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Tunable Zn2+ and Cu2+ calixarene complexes aspolytopic building blocks for guest recognitionCarmela Bonaccorso a , Francesca Nicoletta a , Valeria Zito b , Giuseppe Arena a , DomenicoSciotto a & Carmelo Sgarlata aa Dipartimento di Scienze Chimiche , Università degli Studi di Catania, Viale A. Doria 6 ,95125 , Catania , Italyb Istituto di Biostrutture e Bioimmagini, UOS Catania, CNR, Viale A. Doria 6 , 95125 ,Catania , ItalyPublished online: 22 Aug 2013.

To cite this article: Supramolecular Chemistry (2013): Tunable Zn2+ and Cu2+ calixarene complexes as polytopic buildingblocks for guest recognition, Supramolecular Chemistry, DOI: 10.1080/10610278.2013.824083

To link to this article: http://dx.doi.org/10.1080/10610278.2013.824083

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Tunable Zn21 and Cu21 calixarene complexes as polytopic building blocks for guest recognition

Carmela Bonaccorsoa, Francesca Nicolettaa, Valeria Zitob, Giuseppe Arenaa, Domenico Sciottoa and Carmelo Sgarlataa*

aDipartimento di Scienze Chimiche, Universita degli Studi di Catania, Viale A. Doria 6, 95125 Catania, Italy; bIstituto di Biostrutture eBioimmagini, UOS Catania, CNR, Viale A. Doria 6, 95125 Catania, Italy

(Received 16 May 2013; final version received 5 July 2013)

Two calix[4]arene receptors containing two or four 3-pyridylmethyl pendants at the lower rim and fixed in the cone

conformation have been synthesised. Their complexes with Cu2þ and Zn2þ have been studied via UV–vis absorption

spectroscopy in acetonitrile; 1H NMR spectra provide further insights into the binding sites and show that the macrocycles

suitably arrange their structure to meet the coordination features of the metal ion. Both ligands form with both Cu2þ and

Zn2þ multiple complex species with large stability. The large binding constant values allow to drive the system to the

formation of the desired species by appropriately selecting the metal/ligand ratio. The host–guest binding properties of

N-methylpyridinium (NMPy) with both the free ligands and their metal complexes have been investigated by 1H NMR

spectroscopy in CDCl3/CD3CN (9:1, v/v). The metal ions do not negatively affect the affinity of the calixarenes for NMPy

and also allow for the formation of systems with multiple cavities available for guest inclusion, thus paving the way to new

heteroditopic receptors for molecular recognition in solution.

Keywords: calixarenes; Cu2þ; Zn2þ; metal complexes; guest binding; polytopic receptors

1. Introduction

The design of synthetic receptors able to promote the

selective binding, transformation or transport of charged

and neutral species or biological substrates in solution has

stimulated increasing interest in the last decades due to their

potential application in technological processes as well as

in the modelling of natural systems (1, 2). Metal complexes

of macrocyclic ligands may act as metallo-receptors for

neutral or charged (organic and inorganic) species (3) and

can promote the catalytic transformation of suitable

substrates (4). Calixarenes (5) are an extremely versatile

class of macrocyclic receptors able to complex a variety of

metal ions (6) as well as to selectively recognise both

neutral and charged guests in solution (7).When ametal ion

is complexed, the simultaneous presence of a metal centre

and a tridimensional cavity within the same backbone

provides a multivalent system (8) able to bind small

molecules through the unoccupied sites of the metal ion

coordination sphere and/or to include suitable substrates

into the cavity of the macrocycle. Features, such as ligand

conformation, type and position of the donor atoms, play a

significant role in the binding efficiency of calixarenes

towards the targetmetal ions. Receptors functionalisedwith

N-heterocyclic binding units, which can act cooperatively

in coordinating transitionmetals, allow for the combination

of the complexation properties of nitrogen ligands with the

hydrophobic and confined environment provided by the

cavity, thus yielding sophisticated metalloenzyme mimics

(9) or versatile polytopic receptors for multiple guest

binding (10). Several examples of macrocyclic systems

containing picolyl (11), imidazolyl (12), bipyridyl (13) and

phenanthrolyl (14) functionalities have been described.

We have reported on some 2,20-bypyridyl-functionalisedcalix[4]arenes in the 1,3 alternate conformation and have

investigated their complexing properties towardsmetal ions

in organic solvent (15), water (16) and self assembled

monolayers anchored on gold surfaces (17).

With the aim of designing a heteroditopic host

molecule having two or more binding subunits within

the same macrocyclic platform, suitable for the complexa-

tion of both metals and small molecules, we have

synthesised two new calix[4]arenes functionalised with

two and four 3-pyridylmethyl pendant groups at the lower

rim and fixed in the cone conformation (BPC and TPC,

Scheme 1). The ability of these derivatives to interact with

metal cations is largely dependent on the position of the

nitrogen atoms of the pyridyl ring (18) and, although the

3-pyridylmethyl moieties should ensure a more efficient

‘docking’ of the N-donor atoms close to the central metal

ion, only a limited number of studies have been carried out

on these derivatives.

In this work, we report on the complexing properties of

the bis- and tetra-3-pyridylmethyl calixarenes BPC and

TPC towards Cu2þ and Zn2þ in acetonitrile via UV–vis

q 2013 Taylor & Francis

*Corresponding author. Email: sgarlata@unict.it

Supramolecular Chemistry, 2013

http://dx.doi.org/10.1080/10610278.2013.824083

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absorption measurements; for the latter ion, 1H NMR

experiments have also been performed. Once the

speciation picture has been undoubtedly defined, the

more promising/interesting metal complexes have also

been employed as ditopic hosts for the inclusion of the

N-methylpyridynium cation (19), chosen as a model guest

to investigate the effect of the metal complexation as well

as of the complex stoichiometry on the molecular

recognition process.

2. Results and discussion

2.1 Synthesis of the pyridyl-substituted calixarenes

The synthesis of calix[4]arene derivatives containing four

and two pyridin-3-ylmethoxy moieties at the lower rim

(TPC and BPC, respectively) was carried out according to

the procedure reported for the selective O-alkylation of the

macrocycle (Scheme 1) (20). The reaction of compound 1

with 3-(chloromethyl)pyridine hydrochloride in the pre-

sence of the proper base and different molar ratio between

the reactants allowed for either the exhaustive tetra-O-

alkylation or the regioselective bis-O-alkylation of the

calixarene scaffold.

The 1H NMR spectrum of TPC shows that the protons

on the pyridine units and the aromatic cavity of the

calixarene resonate at low field (Figure 1(a)), whereas no

signals are detected for the phenolic group of the lower rim

of the macrocycle. The signal at 4.94 ppm is assigned to

the OZCH2ZPy methylene and the typical AX system at

3.95 and 2.85 ppm to the bridging methylene protons of the

Scheme 1. Synthesis of the tetra- and bis-pyridyl derivatives of calix[4]arene.

Figure 1. 1H NMR spectra (500MHz, 278C, CDCl3) of the (a) tetra-pyridyl calix[4]arene TPC and (b) bis-pyridyl calix[4]arene BPC.

C. Bonaccorso et al.2

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calixarene scaffold. The above findings indicate that an

exhaustive O-alkylation has occurred at the lower rim and

the calixarene has a blocked cone conformation with C4v

symmetry. Going from lower to higher fields, Figure 1(b)

shows the signals of the pyridyl moieties of the bis-

functionalised calixarene BPC, a multiplet and a pair of

doublets due to the aromatic protons of the cavity and a

singlet at 7.57 ppm ascribed to phenolic groups of the

lower rim which has not undergone O-functionalisation.

The signal of the OZCH2ZPy methylene (5.08 ppm) and

the AX system at 4.26 and 3.38 ppm confirm that the

calixarene is blocked in the cone conformation with C2v

symmetry as a consequence of regioselective 1,3-bis-O-

alkylation.

2.2 Cu21 and Zn21 complex species

The complex formation of TPC and BPC with both Cu2þ

and Zn2þ was studied by UV–vis absorption titrations

in acetonitrile at an ionic strength of 0.1M (NaClO4).

The addition of NaClO4 to TPC or BPC solutions did not

cause any detectable change in the UV–vis absorption

spectrum of the free calixarene thus ruling out any sodium

interaction with both ligands and indicating that NaClO4

may suitably be used as the background electrolyte.

Increasing amounts of copper or zinc perchlorate were

added into the cell containing the ligand solution and

spectra were recorded after each addition. Unfortunately,

safer anions, such as tetrafluoroborate, could not be used

since the anion absorbs significantly within the spectral

region (200–350 nm) selected for the refinement of the

complex formation constants. Titration curves for the M–

L systems (M ¼ Cu2þ, Zn2þ; L ¼TPC, BPC) are shown

in Figures 2 and 3.

Both free TPC and BPC show two absorption bands

(having different intensity) in the UV region: one of the

bands is centred at 226 nm for both ligands, while the other

at 261 and 268 nm for the tetra and bis-pyridyl derivatives,

respectively. Both bands are due to the p–p transitions of

the phenyl and pyridyl moieties of the calixarene. The

addition of copper or zinc solutions induced a remarkable

Figure 3. Typical UV–vis absorption titration curves for the (a) Zn2þ–TPC and (b) Zn2þ–BPC systems in CH3CN at 258C andI ¼ 0.1M (NaClO4). The molar ratio plots are shown in the insets. M/L, metal/ligand ratio.

Figure 2. (Colour online) Typical UV–vis absorption titration curves for the (a) Cu2þ–TPC and (b) Cu2þ–BPC systems in CH3CN at258C and I ¼ 0.1M (NaClO4). The molar ratio plots are shown in the insets. M/L, metal/ligand ratio.

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change of the free ligand UV absorption spectrum and, in

particular, caused a hyperchromic shift of the absorption

band centred at 261 or 268 nm, respectively, indicating the

formation of complex species in solution. The weak

absorption of the free metal never interferes with the UV

absorption bands of the ligands. No charge-transfer bands

were detected in the concentration range employed for the

titrations; such transitions are significant only when

working at concentrations 10 times larger than those

chosen in this study.

The stoichiometries of the Cu2þ–L and Zn2þ–L main

species (L ¼TPC or BPC) were preliminarily figured out

by the mole ratio method (insets of Figures 2 and 3). Plots

of the absorbance versus the equivalents of metal added

show a clear break at M/L ¼ 1 for both the Cu2þ and

Zn2þ–TPC systems (insets of Figures 2(a) and 3(a)).

Surprisingly, two sharp inflections are observed in the plot

when roughly half and one equivalent of either Cu2þ or

Zn2þ are added to a BPC solution (insets of Figures 2(b)

and 3(b)) suggesting the presence of more than one

complex species in solution (likely ML and ML2). The

addition of copper or zinc up to M/L values greater than

one did not cause remarkable effects on the absorption

spectra (and, therefore, on the slope of the molar ratio

plots), thus ruling out the existence of species with a

number of metal ions greater than one.

A multiwavelength analysis of the spectral data

(240–350 nm) was carried out with a software (Hyper-

quad) (21), which refines data from different titrations and

allows for the accurate determination of the species

forming in solution and their stability constants. logK

values obtained with this method are reported in Table 1

and show that both Cu2þ and Zn2þ form with TPC and

BPC very stable complexes having different stoichi-

ometries. Many species and combinations thereof were

offered to the software but the data analysis invariably

converged to the species and values reported in Table 1.

The large affinity constants are at the edge of determin-

ability; these values may be determined with a certain

degree of accuracy only when appropriate (small)

concentrations of the reactants and proper experimental

conditions (sensitive dispenser, small injection volumes of

the titrant, appropriate selection of the wavelengths,

multiwavelength treatment of the data) are chosen.

The large stability of the mononuclear complexes

of TPC may be ascribed to the favourable arrangement

of the four pyridyl arms which satisfy the coordinative

requirements of the central metal ion by operating in a

cooperative way. The complexation of a second ion

implies that each metal ion is bound to two pyridyl

moieties and the metal coordination sphere can be

completed by solvent molecules. For [BPCZnBPC]2þ

the geometric requirements of Zn2þ are fulfilled by the

coordination of two pyridyl moieties from each calixarene

unit. It is well known from the literature that in a weakly

solvating solvent as CH3CN, Zn2þ exists as [Zn

(CH3CN)6]2þ; the coordination of pyridine or pyridine

derivatives (e.g. 3-methyl pyridine or 4-methyl pyridine)

successively replaces solvent molecules leading finally to

a tetra-coordinated complex (22). In [BPCZnBPC]2þ such

an arrangement does not involve any interaction of the

metal ion with the cavity leaving the two cavities ‘free’

and ready for further interactions.

Figure 4 shows the species distribution diagram for the

Zn2þ–TPC and Zn2þ–BPC systems (the species

distribution for the copper complexes is reported in Figure

S1 of Supplementary Information, available online).

As expected for a species having large stability constants,

the main species reach their maximum of formation at the

expected stoichiometric ratio.

The real advantage of dealing with complexes with

such relatively large stability constants is that a metal

complex species of a desired stoichiometry can be easily

obtained in solution by simply choosing the appropriate

ratio between the metal and the ligand. For example,

Figure 4 shows that the only existing complex species for

TPC at a M/L ¼ 1 is [ZnTPC]2þ as much as when mixing

Zn2þ and BPC at M/L ¼ 0.5 [ZnBPC2]2þ is the only

species that forms.

The existence of the metal complexes of both TPC and

BPC was further confirmed by ESI-MS spectra which

showed peaks attributable to the main species reported in

Table 1 (Figures S2 and S3 of Supplementary Information,

available online).

These findings make the above metal complexes

having tunable stoichiometry and, consequently, one or

more ligand cavities available, good candidates as

polytopic hosts for molecular recognition.

2.3 NMR studies on the Zn21 complexes1H NMR study of TPC or TBC solutions containing Zn2þ

at different metal-to-ligand ratios were carried out in

CD3CN to obtain further insights on the binding sites of

the ligands and on structural and conformational proper-

ties of the complexes that cannot be obtained from UV–

Table 1. Stability constants for the complex formation of Cu2þ

and Zn2þ with TPC and BPC in CH3CN at 258C and I ¼ 0.1M(NaClO4).

Reaction logb

Cu2þ þ TPC X [CuTPC]2þ 7.7(2)2Cu2þ þ TPC X [Cu2TPC]

4þ 11.1(2)Zn2þ þ TPC X [ZnTPC]2þ 6.95(5)2Zn2þ þ TPC X [Zn2TPC]

4þ 11.77(9)

Cu2þ þ BPC X [CuBPC]2þ 5.73(8)Cu2þ þ 2BPC X [CuBPC2]

2þ 11.3(1)

Zn2þ þ BPC X [ZnBPC]2þ 7.52(7)Zn2þ þ 2BPC X [ZnBPC2]

2þ 13.12(8)

C. Bonaccorso et al.4

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vis absorption data. No chemical shift change was

observed when increasing amounts of Naþ were added

to the ligand solution, thus confirming that this cation does

not interact with the pyridyl-derivatised calixarenes.

Upon addition of increasing amount of Zn2þ to a TPC

solution, NMR resonances turn into broader signals

indicating that the exchange between the free and

complexed ligand occurs at a slower rate on the NMR

time scale (Figure 5). The binding of the metal cation

definitely affects all the signals of the NMR spectrum of the

free ligand.Whenone equivalent of Zn2þ is added toTPC, i.

e. in the conditions in which only [ZnTPC]2þ forms,

chemical shift changes are observed for the pyridine

moieties and the methylene protons of the O–CH2–Py

groups providing a strong evidence that the metal is in the

proximity of the nitrogen atoms of the binding arms of the

calixarene. The bridging equatorialmethylene protons (Ar–

CH2–Ar) undergo an upfield shift resulting in a decrease of

theDd between the two signals of theAX system (from 1.16

to 0.88 ppm) which indicates that the ligand re-arranges in a

more symmetrical cone conformation upon complexation

(23). Further addition ofZn2þ (up to two equivalents) causes

small but still relevant changes in the NMR spectra as

expected for the binding of a second metal ion at the lower

rim. The protons of the free pyridyl moieties are strongly

affected upon metal complexation as the coordination of

Zn2þ deeply alters the chemical environment of these

binding units; the complexation of a secondmetal ion by the

samepyridyl groups,which are already engaged in ametal–

ligand binding, does not remarkably change the chemical

features and NMR signals of these ligand units. Interest-

ingly, the signals of the methylene protons of the O–CH2–

Py groups andAr–CH2–Ar bridges aswell as protons of the

calixarene scaffold experience small but still detectable

changes, namely an upfield or downfield shift, depending on

the complexation of one or two metal ions (Figure 5). The

formation of species with higher stoichiometry is ruled out

as no detectable chemical shift change is observed at larger

M/L ratio, thus confirming the speciation model found out

by UV–vis absorption titrations.

Addition of Zn2þ affects most of the proton chemical

shifts of the BPC NMR spectrum (Figure 6). Unlike TPC,

only signals due to the methyl-pyridine moieties and the

bridging axial methylene protons become broader upon

complexation (as a result of the fast exchange between the

free and complexed ligand), whereas no significant change

is observed for the aromatic protons of the macrocyclic

cavity and the bridging equatorial methylenes. Likely, due

to the increased flexibility of the bis-substituted calixar-

ene, the complexation of the metal has an effect only on

the signals of the moieties that are actively involved in the

coordination or close to the binding site.

When half equivalent of Zn2þ is added to a BPC

solution, i.e. when the formation of [ZnBPC2]2þ prevails,

significant chemical shift changes are experienced by the

pyridine, the O–CH2–Py methylene, the phenolic OH and

the bridging equatorial methylene protons supporting that

the complexation of the metal occurs at the pyridine

nitrogen atoms at the lower rim of the calixarene. No

change is observed for the signals of the aromatic protons

of cavity, thus the complexation of the metal by the two

calixarenes in the [ZnBPC2]2þ species has to take place

only by a tail-to-tail interaction between the two pairs of

pyridyl units placed at the lower rim of each macrocycle.

Further addition of Zn2þ causes small but still relevant

changes in the NMR spectra, whereas no changes are

observed at M/L ratios greater than one, further supporting

UV–vis absorption findings. As found for TPC, the Ddvalue between the two signals of the AX system due to the

bridging methylene protons decreases by about 0.2 ppm

upon complexation, suggesting that BPC assumes a more

symmetrical cone conformation in both the complex

species that form. Model structures of the metal complexes

of both TPC and BPC with Zn2þ are shown in the

Figure 4. (Colour online) Species distribution diagram for the (a) Zn2þ–TPC and (b) Zn2þ–BPC systems. CTPC ¼ 8 £ 1025M,CBPC ¼ 1 £ 1024M.

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supplementary material (Figure S4 of Supplementary

Information, available online).

2.4 Host–guest interaction

Since the spectrophotometric analysis reveals that the

stoichiometry of the metal complex species studied in this

work may be easily modulated in solution by simply

selecting the appropriate ligand and the ratio betweenM and

L,TPC andBPCwere used to exploreguest encapsulation in

solution. Theproper choice of themetal and its concentration

allows for the formation of hosts which may have one

(e.g. [ZnTPC]2þ) or two (e.g. [ZnBPC2]2þ) tridimensional

Figure 5. (Colour online) Change in the 1H NMR spectra of TPC in CD3CN upon addition of Zn2þ. CTPC ¼ 5 £ 1024M. M/L, metal/ligand ratio.

C. Bonaccorso et al.6

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cavities available for guest recognition. Noticeably, in the

latter case, the double-cavity host is held together by a simple

non-covalent metal-coordination bond between two calixar-

ene ligands.

Information about the inclusion properties of

[ZnTPC]2þ and [ZnBPC2]2þ, as well as of the free

ligands TPC and BPC, towards the N-methylpyridinium

(NMPy) cation has been obtained by 1H NMR titrations

in CDCl3/CD3CN (9:1, v/v), due to the small solubility

of the Zn2þ complexes in pure CDCl3. All NMR

spectra show time-averaged signals for the free and the

complexed species. Pure CD3CN cannot be used as

Figure 6. (Colour online) Change in the 1H NMR spectra of BPC in CD3CN upon addition of Zn2þ. CBPC ¼ 1 £ 1023M. M/L, metal/ligand ratio.

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molecules having relatively acidic groups, such as CD3,

may act as guests and compete for the ligand cavity;

consequently, studies with similar systems have been

mostly carried out in chloroform (24). The inclusion into

the apolar cavity of calix[4]arenes of small neutral organic

guests with acidic CH groups has been also reported in

water (25). The flat aromatic N-methylpyridinium cation,

which has a non-symmetrical charge distribution on the

heterocyclic ring, was chosen as a model guest to

preliminarily examine the molecular recognition capa-

bility of these metal–ligand hosts.

The addition of the guest does not affect the NMR

signals of free TPC and BPC; however, the chemical

shift changes experienced by NMPy signals in the

presence of varying amounts of either TBC or BPC

imply that a guest recognition/interaction process occurs

in solution.

When NMPy is initially added to the [ZnTPC]2þ

complex, the aromatic protons of the calixarene scaffold,

the bridging equatorial and the OZCH2ZPy methylene

protons undergo a remarkable shift implying the

inclusion of the guest into the host cavity (Figure S5 of

Supplementary Information, available online). At larger

guest/host ratio, the pyridyl moieties, the bridging

equatorial and OZCH2ZPy methylene protons of the

host still experience a slight change suggesting that

probably one more molecule of guest might weakly

associate to the pyridyl binding arms at the lower rim of the

calixarene (26). CH–p and p–p interactions between the

guest and the aromatic rings of the host are the driving

forces for the whole association/recognition process.

The addition of NMPy to the [ZnBPC2]2þ species,

which possesses two cavities available for guest encapsula-

tion, causes broadening of the cavity aromatic proton as

well as the bridging axial methylene proton signals indi-

cating that an inclusion event is occurring (Figure S6 of

Supplementary Information, available online). Interest-

ingly, when about two equivalents of guest are added, the

resonances of the pyridyl arms at the lower rim undergo a

noticeable shift and become broader while the calixarene

backbone signals (ArH and axial ArZCH2ZAr) become

sharp again. The overall change observed for the axial

bridging methylene signals further supports the larger

flexibility of the BPC metal complex. The above findings

suggest that two guest molecules may interact with the

[BPCZZnZBPC]2þ host by inclusion in each of the

cavities provided by the tail-to-tail structure of the metal

complex. The association of a second guest molecule could

not occur at the lower rim of the two calixarenes (i.e. at the

Py2ZZnZPy2 linkage) since the pyridyl units of each BPC

ligand are entirely engaged in the coordination of the

central metal ion. Model structures for the NMPy–

[ZnTPC]2þ and NMPy–[ZnBPC2]2þ systems are reported

in Figure 7.

Binding isotherms (Figure 8) show that, as the NMR

titration proceeds, only the NCH3 and the aromatic Ho

proton signals of the guest shift upfield, compared to

the free guest, which clearly indicates that NMPy

interacts with all the hosts investigated. The aromatic

charged guest might be included into the cavity through

cation–p, CH–p and p–p interactions (27). The

observed Dd values (shielding effect due to the host–

guest interaction) are larger when the host is a metal

complex (Figure 8(b) and (d)) rather than a free ligand

(Figure 8(a) and (c)).

The binding constants for the different NMPy–host

systems (where the host is free TPC/BPC or the proper

Zn2þ complex) were determined by analysing the change

of the chemical shifts of the guest as a function of the

host–guest ratio (Table 2).

The affinity of free ligands and the metal complexes

for NMPy is comparable and this shows that the presence

of the metal center does not negatively affect the

recognition of the guest by the calixarene. Remarkably,

a HG2 species was refined together with the HG species

when [ZnBPC2]2þ is employed as the host, further

supporting the idea that this receptor may successfully

offer two cavities for guest inclusion.

Figure 7. (Colour online) Model structures (MOPAC2009, PM6) for the NMPy guest interaction with (a) [ZnTPC]2þ and(b) [ZnBPC2]

2þ.

C. Bonaccorso et al.8

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3. Conclusions

Two new calix[4]arene derivatives having two (BPC) or

four (TPC) 3-pyridylmethyl pendants and blocked in their

cone conformation have been synthesised and character-

ised. The two structures form with both Zn2þ and Cu2þ

different complexes all of which possess relatively large

binding constants. While rendering the study of the metal–

ligand complexes in solution somewhat challenging, the

large binding constant values allow to drive the metal ion-

calixarene systems towards the formation of a desired

species by the appropriate selection of the metal-to-ligand

ratio. The coordination mode of the different species

(e.g. [ZnTPC]2þ and [BPCZnBPC]2þ), in turn, deter-

mines the number of calixarene cavities per metal ion that

may include appropriate guests such as N-methylpyridi-

nium. Binding constant values show that (i) the presence of

the metal ion does not reduce the guest recognition

efficiency of the ligands and (ii) [BPCZnBPC]2þ may

include two NMPy molecules in its cavities. All the above

opens new horizons towards new heteroditopic hosts for

molecular recognition in solution since the metal–

complex may be used as a building block for multiple

guest binding.

4. Experimental

4.1 Materials

All commercially available chemicals, deuterated solvents

as well as copper, zinc and sodium perchlorates were

purchased from Aldrich and were used without further

purification. 1-Methylpyridinium iodide, employed as a

guest, was obtained by reaction of pyridine with methyl

iodide. Acetonitrile for spectrophotometry (Uvasol;

Merck, Darmstadt, Germany) was employed for UV–vis

absorption titrations. Copper and zinc stock solutions were

prepared by dissolving the corresponding salt in

acetonitrile and titrating the resulting solutions with

Figure 8. (Colour online) Binding isotherms for the interaction of NMPy with (a) free TCP, (b) [ZnTPC]2þ, (c) free BPC and(d) [ZnBPC2]

2þ in CDCl3/CD3CN (9:1, v/v).

Table 2. Binding constants of NMPy guest with different hostsin CDCl3/CD3CN (9:1, v/v) at 258C.

Host logb1 logb2

TPC 3.2(2)BPC 3.1(2)[ZnTPC]2þ 3.13(3)[ZnBPC2]

2þ 2.67(2) 5.96(6)

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EDTA using murexide and eriochrome black T,

respectively (28). Safer counter ions (e.g. tetrafluorobo-

rates) could not be employed owing to their interfering

absorption. Caution: Perchlorate salts are shock and heat

sensitive and must be handled with care. Grade A

glassware was used throughout.

4.2 Synthesis of tetra(pyridin-3-ylmethoxy)-calix[4]arene (TPC)

A suspension of calixarene 1 (0.20 g, 0.47mmol), NaH

(60%, 0.85 g, 21.20mmol) and 3-(chloromethyl)pyridine

hydrochloride (1.55 g, 9.42mmol) in anhydrous DMF

(5ml) was stirred under nitrogen at 708C for 20 h. The

reaction mixture was quenched with water and the residue

was collected by filtration, dissolved in CH2Cl2 and

washed with an aqueous Na2CO3 solution. After removal

of CH2Cl2, the crude product was precipitated by methanol

and further purified by column chromatography (SiO2;

CH2Cl2/CH3OH, 95:5) to obtain pure TPC as a white

powder (0.27 g, 72%).1H NMR (CDCl3, 278C, 500MHz): d 8.61

(d, J ¼ 2.0 Hz, 4H, H8), 8.60 (dd, J1 ¼ 4.9 Hz,

J2 ¼ 2.0Hz, 4H, H5), 7.56 (d, J ¼ 7.7Hz, 4H, H6), 7.23

(dd, J1 ¼ 7.7Hz, J2 ¼ 4.9Hz, 4H, H8), 6.61–6.58 (m, 4H,

H1), 6.56–6.54 (m, 8H, H2), 4.94 (s, 8H, H4), 3.95

(d, J ¼ 13.3Hz, 4H, H3ax), 2.85 (d, J ¼ 13.3Hz, 4H, H3eq).13C NMR (CDCl3, 278C, 125MHz): d 154.24, 150.22,

148.79, 137.88, 134.84, 132.85, 128.57, 123.34, 123.04,

73.70, 31.18. ESI-MS:m/z 789 [M þ Hþ], 811 [M þ Naþ].UV–vis absorption (CH3CN, l261 nm): 1 11,760M

21 cm21.

4.3 Synthesis of bis(pyridin-3-ylmethoxy)-calix[4]arene (BPC)

A suspension of calixarene 1 (0.17 g, 0.40mmol), K2CO3

(1.77 g, 12.8mmol) and 3-(chloromethyl)pyridine hydro-

chloride (0.52 g, 3.2mmol) in anhydrous CH3CN (10ml)

was stirred under nitrogen at 508C for 20 h. The reaction

mixture was quenched with water and the residue was

collected by filtration, dissolved in CH2Cl2 and washed

with a Na2CO3 solution. The organic solvent was removed

under reduced pressure and the residue was purified by

column chromatography (SiO2; CH2Cl2 to CH2Cl2/

CH3OH, 95:5). The pure final product was obtained with

a 51% yield (0.13 g).1H NMR (CDCl3, 278C, 500MHz): d 8.77 (s, 2H, H8),

8.63 (d, J ¼ 5.0Hz, 2H, H11), 8.06 (d, J ¼ 7.7Hz, 2H,

H9), 7.57 (s, 2H, H6), 7.25 (dd, J1 ¼ 7.7Hz, J2 ¼ 5.0Hz,

2H, H10), 7.09 (d, J ¼ 7.6 Hz, 4H, H4), 6.83 (d,

J ¼ 7.6Hz, 4H, H2), 6.71 (t, J ¼ 7.6Hz, 4H, H1, H3),

5.08 (s, 4H, H7), 4.26 (d, J ¼ 13.0 Hz, 4H, H5ax), 3.38 (d,

J ¼ 13.0 Hz, 4H, H5eq).13C NMR (CDCl3, 278C,

125MHz): d 153.10, 151.51, 149.69, 148.78, 135.44,

133.00, 132.25, 129.21, 128.58, 127.79, 125.77, 123.93,

119.25, 75.71, 31.41. ESI-MS: m/z 607 [M þ Hþ], 629[M þ Naþ]. UV–vis absorption (CH3CN, l268 nm): 17275M21 cm21.

4.4 UV–vis absorption titrations

Spectrophotometric measurements were carried out at

258C in acetonitrile using an Agilent 8453 diode-array

spectrophotometer. Sodium perchlorate was used to adjust

the ionic strength. Increasing amounts of copper and zinc

perchlorate were added with a precision burette (1ml;

Hamilton, Reno, NV, USA) into the measuring cell

containing a known volume (usually 2ml) of the

calixarene solution (29). In addition, equilibration time

and data recording were controlled by a homemade

software. Time intervals for equilibration and reading were

systematically changed to avoid artifacts. Usually a

solution of the metal ion (CCu2þ ¼ 6.1 to 8.5 £ 1024M,

CZn2þ ¼ 9.0 £ 1024 to 2.6 £ 1023M) in acetonitrile was

added to a solution of either TPC or BPC (5.9 £ 1025 to

1.5 £ 1024M). About 60–70 scans were recorded for each

titration run. At least four independent runs were collected

for each metal–ligand system. UV–vis absorption spectra

were analysed with the software Hyperquad (21) which

allows for a multiwavelength treatment of the data and the

simultaneous refinement of data from different titrations.

The species distribution was calculated by using the

program Hyss (30).

4.5 NMR experiments

NMR experiments were run at 278C on a 500MHz

spectrometer (1H at 499.88MHz and 13C at 125.7MHz)

equipped with a pulse field gradient module (Z-axis) and a

tunable 5mm Varian inverse detection probe (ID-PFG);

chemical shifts (d) are expressed in ppm and are

referenced to residual non-deuterated solvent. NMR data

were processed using MestReC software.

The complex formation of both TPC and BPC with

Zn2þ was studied in CD3CN by adding different aliquots

of a stock solution of zinc perclorate into the NMR tube

containing the ligand (5 £ 1024 to 1 £ 1023M). NMR

spectra were recorded after each addition of the metal

solution (up to 4 equiv.). Changes in the chemical shifts

were measured using the free ligand as the reference.

NMR host–guest titrations were carried out by mixing

1-methylpyridinium (guest) with the proper host (free

TPC, free BPC, [ZnTPC]2þ, [ZnBPC2]2þ, respectively)

in the appropriate ratios in CDCl3/CD3CN, 9:1, v/v mixed

solvent. Stock solutions of the metal complexes (4 £ 1023

to 1 £ 1022M) were first prepared in pure CD3CN and

later diluted with CDCl3 due to poor solubility of both

[ZnTPC]2þ and [ZnBPC2]2þ in the latter solvent. Host

C. Bonaccorso et al.10

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concentration in the NMR tube was typically 4 £ 1024 to

1 £ 1023M for both the free calixarenes and the metal

complexes. The change of chemical shifts of the guest as a

function of the host/guest ratio (H/G) was analysed by

using HyperNMR (31).

Supplementary information (available online)

Experimental on ESI-MS spectra and molecular modeling,

species distribution diagram, ESI-MS spectra, NMR

spectra of host/guest titrations.

Acknowledgements

The authors gratefully acknowledge the partial support of theUniversity of Catania (Progetto d’Ateneo) and MIUR(Firb MERIT RBNE08HWLZ), and they are also grateful toDr Giuseppe Grasso for the ESI-MS spectra of metal complexes.

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Supramolecular Chemistry 11

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Carmela Bonaccorso, Francesca Nicoletta, Valeria Zito,

Giuseppe Arena, Domenico Sciotto and Carmelo Sgarlata

Tunable Zn2þ and Cu2þ calixarene complexes as

polytopic building blocks for guest recognition

1–12

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