密度泛函活性理论预测单取代和多取代苯甲酸的pKa值
黄 莺1,钟爱国2,刘述斌3,4＊
【摘 要】摘 要 酸碱性是分子非常重要的物理化学性质之一通常用pKa值来表示,但由于受稳定性等诸多因素的制约从实验上准确测定一些分子的pKa值仍有困难.从理论和计算上寻找有效和可靠的预测酸碱性的方法仍然是目前文献上活跃的课题.最近,我们从密度泛函活性理论的角度提出了一个简单而有效的方法来计算分子的酸碱性.本文试图把该方法应用于苯甲酸体系,预测单取代和多取代苯甲酸的pKa值.我们发现,本文的预测结果比文献报道最好的计算值都要精确. 【期刊名称】湖南师范大学自然科学学报 【年(卷),期】2011(034)001 【总页数】4
【关键词】关键词 酸碱性;密度泛函活性理论;pKa值
The knowledge of pKavalues,the acid-base dissociation constant,as a measure of the strength of an acid or a base,is essential for the understanding and quantitative treatment of acid-base processes in solution.This
infor
ma-tion
is
relevant
to
chemical
synthesis,pharmacokinetics,drug design,drugmetabolis
m,toxicology,and environmental protection.To develop efficient and reliable computational models to predict pKavalues withab initioand density functional theory（DFT）approaches is still a daunting task,as an ongoing effort in the literature.[1-3]Very recently, we developed an effective method,both efficient and reliable,within the framework of
density functional reactivity theory（DFRT）for the purpose.[4-5]In thiswork,we
apply
the
approach
to
substituted
benzoic
acids,demonstrating its effectiveness and reliability in quantitatively forecasting pKadata for sometimes experimentally inaccessible systems. In theory,the pKavalue of an acid,HA,is defined as the negative logarithm,pKa=-log10Ka,of the equilibrium constantKaof the acid dissociation
reaction,HA?H++A-,withKa=[H+][A-]/[HA].In
ther
modynamics,the equilibrium constantKais related to the standard Gibbs free energy changeΔG°for this reaction,ΔG°= 2.303RTpKa,whereRis the gas constant andTis the temperature in Kelvin.In practice,the pKavalue can be computed through a ther modynamic cycle usingab initioand DFT methods,which is often computationally demanding.[1-3]The new approach we proposed was based on DFRT.[6-9]When a proton is dissociated from an acid molecule,the energy changeΔEof the entire system associated with the process can be expressed as follows[5] whereρ（r）is the electron density andΔv（r）is the change of the external potential due to the dissociation of the proton,which can explicitly be expressed as
whereRHis the coordinate of the leaving proton and{Zi,Ri }are the nuclear charge and coordinates of the other nuclei in the acid molecule,respectively.Put together,this results in[5]
The right hand side of Eq.（3）is nothing but the molecular electrostatic
potential（MEP）on the leaving proton nucleus,suggesting that theMEP of the leaving proton can serve as a linearpredictor of the pKavalue of the acid.Additionally,we demonstrated earlier that theMEP of the acidic atom,O1 in the study（Scheme 1）,is also a reliable indicator of the acid's pKavalue[4].Also,a strong linear relationship between the acidic atom'sMEP and its valence natural atomic orbital（NAO）has been revealed[4].
Scheme 1 Atomic numbering of substituted benzoic acids.R2-R6groups are hydrogen atoms by default.A substituted benzoic acid is denoted by its substituting group.For example,3-Br stands for the systemswith all R being H except for R3=Br.
In thisLetter,we applied the approach to predict the pKavalues for a series of substituted benzoic acid compounds（Scheme 1）.We first consider the 13 singly substituted benzoic acids whose exper imental pKadata are known.[10]Computational details employed for these compounds are available elsewhere[4-5].Table 1 summarizes the results for these compounds（see Scheme 1 for their notation）.Figure 1 displays the strong linear correlations betweenMEP and NAO for both O1（correlation coefficientR2=0.999 8）and H1（R2=0.999 8）.Also shown in the Fig 1（c）is the least square fit result between MEP on O1 and the exper imental pKadata for the 13 species. W ithMEP and NAO descriptors from DFRT for both the acidic atom O1 and the leaving
密度泛函活性理论预测单取代和多取代苯甲酸的pKa值
