Department of Chemistry, McGill University , 801 Sherbrooke Street W., Montréal, QC, Canada H3A 0B8.
Chemical Computing Group Inc. , 1010 Sherbrooke Street W., Montréal, QC, Canada H3A 2R7.
J Chem Inf Model. 2018 Jan 22;58(1):194-205. doi: 10.1021/acs.jcim.7b00645. Epub 2018 Jan 5.
We previously implemented a well-known qualitative chemical principle into an accurate quantitative model computing relative potential energies of conformers. According to this principle, hyperconjugation strength correlates with electronegativity of donors and acceptors. While this earlier version of our model applies to σ bonds, lone pairs, disregarded in this earlier version, also have a major impact on the conformational preferences of molecules. Among the well-established principles used by organic chemists to rationalize some organic chemical behaviors are the anomeric effect, the alpha effect, basicity, and nucleophilicity. These effects are directly related to the presence of lone pairs. We report herein our effort to incorporate lone pairs into our model to extend its applicability domain to any saturated small molecules. The developed model H-TEQ 2 has been validated on a wide variety of molecules from polyaromatic molecules to carbohydrates and molecules with high heteroatoms/carbon ratios. Interestingly, this method, in contrast to common force field-based methods, does not rely on atom types and is virtually applicable to any organic molecules.
我们之前将一个著名的定性化学原理应用于一个准确的定量模型中，以计算构象的相对势能。根据该原理，超共轭强度与供体和受体的电负性相关。虽然我们模型的早期版本适用于σ键，但在早期版本中被忽略的孤对电子也对分子的构象偏好有重大影响。在被有机化学家用于合理化一些有机化学反应的既定原理中，有端基效应、α效应、碱性和亲核性。这些效应直接与孤对电子的存在有关。我们在此报告将孤对电子纳入我们的模型的努力，以将其适用范围扩展到任何饱和小分子。开发的模型 H-TEQ 2 已在各种分子上得到验证，包括多环芳烃分子、碳水化合物和高杂原子/碳比的分子。有趣的是，与常见的基于力场的方法相比，这种方法不依赖于原子类型，几乎适用于任何有机分子。
