Morales-Bayuelo Alejandro
Grupo de Química Cuántica y Teórica de la Universidad de Cartagena, Facultad de Ciencias, Programa de Química, Cartagena de Indias, Colombia.
FONDECYT Postdoctoral Project N0 3150035, Universidad de Talca, Talca, Chile.
J Mol Model. 2016 Jul;22(7):164. doi: 10.1007/s00894-016-3036-7. Epub 2016 Jun 21.
Though QSAR was originally developed in the context of physical organic chemistry, it has been applied very extensively to chemicals (drugs) which act on biological systems, in this idea one of the most important QSAR methods is the 3D QSAR model. However, due to the complexity of understanding the results it is necessary to postulate new methodologies to highlight their physical-chemical meaning. In this sense, this work postulates new insights to understand the CoMFA results using molecular quantum similarity and chemical reactivity descriptors within the framework of density functional theory. To obtain these insights a simple theoretical scheme involving quantum similarity (overlap, coulomb operators, their euclidean distances) and chemical reactivity descriptors such as chemical potential (μ), hardness (ɳ), softness (S), electrophilicity (ω), and the Fukui functions, was used to understand the substitution effect. In this sense, this methodology can be applied to analyze the biological activity and the stabilization process in the non-covalent interactions on a particular molecular set taking a reference compound.
尽管定量构效关系（QSAR）最初是在物理有机化学的背景下发展起来的，但它已被广泛应用于作用于生物系统的化学物质（药物），在这个概念中，最重要的QSAR方法之一是三维定量构效关系（3D QSAR）模型。然而，由于理解结果的复杂性，有必要提出新的方法来突出其物理化学意义。从这个意义上说，这项工作提出了新的见解，即在密度泛函理论框架内，使用分子量子相似性和化学反应性描述符来理解比较分子力场分析（CoMFA）结果。为了获得这些见解，采用了一个简单的理论方案，该方案涉及量子相似性（重叠、库仑算符及其欧几里得距离）和化学反应性描述符，如化学势（μ）、硬度（ɳ）、软度（S）、亲电性（ω）和福井函数，以理解取代效应。从这个意义上说，这种方法可以应用于分析特定分子集上非共价相互作用中的生物活性和稳定过程，并以一种参考化合物作为参照。
