formamide OR C031066
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The end of the late heavy bombardment era coincides with the emergence of life on the Earth 4 billion years ago. This coincidence suggests that the impacts of extraterrestrial bodies might have contributed to the formation of the first molecules involved in early living structures. We have simulated a high-energy synthesis of nucleic acid bases from formamide in the impact of an extraterrestrial body. The high-power laser system PALS was employed in simulation of impact plasma by inducing a laser dielectric breakdown in formamide. In hot and dense plasma, formamide decomposed producing reactive radicals. The radicals reacted with formamide and nucleic acid bases were produced. Formamide was pretreated with laser plasma in the presence of catalysts. The products were analyzed by FTIR spectrometry and GC-MS. Time-resolved emission spectra of formamide discharge plasma were measured. Kinetic models and formation pathways for nucleic acid bases were calculated. The results show that the nucleic acid bases can be synthesized in impact plasma involving CN and NH radicals and formamide.
- MeSH
- biogeneze organel MeSH
- formamidy * chemie MeSH
- katalýza MeSH
- lasery využití MeSH
- nukleové kyseliny * chemie MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí přístrojové vybavení MeSH
- spektroskopie infračervená s Fourierovou transformací přístrojové vybavení MeSH
- Země (planeta) MeSH
Synthesis of RNA nucleobases from formamide is one of the recurring topics of prebiotic chemistry research. Earlier reports suggest that thymine, the substitute for uracil in DNA, may also be synthesized from formamide in the presence of catalysts enabling conversion of formamide to formaldehyde. In the current paper, we show that to a lesser extent conversion of uracil to thymine may occur even in the absence of catalysts. This is enabled by the presence of formic acid in the reaction mixture that forms as the hydrolysis product of formamide. Under the reaction conditions of our study, the disproportionation of formic acid may produce formaldehyde that hydroxymethylates uracil in the first step of the conversion process. The experiments are supplemented by quantum chemical modeling of the reaction pathway, supporting the plausibility of the mechanism suggested by Saladino and coworkers.
N,N-dimethylformamide, a nucleophilic aprotic dipolar solvent, has multipurpose uses, especially in the manufacture of plastics. Its acute toxicity for mammals is low; it is hepatotoxic. Vapors are absorbed by the lungs, in the liquid form it causes cutaneous maceration and is rapidly absorbed through the skin. In the organism it is primarily metabolized to N-monomethylformamide, to a lesser extent to formamide. Urine of individuals exposed to N,N-dimethylformamide was newly found to have higher levels of thioethers, most likely mercapturates, as yet of unknown chemical structure. The correlation between the urinary concentrations of mercapturates (y) and N-monomethylformamide (x) can be expressed by equation y = 4.93 + 0.58 x, with the coefficient of correlation r = 0.90. Part of N,N-dimethylformamide metabolites is likely to react with biopolymers, part of it is excreted as metabolic end products, i.e. carbon dioxide, water and urea. Breakdown to mercapturates may implicate N,N-dimethylformamide as being a potential carcinogen.
- MeSH
- acetylcystein metabolismus moč MeSH
- biotransformace MeSH
- dimethylformamid škodlivé účinky MeSH
- formamidy moč MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Excretion of N,N-dimethylformamide (DMF) and DMF metabolites N-hydroxymethyl-N-methylformamide ("MF"), N-hydroxymethyl-formamide ("F") and N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC) has been monitored in the urine of volunteers during and after their 8-h exposure to DMF vapour at a concentration of 10, 30 and 60 mg.m-3. The pulmonary ventilation in these experiments was typically about 10 l.min-1 and the retention in the respiratory tract was 90%. After exposure to 30mg DMF.m-3, the yield of compound determined in the urine represented 0.3% (DMF), 22.3% ("MF"), 13.2% ("F") and 13.4% (AMCC) of the dose absorbed via the respiratory tract. The excretion curves of the particular compounds attained their maximum 6-8h (DMF), 6-8h ("MF"), 8-14h ("F") and 24-34h (AMCC) after the start of the exposure. The half-times of excretion were approximately 2, 4, 7 and 23 h respectively. In contrast to slow elimination of AMCC after exposure to DMF, AMCC was eliminated rapidly after AMCC intake. This discrepancy could be explained by rate-limiting reversible protein binding of a reactive metabolic intermediate of DMF, possibly methylisocyanate.
- MeSH
- absorpce MeSH
- acetylcystein analogy a deriváty moč MeSH
- dimethylformamid analogy a deriváty farmakokinetika metabolismus MeSH
- dospělí MeSH
- formamidy metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- plíce fyziologie metabolismus MeSH
- rozpouštědla farmakokinetika metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
Dimethylformamide (DMF) is an industrial solvent with hepatotoxic properties. The toxicity of DMF has been associated with its metabolism to S-(N-methylcarbamoyl)glutathione (SMG). The major urinary metabolite of DMF is N-(hydroxymethyl)-N-methylformamide (HMMF). HMMF undergoes oxidation in the formyl moiety, possibly via the intermediacy of its hydrolysis product N-methylformamide (NMF), and the reactive intermediate thus generated reacts with glutathione to yield SMG. Experiments were conducted to elucidate enzymatic details of the metabolism of DMF. Generation of HMMF from DMF in microsomes from rats which had received acetone, an inducer of cytochrome P450 2E1, was increased by 175% over that observed in control microsomes. In liver microsomes from 4 humans the metabolism of DMF to HMMF was inhibited by a monospecific antibody against rat liver P450 2E1, and the metabolic rates were correlated with those of NMF to SMG, a process known to be mediated via P450 2E1. DMF was also metabolized by purified rat liver P450 2E1. The kinetic parameters which characterize the metabolism of DMF or its deuterated isotopomers to the respective HMMF isotopomers, of HMMF to SMG and of NMF to SMG in liver microsomes, were computed from Eadie-Hofstee plots. The affinity of DMF for the metabolizing enzyme in rat liver microsomes is considerably higher (apparent Km = 0.20 mM) than that of NMF (Km = 4.28 mM) or of HMMF (Km = 2.52 mM). The respective values observed with human microsomes are very similar. The apparent Km values for the N-methyl oxidation of N,N-dimethyldeuterioformamide ([2H1]DMF) and N,N-bis(trideuteriomethyl)formamide ([2H6]DMF) in rat microsomes are 0.14 and 0.21 mM, respectively. The apparent Vmax for the oxidation of [2H1]DMF is similar to that computed for DMF, and the Vmax for [2H6]DMF is less than half of that computed for DMF. The kinetic deuterium isotope effect (KDIE) on DMF metabolism was determined in incubations with rat microsomes in three ways: (i) the noncompetitive intermolecular KDIE by the ratio of Vmax/Km for DMF to Vmax/Km for [2H6]DMF, (ii) the competitive intermolecular KDIE as the quotient of metabolic products HMMF to N-(hydroxydideuteriomethyl)-N-(trideuteriomethyl)formamide in incubations of DMF together with [2H6]DMF, and (iii) the intramolecular KDIE as the quotient of the ratio of N-(hydroxymethyl)-N-(trideuteriomethyl)formamide to N-(hydroxydideuteriomethyl)-N-methylformamide generated from N-(trideuteriomethyl)-N-methylformamide ([2H3]DMF). The respective values were found to be (i) 2.4, (ii) 5.0, and (iii) 5.2. DMF inhibited the oxidation of NMF or HMMF to SMG.(ABSTRACT TRUNCATED AT 400 WORDS)
- MeSH
- amidy metabolismus MeSH
- chromatografie plynová MeSH
- dimethylformamid farmakokinetika metabolismus toxicita MeSH
- isomerie MeSH
- jaterní mikrozomy enzymologie účinky léků MeSH
- kinetika MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- oxidace-redukce MeSH
- potkani Sprague-Dawley MeSH
- systém (enzymů) cytochromů P-450 * biosyntéza MeSH
- techniky in vitro MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
