Ab initio metódy elektrónovej hustoty boli použité na štúdium acidít piatich vybraných ACE inhibítorov v izolovanom stave. Acidity sú vyjadrené ako entalpia ?H298 a Gibbsova energia ?G298 deprotonácie pri teplote 298 K. Použitá bola dvojvrstvová ONIOM metóda, ktorá umožňila štúdium acidít vybraných ACE inhibítorov, presnejšou Becke3LYP metódou s bázou 6-311+G(d,p), zatiaľ čo zvyšné časti molekuly boli študované na úrovni Hartree-Fock s bázou 3 - 21G*. Študované ACE inhibítory sú slabé kyseliny s vypočítanými aciditami medzi 1290 - 1420 kJ.mol-1. Zo študovaných liečiv je najkyslejší v izolovanom stave aj vodnom roztoku spiraprilát.
Kľúčové slová: acidita - disociačná konštanta - ACE inhibítory - DFT metóda - SPARC

STUDY OF ACIDITIES OF SELECTED ANGIOTENSIN-CONVERTING ENZYME INHIBITORS

Ab initio density functional theory calculations were used to investigate gas-phase acidities of five selected ACE inhibitors expressed as enthalpy ?H298 and Gibbs energy ?G298 of deprotonation at 298.15 K. This study took advantage of the two layered ONIOM method, which allowed to calculate acidities of selected ACE inhibitors with high accuracy with the Becke3LYP method with 6-311+G(d,p) basis set - the High layer, while the other parts of the molecule were calculated with the Hartree-Fock method with 3-21G* basis set - the Low layer. The investigated ACE inhibitors are weak acids with calculated acidities of about 1290-1420 kJ.mol-1. Of acids studied the highest acidity (in gas-phase and also in water solution) posseses ACE inhibitor spiraprilat.
Key words: acidity - dissociation constant - ACE inhibitors - DFT method - SPARC

M. ŠRAMKO, M. REMKO