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.