Abiotic transformations and decomposition kinetics of 4-carbamoyl-2'-[(hydroxyimino)methyl]-1,1'-(oxydimethylene)-bis(pyridin ium chloride) in aqueous phosphate buffers
| Autor: | Donald J. Ecobichon, Raymond E. Mdachi, Celso E. Connolley-Mendoza, F. M. Fouad, W. D. Marshall |
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| Rok vydání: | 1990 |
| Předmět: |
Cholinesterase Reactivators
Pyridinium Compounds Inorganic chemistry Antidotes Buffers Toxicology Isonicotinic acid Medicinal chemistry Chloride Phosphates chemistry.chemical_compound Drug Stability Amide Oximes medicine Isonicotinamide Aqueous solution Temperature General Medicine Hydrogen-Ion Concentration Oxime Kinetics chemistry Pyridinium medicine.drug |
| Zdroj: | Chemical research in toxicology. 3(5) |
| ISSN: | 0893-228X |
| Popis: | The rate of disappearance of 4-carbamoyl-2'-[(hydroxyimino)methyl]-1,1'-(oxydimethylene) bis (pyridinium chloride) (HI-6) from aqueous phosphate buffers (pH 3.0-9.1) was both pH and temperature sensitive. In midrange buffers (pH 6.0-9.1, mu = 0.2 M) at 37, 25, or 4 degrees C the decomposition followed first-order kinetics consistent with hydroxide-promoted decomposition of the un-ionized drug or with hydrolysis of the ionized oxime anion to result in 4-carbamoyl-2'-hydroxy-1,1'-(oxydimethylene)bis(pyridinium) cation (intermediate 1). The subsequent conversion of intermediate 1 to 4-carboxy-2'-hydroxy-1,1'-(oxydimethylene)bis(pyridinium) cation (intermediate 2) followed higher order kinetics which were consistent with either acid- or base-promoted hydrolysis of the B-ring amide functionality. After approximately 138 days in the dark, the sum of the residual HI-6, intermediate 1, and intermediate 2 in the crude decomposition mixture accounted for 89.9 +/- 10.0% of the initial substrate. Minor byproducts included 4-carbamoyl-2'-carboxy-1,1'-(oxydimethylene)bis(pyridinium) cation, 2-pyridinealdoxime, 2-pyridinecarboxaldehyde, 2-hydroxypyridine, isonicotinamide, isonicotinic acid, and traces of cyanide. In addition, 2-cyanopyridine appeared to be a transient intermediate in more alkaline media. In total, this drug resembles other mono- and bis(pyridinium) aldoximes in terms of the decomposition routes in aqueous solutions at intermediate pHs. |
| Databáze: | OpenAIRE |
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