A noteworthy framework in the context of air separations is Cu I -MFU-4l (CuxZn5-x(Cl/OOCH)4-x(btdd)3; H2btdd= bis(1H-1,2,3triazolo [4,5-b],[4′,5′-i])dibenzo [1,4]dioxin), which features pentanuclear cluster nodes consisting of a central octahedral zinc(II) ion coordinated to four peripheral metal ions-either pyramidal copper(I) or tetrahedral zinc(II) (Figure ). Under ambient conditions, the copper(I) sites in the framework have been shown to strongly and reversibly bind O2, and the favorable calculated ΔG of O2 binding in this material suggests that it may be promising candidate for O2-selective adsorptive air separations. Additionally, in the context of hard-soft acid-base theory, we hypothesized that the intrinsic mismatch between the soft copper(I) ion and hard water molecule may render Cu I -MFU-4l selective for O2 even in the presence of water. Herein, we disclose that Cu I -MFU-4l, synthesized with new optimized procedures that result in higher Cu I loadings, is able to reversibly adsorb O2 from air at ambient temperatures with excellent cyclability, even in the presence of water vapor. Variable-temperature in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and magnetic susceptibility data indicate that O2 binds at the copper(I) sites to form copper(II)-superoxide motifs and that side-and end-on superoxide binding modes in equilibrium over a range of temperatures. We find that differences in the kinetics of O2 and N2 desorption from the framework allow for the isolation of high-purity O2, providing a new approach to separate O2 directly from ambient air.