Geremia Kara L, Seybold Paul G
Department of Chemistry, Wright State University, Dayton, OH, 45435, USA.
J Mol Model. 2019 Jan 3;25(1):12. doi: 10.1007/s00894-018-3892-4.
Purines and related compounds are central ingredients in the genetic code and form the structural framework for many drugs and other bioactive compounds. A key feature of these compounds is their acidity, as expressed by their pK values. For a proper understanding of the behaviors of these compounds, it is important to have a theoretical means for estimating their acidities. Here we present a quantum-chemical quantitative structure-activity relationship (QSAR) study of these compounds aimed at estimating the aqueous pK values of purines and related compounds based on the energy differences in solution ΔE(HO) between the parent compounds and their dissociation products. This method was applied to both the cation → neutral (pK) and neutral → anion (pK) dissociations of the compounds. Computations were performed using density functional theory at the B3LYP/6-31 + G** level with the SM8 aqueous solvent model. Good-quality QSAR regression equations were obtained for both dissociations using the ΔE(HO) descriptor. These equations were applied to estimate missing pK values for compounds in this category, and should also be applicable to the acidities of other related heterocyclic compounds.
嘌呤及相关化合物是遗传密码的核心成分，构成了许多药物和其他生物活性化合物的结构框架。这些化合物的一个关键特性是其酸度，由其pK值表示。为了正确理解这些化合物的行为，拥有一种估算其酸度的理论方法很重要。在此，我们展示了一项针对这些化合物的量子化学定量构效关系（QSAR）研究，旨在基于母体化合物与其解离产物在溶液中的能量差ΔE(HO)估算嘌呤及相关化合物的水相pK值。该方法应用于化合物的阳离子→中性（pK）和中性→阴离子（pK）解离。使用密度泛函理论在B3LYP/6 - 31 + G**水平结合SM8水相溶剂模型进行计算。使用ΔE(HO)描述符，两种解离都获得了高质量的QSAR回归方程。这些方程用于估算此类化合物缺失的pK值，也应适用于其他相关杂环化合物的酸度。
