Solvothermal reactions of Cu(II) nitrate with isophthalic acid (H2IPT) in various solvents create five novel metal coordination polymers, [Cu(IPT)(H2O)](H2O)2 (1), Cu(IPT)(C2H5OH) (2), Cu2(IPT)2(DEF)(H2O) (3) (DEF = N,N′-diethylformamide), [Cu4(IPT)4(DMF)2(C2H5OH)(H2O)](DMF)2 (4) (DMF = N,N′-dimethylformamide), and [Cu2(IPT)2(CH3CN)(H2O)](H2O)2.25 (5), respectively. Structural analyses exhibit that they all form 2D non-interpenetrated square-grid layers based on paddle-wheel Cu2 clusters as nodes and isophthalate as linkers, in which various guest molecules are trapped via either the coordination to open Lewis acid copper sites or inclusion in open channels. The different chemical affinities of the 2D square-grid layers toward various solvent molecules result in guest-induced deviation of these 2D layers and diverse porosities in their frameworks, as realized by the distinct gas adsorption properties.