Industrial Separation Challenges: How Does Supramolecular Chemistry Help?

The chemical industry and the chemical processes underscoring it are under intense scrutiny as the demands for the transition to more sustainable and environmentally friendly practices are increasing. Traditional industrial separation systems, such as thermally driven distillation for hydrocarbon purification, are energy intensive. The development of more energy efficient separation technologies is thus emerging as a critical need, as is the creation of new materials that may permit a transition away from classic distillation-based separations. In this Perspective, we focus on porous organic cages and macrocycles that can adsorb guest molecules selectively through various host-guest interactions and permit molecular sieving behavior at the molecular level. Specifically, we summarize the recent advances where receptor-based adsorbent materials have been shown to be effective for industrially relevant hydrocarbon separations, highlighting the underlying host-guest interactions that impart selectivity and permit the observed separations. This approach to sustainable separations is currently in its infancy. Nevertheless, several receptor-based adsorbent materials with extrinsic/intrinsic voids or special functional groups have been reported in recent years that can selectively capture various targeted guest molecules. We believe that the understanding of the interactions that drive selectivity at a molecular level accruing from these initial systems will permit an ever-more-effective "bottom-up" design of tailored molecular sieves that, in due course, will allow adsorbent material-based approaches to separations to transition from the laboratory into an industrial setting.

Caging the Hofmeister Effect by a Biomimetic Supramolecular Receptor.

The effect of anions on the solubility and function of proteins was recognized in 1888 and is now termed the Hofmeister effect. Numerous synthetic receptors are known that overcome the associated anion recognition bias. However, we are unaware of a synthetic host being used to overcome Hofmeister effect perturbations to natural proteins. Here, we report a protonated small molecule cage complex that acts as an exo-receptor and displays non-Hofmeister solubility behavior, with only the chloride complex remaining soluble in aqueous media. This cage allows for the activity of lysozyme to be retained under conditions where anion-induced precipitation would otherwise cause it to be lost. To our knowledge, this is the first time a synthetic anion receptor is used to overcome the Hofmeister effect in a biological system.

Tuning the porosity of triangular supramolecular adsorbents for superior haloalkane isomer separations.

Distillation-free separations of haloalkane isomers represents a persistent challenge for the chemical industry. Several classic molecular sorbents show high selectivity in the context of such separations; however, most suffer from limited tunability or poor stability. Herein, we report the results of a comparative study involving three trianglamine and trianglimine macrocycles as supramolecular adsorbents for the selective separation of halobutane isomers. Methylene-bridged trianglamine, TA, was found to capture preferentially 1-chlorobutane (1-CBU) from a mixture of 1-CBU and 2-chlorobutane (2-CBU) with a purity of 98.1%. It also separates 1-bromobutane (1-BBU) from a mixture of 1-BBU and 2-bromobutane (2-BBU) with a purity of 96.4%. The observed selectivity is ascribed to the thermodynamic stability of the TA-based host-guest complexes. Based on single crystal X-ray diffraction analyses, a [3]pseudorotaxane structure (2TA⊃1-CBU) is formed between TA and 1-CBU that is characterized by an increased level of noncovalent interactions compared to the corresponding [2]pseudorotaxane structure seen for TA⊃2-CBU. We believe that molecular sorbents that rely on specific molecular recognition events, such as the triangular pores detailed here, will prove useful as next generation sorbents in energy-efficient separations.

Intrinsically Porous Molecular Materials (IPMs) for Natural Gas and Benzene Derivatives Separations.

ConspectusSeparating and purifying chemicals without heat would go a long way toward reducing the overall energy consumption and the harmful environmental footprint of the process. Molecular separation processes are critical for the production of raw materials, commodity chemicals, and specialty fuels. Over 50% of the energy used in the production of these materials is spent on separation and purification processes, which primarily includes vacuum and cryogenic distillations. Chemical manufacturers are now investigating modest thermal approaches, such as membranes and adsorbent materials, as they are more cognizant than ever of the need to save energy and prevent pollution. Porous materials, such as zeolites, metal-organic frameworks (MOFs), and covalent organic frameworks (COFs), have dominated the field of industrial separations as their high surface areas and robust pores make them ideal candidates for molecular separations of gases and hydrocarbons. Separation processes involving porous materials can save 70%-90% of energy costs compared to that of thermally driven distillations. However, most porous materials have low thermal, chemical, and moisture stability, in addition to limited solution processability, which tremendously constrain their broad industrial translation. Intrinsically porous molecular materials (IPMs) are a subclass of porous molecular materials that are comprised of molecular host macrocycles or cages that absorb guests in or around their intrinsic cavity. IPMs range from discrete porous molecules to assemblies with amorphous or highly crystalline structures that are held together by weak supramolecular interactions. Compared to the coordination or dynamic covalent bond-constructed porous frameworks, IPMs possess high thermal, chemical, and moisture stability and maintain their porosity under critical conditions. Moreover, the intrinsic porosity endows IPMs with excellent host-guest properties in solid, liquid (organic or aqueous), and gas states, which can be further utilized to construct diverse separation strategies, such as solid-gas adsorption, solid-liquid absorption, and liquid-liquid extraction. The diversity of host-guest interactions in the engineered IPMs affords a plethora of possibilities for the development of the ideal "molecular sieves". Herein, we present a different take on the applicability of intrinsically porous materials such as cyclodextrin (CD), cucurbiturils (CB), pillararene (P), trianglamines (T), and porous organic cages (POCs) that showed an impressive performance in gas purification and benzene derivatives separation. IPMs can be easily scaled up and are quite stable and solution processable that consequently facilitates a favorable technological transformation from the traditional energy-intensive separations. We will account for the main advances in molecular host-guest chemistry to design "on-demand" separation processes and also outline future challenges and opportunities for this promising technology.

Molecularly-porous ultrathin membranes for highly selective organic solvent nanofiltration.

Engineering membranes for molecular separation in organic solvents is still a big challenge. When the selectivity increases, the permeability tends to drastically decrease, increasing the energy demands for the separation process. Ideally, organic solvent nanofiltration membranes should be thin to enhance the permeant transport, have a well-tailored nanoporosity and high stability in harsh solvents. Here, we introduce a trianglamine macrocycle as a molecular building block for cross-linked membranes, prepared by facile interfacial polymerization, for high-performance selective separations. The membranes were prepared via a two-in-one strategy, enabled by the amine macrocycle, by simultaneously reducing the thickness of the thin-film layers (<10 nm) and introducing permanent intrinsic porosity within the membrane (6.3 Å). This translates into a superior separation performance for nanofiltration operation, both in polar and apolar solvents. The hyper-cross-linked network significantly improved the stability in various organic solvents, while the amine host macrocycle provided specific size and charge molecular recognition for selective guest molecules separation. By employing easily customized molecular hosts in ultrathin membranes, we can significantly tailor the selectivity on-demand without compromising the overall permeability of the system.

A Polymorphic Azobenzene Cage for Energy-Efficient and Highly Selective p-Xylene Separation.

Developing the competence of molecular sorbents for energy-saving applications, such as C8 separations, requires efficient, stable, scalable, and easily recyclable materials that can readily transition to commercial implementation. Herein, we report an azobenzene-based cage for the selective separation of p-xylene isomer across a range of C8 isomers in both vapor and liquid states with selectivity that is higher than the reported all-organic sorbents. The crystal structure shows non-porous cages that are separated by p-xylene molecules through selective CH-π interactions between the azo bonds and the methyl hydrogen atoms of the xylene molecules. This cage is stable in solution and can be regenerated directly under vacuum to be used in multiple cycles. We envisage that this work will promote the investigation of the azo bond as well as guest-induced crystal-to-crystal phase transition in non-porous organic solids for energy-intensive separations.

Separation and Detection of meta- and ortho-Substituted Benzene Isomers by Using a Water-Soluble Pillar[5]arene.

Efficient and energy-saving separation of benzene isomers bearing a diverse range of functional groups is a great challenge due to their overlapping physicochemical properties. Here, we report the successfully use of a water-soluble pillar[5]arene (WP5) as a multifunctional material for the separation and detection of meta/ortho-substituted benzene isomers in water. A liquid-liquid extraction strategy was used for the separation of these benzene isomers based on their different affinity for WP5 in water. The selectivities for the meta over the ortho isomer for xylenes, chlorotoluene, and bromotoluene was 88.6 %, 88.3 %, and 95.0 % respectively, in one extraction cycle. Furthermore, a fluorescence indicator system based on WP5 and a fluorescent dye molecule (10-methylacridinium, D) was adopted and exhibited significant fluorescence and optical discrimination upon the addition of meta- compared to ortho-xylene, which implies that a simple "turn-on" detection can be performed prior to engaging in the separation process.

Self-Immolative Fluorescent and Raman Probe for Real-Time Imaging and Quantification of γ-Glutamyl Transpeptidase in Living Cells.

Characterizing over-expressed enzymes or biomarkers in living cells is critical for the molecular understanding of disease pathology and consequently for designing precision medicines. Herein, a "switch-on" probe is designed to selectively detect γ-glutamyl transpeptidase (GGT) in living cells via a unique ensemble of enhanced fluorescence and surface-enhanced Raman scattering (SERS). In the presence of GGT, the γ-glutamyl bond in the probe molecule is cleaved, thereby activating a fluorescent probe molecule as well as a Raman reporter molecule. Consequently, the detection of GGT is achieved based on both plasmonic fluorescent enhancement and SERS with a detection limit as low as 1.2 × 10-3 U/L (normal range for GGT levels in the blood is 9-48 U/L). The main advantage of this platform is that on the occasion of fluorescence signal interference, especially in the presence of free metal ions in cells, the SERS signals still hold high stability as a backup. This work highlights the benefits of the marriage of two complimentary sensing techniques into one platform that can overcome the major obstacles of detection of real-time biomarkers and imaging in living cells.

A Route to Enantiopure ( O-Methyl)6-2,6-Helic[6]arenes: Synthesis of Hexabromo-Substituted 2,6-Helic[6]arene Derivatives and Their Suzuki-Miyaura Coupling Reactions.

A route to enantiopure ( O-methyl)6-2,6-helic[6]arenes (+)- P-2 and (-)- M-2 has been provided. By the reaction of enantiopure triptycene precursors (+)-1 and (-)-1 in refluxed o-DCB for 12 h in the presence of catalytic amount of FeCl3, and then followed by treatment of the obtained oligomers under the same conditions, (+)- P-2 and (-)- M-2 could be obtained in 51% and 53% total yield, respectively. It was also found that racemic and enantiopure ( O-methyl)6-2,6-helic[6]arenes could be easily brominated by Br2 to give the corresponding hexabromo-substituted helic[6]arene derivatives rac-4, (+)- P-4, and (-)- M-4 in high yields. The crystal structure of (+)- P-4 further confirmed the absolute configuration of the helic[6]arenes and their derivatives. Moreover, a series of hexaaryl-substituted helic[6]arene derivatives 5a-f with deepened cavities could be conveniently synthesized in 55-71% yield by Suzuki-Miyaura coupling reactions of 4 and arylboronic acids. rac-5a could encapsulate chloroform and exhibit self-sorting stacking in solid state. Enantiopure (+)- P-5a-f and (-)- M-5a-f showed mirror images in their CD spectra.

Removal of Anions from Aqueous Media by Means of a Thermoresponsive Calix[4]pyrrole Amphiphilic Polymer.

To address the challenge of removing unwanted anions from aqueous media under extraction-free conditions we have prepared a thermoresponsive amphiphilic polymer with pendent calix[4]pyrrole (C4P) receptors. Because of its amphipathicity, this polymer self-assembles into micelles in water. These micelles contain the C4P receptors buried in a hydrophobic core. This allows uptake of various cesium anions into the micelles. Due to the thermal responsiveness of the hydrophilic block chain, the anion-bearing micelles precipitate in water upon heating. Simple filtration allows their removal from the aqueous environment, thus allowing for effective water purification. Treating the anion-trapped micelles with acidic aqueous solution leads to the competition-induced release of the bound anion and thus recycling the polymeric material.

Synthesis of a water-soluble 2,6-helic[6]arene derivative and its strong binding abilities towards quaternary phosphonium salts: an acid/base controlled switchable complexation process.

A water-soluble 2,6-helic[6]arene derivative was conveniently synthesized, and it showed strong binding abilities towards quaternary phosphonium salts in aqueous solution. Moreover, an acid/base controlled switchable complexation process was also described.

Formation of charge-transfer complexes based on a tropylium cation and 2,6-helic[6]arenes: a visible redox stimulus-responsive process.

Charge-transfer (CT) complexes formed from 2,6-helic[6]arene hosts and a tropylium cation are described in detail. In particular, it was found that the binding and release processes of the guest in the complexes could be efficiently controlled by a redox stimulus, and the responsive process could be visually observed by the color change of the solution. To our knowledge, this represents the first visible redox stimulus-responsive host-guest system formed from the tropylium cation.

Complexation of Racemic 2,6-Helic[6]arene and Its Hexamethyl-Substituted Derivative with Quaternary Ammonium Salts, N-Heterocyclic Salts, and Tetracyanoquinodimethane.

Complexation of racemic 2,6-helic[6]arene 1 and its hexamethyl-substituted derivative 2 with quaternary ammonium salts, N-heterocyclic salts, and tetracyanoquinodimethane have been described in detail. It was found that host 2 could form stable complexes with acetyl choline, thiaacetyl choline, N,N,N-trimethylbenzenammonium salt, pyridinium, and 4,4'-bipyridinium salts in solution and/or in the solid state. The unsubstituted macrocycle 1 showed more significant complexation with the widely tested quaternary ammonium salts and N-heterocyclic salts, and exhibited stronger complexation towards the guests than its derivative 2. Moreover, it was found that macrocycle 1 and its derivative 2 could also complex with neutral electron-deficient tetracyanoquinodimethane (TCNQ), and the association constants were determined to be 2840±94 and 1358±46 m-1 , respectively. These results could make this new macrocycle and its derivatives find wide applications in the design and construction of functional supramolecular assemblies.

Triptycene-Based Chiral Macrocyclic Hosts for Highly Enantioselective Recognition of Chiral Guests Containing a Trimethylamino Group.

A new class of chiral macrocyclic arene composed of three chiral 2,6-dihydroxyltriptycene subunits bridged by methylene groups was designed and synthesized. Structural studies showed that the macrocyclic molecule adopts a hex-nut-like structure with a helical chiral cavity and highly fixed conformation. Efficient resolution was achieved through the introduction of chiral auxiliaries to give a couple of enantiopure macrocycles, which exhibited high enantioselectivity towards three pairs of chiral compounds containing a trimethylamino group.