Biomedical subjects

P Eyer

Publications and source records attributed to P Eyer.

At least 19 recordsLinked to original sources

PubMed1992

Reactions of the Wurster's red radical cation with hemoglobin and glutathione during the cooxidation of N,N-dimethyl-p-phenylenediamine [correction of phenlenediamine] and oxyhemoglobin in human red cells.

N,N-Dimethyl-p-phenylenediamine (DMPD) reacted directly with oxyhemoglobin under formation of ferrihemoglobin and, presumably, the N,N-dimethyl-p-phenylenediamine radical cation (DMPP.+). The apparent second-order rate constant of this reaction was 1 M-1 s-1 (pH 7.4, 37 degrees C). The reaction rate was diminished by catalase (by 1/3) and by superoxide dismutase (by 1/5). The apparent second-order rate constant of ferrihemoglobin formation by DMPD.+ was 5 x 10(3) M-1 s-1. Since DMPD.+ is disproportionated by 50% at pH 7.4, the quinonediimine could not be excluded as the ultimate ferrihemoglobin forming oxidant. To prove this hypothesis, the disproportionation equilibrium was shifted to the radical side by addition of excess DMPD. Ferrihemoglobin formation was thereby increased, indication that the radical was the responsible oxidant. In contrast to ferrihemoglobin formation, reactions with glutathione occurred predominantly with the quinonediimine. The second-order rate constant of this reaction was 4 x 10(5) M-1 s-1 which approaches the value obtained with p-benzoquinone. In contrast to the corresponding reactions of the N,N,N',N'-tetramethyl-p-phenylenediamine radical cation, the disporportionation reaction of DMPD.+ was very fast, k = 2 x 10(6) M-1 s-1. Formation of glutathione disulfide was negligible and the main reaction products were two isomeric glutathione adducts, 2- and 3-(glutathione-S-yl)-N,N-dimethyl-p-phenylenediamine. In human erythrocytes, DMPD produced many equivalents of ferrihemoglobin, diminished glutathione and produced both thioethers. In contrast to ferrihemoglobin formation, DMPD and glutathione disappearance as well as thioether appearance occured only after a marked lag phase. The calculated steady state concentration of DMPD.+ was only 4 x 10(-6) the DMPD concentration, as long as ferrihemoglobin was low. At increasing ferrihemoglobin higher steady state concentrations of the radical are attained. In fact, preformed ferrihemoglobin in red cells significantly accelerated DMPD and glutathione disappearance. This effect was completely prevented in the presence of ferrihemoglobin-complexing cyanide. The presented experiments once more appoint blood as a metabolically competent organ for the biotransformation of aromatic amines.

Erythrocytes↗

PubMed1992

Oxygen-dissociation kinetics in the blood of smokers and non-smokers: interaction between oxygen and carbon monoxide at the hemoglobin molecule.

The importance of smoking as a possible factor in coronary heart disease (CHD) may be related to the effect of carbon monoxide (CO) on oxygen exchange at the hemoglobin molecule (Hb). We examined the kinetics of this process in vitro and ex vivo using a fast-reaction technique (stopped-flow) whereby the dissociation-rate constant of oxygen was determined in the blood of smokers and non-smokers and at fixed HbCO-concentrations in non-smokers blood. In non-smokers, carbon monoxide saturated blood was obtained by gassing with carbon monoxide and mixing the samples with appropriate carbon monoxide free blood to achieve HbCO-concentration in the range of 10-60%. The reaction time course for the oxygen-dissociation was divided into a non-linear-initial phase (loss of the first oxygen molecule) and a subsequent linear phase. The oxygen-dissociation velocity decreased from 96.5 x 10(3) ms-1 to 42.7 x 10(3) ms-1 in the linear phase at pH 7.4 and decreased from 29.2 x 10(3) ms-1 to 20.9 x 10(3) ms-1 at pH 9.2 when the HbCO-concentration was increased to 63%. For the initial phase at pH 7.4, the dissociation velocity decreased depending on the HbCO-concentration. In non-smokers 50% of the bound oxygen was released in 17.5 +/- 2.3 ms (n = 13) whereas in smokers 19.4 +/- 1.8 ms (n = 14) (p less than 0.05) was required.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

HLö 7 dimethanesulfonate, a potent bispyridinium-dioxime against anticholinesterases.

HLö 7 dimethanesulfonate (1-[[[4-(aminocarbonyl)pyridinio]methoxy]methyl]-2,4-bis [(hydroxyimino)methyl]pyridinium dimethanesulfonate) is a broad-spectrum reactivator against highly toxic organophosphorus compounds. The compound was synthesized by a new route with the carcinogenic bis(chloromethyl)ether being substituted by the non-mutagenic bis(methylsulfonoxymethyl)ether. The very soluble dimethanesulfonate of obidoxime was also prepared by this way. HLö 7 dimethanesulfonate is the first water-soluble salt of HLö 7 that should be suitable for the wet/dry autoinjector technology, because aqueous solutions of HLö 7 are not very stable (calculated shelf-life 0.2 years when stored at 8 degrees C, 1 M solution, pH 2.5). The crystalline preparation contains 96% of the syn/syn-isomer, less than 2% of the syn/anti-isomer and some minor identified by-products. HLö 7 was very efficient in reactivating acetylcholinesterase (AChE) blocked by organophosphates as long as ageing did not prevent dephosphylation. HLö 7 was superior to HI 6 (1-[[[4-(aminocarbonyl)pyridinio]methoxy]methyl]-2- [(hydroxyimino)methyl]pyridinium dichloride) in reactivating soman and sarin-inhibited AChE from erythrocytes, and literature data indicate that HLö 7 exceeds HI 6 by far in reactivating tabun-inhibited AChE. In atropine-protected, soman-poisoned mice HLö 7 was three times more potent than HI 6 (protective ratio 5 versus 2.5), and in sarin-poisoned mice HLö 7 was 10 times more potent than HI 6 (protective ratio 8 for both oximes). In atropine-protected guinea-pigs HLö 7 was less effective than HI 6 (protective ratio: 2.3 versus 5.2 for soman; 5.2 versus 6.8 for sarin; 4.3 versus 3.8 for tabun). The mean survival time of anaesthetized guinea-pigs exposed to 5 LD50 soman (6.3 min) was increased by atropine (27 min) and atropine + HLö (57 min). HLö 7 alone did not prolong the survival. The most impressive effect of HLö 7 was on respiration: 3 min after i.v. injection of HLö 7 and atropine, the depressed respiration increased rapidly to 60% of control and remained at that level during the observation period (60 min). With atropine alone, respiration recovered only slowly. Behavioural and physiologic parameters were determined in atropine-protected mice exposed to a sublethal soman dose. The running performance was significantly improved by HLö 7. Even central symptoms, e.g. hypothermia and convulsions, were decreased markedly by HLö 7 (evaluation 60 min after poisoning). The pharmacokinetic data for HLö 7 in male beagle dogs are similar to those of HI 6.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1992

Quantitative determination by ESR of the arylaminyl free radical during the reaction of N,N,N',N'-tetramethyl-p-phenylenediamine with oxyhemoglobin.

Aromatic amines with electron-donating substituents are directly activated by pure oxyhemoglobin with formation of ferrihemoglobin. Of these xenobiotics the N-alkylated p-phenylenediamines are particularly active. With N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) cooxidation with oxyhemoglobin was observed by ESR spectroscopy with formation of the arylaminyl free radical (TMPD+*). Since the radical is rapidly reduced by ferrohemoglobin, a catalytic cycle of ferrihemoglobin formation is sustained with initially very low steady-state concentrations of the radical, e.g. below 0.1%. Ferrihemoglobin is also able to oxidize TMPD to the radical, hence the steady-state concentration of TMPD+* rises with increasing ferrihemoglobin. Radicals of the Wurster's type tend to disproportionate at high rates generating reactive quinonediiminium cations which oxidize and arylate cellular thiols like GSH and protein SH groups. Because the disproportionation rate depends on the square of the radical concentration, quenching of the radicals by ferrohemoglobin to protect cellular thiols will be effective as long as the capacity of the methemoglobin reductase system is not overwhelmed. The results indicate that erythrocytes may play a critical role in activation and detoxication of p-phenylenediamines.

Biotransformation↗

PubMed1991

[Oral administration of activated charcoal-sorbitol suspension as first aid in prevention of poison resorption?].

Due to its paramount adsorption capacity, activated charcoal is supposed to be the remedy of choice for binding a variety of drugs in the gastrointestinal tract. Hence it is surprising--at least according to the advice of German textbooks--that activated charcoal is only recommended for administration after time-consuming treatments like induced emesis and gastric lavage. Particularly with infants at home, a ready-for-use suspension of activated charcoal would allow the early management of acute poisoning. In such cases, inactivation of the poison by adsorption could be particularly helpful, since the period after ingestion is usually short. The charcoal-sorbitol-suspension (30 g activated charcoal in 150 ml of 70% sorbitol) is a creamy preparation which is easy to drink, because density and viscosity prevent sedimentation. The prescription-free drugs can be dispensed by each pharmacist. The present study was undertaken to investigate the influence of sorbitol on the adsorption capacity of activated charcoal. To this end, adsorption isotherms were established in vitro and compared with results in volunteers to whom NAPAP, diphenhydramine or codeine was administered separately. These drugs are gaining increasing importance in medicinal toxicology since they are constituents of various analgesics and cold remedies. To determine absorption, the cumulative urinary excretion was estimated of the parent drugs and their main metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗

PubMed1991

Effects of superoxide dismutase on the autoxidation of 1,4-hydroquinone.

During autoxidation of 1,4-hydroquinone (H2Q, less than 1 mM) at pH 7.4 and 37 degrees C, stoichiometric amounts of 1,4-benzoquinone (Q) and hydrogen peroxide were formed during the initial reaction. The reaction kinetics showed a significant induction period which was abolished by minute amounts of Q. Hydrogen peroxide and catalase were without effect on the autoxidation process. Transition metals apparently were not involved, since chelators like EDTA, DETAPAC, and desferrioxamine or FeSO4 had no influence on the autoxidation kinetics. Superoxide dismutase (SOD) did not abolish the induction period but dramatically enhanced the autoxidation rate by more than two orders of magnitude. The stimulatory effect was first-order in SOD concentration but showed saturation kinetics. The dependence of Q and hydrogen peroxide formation rates on H2Q concentration shows a biphasic behaviour: dependence on the square at low H2Q, but on the square root at high H2Q concentration. As revealed by calculatory simulations the results can be adequately described by the known reaction rate constants. The reaction starts with the comproportionation of H2Q and Q to yield two semiquinone molecules which autoxidize to give two superoxide radicals and two molecules of Q which enter into a new cycle of comproportionation. Because of unfavourable equilibria the autocatalytic reaction soon comes to steady state, and the further reaction is governed by the rate of superoxide removal. At excess SOD, the comproportionation reaction is rate-limiting, thus explaining the saturation effects of SOD. The experiments do not allow a decision between the two functions of SOD; the conventional action as a superoxide:superoxide oxidoreductase or as a semiquinone:superoxide oxidoreductase. In the latter reaction SOD is thought to be reduced by semiquinone with Q formation. In the second step the reduced enzyme would be re-oxidized by a superoxide radical which is formed during autoxidation of the second semiquinone molecule generated in the comproportionation reaction. From thermodynamic considerations, the latter function of SOD appears to be plausible.

Benzoquinones↗

PubMed1991

Formation and reactions of the Wurster's blue radical cation during the reaction of N,N,N',N'-tetramethyl-p-phenylenediamine with oxyhemoglobin.

The aromatic amine N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) reacted directly with oxyhemoglobin in a catalytic reaction resulting in formation of ferrihemoglobin. The second order rate constant of the reaction was found to be 5.5 M-1.s-1. The stable Wurster's blue radical cation produced ferrihemoglobin at rates greater 10(3) M-1.s-1, i.e. more than two orders of magnitude faster than the parent amine. In contrast to the reactions of aminophenols with hemoglobin, free hydrogen peroxide was formed which additionally contributed to ferrihemoglobin formation. Since ferrihemoglobin formation proceeded by two orders of magnitude faster than autoxidation of TMPD, oxyhemoglobin itself acted as an oxidase/peroxidase resulting in electron abstraction from the amino alone pair electrons.

Cations↗

PubMed1991

Reactions of the Wurster's blue radical cation with thiols, and some properties of the reaction products.

Formation of 1-electron oxidation products of aromatic amines in biological systems have been ascertained. The mechanisms of the toxic actions of the aminyl radicals and their corresponding detoxication reactions are much less established. During the studies of reactions of GSH with the N,N,N',N'-tetramethyl-p-phenylenediamine radical cation (TMPD) (Wurster's blue) two pathways were detected: (1) a slow second order reaction (k = 5 M-1.s-1) which gave the parent amine and (ultimately) GSSG, and (2) a fast, complex reaction which yielded 2-(glutathione-S-yl)-N,N,N',N'-tetramethyl-p-phenylenediamine (2-GS-TMPD). From kinetic reasons, this reaction was suggested to be composed of a rapid disproportionation reaction followed by a reductive 1,4-Michael-addition. This reaction pathway prevailed at GSH concentrations below 1 mM. At higher GSH concentrations formation of the thioether was suppressed. This hypothesis was confirmed when the reaction of the highly labile N,N,N',N'-tetramethyl-p-quinonediiminium dication (TMQDI++) with GSH was followed: In this case, thioether formation outweighed clearly reductive mechanisms, the latter yielding ultimately the amine and GSSG. Similar to N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD), 2-GS-TMPD was also capable of producing ferrihemoglobin in a catalytic reaction. Its rate, however, was only 3% that observed with the parent amine. During this reaction the thioether was apparently oxidized to the corresponding quinonediiminium dication, which gave the corresponding quinonemonoimine on acidification.

Cations↗

PubMed1990

Formation of hydrogen peroxide during precipitation of red cells with perchloric acid. A cautionary note for precise determination of pyruvate, GSH, and NAD(P)H.

The instability of pyruvate in neutralized perchloric acid extracts of erythrocytes is well-known from the literature. As shown in this study, the main reason for this phenomenon is a reaction of pyruvate with hydrogen peroxide, which is formed from oxyhemoglobin during acid precipitation. Thereby, pyruvate is oxidized to carbon dioxide and acetate. This decomposition is easily prevented by addition of catalase to the neutralized extracts, whereby authentic pyruvate can be determined precisely. Similarly, GSH and NAD(P)H oxidation in the extracts is prevented by addition of catalase.

Chemical Precipitation↗

PubMed1990

On the mechanism of hydrogen peroxide formation during precipitation of hemoglobin with perchloric acid.

During acid precipitation of hemoglobin, hydrogen peroxide is formed. The oxidant is generated from hemoglobin-bound as well as from physically dissolved oxygen, provided divalent hemoglobin-iron is present. The extent of hydrogen peroxide formation seems to be dependent on the precipitating reagent. From experiments on GSH oxidation during precipitation of red cells and from a literature survey formation of at least one second reactive oxygen species has to be assumed. Different reaction pathways for generating these oxidants during acid precipitation are discussed: Hydroperoxide which is probably liberated by proton catalysis may contribute to the observed oxidation reactions. At pH approximately 1 it rapidly disproportionates yielding oxygen and hydrogen peroxide, which might produce reactive oxidants with hemoglobin intermediates formed during precipitation. In addition a new hypothesis is presented explaining the ability of N-ethylmaleimide to inhibit GSH oxidation during precipitation of red cells. Accordingly, the SH-reagent rapidly penetrates the cell membrane and reacts with GSH before access of protons prevents alkylation.

Chemical Precipitation↗

PubMed1990

Activation and detoxication of aminophenols. II. Synthesis and structural elucidation of various thiol addition products of 1,4-benzoquinoneimine and N-acetyl-1,4-benzoquinoneimine.

1. Nine thioethers of 4-aminophenol with beta-hydroxyethylmercaptan, ranging from mono- to tetra-substituted thioadducts, were prepared from synthetic 1,4-benzoquinoneimine and characterized by 1H-n.m.r. and u.v. spectroscopy. For each compound, extinction coefficients and pKa values of the amino group were determined. 2. Five thioethers of 4-aminophenol with glutathione (GSH) were prepared and characterized by 1H-n.m.r. and u.v. spectroscopy with their respective extinction coefficients and pKa values. Two further thioadducts were tentatively assigned by their u.v. spectroscopic properties. 3. Reaction products of 1,4-[U-14C]benzoquinoneimine and GSH were studied, indicating formation of 4-amino-2-(glutathione-S-yl)phenol, 4-amino-2,3,6-tris(glutathione-S-yl)phenol as the main products. Formation of glutathione disulphide (GSSG) was not detected. In contrast, N-acetyl-1,4-[U-14C]benzoquinoneimine was partly reduced by GSH and formed only the 2-substituted thioadduct. 4. Investigation of the product orientation in the reductive addition of GSH to 2-(glutathione-S-yl)-1,4-benzoquinoneimine and 3-(glutathione-S-yl)-1,4-benzoquinoneimine, respectively, showed that the 3-substituted derivative formed mainly the 3,5-di-substituted thioadduct, whereas the 2-substituted compound formed mainly the 2,3,6-tri-substituted thioadduct. 5. Formation of thioadducts which autoxidize markedly faster than the parent aminophenol indicates that thioether formation is not an obligatory detoxication process.

Aminophenols↗

PubMed1990

Activation and detoxication of aminophenols. III. Synthesis and structural elucidation of various glutathione addition products to 1,4-benzoquinone.

1. Four thioethers of 1,4-hydroquinone with glutathione (GSH) were prepared from 1,4-benzoquinone and characterized by 1H-n.m.r. and partly by 13C-n.m.r. spectroscopy. The structures of three additional thioethers were tentatively assigned by u.v. spectroscopy. 2. The corresponding thioethers of 1,4-benzoquinone with GSH were obtained by oxidation of the corresponding 1,4-hydroquinone thioadducts with PbO2 or potassium ferricyanide. 3. Relative redox potentials of the hydroquinone/benzoquinone thioethers were estimated by determination of their redox equilibria with benzoquinone/hydroquinone. The redox potential of the mono-substituted derivative was 30 mV lower, and that of the di-substituted derivatives 70 mV lower, than that of the unsubstituted couple, thus explaining the readiness of sequential oxidation and addition reactions of the produced thioethers. 4. By use of 1,4-[U-14C]benzoquinone the reaction products with GSH were quantified to elucidate the product orientation. As observed with 1,4-benzoquinoneimine and its thioethers, formation of GSSG was not detected at physiological pH. 5. The high susceptibility of particular thioethers of 1,4-hydroquinone towards (aut)oxidation characterizes these products as reactive intermediates rather than as definitive detoxication products.

Aminophenols↗

PubMed1990

Aniline-, phenylhydroxylamine-, nitrosobenzene-, and nitrobenzene-induced hemoglobin thiyl free radical formation in vivo and in vitro.

We have employed the ESR spin trapping technique in vivo to detect the formation of the 5,5-dimethyl-1-pyrroline-N-oxide (DMPO)/hemoglobin thiyl free radical adduct in the blood of rats following administration of either aniline, phenylhydroxylamine, nitrosobenzene, or nitrobenzene. This DMPO adduct was a six-line, strongly immobilized, radical adduct. Using rat red blood cells, both phenylhydroxylamine and nitrosobenzene were able to induce the formation of the DMPO/glutathiyl free radical adduct and the same DMPO/hemoglobin thiyl free radical adduct was detected in in vivo samples. In experiments using purified rat oxyhemoglobin, a four-line, weakly immobilized, DMPO/hemoglobin thiyl free radical adduct was detected, in addition to the six-line strongly immobilized adduct. When this study was repeated using human red blood cells, we detected only the DMPO/glutathiyl free radical adduct and, when purified human oxyhemoglobin was employed, only the four-line, weakly immobilized, DMPO/hemoglobin thiyl radical adduct could be detected. In a study using reduced glutathione, we found that phenylhydronitroxide free radicals were reduced by glutathione and that glutathione was concomitantly oxidized to its thiyl free radical. We propose that the species responsible for the oxidation of the thiols to yield the thiyl free radicals in vivo and in vitro was the phenylhydronitroxide radical produced from the reaction of phenylhydroxylamine with oxyhemoglobin.

Aniline Compounds↗

PubMed1989

Depletion of mitochondrial coenzyme A and glutathione by 4-dimethylaminophenol and formation of mixed thioethers.

4-Dimethylaminophenol (DMAP), an antidote in cyanide poisoning, has been shown to produce kidney lesions in rats, to damage isolated rat kidney tubules and to impair mitochondrial functions as already described for 4-aminophenol. Since DMAP upon oxidation forms bis- and tris-substituted thioethers with GSH, it was anticipated that mitochondrial toxicity of DMAP might result from CoA depletion. In a model reaction DMAP was oxidized by oxyhemoglobin in the presence of CoA and GSH resulting in formation of tris-(CoA-S-yl)-DMAP, tris-(GSH-S-yl)-DMAP and two mixed thioethers, namely, (CoA-S-yl)-bis-(GSH-S-yl)-DMAP and (GSH-S-yl)-bis-(CoA-S-yl)-DMAP. The compounds were isolated by HPLC and identified spectroscopically, by amino acid analysis and Raney-Nickel desulfuration. Rat liver mitochondria (5 mg protein/ml) incubated under state IV conditions with 20 and 50 microM DMAP were depleted of GSH and total coenzyme A with formation of GSSG and the above-mentioned thioethers which were quantified by isotope dilution techniques using [14C]-labelled DMAP and the isolated, inactive thioethers. The results confirm earlier suggestions that part of the cytotoxicity of DMAP may result from depletion of vital mitochondrial thiols, particularly CoA. Since 4-aminophenol reacts analogously, similar cytotoxic effects can be expected from compounds which on (aut)oxidation form quinoid systems capable of 1.4-addition reactions with nucleophilic thiols.

Aminophenols↗

PubMed1989

Thioether formation--activation or detoxication?

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Acetylation↗

PubMed1989

Studies on the stability and decomposition of the Hagedorn-oxime HLö 7 in aqueous solution.

HLö 7, (pyridinium, 1-[[[4-(aminoarbonyl)pyridinio]methoxy]methyl] -2,4-bis- [(hydroxyimino)methyl] diiodide) has been shown to be efficacious in soman poisoning of mice even in the absence of atropine. To assess possible risks involved in the administration of HLö 7 its degradation products were analyzed at pH 2.5 and pH 7.4, respectively. At pH 2.5, where HLö 7 in aqueous solution was assumed to possess maximal stability, the predicted shelf life (10% decomposition) was about 8 years for 10 mM solutions at 8 degrees C. The apparent energy of activation was 117 kJ/mol. At pH 2.5, attack on the aminal-acetal bond predominated with formation of pyridine-2,4-dialdoxime, 2-cyanopyridine-4-aldoxime, isonicotinamide, and formaldehyde. At pH 7.4, primary attack on the 2-aldoxime group resulted in formation of an intermediate 2-cyano-4-aldoxime derivative which mainly decomposed into cyanide and the corresponding 2-pyridinone, 1-[[[4-(aminocarbonyl)-pyridinio]methoxy]methyl]-4- [(hydroxyimino)methyl] diiodide. In addition, liberated cyanide reacted with the intermediate 2-cyano-4-aldoxime derivative with formation of 2-pyridinone, 1-[[[4-(aminocarbonyl)-pyridinio]-methoxy]methyl]-6-cyano-4- [(hydroxyimino)methyl] diiodide. This cyanide sequestering pathway became significant only at high concentrations (10 mM) of HLö 7, and was marginal at 1 mM HLö 7.

Chromatography, High Pressure Liquid↗

PubMed1988

Study on the stability of the oxime HI 6 in aqueous solution.

HI 6 (Pyridinium, 1-[[[4-(aminocarbonyl)pyridinio]methoxy]methyl]-2-[(hydro xyimino) methyl]-dichloride is an effective antidote against poisoning with extremely toxic organophosphates. Because of conflicting reports on the stability of HI 6 in aqueous solutions, we studied the factors influencing its stability. HI 6 has been shown to be most stable in acidic solution between pH 2 and 3. At that pH, HI 6 decomposes probably by attack of nucleophiles on the methylene carbon atom of the animal-acetal bond of the "ether bridge". HI 6 decomposition follows first order kinetics. From Arrhenius plots of the decay of HI 6 at various concentrations it became obvious that the rate of decomposition increased with increasing HI 6 concentration with simultaneous decrease in the energy of activation. To decide whether the pyridinium compound itself or its anions are responsible for the enhanced decomposition, we studied the influence of chloride, phosphate and iodide. These anions stimulated the decay of HI 6 at increasing strength; their effect, however, was small as compared to that brought about by the pyridinium oxime itself. Since 1-methylisonicotinamide chloride had virtually no effect in contrast to 1-methylpyridinium-2-aldoxime chloride, we conclude that the oximate anion is responsible for the intermolecular attack on HI 6. At present, we recommend storage of HI 6 at concentrations not exceeding 0.1 M in aqueous solution at pH 2.5 and low temperatures. Under these conditions an apparent shelf-life of 20 years is calculated when HI 6 is stored at 8 degrees C.

Cholinesterase Reactivators↗

PubMed1988

Detoxication of N-oxygenated arylamines in erythrocytes. An overview.

1. Reactive N-oxygenated arylamines, namely, N-hydroxyarylamines and nitrosoarenes, are toxic, mutagenic, carcinogenic and allergenic. 2. Erythrocytes are a very sensitive target for these compounds, but little is known of the detoxication capacity of these cells. 3. This overview considers the most important reactions of p-substituted N-oxygenated arylamines in red cells, namely, (i) ferrihaemoglobin formation by N-hydroxyarylamines with concomitant co-oxidation to nitrosoarenes; (ii) compartmentation of nitrosobenzenes by ligation to deoxyhaemoglobin, (iii) reactions of nitrosobenzene with glutathione, (iv) adduct formation of nitrosobenzenes with thiol groups of haemoglobin. 4. To predict the metabolic fate of N-oxygenated arylamines in red cells, the respective kinetic parameters of reactions (i) to (iv) have been determined, and indicate good linear free energy correlations (pH 7.4, 37 degrees C). These data may help to estimate the detoxication capacity of erythrocytes in vivo.

Aniline Compounds↗