Site- and species-specific hydrolysis rates of heroin

Levente Szöcs, Gábor Orgován, Gergo Tóth, Márta Kraszni, Lajos Gergó, Sándor Hosztafi, B. Noszál

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The hydroxide-catalyzed non-enzymatic, simultaneous and consecutive hydrolyses of diacetylmorphine (DAM, heroin) are quantified in terms of 10 site- and species-specific rate constants in connection with also 10 site- and species-specific acid-base equilibrium constants, comprising all the 12 coexisting species in solution. This characterization involves the major and minor decomposition pathways via 6-acetylmorphine and 3-acetylmorphine, respectively, and morphine, the final product. Hydrolysis has been found to be 18-120 times faster at site 3 than at site 6, depending on the status of the amino group and the rest of the molecule. Nitrogen protonation accelerates the hydrolysis 5-6 times at site 3 and slightly less at site 6. Hydrolysis rate constants are interpreted in terms of intramolecular inductive effects and the concomitant local electron densities. Hydrolysis fraction, a new physico-chemical parameter is introduced and determined to quantify the contribution of the individual microspecies to the overall hydrolysis. Hydrolysis fractions are depicted as a function of pH.

Original languageEnglish
Pages (from-to)105-114
Number of pages10
JournalEuropean Journal of Pharmaceutical Sciences
Volume89
DOIs
Publication statusPublished - Jun 30 2016

Fingerprint

Heroin
Hydrolysis
Acid-Base Equilibrium
Morphine
Nitrogen
Electrons

Keywords

  • Ester hydrolysis
  • Heroin
  • Microconstant
  • Protonation
  • Rate constant

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Site- and species-specific hydrolysis rates of heroin. / Szöcs, Levente; Orgován, Gábor; Tóth, Gergo; Kraszni, Márta; Gergó, Lajos; Hosztafi, Sándor; Noszál, B.

In: European Journal of Pharmaceutical Sciences, Vol. 89, 30.06.2016, p. 105-114.

Research output: Contribution to journalArticle

Szöcs, L, Orgován, G, Tóth, G, Kraszni, M, Gergó, L, Hosztafi, S & Noszál, B 2016, 'Site- and species-specific hydrolysis rates of heroin', European Journal of Pharmaceutical Sciences, vol. 89, pp. 105-114. https://doi.org/10.1016/j.ejps.2016.04.028
Szöcs L, Orgován G, Tóth G, Kraszni M, Gergó L, Hosztafi S et al. Site- and species-specific hydrolysis rates of heroin. European Journal of Pharmaceutical Sciences. 2016 Jun 30;89:105-114. https://doi.org/10.1016/j.ejps.2016.04.028
Szöcs, Levente ; Orgován, Gábor ; Tóth, Gergo ; Kraszni, Márta ; Gergó, Lajos ; Hosztafi, Sándor ; Noszál, B. / Site- and species-specific hydrolysis rates of heroin. In: European Journal of Pharmaceutical Sciences. 2016 ; Vol. 89. pp. 105-114.
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