Thyroxine lipophilicity is dominated by its zwitterionic microspecies

Károly Mazák, Gerg Tóth, J. Kökösi, B. Noszál

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Species-specific partition coefficients were determined for a triprotic molecule for the first time. Thyroxine, the vitally important thyroid hormone which exists in solution in the forms of eight microspecies due to its phenolate, amino and carboxylate basic sites, was studied by combined methods of microspeciation and lipophilicity. Partition of the individual microspecies was mimicked by model compounds of the closest possible similarity, then correction factors were determined and introduced. The non-charged microspecies is only 2.40 times as lipophilic as its zwitterionic protonation isomer, showing that for thyroxine the iodinated aromatic rings are the structural elements that determine the lipophilicity of this molecule, and the protonation state of the other substituents plays only a minor role. The overwhelming dominance of the zwitterionic form, however, ensures that its contribution to the overall lipophilicity exceeds 14,500 times that of the non-charged one. This fact is so far the sharpest counter-example of the widespread belief that passive diffusion into lipophilic media is predominated by the non-charged species. The lipophilicity profile of thyroxine is expressed, calculated and depicted in terms of species-specific lipophilicities over the entire pH range.

Original languageEnglish
Pages (from-to)921-925
Number of pages5
JournalEuropean Journal of Pharmaceutical Sciences
Volume47
Issue number5
DOIs
Publication statusPublished - Dec 18 2012

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Thyroxine
Thyroid Hormones

Keywords

  • Deductive method
  • Microscopic partition coefficient
  • Microscopic protonation constant
  • Thyroid hormones
  • Thyroxine
  • Zwitterion lipophilicity

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Thyroxine lipophilicity is dominated by its zwitterionic microspecies. / Mazák, Károly; Tóth, Gerg; Kökösi, J.; Noszál, B.

In: European Journal of Pharmaceutical Sciences, Vol. 47, No. 5, 18.12.2012, p. 921-925.

Research output: Contribution to journalArticle

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