A novel potentiometric screen-printed electrode based on crown ethers/nano manganese oxide/Nafion composite for trace level determination of copper ion in biological fluids.

Copper levels in biological fluids are associated with Wilson's, Alzheimer's, Menke's, and Parkinson's diseases, making them good biochemical markers for these diseases. This study introduces a miniaturized screen-printed electrode (SPE) for the potentiometric determination of copper(II) in some biological fluids. Manganese(III) oxide nanoparticles (Mn2O3-NPs), dispersed in Nafion, are drop-casted onto a graphite/PET substrate, serving as the ion-to-electron transducer material. The solid-contact material is then covered by a selective polyvinyl chloride (PVC) membrane incorporated with 18-crown-6 as a neutral ion carrier for the selective determination of copper(II) ions. The proposed electrode exhibits a Nernstian response with a slope of 30.2 ± 0.3 mV/decade (R2 = 0.999) over the linear concentration range 5.2 × 10-9 - 6.2 × 10-3 mol/l and a detection limit of 1.1 × 10-9 mol/l (69.9 ng/l). Short-term potential stability is evaluated using constant current chronopotentiometry (CP) and electrochemical impedance spectroscopy (EIS). A significant improvement in the electrode capacitance (91.5 µF) is displayed due to the use of Mn2O3-NPs as a solid contact. The presence of Nafion, with its high hydrophobicity properties, eliminates the formation of the thin water layer, facilitating the ion-to-electron transduction between the sensing membrane and the conducting substrate. Additionally, it enhances the adhesion of the polymeric sensing membrane to the solid-contact material, preventing membrane delamination and increasing the electrode's lifespan. The high selectivity, sensitivity, and potential stability of the proposed miniaturized electrode suggests its use for the determination of copper(II) ions in human blood serum and milk samples. The results obtained agree fairly well with data obtained by flameless atomic absorption spectrometry.

Ion-imprinted membranes for lithium recovery: A review.

This review critically examines the effectiveness of ion-imprinted membranes (IIMs) in selectively recovering lithium (Li) from challenging sources such as seawater and brine. These membranes feature customized binding sites that specifically target Li ions, enabling selective separation from other ions, thanks to cavities shaped with crown ether or calixarene for improved selectivity. The review thoroughly investigates the application of IIMs in Li extraction, covering extensive sections on 12-crown-4 ether (a fundamental crown ether for Li), its modifications, calixarenes, and other materials for creating imprinting sites. It evaluates these systems against several criteria, including the source solution's complexity, Li+ concentration, operational pH, selectivity, and membrane's ability for regeneration and repeated use. This evaluation places IIMs as a leading-edge technology for Li extraction, surpassing traditional methods like ion-sieves, particularly in high Mg2+/Li+ ratio brines. It also highlights the developmental challenges of IIMs, focusing on optimizing adsorption, maintaining selectivity across varied ionic solutions, and enhancing permselectivity. The review reveals that while the bulk of research is still exploratory, only a limited portion has progressed to detailed lab verification, indicating that the application of IIMs in Li+ recovery is still at an embryonic stage, with no instances of pilot-scale trials reported. This thorough review elucidates the potential of IIMs in Li recovery, cataloging advancements, pinpointing challenges, and suggesting directions for forthcoming research endeavors. This informative synthesis serves as a valuable resource for both the scientific community and industry professionals navigating this evolving field.

Chiral recognition and discrimination studies of tyrosine enantiomers on (-)-18-crown-6-tetracarboxylic acid as a chiral selector by nuclear magnetic resonance spectroscopy and docking simulations.

Considering the substantial significance of chiral biomolecules, such as amino acids, in our daily routines, we performed chiral recognition and discrimination of tyrosine (Tyr) enantiomers on (-)-(18-crown-6)-2,3,11,12-tetracarboxylic acid [(-)-18-C-6-TA] as crown-ether type chiral selector (CS) by nuclear magnetic resonance (NMR) spectroscopy and docking simulations. In this study, successful discrimination of the enantiomers of Tyr was achieved, as evidenced by the proton chemical shift differences (ΔΔδ) of Tyr enantiomers observed in the 1 H NMR spectra with (-)-18-C-6-TA CS. We compared the results of these two techniques with the findings obtained from high performance liquid chromatography (HPLC) investigations. In both NMR and HPLC experimental and docking simulation studies, a stronger interaction between the L-Tyr enantiomer with (-)-18-C-6-TA CS than the D-Tyr was consistently observed. Also, the binding energy differences (ΔΔEL-D ) found in simulation data that correspond to enantioselectivity aligned well with the NMR experimental result.

Ion-Selective Micropipette Sensor for In Vivo Monitoring of Sodium Ion with Crown Ether-Encapsulated Metal-Organic Framework Subnanopores.

In vivo sensing of the dynamics of ions with high selectivity is essential for gaining molecular insights into numerous physiological and pathological processes. In this work, we report an ion-selective micropipette sensor (ISMS) through the integration of functional crown ether-encapsulated metal-organic frameworks (MOFs) synthesized in situ within the micropipette tip. The ISMS features distinctive sodium ion (Na+) conduction and high selectivity toward Na+ sensing. The selectivity is attributed to the synergistic effects of subnanoconfined space and the specific coordination of 18-crown-6 toward potassium ions (K+), which largely increase the steric hindrance and transport resistance for K+ to pass through the ISMS. Furthermore, the ISMS exhibits high stability and sensitivity, facilitating real-time monitoring of Na+ dynamics in the living rat brain during spreading of the depression events process. In light of the diversity of crown ethers and MOFs, we believe this study paves the way for a nanofluidic platform for in vivo sensing and neuromorphic electrochemical sensing.

Chiral recognition mechanism studies of Tyr-Arg-Phe-Lys-NH2 tetrapeptide on crown ether-based chiral stationary phase.

Even though chiral recognition for crown-ether CSPs is generally understood, on a molecular level, exact mechanisms for the resolution are still unclear. Furthermore, short peptide analytes often contain multiple amino moieties capable of binding to the crown ether selector. In order to extend the understanding in chiral recognition mechanisms, polar organic mode separation of Tyr-Arg-Phe-Lys-NH2 tetrapeptide llll/dddd enantiomers on S- and R-(3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6 stationary phases was studied with 50-mM perchloric acid in methanol as mobile phase. Deviation from the generally acceptable 1:1 stoichiometry was supported by mass spectroscopy analysis of the formed complexes between tetrapeptide enantiomer and crown ether selectors, which revealed adducts possessing 1:1, 1:2, and 1:3 stoichiometry. Further investigation of complexation induced shifts by NMR indicated on different binding mechanisms between llll/dddd enantiomers of Tyr-Arg-Phe-Lys-NH2 and crown ether selectors. Enantioselective proton shifts were observed in studied tetrapeptide tyrosine and phenylalanine residues exclusively for llll enantiomer upon binding with S-(3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6 selector (and dddd enantiomer with R-(3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6 selector), indicating that these two amino acid residues contribute to chiral recognition. The obtained results were in agreement with the LC data.

Effect of the Temperature on the Process of Preferential Solvation of 1,4-Dioxane, 12-Crown-4, 15-Crown-5 and 18-Crown-6 Ethers in the Mixture of N-Methylformamide with Water: Composition of the Solvation Shell of the Cyclic Ethers.

The aim of the work was to analyze the preferential solvation process, and determine the composition of the solvation shell of cyclic ethers using the calorimetric method. The heat of solution of 1,4-dioxane, 12-crown-4, 15-crown-5 and 18-crown-6 ethers in the mixture of N-methylformamide with water was measured at four temperatures, 293.15 K, 298.15 K, 303.15 K, and 308.15 K, and the standard partial molar heat capacity of cyclic ethers has been discussed. 18-crown-6 (18C6) molecules can form complexes with NMF molecules through the hydrogen bonds between -CH3 group of NMF and the oxygen atoms of 18C6. Using the model of preferential solvation, the cyclic ethers were observed to be preferentially solvated by NMF molecules. It has been proved that the molar fraction of NMF in the solvation shell of cyclic ethers is higher than that in the mixed solvent. The exothermic, enthalpic effect of preferential solvation of cyclic ethers increases with increasing ring size and temperature. The increase in the negative effect of the structural properties of the mixed solvent with increase in the ring size in the process of preferential solvation of the cyclic ethers indicates an increasing disturbance of the mixed solvent structure, which is reflected in the influence of the energetic properties of the mixed solvent.

Crown Ether-Based Ion Transporters in Bilayer Membranes.

Bilayer membranes that enhance the stability of the cell are essential for cell survival, separating and protecting the interior of the cell from its external environment. Membrane-based channel proteins are crucial for sustaining cellular activities. However, dysfunction of these proteins would induce serial channelopathies, which could be substituted by artificial ion channel analogs. Crown ethers (CEs) are widely studied in the area of artificial ion channels owing to their intrinsic host-guest interaction with different kinds of organic and inorganic ions. Other advantages such as lower price, chemical stability, and easier modification also make CE a research hotspot in the field of synthetic transmembrane nanopores. And numerous CEs-based membrane-active synthetic ion channels were designed and fabricated in the past decades. Herein, the recent progress of CEs-based synthetic ion transporters has been comprehensively summarized in this review, including their design principles, functional mechanisms, controllable properties, and biomedical applications. Furthermore, this review has been concluded by discussing the future opportunities and challenges facing this research field. It is anticipated that this review could offer some inspiration for the future fabrication of novel CEs-derived ion transporters with more advanced structures, properties, and practical applications.

Ultraviolet Photodissociation Reveals the Molecular Mechanism of Crown Ether Microsolvation Effect on the Gas-Phase Native-like Protein Structure.

Maintaining the protein high-order structures and interactions during the transition from aqueous solution to gas phase is essential to the structural analysis of native mass spectrometry (nMS). Herein, we systematically interrogate the effects of charge state and crown ether (CE) complexation on the gas-phase native-like protein structure by integrating nMS with 193 nm ultraviolet photodissociation (UVPD). The alterations of photofragmentation yields of protein residues and the charge site distribution of fragment ions reveal the specific sites and sequence regions where charge and CE take effect. Our results exhibit the CE complexation on protonated residues can largely alleviate the structure disruption induced by the intramolecular solvation of charged side chains. The influences of CE complexation and positive charge on gas-phase protein structure exhibit generally opposite trends because the CE microsolvation avoids the hydrogen-bonding formation between the charged side chains with backbone carbonyls. Thus, CE complexation leads to a more stable and native-like protein structure in the gas phase.

Enhanced molecular binding affinity toward aromatic dications by anthracene-derived crown ethers in water.

The pursuit of high molecular binding affinity using conventional crown ethers in water remains a challenging task in the field of supramolecular chemistry and may hold great promise in the creation of advanced biocompatible nanoconstructs. In this work, the molecular binding strength toward a series of structurally relevant cationic guests has been greatly enhanced by tetrasulfonated 1,5-dianthracenyl-42-crown-10 and as investigated by means of 1H NMR, UV-vis, and fluorescence spectroscopy, the host-guest association constants can reach up to 108 M-1 order of magnitude in aqueous solution. X-ray crystal diffraction analysis further demonstrates that the aromatic dication can be tightly encapsulated in the ring of anthracene-derived crown ether via multiple π-stacking and electrostatic interactions. Meanwhile, the obtained association constants are remarkably higher than the ones in the cases of the known benzene- and naphthalene-derived sulfonated crown ethers, substantiating that the appropriate extension of π-conjugation in the molecular skeleton of crown ether is a feasible method in attaining a highly affiliative host-guest complex. Taken together, our results indicate that the anthracene-based sulfonated crown ether can be developed as a new family of water-soluble macrocyclic receptors in the fabrication of functional nanoarchitectures.

Fluorescent and Phosphorescent Nitrogen-Containing Heterocycles and Crown Ethers: Biological and Pharmaceutical Applications.

Fluorescent molecules absorb photons of specific wavelengths and emit a longer wavelength photon within nanoseconds. Recently, fluorescent materials have been widely used in the life and material sciences. Fluorescently labelled heterocyclic compounds are useful in bioanalytical applications, including in vivo imaging, high throughput screening, diagnostics, and light-emitting diodes. These compounds have various therapeutic properties, including antifungal, antitumor, antimalarial, anti-inflammatory, and analgesic activities. Different neutral fluorescent markers containing nitrogen heterocycles (quinolones, azafluoranthenes, pyrazoloquinolines, etc.) have several electrochemical, biological, and nonlinear optic applications. Photodynamic therapy (PDT), which destroys tumors and keeps normal tissues safe, works in the presence of molecular oxygen with light and a photosensitizing drugs (dye) to obtain a therapeutic effect. These compounds can potentially be effective templates for producing devices used in biological research. Blending crown compounds with fluorescent residues to create sensors has been frequently investigated. Florescent heterocyclic compounds (crown ether) increase metal solubility in non-aqueous fluids, broadening the application window. Fluorescent supramolecular polymers have widespread use in fluorescent materials, fluorescence probing, data storage, bio-imaging, drug administration, reproduction, biocatalysis, and cancer treatment. The employment of fluorophores, including organic chromophores and crown ethers, which have high selectivity, sensitivity, and stability constants, opens up new avenues for research. Fluorescent organic compounds are gaining importance in the biological world daily because of their diverse functionality with remarkable structural features and positive properties in the fields of medicine, photochemistry, and spectroscopy.

Noncooperative guest binding by metal-free [2 + 2] Schiff-base macrocycles.

Salphen-based [n + n] macrocycles have been widely explored for their unique chemical and topological properties following metal ion coordination. Despite having vastly different reactivity than their coordinated counterparts, fewer studies have focused on metal-free salphen macrocycles. We investigated the binding of [2 + 2] Schiff-base macrocycle host 3, which contains a central 18-crown-6-like cavity and two N2O2 moieties. This macrocycle strongly binds to spherical cationic guests (K11 ≈ 103-104 M-1, DCM/MeCN). The most robust binding was shown for K+ and Na+, followed by Li+ and Rb+. More sterically demanding cationic guests like dibenzylammonium (DBA+) showed almost no binding. The binding pocket in 3 is slightly smaller than 18-crown-6, resulting in binding outside the cavity, which provides a scaffold appropriate for 2 : 1 complexes, where two host molecules sandwich the guest. All host-guest complexes follow a 2 : 1 noncooperative binding model, where each successive binding event is less likely than the previous, unlike coordinated versions of 3, where most binding is 1 : 1.

Separation of the enantiomers of underivatized amino acids by using serially connected dual column high-performance liquid chromatography-tandem mass spectrometry.

In this article, a serially connected dual column liquid chromatography-tandem mass spectrometry (LC-MS/MS) method is described for the simultaneous separation and enantioseparation of proteinogenic amino acids. For this purpose, different achiral and chiral stationary phases (CSP) and mobile phase compositions have been tested. As a result of the optimization studies, the best enatioseparation for amino acids were achieved with a combination of zwitterionic and crown ether stationary phases using a gradient of two mobile phases: A (water:TFA 99.5:0.5, % v/v) and B (acetonitrile:ethanol:TFA 85:15:0.5, % v/v/v). The developed method provided simultaneous enantioseparation of all proteinogenic amino acids under this study including isomeric and isobaric ones except for proline. The method was successfully applied to human lung adenocarcinoma cells (A549) and healthy human lung epithelial cells (BEAS-2B) cultivated with d-amino acid containing cocktails in order to evaluate d-amino acids transfer rate in normal and cancer lines. Thed/l amino acid ratios were different in cancer and normal cell lines cultivated as mentioned above for aspartic acid, cysteine, methionine, phenylalanine, and serine.

Improved Syntheses of 4'-Vinylbenzo-3n-Crown-n Ethers (n = 5-7).

A convenient, high-yielding, and scalable synthetic approach to the construction of 4'-vinylbenzocrown ethers has been developed, which employs a decarboxylation and cyclization strategy. Using this method, a wide-ranging class of vinylbenzocrown ethers can be efficiently obtained. The identity of the crown ethers was further established using single-crystal X-ray diffraction studies. Two of the vinylbenzocrown ethers crystallize with water, affording infinite supramolecular assemblies containing hydrogen-bonded water molecules.

Antimicrobial V-Shaped Copper(II) Pentaiodide: Insights to Bonding Pattern and Susceptibility.

Antimicrobial resistance (AMR) is a major concern for the survival of mankind. COVID-19 accelerated another silent pandemic of AMR through the uncontrolled use of antibiotics and biocides. New generations of antimicrobial agents are needed to combat resistant pathogens. Crown ethers can be used as models for drug action because they are similar to antibiotics. Iodine is a well-known microbicide but is characterized by instability and short-term effectivity. Iodine can be stabilized in the form of polyiodides that have a rich topology but are dependent on their immediate surroundings. In addition, copper has been successfully used since the beginning of history as a biocidal agent. We, therefore, combined iodine and copper with the highly selective crown ether 1,4,7,10-tetraoxacyclododecane (12-crown-4). The morphology and composition of the new pentaiodide [Cu(12-crown-4)2]I5 was investigated. Its antimicrobial activities against a selection of 10 pathogens were studied. It was found that C. albicans WDCM 00054 is highly susceptible to [Cu(12-crown-4)2]I5. Additionally, the compound has good to intermediate antimicrobial activity against Gram-positive and Gram-negative bacilli. The chain-like pentaiodide structure is V-shaped and consists of iodine molecules with very short covalent bonds connected to triiodides by halogen bonding. The single crystal structure is arranged across the lattice fringes in the form of ribbons or honeycombs. The susceptibility of microorganisms towards polyiodides depends on polyiodide bonding patterns with halogen-, covalent-, and non-covalent bonding.

Simultaneous Differentiation of C═C Position Isomerism in Fatty Acids through Ion Mobility and Theoretical Calculations.

Fatty acids play a pivotal role in biological processes and have many isomers, particularly at the C═C position, that influence their biological function. Distinguishing between isomers is crucial to investigating their role in health and disease. However, separating the isomers poses a significant analytical challenge. In this study, we developed a simple and rapid strategy combining ion mobility spectrometry and theoretical chemical calculations to differentiate and quantify the C═C positional isomers in 2-/3-butenoic acid (BA), 2-/3-/4-pentenoic acid (PA), and 2-/3-/5-hexenoic acid (HA). C═C positional isomerism was mobility-differentiated by simple complexation with crown ethers (12C4, 15C5, and 18C6) and divalent metal ions (Mg2+, Ca2+, Mn2+, Fe2+, Co2+, Ni2+, Zn2+, Sr2+, and Ba2+), that is, converting C═C positional isomers with small structural differences into complexes with large structural differences through the interaction with metal ions and crown ethers. Metallized isomers were formed but could not be differentiated due to their complex and overlapping extracted ion mobiliograms (EIMs). Binary crown ether-isomer complexes were not observed, indicating that C═C positional isomers could not be separated by simple mixing with crown ethers. However, significant EIM differences were obtained for the formed ternary complexes, allowing baseline separation for the isomers. Notably, all crown ethers and metal ions have a separation effect with the isomers, with a calculated separation resolution (Rp-p) of 0.07-2.44. Theoretical chemical calculations were performed to provide in-depth structural information for the complexes and explain the separation principle. Theoretical conformational space showed that the divalent metal ions act as a bridge connecting the crown ether and the isomer. Additionally, the ternary complex becomes more compact as the distance between C═C and -COOH increases. Theoretical results can reflect the features of mobility experiments, with relative errors between the experiment collision cross-section (CCS) and theoretical CCS of no more than ±8.06%. This method was also evaluated in terms of quantification, accuracy, and precision repeatability. Overall, this study establishes that the crown ether-metal ion pair can function as a robust unit for differentiating C═C positional isomerism.

A Structure-Adaptive Ligand: The Conformation Changes to Fit with the Lengths and Angles of Tetravalent Bis-Paraquat Guests.

A flexible cylindrical cryptand (1b) with two m-phenylene-26-crown-8 ethers has been prepared, and its complexing properties with respect to tetravalent cationic bis-paraquat guests have been investigated. Diffusion-ordered spectroscopy nuclear magnetic resonance (NMR) and titration experiments using cold electrospray ionization mass spectrometry and 1H NMR revealed that 1b has versatile complexing properties with respect to tetravalent cationic guests used despite the guest molecules' length and shape.

Solid-state and solution-phase characterization of SmII-aza[2.2.2]cryptate and its methylated analogue.

Two new SmII-azacryptates are reported that differ in steric hindrance and Lewis basicity of donor atoms. The sterically hindered complex has a smaller coordination number and a more negative electrochemical potential than the complex with less steric hindrance.

Large Conformational Change in the Isomerization of Flexible Crown Ether Observed at Low Temperature.

The dynamic processes of conformational changes of supramolecules are important to understand the motion in synthetic supramolecules. Although a host-guest complex is the most basic supramolecule, a detailed mechanism of its conformational changes has rarely been studied. Here, we observed the large conformational change of a dibenzo-24-crown-8 complex with four guest ions (Ag+, Na+, K+, and NH4+) at low temperature in the gas phase. The isomerization between the two types of conformers, which have different distances between the two benzene rings, proceeds even at 86 K. Using variable-temperature ion mobility-mass spectrometry (IM-MS) at 100-210 K, the activation energy for the isomerization is determined to be rather small (4.8-9.0 kJ mol-1). Reaction pathway calculations revealed that the isomerization is caused by the sequential rotation of two single bonds in the crown ether ring. The present cryogenic IM-MS study of the host-guest complexes at the molecular level opens an approach to detailed understanding of the motion in supramolecules.

Monosulfonated dibenzo-24-crown-8 and its properties.

In this paper, we describe a method for preparing a monosulfonated dibenzo-24-crown-8 ether, SDB24C8, by direct sulfonation of the parent crown (DB24C8). Since neutral DB24C8 readily interacts with cationic guests, permanently charged SDB24C8 is an advantageous candidate for future supramolecular applications. SDB24C8 can be isolated as a sulfonic acid to be used as it is or converted to a salt of choice. The crystallographic analysis provides the first known host-guest assembly with a DB24C8-based scaffold complexing hydronium and potassium cations. Supramolecular investigations of the interactions of this anionic macrocycle with alkali cations were also performed. According to the expectations, the introduction of the sulfonic group into the DB24C8 scaffold increases the affinities of the receptor. An unusual selectivity of SDB24C8 towards a sodium cation was also observed and further investigated with DFT calculations.

Understanding the Deactivating/Activating Mechanisms in Three Optical Chemosensors Based on Crown Ether with Na+ /K+ Selectivity Using Quantum Chemical Tools.

The optical properties and transduction mechanisms in three reported optical chemosensors based on crown ether with selectivity turn-on luminescence toward Na+ over K+ , were investigated using Density Functional Theory/Time-Dependent Density Functional Theory (DFT/TD-DFT). The analysis of the structural stability of the conformers enables us to understand the optical properties of the sensors and their selectivity toward Na+ . The UV-Vis absorption and the radiative channels of the adiabatic S1 excited state were assessed. In these reported sensors, the Photoinduced Electron Transfer (PET) from the nitrogen and the oxygen (O-atoms of the substituted N-phenylaza group) lone pairs to fluorophore groups lead to a nonradiative deactivation process in the fluorophore to p-conjugated anilino-1,2,3-triazol ionophore. This Intramolecular Charge Transfer (ICT) deactivation produced the luminescence quenching in the free sensors and K+ /C1 complexes. The Na+ /sensor interaction produced a Chelation Enhanced Fluorescence (CHEF) due to the inhibition of the PET and ICT, which was confirmed via the calculated oscillator strength of the emission process. The K+ /sensor interaction displayed the possibility of PET in C3; however, this fact was inconclusive to affirm the quenching of luminescence, the CHEF in C2 and C3 and the selectivity toward Na+ over K+ in these systems. For this reason, simulation of the absorption and emissions spectra (calculated oscillator strength), calculation of the kinetic parameters (in charge transfers and radiative deactivations process), analysis of the metal-ligand interaction character, and the analysis of the structural stability of the conformers were determinant factors to understand the selectivity and the optical properties of these chemosensors. The results suggest that these theoretical tools can also be used to predict the optical properties and Na+ /K+ selectivity of optical chemosensors.