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On the hydrolytic behavior of tinidazole, metronidazole, and ornidazole

✍ Scribed by Jukka-Pekka K. Salo; Jari Yli-Kauhaluoma; Hannele Salomies


Publisher
John Wiley and Sons
Year
2003
Tongue
English
Weight
124 KB
Volume
92
Category
Article
ISSN
0022-3549

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✦ Synopsis


Using two UV-spectrophotometric methods, the hydrolysis of tinidazole was studied at pH 1.00-8.45 at 80 degrees C. The reaction followed apparent first-order kinetics throughout the studied range. No kinetic salt effect was detected, indicating that at least one of the reacting partners forming the transition state has a charge of 0. The reaction rate macro constants M(1)-M(4) were calculated to be 3.35 x 10(-2) M(-1) h(-1), 1.45 x 10(-2) h(-1), 3.76 x 10(-6) M h(-1), and 2.85 x 10(-11) M(2) h(-1), respectively. At pH >or= 7, the uncharged tinidazole was decomposed by the hydroxide ion; the reaction was found out to involve a proton transfer from the ethylsulfonylethyl side chain. At around pH 4.5, the degradation of the uncharged tinidazole was due to the solvent. In more acidic conditions, the reaction mechanism could not be fully resolved. The alkaline hydrolysis of metronidazole was studied on the basis of literature data. A general reaction mechanism was proposed, but an unequivocal explanation for the inflection point in the pH rate profile at pH 6 could not be found. The implications of the proposed reaction mechanism for the hydrolytic behavior of ornidazole were discussed.


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