To target a condensed version of the HKUST-1-like tbo-type MOF MFM-181, a new tetraisophthalate ligand, 3,6-dimethyl-1,2,4,5-tetra(5'-isophthalic acid)benzene, was rationally designed and synthesized based on ligand contraction and conformation preorganization strategy. Compared to its parent compound MFM-181, the resulting MOF ZJNU-10 features smaller cage sizes as well as higher density of open copper sites, thus endowing the material with the promising potential for C2H2/CH4 and CO2/CH4 separations associated with C2H2 purification and natural gas sweetening. At 298 K and atmospheric pressure, the uptake capacities of C2H2 and CO2 reach 151.5 and 108.3 cm3 (STP) g-1, while the IAST-predicted adsorption selectivities of C2H2 and CO2 over CH4 are up to 29.9 and 7.6, respectively.