Molecular Hosts for the Sensing and Separation of 99TcO4.

In recent years, European Union member states have hastened energy policy deliberations to address supply and sustainability concerns, placing a significant emphasis on nuclear energy as a means to achieve decarbonization goals. However, despite its significant role in power generation, nuclear energy faces significant challenges linked to fuel reprocessing and waste disposal, that hinder its broader expansion. In this context, the separation of technetium represents a concerning issue. Indeed, technetium's catalytic activity can impede the extraction of uranium, neptunium, and plutonium, affecting waste reprocessing efficiency. Additionally, the stable form of technetium in aerobic conditions, pertechnetate (TcO4-), poses risks of groundwater contamination due to its mobility and solubility. Hence, sensing and separation of TcO4- is imperative for both nuclear fuel processing and minimising radioactive contamination in the environment. However, the binding of TcO4- and its separation from contaminated solutions present challenges due to the acidic (or basic) waste components and the high ionic strength in real matrices. Supramolecular chemists have addressed these issues by designing receptors inspired by molecular recognition principles. This article explores recent advancements and future directions in TcO4- sensing and separation (using extraction and sorption) with a focus on molecular hosts. Metal-organic receptors will also be discussed.

Triptycene-based diiron(II) mesocates: spin-crossover in solution.

Triptycene-based diiron(II) and dizinc(II) mesocates were obtained using a novel rigid ligand with two pyridylbenzimidazole chelating units fused into the triptycene scaffold. Studies on the diiron(II) assembly in solution showed that the complex undergoes thermal-induced one-step spin-crossover with T1/2 at 243 K (Evans method).

Homoconjugation and Tautomeric Isomerism in Triptycene-Fused Pyridylbenzimidazoles.

The facile, metal-free synthesis and characterization of three new series of triptycene-fused pyridylbenzimidazoles are reported; such compounds possess an imidazole moiety fused within the benzene rings of the trypticene and a pyridine ring installed at position 2 of the imidazole rings. The position of the nitrogen atom of the pyridyl moiety linked to position 2 of the fused benzimidazole scaffold is systematically changed from the ortho to para position. The number of substituted blades bearing the pyridyl-substituted fused benzimidazole scaffolds has been increased from one to three. Such a library of compounds allowed us to evaluate the enhancement of two main effects: tautomeric isomerism and homoconjugation. The characteristic dynamic equilibrium between different isomers induced by prototropic tautomerization was examined by 1H nuclear magnetic resonance spectroscopy. By comparison of the photophysical properties of the new compounds with those of classical planar pyridylbenzimidazoles, the presence of the homoconjugation effect between the different triptycene blades was demonstrated. Fine details of the electronic structure of the new derivatives were unraveled by a computational analysis. The novel compounds can be employed for the construction of intriguing self-assembled supramolecular architectures.

Recent applications of organic cages in sensing and separation processes in solution.

Organic cages are three-dimensional polycyclic compounds of great interest in the scientific community due to their unique features, which generally include simple synthesis based on the dynamic covalent chemistry strategies, structural tunability and high selectivity. In this feature article, we present the advances over the last ten years in the application of organic cages as chemosensors or components in chemosensing devices for the determination of analytes (pollutants, analytes of biological interest) in complex aqueous media including wine, fruit juice, urine. Details on the recent applications of organic cages as selective (back-)extractants or masking agents for potential applications in relevant separation processes, such as the plutonium and uranium recovery by extraction, are also provided. Over the last ten years, organic cages with permanent porosity in the liquid and solid states have been highly appreciated as porous materials able to discriminate molecules of different sizes. These features, combined with good solvent processability and film-forming tendency, have proved useful in the fabrication of membranes for gas separation, solvent nanofiltration and water remediation processes. An overview of the recent applications of organic cages in membrane separation technologies is given.

Gas Permeation through Mechanically Resistant Self-Standing Membranes of a Neat Amorphous Organic Cage.

The synthesis and characterization of a novel film-forming organic cage and of its smaller analogue are here described. While the small cage produced single crystals suitable for X-ray diffraction studies, the large one was isolated as a dense film. Due to its remarkable film-forming properties, this latter cage could be solution processed into transparent thin-layer films and mechanically stable dense self-standing membranes of controllable thickness. Thanks to these peculiar features, the membranes were also successfully tested for gas permeation, reporting a behavior similar to that found with stiff glassy polymers such as polymers of intrinsic microporosity or polyimides. Given the growing interest in the development of molecular-based membranes, for example for separation technologies and functional coatings, the properties of this organic cage were investigated by thorough analysis of their structural, thermal, mechanical and gas transport properties, and by detailed atomistic simulations.

A Supramolecular Approach to Antimicrobial Surfaces.

In this paper, we report on the preparation of Imidazole-functionalized glass surfaces, demonstrating the ability of a dinuclear Cu(II) complex of a macrocyclic ligand to give a "cascade" interaction with the deprotonated forms of grafted imidazole moieties. In this way, we realized a prototypal example of an antimicrobial surface based on a supramolecular approach, obtaining a neat microbicidal effect using low amounts of the described copper complex.

CO2 Separation by Imide/Imine Organic Cages.

Invited for the cover of this issue are the groups of Valeria Amendola at the University of Pavia, Mariolino Carta at the University of Swansea, and Johannes C. Jansen at the CNR-ITM. The image depicts one of the novel imide/imine organic cages that were employed as fillers in mixed-matrix membranes for the selective separation of CO2 from N2 and CH4 . Read the full text of the article at 10.1002/chem.202201631.

Association of Indocyanine Green with Chitosan Oleate Coated PLGA Nanoparticles for Photodynamic Therapy.

Indocyanine green (ICG) is a safe dye widely used in the biomedical field. Its photodynamic effect (PDT), originating from laser irradiation at 803 nm, opens interesting perspectives in theranostic applications. To overcome its low water stability, ICG can be shielded with nanoparticles (NPs). In this work, previously developed NPs based on poly lactic-co-glycolic acid (PLGA) coated with chitosan oleate (CS-OA) and loaded with resveratrol as a hydrophobic model drug have been proposed as an ICG carrier. These systems have been selected for their observed immunostimulatory properties. The possible loading of the dye by adsorption onto NP surface by electrostatic interaction was studied here in comparison with the encapsulation into the PLGA core. The ICG-chitosan (CS) interaction has been characterized by spectrophotometry, spectroscopy and in-cell in vitro assays. Fluorescence quenching was observed due to the ionic interaction between ICG and CS and was studied considering the dye:polymer stoichiometry and the effect of the NP dilution in cell culture medium (DMEM). The NP systems have been compared in vitro, assessing their behaviour in Caco-2 cell lines. A reduction in cell viability was observed after irradiation of ICG associated with NPs, evident also for the samples loaded by adsorption. These findings open the opportunity to exploit the association of PDT's effect on ICG with the properties of CS-OA coated NPs, whose immunostimulatory effect can be associated with PDT mechanism in cancer therapy.

CO2 Separation by Imide/Imine Organic Cages.

Two novel imide/imine-based organic cages have been prepared and studied as materials for the selective separation of CO2 from N2 and CH4 under vacuum swing adsorption conditions. Gas adsorption on the new compounds showed selectivity for CO2 over N2 and CH4 . The cages were also tested as fillers in mixed-matrix membranes for gas separation. Dense and robust membranes were obtained by loading the cages in either Matrimid® or PEEK-WC polymers. Improved gas-transport properties and selectivity for CO2 were achieved compared to the neat polymer membranes.

Chiroptical sensing of perrhenate in aqueous media by a chiral organic cage.

A chiral cage is proposed as an effective chiroptical sensor for perrhenate (surrogate for 99TcO4-) in water, fruit juice and artificial urine media. The key mechanism for the chiroptical sensing resides in the change of dihedral angle of the binaphthyl unit and H-bonds with the guest, resulting in ample changes of the CD signal as a consequence of the binding event.

PEEK-WC-Based Mixed Matrix Membranes Containing Polyimine Cages for Gas Separation.

Membrane-based processes are taking a more and more prominent position in the search for sustainable and energy-efficient gas separation applications. It is known that the separation performance of pure polymers may significantly be improved by the dispersion of suitable filler materials in the polymer matrix, to produce so-called mixed matrix membranes. In the present work, four different organic cages were dispersed in the poly(ether ether ketone) with cardo group, PEEK-WC. The m-xylyl imine and furanyl imine-based fillers yielded mechanically robust and selective films after silicone coating. Instead, poor dispersion of p-xylyl imine and diphenyl imine cages did not allow the formation of selective films. The H2, He, O2, N2, CH4, and CO2 pure gas permeability of the neat polymer and the MMMs were measured, and the effect of filler was compared with the maximum limits expected for infinitely permeable and impermeable fillers, according to the Maxwell model. Time lag measurements allowed the calculation of the diffusion coefficient and demonstrated that 20 wt % of furanyl imine cage strongly increased the diffusion coefficient of the bulkier gases and decreased the diffusion selectivity, whereas the m-xylyl imine cage slightly increased the diffusion coefficient and improved the size-selectivity. The performance and properties of the membranes were discussed in relation to their composition and morphology.

Syntheses and evaluation of new hydrophilic azacryptands used as masking agents of technetium in solvent extraction processes.

The extraction of technetium, present in nitric acid medium as pertechnetate anion, is an issue in solvent extraction processes used to recover uranium and plutonium. In the present study, a complexing agent is added in the aqueous nitric acid solution to bind selectively the pertechnetate anion and prevent its extraction into the organic phase or to back extract it in the aqueous phase. Several azacryptands with the addition of hydrophilic groups were synthesized to improve the solubility of the previously studied cage molecule in nitric acid medium. Solvent extraction tests reveal that all the synthesized ligands have a similar complexation strength towards pertechnetate and are able to maintain this anion in the aqueous phase (0.5 M HNO3). These ligands are able to overcome the Hofmeister bias and selectively bind technetium in nitric acid solution. The azacryptand concentration can be increased by a factor of three in the liquid-liquid extraction conditions compared to our previous work. Coordination studies using microcalorimetry, Single Crystal X-Ray Diffraction (SC-XRD), infrared and Raman spectroscopies show the formation of an inclusion complex with hydrogen bonds stabilizing the oxo-anion within the cavity. This solubility improvement is promising for the introduction of this kind of macrocyclic azacryptands in a solvent extraction process.

A Nanoprobe Based on Gated Mesoporous Silica Nanoparticles for The Selective and Sensitive Detection of Benzene Metabolite t,t-Muconic Acid in Urine.

Benzene is a highly toxic aromatic hydrocarbon. Inhaling benzene can cause dizziness, vertigo, headaches, aplasia, mutations and, in the most extreme cases, cancer. Trans,trans-muconic acid (t,t-MA) is one of the metabolization products of benzene. Although different analytical methods have been reported for the determination of t,t-MA, these are often expensive, require trained personnel, are not suitable for on-site measurements, and use hazardous organic solvents. For these reasons, the development of reliable, selective and sensitive methods for rapid and in situ detection of t,t-MA are of importance. Addressing this challenge, a nanodevice for the selective and sensitive quantification of t,t-MA in urine is reported. The nanodevice used is achieved using mesoporous silica nanoparticles loaded with a dye reporter and capped with a dicopper(II) azacryptand. Pore opening and payload release is induced rapidly (10 min) and selectively with t,t-MA in urine, using a simple fluorimeter without sample pretreatment.

Sensing and Liquid-Liquid Extraction of Dicarboxylates Using Dicopper Cryptates.

We report the investigation of dicopper(II) bistren cryptate, containing naphthyl spacers between the tren subunits, as a receptor for polycarboxylates in neutral aqueous solution. An indicator displacement assay for dicarboxylates was also developed by mixing the azacryptate with the fluorescent indicator 5-carboxyfluorescein in a 50:1 molar ratio. Fluorimetric studies showed a significant restoration of fluorophore emission upon addition of fumarate anions followed by succinate and isophthalate. The introduction of hexyl chains on the naphthalene groups created a novel hydrophobic cage; the corresponding dicopper complex was investigated as an extractant for dicarboxylates from neutral water into dichloromethane. The liquid-liquid extraction of succinate-as a model anion-was successfully achieved by exploiting the high affinity of this anionic guest for the azacryptate cavity. Extraction was monitored through the changes in the UV-visible spectrum of the dicopper complex in dichloromethane and by measuring the residual concentration of succinate in the aqueous phase by HPLC-UV. The successful extraction was also confirmed by 1H-NMR spectroscopy. Considering the relevance of polycarboxylates in biochemistry and in the environmental field, e.g., as waste products of industrial processes, our results open new perspectives for research in all contexts where recognition, sensing, or extraction of polycarboxylates is required.

Organic Cages as Building Blocks for Mechanically Interlocked Molecules: Towards Molecular Machines.

The research on systems able to perform controllable motions under external stimuli arises great interest in the scientific community. Over the years, a library of innovative devices has been produced, classified in different categories according to the molecular or supramolecular level of motion. This minireview aims to highlight some representative studies, in which organic cages are used as building blocks for mechanically interlocked molecules, and in which intramolecular motions are triggered by external input. However, the application of organic cages in the construction of molecular machines is hardly achieved. A good compromise must actually be reached, between flexibility and rigidity of the cage's framework for an effective control of the intra- and/or intermolecular motion in the final mechanical device. Our final goal is to stimulate researchers' curiosity towards cage-like molecules, so that they take on the challenge of converting a cage into a molecular machine.

Towards Building Blocks for Supramolecular Architectures Based on Azacryptates.

In this work, we report the synthesis of a new bis(tris(2-aminoethyl)amine) azacryptand L with triphenyl spacers. The binding properties of its dicopper complex for aromatic dicarboxylate anions (as TBA salts) were investigated, with the aim to obtain potential building blocks for supramolecular structures like rotaxanes and pseudo-rotaxanes. As expected, UV-Vis and emission studies of [Cu2L]4+ in water/acetonitrile mixture (pH = 7) showed a high affinity for biphenyl-4,4'-dicarboxylate (dfc2-), with a binding constant of 5.46 log units, due to the best match of the anion bite with the Cu(II)-Cu(II) distance in the cage's cavity. Compared to other similar bistren cages, the difference of the affinity of [Cu2L]4+ for the tested anions was not so pronounced: conformational changes of L seem to promote a good interaction with both long (e.g., dfc2-) and short anions (e.g., terephthalate). The good affinity of [Cu2L]4+ for these dicarboxylates, together with hydrophobic interactions within the cage's cavity, may promote the self-assembly of a stable 1:1 complex in water mixture. These results represent a good starting point for the application of these molecular systems as building units for the design of new supramolecular architectures based on non-covalent interactions, which could be of interest in all fields related to supramolecular devices.

Perrhenate and pertechnetate complexation by an azacryptand in nitric acid medium.

Technetium is present as the pertechnetate anion in spent nuclear fuel solutions, and its extraction by several extractant systems is a major problem for the liquid-liquid extraction processes used to separate uranium and plutonium. To prevent technetium extraction into the organic phase, a complexing agent may be added to the aqueous nitric acid phase to selectively bind the pertechnetate anion. In the present study, liquid-liquid extraction experiments reveal that technetium distribution ratios are considerably lowered with addition of an azacryptand, which is a good receptor for pertechnetate anion recognition. This ligand is able to overcome the Hofmeister bias and selectively bind techetium in nitric acid solution. Coordination studies using infrared and Raman spectoscopies and DFT calculations show the formation of an inclusion complex with hydrogen bonds stabilizing the oxo-anion within the cavity. For the first time, the cage molecules are studied for an extraction process.

Halide-Controlled Extending-Shrinking Motion of a Covalent Cage.

Herein, we present an example of covalent cages, whose flexible framework undergoes extending-shrinking motion under halide control. In the absence of halide anions, the free cage assumes a flattened conformation: the cavity is compressed along the C3 axis passing through the tertiary amines, and the two tribenzylamine platforms are eclipsed. Halide encapsulation promotes a large conformational rearrangement of the cage, involving an extension of the cavity along the C3 axis and shrinkage along the equatorial plane. Interestingly, the rearrangement is accompanied by the pyramidal inversion of the tertiary amines and by the rotation of the tribenzylamine-based platforms, which become staggered. The imidazolium-containing arms wrap around the spherical anion, leading to a racemic mixture of the M and P helical complexes. As expected from the flexible structure of the cage, the switch between the two limit conformations can be repeated for several cycles under alternating chemical stimuli (AgNO3/TBACl). This result is consistent with the low activation barriers determined by computational investigations. These also allowed us to quantify the energy difference between the shrunk and expanded cage conformations and to hypothesize an energetic pathway along which the conformational rearrangement can occur.

A Catalytic and Selective Scissoring Molecular Tool for Quadruplex Nucleic Acids.

A copper complex embedded in the structure of a water-soluble naphthalene diimide has been designed to bind and cleave G-quadruplex DNA. We describe the properties of this ligand, including its catalytic activity in the generation of ROS. FRET melting, CD, NMR, gel sequencing, and mass spectrometry experiments highlight a unique and unexpected selectivity in cleaving G-quadruplex sequences. This selectivity relies both on the binding affinity and structural features of the targeted G-quadruplexes.

Self-Assembly of Pseudorotaxane Structures from a Dicopper(II) Molecular Cage and Dicarboxylate Axles.

In this work, we employed for the first time a dinuclear bis[tris(2-aminoethyl)amine] cryptate to obtain the self-assembly of pseudorotaxane structures in an aqueous solution. The goal was achieved by exploiting the well-known affinity of the dicopper azacryptate with diphenyl spacers for the terephthalate anion. In particular, a series of molecular threads were synthesized by appending either alkyl or polyoxyethylene chains on both sides of the terephthalate benzene ring. The obtained dicarboxylic acids were precipitated as sodium salts, and their affinity toward the dicopper azacryptate was determined in a methanol/water mixture (pH 7). Experimental investigations showed that the chains' length and nature have a small impact on the 1:1 binding constants, whose values range between 4.98 and 5.18 log units. Computational studies indicated that the molecular axle is threaded through the azacryptate cavity, with the terephthalate group wedged between the two copper ions, coordinating both of them in the apical position (the one that, in the free azacryptate, is occupied by a water molecule). Compared to the inclusion complex with the plain terephthalate anion, a slight strain was found in the pseudorotaxane structure, induced by the inner chain of the thread inside the cavity. These results may be of great interest in all of the fields of science and technology in which host-guest recognition and molecular cages are applied.