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Copper(I) and copper(II) complexes of 5-nitroimidazole conjugated heteroscorpionate ligands have been synthesized. In particular, the new 2,2-bis(pyrazol-1-yl)-N-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)acetamide ligand (L H MN) was synthesized by direct coupling of preformed side chain acid with 5-nitroimidazole and its coordination chemistry was investigated towards Cu(I) and Cu(II) acceptors and compared with that of the related 2,2-bis(3,5-dimethyl-1-H-pyrazol-1-yl)-N-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)acetamide ligand (L Me MN). The copper(II) complexes {[(L Me MN) 2 Cu]Cl 2 } and {[(L H MN) 2 Cu]Cl 2 } were prepared by the reaction of CuCl 2 ·2H 2 O with L H MN or L Me MN ligands in methanol solution. The water soluble copper(I) complexes {[(L Me MN)Cu(PTA) 2 ]}(PF 6 ) and {[(L H MN)Cu(PTA) 2 ]}(PF 6 ) were prepared by the reaction of Cu(CH 3 CN) 4 PF 6 and 1,3,5-triaza-7-phosphaadamantane (PTA) with L H MN or L Me MN ligands in acetonitrile solution. The new Cu(I) and Cu(II) complexes as well as the corresponding uncoordinated ligands were evaluated for their cytotoxic activity against 2D monolayer cultures of multiple human cancer cell lines and 3D-cultured HCT-15 colon cancer spheroids. Morphological analysis by Transmission Electron Microscopy (TEM) revealed the induction of a massive cytoplasmic vacuolization consistent with a paraptotic-like cancer cell death. [ABSTRACT FROM AUTHOR]