1. Catalysis/ Rothenberg, ISBN 978-3-527-31824-7. www.catalysisbook.org 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 feedback@catalysisbook.org

2. Catalysis/ Rothenberg, ISBN 978-3-527-31824-7. www.catalysisbook.org 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

3. Catalysis/ Rothenberg, ISBN 978-3-527-31824-7. www.catalysisbook.org Figure 6.2 CH 3 CH 2 OH

4. Catalysis/ Rothenberg, ISBN 978-3-527-31824-7. www.catalysisbook.org Figure 6.3 color fig

5. Catalysis/ Rothenberg, ISBN 978-3-527-31824-7. www.catalysisbook.org Figure 6.4

6. Catalysis/ Rothenberg, ISBN 978-3-527-31824-7. www.catalysisbook.org Figure 6.5 colour fig

7. Catalysis/ Rothenberg, ISBN 978-3-527-31824-7. www.catalysisbook.org Figure 6.6

8. Catalysis/ Rothenberg, ISBN 978-3-527-31824-7. www.catalysisbook.org Figure 6.7

9. Catalysis/ Rothenberg, ISBN 978-3-527-31824-7. www.catalysisbook.org Figure 6.8 DescriptorsFigures of merit A Catalysts BC

10. Catalysis/ Rothenberg, ISBN 978-3-527-31824-7. www.catalysisbook.org Figure 6.9

11. Catalysis/ Rothenberg, ISBN 978-3-527-31824-7. www.catalysisbook.org Figure 6.10 A B C D A B C D

12. Catalysis/ Rothenberg, ISBN 978-3-527-31824-7. www.catalysisbook.org Figure 6.11

13. Catalysis/ Rothenberg, ISBN 978-3-527-31824-7. www.catalysisbook.org Figure 6.12

14. Catalysis/ Rothenberg, ISBN 978-3-527-31824-7. www.catalysisbook.org Figure 6.13 PP 01000000000 10100000000 01010010000 00101000000 00010100011 00001010000 00100101000 00000010100 00000001000 00001000000 D P1-P2  P1-P2

15. Catalysis/ Rothenberg, ISBN 978-3-527-31824-7. www.catalysisbook.org Figure 6.14 2D topological descriptors 3D molecular mechanics 3D PM3 semi- empirical 10 100 1,000 10,000 100,000 Ligands analysed /h Computational method 3D ab initio

16. Catalysis/ Rothenberg, ISBN 978-3-527-31824-7. www.catalysisbook.org Figure 6.15 O PP D1D1 D2D2 PP P P SAM R<3

17. Catalysis/ Rothenberg, ISBN 978-3-527-31824-7. www.catalysisbook.org Figure 6.16 120 110 100 90 80 70 60 Bite angle [º] Ligands ○ Bite Angle (X-ray) ● Bite Angle (Topological) — Flexibility (PM3) — Flexibility (Topological)

18. Catalysis/ Rothenberg, ISBN 978-3-527-31824-7. www.catalysisbook.org Figure 6.17 colour fig ligating groups M bridge groups residue groups

19. Catalysis/ Rothenberg, ISBN 978-3-527-31824-7. www.catalysisbook.org Figure 6.18

20. Catalysis/ Rothenberg, ISBN 978-3-527-31824-7. www.catalysisbook.org Figure 6.19 descriptor 3 descriptor 2 d ij the model space candidate with high residuals descriptor 1

21. Catalysis/ Rothenberg, ISBN 978-3-527-31824-7. www.catalysisbook.org 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

22. Catalysis/ Rothenberg, ISBN 978-3-527-31824-7. www.catalysisbook.org 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

23. Catalysis/ Rothenberg, ISBN 978-3-527-31824-7. www.catalysisbook.org Figure 6.22 B A residual sample space principal component model space PC 1 PC 2 residual

24. Catalysis/ Rothenberg, ISBN 978-3-527-31824-7. www.catalysisbook.org Figure 6.23

25. Catalysis/ Rothenberg, ISBN 978-3-527-31824-7. www.catalysisbook.org Figure 6.24

26. Catalysis/ Rothenberg, ISBN 978-3-527-31824-7. www.catalysisbook.org Figure 6.25

27. Catalysis/ Rothenberg, ISBN 978-3-527-31824-7. www.catalysisbook.org Figure 6.26 319 93 92 12 307 1 Pd Loading <0.75 302 110 6 70296 40 3 03 70 12 33284 7 1 26 7 11 3 6 1 8 Pd Loading <0.3 LUMO <0.39 Time <3.5 Pd Loading <2.15 R max <3.13 TON TOF

28. Catalysis/ Rothenberg, ISBN 978-3-527-31824-7. www.catalysisbook.org Figure 6.27

29. Catalysis/ Rothenberg, ISBN 978-3-527-31824-7. www.catalysisbook.org Figure 6.28

30. Catalysis/ Rothenberg, ISBN 978-3-527-31824-7. www.catalysisbook.org Figure 6.29 0 mean-centering 0 autoscaling one standard deviation 1 0