Yuxiao Zhang, Dongxu Cui, Kexin Chen, Wei Li, Bo Zhu, Weichao Chen, Xinlong Wang, Zhongmin Su, Ru‐Quan Ye, Chi‐Ming Che, Chunyi Sun
ABSTRACT Encapsulation of metal clusters in porous organic cages (POCs) is a promising strategy for metalloenzyme‐mimetic catalysts. However, constructing POCs with endogenous metal clusters and achieving atomic‐level control over their formation and structural evolution remains a key challenge. Here, we realize the in situ growth of a cubic tetranuclear Ag‐halide cluster in an imine‐based [4+6] POC ( α ‐Ag 4 X 4 @Cage‐2 , X = Cl, Br, I) via coordination‐driven tandem assembly, monitored by time‐resolved mass spectrometry. Upon heating, α ‐Ag 4 X 4 @Cage‐2 (X = Cl, Br) undergoes a single‐crystal‐to‐single‐crystal transformation, with symmetry breaking via Ag–X bond cleavage and structural transition from cubane to distorted hexahedron ( β phase). This is a rare atomic‐level observation of thermally induced structural change of endogenous metal clusters in molecular cages. For CO 2 electroreduction, β ‐Ag 4 X 4 @Cage‐2 reaches 98.7% FE CO at −1.05 V versus RHE with 100 h stability (outperforming its α ‐phase counterpart), a TOF of 100 060 h −1 at 500 mA cm −2 , ranking among top molecular materials. Mechanistic studies reveal that the β ‐Ag 4 X 4 structural distortion disrupts charge symmetry of the four Ag atoms and localizes electrons at the bond‐cleaved Ag site, lowering the energy barrier for key *COOH intermediate formation. This work offers insights into the dynamic evolution of confined metal clusters via precise host–guest structural engineering.