First, we show that the molecular models and simulations reproduce the experimentally measured, pure-component Xe, Kr, and Ar equilibrium adsorption isotherms ( K) in Ni(PyC) 2 . Second, we construct a library of Ni(PyC-X) 2 crystal structure models by, in silico, appending various functional groups X to the PyC ligand of the parent Ni(PyC) 2 and optimizing the geometry. Next, in each Ni(PyC-X) 2 structure, we conduct molecular simulations of noble gas adsorption at dilute conditions and K to predict their Xe, Kr, and Ar Henry coefficients and, from those, their Xe/Kr, Xe/Ar, and Kr/Ar selectivities. Among several Ni(PyC-X) 2 structures predicted to exhibit a higher Xe/Kr selectivity than the parent Ni(PyC) 2 MOF, we then target Ni(PyC-m-NH 2 ) 2 for experimental synthesis, characterization via XRPD, and noble gas adsorption measurements. Finally, we conduct in situ X-ray diffraction studies to elucidate the prominent Xe adsorption sites in Ni(PyC-m-NH 2 ) 2 , corroborated by molecular models and simulations. cause we construct each Ni(PyC-X) 2 structure starting with the parent Ni(PyC) 2 structure, each MOF in our library shares the same topology, unit cell, and coordination environment as the parent MOF in Fig.