Despite the widespread use of bimetallic nanomaterial catalysts, a molecular-level understanding of the synergistic effects is unclear, limiting our ability to pre-design "tailor-made" bimetallic catalysts. We chose bimetallic Au1Ag24(SR)(18) and Au25-xAgx(SR)(18) (x = 2-6) nanoclusters (NCs) as models to investigate the relationship between microstructure and performance, comparing them with the corresponding monometallic NCs. Experimental and theoretical analyses demonstrated that the Au@Ag kernel was the essential structural feature for high activity and super stability of Au1Ag24(SR)(18) catalyst in the alkynylation of CF3-ketone. This structure-activity relationship was successfully extended to other bimetallic systems bearing an Au@Ag kernel, such as Au12Ag32(SR)(30) NC, and is thought to constitute a guiding principle for the intelligent design of high-performance bimetallic catalysts in the future. (C) 2019 Elsevier Inc. All rights reserved.