. From these nitrosoureas, the corresponding diazoalkanes were synthesized and reacted with a carboxylic acid in benzene containing alcohols. The results indicated that the Ge-C bond is more susceptible to hydrolysis than the Si-C bond. More lipophilic dimethylphenylsilyl and -germyl derivatives were more toxic to L-1210 than the crresponding trimethyl derivatives.