Incorporating Photoresponses into Porous Liquids.

Porous liquids combine the properties of a porous solid with those of a liquid, creating a porous flowable media. Since their discovery, these materials have gathered widespread interest within the scientific community, with substantial numbers of new systems being discovered, often with a focus on increasing the pore volume and gas capacity. Which begs the question, what does the future hold for porous liquids? Recently, the first examples of photoresponsive porous liquids have emerged, allowing changes in porosity to be observed under UV irradiation. Here, we expand on our previous report of photoresponsive porous liquids and explore the conceptualisation of responsive porous liquids and how these materials could be developed with the ability to respond to light, thereby offering a potential mechanism of controllable uptake and release in these systems. This concept article summarises different approaches that could be used to incorporate a photoresponse in a porous liquid before discussing recently reported systems, alongside important factors to consider in their design. Finally, by taking inspiration from the methods used to translate porous solids into the liquid state, combined with the field of photoresponsive materials, we discuss potential strategies that could be employed to realise further examples of photoresponsive porous liquids.

Photoresponsive Type III Porous Liquids.

Porous materials are the subject of extensive research because of potential applications in areas such as gas adsorption and molecular separations. Until recently, most porous materials were solids, but there is now an emerging class of materials known as porous liquids. The incorporation of intrinsic porosity or cavities in a liquid can result in free-flowing materials that are capable of gas uptakes that are significantly higher than conventional non-porous liquids. A handful of porous liquids have also been investigated for gas separations. Until now, the release of gas from porous liquids has relied on molecular displacement (e.g., by adding small solvent molecules), pressure or temperature swings, or sonication. Here, we explore a new method of gas release which involves photoisomerisable porous liquids comprising a photoresponsive MOF dispersed in an ionic liquid. This results in the selective uptake of CO2 over CH4 and allows gas release to be controlled by using UV light.

Language Delay in Patients with CLN2 Disease: Could It Support Earlier Diagnosis?

Neuronal ceroid lipofuscinosis type 2 (CLN2 disease) is a rare pediatric disorder associated with rapid neurodegeneration, and premature death in adolescence. An effective enzyme replacement therapy (cerliponase alfa) has been approved that can reduce this predictable neurological decline. The nonspecific early symptoms of CLN2 disease frequently delay diagnosis and appropriate management. Seizures are generally recognized as the first presenting symptom of CLN2 disease, but emerging data show that language delay may precede this. An improved understanding of language deficits in the earliest stage of CLN2 disease may support the early identification of patients. In this article, CLN2 disease experts examine how language development is affected by CLN2 disease in their clinical practices. The authors' experiences highlighted the timings of first words and first use of sentences, and language stagnation as key features of language deficits in CLN2 disease, and how deficits in language may be an earlier sign of the disease than seizures. Potential challenges in identifying early language deficits include assessing patients with other complex needs, and recognizing that a child's language abilities are not within normal parameters given the variability of language development in young children. CLN2 disease should be considered in children presenting with language delay and/or seizures to facilitate earlier diagnosis and access to treatment that can significantly reduce morbidity.

Liquids with Permanent Macroporosity.

Permanent macropores (>50 nm) had not been reported in the liquid state until a recent report by Tao Li and co-workers describing a synthetic strategy to form a porous liquid with dual micro-macroporosity. This is prepared by producing hierarchically porous particles that are surface coated and fluidised by dispersion. Surface micropores enable permanent porosity by steric exclusion of the fluid phase. The material has a considerable water uptake capacity (27 % w/w) due to large (480 nm) unoccupied macropores. This also enables switching of thermal conductivity on uptake of water. These are new properties translated from porous solids to the liquid state.

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.

Liquids with permanent porosity.

Porous solids such as zeolites and metal-organic frameworks are useful in molecular separation and in catalysis, but their solid nature can impose limitations. For example, liquid solvents, rather than porous solids, are the most mature technology for post-combustion capture of carbon dioxide because liquid circulation systems are more easily retrofitted to existing plants. Solid porous adsorbents offer major benefits, such as lower energy penalties in adsorption-desorption cycles, but they are difficult to implement in conventional flow processes. Materials that combine the properties of fluidity and permanent porosity could therefore offer technological advantages, but permanent porosity is not associated with conventional liquids. Here we report free-flowing liquids whose bulk properties are determined by their permanent porosity. To achieve this, we designed cage molecules that provide a well-defined pore space and that are highly soluble in solvents whose molecules are too large to enter the pores. The concentration of unoccupied cages can thus be around 500 times greater than in other molecular solutions that contain cavities, resulting in a marked change in bulk properties, such as an eightfold increase in the solubility of methane gas. Our results provide the basis for development of a new class of functional porous materials for chemical processes, and we present a one-step, multigram scale-up route for highly soluble 'scrambled' porous cages prepared from a mixture of commercially available reagents. The unifying design principle for these materials is the avoidance of functional groups that can penetrate into the molecular cage cavities.

Organic Cage Dumbbells.

Molecular dumbbells with organic cage capping units were synthesised via a multi-component imine condensation between a tri-topic amine and di- and tetra-topic aldehydes. This is an example of self-sorting, which can be rationalised by computational modelling.

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.

Ynamide carbopalladation: a flexible route to mono-, bi- and tricyclic azacycles.

Bromoenynamides represent precursors to a diversity of azacycles by a cascade sequence of carbopalladation followed by cross-coupling/electrocyclization, or reduction processes. Full details of our investigations into intramolecular ynamide carbopalladation are disclosed, which include the first examples of carbopalladation/cross-coupling reactions using potassium organotrifluoroborate salts; and an understanding of factors influencing the success of these processes, including ring size, and the nature of the coupling partner. Additional mechanistic observations are reported, such as the isolation of triene intermediates for electrocyclization. A variety of hetero-Diels-Alder reactions using the product heterocycles are also described, which provide insight into Diels-Alder regioselectivity.

Outcome following multiple subpial transection in Landau-Kleffner syndrome and related regression.

OBJECTIVE: To determine whether multiple subpial transection in the posterior temporal lobe has an impact on long-term outcome in children who have drug-resistant Landau-Kleffner syndrome (LKS) or other "electrical status epilepticus during sleep" (ESES)-related regression. Given the wide variability in outcomes reported in the literature, a secondary aim was to explore predictors of outcome. METHODS: The current study includes a surgery group (n = 14) comprising patients who underwent multiple subpial transection of the posterior temporal lobe and a nonsurgery comparison group (n = 21) comprising patients who underwent presurgical investigations for the procedure, but who did not undergo surgery. Outcomes were assessed utilizing clinical note review as well as direct assessment and questionnaires. RESULTS: The distribution of nonclassical cases was comparable between groups. There were some differences between the surgery and nonsurgery groups at presurgical investigation including laterality of discharges, level of language impairment, and age; therefore, follow-up analyses focused on change over time and predictors of outcome. There were no statistically significant differences between the groups in language, nonverbal ability, adaptive behavior, or quality of life at follow-up. There was no difference in the proportion of patients showing improvement or deterioration in language category over time for either group. Continuing seizures and an earlier age of onset were most predictive of poorer quality of life at long-term follow-up (F2,23 = 26.2, p = <0.001, R(2) = 0.714). SIGNIFICANCE: Both surgery and nonsurgery groups had similar proportions of classic LKS and ESES-related regression. Because no significant differences were found in the changes observed from baseline to follow-up between the two groups, it is argued that there is insufficient evidence to suggest that multiple subpial transection provides additional benefits over and above the mixed recovery often seen in LKS and related regressive epilepsies.

Streamlining the automated discovery of porous organic cages.

Self-assembly through dynamic covalent chemistry (DCC) can yield a range of multi-component organic assemblies. The reversibility and dynamic nature of DCC has made prediction of reaction outcome particularly difficult and thus slows the discovery rate of new organic materials. In addition, traditional experimental processes are time-consuming and often rely on serendipity. Here, we present a streamlined hybrid workflow that combines automated high-throughput experimentation, automated data analysis, and computational modelling, to accelerate the discovery process of one particular subclass of molecular organic materials, porous organic cages. We demonstrate how the design and implementation of this workflow aids in the identification of organic cages with desirable properties. The curation of a precursor library of 55 tri- and di-topic aldehyde and amine precursors enabled the experimental screening of 366 imine condensation reactions experimentally, and 1464 hypothetical organic cage outcomes to be computationally modelled. From the screen, 225 cages were identified experimentally using mass spectrometry, 54 of which were cleanly formed as a single topology as determined by both turbidity measurements and 1H NMR spectroscopy. Integration of these characterisation methods into a fully automated Python pipeline, named cagey, led to over a 350-fold decrease in the time required for data analysis. This work highlights the advantages of combining automated synthesis, characterisation, and analysis, for large-scale data curation towards an accessible data-driven materials discovery approach.

Gas Uptake and Thermodynamics in Porous Liquids Elucidated by 129Xe NMR.

We exploited 129Xe NMR to investigate xenon gas uptake and dynamics in a porous liquid formed by dissolving porous organic cages in a cavity-excluded solvent. Quantitative 129Xe NMR shows that when the amount of xenon added to the sample is lower than the amount of cages present (subsaturation), the porous liquid absorbs almost all xenon atoms from the gas phase, with 30% of the cages occupied with a Xe atom. A simple two-site exchange model enables an estimate of the chemical shift of 129Xe in the cages, which is in good agreement with the value provided by first-principles modeling. T2 relaxation times allow the determination of the exchange rate of Xe between the solvent and cage sites as well as the activation energies of the exchange. The 129Xe NMR analysis also enables determination of the free energy of confinement, and it shows that Xe binding is predominantly enthalpy-driven.

Competitive aminal formation during the synthesis of a highly soluble, isopropyl-decorated imine porous organic cage.

The synthesis of a new porous organic cage decorated with isopropyl moieties (CC21) was achieved from the reaction of triformylbenzene and an isopropyl functionalised diamine. Unlike structurally analogous porous organic cages, its synthesis proved challenging due to competitive aminal formation, rationalised using control experiments and computational modelling. The use of an additional amine was found to increase conversion to the desired cage.

Porous liquids - the future is looking emptier.

The development of microporosity in the liquid state is leading to an inherent change in the way we approach applications of functional porosity, potentially allowing access to new processes by exploiting the fluidity of these new materials. By engineering permanent porosity into a liquid, over the transient intermolecular porosity in all liquids, it is possible to design and form a porous liquid. Since the concept was proposed in 2007, and the first examples realised in 2015, the field has seen rapid advances among the types and numbers of porous liquids developed, our understanding of the structure and properties, as well as improvements in gas uptake and molecular separations. However, despite these recent advances, the field is still young, and with only a few applications reported to date, the potential that porous liquids have to transform the field of microporous materials remains largely untapped. In this review, we will explore the theory and conception of porous liquids and cover major advances in the area, key experimental characterisation techniques and computational approaches that have been employed to understand these systems, and summarise the investigated applications of porous liquids that have been presented to date. We also outline an emerging discovery workflow with recommendations for the characterisation required at each stage to both confirm permanent porosity and fully understand the physical properties of the porous liquid.

Palladium-catalyzed cascade cyclization of ynamides to azabicycles.

Cascade reactions: A modular assembly of azabicycles by using a cascade cyclization/Suzuki coupling/6π-electrocyclization of bromoenynamides is reported. The reaction offers a wide substituent scope on the bicyclic aminodiene products, which can be selectively oxidized as a general approach to aromatic azabicycles.

Enabling Technology for Supramolecular Chemistry.

Supramolecular materials-materials that exploit non-covalent interactions-are increasing in structural complexity, selectivity, function, stability, and scalability, but their use in applications has been comparatively limited. In this Minireview, we summarize the opportunities presented by enabling technology-flow chemistry, high-throughput screening, and automation-to wield greater control over the processes in supramolecular chemistry and accelerate the discovery and use of self-assembled systems. Finally, we give an outlook for how these tools could transform the future of the field.

Integrating Computational and Experimental Workflows for Accelerated Organic Materials Discovery.

Organic materials find application in a range of areas, including optoelectronics, sensing, encapsulation, molecular separations, and photocatalysis. The discovery of materials is frustratingly slow however, particularly when contrasted to the vast chemical space of possibilities based on the near limitless options for organic molecular precursors. The difficulty in predicting the material assembly, and consequent properties, of any molecule is another significant roadblock to targeted materials design. There has been significant progress in the development of computational approaches to screen large numbers of materials, for both their structure and properties, helping guide synthetic researchers toward promising materials. In particular, artificial intelligence techniques have the potential to make significant impact in many elements of the discovery process. Alongside this, automation and robotics are increasing the scale and speed with which materials synthesis can be realized. Herein, the focus is on demonstrating the power of integrating computational and experimental materials discovery programmes, including both a summary of key situations where approaches can be combined and a series of case studies that demonstrate recent successes.

High-Throughput Approaches for the Discovery of Supramolecular Organic Cages.

The assembly of complex molecules, such as organic cages, can be achieved through supramolecular and dynamic covalent strategies. Their use in a range of applications has been demonstrated, including gas uptake, molecular separations, and in catalysis. However, the targeted design and synthesis of new species for particular applications is challenging, particularly as the systems become more complex. High-throughput computation-only and experiment-only approaches have been developed to streamline the discovery process, although are still not widely implemented. Additionally, combined hybrid workflows can dramatically accelerate the discovery process and lead to the serendipitous discovery and rationalisation of new supramolecular assemblies that would not have been designed based on intuition alone. This Minireview focuses on the advances in high-throughput approaches that have been developed and applied in the discovery of supramolecular organic cages.