Population, acid-base, and redox properties of N-acetylcysteine conformers
| Autor: | Márta Kraszni, Béla Noszál, D. Visky |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
chemistry.chemical_classification
Acid-Base Equilibrium education.field_of_study Stereochemistry Population Stereoisomerism Protonation Free Radical Scavengers Hydrogen-Ion Concentration Acetylcysteine chemistry.chemical_compound chemistry Computational chemistry Intramolecular force Drug Discovery Thiol Molecular Medicine Molecule Carboxylate Disulfides Sulfhydryl Compounds education Conformational isomerism Oxidation-Reduction |
| Zdroj: | Journal of medicinal chemistry. 43(11) |
| ISSN: | 0022-2623 |
| Popis: | Rotamers of N-acetyl-L-cysteine (NAC, the most popular mucolytic drug) are characterized in terms of populations, site- and conformer-specific acid-base properties, reducing strength, and molecular pharmacology. A new, general relationship between the bulk- and rotamer-specific basicities is introduced. NAC at high pH predominantly exists in a trans thiolate-carboxylate rotameric form, whereas protonation promotes the occurrence of intramolecular hydrogen bond-forming isomers. Distribution curves of the rotamers are depicted as a function of pH. Rotamer-dependent thiolate basicities differ by up to 0.5 log k units. Carboxylate basicities show slight conformation-dependence only. The membrane-penetrating capabilities from various compartments of the body are assessed on the basis of the pH-dependent charge of the molecule. The thiol-disulfide half-cell potential is calculated, using the correlation between the thiolate basicity and oxidizability. The oxidation-reduction properties of NAC are compared to those of other biological thiols in their definite microscopic forms. The pharmacokinetic behavior is interpreted in terms of the physicochemical parameters, providing molecular/submolecular explanation for several therapeutic properties of NAC. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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