Wrinkled Pd Metallene: Synergistic Geometric and Electronic Engineering for High-Performance Bioorthogonal Catalysis

Abstract Palladium-mediated bioorthogonal catalysis enables in situ activation of therapeutic and diagnostic agents within living systems, yet developing high-efficacy catalysts remains challenging. Herein, we report a wrinkled Pd metallene catalyst (Pd ML) in which nanoscale wrinkling generates abundant active sites and induces lattice strain, thereby optimizing the electronic and geometric configurations of the catalytic centers for high-performance bioorthogonal catalysis. The Pd MLs exhibit substantially enhanced catalytic activity compared to Pd nanoparticles and their wrinkle-free counterpart, flat Pd metallene. Theoretical calculations reveal that the wrinkle-induced lattice strain shifts the d-band center of Pd downward, thereby facilitating the bioorthogonal reaction. Following functionalization with the AS1411 aptamer, the Pd MLs enable targeted activation of an antitumor prodrug and realize efficient tumor suppression both in vitro and in vivo. This work represents the first example of enhancing bioorthogonal catalysis via synergistic geometric and electronic engineering, establishing a rational paradigm for the development of high-performance bioorthogonal catalysts.