Direct absolute pKa predictions and proton transfer mechanisms of small molecules in aqueous solution by QM/MM-MD.
Direct absolute pKa predictions and proton transfer mechanisms of small molecules in aqueous solution by QM/MM-MD.
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DOI：
10.1021/jp400180x
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发表时间：
2013-05
期刊：
影响因子：
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通讯作者：
N. Uddin;Tae Hoon Choi;C. Choi
中科院分区：
文献类型：
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作者：
N. Uddin;Tae Hoon Choi;C. Choi
采用QM/MM-MD结合伞形采样法，采用柔性不对称坐标（FAC），预测了HF、HCOOH、CH 3COOH、CH 3CH 2COOH、H2 CO 3、HOCl、NH 4（+）、CH 3 NH3（+）、H2 O2和CH 3CH 2 OH在水溶液中的pKa值。这种独特的组合产生了非常准确的值，最大和均方根误差分别为0.45和0.22的pKa单位，没有任何数值或实验调整。最初形成的库仑对的稳定性而不是质子转移阶段被证明是速率决定步骤，这意味着所产生的离子的稳定需要大的自由能增加。DWR（水重排度）和pKa之间的显着相关性进行了观察。因此，乙醇的大pKa可以部分归因于大的水重排，这强烈表明在解离区域的水动力学的适当采样对于准确预测pKa是至关重要的。目前的结果显示出一个有前途的协议直接和准确的预测pKa。气相去质子化能量与理论水平的显着变化似乎主要是由平均溶质-溶剂相互作用的类似变化，产生准确的结果被取消。
The pKa values of HF, HCOOH, CH3COOH, CH3CH2COOH, H2CO3, HOCl, NH4(+), CH3NH3(+), H2O2, and CH3CH2OH in aqueous solution were predicted by QM/MM-MD in combination with umbrella samplings adopting the flexible asymmetric coordinate (FAC). This unique combination yielded remarkably accurate values with the maximum and root-mean-square errors of 0.45 and 0.22 in pKa units, respectively, without any numerical or experimental adjustments. The stability of the initially formed Coulomb pair rather than the proton transfer stage turned out to be the rate-determining step, implying that the stabilizations of the created ions require a large free energy increase. A remarkable correlation between DWR (degree of water rearrangements) and pKa was observed. As such, the large pKa of ethanol can be, in part, attributed to the large water rearrangement, strongly suggesting that proper samplings of water dynamics at dissociated regions are critical for accurate predictions of pKa. Current results exhibit a promising protocol for direct and accurate predictions of pKa. The significant variations in the gas phase deprotonation energies with level of theory appear to be mostly canceled by the similar changes in the averaged solute-solvent interactions, yielding accurate results.