A structurally flexible porous metal–organic framework, [Cu^II(bped)₂(H₂O)₂(SiF₆)] ⊃ 4H₂O (Cu-MOF-SiF₆) was prepared from CuSiF₆ and meso-1,2-bis(4-pyridyl)-1,2-ethanediol (bped) in EtOH–H₂O. Cu-MOF-SiF₆ is a three-dimensional (3D) polycatenated framework consisting of two-dimensional (2D) (4,4) topological grid networks which display 2-fold inclined interpenetration in the crystal lattice. The SiF₆²⁻ anions hosted in the one-dimensional channels of Cu-MOF-SiF₆ can be readily exchanged with NO₃⁻ anions while keeping the framework intact, leading to isomorphous Cu-MOF-NO₃. The Cu-MOFs show selective adsorption behaviors due to the host–guest interaction, which is dependent on the anions and the guest size. The MeOH uptake investigation indicates that Cu-MOF-SiF₆ demonstrates a breathing effect, while Cu-MOF-NO₃ exhibits distinctive stepwise MeOH sorption due to the smaller size of NO₃⁻ and the larger voids in the crystal lattice. Cu-MOF-NO₃ also exhibits stepwise sorption for larger EtOH guests, while the uptake of EtOH is blocked in Cu-MOF-SiF₆. In addition, the solids show anion-responsive catalytic properties. Both Cu-MOF-SiF₆ and Cu-MOF-NO₃ efficiently oxidize benzylic compounds to the corresponding carbonyl functionality under mild and convenient reaction conditions, but improved catalytic activity was observed for Cu-MOF-NO₃. The catalysts can be reused with the framework left intact at least three times without losing of any activity.