Theoretical Study of Gas-Phase Acidities of Selected Angiotensin-Converting Enzyme Inhibitors

The structure and gas-phase acidities of six members of large angiotensin-converting enzyme (ACE) inhibitor family cilazaprilat, silanediol, fosinoprilat, AcSDKP, angiotensin_I (terminal part), and RXP_407] have been studied using the ONIOM Becke3LYP/6-311+G(d,p):HF/3-21G^∗ method. The investigated ACE inhibitors are weak acids with calculated acidity of about 1270–1650 kJ mol⁻¹. Of acids studied the highest gas-phase acidity (1273 kJ mol⁻¹) possesses experimental ACE inhibitor RXP_407. This drug, according to the computed pK_a value (3.2), is also in water solution the most acidic compound of the ACE inhibitors investigated.