Sramko Martin, Smiesko Martin, Remko Milan
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Odbojarov 10, SK-832 32 Bratislava, Slovakia.
J Biomol Struct Dyn. 2008 Jun;25(6):599-608. doi: 10.1080/07391102.2008.10507206.
Studies that allow computing values of aqueous proton dissociation constants (pKa), gas phase proton affinities, and the free energy of solvation have been performed for six members of angiotensin-I-converting enzyme (ACE) inhibitor family (captopril, enalaprilat, imidaprilat, ramiprilat, perindoprilat, and spiraprilat). Density functional theory (DFT) calculations using PBE1PBE functional on optimized molecular geometries have been carried out to investigate the thermodynamics of gas-phase protonation. The conductor-like polarizable continuum model (CPCM) solvation method at various levels of theory was applied to calculate the free energy of solvation for the ACE inhibitors and their respective anions. The CPCM solvation calculations were performed on both gas-phase and solvent-phase optimized structures. The combination of gas-phase and solvation energies according to the thermodynamic cycle enabled us to compute accurate pKa values for the all studied molecules.
针对血管紧张素转换酶（ACE）抑制剂家族的六个成员（卡托普利、依那普利拉、咪达普利拉、雷米普利拉、培哚普利拉和螺普利拉）开展了相关研究，这些研究能够计算水相质子解离常数（pKa）、气相质子亲和能以及溶剂化自由能的值。利用PBE1PBE泛函对优化后的分子几何结构进行密度泛函理论（DFT）计算，以研究气相质子化的热力学性质。采用不同理论水平的导体类极化连续介质模型（CPCM）溶剂化方法，计算ACE抑制剂及其各自阴离子的溶剂化自由能。CPCM溶剂化计算在气相和溶剂相优化结构上均进行了。根据热力学循环将气相和溶剂化能相结合，使我们能够计算出所有研究分子的准确pKa值。
