1. Towards More Realistic Molecular Modeling of Homogenous Catalysis: Combined QM/MM and ab initio Molecular Dynamics Investigations Tom K. Woo, Peter M. Margl, Liqun Deng, Luigi Cavallo, Tom Ziegler Department of Chemistry, University of Calgary, Calgary, Alberta, CANADA

2. Brookhart Polymerization Catalyst C&EN Feb. 5, 1996: “Polymer Catalyst System: Dupont Eyes New Polyolefin Business” Brookhart catalyst highly linear to moderately branched Johnson, L. K.; Killian, C. M.; Brookhart, M. J. Am. Chem. Soc. 1995, 117, 2343. high MWs good activities

3. Brookhart Polymerization Catalyst C&EN Feb. 5, 1996: “Polymer Catalyst System: Dupont Eyes New Polyolefin Business” Brookhart catalyst highly linear to moderately branched Johnson, L. K.; Killian, C. M.; Brookhart, M. J. Am. Chem. Soc. 1995, 117, 2343.  temperature: Temp  branching   monomer pressure: [Et]  branching   bulk of substituents: bulk  branching  MW 

4. Polymerization Mechanisms isomerization termination insertion (branched) resting state

5. Polymerization Mechanisms isomerization termination insertion (branched) resting state barriers: barriers: insertion < isomerization < termination

6. “REAL” system PURE QM model system Pure QM Calculations ADF Density Functional Code: Baerends and Ziegler Becke 88 - Perdew 86 energies and gradients static, gas phase simulation of model system

7. Pure QM Results - Calculated Barriers insertion: isomerization: termination: 17.5 kcal/mol 12.8 kcal/mol 10.8 kcal/mol

8. Adding the Bulky Ligands termination Transition States insertion

9. Combined QM/MM - Overview QM region MM region QM region (active site) MO calculation MM region MM force field regions are treated simultaneously QM - MM regions interact via vdW & Coulomb QM electronic system capped “real” system QM system Maseras, F.; Morokuma, K. J. Comp. Chem. 1995, 16, 1170.

10. Insertion Profiles (kcal/mol) 14.7 13.2 10.0 19.4 16.8 6.7 TS PURE QM hybrid QM/MM

11. Orientation of the Aryl Rings resting state & termination TS insertion TS

12. Isomerization 15.3 -0.8 12.8 -1.8 PURE QM hybrid QM/MM

13. Termination Profiles (kcal/mol) TS 19.4 9.7 PURE QM 14.7 18.6 hybrid QM/MM

14. Comparison with Experiment Pure QM: 16.8 QM/MM: 13.2 EXP: 10 - 11 kcal/mol QM then MM: 18.5 insertion barrier

15. QM/MM Exp. insertion < isomerization < termination Order of Barrier Heights Comparison with Experiment 13.215.318.6 Pure QM: 16.8 QM/MM: 13.2 EXP: 10 - 11 kcal/mol QM then MM: 18.5 insertion barrier

16. Relative to Insertion Comparison with Experiment Pure QM (∆∆H el ) QM/MM (∆∆H el ) Exp. (∆∆G) insertionisomerizationtermination 0.0 -4.0-7.1 2.1 1.3*5.6 5.4 *monomer capture may be rate limiting for branching process

17. Primary Effects of Bulky Ligands destabilizes resting state N-C(aryl) torsion important bulkier the groups, the higher the activity diimine methyl important in chain termination Insertion: bulkier the groups, the higher the MW termination: monomer capture may dominate isomerization:

18. Combined QM/MM ab initio MD Coupled AMBER with Car-Parrinello AIMD code PAW code - Peter Blöchl of IBM Zürich Becke 88 - Perdew 86 QM potential 300 K simulation temperature slow growth simulation 2 weeks on an IBM 3CT workstation with 64 MB ram 40 000 time step simulations

19. Reaction Barriers with AIMD thermodynamic integration  free energy barriers reaction coordinate constrained during dynamics RC slowly varied, leading system over barrier relative free energies along RC calculated by:

20. Termination Barrier Exp: 15-16 kcal/mol

21. Brookhart Termination Movie

23. Conclusions implemented QM/MM ab initio molecular dynamics method determined free energy barrier with QM/MM AIMD methods show good promise QM/MM boundary is dubious successfully applied QM/MM method to transition metal based homogenous catalysis

24. Future Work multiple time step AIMD electrostatic coupling in AIMD for solvent simulations validation and calibration of QM/MM method simulation of monomer trapping in Brookhart catalyst

25. Acknowledgments NSERC of Canada Novacor Chemicals of Calgary Alberta Heritage Scholarship Fund Killam Memorial Foundation NSERC TKW Visit our Home Page at: http://www.chem.ucalgary.ca/groups/ziegler Maurice Brookhart Peter Blöchl at IBM Zürich PMM Austrian Fonds zur Förderung de Wissenschaftlichen Forschung