1 An Encapsulated Water Governs Catalysis in a Supramolecular Capsule for Reductive Elimination Reaction from Gold Valerie Vaissier Welborn 1,2,3 and Teresa Head-Gordon 1-5* 1 Kenneth S. Pitzer Center for Theoretical Chemistry 2 Department of Chemistry, University of California, Berkeley 3 Chemical Sciences Division, Lawrence Berkeley National Labs, Berkeley 4 Department of Chemical and Biomolecular Engineering and 5 Department of Bioengineering, University of California, Berkeley E-mail: thg@berkeley.edu Supramolecular assemblies have gained tremendous attention due to their apparent ability to catalyze reactions with the efficiencies of natural enzymes. Using Born-Oppenheimer molecular dynamics and density functional theory, we identify the origin of the catalytic power of the supramolecular assembly Ga4L6 12− on the reductive elimination reaction from gold complexes. By comparing the catalyzed and uncatalyzed reaction in explicit solvent to identify the reaction free energies of the reactants, transition states, and products, we determine that the catalysis arises from an encapsulation of a catalytic moiety- a primary water molecule – that is unlike the biomimetic scenario of catalysis through direct host-guest interactions.