Influence of Ligand Backbone Functional Groups on the Stability of Metal–Organic Cages in Solution

Metal-organic assemblies are frequently functionalized at the heart of the ligand backbone, far from the linkage-defining coordination sites, to bestow solubilizing alkyl chains, binding receptors, or covalently modifiable reaction sites to the whole architecture. Herein, we show that slight alterations to the functional group in the ligand backbone can affect the solution stability of the entire assembly, albeit with a more subtle influence than protecting groups close to the metal node. Consumption of metal-organic cages (MOCs) during ligand exchange, analyzed via HPLC, is faster for those containing more polar methylene alcohol substituents in the ligand backbone; conversely, cages with less polar dithiane functional groups are the most kinetically stable, with the lifetime of the MOCs in solution increasing by over an order of magnitude. Understanding the consequences of ligand backbone modification influences the design of functional MOCs and offers a means of tailoring MOC stability for guest uptake and release.