Siddiqui Shakir Ali, Shaik Sason, Kalita Surajit, Dubey Kshatresh Dutta
Department of Chemistry, School of Natural Sciences, Shiv Nadar Institution of Eminence Delhi-NCR India
Institute of Chemistry, The Hebrew University of Jerusalem Israel Jerusalem Israel
Chem Sci. 2023 Sep 4;14(37):10329-10339. doi: 10.1039/d3sc01720f. eCollection 2023 Sep 27.
The present work outlines a general methodology for designing efficient catalytic machineries that can easily be tweaked to meet the demands of the target reactions. This work utilizes a principle of the designed local electric field (LEF) as the driver for an efficient catalyst. It is demonstrated that by tweaking the LEF, we can catalyze the desired hydroxylation products with enantioselectivity that can be changed at will. Using computation tools, we caged a synthetic analog of heme porphyrin (HM1) and investigated the pharmaceutically relevant conversion of tetralin to tetralol, inside the modified supramolecular cage. The QM/MM calculations demonstrate a resulting catalytic efficiency with virtually absolute selectivity for the tetralin hydroxylation. Our calculations show that the LEF of the supramolecular cage and HM1 exert a strong electric field along the Fe-O reaction axis, which is the main driving force for enhanced reactivity. At the same time, the supramolecular cage applies a lateral LEF that regulates the enantioselectivity. We further demonstrate that swapping the charged/polar substitution in the supramolecular cage switches the lateral LEF which changes the enantioselectivity of hydroxylation from to .
本工作概述了一种设计高效催化机制的通用方法，该方法可轻松调整以满足目标反应的需求。这项工作利用设计局部电场（LEF）原理作为高效催化剂的驱动因素。结果表明，通过调整LEF，我们可以催化所需的羟基化产物，并实现可随意改变的对映选择性。利用计算工具，我们将血红素卟啉（HM1）的合成类似物封装在修饰的超分子笼内，并研究了四氢萘在笼内转化为四氢萘醇这一与药物相关的转化过程。量子力学/分子力学（QM/MM）计算表明，对于四氢萘羟基化反应，所得催化效率具有几乎绝对的选择性。我们的计算表明，超分子笼和HM1的LEF沿Fe-O反应轴施加强电场，这是增强反应活性的主要驱动力。同时，超分子笼施加横向LEF来调节对映选择性。我们进一步证明，在超分子笼中交换带电/极性取代基会改变横向LEF，从而将羟基化反应的对映选择性从 改变为 。
