Calixarene complexes with soft metal ions

In this review calixarene complexes with copper, silver, gold, zinc, cadmium and mercury ions are described, showing their properties and application possibilities. In some cases also resorcinarene and pyrogallolarene metal complexes are presented. The attention is paid to species interesting in the search of artificial enzymes.


Calixarene complexes with copper ions
It is known that Cu 2+ ion plays an important role in biological systems, however it is also a significant environmental pollutant; the detection and determination of this ion receives today growing attention. 44][47][48][49][50] In investigation of calixarenes 1-3 bearing β-ketoimine groups, it was shown that these functions enable their complexation with transition metal ions.Calixarenes 1-3 exist in a cone conformation in solution; with Cu 2+ , Ag + and Hg 2+ ions they yield the 1:1 complexes. 51In the solid state "a polymeric linear chain" is formed as a result of intermolecular interactions between β-ketoimine groups.
The water-soluble calixarene 4, in which the 2,2'-bipyridine units show both hydrophilic and chelating properties, forms complexes with Cu + and Cu 2+ ions.The aqueous solution of 4 treated with [Cu(MeCN) 4 ]PF 6 affords the 1:1 complex Cu + ·4. 52It should be pointed out that Cu + ·4 is very stable, even in the presence of bovine serum albumin and is promising for use in biological media.
The complexation properties of calixarenes 5 and 6 toward Cu 2+ and Zn 2+ ions have been investigated. 53The binding of 5 with metal ion M 2+ (Cu 2+ or Zn 2+ ) is a two-step process, the first step involves the complexation of metal ions with imine functions affording 7 and the second one concerns the binding of two ether oxygen atoms of the pendants to give 8.
It was found that the spacer imine groups of 5 that are in conjugation with the anthryl units are responsible for fluorescence quenching when the metal ion is absent.In free 5 the imine group conjugated with the anthryl unit makes the system rigid; the lone electron pair is delocalized on the π-cloud of the anthracene unit.Due to this rigidity a favorable orbital overlap between the imine nitrogen atom and the π-orbital of anthracene exists, resulting in photoinduced electron transfer (PET) from imine nitrogen atom to the photoexcited anthryl unit.The presence of the conjugated imine moiety in 5 is responsible for the fluorescence quenching of the anthryl unit, since the photoinduced electron transfer (PET) from nitrogen atom of the imine group to the anthryl π-cloud exists.
The binding of the metal ion with imine groups destroys the effect of the lone pairs of nitrogen atoms which had caused the conjugation; therefore the PET is prevented and the fluorescence intensity increases.This fluorescence enhancement is stronger in 5 than in 6 where no imine moiety is present.It was found that 5 acts as a chemosensor for Cu 2+ ; since the increase in the fluorescence intensity for Cu 2+ is higher than for Zn 2+ , these both ions can be differentiated.
The chiral amphiphilic resorcinarene 9 containing four L-proline (Pro) moieties at the wide rim and four undecyl groups at the narrow rim has been synthesized.The molecules of 9 may self-assemble at the air-water interface as stable Langmuir monolayers.In the investigation of the effect of various cations on the stability of Langmuir monolayers it was found that their stability is highly increased in the presence of Cu 2+ ions, while in the presence of Cd 2+ , Co 2+ and Ni 2+ ions only slight stabilization occurs. 54he supramolecular complex Cu 2+ ·9 shows enantioselective recognition properties towards phenylalanine (Phe), with a stronger affinity for D-Phe than for L-Phe.The recognition process occurs via the formation of a ternary complex Cu 2+ ·9·D-Phe.In this complex the Cu 2+ ion is chelated by two carboxylato oxygen atoms and by two nitrogen atoms of Pro and Phe, forming a planar square. 54The above results are promising for the use of macrocyclic receptors of the type of 9 as active layers in the design of enantioselective sensors.

Scheme 1
The complexation of calixazacrowns 10a-c and their homologues 11a,b with Cu 2+ was studied.It was found that Cu 2+ forms with 10a the 1:1 complex i.e.Cu 2+ •10a, and with 11a the 2:1 complex, i.e. (Cu 2+ ) 2 •11a; compounds 10a and 11a are promising for the design of fluorescent chemosensors for Cu 2+ ion. 44It should be mentioned that 10a may form in the solid state channels for small molecules, e.g.methanol.
The presence of the phenanthroline bridge in 15, 16 and 18 enables the chelation of Cu + ions; the formed complexes were tested as ligands for copper ion in the Cu(I) catalyzed cyclopropanation of styrene and indene with ethyl diazoacetate 19. 59It was found that chiral 16 and 18 alter the stereoselectivities of the cyclopropanations of styrene towards cis and indene towards endo products, i.e. in the same direction as in the case of nonmodified 15.
In biological systems the coordination properties of the metal ion are controlled by proteins.In order to mimic such biological coordination, ligands basing on calix [6]arenes functionalized at the narrow rim by nitrogen arms were designed.In these ligands the aza-donors secure the first coordination sphere with one open binding site directed toward the center of calixarene cavity.The calixarene narrow rim defines the second coordination sphere, whereas the aromatic units of the calixarene act as a hydrophobic funnel selecting and driving the guest molecule to the metal center. 60he complexation of Cu + and Cu 2+ ions by tris(pyridine)calix [6]arene 20 has been studied. 61,62It was observed that Cu + ·20 upon addition of MeCN affords complex Cu + ·20·MeCN in which Cu + ion has the tetrahedral (T d ) geometry and is coordinated by three pyridine nitrogen atoms and by nitrogen atom of MeCN ligand situated inside the cavity.
However, in Cu 2+ ·20·MeCN, the Cu 2+ ion has the square-based pyramidal geometry (SBP); in the complex one nitrogen arm is in the apical site, and the water molecule is situated outside the cavity.
In both complexes, i.e.Cu + ·20·MeCN and Cu 2+ ·20·MeCN, as well as in the transition state A the CH-π interactions between the phenyl units of the cavity and the methyl group of MeCN exist.The MeCN unit plays in these complexes an important role since it controls the coordination of Cu + and Cu 2+ ions by combination of the Cu/N (nitrile) bond and second sphere interactions; the presence of MeCN is necessary to maintain the architecture of complexes.The existing host-guest interaction generates a supramolecular stress resulting in a driving force pulling the Cu + or Cu 2+ ions inside the calixarene cavity.The above Cu + /Cu 2+ systems are of interest in the study of biomimetic processes of proteins.
An important difference however exists, resulting from the fact that the second coordination sphere provided by a narrow rim in 22 forms a different electronic environment than in the case of 24 and 25.In 24 and 25 the oxygen atoms connecting phenyl moieties with imidazole units (in 24) or with nitrogen atoms (in 25) are directed inwards.In the case of complexes 22, however, the structure is rigid due to the presence of tmpa, therefore the oxygen atoms connecting phenyl moieties with pyridyl units are directed outwards, i.e. towards the bulk.In this way the dipolar inversion of the second coordination sphere responsible for anion binding occurs.As a result, the Cu 2+ ion in 22 is able to bind a large variety of anions, while in the case of 24 and 25 [65][66][67][68] the anion binding in the cavity is strongly disfavored because of charge-dipole repulsion at the narrow rim.The above complexes are highly biologically relevant to mononuclear active sites of metalloenzymes. 63

Calixarene complexes with silver ions
In the study of calixarene complexes with silver ions [69][70][71][72][73] it was found that calixarenes 26 and 27 containing sulfur atoms as soft binding site may be used as cation sensors for ion-selective electrodes.In order to investigate the influence of neighboring halogen atoms on cation selectivity, the fluorosubstituted (i.e. 28, 29) and dichlorosubstituted ( i.e. 30-32) analogues of 26, 27 were studied. 74The ion-selective electrodes based on 26-32 as neutral ionophores have been prepared, and their selectivity coefficients for Ag + were examined against alkali metal, alkaline earth metal, lead, and some transition metal ions using the fixed interference method (FIM).It was found that they have high Ag + selectivity over Na + , K + , NH 4 + , Ca 2+ , Cu 2+ , Zn 2+ and Cd 2+ interfering ions, except for Hg 2+ .Calixarenes 28-32 contain sulfur atoms as a soft binding site and neighboring halogen atoms as assistant donors taking part in complexation of silver ions.The 1 H NMR analysis has shown that 29 exists as several conformers in solution, and the 19 F NMR spectra of Ag + •29 revealed that the fluorine atoms participate in complexation of silver ion.
Calixarenes 33-36 bearing allyl groups and calixarenes 37a,b containing benzothiazole units have been investigated in view of their affinity towards Ag + ion; among them 34, 37a and 37b were used for construction of Ag + ion-selective electrodes. 75,76It was observed that 37b coordinates Ag + more strongly than 37a .
It was observed that calixarenes 38a-c form 1:1 inclusion complexes with Ag + ; their stability constants, determined by the ESI-MS (electrospray-ionization mass spectrometry) method decrease in the order 38b>38a>38c. 728][79] Although calixarene 39 has low solubility, the amines can solubilize it via acid-base host-guest chemistry, resulting in the abstraction of a single proton from 39 by the amine.Majority of inclusion complexes of 39 are formed in solution by van der Waals interactions of a guest with hydrophobic cavity of 39, leading to 1:1 or 2:1 host-guest systems. 80In the solid state, however, the symmetry of the calixarene is disrupted, therefore simple 1:1 or 2:1 host-guest complexes are not formed.
It was observed that the solution of 39 and AgNO 3 in ethylenediamine 40 after evaporation of excess solvent affords crystals of the clathrate [Ag + · 39·(40) 3 ], i.e. 41.In 41 one molecule of 39 interacts with three ethylenediamine 40 molecules coordinating one Ag + ion.The calixarene 39 serves as a counterion, a single proton being abstracted from one of its phenol groups by the excess ethylenediamine left behind as solvent.In 41 one bidentate-chelating molecule of 40 is situated within the calixarene (endo), whereas two singly coordinated molecules of 40 reside outside the calixarene cavity (exo); the four-coordinate Ag + ion has a distorted tetrahedral geometry. 77he clathrate 41 is further stabilized through a network of hydrogen bonds.The endo coordinated amine units interact with the phenolic hydroxyl groups of calixarene 39.The free amino groups of the two exo molecules of 40 form weak hydrogen bonds with free amino groups of the adjacent molecules of 41.Due to the above hydrogen bonds, the distortion of the capped structural motif takes place.
It was observed that upon deamination occurring by heating the sample 41, its color changes from white to yellow and then to brown, indicating the reduction of the Ag + ion and formation of nanocrystalline clusters consisting of 39 and metallic silver.
The oligophenylene-substituted calix [4]crowns 42a-d form complexes with Ag + ion. 81The binding of crown ether moiety with Ag + ion is weak, therefore the reversible disassembling of the complex in the presence of KI is possible.It should be pointed out that despite weakness, this interaction is useful in the design of supramolecular structures.

Calixarene complexes with gold ions
In the study of calixarene gold complexes 49,82 it was observed that the compound 43 containing four two-coordinate linear gold halide units exists as an equilibrium between two boat conformers 43a and 43b which undergo an easy conformational exchange [83][84][85] in solution.In order to synthesize resorcinarene digold complexes the disilver complexes 44a-c were treated with [AuCl(SMe 2 )].The reactions occur with the precipitation of silver chloride, and as products the resorcinarene digold complexes 45a-c are formed. 83t was found that the reaction of resorcinarene 46 with [AuCl(SMe 2 )] yields polymeric complex [46   83 It should be pointed out that the complex 47 has an unusual polymeric structure in the solid state in which molecules A and B are linked via Au•••Au interactions at each end; in this way two intermolecular aurophilic bonds are formed.The presence of these aurophilic attractions between the chelated S-Au-S gold centers and the linear S-Au-Cl gold centers results in an infinite, alternating pattern of the two different components A and B, which create this polymeric structure.The solid-state structure of the complex 47 contains both the chelate form in A and the terminal ligand form in B.
The reaction of calixarene 48 with four equivalents of [AuCl(THT)] (where THT = tetrahydrothiophene)] affords the tetragold complex 49. 86In the study of stepwise titration of 48 with AuCl(THT) it has been shown that the first complexation step affords a mononuclear species 50, existing in equilibrium with the assembly 51.The NMR study indicates the dynamic behavior of 50; its all four phosphorus atoms are involved in coordination.The chloro-gold units jump from one phosphorus atom to another; it should be pointed out that both intermolecular and intramolecular jumps are possible.Molecular mechanics calculations have shown the tetrahedral geometry of gold centers.
The binding of the second gold unit is more difficult than in the case of the first one.The addition of the second AuCl(THT) molecule leads to the dinuclear gold complex 52 existing in an equilibrium with the assembly 53.The X-ray structure of 53 shows that the linking gold atoms having near-trigonal geometry.The addition of the third AuCl(THT) molecule results in formation of labile complex 54, which upon reaction with the fourth AuCl(THT) molecule yields 49.
1][92] The scanning tunneling microscopy (STM) results indicate that the stability of a large organic compound sublimated onto a Au (111) surface under ultrahigh vacuum conditions may be considerably enhanced by coordinating it to gold atoms prior to deposition.For this purpose gold-functionalized calix [4]arene 55 containing two arms derived from melamine units and terminating by triphenylphosphine groups has been synthesized.ARKAT USA, Inc.

Calixarene complexes with zinc ions
Zinc is widely used in fine chemicals and paint industries, as well as in electroplating; zinc is also present in high protein foods.Excess of Zn 2+ ions is toxic for humans, therefore methods for zinc monitoring are of importance. 93Calixarene zinc complexes are intensively studied; 49,78,[94][95][96] some examples will be shown below.
Investigations of complexing properties of calix [4]arene 56 towards cations and anions have shown that different moieties of the pendant arms serve as active sites for complexation, therefore 56 may be considered as a ditopic receptor.Calixarene 56 forms with Zn 2+ ion the complex Zn 2+ ·56; in this process the hydroxyl and carbonyl groups of the pendant arms at the narrow rim of 56 function as active sites for interaction. 97,98t was established that 4-t-butylcalix [4]arene 39 may be used as a Zn (II) selective potentiometric sensor. 93Poly(vinyl chloride) based membranes containing 39 show a very good selectivity for Zn 2+ over other mono-, bi-and trivalent cations; one should point out their fast response and good reproducibility.The sensor may be used as an indicator ionoselective electrode in the potentiometric titration of Zn 2+ against EDTA 27,28 (EDTA = ethylenediaminetetraacetic acid) and for estimation of zinc ions in industrial waste waters.
It is known that macrocyclic host molecules are promising models for enzymes.When transition metals are coordinated in proximity to the hydrophobic cavities of receptors, the macrocycles function as metalloenzymes. 99Metalloenzyme models acting in aqueous solution have been designed by employing self-assembly of the p-sulfonatocalix [4]arene 57 (used as a macrocyclic host able to bind cationic guests), bicyclic azoalkanes 58-60 100,101 serving as guests, and Zn 2+ as a metal ion. 102In this model the metal-guest bond formation is host-assisted, i.e. is templated by the host.In the soformed ternary complex consisting of 57, the guest and the metal ion, the guest is held by hydrophobic interactions with the host, while the metal ion is held by Coulombic attraction of negative charges situated at the wide rim of 57.If the guest is a weak ligand, the host can assist, i.e. can template the formation of a metal-guest bond.The guest used should be large enough to maximize hydrophobic interactions, and sufficienty small to enable the docking of cations to the wide rim of calixarene 57.The guest should contain functional groups to allow metal-guest interactions.
Bicyclic azoalkanes 58-60 have been chosen as guests.Among them, 58 is the most convenient guest, since its binding constant with 57 is the highest, and its small and spherical shape enables the binding of metal ions. 103The formation of the complex 57·58 and the subsequent binding of metal ion may be controlled by optical spectroscopy, since 58 shows strong fluorescence in water, as well as the near UV absorption.
When 57 is added to an aqueous solution of 58, the 1: 1 complex is formed.The subsequent addition of Zn 2+ results in the formation of a ternary complex Zn 2+ •57•58, in which the azo group of 58 serves as a monodentate ligand.This behavior, i.e. that the host brings 58 and Zn 2+ together is similar to the function of enzyme bringing together the substrate and the catalytic center.The formation of the ternary complex Zn 2+ •57•58 is an example of a cooperative binding. 102It is known that 58 shows in water a high fluorescence, which is quenched upon complexation with 57.When Zn 2+ ions (which do not quench the fluorescence of free 58) are added, the fluorescence of 58 is further decreased, indicating the formation of the ternary complex.
It should be noted that 59 and 60 do not form similar ternary complexes, in the case of 59 due to steric hindrance and in the case of 60 due to charge repulsion between Zn 2+ cations and the positive ammonium group of 60.In these both cases of 59 and 60 the release of the guest occurs, due to the competitive binding of 59 or 60 and Zn with 57. 102These observations indicate the high selectivity of 57, since it forms ternary complex only with 58 and not with 59 or 60, although the structural differences of 59 and 60 as compared to 58 are slight.
The above results show possibility of two modes of binding, i.e. cooperative and competitive binding.The cooperative binding occurs when steric and electrostatic factors are favorable and when the geometry allows the formation of the metal-guest bond.The binding constant of 57•58 increases fourfold by addition of Zn 2+ ; this observation indicates a positive cooperativity of the binding, i.e. the synergistic effect.This increase of binding constant of 57•58 in the presence of metal ion, resulting from metal-guest interaction is promising in sensor design.
UV spectral analysis has revealed that at pH 2 the guest 58 in 57 is protonated to give the complex 58•57•H + .Upon addition of Zn 2+ ions, the complex Zn 2+ •57•58 is formed.That means that in this particular case, Zn 2+ ions do not destabilize the complex of 56 with a cationic guest, i.e. the release of 58 does not occur as it took place in the case of 60, but the guest is deprotonated by Zn 2+ which forms the metal-guest bond.This behavior resembles function of Zn 2+ ions in hydrolytic metalloenzymes, where Zn 2+ ions deprotonate ligands by formation of metal-ligand bonds. 102,104alix [6]arenes may be used as hydrophobic hosts, their large cavity enables inclusion of a variety of organic guests.Since calix [6]arenes are very flexible, in order to obtain a cavity able to include a guest they must be restricted in a cone conformation. 68n order to design biomimetic receptors, the system 61 mimicking metalloenzyme active sites by binding metal center incorporated inside a calix [6]arene cavity with a neutral guest has been developed.This system is based on calix [6]arene bearing three imidazole arms and contains the Zn 2+ ion. 105The imidazole arms are mimicking the histidine residues of the protein.The Zn 2+ ion is coordinated in a tetrahedral geometry.Such funnel complex, increasing Lewis acid character of metal ion in the hydrophobic neutral environment is highly sensitive to different guests (G) of an electron donor character, e.g.RNH 2 , ROH, RCONH 2 , RCN, RCOOH; their encapsulation leads to 61.The hydrophobic pocket is a selective molecular funnel for neutral species.This system 61 is similar to 24, i.e. to copper funnel complex based on calix [6]arene bearing three imidazole arms and Cu 2+ ion, containing the guest molecule G.
In the study of biomimetic zinc funnel complexes basing on calix [6]arene, it was observed that calix [6]arenes 62a•H and 62b•H bearing two imidazole arms and one phenol arm may form three types of complexes with Zn 2+ ion, namely dicationic, monocationic and neutral ones. 1061) It was found that 62a•H reacts with Zn(H 2 O) 6 (ClO 4 ) 2 in THF to give the dicationic complex [Zn(62a•H )(H 2 O)](ClO 4 ) 2, i.e.A in which Zn 2+ is coordinated to three nitrogen atoms, to the linking OH group and to H 2 O molecule.One should mention that in the case of 62b•H the formation of a dicationic complex similar to A was not observed.When the CDCl 3 solution of A was treated with a small neutral guest G, e.g., ROH, RCN, RCONH 2 (ethanol, acetonitrile, propionitrile, acetamide), the exchange of H 2 O for G molecule took place, affording the dicationic complex [Zn(62a•H)(G)](ClO 4 ) 2 .
(2) The reaction of 62a•H and 62b•H with Zn(H 2 O) 6 (ClO 4 ) 2 in MeOH in the presence of triethylamine leads to monocationic complexes [Zn(62•H)](ClO 4 ), i.e.B in which the linking OH group underwent deprotonation to oxygen atom.This complex also binds a guest, although with a lower affinity than the dicationic complex A; as a result [Zn(62•H)(G)](ClO 4 ) is formed.The exchange rate of guest increases in the order [Zn(62a•H)(G)] 2+ < [Zn(62b)(G)] + < [Zn(62a)(G)] + , i.e. following the increase of the donor ability of the calixarene-based coordination core; the stronger is the Zn Lewis acidity, the stronger is the Zn-guest bond and the slower is the exchange rate.
(3) The reaction of 62a•H and 62b•H with Zn(H 2 O) 6 (ClO 4 ) 2 in MeOH in the presence of an anion (X ¯ = OH¯, Cl ¯, N 3 ¯, PhCOO¯) affords neutral complexes [Zn(62)X], i.e C in which the anion X ¯ coordinates Zn 2+ from the outside of the cavity.In these complexes calixarene has a partial cone conformation with one imidazole arm released by the metal center.The other imidazole arm, still bound to the metal center, undergoes self-inclusion into the calixarene cavity and fills it.Therefore the formed complex [Zn(62)X] is unable to endo-bind guests.Thus the coordination of two anions (ArO¯ and X¯) decreases the Lewis acidity of zinc to a point that the metal center does not bind a fifth donor, i.e. the complex [Zn(62)X] cannot include guests into its cavity.The zinc affinity for a guest decreases in the order: dicationic A > monocationic B > neutral C, which does not bind guests at all.
It should be pointed out that the above complexes behave as acid-base switch for guest binding to give ON − OFF system.The dicationic form having the strongest Lewis acidic Zn center represents the ON state; it includes the small guest G. Deprotonation of the phenol group weakens the Zn-G bond; the formed monocationic complex either remains in an ON state or releases G to give the OFF state.Further addition of a base leads to the full OFF state, i.e. the formation of the neutral complex, with the self-inclusion of the imidazole substituent.The process is reversible, addition of an acid to the neutral complex drives back the equilibria to the ON state.Some features of the above systems are similar to behavior of Zn-peptidases of the astacin and serralysin families, in which the active Zn(II) site is coordinated to three histidine residues. 106RKAT USA, Inc.

Scheme 5
Complexing properties of calix [6]arene 63, bearing three primary alkylamino arms have been studied. 105It was found that 63 can be structured by strong acids, e.g.TFA to give a polarized receptor 64.Upon this protonation of 63 leading to 64 the three ammonium groups of 63 become sealed together by the counter-anions.Calixarene 64 , having a hydrophobic π-basic cavity terminating in a tricationic protic site, shows a strong affinity for polar neutral guests G such as alcohols, amides, ureas or nitriles; their encapsulation yields complexes 65. [107][108][109][110] This behavior is due to the self-assembly of the ion-paired platform, closing the narrow rim of the cavity and freezing the calixarene cone conformation, as well as stabilizing the neutral guests via hydrogen bonding and charge-dipole interactions.
It was found that 65 forms with Zn 2+ ion the dinuclear complex 68.Treatment of 68 with a carboxylic acid or a sulfonamide, i.e.XH (X = PhCOO, AcO, MeSO 2 NH) and TEA (TEA = triethanoloamine) affords complex 69, while treatment of 68 with alkylamine and strong acid, e.g.RNH 2 /TFA leads to complex 70.It is of importance that the asymmetry of an enantiopure amino ligand is transmitted to the calixarene core, in this way the asymmetry of the external ligands is sensed by the guest.Complexes 69 and 70 contain the tetrahedral Zn + ion bound to three amino arms and to an exogenous ligand (X or RNH 2 ) protruding outside the cavity.As a result, the metal ion structures the calixarene core, constraining it in a cone conformation suitable for guest inclusion.The formed calixarene cone acts as a polarized receptor; its host properties can be allosterically tuned by the environment via the binding of external ligands to Zn 2+ ion.In the case of the electron rich external ligand, the receptor is less polarized, and highly sensitive to the hydrogen bonding ability of the guest, however in the case of less electron rich external ligand, the receptor becomes more polarized, and more sensitive to the dipole moment of the guest, i.e. the binding of dipolar molecules is more efficient.These properties are different than those of funnel Zn complexes, e.g.61, in which the coordination link of Zn 2+ with the guest plays a dominant role.The above observations are of interest in the search for artificial enzymes. 105n calix [6]tren 71 the cone conformation is restricted by presence of the tren cap.The calix [6]tren 71 is an effective receptor with the cavity consisting of highly π-basic aromatic walls; the grid-like nitrogenous cap is also highly basic.The host properties of 71 can be tuned by the environment, more or less basic or by presence of metal ions.As a result, 71 may include cationic species such as metal ions or ammoniums as well as various neutral molecules.The reaction of 71 with [Zn (ClO 4 ) 2 (H 2 O) 6 and the guest G yields the complex Zn 2+ ·71·G. 104omplexes Zn 2+ •71• G, where the guest G = ROH, RCN, DMF or RCONH 2 are highly resistant; the addition of AcOH, MeI, Et 3 N or a strong base such as NBu 4 OH does not result in deprotonation of the guest or decoordination of Zn 2+ .This high robustness is due to both a strong chelate effect of the tren cap and a cavity-controlled access to the metal center.

Scheme 6
Bimetallic zinc complexes are of interest in catalytic processes involving asymmetric organic syntheses and enzymatic reactions.Bimetallic zinc complexes usually act as catalysts in organic and enzymatic processes by a tandem participation of both zinc atoms.The catalytic activity of calixarenes containing two zinc centres in close proximity to each other, has been studied. 111For this purpose bimetallic zinc complex 72a was used as a catalyst of the ring-opening polymerization of L-lactide 73.The reaction leads to complex 74a which by precipitation with nhexane affords poly(lactic acid) PLA and free 72a.In this process PLA with high molecular weight and a low degree of polydispersity is obtained; it was observed that the catalytic activity of 72b is higher than that of 72a.It should be pointed out that PLA is a polymer promising for its biocompatible and biodegradable properties.
It was established that the catalytic activity of 72 depends only on the external alkyl zinc group serving as an initiator, and is independent on the alkyl zinc group situated inside the calixarene cavity; this zinc atom, immersed in the calixarene cavity does not participate in catalysis.The above results are an example of the single-site catalytic mechanism of a bimetallic zinc calixarene complex. 111,112It should be noted that the calixcrown bimetallic zinc complex 75 also catalyzes ring-opening polymerization of L-lactide to give the complex 76; this process is a confirmation of the zinc single-site catalytic mechanism.
The reaction of the bimetallic zinc complex 77 with B(C 6 F 5 ) 3 in benzene, followed by the addition of a bidentate ligand L, such as bipyridine or phenanthroline affords bimetallic complexes 78, whereas upon treatment with wet trifluoroborane etherate the monometallic complex 79 is formed. 113,114he single-crystal X-ray analysis of 79, obtained from the toluene solution, shows that Zn 2+ is situated at the centre of an octahedron, with four calixarene oxygen atoms in the equatorial plane.Two water molecules are localized at axial positions, one of them being immersed in the calixarene cavity.

Calixarene complexes with cadmium ions
Cadmium is used in industry, e.g. in the production of pigments and anticorrosive coatings, alloys and batteries; due to the presence in natural waters, its determination with the use of simple, disposable devices is necessary.Cadmium is toxic to plants and humans, its toxicity involves the strong affinity to thiol groups, displacing the biologically important zinc. 115Examples of works dealing with calixarene cadmium complexes 49 are described below.
In the study of calix [5]arenes, [116][117][118][119] the complexing properties of calix [5]arene 80b with metal ions have been determined.The complexation of calix [5]arene 80b with Cd 2+ and Hg 2+ ions was investigated by conductometric titrations in methanol and in acetonitrile; it was found that 1:1 complexes are formed, the binding constant of Hg 2+ complex being higher than that of the Cd 2+ complex. 120It is noteworthy that analogous tetrameric calix [4]arene 80a shows more efficient binding ability than 80b towards Cd 2+ and Hg 2+ ions. 120n the search for cadmium sensors it was found that calixarenes 81 and 82 may serve for modification of screen-printed carbon electrodes for complexation of Cd 2+ traces at open circuit. 115It should be noted that 82 has higher configurational stability than 81, since 82 contains tbutyl substituents at the wide rim, and ethylthio substituents at the narrow rim, therefore 82 has greater propensity to the cone conformation.Since 81 does not bear these groups, it may move through the four possible conformations, i.e. cone, partial cone, 1,2-and 1,3-alternate.
The screen-printed carbon electrodes modified with 81 and 82 are able to accumulate Cd 2+ ions; the better results have been obtained in the case of 82.
It should be noted that the screen-printed sensor modified with 82 may be used for the trace determination of Cd 2+ in environmental water samples. 115t was found that calixarene 83, bearing four allyl groups includes Cd 2+ and Tl + ions. 121This behavior served for building of glassy carbon electrode coated with Langmuir-Blodgett (LB) film of 83, able to simultaneous determination of traces of Cd 2+ and Tl + in environmental water; indium does not respond to the above LB film electrode.
The method involves chelation of metal ions from solution on the surface of glassy carbon electrode coated with 83, reduction of the accumulated metal ions and electrochemical stripping of the reductive material back into solution.The electrode can be used to simultaneous determination of Cd 2+ and Tl + .This process is explained by hard soft acid and base (HSAB) principle, Cd 2+ and Tl + ions being soft acids, and allyl group and benzene ring being soft bases.It should be pointed out that the above electrode is environment friendly since it replaces current mercure electrode in environmental analysis.
The chromogenic calixarene 84 containing four azo groups may serve for detection of Cd 2+ and Cu 2+ ions, for this purpose the optical fiber sensor based on 84 has been built. 122The detection of the above ions involves the covering of the optical fiber core by a transparent polymer containing a complexing agent; its absorption properties are modified in the presence of the considered ions.The trapping of the ion in the polymeric cladding, i.e. in the cavities of the chelating molecules induces a variation of the light power transmitted along the fiber.
The detection of metal ions by optical fiber is advantageous as compared to that performed by use of electrochemical techniques, since the probe is miniaturized and no effects of the ionic strength nor of the medium conductivity occur.The method is simple, the detection is done in situ, at ambient temperature and under atmospheric pressure; only source of light, optical fiber and detector are required. 122omplexing properties of chromogenic calixarene 85, bearing two azo moieties towards Cd 2+ ion has been studied by UV/Vis spectroscopy.The formation of the complex occurs in polar solvents like acetonitrile, acetone, methanol and DMF, but not in less polar solvents like CHCl 3 or THF.The most suitable solvent showed to be acetonitrile, ensuring efficient complexation without formation of aggregates.The obtained complexes have 1:1 stoichiometry. 123RKAT USA, Inc.

Calixarene complexes with mercury ions
Mercury is a toxic metal dangerous for human health, its contamination is widespread in the environment.Mercury pollution arises from gold mining and combustion of fossil fuels, as well as from volcanic emissions.A growing attention is paid today to the detection of mercuric ion in the environment and in biological samples. 124Calixarene complexes with mercury ions are a topic of numerous works. 71,125,126t was observed that thiohexyl oligophenylene substituted calixarenes 86a,b form 1:1 complexes with Hg 2+ and with Ag + ions.The association constants were estimated by use of fluorescent titrations in CHCl 3 /MeOH, this value for Hg 2+ •86a being higher than that for ARKAT USA, Inc.
Hg 2+ •86b. 127The 1 H NMR spectroscopy results show that Hg 2+ or Ag + ion is cooperatively bound by the two opposite sulfur atoms of 86a leading to conformationally stable pinched cone structure.It is noteworthy that the binding affinities of 86a,b toward Hg 2+ and Ag 2+ ions are stronger than those of the corresponding monomeric units due to the cooperation effect of the proximate fluoroionophores.
In the study of complexing properties of calixarenes bearing two dansyl groups it was observed that 87 is sensitive towards Hg 2+ ions and exhibits high selectivity.Having in view these properties of 87, its analogue 88, showing an additional grafting ability on the silica surface was designed.
In order to build an optical sensor device, calixarene 88 was grafted on SBA-15 mesoporous silica and the fluorescence properties of the obtained material 88•SBA-15 have been investigated. 128The detection limit is determined by a strong quenching of fluorescence upon the Hg 2+ complexation.It was established that 88•SBA-15 reversibly detects Hg 2+ ions in water and does not interfere with K + , Ca 2+ , Zn 2+ and Cd 2+ ions; it should be pointed out that the response is rapid.
It was found that the complexing ability of calixarene 89 toward metal cations is higher in MeCN than in DMF and MeOH.In MeCN 89 recognizes Hg 2+ over Li + , Na + , Ag + , Ca 2+ , Cu 2+ and Pb 2+ ions, while in DMF and in MeOH 89 interacts only with Hg 2+ and Ag + .In all cases the 1:1 complexes are formed. 129he study of the strength of complexation of 89 with Hg 2+ and Ag + in dependence of solvent has shown that for 89 and Hg 2+ the strength of complexation decreases in the order MeCN > DMF > MeOH while for 89 and Ag + this sequence is MeOH > DMF > MeCN.Due to the inclusion of MeCN in the hydrophobic cavity of 89, the hydrophilic cavity of the resulting complex 89•MeCN becomes more receptive to include metal cations than the cavity of free 89; this behavior results from the allosteric effect. 129ne should mention that in MeCN 89 does not include Cd 2+ ion, while 80a does; this behavior is explained by the fact that the cavity of 80a is larger than that of 89 due to higher electrostatic repulsion of pendant arms of 80a resulting from the presence of four carbonyl groups, therefore the cavity of 80a is more open and, as a result, more able to receive Cd 2+ ion than the cavity of 89. 129he complexation of calixarenes 89 and 90 toward Hg 2+ and Ag + ions in a series of solvents have been investigated.The obtained thermodynamic data were used to assess the effect of solvation of these compounds on their complexing properties. 98,130olubilities and derived Gibbs energies of solutions of 89 and 90 in various solvents have been reported.Solvation of 89 and 90 in one medium relative to another was analyzed from their standard transfer Gibbs energies using acetonitrile as the reference solvent.The standard solution enthalpies were determined for mercury and silver salts in acetonitrile, methanol and DMF.These data have been used to derive their transfer enthalpies from one medium to another.
It was found that the extent of complexation of 89 and 90 with metal cations in different media is not only controlled by the solvation changes of the free cation in various solvents, but also is controlled by the solvation of the ligand and of the metal-ion complex in these solvents.The selectivity of 90 for Hg 2+ relative to Ag + in MeCN is reversed in MeOH and lost in DMF.
Solubility data were used to calculate the standard Gibbs energies of solution.For 89 the strength of solvation decreases in the order: n-BuOH > DMF > EtOH > MeCN > PC > MeOH.For 90 this sequence is as follows: n-BuOH > DMF > MeCN > EtOH > PC > MeOH (PC = propylene carbonate).It was found that the solvation of 89 is higher than that of 90. 130n the study of calixarenes bearing arylazo and allyl groups at the wide rim, forming complexes with transition metal ions it was found that 91 -93 show metal-chelating properties.Calixarenes 91a-93b are very good chromogenic ionophores, especially for Hg 2+ ; the complexation of Hg 2+ by 91b-93b in methanol/chloroform is visible to the naked eye. 131,132The narrow rim modification of 91b,c affords chromoionophores 94b,c which may also be used in metal ion detection. 131One should mention that synthesized in the reported work compounds 92-94 are colored (92a, 93a orange; 92b, 93b, 94b yellow and 92c, 94c red).
Calixarenes 95-98 are yellow; they form 1: 1 complexes with Hg 2+ ion, this process being connected with color changes.The association constants of investigated receptors with Hg 2+ decrease in the order 95>96>97a>98a. 133The p-allyl and p-methoxyphenylazo groups take part in the recognition of Hg 2+ ion; calixarene 95, containing three p-methoxyphenylazo groups binds Hg 2+ stronger than 96 containing two p-methoxyphenylazo groups, as it is seen in the association constant of 95 higher than that of 96.Calixarenes 95 and 96 have one and two allyl groups, respectively, whereas 97a and 98a have one and two thioacetoxypropyl groups, respectively, therefore the binding of Hg 2+ ion by 95 and 96 is stronger than in the case of 96a and 98a.The possible binding modes for Hg 2+ ·95 and Hg 2+ ·96 have been proposed.
5][136][137] Fluorescent chemosensors are mainly based on photoinduced electron transfer (PET), metal-ligand charge transfer (MLCT), intramolecular charge transfer (ICT), 138,139 excimer/exciplex formation, 140,141 imine isomerisation 142 and fluorescence resonance energy transfer (FRET). 143,144t should be pointed out that FRET is today of a great interest for possibility of its use in optical therapy and in cell physiology, as well as in a selective sensing toward molecular or ionic species. 145FRET is an excited-state energy interaction between two fluorophores in which an excited energy donor transfers energy to an energy acceptor without photoemission.Many chemosensors are based on a FRET signal mechanism. 143,144RKAT USA, Inc.
In the study of calixarenes acting as chemosensors towards cations and anions, a calixarene-based chemosensor 99 which functions as Hg 2+ -induced FRET from the pyrenyl excimer (energy donor) to rhodamine unit (energy acceptor) was reported. 124,146,147Chemosensor 99 is a N-tripodal species consisting of two calixarene units, each bearing one pyrenyl group and a rhodamine B unit in a spirolactam form.The pyrenyl groups of neighboring calixarene units are planar, involving a π-π stacking interaction between them.The calixarene units of 99 are flexible, this fact can easily lead to the excimer emission.The excimer emission of pyrenyl and the fluorescence absorption of ring-opened rhodamine have a spectral overlap enabling the functionality of 99 as a FRET chemosensor if the pyrenyl unit is excited.
Addition of Hg 2+ ion to the MeCN solution of 99 leads to the ring opening of the rhodamine spirolactam moieties with a FRET−ON signal mechanism and the energy transfer from pyrenyl excimer (energy donor) to rhodamine (energy acceptor).It is noteworthy that in the absence of Hg 2+ ion, the energy transfer is impossible due to the spirolactam structure of the rhodamine unit (FRET−OFF).Addition of Hg 2+ to the solution of 99 results in the formation of the 1:1 complex Hg 2+ ·99 and in a considerably enhanced fluorescence emission (FRET−ON).

Conclusions and future outlook
The above review, albeit describing only selected examples, sheds some light on the chemistry of calixarene metal complexes.This field of science develops rapidly due to promising properties of such complexes in chemistry as well as in other research areas; [148][149][150][151][152][153][154] here their use as sensors for metal ions 26,27 and as catalysts 22 deserves a special attention.One should point out formation of calixarene complexes with lanthanides [155][156][157] and actinides [158][159][160] in view of the importance of radioactive waste disposal for the environmental protection.Due to the technical progress, one complexes [Cu 2+ ·(R)-12] and [Cu 2+ ·(S)-12] may be used as binary hosts to recognize carbohydrates.The fluorescent titration results have shown that they selectively recognize D-(+)gluconic acid δ-lactone over other carbohydrates, such as D-(+)xylose, D-(-)ribose, 2-deoxy-D-ribose, D-(-)arabinose and D-(+)glucose.

47 ,
consisting of two different species: the dicationic component A and the neutral component B. In the dicationic component A the gold(I) centers have linear S-Au-S coordination, with chelation of each gold(I) center by two sulfur atoms of the thiophosphinate groups.The anions of 47 are [AuCl 2 ]⎯.Thus the dicationic component is analogous to the dications in disilver and digold (I) complexes 44 and 45.The neutral component B has two linear S-Au-Cl units, one at each end of the molecule of 47; two sulfur atoms are noncoordinated.In both components the resorcinarene molecule has a boat conformation in which the thiophosphinate-derivatized arene rings are in the flattened position, and the acylated rings stand upright.

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