高等学校化学学报 ›› 2009, Vol. 30 ›› Issue (11(1)): 103.

• 研究论文 • 上一篇    

水溶液中有机化合物pKa值的量子化学计算研究

丁晓琴, 孙杨, 丁俊杰, 陈冀胜   

  1. 北京药物化学研究所, 北京 102205
  • 收稿日期:2009-07-28 出版日期:2009-11-30 发布日期:2009-11-30
  • 通讯作者: 丁晓琴, 女, 博士, 教授, 主要从事药物分子设计、合成及量子化学计算研究. E-mail: dingxiaoqin2008@126.com

Quantum Chemical Calculations on pKa Values of Oranic Compounds in Aqueous Solution

DING Xiao-Qin*, SUN Yang, DING Jun-Jie, CHEN Ji-Sheng   

  1. Beijing Institute of Pharmaceutical Chemistry, Beijing 102205, China
  • Received:2009-07-28 Online:2009-11-30 Published:2009-11-30
  • Contact: DING Xiao-Qin. E-mail: dingxiaoqin2008@126.com

摘要:

采用密度泛函量子化学计算方法, 在B3LYP/6-31+G(d,p)水平上采用极化连续模型(PCM), 对醇、酚、羧酸、芳香胺和脂肪胺等多类化合物在水溶液中的pKa值进行了计算. 与实验值比较, 多数化合物绝对误差小于1个pKa单位, pKa计算值与实验值相关系数均大于0.94. 可见, 采用量子化学计算的方法可准确预测化合物的pKa值, 并可以扩展应用到药物结构与性能关系、ADMET虚拟筛选、有机合成路线设计和优化等研究领域.

关键词: pKa值; 密度泛函; 连续极化模型

Abstract:

Quantum chemical calculations of the pKa values were performed using DFT method with 6-31+g(d,p) basis set for more than 200 compounds of alcohol, phenol, carboxylic acid, aliphatic amines, aromatic amine and nitrogen heterocyclics etc. The solution-phase calculations use polarized continuum solution(PCM) model with default set in water. The residue of most compounds is less than 1 pKa unit. Correlation coefficient between experiment results and forecast results is better than 094. The results can help us to research reaction activity difference between different molecules or different groups in one molecule. Quantum Chemical calculations of the pKa values will be instructive to computer aided molecular design and organic synthetic route design and optimization.

Key words: pKa value; Density functional theory, Polarized continuum solution(PCM)

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