A hexacationic cage 3 6+ was synthesized via hydrazone condensation in aqueous acid. Cage 3 6+ bears three biscationic arms, each of which contains four relatively acidic protons, including one NH and three CH protons. These hydrogen bond donors, as well as its intrinsic cationic nature, enable cage 3 6+ to encapsulate two anions concurrently within its cavity. The axial asymmetrical nature of the biscationic arms allow the cage to recognize two different anions in a selective manner, to encompass bound heteroanion dimers, such as Cl − •NO3 − and Cl − • Br − . Single crystal X-ray diffraction analyses reveal that in the solid state the two anions are constrained in ultraclose proximity within the cage; e.g., the Cl − •••Cl − and Cl − •••Br − distances are 3.2 and 2.9 Å, respectively, which are shorter than the sum of their van der Waals radii. Evidence consistent with the sequential binding of two identical or disparate anions in CD 3 CN is also presented.

A triangular‐prism shaped cage was self‐assembled by the formation of a dynamic covalent bond, namely a hydrazone, in acidic aqueous solution. The hexacationic host bears a number of relatively acidic protons pointing inside the cage cavity, which is able to accommodate an iodide anion selectively in water over other halide anions such as F−, Cl−, and Br−, which are more hydrated. As a comparison, a macrocycle analogue bearing fewer positive charges and fewer hydrogen bond donors shows no anion binding ability. As inferred from the single‐crystal structure and theoretical calculations, the ability of the cage to selectively recognize iodide anions results from the combination of electrostatic forces, C−H⋅⋅⋅I− hydrogen bonds, and the hydrophobic effect.

Here, we announce the establishment of a new family of organic molecular cages, named cagearenes, by taking advantage of a versatile strategy. That is precursors grafted by 1,4-dimethoxybenzene groups are...

Stimulator of interferon genes (STING) orchestrates the production of proinflammatory cytokines in response to cytosolic double-stranded DNA; however, the pathophysiological significance and molecular mechanism underlying the folding and maturation of nascent STING protein at the endoplasmic reticulum (ER) remain unknown. Here we report that the SEL1L–HRD1 protein complex—the most conserved branch of ER-associated degradation (ERAD)—is a negative regulator of the STING innate immunity by ubiquitinating and targeting nascent STING protein for proteasomal degradation in the basal state. SEL1L or HRD1 deficiency in macrophages specifically amplifies STING signalling and immunity against viral infection and tumour growth. Mechanistically, nascent STING protein is a bona fide substrate of SEL1L–HRD1 in the basal state, uncoupled from ER stress or its sensor inositol-requiring enzyme 1α. Hence, our study not only establishes a key role of SEL1L–HRD1 ERAD in innate immunity by limiting the size of the activable STING pool, but identifies a regulatory mechanism and therapeutic approach to targeting STING.