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Lipophilicity Behavior of Model and Medicinal Compounds containing a suilfide, sulfoxide, or sulfone moiety
Author(s) -
Caron Giulia,
Gaillard Patrick,
Carrupt PierreAlain,
Testa Bernard
Publication year - 1997
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19970800210
Subject(s) - lipophilicity , chemistry , tautomer , intramolecular force , moiety , intermolecular force , sulfoxide , molecular dynamics , stereochemistry , computational chemistry , organic chemistry , molecule
This study was designed to unravel lipophilicity changes associated with the oxidation state of the S‐atom in model compounds, drugs, and metabolites, special attention being given both to intermolecular and intramolecular effects. The methods used were experimental (potentiometry, CPC, and shake‐flask techniques to measure lipophilicity, 13 C‐NMR spectroscopy to investigate tautomeric equilibria) and computational (quenched molecular dynamics and molecular lipophilicity potential). Simple, monofunctional model compounds were used to assess intermolecular forces, as revealed by the Δlog P oct–alk and Δlog P oct–chf parameters. Drugs and their metabolites proved to be good probes to study intramolecular effects in both neutral and anionic forms, as revealed by the difference between calculated and experimental log P oct values (the diff (log P exp–calc ) parameter). Sulindac and its metabolites showed a normal partitioning behavior, whereas the lipophilicity of sulfmpyrazone and its metabolites' was markedly affected by tautomeric and conformational equilibria.