Controlled isomerization of individual {alpha-P2W12O48} polyoxotungstate building blocks under the constricted conditions of the macrocyclic [P8W48O184](40-) archetype ({P8W48}) is linked to site-specific Cull coordination. The derivatives [alpha gamma alpha gamma-P8W48O184{Cu(H2O)}(2)](36-) (1), [gamma gamma gamma gamma-P8W48O184{Cu(H2O)(0.5)}(4)](32-) (2), and [alpha gamma gamma gamma-P8W48O184{Cu(H2O)}(3)](34-) (3) feature the {alpha gamma alpha gamma-P8W48} and the hitherto unknown {gamma gamma gamma gamma-P8W48} and {alpha gamma gamma gamma-P8W48} isomers based on {alpha-P2W21} and/or Cu-II-stabilized {gamma-P2W12} units and form from the reactions of the classical {P8W48} (={alpha alpha alpha alpha-P8W48}) and CuCl2 in sodium acetate medium (pH 5.2). All products were thoroughly characterized in both the solid state and aqueous solutions, including electrocatalysis assessments.