Catalytic conversion of biomass-derived synthesis gas to ethanol and other C oxygenates has received considerable attention recently due to the strong demands for alternative, renewable energy sources. Combining experimental measurements with first-principles-based kinetic modeling, we investigated the reaction kinetics of ethanol synthesis from CO hydrogenation over SiO2 -supported Rh/Mn alloy catalysts. We find that an Mn promoter can exist in a binary alloy with Rh and play a critical role in lowering the CO insertion reaction (CO + CHx (x = 1-3)) barriers thus improving the selectivity toward ethanol and other C-2(+) oxygenates, although the barrier toward methane formation is unaffected. The postulation of supported Rh/Mn alloy nanoparticle being the active phase is supported by our experimental characterization using X-ray photoelectron spectroscopy, transmission electron microscopy, and X-ray diffraction of practically used Rh/Mn/SiO2 catalysts. First-principles density functional theory (DFT) calculations further confirmed that the binary Rh/Mn alloy is thermodynamically more stable than the mixed metal/metal oxides under the reducing reaction condition. The reaction kinetics of CO hydrogenation to ethanol on the three-dimensional Rh/Mn nanoparticle under experimental operating conditions was studied using kinetic Monte Carlo (KMC) simulations. The simulated reaction kinetics is qualitatively consistent with experimental observations. Finally, the effects of various promoters (M = Ir, Ga, V, Ti, Sc, Ca, and Li) on the CO insertion reaction over Rh/M alloy nanoparticles were investigated using DFT calculations. We found alloying the promoters with the electronegativity difference, Delta chi, between the promoter (M) and Rh being 0.7 is the most effective in lowering the barriers of CO insertion reaction, which leads to higher selectivity to ethanol. This conclusion is in excellent accord with the reported catalytic performance of CO hydrogenation over Rh-based catalysts with different promoters. We believe that the electronegativity difference criterion is very useful in improving the catalytic performance using transition metal-based catalysts for ethanol synthesis from CO hydrogenation. (C) 2010 Elsevier Inc. All rights reserved.