Showing papers on "Triazene published in 1990"

Evidence for an unstable DNA adduct from N-nitroso-N-methylaniline.

Abstract: N-Nitroso-N-methylaniline (NMA) is an esophageal carcinogen in F344 rats. Attempts to detect binding of NMA to DNA or RNA have not been successful. NMA is not mutagenic in the standard Ames bacterial assay, and it did not induce sister chromatid exchanges in mammalian cells. NMA forms the benzenediazonium ion (BDI) during metabolism. This ion has been known to react with aromatic amines, such as adenine, to form triazene coupling products. The purpose of this research was to demonstrate that a triazene adduct, which would be expected to be hydrolytically unstable, was formed by coupling with the adenine residues in DNA. Liver DNA from a rat treated with NMA or from in vitro reactions of BDI with DNA was treated with sodium borohydride. This reaction was shown to result in the reduction of 6-(1-phenyltriazeno)purine to 6-hydrazinopurine (N6-aminoadenine). The hydrolysate of the DNA, presumably containing the hydrazine, was treated with 4-(dimethylamino)naphthaldehyde, and the resulting hydrazone was isolated by reverse-phase HPLC using fluorescence detection. The identity of the adduct was demonstrated by high-resolution mass spectrometry. These data suggest strongly that NMA forms an unstable triazene adduct with adenine in DNA both in vitro and in vivo.

Synthesis of 3-[125I]-iodo-phencyclidine for biological studies

Abstract: After verification of the biological activity of 3-iodo-PCP by binding studies to the N-methyl D-aspartate gated channel, 3-[125I]iodo-PCP was prepared by reaction of sodium iodide with a triazene precursor. The radiochemical yield was optimized and after HPLC purification, 3-[125I]iodo-PCP was obtained with a high radiochemical purity.

Mechanisms and products of azo coupling in histochemical protease procedures based on primary aromatic amines as unspecific moieties.

Abstract: It is presumed that the azo dyes generated by histochemical protease reactions are formed by substitution of a reactive aromatic carbon. They are referred to as dyes of the C-azo series. To confirm this assumption, the absorption spectra between 330 and 630 nm of azo dyes resulting from coupling between various aromatic amines of the aniline and naphthylamine series and the diazonium salts Fast Blue B and Fast Garnet GBC were studied in test tube experiments. Some of the amines were blocked by methylation to prevent coupling either at the amino group (N-methylated) or at the aromatic nucleus (C-methylated). Coupling was performed in buffered aqueous solutions of the diazonium salts. For analysis the azo dyes were dissolved in dimethylformamide. For acid rearrangement these solutions were acidified and incubated at elevated temperatures. After detection of dipeptidyl peptidase IV in tissue sections using Gly-Pro-4-methoxy-2-naphthylamine as substrate, the resulting dye was extracted and compared with the test tube compounds. All aromatic amines yielded azo dyes. Dyes extracted from sections and those test tube compounds derived from unmethylated or C-methylated amines showed almost identical spectral maxima, whereas dyes formed by N-methylated amines yielded different spectra. Acid rearrangement did not influence the spectral maxima of the N-methylated amine-derived dyes. Dyes resulting from C-methylated amines were destroyed. The results indicate that under histochemical conditions diazonium salts react primarily with the liberated free amino group but not with the aromatic nucleus of the unspecific moiety. Therefore, it is proposed that the formula of the final reaction product in naphthylamine-based protease histochemistry should be given as an N-azo dye, e.g., as a triazene.

Reactivity of proton and general acid with 1,3-bis-(4-methylphenyl)triazene in aqueous methanol

Abstract: The effect of concentration of benzoic acid and composition of the binary solvent water-methano' on the rate of decomposition of 1.3-bis(4-methylphenyl)triazene has been studied. It has been found that both general acid catalysis by undissociated benzoic acid and catalysis by the proton are significant. The rate constant kHA of general acid catalysis decreases monotonously with decreasing amount of water in the mixture due to preferred solvation of the activated complex as compared with the educts. The rate constant kH of the catalysis by proton in its dependence on methanol concentration exhibits a minimum for 80% (by wt.) of methanol in the mixture. This phenomenon is caused by formation of the conjugated acid from more basic methanol and proton with simultaneous solvation by water and methanol; the particle thus formed is a weaker acid as compared with the complexes existing in water or in methanol. The kH value is higher in methanol than in water due to preferred solvation of the educts as compared with that of the transition state.

Kinetic investigation of the aqueous stability and antitumor activity of a hydrosoluble diaryltriazene, AVIS, related to the antimetastatic agent DM-COOK.

Abstract: The aim of this study is to investigate the hydrolysis of 1,3-di(p-carboxyphenyl)triazene dipotassium salt, AVIS (1), over a pH range of 2.60-8.50. This compound decomposes into p-aminobenzoic acid and the corresponding diazonium cation with no formation of alkylcarbo cations; the same compounds are formed from hydrolyses of DM-COOK (2), an antimetastatic agent, and of its possible demethylated metabolite, MM-COOK (3), a chemical xenogenization inducer. In these latter cases, however, a methylcarbo cation is formed. The pH dependence of the pseudo-first-order rate constants is intermediate between 2 and 3. Preliminary data on its toxicity and antitumor activity on both Lewis lung carcinoma and TLX5 lymphoma seem to indicate the essential role of alkylcarbo cation in mediating the antitumor action of aryldimethyltriazenes.