Ion-pair Receptor Research Articles

ChemInform Abstract: Pyrrole, Imidazole, and Triazole Derivatives as Ion‐Pair Recognition Receptors

AbstractReview: [32 refs.

Enantioselective recognition of sodium carboxylates by an 1,8-diaminoanthracene based ion pair receptor containing amino acid units

An anthracene based ion pair receptor containing two amino acid units supported by cation and anion binding domains has been synthesized and shown to exhibit enhanced anion binding affinities in the presence of sodium cations. The receptor’s ability to recognize enantiomers was studied using chiral carboxylates derived from 2-phenylbutyric acid, mandelic acid, and three Boc-protected amino acids. Sodium cation coordination does not influence chiral recognition but does affect the strength of anion binding. The greatest enhancement of anion binding in the presence of sodium cations was found for halides, and the highest enantiodiscrimination was found for Boc-N-tryptophan. Comparative anion and salt binding studies revealed that the simultaneous action of multiple binding domains in the structure of receptor 1 is responsible for its stronger salt association and better enantioselectivity than in the case of mono-supported receptor 2.

Dual Sensing by Simple Heteroditopic Salt Receptors Containing an Anthraquinone Unit.

We synthesized simple ion pair receptors consisting of a crown ether cation binding site and an anthraquinone-supported thiourea anion binding domain and studied their anion-, cation-, and salt-binding properties using spectroscopic, spectrophotometric, and electrochemical measurements in acetonitrile solution. Apart from carboxylate anions, which cause deprotonation, all the anions tested were found to associate with receptor 1 more strongly in the presence of sodium cations, whereas in the presence of potassium or ammonium cation the anion binding strength was greatly diminished. A homotopic anion receptor 3, lacking a crown ether unit, was unable to bind sodium salt more strongly than tetrabutylammonium salts. Solution and solid-state X-ray measurements revealed that strong sodium coordination with the cation-binding domain is responsible for the salt-binding enhancement. Electrochemical measurements showed that the addition of anions to the receptor 1 pretreated with sodium cations resulted in greater changes in reduction potentials compared to the addition of anions to receptor 1 in the absence of Na(+).

An ion pair receptor facilitating the extraction of chloride salt from the aqueous to the organic phase

A squaramide supported molecular receptor with the ability to extract chloride salt from the aqueous to the organic phase was synthesized and characterized.

Cooperative binding and extraction of sodium nitrite by a ditopic receptor incorporated into a polymeric resin.

Simple ion pair receptors were synthesised and characterized in solution. The modular design of these receptors facilitated the preparation of a functionally analogous polymeric material able to extract sodium nitrite from acetonitrile solution.

Highly effective ion-pair receptors based on 2,2-bis(aminomethyl)-propionic acid.

Compounds 2 and 3 were designed and prepared as heteroditopic ion-pair receptors. The design features a 2,2-bis(aminomethyl)propionic acid core to connect and pre-organize binding groups. The cation binding is provided by a sodium selective N-acyl aza-18-crown-6 subunit whereas for anion complexation, two urea groups (receptor 2) or two squaramide groups (receptor 3) were introduced. Beyond acting as anion binding sites, the urea and squaramide groups were used to support sodium cation complexation through metal carbonyl oxygen lone pair interactions. The receptors were found to bind sodium salts of chloride, bromide and nitrate much more strongly than the corresponding ions accompanied by counterions that do not coordinate to the receptor. For example, chloride binding to receptor 2 enhances the strength of sodium complexation by up to 23 times. Conversely, sodium binding enhances chloride recognition by a factor of three. Receptor 3 containing squaramide units, binds sodium chloride and bromide with a similar albeit lower cooperativity. Moreover, unprecedentedly tight binding of these salts was achieved, with association constants as high as log Ka = 6.52 M-1 for NaCl salt complexation.

Ion-pair recognition of amidinium salts by partially hydrogen-bonded heteroditopic cyclo[6]aramide

Convergent heteroditopic cyclo[6]aramide is able to serve as ion-pair receptor for binding biologically important types of amidinium hydrochlorides as contact ion pair through host–guest interactions.

Smart molecules for imaging, sensing and health (SMITH).

This autobiographical review provides a personal account of the author’s academic journey in supramolecular chemistry, including brief summaries of research efforts in membrane transport, molecular imaging, ion-pair receptors, rotaxane synthesis, squaraine rotaxanes, and synthtavidin technology. The article concludes with a short perspective of likely future directions in biomedical supramolecular chemistry.

Electrostatic and Allosteric Cooperativity in Ion-Pair Binding: A Quantitative and Coupled Experiment-Theory Study with Aryl-Triazole-Ether Macrocycles.

Cooperative binding of ion pairs to receptors is crucial for the manipulation of salts, but a comprehensive understanding of cooperativity has been elusive. To this end, we combine experiment and theory to quantify ion-pair binding and to separate allostery from electrostatics to understand their relative contributions. We designed aryl-triazole-ether macrocycles (MC) to be semiflexible, which allows ion pairs (NaX; X = anion) to make contact, and to be monocyclic to simplify analyses. A multiequilibrium model allows us to quantify, for the first time, the experimental cooperativity, α, for the equilibrium MC·Na(+) + MC·X(-) ⇌ MC·NaX + MC, which is associated with contact ion-pair binding of NaI (α = 1300, ΔGα = -18 kJ mol(-1)) and NaClO4 (α = 400, ΔGα = -15 kJ mol(-1)) in 4:1 dichloromethane-acetonitrile. We used accurate energies from density functional theory to deconvolute how the electrostatic effects and the allosteric changes in receptor geometry individually contribute to cooperativity. Computations, using a continuum solvation model (dichloromethane), show that allostery contributes ∼30% to overall positive cooperativity. The calculated trend of electrostatic cooperativity using pairs of spherical ions (NaCl > NaBr > NaI) correlates to experimental observations (NaI > NaClO4). We show that intrinsic ionic size, which dictates charge separation distance in contact ion pairs, controls electrostatic cooperativity. This finding supports the design principle that semiflexible receptors can facilitate optimal electrostatic cooperativity. While Coulomb's law predicts the size-dependent trend, it overestimates electrostatic cooperativity; we suggest that binding of the individual anion and cation to their respective binding sites dilutes their effective charge. This comprehensive understanding is critical for rational designs of ion-pair receptors for the manipulation of salts.

N-H Hydrogen Bonding in Porphyrins - from Conformational Design to Supramolecular Chemistry

Typically porphyrin N-H units are not involved in intermolecular hydrogen bonds as they are ‘shielded’ by the macrocycle system. However, two possibilities exist to utilize the pyrrole nitrogen atoms in such bonds: a) Porpho(di)methenes and phlorins (calixphyrin-type systems) contain sp3-hybridized meso positions and the interruption of the aromatic system gives rise to specific cavities and often roof- or bowl-shaped conformations making the core nitrogen and N–H units more accessible for coordination. b) Likewise, saddle-distorted nonplanar porphyrins are very basic and can bind anions and neutral molecules via N-H hydrogen bonds in the core. Similarly, specific conformations and binding motifs can be accessed in porphyrin dications depending on the type, number, regiochemistry and steric bulk of substituents in the respective free base porphyrin. Here we give a brief overview of the different approaches and illustrate their use with regard to the design of ion-pair receptors for small molecules and anions and the formation of potentially functional supramolecular complexes.

Electrochemical and Fluorescent Ferrocene-Imidazole-Based Dyads as Ion-Pair Receptors for Divalent Metal Cations and Oxoanions.

In the tricyclic bis(heteroaryl)substituted ferrocenyl-imidazo-quinoxalines 7 and 8, the presence of redox and fluorescent units at the heteroaromatic core, which can act as a ditopic binding site, made these molecules potential candidates as electro-optical ion-pair recognition receptors. In this context, both molecules behave as ion-pair receptors for cations and anions, which individually had demonstrated their ability to form the corresponding cationic and anionic complexes. These receptors also show an important enhancement of anion binding by co-bound cations, whereas no affinity of the free receptors by the anion is observed. Similarly, receptors 7 and 8 display a dramatic increase in the cation binding by the action of their anionic complexes, while no affinity of the free receptors by the cations was detected. Interestingly, both receptors exhibit a remarkable enhancement of anions and cations binding, although no affinity of the free receptors by the ions is observed. In all cases, the ion-pair formation is detected by a perturbation of the redox potential of the ferrocene moiety and a remarkable enhancement in the emission band.

N-H Hydrogen Bonding in Porphyrins - from Conformational Design to Supramolecular Chemistry

Typically porphyrin N-H units are not involved in intermolecular hydrogen bonds as they are ‘shielded’ by the macrocycle system. However, two possibilities exist to utilize the pyrrole nitrogen atoms in such bonds. A) Porpho(di)methenes and phlorins (calixphyrin-type systems) contain sp3-hybridized meso positions and the interruption of the aromatic system gives rise to specific cavities and often roof- or bowl-shaped conformations making the core nitrogen and N–H units more accessible for coordination. B) Likewise, saddle-distorted nonplanar porphyrins are very basic and can bind anions and neutral molecules via N-H hydrogen bonds. Similarly, specific conformations and binding motifs can be accessed in porphyrin dications (N22,N24-dihydroporphyrins) depending on the type, number, regiochemistry and steric bulk of substituents in the respective free base porphyrin. The different approaches will be compared and analyzed with regard to the design of ion-pair receptors for small molecules and anions and the formation of functional supramolecular complexes.

Surprising Stability of an Al/P‐Based Frustrated Lewis‐Pair Towards Protolysis: HX Adducts (X = F, Cl) with Intramolecular H···X Hydrogen Bonds

AbstractThe Al/P‐based Frustrated Lewis Pair (FLP) Mes2P‐C(=CH‐Ph)‐Al(CMe3)2 (1) reacted with anhydrous HF and HCl as an ion pair receptor by coordination of the proton to phosphorus and the halide anion to aluminum. Short intramolecular distances and the molecular conformation indicate the presence P–H···X–Al hydrogen bonds (X = F, Cl) and an approach of the phosphorus and halogen atoms with a possible weak P···X interaction.

A simple and highly selective 2,2-diferrocenylpropane-based multi-channel ion pair receptor for Pb(2+) and HSO4(-).

A structurally simple, 2,2-diferrocenylpropane-based ion pair receptor 1 was synthesized and characterized by (1)H NMR, (13)C NMR, HRMS, elemental analyses, and single-crystal X-ray diffraction. The ion pair receptor 1 showed excellent selectivity and sensitivity towards Pb(2+) with multi-channel responses: a fluorescence enhancement (more than 42-fold), a notable color change from yellow to red, redox anodic shift (ΔE1/2 = 151 mV), while HSO4(-) promoted fluorescence enhancement when Pb(2+) or Zn(2+) was bonded to the cation binding-site. (1)H NMR titration and density functional theory were performed to reveal the sensing mechanism based on photo-induced electron transfer (PET).

Ion pair-induced conformational motion in calix[4]arene-strapped calix[4]pyrroles.

In order to understand the still-poorly understood interplay between calix[4]arene conformations and cation and anion recognition in multicomponent systems, the ion pair receptors 1 and 2 were synthesized. In solution and in the solid state, the calix[4]arene subunit of receptor 1 adopts a cone conformation, while that of 2 interconverts between the cone and the partial cone conformation. These geometric features differ from previous systems where the calix[4]arene moiety was locked in the 1,3-alternate conformation. A combination of 1H NMR spectroscopic analyses and single crystal X-ray diffraction studies reveal that receptor 1 binds the fluoride and the chloride anion via significantly different binding modes, displaying, for instance, 1 : 1 and 2 : 3 binding stoichiometries with CsF and CsCl, respectively. In the case of 2, the conformation of the calix[4]arene constituent of 2 is highly dependent on the size and quantity of anions present. For example, upon treatment of 2 with the fluoride anion (as both the TBA+ and Cs+ salts), the calix[4]arene unit coexists as cone and partial cone conformers that are inter-convertible. In the presence of excess CsF, the aromatic rings of the calix[4]arene subunit becomes locked in the pinched cone conformation with the result that an ion pair-mediated coordination polymer is formed. In the presence of excess CsCl, the calix[4]arene unit of 2 adopts only the partial cone conformation stabilized by aryl CH-anion hydrogen bonding interactions. The present systems constitute a rare set of related receptors wherein the effects of conformational changes are so tightly coupled with ion recognition.

Elucidating the structures and cooperative binding mechanism of cesium salts to the multitopic ion-pair receptor through density functional theory calculations.

Designing new and innovative receptors for the selective binding of radionuclides is central to nuclear waste management processes. Recently, a new multi-topic ion-pair receptor was reported which binds a variety of cesium salts. Due to the large size of the receptor, quantum chemical calculations on the full ion-pair receptors are restricted, thus the binding mechanisms are not well understood at the molecular level. We have assessed the binding strengths of various cesium salts to the recently synthesized multi-topic ion-pair receptor molecule using density functional theory based calculations. Our calculations predict that the binding of cesium salts to the receptor predominantly occurs via the cooperative binding mechanism. Cesium and the anion synergistically assist each other to bind favorably inside the receptor. Energy decomposition analysis on the ion-pair complexes shows that the Cs salts are bound to the receptor mainly through electrostatic interactions with small contribution from covalent interactions for large ionic radius anions. Further, QTAIM analysis characterizes the importance of different inter-molecular interactions between the ions and the receptor inside the ion-pair complexes. The role of the crystallographic solvent molecule contributes significantly by ~10 kcal mol(-1) to the overall binding affinities which is quite significant. Further, unlike the recent molecular mechanics (MM) calculations, our calculated binding affinity trends for various Cs ion-pair complexes (CsF, CsCl and CsNO3) are now in excellent agreement with the experimental binding affinity trends.

ChemInform Abstract: Calix[4]pyrrole‐Based Ion Pair Receptors

AbstractReview: 30 refs.

Tetrakis(bicyclo[2.2.2]oct‐2‐ene)‐Fused Calix[4]pyrrole

AbstractTetrakis(bicyclo[2.2.2]oct‐2‐ene)‐fused calix[4]pyrrole, 5, was obtained starting from (E)‐1,2‐bis(phenylsulfonyl)ethylene. This new calixpyrrole derivative is the prospective precursor of tetrabenzocalix[4]pyrrole, a potential ion‐pair receptor and an attractive species as a possible deep‐walled ‘molecular container’.

Calix[4]pyrrole-based ion pair receptors.

Ion pair receptors, which are able to bind concurrently both a cation and an anion, often display higher selectivity and affinity for specific ion pairs than simple ion receptors capable of recognizing primarily either a cation or an anion. This enhancement in recognition function is attributable to direct or indirect cooperative interactions between cobound ions via electrostatic attractions between oppositely charged ions, as well as to positive allosteric effects. In addition, by virtue of binding the counterions of the targeted ion, ion pair receptors can minimize the solvation of the counterions, which can otherwise have a negative effect on the interactions between the receptors and the targeted ions. As a result of their more favorable interactions, ion pair receptors are attractive for use in applications, such as extraction and sensing, where control of the binding interactions is advantageous. In this Account, we illustrate this potential in the context of ion pair receptors based on the calix[4]pyrrole scaffold. Both simple ditopic ion pair receptors, containing sites for the recognition of a single anion and single cation, and so-called multitopic ion pair receptors will be discussed. The latter systems differ from conventional, so-called ditopic ion pair receptors in that they contain more than one binding site for a given targeted ion (e.g., a cation). This permits a level of selectivity and control over binding function not normally seen for simple ion or ion pair receptors containing one or two binding sites, respectively. Calix[4]pyrroles are macrocyclic compounds consisting of four pyrrole units linked via fully substituted sp(3) hybridized meso carbon atoms. They are effective receptors for Lewis basic anions (e.g., halides) in typical organic media and under certain conditions will recognize ion pairs containing charge diffuse cations, such as a small alkylammonium, imidazolium, or cesium cations. The calix[4]pyrrole framework is further attractive in that it is relatively easy to modify. In particular, functionalization of the β-pyrrolic carbon and meso-carbon atoms with simple crown ethers or calix[4]arene crown ethers can produce heteromultitopic ion pair receptors containing more than two cation binding sites. This allows the interactions between receptors and ions to be manipulated on a higher level than can be achieved using simple ion receptors or heteroditopic ion pair receptors and has made these systems attractive for use in ion transport, recognition, and extraction. Recent progress in developing calix[4]pyrroles as both multitopic and more conventional ion pair receptors is summarized in this Account. The emphasis will be on our own work.

Ferrocene–Triazole–Pyrene Triads as Multichannel Heteroditopic Recognition Receptors for Anions, Cations and Ion Pairs

A number of functionalized ferrocene–triazole–pyrene triads, available from 1,1′-bis(azido)ferrocene by initial upper arm regioselective formation, through a copper-catalyzed click reaction, and subsequent nitrogen-containing bottom arm formation, through the remaining nitrogen functionality, have been designed, prepared, and structurally characterized as potential multichannel heteroditopic receptors for ions. The versatility of the bottom arm formation enables the decoration of the triad core with an additional nitrogen-based binding site, linked to substituents displaying different optical properties. As a consequence, the resulting disubstituted ferrocene derivatives have been shown to be excellent anion, cation, and ion pair multichannel recognition receptors. In order to gain insight into the coordination modes and into the nature of the anion contact ion pair formed, quantum chemical calculations were also carried out.