Adaptive Behavior of Dynamic Orthoester Cryptands.

The integration of dynamic covalent bonds into macrocycles has been a tremendously successful strategy for investigating noncovalent interactions and identifying effective host-guest pairs. While numerous studies have focused on the dynamic responses of macrocycles and larger cages to various guests, the corresponding constitutionally dynamic chemistry of cryptands remains unexplored. Reported here is that cryptands based on orthoester bridgeheads offer an elegant entry to experiments in which a metal ion selects its preferred host from a dynamic mixture of competing subcomponents. In such dynamic mixtures, the alkali metal ions Li+ , Na+ , K+ , Rb+ , and Cs+ exhibit pronounced preferences for the formation of cryptands of certain sizes and donor numbers, and the selection is rationalized by DFT calculations. Reported is also the first self-assembly of a chiral orthoester cryptate and a preliminary study on the use of stereoisomers as subcomponents.

NMR Studies on Li⁺, Na⁺ and K⁺ Complexes of Orthoester Cryptand o-Me2-1.1.1.

Cryptands, a class of three-dimensional macrobicyclic hosts ideally suited for accommodating small guest ions, have played an important role in the early development of supramolecular chemistry. In contrast to related two-dimensional crown ethers, cryptands have so far only found limited applications, owing in large part to their relatively inefficient multistep synthesis. We have recently described a convenient one-pot, template synthesis of cryptands based on O,O,O-orthoesters acting as bridgeheads. Here we report variable-temperature, ¹H-1D EXSY and titration NMR studies on lithium, sodium, and potassium complexes of one such cryptand (o-Me2-1.1.1). Our results indicate that lithium and sodium ions fit into the central cavity of the cryptand, resulting in a comparably high binding affinity and slow exchange with the bulk. The potassium ion binds instead in an exo fashion, resulting in relatively weak binding, associated with fast exchange kinetics. Collectively, these results indicate that orthoester cryptands such as o-Me2-1.1.1 exhibit thermodynamic and kinetic properties in between those typically found for classical crown ethers and cryptands and that future efforts should be directed towards increasing the binding constants.

Self-assembly of dynamic orthoester cryptates.

The discovery of coronands and cryptands, organic compounds that can accommodate metal ions in a preorganized two- or three-dimensional environment, was a milestone in supramolecular chemistry, leading to countless applications from organic synthesis to metallurgy and medicine. These compounds are typically prepared via multistep organic synthesis and one of their characteristic features is the high stability of their covalent framework. Here we report the use of a dynamic covalent exchange reaction for the one-pot template synthesis of a new class of coronates and cryptates, in which acid-labile O,O,O-orthoesters serve as bridgeheads. In contrast to their classic analogues, the compounds described herein are constitutionally dynamic in the presence of acid and can be induced to release their guest via irreversible deconstruction of the cage. These properties open up a wide range of application opportunities, from systems chemistry to molecular sensing and drug delivery.

Orthoester exchange: a tripodal tool for dynamic covalent and systems chemistry.

Reversible covalent reactions have become an important tool in supramolecular chemistry and materials science. Here we introduce the acid-catalyzed exchange of O,O,O-orthoesters to the toolbox of dynamic covalent chemistry. We demonstrate that orthoesters readily exchange with a wide range of alcohols under mild conditions and we disclose the first report of an orthoester metathesis reaction. We also show that dynamic orthoester systems give rise to pronounced metal template effects, which can best be understood by agonistic relationships in a three-dimensional network analysis. Due to the tripodal architecture of orthoesters, the exchange process described herein could find unique applications in dynamic polymers, porous materials and host-guest architectures.