Heme-Cu/O-2 adducts are of interest in the elucidation of the fundamental metal-O-2 chemistry occurring in heme-Cu enzymes which effect reductive O-O cleavage of dioxygen to water. In this report, the chemistry of four heme-peroxo-copper [Fe-III-(O-2(2-))-Cu-II](+) complexes (1-4), varying in their ligand architecture, copper-ligand denticity, or both and thus their structures and physical properties are compared in their reactivity toward CO, PPh3, acids, cobaltocene, and phenols. In 1 and 2, the copper(II) ligand is N-4-tetradentate, and the peroxo unit is bound side-on to iron(III) and end-on to the copper(II). In contrast, 3 and 4 contain a N-3-tridentate copper(II) ligand, and the peroxo unit is bound side-on to both metal ions. CO "displaces" the peroxo ligand from 2-4 to form reduced CO-Fe-II and CO-Cu-I species. PPh3 reacts with 3 and 4 displacing the peroxide ligand from copper, forming (porphyrinate)Fe-III-superoxide plus Cu-I-PPh3 species. Complex 2 does not react with PPh3, and surprisingly, 1 reacts neither with PPh3 nor CO, exhibiting remarkable stability toward these reagents. The behavior of 1 and 2 compared to that of 3 and 4 correlates with the different denticity of the copper ligand (tetra vs tridentate). Complexes 1-4 react with HCl releasing H2O2, demonstrating the basic character of the peroxide ligand. Cobaltocene causes the two-electron reduction of 1-4 giving the corresponding mu-oxo [Fe-III-(O2-)-Cu-II](+) complexes, in contrast to the findings for other heme-peroxo-copper species of different design. With t-butyl-substituted phenols, no reaction occurs with 1-4. The results described here emphasize how ligand design and variations influence and control not only the structure and physical properties but also the reactivity patterns for heme-Cu/O-2 adducts. Implications for future investigations of protonated heme/Cu-peroxo complexes, low-spin analogues, and ultimately O-O cleavage chemistry are discussed.