Catalysis/ Rothenberg, ISBN Catalysis: Concepts and Green Applications Lecture slides for Chapter 6: Computer applications in catalysis research. Most of the graphics here were drawn using PowerPoint and Chemdraw (version Ultra 9.0). Feel free to modify and/or add your own pyrotechnics. Please send any feedback to

Catalysis/ Rothenberg, ISBN Figure 6.1 catalyst design catalytic cycles (catalytic processes) active intermediates mechanistic studies activation/ deactivation Reaction kinetics 3D descriptors 2D descriptors empirical scales QSAR/ QSPR ab initio, DFT semi-empirical methods Quantum mechanics Monte-Carlo methods molecular dynamics Classical mechanics QM/MM hybrid methods

Catalysis/ Rothenberg, ISBN Figure 6.2 CH 3 CH 2 OH

Catalysis/ Rothenberg, ISBN Figure 6.3 color fig

Catalysis/ Rothenberg, ISBN Figure 6.4

Catalysis/ Rothenberg, ISBN Figure 6.5 colour fig

Catalysis/ Rothenberg, ISBN Figure 6.6

Catalysis/ Rothenberg, ISBN Figure 6.7

Catalysis/ Rothenberg, ISBN Figure 6.8 DescriptorsFigures of merit A Catalysts BC

Catalysis/ Rothenberg, ISBN Figure 6.9

Catalysis/ Rothenberg, ISBN Figure 6.10 A B C D A B C D

Catalysis/ Rothenberg, ISBN Figure 6.11

Catalysis/ Rothenberg, ISBN Figure 6.12

Catalysis/ Rothenberg, ISBN Figure 6.13 PP D P1-P2  P1-P2

Catalysis/ Rothenberg, ISBN Figure D topological descriptors 3D molecular mechanics 3D PM3 semi- empirical ,000 10, ,000 Ligands analysed /h Computational method 3D ab initio

Catalysis/ Rothenberg, ISBN Figure 6.15 O PP D1D1 D2D2 PP P P SAM R<3

Catalysis/ Rothenberg, ISBN Figure Bite angle [º] Ligands ○ Bite Angle (X-ray) ● Bite Angle (Topological) — Flexibility (PM3) — Flexibility (Topological)

Catalysis/ Rothenberg, ISBN Figure 6.17 colour fig ligating groups M bridge groups residue groups

Catalysis/ Rothenberg, ISBN Figure 6.18

Catalysis/ Rothenberg, ISBN Figure 6.19 descriptor 3 descriptor 2 d ij the model space candidate with high residuals descriptor 1

Catalysis/ Rothenberg, ISBN Figure 6.20 Feed back figures of merit and update models create catalyst library START select subset for 2D models analyse and choose new set analyse using 3D models make and test new generation END optimal performance? Yes No A virtual library containing 10 7 ligand-metal complexes The 2D models select subsets of 10,000 catalysts The best 500 catalysts from the 2D models are chosen for the next step The best 20 catalysts from the 3D models are then synthesised and tested Refine using GAs and meta- modelling

Catalysis/ Rothenberg, ISBN Figure 6.21 PCA choose relevant PCs prepare dataset data analysis MLR average values ANNs / trees PLS regression linear models pre-processing divide in subsets remove outliers reduce dimensionality find clusters, key variables and correlations nonlinear models model validation independent test sets cross-validation y-randomising chemical knowledge variable importance

Catalysis/ Rothenberg, ISBN Figure 6.22 B A residual sample space principal component model space PC 1 PC 2 residual

Catalysis/ Rothenberg, ISBN Figure 6.23

Catalysis/ Rothenberg, ISBN Figure 6.24

Catalysis/ Rothenberg, ISBN Figure 6.25

Catalysis/ Rothenberg, ISBN Figure Pd Loading < Pd Loading <0.3 LUMO <0.39 Time <3.5 Pd Loading <2.15 R max <3.13 TON TOF

Catalysis/ Rothenberg, ISBN Figure 6.27

Catalysis/ Rothenberg, ISBN Figure 6.28

Catalysis/ Rothenberg, ISBN Figure mean-centering 0 autoscaling one standard deviation 1 0