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

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, high MWs good activities

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,  temperature: Temp  branching   monomer pressure: [Et]  branching   bulk of substituents: bulk  branching  MW 

Polymerization Mechanisms isomerization termination insertion (branched) resting state

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

“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

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

Adding the Bulky Ligands termination Transition States insertion

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.

Insertion Profiles (kcal/mol) TS PURE QM hybrid QM/MM

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

Isomerization PURE QM hybrid QM/MM

Termination Profiles (kcal/mol) TS PURE QM hybrid QM/MM

Comparison with Experiment Pure QM: 16.8 QM/MM: 13.2 EXP: kcal/mol QM then MM: 18.5 insertion barrier

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

Relative to Insertion Comparison with Experiment Pure QM (∆∆H el ) QM/MM (∆∆H el ) Exp. (∆∆G) insertionisomerizationtermination * *monomer capture may be rate limiting for branching process

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:

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 time step simulations

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:

Termination Barrier Exp: kcal/mol

Brookhart Termination Movie

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

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

Acknowledgments NSERC of Canada Novacor Chemicals of Calgary Alberta Heritage Scholarship Fund Killam Memorial Foundation NSERC TKW Visit our Home Page at: Maurice Brookhart Peter Blöchl at IBM Zürich PMM Austrian Fonds zur Förderung de Wissenschaftlichen Forschung