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ENeurologicalSci Jun 2024A case-control study of sporadic amyotrophic lateral sclerosis (ALS) in a mountainous village in the French Alps discovered an association of cases with a history of...
A case-control study of sporadic amyotrophic lateral sclerosis (ALS) in a mountainous village in the French Alps discovered an association of cases with a history of eating wild fungi (false morels) collected locally and initially identified and erroneously reported as . Specialist re-examination of dried specimens of the ALS-associated fungi demonstrated they were members of the group, namely , species that have been reported to contain substantially higher concentrations of gyromitrin than present in . Gyromitrin is metabolized to monomethylhydrazine, which is responsible not only for the acute oral toxic and neurotoxic properties of false morels but also has genotoxic potential with proposed mechanistic relevance to the etiology of neurodegenerative disease. Most ALS patients had a slow- or intermediate-acetylator phenotype predicted by - () genotyping, which would increase the risk for neurotoxic and genotoxic effects of gyromitrin metabolites.
PubMed: 38770222
DOI: 10.1016/j.ensci.2024.100502 -
Heliyon Mar 2023N- Nitrosodimethyl amine, the simplest member of the N-Nitrosamine family, is a carcinogenic and mutagenic agent that has gained considerable research interest owing to...
N- Nitrosodimethyl amine, the simplest member of the N-Nitrosamine family, is a carcinogenic and mutagenic agent that has gained considerable research interest owing to its toxic nature. Ozonation of industrially important hydrazines, such as unsymmetrical dimethylhydrazine (UDMH) or monomethylhydrazine (MMH), has been associated with NDMA formation and accumulation in the environment. UDMH/MMH - ozonation also leads to several other transformation products such as acetaldehyde dimethyl hydrazine (ADMH), tetramethyl tetra azene (TMT), diazomethane, methyl diazene, etc, which can be either precursors or competitors for NDMA formation. However, the relevant chemistry detailing the formation of these transformation products from UDMH/MMH -ozone reaction and their subsequent conversion to NDMA is not well understood. In this work, we explored the formation mechanism of ADMH and TMT from UDMH-ozonation and their further oxidation to NDMA using the second-order Moller Plesset perturbation theory employing the 6-311G(d) basis set. We have also investigated how MMH selectively forms methyl diazene and diazomethane under normal conditions and NDMA in the presence of excess ozone. Our calculations indicate that the reactions proceed via an initial H abstraction from the hydrazine -NH group, followed by the oxidation of the generated N-radical species. The formation of ADMH from the UDMH-ozone reaction involves an acetaldehyde intermediate, which then reacts with a second UDMH molecule to generate ADMH. The preferable attack of ozone molecule on N=C bond of ADMH generates DMAN intermediate, which subsequently undergoes oxidation to form NDMA. Unlike other transformation products, TMT formation occurs via the dimerization of DMAN. Though there exists an N=N bond in the TMT, which are preferable attacking sites for ozone, experimental studies show the lower yields of NDMA formation, which corroborates with the high activation barrier required for the process (42 kcal/mol). Overall, our calculated results agree well with the experimental observations and rate constants. Computational calculations bring new insights into the electronic nature and kinetics of the elementary reactions of this pathway, enabled by computed energies of structures that are not possible to access experimentally.
PubMed: 36967895
DOI: 10.1016/j.heliyon.2023.e14511 -
Frontiers in Neuroscience 2023The identity and role of environmental factors in the etiology of sporadic amyotrophic lateral sclerosis (sALS) is poorly understood outside of three former... (Review)
Review
The identity and role of environmental factors in the etiology of sporadic amyotrophic lateral sclerosis (sALS) is poorly understood outside of three former high-incidence foci of Western Pacific ALS and a hotspot of sALS in the French Alps. In both instances, there is a strong association with exposure to DNA-damaging (genotoxic) chemicals years or decades prior to clinical onset of motor neuron disease. In light of this recent understanding, we discuss published geographic clusters of ALS, conjugal cases, single-affected twins, and young-onset cases in relation to their demographic, geographic and environmental associations but also whether, in theory, there was the possibility of exposure to genotoxic chemicals of natural or synthetic origin. Special opportunities to test for such exposures in sALS exist in southeast France, northwest Italy, Finland, the U.S. East North Central States, and in the U.S. Air Force and Space Force. Given the degree and timing of exposure to an environmental trigger of ALS may be related to the age at which the disease is expressed, research should focus on the lifetime exposome (from conception to clinical onset) of young sALS cases. Multidisciplinary research of this type may lead to the identification of ALS causation, mechanism, and primary prevention, as well as to early detection of impending ALS and pre-clinical treatment to slow development of this fatal neurological disease.
PubMed: 36860617
DOI: 10.3389/fnins.2023.1005096 -
Molecules (Basel, Switzerland) Nov 2020Recently discovered hybrid perovskites based on hypophosphite ligands are a promising class of compounds exhibiting unusual structural properties and providing...
Recently discovered hybrid perovskites based on hypophosphite ligands are a promising class of compounds exhibiting unusual structural properties and providing opportunities for construction of novel functional materials. Here, we report for the first time the detailed studies of phonon properties of manganese hypophosphite templated with methylhydrazinium cations ([CHNHNH][Mn(HPO)]). Its room temperature vibrational spectra were recorded for both polycrystalline sample and a single crystal. The proposed assignment based on Density Functional Theory (DFT) calculations of the observed vibrational modes is also presented. It is worth noting this is first report on polarized Raman measurements in this class of hybrid perovskites.
Topics: Calcium Compounds; Cations; Density Functional Theory; Ions; Manganese; Materials Testing; Microscopy, Confocal; Models, Molecular; Monomethylhydrazine; Oxides; Phosphites; Quantum Theory; Software; Spectrophotometry, Infrared; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis, Raman; Temperature; Titanium; Vibration
PubMed: 33182446
DOI: 10.3390/molecules25215215 -
Molecules (Basel, Switzerland) May 2012Sixteen novel pyrazole acyl thiourea derivatives 6 were synthesized from monomethylhydrazine (phenylhydrazine) and ethyl acetoacetate. The key...
Sixteen novel pyrazole acyl thiourea derivatives 6 were synthesized from monomethylhydrazine (phenylhydrazine) and ethyl acetoacetate. The key 5-chloro-3-methyl-1-substituted-1H-pyrazole-4-carbonyl chloride intermediates 4 were first generated in four steps through cyclization, formylation, oxidation and acylation. Thess were then reacted with ammonium thiocyanate in the presence of PEG-400 to afford 5-chloro-3-methyl-1-substituted-1H-pyrazole-4-carbonyl isothiocyanates 5. Subsequent reaction with fluorinated aromatic amines resulted in the formation of the title compounds. The synthesized compound were unequivocally characterized by IR, ¹H-NMR, ¹³C-NMR and elemental analysis and some of the synthesized compounds displayed good antifungal activities against Gibberella zeae, Fusarium oxysporum, Cytospora mandshurica and anti-TMV activity in preliminary antifungal activity tests.
Topics: Acetoacetates; Acylation; Antifungal Agents; Antiviral Agents; Cyclization; Fusarium; Gibberella; Hydrocarbons, Fluorinated; Microbial Sensitivity Tests; Oxidation-Reduction; Phenylhydrazines; Polyethylene Glycols; Pyrazoles; Structure-Activity Relationship; Thiocyanates; Thiourea; Tobacco Mosaic Virus
PubMed: 22555301
DOI: 10.3390/molecules17055139 -
Journal of the American Society For... May 2007Protonated ammonia and hydrazines (MH(+)) form complexes with ketones and the differences in masses and mobilities of the resulting ions, MH(+)(ketone)(n), are...
Protonated ammonia and hydrazines (MH(+)) form complexes with ketones and the differences in masses and mobilities of the resulting ions, MH(+)(ketone)(n), are sufficient for separation in an ion mobility spectrometer at ambient pressure. The highest mass ion for any of the protonated molecules is obtained when the ketone is present at elevated concentrations in the supporting atmosphere of both the source and drift regions of the spectrometer so that an ion maintains a discrete composition and mobility. The sizes of the ion-molecule complexes were found to depend on the number of H atoms on the protonated nitrogen atom--four for ammonia, three for hydrazine, two for monomethylhydrazine, and one for 1,1-dimethylhydrazine, and the drift times of these ions were proportional to the size of the ion-molecule complex. Unexpected side products, including protonated hydrazones and azines, and associated ketone clusters, were isolated to a single drift tube containing ceramic parts and could not, from CID studies, be attributed to gas-phase ion chemistry. These findings illustrate that mobility resolution of ions in IMS and IMS/MS experiments can be enhanced through chemical modification of the supporting gas atmosphere without changes in the core ion.
Topics: Air; Air Pressure; Ammonia; Hydrazines; Ketones; Mass Spectrometry; Protons
PubMed: 17376700
DOI: 10.1016/j.jasms.2007.01.014 -
Proceedings of the National Academy of... Oct 1999Soluble glucose dehydrogenase (s-GDH) from the bacterium Acinetobacter calcoaceticus is a classical quinoprotein. It requires the cofactor pyrroloquinoline quinone (PQQ)...
Soluble glucose dehydrogenase (s-GDH) from the bacterium Acinetobacter calcoaceticus is a classical quinoprotein. It requires the cofactor pyrroloquinoline quinone (PQQ) to catalyze the oxidation of glucose to gluconolactone. The precise catalytic role of PQQ in s-GDH and several other PQQ-dependent enzymes has remained controversial because of the absence of comprehensive structural data. We have determined the crystal structure of a ternary complex of s-GDH with PQQ and methylhydrazine, a competitive inhibitor of the enzyme. This complex, refined at 1.5-A resolution to an R factor of 16.7%, affords a detailed view of a cofactor-binding site of s-GDH. Moreover, it presents the first direct observation of covalent PQQ adduct in the active-site of a PQQ-dependent enzyme, thereby confirming previous evidence that the C5 carbonyl group of the cofactor is the most reactive moiety of PQQ.
Topics: Binding Sites; Crystallography, X-Ray; Glucose Dehydrogenases; Models, Chemical; Models, Molecular; Molecular Sequence Data; Monomethylhydrazine; Protein Binding; Protein Conformation; Quinolones; Quinones
PubMed: 10518528
DOI: 10.1073/pnas.96.21.11787 -
The American Journal of Pathology Oct 1996Folate deficiency enhances colorectal carcinogenesis in dimethylhydrazine-treated rats. Folate is an important mediator of DNA methylation, an epigenetic modification of...
Folate deficiency enhances colorectal carcinogenesis in dimethylhydrazine-treated rats. Folate is an important mediator of DNA methylation, an epigenetic modification of DNA that is known to be dysregulated in the early stages of colorectal cancer. This study investigated the effect of dimethylhydrazine on DNA methylation of the colonic p53 gene and the modulation of this effect by dietary folate. Sprague-Dawley rats were fed diets containing 0, 2, 8, or 40 mg of folate/kg of diet. Five weeks after diet initiation, dimethylhydrazine was injected weekly for fifteen weeks. Folate-depleted and folate-replete control animals did not receive dimethylhydrazine and were fed the 0- and 8-mg folate diets, respectively. The extent of p53 methylation was determined by a quantitative HpaII-polymerase chain reaction. In exons 6 and 7, significant p53 hypomethylation was observed in all dimethylhydrazine-treated rats relative to controls (P < 0.01), independent of dietary folate. In exon 8, significant p53 hypomethylation was observed only in the dimethylhydrazine-treated folate-depleted rats compared with controls (P = 0.038) and was effectively overcome by increasing levels of dietary folate (P = 0.008). In this model, dimethylhydrazine induces exon-specific p53 hypomethylation. In some exons, this occurs independent of dietary folate, and in others, increasing levels of dietary folate effectively override the induction of hypomethylation in a dose-responsive manner. This may be a mechanism by which increasing levels of dietary folate inhibit colorectal carcinogenesis.
Topics: Animals; Colon; Colorectal Neoplasms; DNA Methylation; Disease Models, Animal; Exons; Folic Acid; Genes, p53; Male; Monomethylhydrazine; Precancerous Conditions; Rats; Rats, Sprague-Dawley
PubMed: 8863662
DOI: No ID Found