Ester-type compounds are important drugs as directly binding active principles, but also, as prodrugs that provide the acting agent after hydrolytic decomposition. The profound characterisation of the kinetics of ester hydrolysis is therefore equally important to interpret and design metabolic processes and prodrug → drug transitions. The extramolecular factors (temperature, ionic strength, solvent etc.) influencing the rate constant values have extensively been studied. Contrary to that, few data can be found on the effect and magnitude of the intramolecular factors (substituent effect, neighbour-group protonation). This paper reports the introduction and determination of microscopic rate constants of ester hydrolysis, a new physicochemical parameter, which is defined in the sense of the protonation state of the basic site(s) adjacent the ester group The microscopic rate constants of phenylalanine-methyl-ester hydrolysis are determined and interpreted. Also, the principles to characterise the rate of monobasic double esters at the submolecular level, exemplified by cocaine, are established.
|Translated title of the contribution||Characterization of the kinetics of ester hydrolysis at the submolecular level|
|Number of pages||8|
|Journal||Acta pharmaceutica Hungarica|
|Publication status||Published - Jun 1 1999|
ASJC Scopus subject areas
- Pharmaceutical Science