Dipyrrolylmethane-based macrobicyclic azacryptand: synthesis, X-ray structures, conformational and anion binding properties

A new class of macrobicyclic azacryptand containing dipyrrolylmethane subunits with nitrogen bridgeheads was synthesized by the Mannich reaction of the dipyrrolylmethane in the presence of aqueous ammonia. The azacryptand exhibits a staggered conformation in the solid state, but is in a dynamic equilibrium with the eclipsed conformation in solution studied by the variable-temperature (1)H NMR methods. The azacryptand has a specific size suitable only for fluoride ion; large anions such as NO(3)(-) bind in the clefts of the macrobicycle as shown by the X-ray structures of its fluoride ion inclusion and the nitrate anion complexes. The anion binding studies showed that it has high selectivity and affinity for fluoride ion in acetone over other anions studied, which was supported by (1)H and (19)F NMR methods. The azacryptand has fast fluoride ion-mediated proton-deuterium exchanges with acetone-d(6) studied by the (19)F NMR method.     

Coumarin-strapped calix[4]pyrrole: a fluorogenic anion receptor modulated by cation and anion binding

A new strapped calix[4]pyrrole containing a fluorophore as part of the strap has been synthesized and characterized. Association constants with various anions have been determined using both fluorescence titration and isothermal titrations calorimetry (ITC). The two sets of association constants were found to be in good agreement with one another. The fluorescence emission properties of this new receptor could be controlled by addition of Na+ (or H2O) and anions. However, the fluorescence quenching by anions is only observed in the presence of Na+ (or H2O). All the experimental evidence is consistent with the notion that independent PET processes are modulated by separate cation and anion recognition events. As such, this system operates as an elementary logic gate wherein anion and cation concentrations serve as the input and fluorescence intensity changes provide the output.     

Macrocyclic bis-urea receptor: Synthesis,crystal structure and phosphate binding properties

A macrocyclic bis-urea receptor (L1) and two acyclic bis-urea analogues (L2 and L3) have been synthesized. The crystal structure of L1 was obtained. The experimental results show that the receptor L1 has high selectivity to H₂PO₄^?. Meanwhile, compared with the acyclic receptors L2 and L3, L1 has higher binding ability to H₂PO₄^?. The results of density functional theory (DFT) calculations deepened our understanding on L1 conformations stability and its anion-binding property.     

A highly efficient, preorganized macrobicyclic receptor for halides based on CH... and NH...anion interactions

The preorganized, macrobicyclic azaphane (1) exhibits remarkable strong, selective fluoride binding comparable to the most effective bis(tren) cryptands despite binding anions via only three NH groups coupled with three CH hydrogen bond donors. The lower intrinsic affinity of CH donors is compensated by the high degree of preorganization exhibited by azacyclophane 1. Compound 1 is prepared via a tripod-tripod cyclization reaction between 1,3,5-tris-bromomethyl-benzene and an aliphatic tripodal hexatosylated polyamine, followed by the reduction of the resulting bicyclic tosylamine. The crystal structures of the bicyclic tosylamine 2 and four macrobicyclic polyammonium halide salts of 1 are reported. X-ray studies revealed the formation of inclusive 1:1 complexes of 1 with fluoride, chloride, bromide, and iodide. Potentiometric titrations showed very high binding constants for fluoride and chloride with a F(-)/Cl(-) selectivity of more than five logarithmic units. The final geometry of the anion cryptates is largely determined by optimization of NH and CH...anion interactions coupled with unfavorable anion-pi repulsion for the larger anions.     

Thermodynamic parameters for the binding of sulfate by open chain polyammonium cations

The interaction of sulfate with some open chain polyammonium cations was quantitatively studied by potentiometric (H(+)-glass electrode) measurements. Enthalpy changes, for some systems, were determined calorimetrically. Some literature data were also considered in the discussion of results. In all the systems, A(SO4)Hi(i-2) species are formed (i = 1, ...m; m = maximum protonation degree of amine), and, for i > or = 4, also A(SO4)2Hi(i-4) species were found. Both the stability and the formation enthalpies, for these complexes, are a direct function of the charges of reactants, and some empirical relationships are reported. A small, but significant, difference was found between the stability of unsubstituted and N-alkylsubstituted polyammonium cation-sulfate complexes.     

Anion-receptor molecules: Synthesis of a chiral and functionalized binding subunit,a bicyclic guanidinium group derived from L- or D- asparagine

The optically active (4S,8S)-4, 8-bis(hydroxymethyl)-1,5,7-triazabicyclo[4.4.0]dec-5-ene ((S,S)- 1 ) has been synthesized in nine steps from L -asparagine with a total yield of 5.1%. Similarly, the enantiomer (R,R)- 1 has been prepared from D -asparagine. (S,S)- and (S,S)- 1 are representative examples of rigid and functionalized bicyclic guanidine systems and constitute useful intermediates in the construction of chiral selective anion-receptor molecules.     

Fluoride anion binding by cyclic boronic esters: influence of backbone chelate on receptor integrity

A systematic investigation of fluoride anion binding properties as a function of chelate backbone has been carried out for ferrocene functionalised boronic esters of the types FcB(OR)2 and fc[B(OR)2]2 [Fc = ferrocenyl = (eta5-C5H5)Fe(eta5-C5H4); fc = ferrocendiyl = Fe(eta5-C5H4)2]. Cyclic boronic esters containing a saturated five- or six-membered chelate ring are readily synthesized from ferrocene, and selectively bind fluoride via Lewis acid/base chemistry in chloroform solution. The resulting complexes are characterized by relatively weak fluoride binding (e.g.K = 35.8 +/- 9.8 M(-1) for FcBO2C2H2Ph2-S,S), and by cathodic shifts in the ferrocene oxidation potential that form the basis for electrochemical or colorimetric fluoride detection. The fluoride selectivity of these systems is attributed to relatively weak Lewis acidity, resulting in weak F- binding, and essentially no binding of potentially competitive anions. By contrast, more elaborate Lewis acid frameworks based on calix[4]arene (calixH4), such as (FcB)2calix or fcB2calix, do not survive intact exposure to standard fluoride sources (e.g. [nBu4N]F.xH2O solutions in chloroform or acetonitrile). Instead B-O bond cleavage occurs yielding the parent calixarene; the differences between alkoxo- and aryloxo-functionalised derivatives can be rationalised, at least in part, by consideration of the differences in electron donating capabilities of RO- (R = alkyl, aryl).     

Evaluation of the binding ability of a macrobicyclic receptor for anions by potentiometry and molecular dynamics simulations in solution

The macrobicycle derived from bis-tren and containing diphenoxy groups as spacers, L¹, was synthesized and used as receptor for anions. The binding ability of the new receptor for some aromatic carboxylates [phthalate (ph²⁻), isophthalate (iph²⁻), terephthalate (tph²⁻), benezenetricarboxylate (btc³⁻), and the herbicide 4-amino-3,5,6-trichloro-2-pyridinecarboxylate (ATCP⁻)], and the aliphatic cyclohexanetricarboxylate (ch³⁻) anions was evaluated by potentiometric measurements and molecular dynamic simulation in solution. The association constants were determined by potentiometry in H₂O/MeOH (1:1 v/v) at 298.2 K and 0.10 mol dm⁻³ in KCl. The strongest association was found with btc³⁻ anion and the effective binding constants at pH 5.5 follow the order: btc³⁻>tph²⁻>ph²⁻≈iph²⁻>ch³⁻≈ATCP⁻. Molecular dynamics simulations carried out for the associations of (H₆L¹)⁶⁺ with btc³⁻, tph²⁻ and iph²⁻ in the same mixture of solvents indicated that these anions interact with the receptor by a combination of electrostatic and multiple N-H?OC hydrogen bond interactions. It was also verified that in the recognition process the tph²⁻ remained encapsulated over the entire time of simulation while the btc³⁻ is partially inserted into the receptor cavity with one carboxylate group largely exposed to water solvent molecules, and iph²⁻ anion exhibited an intermediate binding behaviour. The free energy difference between btc³⁻ and iph²⁻ associations estimated by free energy calculations is in excellent agreement with the difference found from the experimental values for the corresponding association constants, which indicates that the unconstrained molecular dynamics simulations carried out with these two anions are realistic pictures of their molecular recognition processes.     

Recognition of anions by polyammonium macrocyclic and cryptand receptors: Influence of the dimensionality on the binding behavior

Seven pairs of macrocyclic/cryptand polyamines, differing only in the added dimensionality, were selected and evaluated as receptors for anions in aqueous solution. The main differences on binding properties of protonated macrocycles and protonated cryptands as receptors for anions were analyzed through the association constants and structural data from the literature. Reported stepwise association constant values were critically evaluated on the basis of diagrams of log K_eff in function of pH, being K_eff the effective constant values.     

Macrocyclic anion receptors based on directed hydrogen bonding interactions

Natural anion receptors use charge-neutral dipoles to bind small anions with high affinities and selectivities. A convergent and rigid display of hydrogen bond donors such as amide, thiourea and urea functional groups in macrocyclic scaffolds would be one of the most efficient ways to create synthetic anion receptors that mimic natural ones. In this article, we present examples of natural anion receptors and discuss the synthesis of neutral macrocyclic receptors and their anion binding properties.     

ATP recognition and sensing with a phenanthroline-containing polyammonium receptor

A new polyammonium receptor is able to selectively recognise and sense ATP among triphosphate nucleotides, thanks to ATP-induced quantitative quenching of its fluorescence emission.     

Anion and cation binding by a pendant arm cyclam and its macrobicyclic derivatives

A series of transition-metal complexes of N,N',N',N'-tetra(3-hydroxypropyl)cyclam (L1) are reported. The X-ray structures of the compounds reveal pendant arm coordination of one of the alcohol groups to give square-pyramidal metal centres with simultaneous hydrogen bonding to the counter anions. Ligand L1 has been elaborated to form a series of macrotricyclic derivatives that form 1 ratio 1 complexes with Cu(II) and Ni(II). The X-ray structure of the tetrahydrate and protonated forms of L1 are also reported.     

Thermodynamic parameters for the binding of inorganic and organic anions by biogenic polyammonium cations

Thermodynamic parameters for the interaction of protonated biogenic polyamines with inorganic or organic polyanions were studied potentiometrically (H(+)-glass electrode) and calorimetrically, at 25 degrees C. No background salt was used in the measurements to avoid interferences, and the formation constants and formation enthalpies were extrapolated to zero ionic strength. Species formed are ALH(r) [L=Cl(-), SO(4)(2-), HPO(4)(2-), P(2)O(7)(4-) and P(3)O(10)(5-); tartrate, malate, citrate, glutamate, 1,2,3-propanetricarboxylate, 1,2,3,4-butanetetracarboxylate], with r=1,2...(n+m-2) and r=1,2...(n+m-1) for inorganic and organic ligands, respectively (n, m=maximum degree of protonation of amine and ligand, respectively). The stability of the various species formed is a function of charges involved in the formation reaction. DeltaH(0) values are generally positive, and therefore these complexes are entropically stabilized. Results are discussed in connection with several previously reported data on similar systems. DeltaG(0) and TDeltaS(0) follow a linear trend as a function of polyammonium cation and inorganic or carboxylic anion charges. DeltaG(0) and TDeltaS(0) charge relationships are reported. In particular, mean values of DeltaG(0) and TDeltaS(0) for single interaction were calculated: DeltaG(0)=7.0 kJ mol(-1) n(-1), TDeltaS(0)=9.1 kJ mol(-1) n(-1) and DeltaG(0)=5.7 kJ mol(-1) n(-1) and TDeltaS(0)=8.7 kJ mol(-1) n(-1), for the species of inorganic and organic polyanions, respectively (n=number of possible salt bridges). A linear relationship was also found for TDeltaS(0) versus DeltaG(0), whose equation is TDeltaS(0)=-7-1.39 DeltaG(0) (with r=0.9409; r, correlation coefficient). The body of correlations found for these thermodynamic parameters shows quite good predictive value.     

Sulfate as a synergistic anion facilitating iron binding by the bacterial transferrin FbpA: the origins and effects of anion promiscuity

The ferric binding protein, FbpA, has been demonstrated to facilitate the transport of naked Fe3+ across the periplasmic space of several Gram-negative bacteria. The sequestration of iron by FbpA is facilitated by the presence of a synergistic anion, such as phosphate or sulfate. Here we report the sequestration of Fe3+ by FbpA in the presence of sulfate, at an assumed periplasmic pH of 6.5 to form FeFbpA-SO4 with K'(eff) = 1.7 x 10(16) M(-1) (at 20 degrees C, 50 mM MES, 200 mM KCl). The iron affinity of the FeFbpA-SO4 protein assembly is 2 orders of magnitude lower than when bound with phosphate and is the lowest of any of the FeFbpA-X assemblies yet reported. Iron reduction at the cytosolic membrane receptor may be an essential aspect of the periplasmic iron-transport process, and with an E(1/2) of -158 mV (NHE), FeFbpA-SO4 is the most easily reduced of all FeFbpA-X assemblies yet studied. The variation of FeFbpA-X assembly stability (K'(eff)) and ease of reduction (E(1/2)) with differing synergistic anions X(n-) are correlated over a range of 14 kJ, suggesting that the variations in redox potentials are due to stabilization of Fe3+ in FeFbpA-X by X(n-). Anion promiscuity of FbpA in the diverse composition of the periplasmic space is illustrated by the ex vivo exchange kinetics of FeFbpA-SO4 with phosphate and arsenate, where first-order kinetics with respect to FeFbpA-SO4 (k = 30 s(-1)) are observed at pH 6.5, independent of entering anion concentration and identity. Anion lability and influence on the iron affinity and reduction potential for FeFbpA-X support the hypothesis that synergistic anion exchange may be an important regulator in iron delivery to the cytosol. This structural and thermodynamic analysis of anion binding in FeFbpA-X provides additional insight into anion promiscuity and importance.     

Protonation of polyamines in NaCl aqueous solution and binding of Cl by polyammonium cations

Equilibrium constants relative to the binding of Cl⁻ by nine open chain polyammonium cations (di, tri and tetra) were determined by potentiometric measurements (H⁺-glass electrode), at T=25°C. To this end the protonation constants of these amines were measured in NaCl aqueous solutions, in the ionic strength range 0.1<I≤1 mol dm⁻³. The different amines (some of which are N-alkyl substituted) were chosen in order to consider several factors affecting the values of protonation constants, the chloride complex formation constants and the dependence on ionic strength of apparent protonation constants. As concerns these last two points, it was found that fully N-alkyl substituted amines behave in a very similar way, with respect to partially or non-substituted ones. Simple linear relationships are reported involving chloride formation constants, parameters for the dependence on ionic strength of protonation constants and charges in polyammonium cations. The complexes formed by two linear polyamines with NO₃⁻ have also been studied for comparison. Literature data are examined.     

Supramolecular electron transfer by anion binding

Anion binding has emerged as an attractive strategy to construct supramolecular electron donor-acceptor complexes. In recent years, the level of sophistication in the design of these systems has advanced to the point where it is possible to create ensembles that mimic key aspects of the photoinduced electron-transfer events operative in the photosynthetic reaction centre. Although anion binding is a reversible process, kinetic studies on anion binding and dissociation processes, as well as photoinduced electron-transfer and back electron-transfer reactions in supramolecular electron donor-acceptor complexes formed by anion binding, have revealed that photoinduced electron transfer and back electron transfer occur at time scales much faster than those associated with anion binding and dissociation. This difference in rates ensures that the linkage between electron donor and acceptor moieties is maintained over the course of most forward and back electron-transfer processes. A particular example of this principle is illustrated by electron-transfer ensembles based on tetrathiafulvalene calix[4]pyrroles (TTF-C4Ps). In these ensembles, the TTF-C4Ps act as donors, transferring electrons to various electron acceptors after anion binding. Competition with non-redox active substrates is also observed. Anion binding to the pyrrole amine groups of an oxoporphyrinogen unit within various supramolecular complexes formed with fullerenes also results in acceleration of the photoinduced electron-transfer process but deceleration of the back electron transfer; again, this is ascribed to favourable structural and electronic changes. Anion binding also plays a role in stabilizing supramolecular complexes between sulphonated tetraphenylporphyrin anions ([MTPPS](4-): M = H(2) and Zn) and a lithium ion encapsulated C(60) (Li(+)@C(60)); the resulting ensemble produces long-lived charge-separated states upon photoexcitation of the porphyrins.     

Thermodynamic parameters for the binding of polycarboxylic anions by fully methyl substituted linear polyammonium cations

Enthalpy changes for the binding of malonate, citrate, 1,2,3-propanetricarboxylate and 1,2,3,4-butanetetracarboxylate by fully methyl substituted linear polyammonium cations (with the general formula C3nNnH(8n + 2)n+, with n = 1,2,3) were determined calorimetrically. Enthalpy changes were also determined for the binding of malonate by unsubstituted polyammonium cations (with the general formula C2(n - 1)NnH(6n - 2)n+, n = 1...6). delta H0/kJ mol-1 values are always positive and strongly dependent on the charges involved in the formation reaction. Mean values for delta G0 and T delta S0 were obtained as a function of the charge product zeta = Zanion/ Zcation: -delta G0/kJmol-1 = (4.0 +/- 0.4) zeta, T delta S0/kJmol-1 = (5.9 +/- 0.1) zeta (substituted polyamines), and -delta G0/kJmol-1 = (3.5 +/- 0.2) zeta, T delta S0/kJmol-1 = (5.0 +/- 0.4) zeta (unsubstituted polyamines). For both classes of amines it was found that T delta S0 vs. delta G0 is linear with a correlation coefficient of r = 0.9618. Crude approximation gives -delta G0/kJmol-1 = (7.0 +/- 0.4) n-1, T delta S0/kJmol-1 = (10.0 +/- 0.8) n-1 for unsubstituted amines and -delta G0/kJmol-1 = (8.0 +/- 0.8) n-1, T delta S0/kJmol-1 = (11.8 +/- 2.0) n-1 (n = number of possible salt bridges, or single interactions) for substituted amines.