Unavailable surface structures of nanocatalysts often pose a challenge to molecular-level understanding of catalytic mechanisms. Recent progress in the structural characterization of gold nanoclusters with atomic precision has enabled them to serve as excellent model systems to scrutinize structure-reactivity correlation. Here a case study is reported in which the full structure of the Au-25(SCH2CH2Ph)(18) nanocluster catalyst allows detailed mechanistic insight into the Suzuki cross coupling reaction pathways at the atomic/molecular level-in particular, the promotional effect of imidazolium-based ionic liquids (ILs) on the coupling reaction between phenylboronic acid and p-iodoanisole. The catalytic mechanisms are studied using UV-vis spectroscopy, MALDI mass spectrometry, density functional theory (DFT) calculations, and classical molecular dynamics (MD) simulations. Partial removal of thiolate ligands (-SR) and "Au-SR" units from the protected Au-25 cluster through interactions with imidazolium cations is deemed the promotion mechanism in the cross-coupling reaction. Both the experiment and DFT calculation indicate that the acidic proton at position 2 of the imidazolium ions plays an important role in the detachment of SR ligands and Au atoms from the nanocluster surface, which in turn allows the cross-coupling reaction to occur at a much milder temperature than in the absence of the IL promoter. Results suggest that oxidation of the active gold species not only prevents further fragmentation of the nanoparticles by the ILs but also increases the interaction of reactants with the catalysts, thereby improving the conversion rate. (C) 2016 Elsevier Inc. All rights reserved.