1. Interplay of theory and computations in science - Examples drawn from theoretical/experimental studies of  Reaction rates  On-water catalysiorganic reactions  Isotope fractionation  Single-molecule fluctuations Rudolph Marcus California Institute of Technology KITPC Workshop on Dynamics of Biomolecular Machinery Beijing August 6, 2009

4. ELECTRON TRANSFER MECHANISM Reaction Coordinate Free Energy

5. Rate Constant for Electron Transfer

12. Time-dependent Stokes Shift Reaction Coordinate Free Energy

13. Time-dependent Stokes Shift Calculated from Solvent Dielectric dispersion Hsu, Song &RAM JPC 1997

14. Time-dependent Stokes Shift. Coumarin 343 in Water Hsu, Song & RAM JPC B 1997.… Experiment ----- Theory, no adjustable parameters

15. Free Energy Surfaces Protein Reorganization

16. A H ~ 10 17 /s at low T Klinman et al. 1999, 2004 RAM 2008/2009 Thermophilic Alcohol Dehydrogenase - Oxidation of Benzyl Alcohol

17. Fluctuations in Catalysis Rate & Spectral Diffusion Chloresterol oxidase oxidation of FAD Using data of Xie et al., Science 1998. Prakash & RAM PNAS 2007

18. Equation relating Correlation Functions: Electrostatic Fluctuations at Active Site Prakash & RAM PNAS 2007

19. Fluctuations and Dielectric Dispersion Prakash & RAM JPC B 2008

20. Fluctuations in Enzyme Catalysis & Dielectric Dispersion Prakash & RAM PNAS 2007 Lipase catalyzed ester hydrolysis

21. Fluctuations for galactosidase Prakash & RAM 2008

22. Enzymes - Summary When is the kinetic isotope effect H/D T- independent? What does the breakpoint and pre-exponential factors of rate constants for a thermophilic enzyme tell us about flexibility? When do different single molecule time-correlation functions agree for the same enzyme and why? When does one expect “normal” Arrhenius preexponential factors A for H transfer? Does one expect a small A for proton-coupled electron transfer?

23.  An On-Water Cycloaddition Reaction Sharpless et al. 2005

24. SolventConc. [M]Time to completion Toluene2> 120 h DMSO236 h MeOH218 h MeOH/H 2 O (3:1 homogeneous)24 h Neat liquids4.5348 h on H 2 O (heterogeneous)4.5310 min MeOH/H 2 O (1:1 heterogeneous)4.5310 min on C 6 F 14 4.5336 h Sharpless and co-workers, Angew. Chem. Int. Ed. 44, 3275 (2005) Reaction Time Data

25. Ice Surface http://www.lsbu.ac.uk/water/ice1h.html

26. SolventReaction timeExperiment (s -1 )TST (s -1 ) Neat48 h4  10 -6 5  10 -7 Homogeneous 4 h9  10 -4 - on H 2 O10 min0.50.2 TST Rate Constants Compared with Experimental Rates Interfacial H-Bond formation is the key to the on-water rate acceleration

28. Interaction of Theory, Computation & Experiment Not Discussed Here Mass-independent isotope effect in stratosphere Combustion/atmospheric reactions and RRKM Fluorescence blinking of semiconductor QDs Vibrational adiabaticty, born of computatiom