Anion Binding Research Articles

A Unique Case of 'in Situ' Bifluoride Triggered Formation of Supramolecular Organogels Using Isophthalamide Hydrogen Bond Donating Receptors.

A novel isopthalamide based receptor H2L2 featuring two p-benzoic acid units has been synthesised and its anion binding properties analysed by 1H-NMR spectroscopy in DMSO-d6/0.5 % H2O. As expected, in the presence of tetrabutylammonium (TBA) fluoride the deprotonation of the carboxylic acid moieties was observed. However, the deprotonated receptor L22- was able to bind the in situ formed HF2 - via the formation of H-bonds with the amide NHs. When H2L2 was dissolved in THF and 4 equivalents of TBAF were added in CH3CN a unique sol-gel transition occurred giving rise to a stable thixotropic supramolecular gel. Theoretical calculations elucidated the gelation mechanism and strongly support the findings observed experimentally.

Scalable Mechanochemical Synthesis of Biotin[6]uril.

Biotin[6]uril, a chiral, water-soluble and anion binding macrocycle, is formed via dynamic covalent chemistry. In this study, we present a scalable and high-yielding synthesis of biotin[6]uril via a mechanochemical solid-state approach. The optimized protocol involves mechanical grinding of solid d-biotin with paraformaldehyde in the presence of 0.3 equivalents of 48 % aqueous HBr, which functions as a catalyst, template, and liquid grinding additive. This mechanochemical process is carried out in a shaker or planetary mill, followed by aging at an elevated temperature to produce biotin[6]uril with an HPLC yield of up to 96 %. The condensation and macrocyclization reaction was successfully scaled up 82-fold, producing nearly 20 g of biotin[6]uril with a high 92 % isolated yield and 91 % purity. Compared to conventional solution-based method, this mechanochemical approach offers several advantages, including significantly higher yields, shorter reaction times, enhanced scalability, simpler operational requirements, and substantially lower process mass intensity.

Trapping Anions within Stacks of Tetra-Urea Macrocycles.

Designing molecular receptors that bind anions in water is a significant challenge, and an even greater difficulty lies in using these receptors to remove anions from water without resorting to the hazardous liquid-liquid extraction approach. We here demonstrate an effective and synthetically simple strategy toward these goals by exploiting ion-pair assembly of macrocycles. Our anion binding ensemble consists of an octa-chloro tetra-urea macrocyclic anion receptor (ClTU), which forms water-dispersible aggregates, and a tetra-cationic fluorescent dye 5,10,15,20-tetrakis(1-methyl-4-pyridinio)porphyrin (TMPyP4), which provides Coulombic stabilization and fluorescence reporting of anion binding in an ion-pair assembly. The ability of ClTU to form oligomeric/polymeric stacks with chloride ions and countercations was demonstrated by X-ray crystallographic and 1H NMR studies in DMSO. In water, the addition of anions to a mixture of ClTU and TMPyP4 led to the formation of ion-pair assemblies showing quenched fluorescence from TMPyP4 and apparent selectivity in the order of CrO42- ≈ SO42- > Cl- > ClO4- ≈ NO3- > AcO- > F- > H2PO4-. The assembly can be applied to remove traces of toxic CrO42- anions from tap water simply by using syringe filters to separate large aggregates from water. Molecular dynamics studies support the formation of columnar stacks of ClTU in solution, which allow for insertion of both anionic guests and cationic TMPyP4 dyes.

Substituent-Driven Anion-Binding Selectivity in Aliphatic Chain-Substituted 1,2-Phenylene Urea Macrocycles and Optimized Synthetic Methodology.

1,2-Phenylene tetraurea macrocycles recently attracted attention as self-assembled channel-making compounds with high selectivity to chlorides. Here, we report on the introduction of aliphatic chains in the periphery of the 1,2-phenylene tetraurea macrocycle, which led to deterioration in the ability of the macrocycle to form channels and to a reversal of anion binding preferences in favour of dihydrogen phosphate. In addition, we have developed a new method of synthesis of 1,2-phenylene tetraurea macrocycle, using a direct click of two diamino ureido derivatives by triphosgene in the presence of chloride template. This approach saves time and eliminates demanding isolation of the non-cyclic tetrameric intermediates.

Facile synthesis and anion binding properties of a preorganized macrocyclic receptor.

Herein, we report a novel Schiff base macrocyclic receptor (MR). The structure of MR was characterized by NMR, UV-vis and fluorescence spectroscopy, revealing that it was a rigid and preorganized planar π-conjugated fluorescent macrocycle. Furthermore, MR showed effective binding properties with tetrabutylammonium halides TBAX (X = Cl, Br, and I) which were investigated by the NMR titration method and molecular modelling.

Submicromolar fluorescence 'turn-on' detection of fluoride anions using meso-(tetra-aryl) calix[4]pyrrole.

Meso-(tetra-aryl) picket calix[4]pyrrole 1 featuring p-fluorophenyl groups at all four meso-positions in a cis-configuration has been synthesized and characterized unambiguously using single-crystal X-ray diffraction analysis. This pre-organized system possesses a deep binding pocket created by the four aryl groups so that anions can be accommodated through anion-π interactions and four-point N-H⋯anion hydrogen bonds. Single-crystal X-ray diffraction analysis of the CsF and TEAF (TEA = tetraethylammonium) complexes of receptor 1 unequivocally confirms the formation of 1 : 1 complexes, revealing the binding modes in the solid state. The anion binding studies conducted in acetonitrile confirmed that the receptor forms stable 1/1 complexes with fluoride anions and coumarin anion 2- in solution. The host-coumarin ensemble 3 was then applied for the detection of fluoride anions through a fluorescent dye displacement assay (FDDA). The highly fluorescent coumarin anion becomes completely non-fluorescent upon complexation with receptor 1, and its fluorescence is recovered in a concentration-dependent manner upon the addition of fluoride anions. This system proves to be an excellent 'turn-on' sensor for detecting fluoride anions with high selectivity and sensitivity, with a detection limit for fluoride anions estimated at 177 nM.

A Squaramide-Crown Ether-Based Receptor and Polymer for Enhanced Lithium Chloride Extraction.

A non-mulitmacrocyclic ion pair receptor with the ability to cooperatively bind lithium cations and halide anions is presented. These receptors feature a squaramide function for anion binding and are directly linked to a benzo-4-crown-12 unit to achieve selectivity toward lithium salts. Ion pair receptors 1 and 3 demonstrated stronger anion binding in the presence of cobound cations, while anion receptor 2 lacks this property. X-ray measurements supported the simultaneous binding capability of ion pair receptors for both cations and anions. Under solid-liquid extraction (SLE) conditions in acetonitrile, ion pair receptors 1 and 3 selectively extract lithium salts. The more lipophilic receptor 1 can extract LiCl in liquid-liquid extraction (LLE) and SLE, with the latter process notably more selective and effective. Improved LLE extraction of lithium chloride was achieved using copolymer 5 containing receptor units in the structure. The inability of receptor 2 or benzo-12-crown-4 ether to extract salts is attributed to the absence of a heteroditopic binding domain in their structures. This underscores the significant influence of both anion and cation binding domains in the receptor structures on the effective and selective extraction of lithium halide salts. The selectivity of these receptors and the polymeric material toward lithium salts suggests significant potential for extracting lithium from brine solutions with elevated halide content.

Mechanoelectrical Transduction through Anion Recognition with Naphthalenediimide Monolayers at the Air-Water Interface.

In biological systems, various stimuli and energies are transduced into membrane potentials via ion transport or binding. The application of this concept to artificial devices may result in biomimetic signal transmitters and energy harvesters. In this study, we investigated the mechanical control of fluoride anion recognition with naphthalenediimide (NDI) monolayers at the air-water interface. Similar to the mechanosensitive ion channels in biological membranes, mechanical stimuli modulated the packing manner of the NDI monolayers, which reproducibly triggered anion binding and concomitant shifts in the membrane potential. Furthermore, mechanical stimuli resulted in anion binding or release, depending on the structure of the alkyl side chains attached to the NDI core, which was explained by the difference in the packing manner of the NDI monolayers. These findings provide insights into the development of novel mechanoelectrical transduction systems that mimic biological processes.

Syntheses of Variants of π(σ) Aromatic Modified N-Methyl N-Confused Porphyrinoids with Adaptive Properties.

Retrosynthetically designed and syntheses of three unprecedented core modified N-confused porphyrinoids exhibiting vis-NIR absorption with tunable aromaticity is reported. Controlled modification of types of oxidants (chloranil vs. DDQ) has led to the isolation of 18π-aromatic porphyrinoid 7 (upon chloranil oxidation) while DDQ oxidation has led to 18 e σ-aromatic porphyrinoids 8 and 9. All the three SN3 hybrid N-confused porphyrinoids 7-9 have been thoroughly characterized via solution state spectroscopic measurements and in-depth DFT studies for concluding π-aromaticity of 7 and σ-aromaticity of 8 and 9. While 7 could recognize the fluoride anion with high selectivity via deprotonation rather than an anion recognition based mechanism, acetate anion binding studies clearly revealed NH⋅⋅⋅AcO- H-bonding interaction in the host-guest complex [7-AcO-] supporting an anion recognition based mechanism. Porphyrinoids 8 and 9 remain unsusceptible to anion recognition. The conformational preorganization and anion induced deprotonation leading to conformational reorganization have been extensively studied by solution state spectroscopic techniques and in depth DFT level theoretical calculations.

An Ion Pair Receptor for Selective Solid-Liquid Extraction of LiCl.

We have synthesized a new ion pair receptor (2) consisting of a cone-calix[4]arene bearing a combination of ethyl esters and ethers as a cation binding site and a calix[4]pyrrole subunit acting as an anion binding site. Ion pair receptor 2 complexes LiCl, NaCl, and CsCl among alkali metal chloride salts with distinct complexation modes and affinities in 10 % methanol-d4 in chloroform-d. For instance, relatively small Li+ and Na+ cations are bound to the oxygen atoms of the functionalized calix[4]arene lower rim with Cl- being hydrogen bonded to the calix[4]pyrrole NHs while the larger Cs+ cation is bound to the cone-shaped calix[4]pyrrole cavity via a π-cation interaction. By contrast, in the co-presence of all MCl salts (M=Li, Na, K, Rb, and Cs), receptor 2 binds LiCl with complete selectivity. Besides, receptor 2 is capable of extracting LiCl selectively into a chloroform or a dichloromethane organic phase from its solid source containing all other MCl salts.

Kinetic Implications of IP6 Anion Binding on the Molecular Switch of the HIV-1 Capsid Assembly.

HIV-1 capsid proteins (CA) self-assemble into a fullerene-shaped capsid, enabling cellular transport and nuclear entry of the viral genome. A structural switch comprising the Thr-Val-Gly-Gly (TVGG) motif either assumes a disordered coil or a 310 helix conformation to regulate hexamer or pentamer assembly, respectively. The cellular polyanion inositol hexakisphosphate (IP6) binds to a positively charged pore of CA capsomers rich in arginine and lysine residues mediated by electrostatic interactions. Both IP6 binding and TVGG coil-to-helix transition are essential for pentamer formation. However, the connection between IP6 binding and TVGG conformational switch remains unclear. Using extensive atomistic simulations, we show that IP6 imparts structural order at the central ring, which results in multiple kinetically controlled events leading to the coil- to-helix conformational change of the TVGG motif. IP6 facilitates the helix-to-coil transition by allowing the formation of intermediate conformations. Our results identify the key kinetic role of IP6 in HIV-1 pentamer formation.

Comparison of protonation and anion binding preference of Chatt-type tungsten dinitrogen complex: DFT studies

In this paper, preference of protonation and anion binding to Chatt-type tungsten complex [W(Ph2(Ch2)2Ph2)2(N2)2] was investigated. Optimization of metal complexes [W(PH2(CH2)2PH2)2(N2)2], [W(PH2(CH2)2PH2)2N2FH], [W(PH2(CH2)2PH2)2(N2)2H] and [W(PH2(CH2)2PH2)2N2F] was carried out using density functional theory (DFT). Diethyl ether solution of HBF4 was used as a proton source. DFT calculations were carried out to understand the reactivity pattern shown by Chatt-type dinitrogen (N2) complex. Thermodynamic energy values for the protonation of coordinated dinitrogen followed by anion binding; anion binding followed by protonation; and simultaneous reaction of protonation of dinitrogen and anion binding have been calculated. The energy values revealed that the protonation of dinitrogen followed by anion binding is preferable over anion binding followed by protonation.

Increased phosphorescence of cyclometalated Ir(III) complex with a planar triarylborane moiety upon fluoride anion binding

Abstract A luminescent Ir(III) complex functionalized with a planar triarylborane moiety was prepared. This complex exhibits unique photophysical properties derived from the electron-withdrawing effect of the triarylborane moiety. A significant change in electron density occurs upon binding of F– to the electron-deficient boron center, resulting in decreased absorption and enhanced emission.

Multiplex Pulsed Current Sensors for Anion Detection

Low-cost and stable sensors are needed for long-duration monitoring of nitrate and phosphate in waterways to help improve farming practices and understand the negative environmental and economic impacts caused by the release of these ions. One established platform that shows promise for detecting these ions is the use of solid-contact ion selective electrodes (SC−ISEs). Conventional SC-ISE measurements monitor electrode potential under open circuit conditions to quantify the amount of one target analyte. These conventional SC-ISEs rely on highly engineered membrane materials that are formulated to selectively bind to the target ion. These engineered membrane materials can achieve high selectivity for nitrate and phosphate, but are vulnerable to certain interferents, require frequent calibration, and have poor long-term stability. In recent work, we demonstrated the use of pulsed current technique for anion detection in SC-ISEs, which allows for anion detection based on differences in anion diffusion through the membrane rather than selective anion binding – opening up a wide range of materials as candidates for ion sensing membranes. In this report, we employ pulsed current measurement to examine anion detection using three common polymers as membrane layers: polyvinyl acetate (PVA), polyvinylchloride (PVC), and polyacrylonitrile (PAN). We measure the potential vs. time response for these three membrane materials in solutions containing various anions such as nitrate, phosphate, chloride, and carbonate at varying pulse currents. Afterwards, we employ tree-based and neural-based machine learning algorithms to examine the feasibility of detecting multiple ions simultaneously using the combined response data from multiple electrodes. Our experiments illustrate that our method for anion detection, used with machine learning analysis, is useful for investigating the interaction mechanisms of anions with the polymer matrix.

Synthesis of novel imino-coumarin and acrylonitile 2-benzazole hybrids as potent anticancer agents targeting tubulin

Building on previous research indicating the robust biological effects of coumarins, we focused on exploring imino-coumarin 2-benzazole conjugates. Compounds were tested for antiproliferative activity in vitro, with the most active ones further examined to determine the mechanism of biological action.Five derivatives exhibited significant antiproliferative activity against all tested cancer cells (IC50 ranging from 0.04 to 8.5 μM), falling within the low micromolar/submicromolar range of inhibitory concentrations. Three compounds had remarkable antiproliferative effects against Capan-1 (IC50 0.04–0.05 μM) and DND-41 (IC50 0.06–0.07 μM). Promising compounds were further investigated, confirming their mechanism of action through tubulin polymerization inhibition.Computational docking and molecular dynamics simulations confirmed the high affinity of potent derivatives for the tubulin colchicine site and justified the suitability of the employed skeleton by identifying crucial protein–ligand interactions promoting binding. This insight highlights a strategy for further potency improvements through substituents that can donate hydrogen bonds or bear a positive charge, allowing such ligands to more optimally adapt to the identified anionic binding site environment.

End Group Effects on Anion Binding in Tetraglycine Peptide: A Computational Study.

The importance of anions in various processes has led to a search for molecules that can effectively recognize and interact with these anions. This study explores how the tetraglycine [(Gly)4] peptide in its zwitterionic, neutral, and terminally capped forms acts as a receptor for H2PO4 - and HSO4 - anions within the framework of supramolecular host-guest chemistry. Using molecular dynamics (MD) simulations, we obtained the conformations of the receptor-anion complexes. Density functional theory (DFT), quantifies the complexes' interaction energies in both gas and solvent phases. Proton transfer within the zwitterionic complex with H2PO4 - anion alters peptide charge distribution, affecting its conformation and binding site arrangement, as analysed by quantum mechanics/molecular mechanics (QM/MM) methods. Symmetry-adapted perturbation theory (SAPT) and noncovalent interactions analysis highlight the role of electrostatic interactions in these receptor-anion complexes. It emphasizes the key interactions such as N-H⋅⋅⋅⋅O and O-H⋅⋅⋅O=C between the peptide backbone and anions and elucidates the molecular recognition mechanism driven by crucial noncovalent interactions. The termination of the peptide's end groups modulates anion binding sites from the backbone to the charged N-terminal, resulting in distinct binding sites. Our findings provide insights for designing peptides tailored to function as anion receptors in diverse supramolecular chemistry applications.

Unlocking Mechanism of Anion and Cation Interaction on Ion Conduction of Polymer Based Electrolyte in Metal Batteries

AbstractPolymer based electrolyte shows advantages in compatibly improving safety and interface stability of batteries, while its limited ion conductivity and transfer number make it difficult to apply in batteries with high energy density. Herein, by designing four crosslinking polyesters with different electron withdrawing group (EWG), it is found that strengthening the binding of EWG to anion for weakening the binding of anion to Li+ is critical for high Li+ transfer number ( ) and ionic conductivity of electrolyte. As a result, poly (2,2,3,3‐tetrafluoropropyl methacrylate) (PTFM) based gel polymer electrolyte (GPE) shows an ionic conductivity of 0.78 mS cm−1 and a of 0.85, much higher than those of poly (methyl methacrylate) (PMMA) without EWG. Moreover, PTFM based GPE shows excellent flame retardancy property. Li||PTFM||NCM811 batteries with an ultrahigh capacity of 5.5 mAh cm−2 show stable cycles of 5 times to that of Li||PMMA||NCM811. Moreover, the assembled graphite||PTFM||NCM811 pouch cell shows a capacity retention rate of 92 % after 500 cycles. This work clarifies the mechanism of cation/anion interaction on ionic conductivity of GPE, which is important to develop high‐performance devices with good safety and flexibility.

Unlocking Mechanism of Anion and Cation Interaction on Ion Conduction of Polymer Based Electrolyte in Metal Batteries.

Polymer based electrolyte shows advantages in compatibly improving safety and interface stability of batteries, while its limited ion conductivity and transfer number make it difficult to apply in batteries with high energy density. Herein, by designing four crosslinking polyesters with different electron withdrawing group (EWG), it is found that strengthening the binding of EWG to anion for weakening the binding of anion to Li+ is critical for high Li+ transfer number ( ) and ionic conductivity of electrolyte. As a result, poly (2,2,3,3-tetrafluoropropyl methacrylate) (PTFM) based gel polymer electrolyte (GPE) shows an ionic conductivity of 0.78 mS cm-1 and a of 0.85, much higher than those of poly (methyl methacrylate) (PMMA) without EWG. Moreover, PTFM based GPE shows excellent flame retardancy property. Li||PTFM||NCM811 batteries with an ultrahigh capacity of 5.5 mAh cm-2 show stable cycles of 5 times to that of Li||PMMA||NCM811. Moreover, the assembled graphite||PTFM||NCM811 pouch cell shows a capacity retention rate of 92 % after 500 cycles. This work clarifies the mechanism of cation/anion interaction on ionic conductivity of GPE, which is important to develop high-performance devices with good safety and flexibility.

Synthesis and anion binding properties of (thio)urea functionalized Ni(II)-salen complexes.

Salen ligands (salen = N,N'-ethylenebis(salicylimine)) are well-known for their versatility and widespread utility in chelating metal complexes. However, installation of hydrogen-bonding units on the salen framework, particularly functional groups that require amine-based precursors such as (thio)ureas, is difficult to achieve without the use of protecting group strategies. In this report, we show that the phenylketone analog of salicyladehyde is a stable alternative that enables the facile installation of hydrogen bonding (thio)urea groups on the salen scaffold, thus imparting anion binding abilities to a metal salen complex. Synthesis of symmetric N-phenyl(thio)urea salen ligands functionalized at the 3,3'-position and an unsymmetric salen ligand with N-phenylurea at the 5-position was achieved. Subsequent metalation with nickel(II) acetate afforded the nickel(II) complexes that were investigated for their anion binding properties towards F-, Cl-, Br-, CH3COO-, and H2PO4-. Solid-state structures of the nickel(II) complexes as well as the Cl- bound dimer of the symmetric urea complex were obtained. The unusual acidity of the (thio)urea groups is reflected in the pKa-dependent anion binding behavior of the nickel(II) complexes, as elucidated by 1H and 19F Nuclear Magnetic Resonance (NMR) spectroscopy and Diffusion Ordered Spectroscopy (DOSY) experiments.

Off-On Photo- and Redox-Triggered Anion Transport Using an Indole-Based Hydrogen Bond Switch.

A stimulus-responsive indole-based hydrogen bonding switch is reported, which enables off-on activation of transmembrane ion transport in response to photo- and redox triggers. This is achieved by alkylation of an indole-based anionophore, preorganized through intramolecular hydrogen bonding, with o-nitrobenzyl and azobenzene cages. This renders the anionophore inactive through formation of a six-membered intramolecular hydrogen bonding interaction and locking of the anion binding protons. Decaging with biologically relevant light and redox stimuli leads to efficient activation of anion transport across lipid bilayer membranes by unlocking the hydrogen bond donors, such that they are now available for anion binding and transport.