Population, acid-base, and redox properties of N-acetylcysteine conformers

B. Noszál, Dóra Visky, Márta Kraszni

Research output: Contribution to journalArticle

56 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2176-2182
Number of pages7
JournalJournal of Medicinal Chemistry
Volume43
Issue number11
DOIs
Publication statusPublished - Jun 1 2000

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Acetylcysteine
Alkalinity
Oxidation-Reduction
Sulfhydryl Compounds
Acids
Population
Expectorants
Disulfides
Pharmacokinetics
Hydrogen
Protonation
Isomers
Pharmacology
Conformations
Hydrogen bonds
Membranes
Pharmaceutical Preparations
Molecules
Therapeutics

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Population, acid-base, and redox properties of N-acetylcysteine conformers. / Noszál, B.; Visky, Dóra; Kraszni, Márta.

In: Journal of Medicinal Chemistry, Vol. 43, No. 11, 01.06.2000, p. 2176-2182.

Research output: Contribution to journalArticle

Noszál, B. ; Visky, Dóra ; Kraszni, Márta. / Population, acid-base, and redox properties of N-acetylcysteine conformers. In: Journal of Medicinal Chemistry. 2000 ; Vol. 43, No. 11. pp. 2176-2182.
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