Co(II), Cu(II), and Ni(II) Coordination Complexes: Synthesis, Characterization, Experimental, and Computational Study on Potential Antiplasmodial Activity

In this work, the synthesis and structural characterization of coordination complexes C1 (Co−Cl), C2 (Cu−Cl), C3 (Co−Br), and C4 (Ni−Cl) with the ligand 2‐( tert ‐butoxy)‐6‐(1H‐imidazol‐1‐yl)pyridine ( L ) was carried out. The X‐ray diffraction reveals the presence of four equatorial L and two axial halogens as coligands. The synthesized complexes crystallize in a P −1 space group. Topological analysis using ToposPro assigned the discrete 1,6M7‐1 topology, in which ZA1 and ZA2 represent nonequivalent supramolecular ligand contacts, while the suffix −1 denotes the first nonisomorphic net not included in the RCSR database. The complexes were evaluated against Plasmodium falciparum , showing the high influence of the metal coordination in the modulation of the antiplasmodial activity relative to the free ligand, particularly against the resistant phenotype. All evaluated complexes retained inhibitory effects against both chloroquine‐sensitive and chloroquine‐resistant P. falciparum strains. Among the series, C3 and C4 emerged as the most promising candidates due to their favorable balance between antiplasmodial activity, selectivity, and low hemolytic profile. Computational analyses further revealed that modulation of the electronic properties, chemical softness, and lipophilic profiles of the complexes may contribute to their distinct biological behavior, while molecular docking suggested plausible interactions with parasite‐associated enzymatic targets.