Halogen‐Substituted Binuclear Copper Complexes as Efficient Catalysts for Azide–Alkyne Cycloaddition Reactions

ABSTRACT This study investigated the catalytic potential of novel binuclear copper complexes with halogen‐based ligands (Com‐X, X = F, Cl, Br, I) in copper(I)‐catalyzed azide–alkyne cycloaddition (CuAAC) reactions. All calculations were performed via the MN12‐L functional, where the Def2‐SVP basis set was employed for all atoms, whereas the copper centers were treated with the Def2‐TZVP basis set. The results highlight the thermodynamic stability and electronic properties of these complexes, alongside their noncovalent interactions and reduced density gradient (RDG) analyses. Importantly, the relationship between electronic descriptors (hardness, softness, electrophilicity, and charge transfer capacity) and catalytic activity was explicitly established, showing that the greater softness and charge transfer ability of Com‐Br correlate with its lower activation barrier. Among the tested systems, Com‐Br demonstrated the most favorable balance of electronic and steric effects, resulting in the lowest Gibbs free energy barrier for the key transition state. The solvent effects further revealed significant variations in the energy profiles, underscoring the influence of the reaction medium. The insights provided herein lay a robust theoretical foundation for understanding the structure–activity relationships in multinuclear copper catalysts, and they offer promising directions for the design and experimental validation of efficient, sustainable CuAAC systems.