dc.contributor.author |
Noszál, Béla |
|
dc.contributor.author |
Visky, Dóra |
|
dc.contributor.author |
Kraszni, Márta |
|
dc.date.accessioned |
2023-06-06T11:56:16Z |
|
dc.date.available |
2023-06-06T11:56:16Z |
|
dc.date.issued |
2000 |
|
dc.identifier |
0034212604 |
|
dc.identifier.citation |
journalVolume=43;journalIssueNumber=11;journalTitle=JOURNAL OF MEDICINAL CHEMISTRY;pagerange=2176-2182;journalAbbreviatedTitle=J MED CHEM; |
|
dc.identifier.uri |
http://repo.lib.semmelweis.hu//handle/123456789/9438 |
|
dc.identifier.uri |
doi:https://doi.org/10.1021/jm9909600 |
|
dc.description.abstract |
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. |
|
dc.format.extent |
2176-2182 |
|
dc.relation.ispartof |
urn:issn:0022-2623 |
|
dc.title |
Population, acid-base, and redox properties of N-acetylcysteine conformers |
|
dc.type |
Journal Article |
|
dc.date.updated |
2023-05-11T13:25:30Z |
|
dc.language.rfc3066 |
en |
|
dc.rights.holder |
NULL |
|
dc.identifier.mtmt |
1478242 |
|
dc.identifier.wos |
000087425700011 |
|
dc.identifier.pubmed |
10841796 |
|
dc.contributor.institution |
Gyógyszerészi Kémiai Intézet |
|
dc.mtmt.swordnote |
Chemicals/CAS: acetylcysteine, 616-91-1; disulfide, 16734-12-6; hydrogen, 12385-13-6, 1333-74-0;
Acetylcysteine, 616-91-1; Disulfides; Free Radical Scavengers; Sulfhydryl Compounds
Megjegyzés-21966279
Chemicals/CAS: acetylcysteine, 616-91-1; disulfide, 16734-12-6; hydrogen, 12385-13-6, 1333-74-0; Acetylcysteine, 616-91-1; Disulfides; Free Radical Scavengers; Sulfhydryl Compounds
Megjegyzés-21966323
Chemicals/CAS: acetylcysteine, 616-91-1; disulfide, 16734-12-6; hydrogen, 12385-13-6, 1333-74-0; Acetylcysteine, 616-91-1; Disulfides; Free Radical Scavengers; Sulfhydryl Compounds
Megjegyzés-21962096
Chemicals/CAS: acetylcysteine, 616-91-1; disulfide, 16734-12-6; hydrogen, 12385-13-6, 1333-74-0;
Acetylcysteine, 616-91-1; Disulfides; Free Radical Scavengers; Sulfhydryl Compounds |
|