Department of Physical Chemistry and Molecular Modeling, Faculty of Chemistry, University of Opole, 48 Oleska Street, 45-052 Opole, Poland.
Molecules. 2020 Aug 28;25(17):3931. doi: 10.3390/molecules25173931.
We report on the density functional theory (DFT) modelling of structural, energetic and NMR parameters of uracil and its derivatives (5-halogenouracil (5XU), X = F, Cl, Br and I) in vacuum and in water using the polarizable continuum model (PCM) and the solvent model density (SMD) approach. On the basis of the obtained results, we conclude that the intramolecular electrostatic interactions are the main factors governing the stability of the six tautomeric forms of uracil and 5XU. Two indices of aromaticity, the harmonic oscillator model of aromaticity (HOMA), satisfying the geometric criterion, and the nuclear independent chemical shift (NICS), were applied to evaluate the aromaticity of uracil and its derivatives in the gas phase and water. The values of these parameters showed that the most stable tautomer is the least aromatic. A good performance of newly designed xOPBE density functional in combination with both large aug-cc-pVQZ and small STO(1M)-3G basis sets for predicting chemical shifts of uracil and 5-fluorouracil in vacuum and water was observed. As a practical alternative for calculating the chemical shifts of challenging heterocyclic compounds, we also propose B3LYP calculations with small STO(1M)-3G basis set. The indirect spin-spin coupling constants predicted by B3LYP/aug-cc-pVQZ(mixed) method reproduce the experimental data for uracil and 5-fluorouracil well.
我们报告了密度泛函理论（DFT）对尿嘧啶及其衍生物（5-卤代尿嘧啶（5XU），X = F，Cl，Br 和 I）在真空和水中的结构、能量和 NMR 参数的建模，使用了极化连续体模型（PCM）和溶剂模型密度（SMD）方法。基于获得的结果，我们得出结论，分子内静电相互作用是决定尿嘧啶和 5XU 六种互变异构形式稳定性的主要因素。两个芳香性指数，满足几何标准的谐振子模型芳香性（HOMA）和核独立化学位移（NICS），被应用于评估尿嘧啶及其衍生物在气相和水中的芳香性。这些参数的值表明，最稳定的互变异构体是最不芳香的。我们观察到，新设计的 xOPBE 密度泛函与大 aug-cc-pVQZ 和小 STO(1M)-3G 基组相结合，在真空和水中预测尿嘧啶和 5-氟尿嘧啶化学位移的性能良好。作为计算具有挑战性的杂环化合物化学位移的实用替代方法，我们还提出了使用小 STO(1M)-3G 基组的 B3LYP 计算。B3LYP/aug-cc-pVQZ（混合）方法预测的间接自旋-自旋耦合常数很好地再现了尿嘧啶和 5-氟尿嘧啶的实验数据。
