ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Two-Layer ONIOM Calculation of Gas-Phase Acidities of Selected ACE Inhibitors

M. Smieško and M. Remko

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, SK-832 32 Bratislava

E-mail: remko@fpharm.uniba.sk

Received: 15 January 2003

Abstract: Ab initio density functional theory calculations were used to investigate gas-phase acidities of three selected ACE inhibitors expressed as enthalpy of deprotonation at 298.15 K (ΔH_298K). This study took advantage of the recently developed ONIOM method, which allowed to calculate properties of dissociating functional groups of ACE inhibitors with high accuracy with the Becke3LYP method with 6-311+G(d,p) basis set – the High layer, while the other atoms were included in the Low layer, for which the Hartree—Fock method with 3-21G* basis set was used. Structure and reactivity of captopril, perindoprilat, and omapatrilat and their respective ionic forms are discussed.

Full paper in Portable Document Format: 582a71.pdf

Chemical Papers 58 (2) 71–78 (2004)