Chirality plays a crucial role in pharmaceutical development, as enantiomers often display distinct therapeutic, pharmacokinetic, and safety profiles. Calcium channel blockers (CCBs), a cornerstone in antihypertensive therapy, frequently possess one or more chiral centers, making enantioselective analysis essential for pharmacological and regulatory accuracy. Despite growing evidence of stereoselective differences, most marketed CCBs remain available as racemates, underscoring the need for refined analytical approaches. This review aims to bridge that gap by critically synthesizing advances in analytical, bioanalytical, and regulatory strategies for chiral CCBs. Key separation platforms-including high-performance liquid chromatography (HPLC), capillary electrophoresis (CE), gas chromatography (GC), and supercritical fluid chromatography (SFC)-are evaluated with emphasis on chiral stationary phases such as polysaccharides, cyclodextrins, macrocyclic antibiotics, and crown ethers. Recent innovations in hyphenated mass spectrometry, spectroscopic techniques, and eco-friendly miniaturized systems are highlighted for their ability to enhance enantioselectivity, reduce solvent consumption, and improve sensitivity in complex matrices. Case studies illustrate the pharmacokinetic and pharmacodynamic relevance of individual enantiomers, reinforcing the clinical impact of chirality in CCB therapy. The review concludes by identifying current limitations and exploring future directions, including AI-assisted selector design, green chemistry integration, and lab-on-chip platforms to advance personalized antihypertensive treatment.

Anion-mediated enhancement of antibiotic adsorption on crown ether covalent organic frameworks

Crown ether-ammonium inclusion compounds have attracted great interest in the fields of supramolecular chemistry, crystal engineering, and molecular switches due to their tunable host-guest dynamics and stimuli-responsive phase transitions. However, most reported systems exhibit phase transitions only below room temperature, limiting practical applications, and their luminescence properties remain largely unexplored. Herein, we report a host-guest inclusion compound, [(2-fluorophenethylaminium)(18-crown-6)][PF6] (1) that undergoes a reversible phase transition at 404 K, approaching the highest values reported in crown ether-based systems. Single-crystal X-ray diffraction confirms that the ammonium cation is tightly anchored within the 18-crown-6 cavity through N-H⋯O hydrogen bonds. Remarkably, the regioisomeric 3-fluoro (2) and 4-fluoro (3) analogues show no detectable phase transition, yet all three isomers display intense blue emission under 365 nm UV irradiation. This contrast demonstrates that 2-fluorine substitution is essential for the high-temperature transition, while luminescence arises from supramolecular confinement and does not depend on the fluorine substitution position. Density functional theory calculations support an intermolecular charge-transfer mechanism: the HOMO is localized on the crown ether oxygen atoms, the LUMO on the aromatic ring of the cation, with a calculated HOMO-LUMO gap of 4.49 eV. Collectively, these results demonstrate decoupling of the two functions, where the phase transition is governed by fluorine regiochemistry and emission is controlled by confinement effects. This decoupling provides a design principle for independently tuning thermal and optical properties in multifunctional molecular crystals.

We report the synthesis and the characterization of a multicomponent molecular machine based on a [3]rotaxane architecture. The system is composed by two crown ether macrocycles and an axle with three recognition sites for the rings: ammonium (AmH+), bipyridinium (Bpy2+), and triazolium (Trz+). The position of the two rings can be precisely controlled via a sequence of chemical and electrochemical inputs: the two rings can be located on neighboring stations, forced on the same station or separated at the opposite extremities of the axle. This complex mechanism is elucidated by a combination of NMR spectroscopy and voltammetric techniques, allowing to characterize the thermodynamics of the reaction network. The investigation shows that each ring is influenced by the presence and position of the other, resulting in a coupled motion, a critical feature for the development of next-generation molecular machines.

Superabsorbent polymer microparticles incorporating with crown ether for swelling-enhanced selective and rapid lithium capture.

Herein, we report the Li+-induced modulation of single-molecule conductance in a crown ether derivative using the scanning tunnelling microscope break junction (STM-BJ) technique. Upon Li+ coordination, the conductance decreases from 10-3.7G0 to 10-4.2G0. Experimental results reveal that the conductance decrease arises from a coordination-induced conformational transition, which extends the molecular junction and weakens the molecule-electrode coupling. These findings establish a clear structure-conductance correlation in crown ether systems and provide insights into the design of ion-responsive molecular electronic devices.

Recent advances in anion exchange membrane water electrolyzers (AEMWEs) have been primarily driven by anion exchange membranes (AEMs) prepared via superacid-catalyzed polymerization. However, the reliance on highly corrosive trifluoromethanesulfonic acid (TFSA; pKa = -14.7) employed both as catalyst and solvent poses significant safety, handling, and scalability challenges for industrial AEM manufacturing. Herein, we report a nonsuperacid polymerization strategy for AEMs, utilizing methanesulfonic acid (MSA; pKa = -1.9) to catalyze the Friedel-Crafts alkylation between electrophilic aminobenzaldehyde and electron-rich dibenzo-18-crown-6. Crown ether incorporation expands interchain spacing, thereby facilitating the formation of continuous hydrophilic ion-conducting channels. Furthermore, complexation of potassium ions with crown ether moieties weakens the electrostatic interaction between K+ and OH-, thereby lowering the dissociation energy of the KOH electrolyte. As a result, the optimized QPCA-70 membrane exhibits a high alkaline conductivity of 628.93 mS cm-1 at 80°C and delivers a current density of 8.8 A cm-2 at 2.0V using a NiFeCo anode. Critically, MSA serves as a safer, more practical, and cost-effective alternative to TFSA: it eliminates the extreme hazards associated with superacid handling, thereby enabling scalable, industrially viable, and low-risk AEM production.

A new chalcone-functionalized macrocyclic crown ether was synthesized as a highly functional scaffold, which combines supramolecular recognition, photophysical properties, environmental, and biological usage. The target compound was produced through a step-by-step approach and completely characterized through spectroscopic methods such as ¹H-NMR, ¹³C-NMR and DEPT-135 and Mass spectrophotometry. The addition of the chalcone moiety into the macrocyclic structure provided the system with specific fluorescence properties which were revealed broad π- π* and intramolecular charge-transfer emission, with enhanced intensity governed by conjugation and macrocyclic rigidity. The material was found to have an effective adsorption capacity with respect to the representative organic dyes (methylene blue dye) in aqueous. The synthesized compounds demonstrated promising dye removal performance toward methylene blue under laboratory conditions, suggesting their potential applicability in future wastewater remediation studies. Host-guest interactions, π-π stacking, and electrostatic effects have been proposed in the studies of adsorption to be significant in the removal process. Simultaneously, the products possessed modest antibacterial effects on Gram-positive and Gram-negative strains Staphylococcus aureus and Escherichia coli. In an attempt to justify the detected biological activity, molecular docking experiments were conducted, which showed positive binding interactions between the chalcone unit and the target proteins, which confirms the experimental results. The concerted findings emphasize the benefit of incorporating a chalcone chromophore into a macrocyclic system of crowns ether to create a highly flexible system with synergistic structural and functional characteristics. These findings affirm the chalcone-based macrocyclic ethers as multifunctional scaffold with potential applications in the development of antibacterial, in wastewater remediation and photo functional materials.

In this study, a novel extractant, 12-crown-4-ether-calix[4]arene (12C4@C[4]A), was designed for the selective recovery of lithium from the leach solution of end-of-life lithium-ion batteries. Density functional theory (DFT) results demonstrate that 12C4@C[4]A exhibits superior Li+ complexation affinity compared with three reference host molecules, namely 12-crown-4 (12C4), benzo-12-crown-4 (B12C4), and calix[4]arene (C[4]A). This exceptional binding is predominantly governed by the synergistic host-guest interaction between the crown ether oxygen donors and the aromatic π system of the C[4]A unit. In contrast, strong steric hindrance suppresses 12C4@C[4]A complexation with common competing metal ions (Ni2+, Co2+, and Mn2+), thereby rendering its highly selective for lithium-ion recovery. Overall, these findings identify 12C4@C[4]A as a promising supramolecular extractant for efficient and selective lithium recovery from end-of-life lithium-ion batteries. DFT calculations were performed using Gaussian 16, Multiwfn 3.6, and molecular visualizations were generated with VMD. Geometry optimizations were carried out at the M06-2X/def2-SVP level, followed by single-point energy calculations at the M06-2X/def2-TZVP level. The Boys-Bernardi counterpoise method was applied to correct for basis set superposition error (BSSE), and thermodynamic parameters including internal energy and Gibbs free energy changes were evaluated for complex formation. Structural optimization, electrostatic potential (ESP), frontier molecular orbitals (FMOs), Hirshfeld charge transfer, natural bond orbital (NBO), reduced density gradient (RDG), independent gradient model (IGM), and atoms in molecules (AIM) analyses were performed to elucidate the host-guest recognition mechanism.

Chiral 3,4-dihydro-2H-1,2,4-benzothiadiazine-1,1-dioxides (DHBDs) are core structural units in numerous biologically active molecules and chiral drug molecules. However, current catalytic synthetic methods for chiral DHBDs exhibit limitations, including limited substrate versatility and relatively unsatisfactory stereocontrol efficiency. This study has successfully developed a novel crown ether-derived chiral phosphoric acid catalyst, which can effectively catalyze the asymmetric tandem acetalization reaction between 2-aminobenzenesulfonamides and aldehydes, affording 36 chiral DHBDs under optimized conditions in 63-91% yield and 82-99% ee. Notably, this catalytic system exhibits broad substrate applicability, demonstrating high catalytic activity and excellent enantioselectivity toward both aromatic and aliphatic aldehydes, featuring simple operation and enabling gram-scale preparation. It is evidenced that the electron-rich, flexible structural features of crown ethers allow them to adaptively accommodate substrates through noncovalent interactions and therefore effectively promote the reactions in high reactivity and stereoselectivity.

Aliphatic diamines possess two amino functional groups and exhibit diverse chemical properties and tunable molecular structures. By selecting the guest [(C2H2n+4N2), n = 2–6] and host 18-crown-6, and controlling the design and assembly processes via modulation by thiocyanate and a manganese salt, a series of dumbbell-shaped crown ether complexes, (C2H2n+6N2)2+(18-crown-6)2[Mn(NCS)4]2−·(δn,2C2H3N), n = 2–6, (1)–(5), was synthesized and analyzed by single-crystal X-ray diffraction (SCXRD) at 100 K and 293 K. Variable-temperature infrared and XRD analyses confirmed that compounds 3 and 5 underwent a phase transition. As the length of the carbon chain increases and alternates between odd and even, the interplanar dihedral angle of the crown ether exhibits a distinct pattern: Even-number chains arrange in parallel, whereas odd-number chains form a pronounced angle. This structural pattern influences macroscopic deformation of the crystal and induces corresponding periodic variations in the dielectric and electrochemical properties. The wide-bandgap insulators and magnetic properties are primarily governed by the inorganic components of the system and are less influenced by the organic portion. This study reveals principles for regulating supramolecular conformation and functional properties through the parity of the organic chain lengths, providing a strategy for the molecular-level design of supramolecular crystal materials with ordered structures and tunable properties.

Precise conformational control of flexible supramolecular moieties (e.g., crown ethers) in crystalline-state adsorbents is essential for efficient host-guest recognition. Traditional strategies relying on covalent chemistry are often limited by either tedious synthesis or a sacrifice of conformational flexibility. Here, we introduce a simple non-covalent anchoring strategy where 18-crown-6 (18Cr6) molecules are in-situ embedded between the interlayer galleries of a perforated thiostannate framework (18Cr6-SnS) in one-pot synthesis. This architecture not only ensures ordered alignment of crown ethers but also preserves the intrinsic coordination freedom, thereby enabling exceptional Sr2+ binding affinity. 18Cr6-SnS exhibits a record-high distribution coefficient (Kd = 4.9 × 106mL/g) under neutral conditions and excellent selectivity in simulated acidic high-level liquid waste, displaying high separation factors (Kd Sr/Kd M) for Cs+ (96), Eu3+ (245), and Ni2+ (621) in 1M HNO3. Experimental and theoretical analyses reveal that the superior Sr2+ recognition arises from the conformational adaptability of intercalated crown ethers, coupled with adjustable interlayer spacing. This work establishes a cost-effective and scalable route to develop advanced adsorbents by synergizing host materials with flexible supramolecular receptors for critical energy and environmental applications.

Similar to the selective filter of biological ion channels, crown ethers have numerous dipole moments arranged around its interior, forming spatially confined electronegativity capable of attracting target ions while rejecting other species. In this light, crown-ether-based membranes have the potential to render both benign ion selectivity and high throughput and therefore enable highly efficient osmotic energy harvesting, however not yet implemented. Herein, we develop biomimetic sodium-selective channels via de novo encapsulation of diazacrown ethers into UiO-66 membranes. The embedding of such azamacrocycles exclusively enhances Na+ flux while blocking other cations, leading to the concurrent enhancement of Na+ selectivity and permeability. This can be ascribed to the interplay between ion dehydration and azamacrocycle-cation recognition, which resulted in a lower energy barrier for Na+ transport in contrast to other cations. The optimized permeability-selectivity combination enables the azamacrocycle-encapsulated membranes highly favorable in terms of osmotic energy harvesting, where an impressive output power density of 11.5 W m-2 is achieved by mixing natural seawater and river water. This work presents a methodology for developing high-performance ion-selective membranes with biomimetic channel structures, suitable for applications involving complicated separation processes and energy conversion systems.

Lithium metal batteries hold great promise for future energy storage due to their high energy density and potential for fast charging, making them ideal for applications in electric vehicles and portable electronics. However, lithium metal batteries usually suffer from rapid performance degradation because of the unstable electrode/electrolyte interface. To address this, we integrate bionic ion channels into commercial battery separators. This structure features metal-organic framework (MOF)-encapsulated benzo-12-crown-4-ether, mimicking biological ion channels. It enables rapid Li+ transport and uniform flux distribution, which suppress lithium dendrite growth. The crown ether sites in bionic ion channels weaken Li+-solvent coordination, forming an anion-rich solvation sheath. These anions preferentially decompose, generating a passivation layer at the anode interface that is rich in inorganic LiF and Li3N. Consequently, Li||Li symmetric cells achieve stable plating/stripping for over 1500h, and LiFePO4||Li full cells retain 86% capacity after 1200 cycles. This work provides a promising strategy for synergistic regulation of Li+ flux and interfacial chemistry through bionic design.

Efficient separation of lithium isotopes (6Li and 7Li) is critical for sustainable nuclear energy. The crown ether system exhibits outstanding lithium isotope separation performance, with the anion exerting a significant influence; however, the molecular-level mechanism of action of anions and how this affects the separation process remain unclear. This limits the design of higher performance separation systems. Through combining 6Li/7Li separation experiments, 7Li NMR spectroscopy, and quantum chemical calculations, this work makes it clear that anions control the separation factor by changing the Li+ coordination microenvironment. Through manipulation of hydration and crown ether encapsulation, charge-delocalized anions provide a coordinating environment around Li+ that balances the bond strengths inside a crown-ether container. This balance of the bonding state improves the thermodynamic driving force for the 6Li/7Li exchange between the aqueous and organic phases and substantially increases the separation coefficient. This study provides an efficient screening method for lithium isotope separation and offers theoretical guidance for designing and optimizing more efficient lithium isotope separation systems.

ConspectusAqueous zinc-ion batteries (ZIBs) are increasingly recognized as leading candidates for grid-scale energy storage owing to their intrinsic safety, material abundance, and low cost. However, their practical deployment is fundamentally constrained by a self-amplifying failure cycle at the zinc anode, wherein inhomogeneous Zn2+ flux induces dendritic growth, which exacerbates the hydrogen evolution reaction (HER) and promotes the formation of insulating passivation layers (e.g., Zn4SO4(OH)6·xH2O). Conventional mitigation strategies, such as structural engineering of the anode, surface coatings, or electrolyte optimization, are largely static and lack the dynamic adaptability required to stabilize the evolving electrode-electrolyte interface over extended cycling. In this context, supramolecular chemistry, governed by reversible noncovalent interactions, molecular recognition, and self-assembly, offers a transformative and dynamic platform to address the root causes of ZIB instability. This Account systematically elucidates the core mechanisms by which supramolecular systems operate: (1) host-guest recognition, wherein macrocyclic hosts (e.g., cyclodextrins, cucurbiturils, crown ethers) selectively bind Zn2+ or anions to reconfigure solvation structures and direct uniform ion transport; (2) interface stabilization via self-assembled supramolecular layers that create water-deficient, flexible artificial SEI layers to suppress parasitic reactions; and (3) dynamic hydrogen-bond networks that enable real-time adaptation, self-repair, and mechanical buffering against volume fluctuations. We highlight key contributions from our group and others across diverse application domains, including host-guest electrolyte additives, supramolecular gel electrolytes, and interfacial engineering, demonstrating precise control over Zn2+ deposition behavior (e.g., epitaxial (002) growth), effective HER suppression, and enhanced performance under extreme conditions such as low temperature. Through integration of advanced in situ characterization and multiscale simulations, we establish structure-property relationships that inform the rational design of next-generation supramolecular systems. Finally, we outline critical challenges and future directions, including elucidation of noncovalent interaction dynamics under operando conditions, development of multifunctional hosts with tailored selectivity, scalable and sustainable synthesis, and full-cell validation (e.g., suppression of cathode dissolution). This Account underscores that supramolecular chemistry, through its dynamic and adaptive nature, overcomes the inherent limitations of conventional static approaches and paves the way toward durable, high-performance ZIBs for sustainable energy storage.

Me3NO is well known for undergoing an oxygen-atom transfer reaction, while the C-H activation of Me3NO with organometallic complexes is far less explored. Herein, we report the synthesis and characterization of two hydroxo-bridged dinuclear complexes [Dy(12-crown-4)(µ-OH)(CH3CN)I]2I2(CH3CN)2 (3) and [Dy(15-crown-5)(µ-OH)(CH3CN)]2I4 (4), which were formed by the reactions of different crown ether supported complexes [Dy(12-crown-4)2(CH3CN)]I3 (1) and [Dy(15-crown-5)(CH3CN)2I]I2 (2) with Me3NO, respectively. The observation of bridging hydroxo groups in complexes 3 and 4 indicates that Me3NO underwent C-H activation along with OAT during the reactions. In contrast, the reactions of 1 and 2 with H2O led to two hydrated adducts [Dy(12-crown-4)2(H2O)](CH3CN)3I3 (5) and [Dy(15-crown-5)(CH3CN)2(H2O)]I3 (6), respectively.

Indene-annulated perylenes merge cyclopentadiene-like benzylic acidity with the multielectron redox chemistry of rylene carbonyl scaffolds, creating discrete redox–protonation (“Pourbaix”) spaces in which electron transfer and acid–base processes become intrinsically coupled. Here we map the accessible states of doubly and singly pentannulated perylenediimides and perylene tetraesters using absorption/emission spectroscopy, electrochemistry and spectroelectrochemistry, and DFT analysis. Voltammograms of all derivatives show two quasi-reversible, largely core-centered reductions, yet the pentannulated tetraesters uniquely undergo electrochemically induced γ-deprotonation prior to core reduction, consistent with electrogenerated-base chemistry. Chemical stimulation reveals pronounced chemodivergence: potassium tert-butoxide readily produces deprotonated “dienolate” NIR chromophores in the pentannulated tetraester series, whereas the corresponding diimides first form perylene-centered radical anions/dianions that evolve into benzylic anions and higher multianions in a cation-dependent manner, with crown ether sequestering K+ and reshaping reaction trajectories. Strong reductants enable entry into highly reduced charge states, including an X-ray-verified salt of a pentannulated diimide trianion displaying diverse potassium binding motifs, underscoring the non-innocent role of ion pairing. Oxidation of deprotonated dianions furnishes weakly coupled neutral diradicaloids with NIR absorption. These results establish indene-annulated rylenes as multistate NIR chromophores whose experimentally accessible Pourbaix subsets can be programmed by redox bias, base strength, and cation coordination, with direct implications for organic electrochromism and rylene-based energy-storage chemistries.

Defect formation in perovskite nanograins in the polycrystalline films is governed by the solution-state coordination chemistry of halide perovskite precursor species, which have been employed to form less-defective films with large grains in solar cells. However, the coordination dynamics of bromoplumbate complexes in solution to form small grains for light-emission have been rarely studied in the context of defect suppression. In this work, we investigated the interplay between crown ether complexation and solvent coordination strength in perovskite precursor solutions, which governs the dispersion of precursor species and the formation of bromoplumbate complexes. Both crown ethers and polar aprotic solvents such as N,N-dimethylformamide (DMF) and dimethyl sulfoxide (DMSO) act as Lewis bases, competing for coordination with lead cations in the precursor solution. In weakly coordinating DMF, crown ethers can more effectively complex with precursors, shifting the coordination equilibrium toward high-valent bromoplumbate species unlike in strongly coordinating DMSO. This control yielded defect-suppressed perovskite films with nanograins with higher photoluminescence compared to those formed in strongly coordinating solvents of DMSO. These insights into bromoplumbate chemistry provide a basis for rational solvent and additive selection toward defect suppression and enhanced light-emitting performance.

The influence of functional groups on the solvate state of crown ethers and the stability of their metal complexes when changing the composition of the solvent