Waterproof architectures through subcomponent self-assembly

Metal-organic containers are readily prepared through self-assembly, but achieving solubility and stability in water remains challenging due to ligand insolubility and the reversible nature of the self-assembly process. Here we have developed conditions for preparing a broad range of architectures that are both soluble and kinetically stable in water through metal(II)-templated (M-II = Co-II, Ni-II, Zn-II, Cd-II) subcomponent self-assembly. Although these structures are composed of hydrophobic and poorlysoluble subcomponents, sulfate counterions render them water-soluble, and they remain intact indefinitely in aqueous solution. Two strategies are presented. Firstly, stability increased with metalligand bond strength, maximising when NiII was used as a template. Architectures that disassembled when Co-II, Zn-II and Cd-II templates were employed could be directly prepared from NiSO4 in water. Secondly, a higher density of connections between metals and ligands within a structure, considering both ligand topicity and degree of metal chelation, led to increased stability. When tritopic amines were used to build highly chelating ligands around Zn-II and Cd-II templates, cryptate-like water-soluble structures were formed using these labile ions. Our synthetic platform provides a unified understanding of the elements of aqueous stability, allowing predictions of the stability of metal-organic cages that have not yet been prepared.