STUDIES ON THE RELATIONSHIP BETWEEN IN-VITRO METABOLISM AND CERTAIN PHYSICOCHEMICAL CHARACTERISTICS OF SOME 9-ALKYL- 9-ARALKYL ADENINES/

Previous studies demonstrated that biological N-1-oxidation occurred f or some 9-alkyl-/9-aralkyladenines, but not for others, when mammalian hepatic microsomal incubates were used as enzyme source. In order to understand the mechanisms controlling the metabolic fate of these comp ounds, the relationship between N-1-oxidation and certain physicochemi cal characteristics of these substrates was studied. It was found that there was no marked link between N-1-oxidation and the computer predi cted pKa values of the substances studied. However, a computer predict ed LogP value in the range 1.5-4 seems to be the most favourable for N -1-oxidation. The H-1-NMR and C-13-NMR spectroscopic characteristics o f the substrates, which reflect certain electronic characteristics of the purine moiety, also showed a correlation with their N-1-oxidation. The electronic effects of the substrates in relation to their metabol ism was investigated using computer modelling techniques; the results showed that different substituents at the 9-position of adenine may mo dify the electronic characteristics of the purine moiety thus affectin g their metabolism. The conformation of the substrates N-1-oxidative m etabolism.