The automation of workflows in computational chemistry becomes increasingly more important. The tool PyFrag 2019 of the Amsterdam Modeling Suite is an example for this.[1,2] PyFrag automates the individual computational steps needed to perform an in-depth analysis of chemical bonds and their changes during chemical reactions with the activation strain model.
In its newly overhauled version, PyFrag 2019 has already been employed in multiple computational studies concerning homogeneous catalysis. For example the influence of adjacent aromatic structures on the metal-catalyzed activation of C-H bonds was analyzed in great detail with PyFrag. As a result of this analysis, the lower barrier for the activation of such C-H bonds compared to their aliphatic counterparts could be explained in terms of the involved frontier orbitals.
In the following the difference in the observed behaviors of different complex centers for the catalysis of cross-coupling reactions was examined. Especially various different types of iron catalysts were studies and their behavior for reaction barrier heights were compared those obtained with palladium complexes. Closed-shell iron d8 complexes were thereby identified as potentially excellent substitutes for the more expensive palladium catalysts conventionally used in such reactions.
In further work whose publication is currently in preparation, the steric and electronic effects of such iron catalysts are examined in more detail. The knowledge and understanding gained thereby is key to design and optimize new, inexpensive catalysts for a given reaction by systematically screening different complex ligands.
Xiaobo Sun will defend his thesis Activating Bonds: Rational Design of Iron-Based Catalysts for Cross-Coupling, with Prof. Bickelhaupt as a promotor on 16 September 2019. The thesis can be downloaded from the VU website.
See also the PyFrag documentation in ADF.
 X. Sun, T. M. Soini, J. Poater, T. A. Hamlin, F. M. Bickelhaupt, “PyFrag 2019—Automating the exploration and analysis of reaction mechanisms” J. Comput. Chem. 40 (2019), 2227-2233
 P. Vermeeren, X. Sun, F. M. Bickelhaupt, “Arylic C–X Bond Activation by Palladium Catalysts: Activation Strain Analyses of Reactivity Trends” Scientific Reports 8 (2018), 10729
 X. Sun, M V. J. Rocha, T. A. Hamlin, J. Poater, F. M. Bickelhaupt, “Understanding the differences between iron and palladium in cross-coupling reactions” Phys. Chem. Chem. Phys. 21 (2019), 9651-9664Key conceptsADF bonding analysis catalysis inorganic chemistry Reactivity