title: Site- and species-specific hydrolysis rates of heroin.
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.
authors.affiliation: Semmelweis University, Department of Pharmaceutical Chemistry, Research Group for Drugs of Abuse and Doping Agents, Hungarian Academy of Sciences, Hőgyes E. u. 9, H-1092 Budapest, Hungary.
authors.forename: Levente
authors.initials: L
authors.lastname: Szöcs
authors.affiliation: Semmelweis University, Department of Pharmaceutical Chemistry, Research Group for Drugs of Abuse and Doping Agents, Hungarian Academy of Sciences, Hőgyes E. u. 9, H-1092 Budapest, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Orgován
authors.affiliation: Semmelweis University, Department of Pharmaceutical Chemistry, Research Group for Drugs of Abuse and Doping Agents, Hungarian Academy of Sciences, Hőgyes E. u. 9, H-1092 Budapest, Hungary.
authors.forename: Gergő
authors.initials: G
authors.lastname: Tóth
authors.affiliation: Semmelweis University, Department of Pharmaceutical Chemistry, Research Group for Drugs of Abuse and Doping Agents, Hungarian Academy of Sciences, Hőgyes E. u. 9, H-1092 Budapest, Hungary.
authors.forename: Márta
authors.initials: M
authors.lastname: Kraszni
authors.affiliation: Eötvös Loránd University, Faculty of Informatics, Department of Numerical Analysis, Hungary.
authors.forename: Lajos
authors.initials: L
authors.lastname: Gergó
authors.affiliation: Semmelweis University, Department of Pharmaceutical Chemistry, Research Group for Drugs of Abuse and Doping Agents, Hungarian Academy of Sciences, Hőgyes E. u. 9, H-1092 Budapest, Hungary.
authors.forename: Sándor
authors.initials: S
authors.lastname: Hosztafi
authors.affiliation: Semmelweis University, Department of Pharmaceutical Chemistry, Research Group for Drugs of Abuse and Doping Agents, Hungarian Academy of Sciences, Hőgyes E. u. 9, H-1092 Budapest, Hungary. Electronic address: noszal.bela@pharma.semmelweis-univ.hu.
authors.forename: Béla
authors.initials: B
authors.lastname: Noszál
mesh_terms: D002384:Catalysis; D003932:Heroin / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D006878:Hydroxides / Q000737:chemistry; D009020:Morphine / Q000737:chemistry; D009022:Morphine Derivatives / Q000737:chemistry; D009584:Nitrogen / Q000737:chemistry; D012996:Solutions / Q000737:chemistry
chemical_list: D006878:Hydroxides; D009022:Morphine Derivatives; D012996:Solutions; D003932:Heroin; D009020:Morphine; C031356:hydroxide ion; C026979:6-O-monoacetylmorphine; D009584:Nitrogen
keywords: Ester hydrolysis; Heroin; Microconstant; Protonation; Rate constant