A smart and responsive crystalline porous organic cage membrane with switchable pore apertures for graded molecular sieving.

Membranes with high selectivity offer an attractive route to molecular separations, where technologies such as distillation and chromatography are energy intensive. However, it remains challenging to fine tune the structure and porosity in membranes, particularly to separate molecules of similar size. Here, we report a process for producing composite membranes that comprise crystalline porous organic cage films fabricated by interfacial synthesis on a polyacrylonitrile support. These membranes exhibit ultrafast solvent permeance and high rejection of organic dyes with molecular weights over 600 g mol-1. The crystalline cage film is dynamic, and its pore aperture can be switched in methanol to generate larger pores that provide increased methanol permeance and higher molecular weight cut-offs (1,400 g mol-1). By varying the water/methanol ratio, the film can be switched between two phases that have different selectivities, such that a single, 'smart' crystalline membrane can perform graded molecular sieving. We exemplify this by separating three organic dyes in a single-stage, single-membrane process.

Materials Precursor Score: Modeling Chemists' Intuition for the Synthetic Accessibility of Porous Organic Cage Precursors.

Computation is increasingly being used to try to accelerate the discovery of new materials. One specific example of this is porous molecular materials, specifically porous organic cages, where the porosity of the materials predominantly comes from the internal cavities of the molecules themselves. The computational discovery of novel structures with useful properties is currently hindered by the difficulty in transitioning from a computational prediction to synthetic realization. Attempts at experimental validation are often time-consuming, expensive, and frequently, the key bottleneck of material discovery. In this work, we developed a computational screening workflow for porous molecules that includes consideration of the synthetic difficulty of material precursors, aimed at easing the transition between computational prediction and experimental realization. We trained a machine learning model by first collecting data on 12,553 molecules categorized either as "easy-to-synthesize" or "difficult-to-synthesize" by expert chemists with years of experience in organic synthesis. We used an approach to address the class imbalance present in our data set, producing a binary classifier able to categorize easy-to-synthesize molecules with few false positives. We then used our model during computational screening for porous organic molecules to bias toward precursors whose easier synthesis requirements would make them promising candidates for experimental realization and material development. We found that even by limiting precursors to those that are easier-to-synthesize, we are still able to identify cages with favorable, and even some rare, properties.

Continuous and scalable synthesis of a porous organic cage by twin screw extrusion (TSE).

The continuous and scalable synthesis of a porous organic cage (CC3), obtained through a 10-component imine polycondensation between triformylbenzene and a vicinal diamine, was achieved using twin screw extrusion (TSE). Compared to both batch and flow syntheses, the use of TSE enabled the large scale synthesis of CC3 using minimal solvent and in short reaction times, with liquid-assisted grinding (LAG) also promoting window-to-window crystal packing to form a 3-D diamondoid pore network in the solid state. A new kinetically trapped [3+5] product was also observed alongside the formation of the targeted [4+6] cage species. Post-synthetic purification by Soxhlet extraction of the as-extruded 'technical grade' mixture of CC3 and [3+5] species rendered the material porous.

Controlling Gas Selectivity in Molecular Porous Liquids by Tuning the Cage Window Size.

Control of pore window size is the standard approach for tuning gas selectivity in porous solids. Here, we present the first example where this is translated into a molecular porous liquid formed from organic cage molecules. Reduction of the cage window size by chemical synthesis switches the selectivity from Xe-selective to CH4 -selective, which is understood using 129 Xe, 1 H, and pulsed-field gradient NMR spectroscopy.

From Concept to Crystals via Prediction: Multi-Component Organic Cage Pots by Social Self-Sorting.

We describe the a priori computational prediction and realization of multi-component cage pots, starting with molecular predictions based on candidate precursors through to crystal structure prediction and synthesis using robotic screening. The molecules were formed by the social self-sorting of a tri-topic aldehyde with both a tri-topic amine and di-topic amine, without using orthogonal reactivity or precursors of the same topicity. Crystal structure prediction suggested a rich polymorphic landscape, where there was an overall preference for chiral recognition to form heterochiral rather than homochiral packings, with heterochiral pairs being more likely to pack window-to-window to form two-component capsules. These crystal packing preferences were then observed in experimental crystal structures.

Synthesis of a Large, Shape-Flexible, Solvatomorphic Porous Organic Cage.

Porous organic cages have emerged over the last 10 years as a subclass of functional microporous materials. However, among all of the organic cages reported, large multicomponent organic cages with 20 components or more are still rare. Here, we present an [8 + 12] porous organic imine cage, CC20, which has an apparent surface area up to 1752 m2 g-1, depending on the crystallization and activation conditions. The cage is solvatomorphic and displays distinct geometrical cage structures, caused by crystal-packing effects, in its crystal structures. This indicates that larger cages can display a certain range of shape flexibility in the solid state, while remaining shape persistent and porous.

Accelerated robotic discovery of type II porous liquids.

Porous liquids are an emerging class of materials and to date little is known about how to best design their properties. For example, bulky solvents are required that are size-excluded from the pores in the liquid, along with high concentrations of the porous component, but both of these factors may also contribute to higher viscosities, which are undesirable. Hence, the inherent multivariate nature of porous liquids makes them amenable to high-throughput optimisation strategies. Here we develop a high-throughput robotic workflow, encompassing the synthesis, characterisation and property testing of highly-soluble, vertex-disordered porous organic cages dissolved in a range of cavity-excluded solvents. As a result, we identified 29 cage-solvent combinations that combine both higher cage-cavity concentrations and more acceptable carrier solvents than the best previous examples. The most soluble materials gave three times the pore concentration of the best previously reported scrambled cage porous liquid, as demonstrated by increased gas uptake. We were also able to explore alternative methods for gas capture and release, including liberation of the gas by increasing the temperature. We also found that porous liquids can form gels at higher concentrations, trapping the gas in the pores, which could have potential applications in gas storage and transportation.

Computationally-inspired discovery of an unsymmetrical porous organic cage.

A completely unsymmetrical porous organic cage was synthesised from a C2v symmetrical building block that was identified by a computational screen. The cage was formed through a 12-fold imine condensation of a tritopic C2v symmetric trialdehyde with a ditopic C2 symmetric diamine in a [4 + 6] reaction. The cage was rigid and microporous, as predicted by the simulations, with an apparent Brunauer-Emmett-Teller surface area of 578 m2 g-1. The reduced symmetry of the tritopic building block relative to its topicity meant there were 36 possible structural isomers of the cage. Experimental characterisation suggests a single isomer with 12 unique imine environments, but techniques such as NMR could not conclusively identify the isomer. Computational structural and electronic analysis of the possible isomers was used to identify the most likely candidates, and hence to construct a 3-dimensional model of the amorphous solid. The rational design of unsymmetrical cages using building blocks with reduced symmetry offers new possibilities in controlling the degree of crystallinity, porosity, and solubility, of self-assembled materials.

Investigating the breakdown of the nerve agent simulant methyl paraoxon and chemical warfare agents GB and VX using nitrogen containing bases.

A range of nitrogen containing bases was tested for the hydrolysis of a nerve agent simulant, methyl paraoxon (MP), and the chemical warfare agents, GB and VX. The product distribution was found to be highly dependant on the basicity of the base and the quantity of water used for the hydrolysis. This study is important in the design of decontamination technology, which often involve mimics of CWAs.

Ultra-Fast Molecular Rotors within Porous Organic Cages.

Using variable temperature 2 H static NMR spectra and 13 C spin-lattice relaxation times (T1 ), we show that two different porous organic cages with tubular architectures are ultra-fast molecular rotors. The central para-phenylene rings that frame the "windows" to the cage voids display very rapid rotational rates of the order of 1.2-8×106  Hz at 230 K with low activation energy barriers in the 12-18 kJ mol-1 range. These cages act as hosts to iodine guest molecules, which dramatically slows down the rotational rates of the phenylene groups (5-10×104  Hz at 230 K), demonstrating potential use in applications that require molecular capture and release.

Pyrene-cored covalent organic polymers by thiophene-based isomers, their gas adsorption, and photophysical properties.

Two new pyrene-cored covalent organic polymers (COPs), CK-COP-1 and CK-COP-2, were synthesized via the one-step polymerization of two thiophene-based isomers, 1,3,6,8-tetra(thiophene-2-yl) pyrene (L1 ) and 1,3,6,8-tetra(thiophene-3-yl) pyrene (L2 ). The resulting pyrene-cored COPs exhibit rather different surface areas of 54 m2 g-1 and 615 m2g-1 for CK-COP-1 and CK-COP-2, respectively. The CO2 uptake capacities of CK-COP-1 and CK-COP-2 also show different values of 2.85 and 9.73 wt % at 273 K, respectively. Furthermore, CK-COP-2 offers not only a larger CO2 adsorption capacity but also a better CO2/CH4 selectivity at 273 K compared with CK-COP-1. CK-COP-1 and CK-COP-2 also exhibit considerable differences in their photophysical property. The different structure and properties of CK-COPs could be attributed to the isomer effect of their corresponding thiophene-based monomers. © 2017 Authors. Journal of Polymer Science Part A: Polymer Chemistry Published by Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 2383-2389.

Computationally-Guided Synthetic Control over Pore Size in Isostructural Porous Organic Cages.

The physical properties of 3-D porous solids are defined by their molecular geometry. Hence, precise control of pore size, pore shape, and pore connectivity are needed to tailor them for specific applications. However, for porous molecular crystals, the modification of pore size by adding pore-blocking groups can also affect crystal packing in an unpredictable way. This precludes strategies adopted for isoreticular metal-organic frameworks, where addition of a small group, such as a methyl group, does not affect the basic framework topology. Here, we narrow the pore size of a cage molecule, CC3, in a systematic way by introducing methyl groups into the cage windows. Computational crystal structure prediction was used to anticipate the packing preferences of two homochiral methylated cages, CC14-R and CC15-R, and to assess the structure-energy landscape of a CC15-R/CC3-S cocrystal, designed such that both component cages could be directed to pack with a 3-D, interconnected pore structure. The experimental gas sorption properties of these three cage systems agree well with physical properties predicted by computational energy-structure-function maps.

Understanding gas capacity, guest selectivity, and diffusion in porous liquids.

Porous liquids are a new class of material that could have applications in areas such as gas separation and homogeneous catalysis. Here we use a combination of measurement techniques, molecular simulations, and control experiments to advance the quantitative understanding of these liquids. In particular, we show that the cage cavities remain unoccupied in the absence of a suitable guest, and that the liquids can adsorb large quantities of gas, with gas occupancy in the cages as high as 72% and 74% for Xe and SF6, respectively. Gases can be reversibly loaded and released by using non-chemical triggers such as sonication, suggesting potential for gas separation schemes. Diffusion NMR experiments show that gases are in dynamic equilibrium between a bound and unbound state in the cage cavities, in agreement with recent simulations for related porous liquids. Comparison with gas adsorption in porous organic cage solids suggests that porous liquids have similar gas binding affinities, and that the physical properties of the cage molecule are translated into the liquid state. By contrast, some physical properties are different: for example, solid homochiral porous cages show enantioselectivity for chiral aromatic alcohols, whereas the equivalent homochiral porous liquids do not. This can be attributed to a loss of supramolecular organisation in the isotropic porous liquid.

Dual-stimuli responsive injectable microgel/solid drug nanoparticle nanocomposites for release of poorly soluble drugs.

An in situ forming implant (ISFI) for drug delivery combines the potential to improve therapeutic adherence for patients with simple administration by injection. Herein, we describe the preparation of an injectable nanocomposite ISFI composed of thermoresponsive poly(N-isopropylacrylamide) based microgels and solid drug nanoparticles. Monodisperse poly(N-isopropylacrylamide) or poly(N-isopropylacrylamide-co-allylamine) microgels were prepared by precipitation polymerisation with mean diameters of approximately 550 nm at 25 °C. Concentrated dispersions of these microgels displayed dual-stimuli responsive behaviour, forming shape persistent bulk aggregates in the presence of both salt (at physiological ionic strength) and at body temperature (above the lower critical solution temperature of the polymer). These dual-stimuli responsive microgels could be injected into an agarose gel tissue mimic leading to rapid aggregation of the particles to form a drug depot. Additionally, the microgel particles aggregated in the presence of other payload nanoparticles (such as dye-containing polystyrene nanoparticles or lopinavir solid drug nanoparticles) to form nanocomposites with high entrapment efficiency of the payload. The resulting microgel and solid drug nanoparticle nanocomposites displayed sustained drug release for at least 120 days, with the rate of release tuned by blending microgels of poly(N-isopropylacrylamide) with poly(N-isopropylacrylamide-co-allylamine) microgels. Cytotoxicity studies revealed that the microgels were not toxic to MDCK-II cells even at high concentrations. Collectively, these results demonstrate a novel, easily injectable, nanocomposite ISFI that provides long-term sustained release for poorly water-soluble drugs without a burst release.

A Perspective on the Synthesis, Purification, and Characterization of Porous Organic Cages.

Porous organic cages present many opportunities in functional materials chemistry, but the synthetic challenges for these molecular solids are somewhat different from those faced in the areas of metal-organic frameworks, covalent-organic frameworks, or porous polymer networks. Here, we highlight the practical methods that we have developed for the design, synthesis, and characterization of imine porous organic cages using CC1 and CC3 as examples. The key points are transferable to other cages, and this perspective should serve as a practical guide to researchers who are new to this field.

Periphery-Functionalized Porous Organic Cages.

By synthesizing derivatives of a trans-1,2-diaminocyclohexane precursor, three new functionalized porous organic cages were prepared with different chemical functionalities on the cage periphery. The introduction of twelve methyl groups (CC16) resulted in frustration of the cage packing mode, which more than doubled the surface area compared to the parent cage, CC3. The analogous installation of twelve hydroxyl groups provided an imine cage (CC17) that combines permanent porosity with the potential for post-synthetic modification of the cage exterior. Finally, the incorporation of bulky dihydroethanoanthracene groups was found to direct self-assembly towards the formation of a larger [8+12] cage, rather than the expected [4+6], cage molecule (CC18). However, CC18 was found to be non-porous, most likely due to cage collapse upon desolvation.

Hyperporous Carbons from Hypercrosslinked Polymers.

Porous carbons with extremely high surface areas are produced through the carbonization of hypercrosslinked benzene, pyrrole, and thiophene. Such carbons show largely microporous and mesoporous domains and exhibit Brunaeur-Emmett-Teller surface areas up to 4300 m2 g-1 . The best performing material also displays exceptionally high CO2 and H2 uptakes.

Dynamic flow synthesis of porous organic cages.

The dynamic covalent synthesis of two imine-based porous organic cages was successfully transferred from batch to continuous flow. The same flow reactor was then used to scramble the constituents of these two cages in differing ratios to form cage mixtures. Preparative HPLC purification of one of these mixtures allowed rapid access to a desymmetrised cage molecule.

Sponge-Like Behaviour in Isoreticular Cu(Gly-His-X) Peptide-Based Porous Materials.

We report two isoreticular 3D peptide-based porous frameworks formed by coordination of the tripeptides Gly-L-His-Gly and Gly-L-His-L-Lys to Cu(II) which display sponge-like behaviour. These porous materials undergo structural collapse upon evacuation that can be reversed by exposure to water vapour, which permits recovery of the original open channel structure. This is further confirmed by sorption studies that reveal that both solids exhibit selective sorption of H2 O while CO2 adsorption does not result in recovery of the original structures. We also show how the pendant aliphatic amine chains, present in the framework from the introduction of the lysine amino acid in the peptidic backbone, can be post-synthetically modified to produce urea-functionalised networks by following methodologies typically used for metal-organic frameworks built from more rigid "classical" linkers.

Chemical and structural stability of zirconium-based metal-organic frameworks with large three-dimensional pores by linker engineering.

The synthesis of metal-organic frameworks with large three-dimensional channels that are permanently porous and chemically stable offers new opportunities in areas such as catalysis and separation. Two linkers (L1=4,4',4'',4'''-([1,1'-biphenyl]-3,3',5,5'-tetrayltetrakis(ethyne-2,1-diyl)) tetrabenzoic acid, L2=4,4',4'',4'''-(pyrene-1,3,6,8-tetrayltetrakis(ethyne-2,1-diyl))tetrabenzoic acid) were used that have equivalent connectivity and dimensions but quite distinct torsional flexibility. With these, a solid solution material, [Zr6 O4 (OH)4 (L1)2.6 (L2)0.4 ]⋅(solvent)x , was formed that has three-dimensional crystalline permanent porosity with a surface area of over 4000 m(2) g(-1) that persists after immersion in water. These properties are not accessible for the isostructural phases made from the separate single linkers.