Kitaro Yoshida

A model for metabolic activation of dialkylnitrosamines. Oxidative dealkylation of N-nitroso-2-(alkylamino)acetonitrile by flavin mimic in aqueous solution

Abstract Oxidation-active flavin mimic, benzo[1,2-g, 5,4-g′]dipteridine (BDP), is found to react with N-nitroso-2-(alkylamino)acetonitrile via oxidative dealkylation in aqueous solution. From the kinetic investigations, the oxidation mechanism is proposed.

N-nitroso compounds. Part 3. Hydrolysis of N,N′-dimethyl-N′-(p-nitrophenyl)-N-nitrosourea in aqueous basic solution. Effect of a cationic micelle on the hydrolysis of substituted N-nitrosourea

The hydrolysis of the title N-nitrosourea has been studied kinetically in various amine buffers (pH 8–11) at 36.8 °C. The reaction proceeds through hydroxide ion attack at the carbonyl carbon to form a tetrahedral intermediate, which collapses to an arylcarbamate ion, releasing an N-nitrosamino fragment. The effect of the buffer concentration on the hydrolysis rate is explained in terms of general base catalysis. Nucleophilic attack of unhindered amines at the carbonyl carbon also occurs under the hydrolytic conditions. With bulkier amines, however, the concurrent nucleophilic reaction is excluded because of steric hindrance around the carbonyl group. The micellar effect on the hydrolysis rate has also been investigated using cetyltrimethylammonium bromide (CTABr). The rate enhancement of the hydrolysis by the CTABr micelle is shown to be six-fold at pH 8.05. However, with an alternative N-nitrosourea bearing a labile hydrogen on N′, a much larger micellar catalysis was observed for the elimination of the hydrogen in the presence of OH–.

N-nitroso compounds. Part 5. Hydrogen–deuterium exchange of N-nitroso-2-(alkyl or arylamino)acetonitriles in aqueous solution

The hydrogen–deuterium exchange of the cyanomethyl protons of a series of nitrosamines, RN(NO)CH2CN (R = alkyl, benzyl, p-substituted phenyl, and cyanomethyl), has been investigated kinetically in CD3COCD3–D2O or CD3CN–deuteriated phosphate buffer at 35.1 °C. The order of the ring substituents of the arylnitrosamines is found to be p-MeO > H > p-Cl. The electronic effect of the R group on the relative stability of the nitrosamino carbanion is discussed in relation to the resonance structure of the nitrosamines in aqueous solution.

A REMARKABLE RATE-ACCELERATING METAL ION EFFECT ON THE INTRAMOLECULAR TRANSESTERIFICATION REACTION OF A PHOSPHODIESTER IN ACETONITRILE

The intramolecular transesterification reaction of 2-hydroxypropyl 4-nitrophenyl phosphate is greatly accelerated (105–106 fold) by the addition of divalent metal ions such as Zn2+ and Cu2+ in MeCN without a base; the metal ion effect is quite sensitive to the content of H2O in MeCN.