 Synthetic framework materials are appealing candidates for the fabrication of separation membranes but realizing precise control of aperture distribution and separation threshold remains challenging. Here, the authors show a two-dimensional processable supramolecular framework which can be used in the fabrication of separation membranes by integrating directional organic host-guest motifs and inorganic functional polyanonic clusters. This article was authored by Kuohua Zhong, Shin-Yu Li, Gan Chen, and others.