一元醇亲脂性基于理论线性溶解能相关的QSPR研究

QSPR research on the lipophilicity of monohydric alcohols based on theoretical linear solvation energy relationship

基于理论线性溶解能相关的思想,对117个一元醇(训练集含85个,外推集含32个)分别用HyperChem 7.5中的CNDO、INDO、MINDO3、MNDO、MNDOd、AM1和PM3量子化学方法进行结构优化和振动分析,计算了分子平均极化率α、偶极矩μ、最正氢原子电荷qH+、最负原子电荷q-、前线轨道能级ELUMO和EHOMO、经零点能校正的总能Etotal和标准生成热Hf等参数,将所得训练集参数对lgKow实验值进行了逐步回归建模和预测。研究表明,各方法计算的同一参数大多存在显著差异, PM3对结构适应性和优化效率最好,其参数所建方程是最优模型,可靠性最高,稳定性和预测精度好,应用于外推集化合物以及含饱和碳环、双键或苯环的非同系物也能取得良好结果。该模型可以揭示,一元醇主要作为质子受体以羟基氧原子接受溶剂质子实现向有机相转移,除极化作用外溶质溶剂的相互作用是以静电为主而价键较弱的分子间氢键。

The optimized stable configurations of 117 monohydric alcohols （85 in training set, 32 in extrapolating set） were obtained using CNDO, INDO, MINDO3, MNDO, MNDOd, AM1 and PM3 Hamiltonians in HyperChem 7.5 software package, and confirmed by vibration analysis at same leveles. Based on theoretical linear solvation energy relationship, the quantum chemistry parameters were calculated selectively from the structures, such as molecular mean polarizability α, dipole moment μ, the most positive charge of hydrogen atom qH ^＋ , the most negative charge of atom q^- , the frontier orbital eigenvalues ELUMO and EHOMO along with total energy Etotal and formation heat Hf modified with zero point energy. Whereafter the correlations between the training parameter sets corresponding to the Hamiltonians and the experimented lgKow were studied respectively by stepwise regression analysis. The results showed that the most of same parameters computed by different Hamiltonians were numerically considerable differences one another. PM3 was the best of all in aspects of applicability and optimizing efficiency to the structures. The equation established by the parameters from PM3 was the optimal one of all modeles, as having the highest reliability, satisfactory fitting effects and predicted precision. For the extrapolating set and nonhomologous compounds containing saturated C-ring, double-bond or phenyl, applying this model to forecast lgKow can well consist with the estimated and experimented lgKOW quoted from SRC＇s physical properties database. Also, this model may explain that these alcohols, mainly as proton-acceptors, can receive protons provided by n-octanol with hydroxyl-oxygen atoms so as to partition into organic phase. The interactions between solute and solvent were a hydrogen-bond chiefly consisted of Coulomb force but valence-bond bing relatively weak, except for the polarization.