Atomistic Insights into Aqueous Phase Carbonyl Hydrogenation over Ru Catalysts from a Hybrid QM/MM/ML Potential

The aqueous-phase hydrogenation of methyl ethyl ketone (2-butanone, MEK) to 2-butanol over Ru(0001) was investigated as a model system to elucidate condensed-phase effects in the catalytic hydrogenation of carbonyl-containing feedstocks. A hybrid quantum mechanical/molecular mechanical/machine learning free-energy perturbation (QM/MM/ML-FEP) framework was employed to quantify solvent effects on the relative stabilization of surface intermediates and transition states. Microkinetic modeling reveals that the Alkoxy pathway is favored over the Hydroxy pathway across all environments—dry gas, co-fed water vapor, and liquid water. Water plays a dual mechanistic role: it directly promotes hydrogenation of the carbonyl oxygen via proton shuttling/hydrogen-atom transfer from adsorbed H2O/OH species, and it acts as a solvent that modulates the adsorption strength of surface intermediates and transition states. In the co-fed water vapor system, the second hydrogenation step proceeds through H-mediated (63%), H₂O-mediated (31%), and OH-mediated (5%) pathways, whereas in liquid water, the reaction occurs exclusively through the H₂O-mediated pathway, enhancing the overall turnover frequency by an order of magnitude and shifting the rate controlling step from the second to the first hydrogenation of the carbonyl carbon. These findings demonstrate that the enhanced activity of aqueous-phase Ru-catalyzed carbonyl hydrogenation arises from both the direct participation of water in the mechanism and its solvent-induced stabilization and destabilization of key surface states.