Halogen bonding in Halopyridine‐Copper(II) Complexes. A comprehensive solid‐state and interaction study with human serum albumin

Fifty-four halopyridines were classified into six series based on halogen substituent positions at ortho, meta, and para to the pyridinic nitrogen. Complexation of these halopyridines with CuCl2 and CuBr2 from acetonitrile and ethanol resulted in 158 X-ray structures, including five mixed-ligand-Cu(II) complexes. The dataset provides generalizable insights into coordination structures governed by the halogen atom and position. Bonding and structural analysis across the six halopyridine series, considering bond lengths, angles, and coordination geometries, reveals no more than 19 distinct structural motifs. Across this diverse structural landscape, each halopyridine series adopts a maximum of six coordination structure motifs. The halogen position determines whether crystallization yields single crystals or non-crystalline solids. The ortho-halogens display unique dual properties. Their σ-hole participates in the CX···Cl/BrCu (X = F, Cl, Br, I) halogen bonding, while their electron-belt simultaneously participates in intramolecular CX···Cu interactions, influencing whether ortho-halogens adopt cis- or trans-arrangements in Cu(II) complexes. The density functional theory-computed energies of C–X···Cu interactions vary from 1 to 4 kcal mol−1, depending on the halogen atom identity. Docking studies with human serum albumin reveal stabilizing protein-halopyridine-Cu(II) interactions. These findings provide a framework for the rational design of halopyridine-Cu(II) complexes for applications in materials and bioinorganic chemistry.