Different Modes of Anion Response Cause Circulatory Phase Transfer of a Coordination Cage with Controlled Directionality

Controlled directional transport of molecules is essential to complex natural systems, exemplified by cellular transport up to organismal circulatory systems. In contrast to these natural systems, synthetic systems that enable transport of molecules between several spatial locations on the macroscopic scale, when external stimuli are applied, remain to be explored. Here we report the transfer of a supramolecular cage with controlled directionality between three phases, based on the cage that responds reversibly in two distinct ways to different anions. Notably, circulatory phase transfer of the cage was demonstrated based on a system where the three layers of solvent are arranged within a circular track. The direction of circulation between solvent phases depended upon the order of addition of anions.European Research Council (695009), UK Engineering and Physical Sciences Research Council (EPSRC, EP/P027067/1

Post-assembly Modification of Phosphine Cages Controls Host-Guest Behavior.

We report the design, synthesis, and post-assembly modification of a new phosphine-paneled supramolecular cage framework, the anion binding ability of which can be modified rationally through selective post-assembly functionalization. The parent phosphine-paneled cage can be modified in situ through oxidation, methylation, or auration. These covalent and coordinative modifications to the exterior of the cage strongly influence the guest-binding properties of the host.European Research Council (695009), UK Engineering and Physical Sciences Research Council (EPSRC, EP/P027067/1

Sequence-Dependent Guest Release Triggered by Orthogonal Chemical Signals.

Three Zn(II)4L4 coordination cages, assembled from trisiminopyridine ligands, exhibit differences in their guest-binding selectivities and reactivity with tris(2-aminoethyl)amine (tren), which enabled the design of a molecular network that responded in distinct ways to different chemical signals. When two of these cages were present in solution together, one of them was observed to selectively encapsulate chloroform, and the other was observed to selectively encapsulate cyclohexane. The two guests could be released sequentially, in a specified order defined by the input of two separate chemical signals: tren and perrhenate. Furthermore, the observed reactivity of tren with the initial cage mixture provided control over the uptake and release of perrhenate within the third cage formed in situ. One of these tetrahedral cages has been identified as a tight (K(a) > 10(7) M(-1)) and selective host for perrhenate, an anion of great physicochemical similarity to pertechnetate, both having uses in nuclear medicine.This work was supported by the European Research Council. We thank Diamond Light Source (UK) for synchrotron beamtime on I19 (MT8464) and Dr. Rana A. Bilbeisi for a preliminary screening of guests for cage 1.This is the author accepted manuscript. The final version is available from the American Chemical Society via http://dx.doi.org/10.1021/jacs.5b1301

Improved Acid Resistance of a Metal-Organic Cage Enables Cargo Release and Exchange between Hosts.

The use of di(2-pyridyl)ketone in subcomponent self-assembly is introduced. When combined with a flexible triamine and zinc bis(trifluoromethanesulfonyl)imide, this ketone formed a new Zn4 L4 tetrahedron 1 bearing twelve uncoordinated pyridyl units around its metal-ion vertices. The acid stability of 1 was found to be greater than that of the analogous tetrahedron 2 built from 2-formylpyridine. Intriguingly, the peripheral presence of additional pyridine rings in 1 resulted in distinct guest binding behavior from that of 2, affecting guest scope as well as binding affinities. The different stabilities and guest affinities of capsules 1 and 2 enabled the design of systems whereby different cargoes could be moved between cages using acid and base as chemical stimuli.European Research Council (695009), UK Engineering and Physical Sciences Research Council (EPSRC EP/P027067/1

Subcomponent Flexibility Enables Conversion between D4-Symmetric Cd(II)8L8 and T-Symmetric Cd(II)4L4 Assemblies.

A flexible tris-formylpyridine subcomponent A was observed to produce three distinct products following Cd(II)-templated self-assembly with different anilines. Two of the products were Cd(II)4L4 tetrahedra, one with ligands puckered inward, and the other outward. The third product was a Cd(II)8L8 structure having all mer stereochemistry, contrasting with the fac stereochemistry of the tetrahedra. These three complexes were observed to coexist in solution. The equilibrium between them could be influenced through guest binding and specific interactions between aniline subcomponents, allowing a selected one of the three to predominate under defined conditions.This work was supported by the UK Engineering and Physical Sciences Research Council (EPSRC EP/M008258/1). The authors thank the Department of Chemistry NMR facility, University of Cambridge, and the EPSRC UK National Mass Spectrometry Facility at Swansea University. J. M. acknowledges postdoctoral fellowship support from Fundación Ramón Areces.This is the final version of the article. It first appeared from the American Chemical Society via http://dx.doi.org/10.1021/jacs.5b1295

Design Principles for the Optimization of Guest Binding in Aromatic-Paneled FeII4L6 Cages.

A series of aromatic-paneled FeII4L6 cages was synthesized through iron(II)-templated subcomponent self-assembly of 2-formylpyridine and C2-symmetric diamine building blocks having differing geometries, including many with a large degree of lateral offset between metal-binding sites. The new cages were characterized using X-ray crystallography, NMR spectroscopy, and mass spectrometry. Investigations of the guest binding properties of the cages provided insights into the structural factors important for the observation of guest binding. Both the size and arrangement of the aromatic panels were shown to be crucial for achieving effective encapsulation of large hydrophobic guests, including fullerenes, polycyclic aromatic hydrocarbons, and steroids, with subtle differences in the structure of subcomponents resulting in incommensurate effects on the binding abilities of the resulting hosts. Cages with large, offset aromatic panels were observed to be the most effective hosts as a result of a preference for a ligand conformation where the aromatic panels lie tangent to the edges of the tetrahedron, thus maximizing cavity enclosure

Pyrene-edged Fe(II)4L6 cages adaptively reconfigure during guest binding.

Differential guest-binding behavior was observed between two pyrene-edged Fe4L6 cages, prepared from isomeric bis(4-aminophenyl)pyrene derivatives, 2-formylpyridine and iron(II). The cage based on a 1,6-pyrene scaffold possesses an enclosed cavity suitable for the encapsulation of large hydrophobic guests including fullerenes, polycyclic aromatic hydrocarbons, and large, structurally complex natural products such as steroids. Addition of the fullerenes C60 and C70 to the cage brought about a re-equilibration among the different cage diastereomers in order to maximize the binding affinity of the system. Density functional theory was employed to rationalize the experimentally observed energy differences for C60 binding within the cage diastereomers. In contrast, the cage isomer based on a 2,7-pyrene scaffold has a more porous cavity and did not show affinity for neutral hydrophobic guests.This work was supported by the UK Engineering and Physical Sciences Research Council (EPSRC) and the US National Science Foundation (NSF CHE-1124244)This is the final version of the article. It was first published by ACS at http://pubs.acs.org/doi/abs/10.1021/ja507617

Covalent Post-assembly Modification Triggers Multiple Structural Transformations of a Tetrazine-Edged Fe4L6 Tetrahedron

Covalent post-assembly modification (PAM) reactions are useful synthetic tools for functionalizing and stabilizing self-assembled metal-organic complexes. Recently, PAM reactions have also been explored as stimuli for triggering supramolecular structural transformations. Herein we demonstrate the use of inverse electron-demand Diels-Alder (IEDDA) PAM reactions to induce supramolecular structural transformations starting from a tetrazine-edged FeII4L6 tetrahedral precursor. Following PAM, this tetrahedron rearranged to form three different architectures depending on the addition of other stimuli: an electron-rich aniline or a templating anion. By tracing the stimulus-response relationships within the system, we deciphered a network of transformations that mapped different combinations of stimuli onto specific transformation products. Given the many functions being developed for self-assembled three-dimensional architectures, this newly established ability to control the interconversion between structures using combinations of different stimulus types may serve as the basis for switching the functions expressed within a system.D.A.R. acknowledges the Gates Cambridge Trust. B.S.P. acknowledges the Royal Commission for the Exhibition of 1851 Fellowship and Corpus Christi College, Cambridge. This work was supported by the UK Engineering and Physical Sciences Research Council (EP/M01083X/1)

Tetramine Aspect Ratio and Flexibility Determine Framework Symmetry for Zn8L6 Self-Assembled Structures

We derive design principles for the assembly of rectangular tetramines into Zn8L6 pseudo-cubic coordination cages. Because of the rectangular, as opposed to square, geometry of the ligand panels, and the possibility of either Delta or ? handedness of each metal center at the eight corners of the pseudo-cube, many different cage diastereomers are possible. Each of the six tetra-aniline subcomponents investigated in this work assembled with zinc(II) and 2-formylpyridine in acetonitrile into a single Zn8L6 pseudo-cube diastereomer, however. Each product corresponded to one of four diastereomeric configurations, with T, T-h, S-6 or D-3 symmetry. The preferred diastereomer for a given tetra-aniline subcomponent was shown to be dependent on its aspect ratio and conformational flexibility. Analysis of computationally modeled individual faces or whole pseudo-cubes provided insight as to why the observed diastereomers were favored