Estimation of Molecular Acidity via Electrostatic Potential at the Nucleus and Valence Natural Atomic Orbitals
详细信息 查看全文
- 作者：Shubin Liu ; Lee G. Pedersen
- 刊名：Journal of Physical Chemistry A
- 出版年：2009
- 出版时间：April 16, 2009
- 年：2009
- 卷：113
- 期：15
- 页码：3648-3655
- 全文大小：174K
- 年卷期：v.113,no.15(April 16, 2009)
- ISSN：1520-5215
文摘
An effective approach of estimating molecular pKa values from simple density functional calculations is proposed in this work. Both the molecular electrostatic potential (MEP) at the nucleus of the acidic atom and the sum of valence natural atomic orbitals are employed for three categories of compounds, amines and anilines, carbonyl acids and alcohols, and sulfonic acids and thiols. A strong correlation between experimental pKa values and each of these two quantities for each of the three categories has been discovered. Moreover, if the MEP is subtracted by the isolated atomic MEP for each category of compounds, we observe a single unique linear relationship between the resultant MEP difference and experimental pKa data of amines, anilines, carbonyl acids, alcohols, sulfonic acids, thiols, and their substituents. These results can generally be utilized to simultaneously estimate pKa values at multiple sites with a single calculation for either relatively small molecules in drug design or amino acids in proteins and macromolecules.