Binding modes of high stoichiometry guest complexes with a Co8L12 cage uncovered by mass spectrometry.

We demonstrate how different modes of guest binding with a Co8L12 cubic cage can be determined using ESI-MS. High stoichiometry guest binding was observed, with the guests preferentially binding externally, but internal guest inclusion was also seen at higher guest loading.

Encapsulation in Charged Droplets Generates Distorted Host-Guest Complexes.

The ability of various hydrogen-bonded resorcinarene-based capsules to bind α,ω-alkylbisDABCOnium (DnD) guests of different lengths was investigated in solution and in the gas-phase. While no host-guest interactions were detected in solution, encapsulation could be achieved in the charged droplets formed during electrospray ionisation (ESI). This included guests, which are far too long in their most stable conformation to fit inside the cavity of the capsules. A combination of three mass spectrometric techniques, namely, collision-induced dissociation, hydrogen/deuterium exchange, and ion-mobility mass spectrometry, together with computational modelling allow us to determine the binding mode of the DnD guests inside the cavity of the capsules. Significant distortions of the guest into horseshoe-like arrangements are required to optimise cation-π interactions with the host, which also adopt distorted geometries with partially open hydrogen-bonding seams when binding longer guests. Such quasi "spring-loaded" capsules can form in the charged droplets during the ESI process as there is no competition between guest encapsulation and ion pair formation with the counterions that preclude encapsulation in solution. The encapsulation complexes are sufficiently stable in the gas-phase - even when strained - because non-covalent interactions significantly strengthen in the absence of solvent.

Composition-driven archetype dynamics in polyoxovanadates.

Molecular metal oxides often adopt common structural frameworks (i.e. archetypes), many of them boasting impressive structural robustness and stability. However, the ability to adapt and to undergo transformations between different structural archetypes is a desirable material design feature offering applicability in different environments. Using systems thinking approach that integrates synthetic, analytical and computational techniques, we explore the transformations governing the chemistry of polyoxovanadates (POVs) constructed of arsenate and vanadate building units. The water-soluble salt of the low nuclearity polyanion [V6As8O26]4- can be effectively used for the synthesis of the larger spherical (i.e. kegginoidal) mixed-valent [V12As8O40]4- precipitate, while the novel [V10As12O40]8- POVs having tubular cyclic structures are another, well soluble product. Surprisingly, in contrast to the common observation that high-nuclearity polyoxometalate (POM) clusters are fragmented to form smaller moieties in solution, the low nuclearity [V6As8O26]4- anion is in situ transformed into the higher nuclearity cluster anions. The obtained products support a conceptually new model that is outlined in this article and that describes a continuous evolution between spherical and cyclic POV assemblies. This new model represents a milestone on the way to rational and designable POV self-assemblies.

A light-fuelled nanoratchet shifts a coupled chemical equilibrium.

Biological molecular machines enable chemical transformations, assembly, replication and motility, but most distinctively drive chemical systems out of-equilibrium to sustain life1,2. In such processes, nanometre-sized machines produce molecular energy carriers by driving endergonic equilibrium reactions. However, transforming the work performed by artificial nanomachines3-5 into chemical energy remains highly challenging. Here, we report a light-fuelled small-molecule ratchet capable of driving a coupled chemical equilibrium energetically uphill. By bridging two imine6-9 macrocycles with a molecular motor10,11, the machine forms crossings and consequently adopts several distinct topologies by either a thermal (temporary bond-dissociation) or photochemical (unidirectional rotation) pathway. While the former will relax the machine towards the global energetic minimum, the latter increases the number of crossings in the system above the equilibrium value. Our approach provides a blueprint for coupling continuous mechanical motion performed by a molecular machine with a chemical transformation to reach an out-of-equilibrium state.

Light-controlled interconversion between a [c2]daisy chain and a lasso-type pseudo[1]rotaxane.

A light-responsive self-complementary crown ether/ammonium conjugate bearing an arylazopyrazole photoswitch as a spacer can be switched between a [c2]daisy chain (E-isomer) and a lasso-type pseudo[1]rotaxane (Z-isomer) by light.

Direct Cu-mediated aromatic 18F-labeling of highly reactive tetrazines for pretargeted bioorthogonal PET imaging.

Pretargeted imaging can be used to visualize and quantify slow-accumulating targeting vectors with short-lived radionuclides such as fluorine-18 - the most popular clinically applied Positron Emission Tomography (PET) radionuclide. Pretargeting results in higher target-to-background ratios compared to conventional imaging approaches using long-lived radionuclides. Currently, the tetrazine ligation is the most popular bioorthogonal reaction for pretargeted imaging, but a direct 18F-labeling strategy for highly reactive tetrazines, which would be highly beneficial if not essential for clinical translation, has thus far not been reported. In this work, a simple, scalable and reliable direct 18F-labeling procedure has been developed. We initially studied the applicability of different leaving groups and labeling methods to develop this procedure. The copper-mediated 18F-labeling exploiting stannane precursors showed the most promising results. This approach was then successfully applied to a set of tetrazines, including highly reactive H-tetrazines, suitable for pretargeted PET imaging. The labeling succeeded in radiochemical yields (RCYs) of up to approx. 25%. The new procedure was then applied to develop a pretargeting tetrazine-based imaging agent. The tracer was synthesized in a satisfactory RCY of ca. 10%, with a molar activity of 134 ± 22 GBq µmol-1 and a radiochemical purity of >99%. Further evaluation showed that the tracer displayed favorable characteristics (target-to-background ratios and clearance) that may qualify it for future clinical translation.