Neutron powder diffraction experiments on D-2-loaded NOTT-112 reveal that the axial sites of exposed Cu(II) ions in the smallest cuboctahedral cages are the first, strongest binding sites for D-2 leading to an overall discrimination between the two types of exposed Cu(II) sites at the paddlewheel nodes. Thus, the Cu(II) centers within the cuboctahedral cage are the first sites of D-2 binding with a Cu-D-2 distance of 2.23(1) angstrom.