Abstract：
Extensive research has already provided reliable methods for the in silico prediction of pKa, while a trustworthy strategy for pKb determination is still being sought. Indeed, the approaches previously exploited for computing pKa have shown their weakness in predicting pKb. In the light of the exceptional reliability demonstrated in the pKa calculation of a wide panel of organic acids, in this work, we exploited our \"easy to use methodology\", based on the direct approach, to predict the pKb of primary amines. Herein, CAM-B3LYP was compared to WB97XD and B3PW91, exploring the solvation model based on density (SMD) and the polarizable continuum model (PCM), in the presence of two explicit water molecules. Noteworthy, CAM-B3LYP and WB97XD returned completely different solvent accessible surfaces (SAS) and electron potential maps (EPM) for the bases and the conjugated acids, independently from the nature of the substituents. Once again, CAM-B3LYP/SMD/2H2O method confirmed its remarkable reliability, leading to a minimum average error (MAE) lower than 0.3. This outstanding result strengthens the trustworthiness of our method, already successfully applied to predict the pKa of different substituted phenols and carboxylic acids. Thus, our \"easy-to-use\" process can predict also the pKb of primary ammines and anilines, always ensuring consistent outputs.
摘要：
广泛的研究已经为pKa的计算机预测提供了可靠的方法，同时仍在寻求一种可靠的pKb确定策略。的确,以前用于计算pKa的方法已经显示出它们在预测pKb方面的弱点。鉴于在大量有机酸的pKa计算中证明了其出色的可靠性，在这项工作中，我们利用了我们的“易于使用的方法”，基于直接的方法，来预测伯胺的pKb。在这里，将CAM-B3LYP与WB97XD和B3PW91进行了比较，探索了基于密度（SMD）和可极化连续体模型（PCM）的溶剂化模型，在存在两个明确的水分子的情况下。值得注意的是,CAM-B3LYP和WB97XD返回了碱和共轭酸的完全不同的溶剂可及表面（SAS）和电子电位图（EPM），独立于取代基的性质。再一次,CAM-B3LYP/SMD/2H2O法证实了其显著的可靠性,导致最小平均误差（MAE）低于0.3。这一突出的结果加强了我们方法的可信性，已经成功地应用于预测不同取代酚和羧酸的pKa。因此，我们的“易于使用”过程还可以预测初级胺和苯胺的pKb，始终确保一致的输出。
