Ditopic Binding Research Articles

Cleft‐Induced Ditopic Binding of Spherical Halides with a Hexaurea Receptor

AbstractA tripodal‐based hexaurea receptor with two clefts (inner cleft and outer cleft) has been studied for spherical halides by 1H NMR, UV‐Vis titrations, and theoretical calculations using density functional theory (DFT). As demonstrated from experimental and computational results, the receptor exhibits cleft‐induced binding for halides in a 1 : 2 binding mode, showing the binding strength in the order of fluoride > chloride > bromide > iodide. The strongest affinity for fluoride is attributed due to the best fit of two fluoride anions at the two clefts within the host‘s cavity. This is also supported by DFT calculations, suggesting that each anion is stabilized by six NH⋅⋅⋅F bonds ‐ one at the inner cleft and other at the outer cleft. In addition, the synthesized receptor, as examined on HeLa cells, has been found to show good biocompatibility.

Benchmark Ditopic Binding of Cl- and Cs+ by the Macrocycle Hexacyclen.

The ditopic binding of organic and inorganic anions and cations constitutes a distinct feature of polyazamacrocycles that underlies their action as intermediate docking and exchange ionophoric sites for tailored supramolecular synthesis and sensors. This work investigates the Cl- and Cs+ complexes formed by hexacyclen (1,4,7,10,13,16-hexaazacyclooctadecane, ha18c6), a benchmark building block of ion-pair polyamine receptors. IR action spectroscopy is employed to characterize the anionic and cationic complexes under controlled environmental conditions in an ion trap. This allows for accurate modeling of the isolated complexes with quantum chemical computations. A comparison of the experimental and computational spectra serves to assess the low-energy conformers dominantly populated at room temperature, which comprise, in both cases, three structures of Cs , C2 , and C3v symmetry with relative energies within about 5 kJ mol-1 . The ion-pair complex Cl- -ha18c6-Cs+ is predicted to host the cation and anion on opposite sides of the macrocycle in a C3v conformation that does not correlate with the lowest energy structures of the binary complexes. This indicates that the formation of the ion-pair complex in its most stable conformation demands a rearrangement of the hexacyclen ring structure upon the incorporation of the counterion.

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.

MRI sensing of neurotransmitters with a crown ether appended Gd(3+) complex.

Molecular magnetic resonance imaging (MRI) approaches that detect biomarkers associated with neural activity would allow more direct observation of brain function than current functional MRI based on blood-oxygen-level-dependent contrast. Our objective was to create a synthetic molecular platform with appropriate recognition moieties for zwitterionic neurotransmitters that generate an MR signal change upon neurotransmitter binding. The gadolinium complex (GdL) we report offers ditopic binding for zwitterionic amino acid neurotransmitters, via interactions (i) between the positively charged and coordinatively unsaturated metal center and the carboxylate function and (ii) between a triazacrown ether and the amine group of the neurotransmitters. GdL discriminates zwitterionic neurotransmitters from monoamines. Neurotransmitter binding leads to a remarkable relaxivity change, related to a decrease in hydration number. GdL was successfully used to monitor neural activity in ex vivo mouse brain slices by MRI.

Ferrocenylbenzobisimidazoles for Recognition of Anions and Cations

The preparation of 2,7-disubstituted benzobisimidazoles decorated with substituents displaying different electrooptical properties is described. The presence of redox, chromogenic, and fluorescent groups at the heteroaromatic core, which acts as ditopic binding site, made these receptors potential candidates as multichannel probes for ions. The triad 4 behaves as a selective redox and fluorescent chemosensor for HSO4(-) and Hg(2+) ions, whereas receptor 5 acts as a redox and chromogenic chemosensor molecule for AcO(-) and SO4(2-) anions. The change in the absorption spectra is accompanied by a color change from yellow to orange, while sensing of Zn(2+), Hg(2+), and Pb(2+) cations is carried out only by electrochemical techniques. Receptor 6 exhibits a remarkable cathodic shift of the oxidation wave only in the presence of AcO(-), H2PO4(-), and HP2O7(3-) anions, whereas addition of Pb(2+) induces an anodic shift. A new low energy band in the absorption spectra, which is responsible for the color change from colorless to pale yellow, and an important increase of the monomer emission band is observed only in the presence of H2PO4(-), and HP2O7(3-) anions. The most salient feature of the receptor 6 is its ability to act as a multichannel (redox, chromogenic, and fluorescent) chemodosimeter for Cu(2+), and Hg(2+) metal cations.

Functionalized BODIPY with various sensory units – a versatile colorimetric and luminescent probe for pH and ions

A series of BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) derivatives containing ion- and pH-sensory units have been successfully designed and synthesized. One of the compounds was structurally characterized by X-ray crystallography. Owing to the presence of an ICT absorption band, one of the compounds was found to show pronounced solvatochromic behavior in different organic solvents. Their emission energies in various solvents show a linear dependence on the Lippert solvent parameter. The cation-binding properties of the complexes with different metal ions (alkali metal, alkaline earth metal and transition metal ions) have been studied using UV-vis and emission spectroscopies. A 1:1 complexation to metal ions (Li(+), Na(+), Mg(2+), Ba(2+), Zn(2+), Cd(2+)) was found for the compound with one azacrown moiety in acetonitrile while another one with two azacrown moieties was shown to form 1:2 complexes with Zn(2+) and Mg(2+) cations. Their stability constants have been determined by both UV-vis and emission spectrophotometric methods. By introducing triarylborane moieties into the meso position and the 2-position of the BODIPY skeleton, different electronic absorption spectral changes together with an emission diminution were observed in response to fluoride ions. Ditopic binding study of 5, which was functionalized with both azacrown and triarylborane moieties, showed emission enhancement in the presence of Mg(2+) and F(-). These findings suggest that these BODIPY derivatives are capable of serving as versatile colorimetric and luminescence probes for pH, cations and F(-).

Synthesis, Structure, and Properties of Supramolecular Charge-Transfer Complexes between Bis(18-crown-6)stilbene and Ammonioalkyl Derivatives of 4,4′-Bipyridine and 2,7-Diazapyrene

4,4'-Bipyridine and 2,7-diazapyrene derivatives (A) having two ammonioalkyl N-substituents were synthesized. The complex formation of these compounds with bis(18-crown-6)stilbene (D) was studied by spectrophotometry, cyclic voltammetry, (1)H NMR spectroscopy, and X-ray diffraction analysis. In MeCN, π-donor D and π-acceptors A form supramolecular 1:1 (D·A) and 2:1 (D·A·D) charge-transfer complexes. The D·A complexes have a pseudocyclic structure as a result of ditopic binding of the ammonium groups to the crown-ether fragments. The better the geometric matching between the components, the higher the stability of the D·A complexes (log K up to 9.39). A key driving force of the D·A·D complex formation is the excessive steric strain in the precursor D·A complexes. The pseudocyclic D·A complexes involving the ammoniopropyl derivative of 4,4'-bipyridine were obtained as single crystals. Crystallization of the related ammonioethyl derivative was accompanied by transition of the D·A complexes to a structure of the (D·A)(m) coordination polymer type.

Ditopic Binding of Alkali Halide Ions to Trimethylboroxine

Trimethylboroxine (TMB) is a six-membered ring compound containing Lewis acidic boron and Lewis basic oxygen atoms that can bind halide anion and alkali metal cation, respectively. We employed Fourier transform ion cyclotron resonance spectroscopy to study the gas-phase binding of LiBrLi + and F � (KF)2 to TMB. TMB forms association complexes with both LiBrLi + and F - (KF)2 at room temperature, providing direct evidence for the ditopic binding. Interestingly, the TMB·F � (KF)2 anion complex is formed 33 times faster than the TMB·Li + BrLi cation complex. To gain insight into the ditopic binding of an ion pair, we examined the structures and energetics of TMB·Li + , TMB·F - , TMB·LiF (the contact ion pair), and Li + ·TMB·F - (the sep- arated ion pair) using Hartree-Fock and density functional theory. Theory suggests that F - binds more strongly to TMB than Li + and the contact ion-pair binding (TMB·LiF) is more stable than the separated ion-pair binding (Li + ·TMB·F - ).

Ditopic binding of cyclodextrin-included ligands in trigonal silver(I) complexes

The X-ray crystal structures of trigonal silver(I) cyclodextrin complexes of introverted bidentate sulfur ( 1) and phosphorus ( 2) ligands give a clear indication on how a cyclodextrin-included ligand may bind in a ditopic fashion both the encapsulated metal ion and the cyclodextrin inner wall. In the solid state, the silver-coordinated water molecule of complex [Ag(H 2O)( 1)]BF 4 induces a major distortion of the macrocyclic structure, along with dramatic conformational changes in the two opposite glucose units with which it is hydrogen bonded. In complex [AgBr( 2)], the included bulky bromide anion, which lacks hydrogen bonding capability, does not affect the overall circular shape of the cyclodextrin receptor. A 1H– 19F HOESY experiment conducted on the silver(I) complex of 1 in CDCl 3 showed that in this solvent, the water molecule is displaced by the BF 4 counterion at the metal coordination site, the cavity being here no longer distorted.

Congested Cyclometalated Platinum(II) Ditopic Frameworks and Their Phosphorescent Responses to S-Containing Amino Acids

New phosphorescent platinum(II) molecular hosts featuring a tridentate N,C,N-coordinating ligand, a conformationally rigid organic linker, and a binding group have been prepared. The complexes have been fully characterized by various spectroscopic techniques, and the X-ray crystal structure of one derivative has been determined. Their photophysical properties have been studied, and intense green metal-perturbed 3IL emission is observed in solution at room temperature. The luminescent responses of these Pt(II) hosts to amino acids have been investigated: emission quenching and UV−vis absorption changes in polar/aqueous media are detected for terminal thiols only, and unusual preferential binding is apparent for cysteine over homocysteine. The nature of the host−guest interactions has been examined by quantitative and comparative binding studies, mass spectrometry, and DFT calculations, which indicate that these observations may be ascribed to the presence of rigidly positioned ditopic binding sites.

Ditopic binding of perchlorate anion to hexaazamacrocyclic hosts.

Two structures of perchlorate with thiophene and p-xylyl based hexaazamacrocycles, have been determined by single crystallographic studies that show the ditopic recognition via N⋯O bonds of 2.90 and 3.02 A, respectively.

Binding of Nucleotides and Nucleosides to Per(6‐guanidino‐6‐deoxy)cyclodextrins in Solution

AbstractThe binding of α‐, β‐, and γ‐per(6‐guanidino‐6‐deoxy)cyclodextrins (ag, bg, and gg, respectively) with nucleotides (5′‐dAMP, 5′‐AMP, and 5′‐dCMP) and nucleosides (2′‐dA and 2′‐dC) was studied with NMR spectroscopy in aqueous solution. Nucleotides formed strong complexes with bg and gg (not ag) through ditopic binding. Multiple Coulombic attractive forces between the guanidino groups and the single phosphate group of the nucleotides drove inclusion of the entire ribose ring into the cavity, in both deoxy‐ and ribonucleotides, whereas the base moiety was only partially included. In contrast, no interaction was observed between guanidino cyclodextrins and nucleosides. The prevailing stoichiometries in all nucleotide/bg and nucleotide/gg complexes were 1:2, except for 5′‐dAMP/bg where oligomeric aggregates formed. The anti orientation of the nucleotides was preserved upon inclusion. The populations of conformers due to ribose pucker, 2′‐endo (S) and 3′‐endo (N), were practically undisturbed by inclusion. Interestingly, in the nucleotide/bg complexes at 278 K two nucleotide conformers were observed with distinctly different signals in slow mutual exchange owing to cavity restriction and a slow ribose pucker rate, which resulted in the observation of 3′‐endo (N) conformer separate from 2′‐endo (S) conformer for the first time.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Metal Phthalocyanine and Crown Ether–Based Membranes for the Potentiometric Determination of Phenylalanine Methyl Ester Using an Ion-Selective Electrode

Tetracrown-substituted metal phthalocyanines and metal phthalocyanine–crown ether mixtures are used as ionophores for plasticized PVC membranes of ion-selective electrodes for the ditopic binding and potentiometric determination of phenylalanine methyl ester. The complexation of the reagent with phenylalanine methyl ester is confirmed by extraction data and absorption spectra. Ion-selective electrodes are proposed for the monitoring of phenylalanine methyl ester in the biocatalytic synthesis of aspartame.

Mutually induced formation of host-guest complexes between p-sulfonated calix[8]arene and photolabile cholinergic ligands.

Adaptive systems: The conformationally flexible p-sulfonated calix[8]arene and photolabile cholinergic ligands adapt to each other and select the right conformers to form ditopic binding complexes (see schematic representation), thus mimicking ligand binding in biological receptors or enzymes.

Molecular Tweezers for Dicarboxylic Acids Based on a Saddle-Shaped Metallomacrocyclic Platform

A new metal containing molecular receptor was prepared from a 15-membered nickel(II) macrocyclic cyclidene platform and two cyclic tetramine (cyclen) recognition cites. In the saddle shaped conformation of the platform, the cyclen receptors are positioned for ditopic binding of difunctional substrates. NMR titration experiments demostrate that the molecule binds dicarboxylic acids in DMSO with apparent equilibrium constants ranging from 10 to 104 M-1. Incusion of dicarboxylates into the protonated macrocyclic host is shape-selective, with cis-1,2-dicarboxylates (succinate, maleate, and o-phthalate) being the best guests.

Synthesis and binding properties of cyclodextrin trimers

A series of cyclodextrin trimers and dimers were prepared and examined as binders for appropriate trimeric and dimeric aminoacid amides. Tritopic binding was stronger than ditopic binding, although the free energies were not strictly additive. Such trimers are attractive prospects for the binding of polypeptides and proteins.

Chemical Switching of Vesicle Bilayer Membrane Disruption by Bis(crown ether) Bolaamphiphiles

Bis(crown ether) bolaamphiphiles derived from 18-crown-6 dicarboxylic acid were prepared, and their ability to release vesicle encapsulated 5[6]-carboxyfluorescein was determined. Bolaamphiphiles with a linear central spacer are poor membrane disrupting agents except in the presence of alkaline earth metal cations or ethylenediammonium cation. Divalent ion enhancement of membrane disruption is cation selective and can be used to determine the apparent association constant of the bolaamphiphile crown ether with the added cation. The cis-isomer of a thioindigo bis(crown ether) bolaamphiphile is an active membrane disrupting agent, but the trans-isomer is significantly less active. In homogeneous solution, cis-to-trans thermal and photochemical isomerization is retarded by added alkaline earth metal salts, indicating that cooperative ditopic binding of the cations occurs despite the inherent flexibility of the bolaamphiphile. The membrane disruption mechanism occurs via U-shaped conformations of the bolaamph...

Ditopic binding of nucleotides by heptakis(6-hydroxyethylamino-6-deoxy)-β-cyclodextrin

The potential of heptakis(6-hydroxyethylamino-6-deoxy)-β-cyclodextrin (1) as a ditopic receptor capable of electrostatic interaction and hydrogen bonding by its amino side-chains, together with inclusion in its hydrophobic cavity, has been assessed for nucleotides as guest molecules. The interaction of 1 with adenosine-5′-triphosphate (ATP) and adenosine-5′-monophosphate (AMP) has been studied by potentiometry in water. Exceptionally strong binding is observed for fully protonated 1 with ATP4– (K = 1010 M–1) relative to AMP2– (K = 106 M–1), consistent with stronger electrostatic interaction with the former. Binding of AMP and p-nitrophenyl phosphate is of the same order of magnitude, while the complexes formed with ribose-5-phosphate are much weaker. The NMR changes observed upon addition of the nucleotides to 1 confirm interaction with the amino sites, together with inclusion in the cyclodextrin cavity.

Ditopic binding by a self-assembled receptor: Metal in a structural and functional role

Ditopic binding by a self-assembled receptor: Metal in a structural and functional role

A novel receptor for ditopic binding of alkali metal halides

The aluminum phenolate 2 having a crown ether ribbon is a selective ditopic host for lithium and potassium salts LiX and KX (X = Cl, Br, I), whereas LiF and KF show no interaction.