Authors: Adarsh V. Kalikadien | Evgeny A. Pidko | Vivek Sinha
Source: ChemRxiv (preprint, 2021-05-21)
Field: Materials Science — Materials Chemistry

ChemSpaX: Exploration of Chemical Space by Automated Functionalization of Molecular Scaffold &lt;div&gt;Local chemical space exploration of an experimentally synthesized material can be done by making slight structural&lt;/div&gt;&lt;div&gt;variations of the synthesized material. This generation of many molecular structures with reasonable quality,&lt;/div&gt;&lt;div&gt;that resemble an existing (chemical) purposeful material, is needed for high-throughput screening purposes in&lt;/div&gt;&lt;div&gt;material design. Large databases of geometry and chemical properties of transition metal complexes are not&lt;/div&gt;&lt;div&gt;readily available, although these complexes are widely used in homogeneous catalysis. A Python-based workflow,&lt;/div&gt;&lt;div&gt;ChemSpaX, that is aimed at automating local chemical space exploration for any type of molecule, is introduced.&lt;/div&gt;&lt;div&gt;The overall computational workflow of ChemSpaX is explained in more detail. ChemSpaX uses 3D information,&lt;/div&gt;&lt;div&gt;to place functional groups on an input structure. For example, the input structure can be a catalyst for which one&lt;/div&gt;&lt;div&gt;wants to use high-throughput screening to investigate if the catalytic activity can be improved. The newly placed&lt;/div&gt;&lt;div&gt;substituents are optimized using a computationally cheap force-field optimization method. After placement of&lt;/div&gt;&lt;div&gt;new substituents, higher level optimizations using xTB or DFT instead of force-field optimization are also possible&lt;/div&gt;&lt;div&gt;in the current workflow. In representative applications of ChemSpaX, it is shown that the structures generated by&lt;/div&gt;&lt;div&gt;ChemSpaX have a reasonable quality for usage in high-throughput screening applications. Representative applications&lt;/div&gt;&lt;div&gt;of ChemSpaX are shown by investigating various adducts on functionalized Mn-based pincer complexes,&lt;/div&gt;&lt;div&gt;hydrogenation of Ru-based pincer complexes, functionalization of cobalt porphyrin complexes and functionalization&lt;/div&gt;&lt;div&gt;of a bipyridyl functionalized cobalt-porphyrin trapped in a M2L4 type cage complex. Descriptors such as&lt;/div&gt;&lt;div&gt;the Gibbs free energy of reaction and HOMO-LUMO gap, that can be used in data-driven design and discovery&lt;/div&gt;&lt;div&gt;of catalysts, were selected and studied in more detail for the selected use cases. The relatively fast GFN2-xTB&lt;/div&gt;&lt;div&gt;method was used to calculate these descriptors and a comparison was done against DFT calculated descriptors.&lt;/div&gt;&lt;div&gt;ChemSpaX is open-source and aims to bolster the efforts of the scientific community towards data-driven material&lt;/div&gt;&lt;div&gt;discovery.&lt;/div&gt; Chemical space ; Workflow ; Homogeneous ; Chemistry ; Catalysis ; Molecule ; Computer science ; Nanotechnology ; Combinatorial chemistry ; Mathematics ; Materials science ; Drug discovery ; Combinatorics ; Organic chemistry ; Biochemistry Machine Learning in Materials Science ; Advanced Polymer Synthesis and Characterization ; Catalysis and Hydrodesulfurization Studies