Anion Binding Properties Research Articles

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.

Dual-Hydrogen Bond Donor-Functionalized Carbon Nanotube Fibers: Enhancing Anion-Sensing Performance Through Functionalization Approaches.

In this study, chemiresistive anion sensors are developed using carbon nanotube fibers (CNTFs) functionalized with squaramide-based dual-hydrogen bond donors (SQ1 and SQ2) and systematically compared the sensing properties attained by two different functionalization methods. Model structures of the selectors are synthesized based on a squaramide motif incorporating an electron-withdrawing group. Anion-binding studies of SQ1 and SQ2 are conducted using UV-vis titrations to elucidate the anion-binding properties of the selectors. These studies revealed that the chemical interaction with acetate (AcO-) induced the deprotonation of both SQ1 and SQ2. Selectors are functionalized onto the CNTFs using either covalent or non-covalent functionalization. For covalent functionalization, SQ1 is chemically formed on the surface of the CNTFs, whereas SQ2 is non-covalently functionalized to the surface of the CNTFs assisted by poly(4-vinylpyridine). The results showed that non-covalently functionalized CNTFs exhibited a 3.6-fold higher sensor response toward 33.33mm AcO- than covalently functionalized CNTFs. The selector library is expanded using diverse selectors, such as TU- and CA-based selectors, which are non-covalently functionalized on CNTFs and presented selective AcO--sensing properties. To demonstrate on-site and real-time anion detection, anion sensors are integrated into a sensor module that transferred the sensor resistance to a smartphone via wireless communication.

Amino acid – Squaramide conjugates as anion binding receptors

Squaramides have garnered significant attention as anion binding motifs and have become a popular supramolecular synthon owing to their unique structural features and propensity to form strong hydrogen bond interactions particularly with anionic species. However, their conjugation to biomaterials to form biomimetic receptors remains underexplored even though such species would combine the biocompatibility of amino acids with the strong hydrogen bonding propensity of squaramides and may prove useful across broad applications in the chemical and biological sciences. In this study, we present the design and synthesis of a series of amino acid – squaramide conjugates (AASqs) 1 – 5, as well as studying their anion recognition properties. 1–5 were prepared using facile synthetic methods and their anion binding properties were investigated via 1H NMR titrations with a range of anions in 0.5 % H2O in DMSO‑d6. Our findings constitute a cautionary tale, where it was shown that the presence of the C-terminal carboxylic acid of the amino acids complicate the binding behaviour of the receptors towards anions. We show that the C-terminal carboxylates compete with other anionic species for the squaramide binding site leading to complex binding equilibria in solution. However, upon esterification of the C-termini to afford compound 5, a simplification of the binding profile was observed and was easily fitted to a 1:1 (Receptor:Anion) binding stoichiometry. This work sheds light on the potential of AASqs as anion binding receptors whilst underlining the influence of the C-terminus on anion recognition. It also provides a direct solution to mitigate the complex binding behaviour of 1–4 through esterification and will prove useful in the design of more complex squaramide bioconjugates.

Anion-Binding Properties of Short Linear Homopeptides.

A comprehensive thermodynamic and structural study of the complexation affinities of tetra (L1), penta (L2), and hexaphenylalanine (L3) linear peptides towards several inorganic anions in acetonitrile (MeCN) and N,N-dimethylformamide (DMF) was carried out. The influence of the chain length on the complexation thermodynamics and structural changes upon anion binding are particularly addressed here. The complexation processes were characterized by means of spectrofluorimetric, 1H NMR, microcalorimetric, and circular dichroism spectroscopy titrations. The results indicate that all three peptides formed complexes of 1:1 stoichiometry with chloride, bromide, hydrogen sulfate, dihydrogen phosphate (DHP), and nitrate anions in acetonitrile and DMF. In the case of hydrogen sulfate and DHP, anion complexes of higher stoichiometries were observed as well, namely those with 1:2 and 2:1 (peptide:anion) complexes. Anion-induced peptide backbone structural changes were studied by molecular dynamic simulations. The anions interacted with backbone amide protons and one of the N-terminal amine protons through hydrogen bonding. Due to the anion binding, the main chain of the studied peptides changed its conformation from elongated to quasi-cyclic in all 1:1 complexes. The accomplishment of such a conformation is especially important for cyclopeptide synthesis in the head-to-tail macrocyclization step, since it is most suitable for ring closure. In addition, the studied peptides can act as versatile ionophores, facilitating transmembrane anion transport.

Anion-Binding Properties of Aliphatic Symmetric Squaramide Receptors.

Squaramides (SQs), which are very popular for their H-bonding ability, have attracted great interest due to their wide range of applications such as asymmetric synthesis, pharmacology, and anion transportation. In this study, aliphatic symmetric SQs based on cis/trans-1,2-diaminocyclohexane (DACH) substituted with cyclic tertiary amines, synthesized in four steps under simple reaction conditions, were investigated for the first time for their ability to bind Cl-, Br-, and I- anions. The changes in cis/trans geometric isomers and the cyclic ring (pyrrolidine vs piperidine) were found to have a combined effect on the degree of anion binding. The spectroscopic titrations of the SQs with TBA-Cl, TBA-Br, and TBA-I in the range of 0.2 to 20.0 equiv were monitored by 1H NMR, and the analyses of the magnitude of chemical shift differences in the NH peaks of the SQs in course of titration were performed by DynaFit and BindFit programs for the calculation of their Ka values. All symmetric SQs I-IV were found to selectively bind Cl- anion more strongly than Br- anion to varying degrees depending on the SQ derivatives. Especially, SQ IV, which has a symmetric trans-DACH and a pyrrolidine ring, was found to have the highest Cl- anion-binding ability compared to the other SQs. However, the SQs did not show any change in the chemical shift of the NH proton in 1H NMR upon successive addition of TBA-I, indicating that they do not interact with I- anion. The stoichiometries of the complexation behavior of SQs I-IV toward Cl- and Br- anions were also analyzed by Job plots.

Binding Properties of Small Electrophilic Anions [B6 X5 ]- and [B10 X9 ]- (X=Cl, Br, I): Activation of Small Molecules Based on π-Backbonding.

Superelectrophilic anions constitute a special class of molecular anions that show strong binding of weak nucleophiles despite their negative charge. In this study, the binding characteristics of smaller gaseous electrophilic anions of the types [B6 X5 ]- and [B10 X9 ]- (with X=Cl, Br, I) were computationally and experimentally investigated and compared to those of the larger analogues [B12 X11 ]- . The positive charge of vacant boron increases from [B6 X5 ]- via [B10 X9 ]- to [B12 X11 ]- , as evidenced by increasing attachment enthalpies towards typical σ-donor molecules (noble gases, H2 O). However, this behavior is reversed for σ-donor-π-acceptor molecules. [B6 Cl5 ]- binds most strongly to N2 and CO, even more strongly than to H2 O. Energy decomposition analysis confirms that the orbital interaction is responsible for this opposite trend. The extended transition state natural orbitals for chemical valence method shows that the π-backdonation order is [B6 X5 ]- >[B10 X9 ]- >[B12 X11 ]- . This predicted order explains the experimentally observed red shifts of the CO and N2 stretching fundamentals compared to those of the unbound molecules, as measured by infrared photodissociation spectroscopy. The strongest red shift is observed for [B6 Cl5 N2 ]- : 222 cm-1 . Therefore, strong activation of unreactive σ-donor-π-acceptor molecules (commonly observed for cationic transition metal complexes) is achieved with metal-free molecular anions.

Does Larger Cavity-Size Really Help Bigger Anions to Bind? A Scrutiny on Core-Expanded Calix[4]pyrroles and Their Properties.

Calix[4]pyrroles are an important class of oligopyrrolic macrocycles and have found applications in many diverse fields including anion recognition. To modulate the properties of the calix[4]pyrrole, several structural modifications are realized. The core-expansion has attracted extra attention as it provides larger cavity-size compared to parent calix[4]pyrrole(s). This review highlights the synthetic development of various core-expanded calix[4]pyrroles and their applications in anion-binding properties. Emphasis is given to the changes in the binding properties observed with expanded versions of calix[4]pyrrole(s) in both solution and the solid states. The expanded versions of calix[4]pyrrole do not always show higher binding affinities for larger anions as anticipated. Rather, they display reduced affinities with the anions. The truncated form or asymmetric nature of the expanded versions of calix[4]pyrrole does not probably allow to access all the available binding sites for the anions and hence reduced binding affinities are observed. The receptors which contain a greater number of binding sites and are somehow rigid or preorganized apparently show enhanced binding affinities for anions. The relative binding constants for halide series indicate that the enlarged molecules are more beneficial for largest iodide among others. However, most of the receptors show selectivity towards smallest fluoride over other anions studied.

Investigation of Chloride Anion Binding Properties of Glipizide Drug

This study addresses the anion binding property of Glipizide (GLP), an oral antidiabetic a second-generation drug member of the sulphonylurea (SU) family. GLP effectively interacts with Cl- anion according to 1H-NMR spectroscopic titrations of successive tetrabutylammonium chloride (TBACl) in deuterated chloroform (CDCl3) and dimethyl sulfoxide (d6-DMSO). Upon the addition of TBACl, the change in chemical shift was observed for both N-H protons of SU in CDCl3, whereas it causes a difference in the shift of only one of N-H proton in SU in d6-DMSO. In addition, the data obtained from 1H-NMR spectroscopic titrations was analyzed by DynaFit program to calculate the binding constant (Ka) value between GLP and Cl- anion. It was found that GLP binds Cl- anion in CDCl3 with higher affinity (Ka=77.37 M-1, Fitplot for N-Hh proton at δ=6.47 ppm) than in d6-DMSO (Ka=38.53 M-1, Fitplot for N-Hh proton at δ=6.32 ppm).

Hybrid zipper-like chitosan-carboxymethyl cellulose-ferric adsorbents for tunable anion adsorption

Composite materials (CCFe and CGCFe) were prepared from carboxymethyl cellulose, chitosan, glutaraldehyde, and iron III species. The composite materials were characterized by FTIR, TGA, ICP-OES and SEM studies that provided evidence of cross-linking between chitosan and glutaraldehyde, along with variable iron doping and morphology of the composites. The equilibrium uptake study indicates that CGCFe surpassed the adsorption capacity of CCFe, where greater uptake was noted at lower versus higher temperatures (283 – 303 K). The monolayer adsorption capacity (Qm; mg g−1) of CGCFe for 2-naphthoxy acetic acid (S6) was 263 mg/g and 484 mg/g at alkaline and acidic pH conditions, according to the Sips and Langmuir isotherm models. The composite materials show limited discrimination of OSPW naphthenate components. Regeneration studies revealed that CGCFe retained 95% of its adsorption capacity after 5 cycles via a “zippering effect” in the presence of saline water. The enhanced regeneration and zipper-like structural transition of CGCFe represents a unique application of saline responsive supramolecular function driven by changes in ionic strength. This study advances the design of modular polysaccharide adsorbents according to the insight on the role of Fe (III) species, cross-linking effects, and biopolymer structure that relate to anion binding properties in aqueous solution.

Tetraurea Macrocycles: Template-Directed One-Pot Synthesis and Anion Binding Properties

Given the significance of anion in life, study of anion recognition attracted great attentions in the past decades. Macrocyclic receptors display intriguing anion binding properties; however, the synthesis of macrocycles is challenging. Here, we reported a new strategy of making tetraurea in one-step. By using 1-butyl-3-methylimidazolium ([hmim][X], X = anion) as the solvent and template reagent, tetraurea macrocycle comprised of bis(urea) binding moiety and hexyl chain spacers is selectively formed with high yield. The obtained macrocycles displayed interesting anion binding properties as indicated by single crystal X-ray diffraction structures and computational modelling.

Quantitative Determination of Anion Binding Strenght with A Tripodal Hexaurea Receptor

Anions are ubiquitous, and their related activities are closely related to human life and production. Thus, study of anion recognition is significant by understanding the binding affinity and selectivity. The tripodal hexaurea receptor has three flexible arms that can form an interior cavity for anion binding. Yet its anion binding property remains unclear. Here, by taking hexyl chain substituted hexaurea receptor as an example, we quantitatively determined the anion binding affinities by using 1H NMR titrations. The chloride binding affinity was determined by direct titration, and the sulfate and phosphate binding constants were determined by competing titrations. In 5% v/v H2O/DMSO-d6, the binding affnities of Cl–, SO42–, and PO43– were determined to be 93 M−1, 7.3×103 M−1, and 8.4×105 M−1, respectively. The phosphate binding affnity is about 117-fold and 9048-fold stronger than sulfate and chloride binding, respectively. Crystal structure also supports strong binding of phosphate.

Limitations of non-polarizable force fields in describing anion binding poses in non-polar synthetic hosts.

Transmembrane anion transport by synthetic ionophores has received increasing interest not only because of its relevance for understanding endogenous anion transport, but also because of potential implications for therapeutic routes in disease states where chloride transport is impaired. Computational studies can shed light on the binding recognition process and can deepen our mechanistic understanding of them. However, the ability of molecular mechanics methods to properly capture solvation and binding properties of anions is known to be challenging. Consequently, polarizable models have been suggested to improve the accuracy of such calculations. In this study, we calculate binding free energies for different anions to the synthetic ionophore, biotin[6]uril hexamethyl ester in acetonitrile and to biotin[6]uril hexaacid in water by employing non-polarizable and polarizable force fields. Anion binding shows strong solvent dependency consistent with experimental studies. In water, the binding strengths are iodide > bromide > chloride, and reversed in acetonitrile. These trends are well captured by both classes of force fields. However, the free energy profiles obtained from potential of mean force calculations and preferred binding positions of anions depend on the treatment of electrostatics. Results from simulations using the AMOEBA force-field, which recapitulate the observed binding positions, suggest strong effects from multipoles dominate with a smaller contribution from polarization. The oxidation status of the macrocycle was also found to influence anion recognition in water. Overall, these results have implications for the understanding of anion host interactions not just in synthetic ionophores, but also in narrow cavities of biological ion channels.

Two carbazole disulfonamide-diamide macrocycles with semi-flexible meta-xylyl linkages for anion recognition

Two novel carbazole disulfonamide-diamide macrocycles 1 and 2 with semi-flexible meta-xylyl linkages were designed, synthesized, and assessed for their anion binding properties, via1H NMR and UV-vis titration studies.

Anion binding and transport with meso-alkyl substituted two-armed calix[4]pyrroles bearing urea and hydroxyl groups.

Calix[4]pyrroles bearing hydroxyl (1) or urea (3) groups attached to the meso-positions with propyl linkers were synthesized as cis- and trans-isomers. The anion binding properties of cis-1 and cis-3 were screened with ion-mobility mass spectrometry, where cis-1 formed complexes with Cl-, Br- and H2PO4-, whereas cis-3 formed complexes with most of the investigated anions, including Cl-, Br-, I-, NO3-, ClO4-, OTf-, SCN- and PF6-. The structures of the chloride complexes were further elucidated with density functional theory calculations and a crystal structure obtained for cis-1. In solution, chloride and dihydrogenphosphate anion binding with cis-1 and cis-3 were compared using 1H NMR titrations. To assess the suitability of two-armed calix[4]pyrroles as anion transporters, chloride transport studies of cis-1, cis-3 and trans-3 were performed using large unilamellar vesicles. The results revealed that cis-3 had the highest activity among the investigated calix[4]pyrroles, which was related to the improved affinity and isolation of chloride inside the binding cavity of cis-3 in comparison to cis-1. The results indicate that appending calix[4]pyrroles with two hydrogen bonding arms is a feasible strategy to obtain anion transporters and receptors with high anion affinity.

Spatially Designed Supramolecular Anion Receptors Based on Pillar[5]arene Scaffolds: Synthesis and Halide Anion Binding Properties.

Urea-functionalized anion receptors based on brominated functionalized pillar[5]arenes were prepared. The binding affinity toward halide anions was investigated and probed using 1H NMR titration and isothermal titration calorimetry (ITC). The complexation behavior was affected by the structure of the receptor and the nature of the anionic guest. The synthesized receptors are highly selective toward fluoride resulting in the formation of a 1:2 host-to-guest complex. The anion receptor based on the 1,3-alternate pillar[5]arene regioisomer shows the highest affinity toward fluorine anions. No significant interactions were observed with larger bromine anions. The formation of a self-assembled supramolecular polymer driven by hydrogen bonds in solution was demonstrated by diffusion-ordered spectroscopy (DOSY), ITC, and dynamic light scattering (DLS) measurements. From ITC dilution experiments, we found that the supramolecular polymer self-assembly at higher concentrations is a spontaneous process as indicated by the positive value of Gibbs free energy (ΔG = 12.04 kJ mol-1).

Tuning anion binding properties of Bis(indolyl)methane Receptors: Effect of substitutions on optical responses

Chromogenic probes based onoxidizedbis(indolyl)methanes have been synthesized with varying substituents (R = -Me [1], -OMe [2], –OH, [3]) on the central aryl ring. In addition to electronic influence, the involvement of substituents in ion–dipole and charge-assisted hydrogen bonding interactions significantly alters the solvatochromic response and pH-sensitive behavior. In polar aprotic solvents, like CH3CN, a concentration-dependent stepwise color change was observed with F- ions. In the case of2, a reversible hydrogen bonding interaction between the deprotonated probe and HF2- dimer might be responsible for that, while step-wise deprotonation caused by F- ions could be the probable reason with3. Since the formation of HF2- is energetically unfavorable in a polar protic solvent, the response of 2 with F- ions appears to be very different in EtOH medium. Interestingly, no such alteration in anion sensing behavior was noticed with3going from an aprotic to a protic solvent.

Anion binding studies with anthraimidazoledione-based positional isomers: A comprehensive analysis of different strategies for improved selectivity

In the present work, we have reported the design of three different positional isomers of anthraimidazoledione-based charge transfer probes and their anion-binding properties under various conditions. In the acetonitrile medium, the meta isomer showed ratiometric optical response towards basic anions, such as F−, CN−, AcO− and H2PO4−. Based on the differences in the hydrogen bonding ability of these anions, we observed distinguishable output signal, particularly in fluorescence. Though meta and para isomers showed effective interaction with anions, the response was relatively weak for the ortho isomer. We suspected that the presence intramolecular hydrogen bond between pyridine nitrogen and imidazole –NH group might be responsible for such poor performance. Further, we have employed two different strategies to improve the selectivity towards anions. In the first case, selective recognition of anions was achieved using suitable metal ions (Cu2+, Zn2+, Ca2+, and Al3+) as masking agents. On the contrary, we have varied the water content (0, 10, 30 and 50% v/v) in the acetonitrile-water mixture in the second case. The anions with relatively large hydration enthalpy showed no detectable interaction with probe in presence of water. Finally, we used the present system to detect cyanide ion in various natural water samples (tap, pond, and seawater). Also, low-cost reusable paper strips were developed as an alternative method for rapid, on-location detection of CN− ions.

Synthesis and anion binding properties of carbazole-based macrocycles with bis-sulfonamide and bis-amide groups

Two carbazole-based macrocycles 1 and 2 with bis-sulfonamide and bis-amide groups were facilely synthesized and carefully evaluated for their anion binding properties, via 1H NMR, UV–vis, and X-ray diffraction studies. Both macrocycles exhibited strong and selective binding to CH3COO−, PhCOO−, and F− ions (Ka > 6500 M−1 for the resultant 1:1 complexes) in the strongly polar solvent DMSO-d6, over the other anions tested. Interestingly, pyridine-2,6-diamide-containing macrocycle 2 showed a nearly 6-fold enhancement in affinity for Cl−, relative to the isophthalamide-containing analogous macrocycle 1. Additionally, the complexation between Cl− and macrocycle 2 was about one order of magnitude stronger than its acyclic analogue 3. More interestingly, given unique chemical shift changes experienced by two macrocycles upon addition of Cl−, this allowed them to serve as useful receptors for discriminating chloride from other anions in DMSO-d6. Finally, the X-ray crystallographic analysis provided convincing evidence for the binding of F− to macrocycle 2 (via three N–H⋯F− hydrogen bonds from one carbazole NH and two sulfonamide NHs groups, if excluding the bridging water molecules), fully consistent with the solution-phase 1H NMR titration experiments.

Acyl hydrazone-based reversible optical switch for reporting of cyanide ion in industrial wastewater samples

The anion binding property of a series of easily synthesizable, isonicotine acid hydrazide based optical switches were studied in the semi-aqueous environment. Irrespective to the position of the hydrazide units, all three compounds show color change (as well as turn-off fluorescence response) with CN− ion, presumably due to hydrogen bonding triggered intramolecular charge transfer interaction. The compound with phenanthroline as the signaling unit, shows effective E Z isomerization with substantial amount of kinetically stable Z-isomer in the equilibrium, stabilized by intramolecular hydrogen bonding. This compound showed a 1:1 binding interaction with CN− ion due to its ‘U’ shaped conformation. On the other hand, compound with two isoniazid hydrazide moieties at 1,4-positions, shows 1:2 interaction with CN− ions. Further, the probe molecules were utilized for the detection of CN− ions in water samples collected from different natural resources. Low-cost portable optical kit based on reusable paper strips were designed for rapid, on-location detection purpose.

Fine-tuning the acceptor–donor ability of star shaped triarylborane–triphenylamine conjugates: synthesis, characterization and anion binding studies

A modest approach to design and synthesize functionalized triarylborane–triarylamine based donor–acceptor systems, compounds1–3, and the investigation of the photophysical, solvatochromic, solid state emissive and anion binding properties.