Microscopic Protonation/Deprotonation Equilibria of the Anti‐Inflammatory Agent Piroxicam

Krisztina Takács‐Novák, József Kökösi, Benjámin Podányi, Béla Noszál, Ruey‐Shiuan ‐S Tsai, Giuseppe Lisa, Pierre‐Alain ‐A Carrupt, Bernard Testa

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

The microscopic ionization behavior of piroxicam was investigated using two different approaches, i.e., direct UV spectroscopy and an indirect analogue approach (deductive method). The best microscopic pKa values (pKa12 = 4.60, pKa21 = 5.40, pKa22 = 2.72, and pKa11 = 1.92) were obtained by the deductive method using as pKa22 the pKa of the enolic O‐methylated piroxicam 2. The results show remarkable electrostatic effects in the protonation/deprotonation equilibria, a marked increase in the acidity of the enolic function (2.68 pKa units) being caused by the pyridinium group. The electronic structure of piroxicam was studied based on 1H‐NMR chemical shifts at various ionization states, indicating an extended electron conjugation through the molecule. The partition measurements in octan‐1‐ol/H2O of zwitterionic compound 3 (the pyridyl N‐methyl derivative of piroxicam (1)) suggest that the two opposite charges in zwitterionic piroxicam are indeed in a close intramolecular proximity.

Original languageEnglish
Pages (from-to)553-562
Number of pages10
JournalHelvetica Chimica Acta
Volume78
Issue number3
DOIs
Publication statusPublished - May 10 1995

ASJC Scopus subject areas

  • Catalysis
  • Biochemistry
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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