Much like lead-optimization in drug discovery, we aimed to judiciously tune the chemistry of a "lead" MOF, Ni(PyC) 2 in Fig. , for Xe/Kr separations to enhance its Xe/Kr selectivity and Xe uptake at room temperature. We conducted a virtual screening of Ni(PyC) 2 analogues to guide experimental pursuits in the laboratory. First, we confirmed that molecular models and simulations reproduce the experimentally measured Xe, Kr, and Ar adsorption isotherms in Ni(PyC) 2 (see Fig.