Spectroscopic study of N-nitroso compounds decomposition in presence of DNA bases.

Decomposition kinetics of N-ethyl-N-nitrosourea (ENU) as well as that of N-methyl-N-nitroso-N'-nitroguanidine (MNNG) in water medium was studied by means of differential UV spectroscopy. Rate constants of the first order reaction were evaluated. The influence of DNA bases on decomposition rate of above-mentioned compounds was also estimated. With the help of NMR spectroscopy there were identified several products of decomposition as well as those of interaction of the studied compounds with DNA bases.

Reactivity of free and coordinated radicals in biology and chemical carcinogenesis. II. Electron transfer from 3,4-benzopyrene to molecular oxygen and to peroxides, and interpretation of ESR signals of the intermediate radicals of oxidation.

Already a trace of oxygen mediates the one-electron transfer from 3,4-benzopyrene (benzo(a)pyrene, BP) to hydrogen peroxide or to tert. butyl hydroperoxide (ROOH), leading in this way to generation of highly reactive HO X, HO2 X or RO X and RO2 X radicals in nonpolar solvents at biological temperatures. At slightly higher concentration of O2 in solution and at moderately elevated temperature (40-60 degrees C) a stable radical pair (HO-BPO X)2 in equilibrium with its diamagnetic dimer of quinone-hydroquinone type is formed. The paradiamagnetic equilibrium of this redox system is reversibly shifted with temperature. At low temperature (up to -40 degrees C) the paramagnetism disappears. The precursor of the radical pair, which can be decomposed, applying a polar solvent, is the keto form of the hydroxy derivative (6-HO-BP) at ambient temperature. According to the study of highly resolved ESR spectra of the primary temporarily formed ion radical pair [BP+ X O-2 X] of BP oxidation in the dark, of the secondary radical pair (HO-BPO X)2 and of the coordinated unhindered phenoxy radicals of hydroxy derivatives BPO X CoIII, the mechanisms of one-electron or of hydrogen-atom transfer from radical intermediates of BP to potential biological targets is discussed.

Reactivity of free and coordinated radicals in biology and chemical carcinogenity. I. Coordinated phenoxy radicals generated by hydrogen transfer from hydroxy derivatives of 3,4-benzopyrene.

The tautomeric keto form of 6-, 7- and 8-hydroxy-3,4-benzopyrene (BP) prevails in nonpolar solvents at laboratory temperature, in contrast with the enol form of 9-HO-BP and 3-HO-BP, as it was shown according to the ESR study of H-transfer reactions initiated by tert. butyl peroxy radicals coordinated upon the hydroxy derivative of cobalt(III)-acetylacetonate [HO-Co(acac)2]. A further hydroxylation of the keto form of 6-HO-BP, mainly in the position 3, in the thermal interval 40-60 degrees C and the presence of oxygen was observed. Because of lack of steric hindrance in the neighborhood of the position 3 or 9 the primarily formed phenoxy radical after H-abstraction remains stabilized as sigma-coordinated radical on CoIII. Such a radical complex can be destroyed after addition of polar solvents (e.g. methanol). During autooxidation of BP in aerated solutions, similarly as during enzymatic oxidation, a relatively great concentration of high-stable radicals accumulates in nonpolar solvents and in the absence of peroxides. The paramagnetic species is interpreted as a radical pair of two nondissociated semiquinones. In discussion of the carcinogenic activity of oxidative products of BP, not only the enzymatically formed, but also the randomly formed radical intermediates in the first steps of autooxidation must be taken into consideration, which reactivity to biological targets is mediated with the polarity of the biological medium.

Electrochemical properties of polycyclic compounds studied by the polarographic method in anhydrous systems. VIII. The influence of proton-donor on reduction of carcinogenic nitrogen compounds in dimethylformamide.

The authors have studied the electrochemical behavior of a series of carcinogenic and inactive heterocyclic compounds in anhydrous medium in the presence of a proton-donor. As anhydrous medium the authors used anhydrous dimethylformamide as proton-donor phenol. In the presence of proton-donor there had occurred on polarographic reduction of the employed carcinogenic heterocyclic compounds changes in the number of polarographic waves. Between the two original waves in these compounds there arose in the presence of phenol a new wave. In non-carcinogenic heterocyclic compounds such an effect of phenol was not noted. In the present paper the authors discuss the possible mechanism of electroreduction of carcinogenic and inactive heterocyclic compounds in anhydrous medium in the presence of a proton-donor.

Electrochemical properties of polycyclic compounds studied by the polarographic method in anhydrous systems. VII. Polarographic oxidation of carcinogenic hydrocarbons in dimethylformamide.

The electrooxidation of polycyclic carcinogenic hydrocarbons in dimethylformamide solutions was studied by polarography. The results generally have confirmed that a correlation exists between oxidation potentials and carcinogenic activity of the studied polycyclic aromatic hydrocarbons. The half-wave potentials of the polarographic curves have been found to be directly related to the root xn of the Hückel secular equation for the highest bonding orbital and to the reduction potentials measured in dimethylformamide.

Carcinogenicity and polarographic behaviour of dibenzo[a,h]pyrene, 4,11-diazadibenzo[a,h]pyrene and 7,14-diazadibenzo[a,h]pyrene.

In a simultaneous test of carcinogenicity the writers have studied the activities of dibenzo[a,h]pyrene (I), 4,11-diazadibenzo[a,h]pyrene (II) and 7,14-diazadibenzo[a,h]pyrene (III). These compounds were dispersed in paraffin disks and subcutaneously implanted in rats. Each experimental group consisted of 30 animals. The number of sarcomas induced by (I) and (II) was 23 and 16 respectively. The compound (III) has proved wholly inactive. Tumorigenicity of (I) and (II) was found to be proportional to their electron donation and inversely proportional to their electron acceptance in the performed polarographic test. Inactivity of (III) is being discussed from the aspect of molecular geometry.

Carcinogenicity and polarographic behavior of dibenz[a,h]anthracene, dibenz[a,h]acridine and dibenz[a,h]phenazine.

In a simultaneous test of carcinogenicity the authors have studied the activities of dibenz-[a,h]anthracene, dibenz[a,h]acridine and dibenz-[a,h]phenazine. These compounds were dispersed in paraffin disks and subcutaneously implanted in rats. Each experimental group consisted of 30 animals. The number of sarcomas induced by the above-mentioned compounds was 20, 5 and 3 respectively. Tumorigenicity of the aza analogues of dibenz[a,h]anthracene was proportional to their electron donation and inversely proportional to their electron acceptance in the performed polarographic test. The authors discuss the possibilities of using polarography as a screening test for the exclusion of carcinogenic polycyclic compounds.

Electrochemical properties of polycyclic compounds studied by the polarographic method in anhydrous systems. VI. The influence of proton-donor on reduction of carcinogenic aromatic hydrocarbons in anhydrous environment.

The authors have studied the electrochemical behaviour of a series of carcinogenic and inactive aromatic hydrocarbons in anhydrous environment in the presence of a proton-donor. As anhydrous environment the authors used water-free dimethylformamide and dimethylsulfoxide; as proton-donor phenol. Phenol gave rise to quantitative changes in the number of polarographic waves when the carcinogenic aromatic hydrocarbons were undergoing reduction. Between the two original waves there originated in the presence of phenol a new polarographic wave in these hydrocarbons. In inactive analogues of the investigated hydrocarbons no such effect of phenol has been ascertained. In their present study the authors discuss the potential mechanism of electroreduction of carcinogenic and inactive aromatic hydrocarbons in anhydrous environment in the presence of a proton-donor and compare the values of half-wave potentials of the investigated compounds measured in water-free dimethylformamide, dimethylformamide + phenol and in ethylenglycolmonomethylether.

Electrochemical properties of polycyclic compounds studied by the polarographic method in anhydrous systems. V. Oxidation potentials of carcinogenic hydrocarbons in acetonitrile.

The half-wave oxidation potentials of polycyclic carcinogenic hydrocarbons have been studied at the rotating platinum electrode in anhydrous acetonitrile with sodium perchlorate as the supporting electrolyte. The good agreement was obtained by the comparison of the carcinogenic activity of studied compounds with the values of the oxidation potentials. The values of the oxidation half-wave potentials were correlated also with the reduction potentials measured in acetonitrile and with the root xn of the Hückel secular equation for the highest bonding orbital.

Electrochemical properties of polycyclic compounds studied by the polarographic method in anhydrous systems. IV. Polarographic study of carcinogenic and noncarcinogenic hydrocarbons in ethylenglycolmonomethylether.

An experiment was carried out to determine whether there is any correlation between the values of polarographic reduction potentials of polycyclic hydrocarbons and their carcinogenic activity. A comparison of half-wave potentials of polarographic wave I and II of pyrene benzologs revealed that the carcinogenic ones become reduced in ethylenglycolmonomethylether on a mercury dropping electrode at more positive potentials than the inactive benzo- and dibenzopyrenes. The discussion bears both on the reduction mechanism of the compounds and on the relationship between the half-wave potentials and the absorption electron spectra measured in the same solvent.

Electrochemical properties of polycyclic compounds studied by the polarographic method in anhydrous systems. III. Polarographic reduction potentials of carcinogenic nitrogen compounds in dimethylsulfoxide.

The polarographic reduction of a series carcinogenic and noncarcinogenic polycyclic nitrogen compounds in anhydrous dimethylsulfoxide containing tetrabuthylammonium perchlorate as supporting electrolyte has been studied. The obtained results were compared with the number or with the position of nitrogen atoms in the molecules and with their carcinogenic activity. The values of half-waves potentials generally confirmed the mechanism proposed for the reduction of aromatic polycyclic carcinogenic hydrocarbons based on the polarographic experiments in dimethylsulfoxide. Agreement of the obtained results with the data reported by polarographic study in anhydrous dimethylformamide indicates, that the polarographic behavior of polycyclic nitrogen compounds in dimethylsulfoxide is very similar.

Electrochemical properties of polycyclic compounds studied by the polarographic method in anhydrous systems. II. Polarographic study of carcinogenic nitrogen compounds in dimethylformamide and comparison of half-wave potentials with quantum-chemical calculations of molecular orbitals.

Reduction of half-wave potentials and the mechanism of reduction of 20 polycyclic nitrogen compounds were studied on a dropping-mercury electrode in anhydrous dimethylformamide using tetrabuthylammonium perchlorate as the supporting electrolyte. The measured values of the reducing half-wave potentials of the polycyclic aza-compounds were compared in view of their carcinogenic activity with parental carcinogenic polycyclic hydrocarbons. Electrochemical measurements have confirmed that the size of the shift in reducing potentials towards the more positive values and the decline of the carcinogenic activity generally depend on the number and position of the nitrogen atoms in the molecule of the polycyclic nitrogen compound under study. At the same time, the experimental electrochemical measurements were matched with the results of the quantum-chemical calculations of the molecular orbitals and this showed a good agreement to exist between the values of reducing half-wave potentials obtained by experimental measurement and by calculation.