Substituent‐Driven Switch Between Os…O and O…H Interaction and the Emerging Cooperative/Anti‐Cooperative Effect in X–Py·OsO 4 ·H 2 O Ternary Complexes

In this study, we present a quantum mechanical investigation of Osme‐bonded binary and ternary complexes formed between OsO 4 , substituted pyridines (X–Py; X = NH 2 , OCH 3 , OH, CH 3 , F, Cl, CF 3 , CN, and NO 2 ), and H 2 O molecule, highlighting their potential relevance for higher‐order cocrystal design without relying predominantly on hydrogen bond. The binding energies of Os…N Osme‐bonded binary complexes (−39.1 to −26.5 kJ/mol) exhibit pronounced substituent dependence and correlate strongly with descriptors like proton affinity, ionization potential, and V s,min . Atoms in molecule (AIM) analyses confirm partial covalent character of Os…N bond, stabilized by charge transfer and hyperconjugation effects. Incorporation of H 2 O results in structurally distinct ternary motifs, whose cooperative or anti‐cooperative nature can be selectively tuned through rational pyridine substitution. Unsubstituted pyridine forms two ternary arrangements (type I and type II), whereas substitution markedly alters the stability and existence of these motifs, particularly for type II complexes. For type II complexes, electron‐donating groups promote hydrogen bonding and reinforce Os…N interactions, resulting in pronounced cooperativity, while electron‐withdrawing groups favor alternative Os…O pathways and induce anti‐cooperativity. Overall, this study shows how substituent‐induced OsO 4 distortion controls σ‐hole accessibility, directing Osme versus hydrogen bonding to tune structure, cooperativity, and stability in multicomponent assemblies.