Instituto de Tecnologı́a Quı́mica (UPV-CSIC), Universidad Politécnica de Valencia, Avenida Naranjos s/n, 46022 Valencia, Spain.
Molecular Topology and Drug Design Unit, Department of Physical Chemistry, University of Valencia, 46010 Valencia, Spain.
J Chem Inf Model. 2020 Jun 22;60(6):2819-2829. doi: 10.1021/acs.jcim.0c00231. Epub 2020 Jun 10.
The presence of organic structure directing agents (templates) in the synthesis of zeolites allows the synthesis to be directed, in many cases, toward structures in which there is a large stabilization between the template and the zeolite micropore due to dispersion interactions. Although other factors are also important (temperature, pH, Si/Al ratio, etc.), systems with strong zeolite-template interactions are good candidates for an application of new computational algorithms, for instance those based in molecular topology (MT), that can be used in combination with large databases of organic molecules. Computational design of new templates allows the synthesis of existing and new zeolites to be expanded and refined. Three zeolites with similar 3-D large pore systems, BEA, BEC, and ISV, were selected with the aim of finding new templates for their selective syntheses. Using a training set of active and inactive templates (obtained from the literature) for the synthesis of target zeolites, it was possible to select chemical descriptors related to activity, meaning a good candidate template. With a discriminant function defined upon MT, the screening through a database of organic molecules led to a small subset (preselection) of candidate templates for the synthesis of BEA, BEC, and ISV. As far as we know, this is the first time that topological/topochemical descriptors, which do not consider 3-D information on the molecules, have been used to predict the activity of zeolite structure directing agents (SDAs). Following the prediction of SDAs using MT, an automated approach of sequential template filling of micropores based on a combination of Monte Carlo and lattice energy minimization was applied for all the candidate templates in the three zeolites. Two results can be obtained from this: an evaluation of the quality of the molecular topology QSAR models leading to the preselection of templates, and a final selection of candidate templates for the selective synthesis of BEA, BEC, and ISV. Regarding the latter, a good template will be that which maximizes the zeolite-template dispersion interactions with one, and only one, of the three zeolites. The presented methodology can be used to find alternative (maybe cheaper or perhaps more selective) templates than those already known.
沸石的合成中存在有机结构导向剂（模板），这使得在许多情况下可以进行导向合成，其中由于分散相互作用，模板和沸石微孔之间存在很大的稳定性。尽管其他因素也很重要（温度、pH 值、Si/Al 比等），但具有强沸石-模板相互作用的系统是新计算算法应用的良好候选者，例如基于分子拓扑（MT）的那些算法，这些算法可以与有机分子的大型数据库结合使用。新模板的计算设计允许扩展和改进现有和新型沸石的合成。选择了三种具有相似三维大孔体系的沸石（BEA、BEC 和 ISV），旨在为它们的选择性合成寻找新的模板。使用目标沸石合成的活性和非活性模板（从文献中获得）的训练集，可以选择与活性相关的化学描述符，即良好的候选模板。使用基于 MT 的判别函数，对有机分子数据库进行筛选，得到 BEA、BEC 和 ISV 合成的候选模板的一个小子集（预选）。据我们所知，这是第一次使用不考虑分子 3-D 信息的拓扑/拓扑化学描述符来预测沸石结构导向剂（SDA）的活性。在使用 MT 预测 SDA 之后，针对三种沸石中的所有候选模板应用了基于蒙特卡罗和晶格能最小化组合的微孔顺序模板填充的自动化方法。从这两种方法可以得到两个结果：对导致模板预选的 SDA 的 QSAR 模型的质量评估，以及对 BEA、BEC 和 ISV 选择性合成的候选模板的最终选择。关于后者，好的模板将是与三种沸石中的一种沸石最大化沸石-模板分散相互作用的模板。所提出的方法可用于寻找替代模板（可能更便宜或更具选择性），而不是已经知道的模板。
