First principle quantum chemical methods and atomistic simulations are used to probe active sites, ensembles, and reaction environments and assist in their design for metal catalyzed reactions. Heterogeneous catalytic reactions which take place over one- or two-metal-atom centers such as hydrogenation and dehydrogenation resemble analogous homogeneous systems and tend to be structure insensitive. Alloys can be used in order to improve the selectivity of these reactions to specific products by shutting down unwanted paths that lead to byproduct formation. The activity for these reactions, however, does not change appreciably with changes in structure or surface composition. For hydrogenation, this is due to a balance between lower hydrogen surface coverages which decrease the rate and more weakly bound hydrocarbon intermediates which increase the rate. Reactions that require larger ensemble sizes such as N-2 activation, ethane hydrogenolysis, hydrocarbon coupling, and vinyl acetate synthesis are much more structure sensitive. Both the activity and the selectivity can be improved in these systems by the optimal design of the specific sites and bifunctional ensembles. An ab initio based kinetic Monte Carlo simulation scheme was developed and used to engineer Pd/Au alloys in order to improve the activity for vinyl acetate synthesis by about a factor of 2 and the selectivity by about 5%. Altering the properties of the solution phase offers a means to probe and manipulate part of the 3D atomic structure around the active sites. More specifically we examine the activation of water over Pt, PtRu, and Ru surfaces in the presence as well as the absence of solution. Our results show that Pt, Ru, and the water solution work together synergistically to provide a low energy heterolytic path for the activation of water to form OH*((-)), H5O2+(aq), and le- Ab initio MD simulations were subsequently used and uncovered a new path for the diffusion of hydroxyl across the surface which involves a sequence of proton transfer reactions. (C) 2003 Elsevier Science (USA). All rights reserved.