Cation-π Interaction in complex formation between Tl+ Ion and Calix[4]crown-6 and some calix[4]biscrown-6 derivatives: Thallium-203 NMR, proton NMR, and X-ray evidence

Article abstract of DOI:10.1021/ic100097v

Metallocapped complexation of the thallium(I) ion with calix[4]crown-6 (1) and three different calix[4]biscrown-6 derivatives (2-4) has been investigated by a combination of ²⁰³Tl and ¹H NMR in a CD ₃CN/CDCl₃ (4:1 v/v) solution. The results clearly revealed the formation in solution of mono- and dithallium(I) complexes in which the metal cations are held in the ligands cavities close to the calix[4]arene ring. In addition, a solid state mononuclear complex between 1,3-calix[4]bis-o-benzo- crown-6 (3) and TlClO₄ was prepared, and its X-ray crystal structure was determined. The results of the structural data in solution and the solid state suggested that the calix[4]crown-6 derivatives considered provide π cavities as active sites for the complexation of thallium(I) ions.

Full text of DOI:10.1021/ic100097v

6874 Inorg. Chem. 2010, 49, 6874–6882
DOI: 10.1021/ic100097v
Cation-π Interaction in Complex Formation Between Tlþ Ion and Calix[4]crown-6
and Some Calix[4]biscrown-6 Derivatives: Thallium-203 NMR, Proton NMR, and
X-ray Evidence
Hedayat Haddadi and Naader Alizadeh*
Department of Chemistry, Faculty of Basic Sciences, Tarbiat Modares University,
P.O. Box 14115-175, Tehran, Iran
Mojtaba Shamsipur
Departments of Chemistry, Razi University, Kermanshah, Iran
Zouhair Asfari
ꢀ
Laboratoire de Chimie Analytique et Sciences Separatives, UMR 7178 IPHC-DSA, ECPM,
25 Rue Becquerel, 67087, Strasbourg Cedex, France
Vito Lippolis
ꢁ
Dipartimento di Chimica Inorganica ed Analitica, Universita degli Studi di Cagliari, S.S. 554 Bivio per Sestu,
09042 Monserrato (CA), Italy
Carla Bazzicalupi
ꢁ
Dipartimento di Chimica “Ugo Schiff”, Universita degli Studi di Firenze, Polo Scientifico, Via della Lastruccia
3, 50019 Sesto Fiorentino (FI), Italy
Received January 17, 2010
Metallocapped complexation of the thallium(I) ion with calix[4]crown-6 (1) and three different calix[4]biscrown-6
derivatives (2-4) has been investigated by a combination of 203Tl and 1H NMR in a CD3CN/CDCl3 (4:1 v/v) solution.
The results clearly revealed the formation in solution of mono- and dithallium(I) complexes in which the metal cations
are held in the ligands’ cavities close to the calix[4]arene ring. In addition, a solid state mononuclear complex between
1,3-calix[4]bis-o-benzo-crown-6 (3) and TlClO4 was prepared, and its X-ray crystal structure was determined. The
results of the structural data in solution and the solid state suggested that the calix[4]crown-6 derivatives considered
provide π cavities as active sites for the complexation of thallium(I) ions.
Introduction
with potassium.1-3 Because of poor NMR properties of
potassium(I) (including natural abundance, gyromagnetic
ratio, and chemical shift range) relative to those of thallium(I),
The thallium(I) ion has long been proposed as a suitable
mimic of alkali metal ions in biological systems due to its
chemical simiþlarity to group 1 þmetals and favorable size
˚
˚
(1.33 A for K vs 1.40 A for Tl ) and dehydration energy
(80 kcal mol-1 for Kþ vs 82 kcal mol-1 for Tlþ) comparison
(1) Pauling, L. The nature of the chemical bond and the structure of
molecules and crystals. An introduction to modern structural chemistry, 3rd
ed.; Cornell University Press: Ithaca, NY, 1960; p 644.
(2) Cox, B. G.; Schneider, H. Coordination and transport properties of
macrocyclic compounds in solution; Elsevier: Amsterdam, NY, 1992; p 420.
(3) Brown, I. D. Acta Crystallogr., Sect. B 1988, 44, 545.
*To whom correspondence should be addressed. Fax: þ98-21-82883455.
E-mail: alizaden@modares.ac.ir.
r
pubs.acs.org/IC
Published on Web 07/07/2010
2010 American Chemical Society

Article
Inorganic Chemistry, Vol. 49, No. 15, 2010 6875
many researchers have used thallium(I) NMR instead of
potassium(I) NMR for the analysis of binding sites and
determination of monovalent cation selectivities.4,5 Most bio-
macromolecules including phospholipids,6-10 carbohydr-
ates,11-14 proteins,15,16 and nucleic acids17-21 possess a structural
and/or functional requirement for monovalent cations.
Scheme 1. Calix[4]arenes Considered in This Paper
The synthesis of polynuclear complexes that can be studied
in solution is an important topic in view of the potential role
of such species in multi-metal-centered catalysis in both
biological and industrial reactions.22 Various enzymes,
including P1 nuclease, DNA polymerase I, phospholipase C,
and alkaline phosphatase, use the synergic action of two
metal centers for the hydrolytic cleavage of phosphate ester
bonds.23,24 205Tl NMR has been previously used as a suitable
probe to investigate the binding sites of interaction of the
thallium(III) ion with macrobiomolecules like transferrin,25
yeast pyruvate kinase (yPK),26 gramicidin,27 and nucleic
acids.4 Bertini et al. showed that 205Tl NMR is a convenient
probe in monitoring the occupancy of the two available binding
sites of transferrin, and they characterized the dithallium(III)-
transferrin and the monothallium(III) derivatives with bicarbo-
1
nate as a synergistic ion.25 Gill et al. used heteronuclear H-
205Tl NMR and direct 205Tl NMR detection to characterize the
binding of Tlþ to nucleic acid d(G4T4G4)2 in a site-specific
manner4
Calixarenes and related macrocycles have received con-
siderable attention for their host-guest chemistry, and their
ability to bind metal ions.28 There is currently increasing
interest in the synthesis and structural characterization of
new metallocalixarenes.29 Among calixarene-based ligands,
calix[4]biscrown ethers have received particular attention.
(4) Gill, L. M.; Scott, A.; Strobel, P. J.; Loria, J. J. Am. Chem. Soc. 2005,
127, 16723.
(5) Matthews, S. E.; Nicholas, H. R.; Vitor, F. M.; Drew, G. B.; Paul,
D. B. Inorg. Chem. 2003, 42, 729–734.
(6) Mattai, J.; Hauser, H.; Demel, R. A.; Shipley, G. G. Biochemistry
1989, 28, 2322.
(7) Tessier, C.; Quinn, P.; Koumanov, K.; Trugnan, G.; Rainteau, D.;
Wolf, C. Eur. Biophys. J. 2004, 33, 513.
(8) Toner, M.; Vaio, G.; McLaughlin, A.; McLaughlin, S. Biochemistry
1988, 27(19), 7435–7443.
(9) Coughlin, R. T.; Tonsager, S.; McGroarty, E. J. Biochemistry 1983,
22(8), 2002.
(10) Roux, M.; Bloom, M. Biochemistry 1990, 29, 7077.
(11) Moulik, S. P.; Khan, D. P. Carbohydr. Res. 1975, 41, 93.
(12) Kitamura, N.; Ikekita, M.; Sato, T.; Akimoto, Y.; Hatanaka, Y.;
Kawakami, H.; Inomata, M.; Furukawa, K. Proc. Natl. Acad. Sci. U.S.A.
2005, 102, 2796.
(13) Kano, K.; Kitae, T.; Shimofuri, Y.; Tanaka, N.; Mineta, Y. Chemistry
2000, 6, 2705.
(14) Lerner, L.; Torchia, D. A. J. Biol. Chem. 1986, 261, 12706.
(15) Hess, B.; Haeckel, R. Nature 1967, 214, 848.
(16) Nowak, T.; Mildvan, A. S. Biochemistry 1972, 11(15), 2819–2828.
(17) Shiman, R.; Draper, D. E. J. Mol. Biol. 2000, 302, 79.
(18) Basu, S.; Strobel, S. A. RNA 1999, 5, 1399.
(19) Basu, S.; Rambo, R. P.; Strauss-Soukup, J.; Cate, J. H.; Ferre-D’Amare,
A. R.; Strobel, S. A.; Doudna, J. A. Nat. Struct. Biol. 1998, 5, 986.
(20) Adams, P. L.; Stahley, M. R.; Kosek, A. B.; Wang, J.; Strobel, S. A.
Nature 2004, 430, 45.
ꢀ
Thuery et al. have reported a series of 1:1 and 2:1 complexes
of alkali metal ions with a 1,3-calix[4]biscrown ether.30 In
particular, calix[4]biscrown-6’s exhibited a high selectivity
toward the Tlþ ion against other monovalent ions such as
Agþ, Kþ, Naþ, and Csþ.31 In continuation of our research
activities on the complexation behavior of thallium(I) ion
with different macrocyclic ligands,32-35 in this work we have
used 203Tl and 1H NMR to examine the binding sites of four
different calix[4]arene mono- and bis-18-crown-6 derivatives
(Scheme 1) with the thallium(I) ion. The resulting data on
cation binding clearly revealed the multisite interaction of
(29) (a) Corazza, F.; Floriani, C.; Chiesi-Villa, A.; Rizzoli, C. Inorg.
Chem. 1991, 30, 4465. (b) Giannini, L.; Solari, E.; Zanotti-Gerosa, A.; Floriani,
C.; Chiesi-Villa, A.; Rizzoli, C. Angew. Chem. 1997, 109, 763. Giannini, L.;
Solari, E.; Zanotti-Gerosa, A.; Floriani, C.; Chiesi-Villa, A.; Rizzoli, C. Angew.
Chem., Int. Ed. Engl. 1997, 36, 763. (c) Acho, J. A.; Doerrer, L. H.; Lippard, S. J.
Inorg. Chem. 1995, 34, 2542.
(21) Conn, G. L.; Gittis, A. G.; Lattman, E. E.; Misra, V. K.; Draper,
D. E. J. Mol. Biol. 2002, 318, 963.
ꢀ
(30) (a) Thuery, P.; Nierlich, M.; Bressot, C.; Lamare, V.; Dozol, J. F.;
Asfari, Z.; Vicens, J. J. Incl. Phenom. 1996, 23, 305. (b) Asfari, Z.; Naumann,
ꢁ
(22) Seneque, O.; Campion, M.; Douziech, B.; Giorgi, M.; Riviere, E.;
ꢀ
C.; Vicens, J.; Nierlich, M.; Thuery, P.; Bressot, C.; Lamare, V.; Dozol, J. F. New
Journaux, Y.; Le Mest, Y.; Reinaud, O. Eur. J. Inorg. Chem. 2002, 2007.
(23) Strater, N.; Lipscomb, W. N.; Klabunde, T.; Krebs, B. Angew.
Chem., Int. Ed. Engl. 1996, 35, 2024.
ꢀ
J. Chem. 1996, 20, 1183. (c) Thuery, P.; Nierlich, M.; Lamare, V.; Dozol, J. F.;
Asfari, Z.; Vicens, J. Acta Crystallogr., Sect. C 1996, 52, 2729. (d) Thuery, P.;
Nierlich, M.; Asfari, Z.; Vicens, J. J. Incl. Phenom. 1997, 27, 169. (e) Thuery, P.;
M. Nierlich, M.; Bryan, J. C.; Lamare, V.; Dozol, J. F.; Asfari, Z.; Vicens, J.
J. Chem. Soc., Dalton Trans. 1997, 4191.
(31) Roper, E. D.; Talanov, V. S.; Butcher, R. J.; Talanova, G. G.;
Galina, G. Superamol. Chem. 2008, 20, 217.
(32) Alizadeh, N.; Shamsipur, M. J. Chin. Chem. Soc. 1998, 45, 241.
(33) Bordbar, M.; Shamsipur, M.; Alizadeh, N. Bioorg. Med. Chem. 2005,
13, 2253.
(34) Bordbar, M.; Shamsipur, M.; Alizadeh, N. J. Photochem. Photobiol.
A, Chem. 2006, 178, 83–89.
ꢀ
ꢀ
(24) Wilcox, D. E. Chem. Rev. 1996, 96, 2435.
(25) Bertini, I.; Luchinat, C.; Messori, L. J. Am. Chem. Soc. 1983, 105,
1347.
(26) Loria, J .P.; Nowak, T. Biochemistry 1998, 37, 6967.
(27) Hinton, J. F.; Young, G.; Millett, F. S. Biochemistry 1982, 21, 651.
(28) For reviews on calixarenes, see for example: (a) Gutsche, C. D.
Calixarenes; The Royal Society of Chemistry: Cambridge, U. K., 1989. (b) Vincens,
€
J.; Bohmer, V. Calixarenes: A Versatile Class of Macrocyclic Compounds; Kluwer:
Dordrecht, The Netherlands, 1991. (c) Gutsche, C. D. Prog. Macrocycl. Chem.
€
1987, 3, 93. (d) Bohmer, V. Angew. Chem. 1995, 107, 785. Angew. Chem., Int. Ed.
Engl. 1995, 34, 713. (e) Roundhill, D. M. Prog. Inorg. Chem. 1995, 43, 533.
Roundhill, D. M. Chem. Rev. 1997, 97, 1713.
(35) Alizadeh, N.; Bordbar, M.; Shamsipur, M. Bull. Chem. Soc. Jpn.
2006, 78, 1763.

6876 Inorganic Chemistry, Vol. 49, No. 15, 2010
Haddadi et al.
calix[4]crown-6 and three calix[4]biscrown-6 derivatives
toward the Tlþ ion.
atoms were refined anisotropically. All of the hydrogen atoms
were introduced at calculated positions and refined using a
riding model.
[Tl(3)(MeCN)(H2O)]ClO4. C58H65ClNO17Tl, Mw = 1287.93,
orthorhombic, Pbca (No.61), a=19.171(2), b=19.282(1), c=
Experimental Section
3
29.746(2) A, V = 10995.8(15) A , Z = 8, Fcalcd = 1.556 g cm-3
,
Chemicals. Deuterated acetonitrile and chloroform were
purchased from Armar Chemicals. Thallium(I) perchlorate
was prepared by treating 1 g of thallium(I) nitrate with 4 mL of
3 M perchloric acid, evaporating to dryness, and recrystallizing
three times from water and drying at 120 °C. All other materials
were of reagent grade from Merck and used as received. Calix[4]-
crown-6 (1), 1,3-calix[4]biscrown-6 (2), 1,3-calix[4]bis-o-benzo-
crown-6 (3), and 1,3-alternate calix[4]arene-1,3-crown-6;2,4-(1,2-
phenylene)-crown-6 (4) were prepared and purified as described in
our previous publications.36-38
˚
˚
2θmax = 49.42°, μ (MokR) = 3.060 mm-1, and colorless pris-
matic crystals (0.2 ꢀ 0.1 ꢀ 0.1 mm3). Empirical absorption
corrections (Tmin = 0.533, Tmax = 1.000), 28 475 measured reflec-
tions, and 8952 unique reflections (Rint = 0.0587) of which 5043
had [I > 2σ(I)]. At final convergence, R1 [I > 2σ(I)] = 0.0516,
wR2 (all data) = 0.1343 for 720 refined parameters, S = 0.920,
-3
˚
(Δ/σ)max = 0.007, and ΔFmax = 1.629 e A
.
X-ray crystallographic data in CIF format have been depo-
sited with the Cambridge Crystallographic Data Centre, CCDC
no. 772564. Copies of the data can be obtained free of charge on
application to CCDC, 12 Union Road, Cambridge CB2 1EZ,
U.K. (fax: (þ44) 1223-336-033; e-mail: deposit@ccdc.cam.ac.uk).
Synthesis of [Tl(3)MeCN]ClO4. Calix 3 (0.03 mmol) was
dissolved in acetonitrile-chloroform (4:1 v/v, 3 mL) and treated
with an equivalent amount of TlClO4 (0.03 mmol). The slow
evaporation of solvent at room temperature, over one week,
resulted in well-defined colorless crystals, which were suitable
for X-ray crystallography, after their separation and drying
under a vacuum.
Results and Discussion
Complexation of Tlþ Ion with Calix[4]crown-6 (1).
Thallium-203 NMR Study. In order to investigate the bind-
ing sites of the thallium(I) ion inside the calix 1 cavity, the
thallium-203 NMR spectra of a 0.01 M Tlþ solution in
CD3CN/CDCl3 (4:1 v/v) in the presence of varying con-
centrations of 1were recorded. As seen, because of the higher
flexibility of 1compared with that of 2-4, the thallium(I) ion
possesses a fast exchange rate between the solvated (at -199
ppm) and the 1:1 complexed sites (at -141 ppm), resulting in
a population averaged single NMR signal in the entire range
of ligand-to-metal molar ratios (R) considered. However,
no signal is observed at the molar ratio values of 0.4-0.8,
most probably due to broadening of the signal, as a result of
fast metal exchange between the free and complexed thal-
lium ion.42
Proton NMR Study. It was found that nearly all of the
spectral NMR peaks for the skeletal aromatic ring pro-
tons and glycolic crown ether protons of ligand 1 shift to
lower frequencies upon its complexation with the Tlþ ion,
the magnitude of the shift being significantly different for
the various protons of the ligand. The 1H NMR spectra
for the aromatic section of calix 1 upon the stepwise addi-
tion of Tlþ to a 0.002 M solution of the ligand in a CD3CN/
CDCl3 (4:1 v/v) mixed solvent are shown in Figure 1A. It
is seen that, upon complexation with Tlþ, the largest shifts
(upfield or downfield) are observed for the two identical
protons of the phenyl-OH protons and the four identical
protons of the -CH- aryl groups.
Thallium-203 NMR Studies. All thallium-203 NMR experi-
ments were performed at 11.7 T (285 MHz 203Tl) on a Bruker DRX-
500 pulsed Fourier transform NMR spectrometer. Typical NMR
parameters are as follows: a spectral frequency of 285.677 MHz, a
spectral width of 150 kHz, a 30° flip angle, a pulse repetition time
of 1 s, an acquisition time of 0.039 s, an FID resolution = 12.7 Hz/
point, and a number of scans = 128-256. All 203Tl spectra were
internally referenced to a capillary tube containing 0.05 M of
TlClO4 in D2O/CD3OD (2:3 v/v). The complexation behavior of
the ligands 1-4 toward the thallium(I) ion was studied by adding
the ligand into the NMR tube containing 0.01 M thallium(I) per-
chlorate in a CD3CN/CDCl3 (4:1 v/v) mixed solvent at 298 K.
Stepwise additions of the ligand were made, and the chemical shifts
were recorded.
Proton NMR Studies. 1H NMR measurements were recorded
at 298 K using a Bruker DRX-500 pulsed Fourier transform NMR
spectrometer. Typical operating conditions for routine proton
measurements involved a flip angle of 30°, a spectral frequency
of 500.133 MHz, a spectral width of 5 kHz, a delay time of 6.0 s,
and and acquisition time (AQ) of 1.586 s. Solutions of the ligands
1-4 (0.002 M) were prepared in CD3CN/CDCl3 (4:1 v/v) mixed
solvent in a 5-mm NMR tube using the TMS signal as an internal
reference.
Caution! Although we have not encountered any problems, it
should be noted that perchlorate salts of metal complexes with
organic ligands are potentially explosive and should be handled
only in small quantities with appropriate precautions.
X-Ray Crystallography. The single crystal data for [Tl(3)-
MeCN]ClO4 were collected at 150 K via ω scans and graphite-
monochromated Mo KR radiation (λ = 0.7107 A) on an Oxford
˚
The variations of -OH and p-H of aryl chemical shifts
versus the Tlþ/calix 1 molar ratio (R0) are shown in
Figure 1B. The resulting plots clearly indicate the quanti-
tative formation of a complexed species with a 1:1 (Tlþ/
calix 1) stoichiometry.
Diffraction Xcalibur 3 CCD area detector diffractometer equip-
ped with an Oxford Cryosystems open-flow nitrogen cryostat.
The data set was corrected for Lorentz polarization effects and
for absorption using empirical absorption correction SCALE3
ABSPACK.39 The structure was solved by direct methods using
SIR-200440 and refined using SHELXL-97.41 All non-hydrogen
A close comparison of the Δδ (δcomplex - δfree ligand
)
values of the host protons after complexation with guest
ions shows that the phenyl-OH protons give the highest
Δδ value of -0.41 ppm, followed by the -CH2- protons
in the bridging group toward the crown loop (Δδ =
-0.19 ppm) as well as the -CH2- protons in the bridging
group at the opposite direction of crown loop (Δδ =
þ0.12 ppm), supporting the fact that the thallium(I) guest
ion may penetrate into the calix[4]arene cavity close to the
phenyl-OH proton. These observations indicate that the
Tlþ ion, as a soft electron acceptor with strong afinity
(36) Asfari, Z.; Nicoille, X.; Vicens, J. J. Incl. Phenom. 1999, 33, 251.
(37) Asfari, Z.; Bressot, C.; Vicens, J.; Hill, C.; Dozol, J.-F.; Rouquette,
H.; Eymard, S.; Lamare, V.; Tournois, B. Anal. Chem. 1995, 67, 3133.
(38) Asfari, Z.; Thuery, P.; Nierlich, M.; Vicens, J. Tetrahedron Lett.
1999, 40, 499.
(39) CrysAlis RED and Scale3 Abspack, version 1.171.32.29; Oxford
Diffraction Ltd: Abingdon, Oxfordshire, UK.
(40) Burla, M. C.; Caliandro, R.; Camalli, M.; Carrozzini, B.; Cascarano,
G. L.; De Caro, L.; Giacovazzo, C.; Polidori, G.; Spagna, R. J. Appl.
Crystallogr. 2005, 38, 381.
(41) SHELXL 97: Sheldrick, G. M. Acta Crystallogr., Sect. A 2008,
64, 112.

Article
Inorganic Chemistry, Vol. 49, No. 15, 2010 6877
encapsulated inside the two ligand cavities to form inter-
molecular complexes, which thus leads to an efficient
shielding of the Tlþ ion.
The spectra shown in Figure 2 revealed two distinct
signals at -199 ppm for the free species and at -361 ppm
for 2:1 [Tl2(calix 2)]2þ complexed species, at ligand-to-
metal ion molar ratios 0 < R e 0.2, emphasizing the
occurrence of a slow exchange in the system, on the
thallium-203 NMR time scale. Meanwhile, upon further
addition of the ligand, to R > 0.5, a new signal is observed
at -399 ppm for the corresponding mononuclear species
[Tl(calix 2)]þ as a result of another slow exchange of the
Tlþ ion between the [Tl2(calix 2)]2þ and [Tl(calix 2)]þ
complexed species. The results clearly revealed the for-
mation of stable 2:1 and 1:1 (metal/ligand) complexes
with very slow exchange of the cation between these two
complexed sites on the NMR time scale.
Similar results were obtained in the case of calix 3 and
interpreted in terms of the formation of dinuclear
[Tl2(calix 3)]2þ complexed species when R e 0.5, with a
slow exchange between the solvated thallium(I) ion and
its dinuclear complex, and also the occurrence of another
slow exchange between the mono- and dinuclear com-
plexes at 0.5<R<1. Table 1 shows all of the chemical
shifts for the resulting 1:1 and 2:1 complexes detected in
this work. It is worth mentioning that, according to
Table 1, while the thallium-203 chemical shifts for the
1:1 complexes of the Tlþ ion with calix[4]biscrown-6
derivatives 2 and 3 are observed at about -400 ppm, that
for the Tlþ-calix 1 system is located at about -140 ppm
(i.e., about 160 ppm downfield from the former ones).
Such a relatively large chemical shift difference is due to
quite different electronic environments of the Tlþ ion
complexed with calix 1 relative to the corresponding
complexes with calix derivatives 2 and 3. First of all, it
should be noted that the calix[4] cavity in the case of the
calix 1 derivative is in con-conformation, while those in
calix derivatives 2 and 3 are 1,3-alternative conformers,
which results in different π-cation interactions. The large
Figure 1. (A) Proton NMR spectra of the aromatic region of calix 1 at
various Tlþ/calix 1 molar ratios in CD3CN/CDCl3 (4:1 v/v) at 298 K. (B)
The variation of proton chemical shifts for -OH protons (0, left scale)
and p-H of aryl (b, right scale) as a function of Tlþ/calix 1 molar ratios.
1
shift of -0.41 ppm, from 7.69 to 7.28 ppm in H NMR
spectra, was observed for the -OH signal of calix 1 upon
complexation with the Tlþ ion, reflecting the strong
interaction of the Tlþ ion with the hydroxyl groups of
the ligand and, consequently in the different electro-
nic environment of the complexed Tlþ ion. Moreover,
our crystallographic studies of the 1:1 Tlþ-calix 3 com-
plex (see the following sections and Figure 7) revealed
that the second cavity defined by calix 3 is partially
occupied by an acetonitrile molecule, the methyl group
of which interacts with one of the aromatic rings bearing
the polyoxa chain coordinated to the Tlþ ion, which can
also affect the electronic environment of the complexed
Tlþ ion.
Figure 2. Thallium-203 NMR spectra of calix 2 at various ligand/Tlþ
molar ratios in CD3CN/CDCl3 (4:1 v/v) at 298 K.
toward the π-basic calix[4]arene cavity, may also give
cation-π coordination.43
Complexation of Tlþ Ion with 1,3-Calix[4]biscrown-6 (2)
and 1,3-Calix[4]bis-o-benzo-crown-6 (3). Thallium-203
NMR Study. The thallium-203 NMR spectra of a 0.01
M Tlþ solution in CD3CN/CDCl3 (4:1 v/v) in the pre-
sence of varying concentrations of calix 2 were recorded,
and the results are shown in Figure 2. As is obvious, the
thallium-203 NMR signal of the solvated Tlþ ion shifts
appreciably to much higher magnetic fields upon forma-
tion of the 1:1 and 2:1 (metal-to-ligand) complexes with
calix 2, revealing the fact that the guest cations can be
Proton NMR Study. The H NMR spectra of the aro-
1
matic region of calix 2 at various Tlþ/ligand molar ratios
(R0) in CD3CN/CDCl3 (4:1 v/v) at 298 K are shown in
Figure 3A. It should be noted that the corresponding H
1
NMR spectra of calix 3 showed a more or less similar trend,
and thus it is not shown here. As is obvious from Figure 3A,
the signals of the free calix 2 split into two distinct signals
which shifted and broadened upon addition of the cation;
for example, the doublet centered at 7.13 ppm due to the
m-H of aryl for the free 2 (R0 = Tlþ/calix 2 = 0) is split

6878 Inorganic Chemistry, Vol. 49, No. 15, 2010
Haddadi et al.
Table 1. Thallium-203 NMR Chemical Shift (ppm) of Different Complexes of Thallium-Calixarenes
Tlþ/calix
code
name
1:1
2:1
calix 1
calix 2
calix 3
calix 4
calix[4]crown-6
1,3-calix[4]biscrown-6
1,3-calix[4]bis-o-benzo-crown-6
calix[4]arene-1,3-crown-6;2,4-(1,2-phenylene)-crown-6
-141.3
-399.1
-401.6
-359.6
-363.8
-361.5
-367.4
-415.2
-312.2
signals for all of the protons corresponding to the empty
and filled cavities of such unsymmetrical mononuclear
species. However, according to the corresponding 1H NMR
spectra for aromatic (Figure 3A) and glycolic (not shown)
regions at R0 = 1, the signals are quite broad, and no distinct
separate signals are observed for unsymmetrical mononuc-
lear species. One easy hypothesis for this observation is that
the Tlþ ion can intramolecularly alternate rapidly on the
NMR time scale between the two crown cavities by migrating
through the π-basic hole of the calix[4]arene moiety in calix 2
and calix 3 (Scheme 2).þIn fact, it could be postulated that the
complexation of the Tl ion with calix 2 at R0 < 1 is a three-
site exchange system and at R0=1 a two-site exchange system,
as illustrated in Scheme 2. Meanwhile, as can be seen from
Figure 3A, further addition of the thallium(I) ion to reach
R0 > 1 will result in a stepwise decoalescence of most proton
signals, due to the stepwise occupation of the two crown sites
of calix 2 and the consequent reduction of the intramolecular
exchange rate.
There is also a three-site exchange system for 1 < R0 < 2,
with two available sites for mononuclear intramolecular
exchange as well as a possible exchange between mono-
nuclear and dinuclear complexes (Scheme 2b).
As is obvious from Figure 3A, at a molar ratio of R0 = 2
(corresponding to the formation of a [Tl2(calix 2)]2þ
complex), a well resolved doublet is observed for aromatic
1
protons (m-H of aryl in the calix cavity) in the H NMR
spectrum of the 2:1 symmetrical dinuclear complex. Accord-
ingly, it can be concluded that the thallium(I) ions stand on
the main symmetry axis of the [Tl2(calix 2)]2þ complex.
Similar results have been obtained in the case of the calix 3
complex and interpreted in terms of the formation of
unsymmetrical mononuclear species at a molar ratio of
R0 e 1, with slow intermolecular and fast intramolecular
exchange of the cation between the two crown sites of calix 3.
A rapid exchange between mono- and binuclear species and
also intramolecular exchange between mononuclear com-
plexes was also observed when the molar ratio was R0 > 1.
Variable Temperature 1H NMR Study. In order to
further elucidate the inter- and intramolecular Tlþ com-
plexation behavior shown in Scheme 2, the variable
Figure 3. (A) Proton NMR spectra of the aromatic unit of calix 2 at
various Tlþ/ligand molar ratios in CD3CN/CDCl3 (4:1 v/v) at 298 K. (B)
The variation in chemical shift of the O-CH2-CH2-O proton of calix 3
as a function of the Tlþ/ligand molar ratio.
into two distinct doublets at R0 = 0.5 centered at δ 7.12 and
7.26 ppm corresponding to the empty and filled cavities of
the unsymmetrical mononuclear [Tl(calix 2)]þ species, re-
spectively. Similar 1H NMR results have also been reported
by Thuery et al.30 for the complexation of the Csþ ion with
ꢀ
1,3-calix[4]biscrown-6 at 0 < R0 < 1, which was related to
the occurrence of a slow exchange between the free and
complexed host.
1
Figure 3B shows the variation in chemical shift of
O-CH2-CH2-O protons of the benzo-18-crwon-6 sub-
stituent of calix 3 (Figure 3B) as a function of the Tlþ/
ligand molar ratio (R0). As can be seen, the molar ratio
plots show two distinct regimes: the first is in the range of
R0 = 0-1, and the second is in the range of R0 = 1-2,
with two clear inflection points at metal-to-ligand molar
ratios of 1 and 2, emphasizing the successive and quanti-
tative formation of the two complex species [Tl(calix 3)]þ
temperature H NMR was carried out in a CD3CN/
CDCl3 (4:1 v/v) solution at different metal ion to calix 2
molar ratios. Figure 4 depicts the representative proton
NMR spectra of a Tlþ/calix 2 system of metal/ligand
molar ratios, R0, of 1.0, 1.3, 1.5, and 2.0 at five different
temperatures in the range of 223-293 K. The spectra
show two groups of signals: (i) signals at chemical shifts of
6.85-7.15 ppm composed of triplets due to the p-H and
(ii) those at chemical shifts 7.15-7.35 ppm composed of
doublets related to the m-H of aryl groups of the calix
cavity.
and [Tl2(calix 3)]2þ
.
Since theþmononuclear complexes of [Tl(calix 3)]þ and
[Tl(calix 2)] are formed quantitatively at around R0 = 1,
one can expect to observe at least two separate 1H NMR
As is obvious from Figure 4, at R0 = 1 and at the highest
temperature of 293 K, a broadened m-H doublet is observed

Article
Inorganic Chemistry, Vol. 49, No. 15, 2010 6879
Scheme 2. Multisite Exchange Equilibria between Calix 2 and Thallium(I) Ion: (a) Tlþ/Calix 2 Molar Ratio e 1 and (b) Tlþ/Calix 2 Molar Ratio g 1
at about 7.20-7.27 ppm, which becomes sharper and shifts
to some extent to higher frequencies at lower temperatures.
Such a broad single doublet insists the occurrence of a fast
exchange between forms 2 and 3 depicted in Scheme 2a. It is
interesting to note that, as the temperature decreases, the
exchange rate decreases and, consequently, the single doub-
let begins to split into two doublets, each of which belonging
to the m-H of aryl groups of the calix cavity in the two 1:1
complex conformers given by forms 2 and 3 in Scheme 2a. A
more or less similar temperature effect is observed for p-H
triplets of the aryl groups of the calix cavity, over a chemical
shift range of 6.85-7.15 ppm.
tence of two different triplets for the p-H protons of the
aryl groups, at all temperatures studied, revealed the fact
that in the 2:1 complex formed the four p-H’s are divided
into two groups, one close to the Tlþ ions and one far
away from them. This is most probably due to the fact
that, upon complexation with the metal ions, each of the
crown ether moieties of calix 2 adopts a kind of boat-
shaped configuration to conveniently encapsulate the
thallium(I) ion (see the crystallographic structure shown
in Figure 7). It is interesting to note that at 1 e R0 < 2
(Figure 4A-C), there are three different triplets present in
the 6.85-7.15 ppm region of the corresponding 1H NMR
spectra for the p-H’s of the aryl groups of calix 2, one due
to the unoccupied crown site of the ligand and two others
for the occupied site, as mentioned above for the case of
the [Tl2(calix 2)]2þ complex.
However, upon increasing the [Tlþ]/[calix 2] molar
ratio from 1.0 to 1.3 and 1.5 (Figures 4B and C, res-
pectively), a new doublet signal begins to show up, at
higher chemical shifts than that for the 1:1 complex, for
the m-H aryl groups of the calix 2 cavity, which becomes
sharper at lower temperatures, expectedly. Such an ob-
servation implies that there are two exchangeable forms
corresponding to the binuclear and mononuclear species
in solution. It is worth mentioning that the relative area
of these two doublets is proportional to the corresponding
molar ratios at lower temperatures. The observed behavior
is in support of the multisite exchange equilibria between
calix 2 and the thallium(I) ion shown in Scheme 2b.
Complexation of Tlþ Ion with 1,3-Alternate Calix[4]-
arene-1,3-(18-crown-6;2,4-(1,2-phenylene)-18-crown-6
(Calix 4). Thallium-203 NMR Study. The thallium-203
NMR spectra of a 0.01 M Tlþ solution in CD3CN/CDCl3
(4:1 v/v) in the presence of varying concentrations of calix
4 were recorded, and the results are shown in Figure 5.
As can be seen, at molar ratios R < 0.5, the thallium-203
NMR spectra of the inclusion complexes of calix 4 with
the thallium(I) ion normally show three distinct signals
for the free and complexed guest species, one signal for the
solvated (at -199 ppm) and two upfield signals for the 2:1
[Tl2(calix 4)]2þ complex (at -312 and -362 ppm), indi-
cating a very slow exchange of the Tlþ ion between the
solvated and complexed sites, within the thallium-203
NMR time scale. Obviously, upon the addition of calix 4
to the thallium(I) ion solution at R = 0.5, both crown
units of the host molecule will be occupied; in them, the
two Tlþ ions will possess a more or less different electro-
nic environment. It is worth mentioning that, in a recent
publication, Matthews et al. have reported the ability of
using the thallium-205 NMR to observe the intermediate
species in solution, in which a small change in electronic
On the other hand, the observation of at least three
triplets for the p-H’s of the aryl groups of the calix 2
cavity, at lower temperatures, not only confirms the
exchange between the 2:1 and 1:1 Tlþ-calix 2 complexed
species but also reveals the fact that, in both 1:1 and 2:1
forms, the para-hydrogen atoms of the aryl groups have
different magnetic environments (see below the crystal-
lographic structure of [Tl(3)(MeCN)(H2O)]þ).
Finally, at a [Tlþ]/[calix 2] molar ratio of 2 (Figure 4 D),
both crown sites of the calix molecule are occupied by
two thallium(I) ions so that all m-H aryl groups possess
similar magnetic environments, which result in a single
doublet at all temperatures studied. However, the exis-

6880 Inorganic Chemistry, Vol. 49, No. 15, 2010
Haddadi et al.
Figure 5. Thallium-203 NMR spectra of calix 4 at various ligand/Tlþ
molar ratios in CD3CN/CDCl3 (4:1 v/v) at 298 K.
solution, two new distinct signals at -367 and -415 ppm,
due to the formation of the 1:1 [Tl(calix 4)]þ begin to grow
at the expense of the signals at -312 and -362 ppm of the
complex [Tl2(calix) 4]2þ. As is obvious from Figure 5, at
molar ratios of R = 1 or greater, the thallim-203 NMR
spectra only shows the two NMR signals corresponding
to the 1:1 [Tl(calix 4)]þ complex. One easy interpreta-
tion of the observations is that the calix 4 ligand possesses
two binding sites with different binding abilities for the
thallium(I) ion.44 This interpretation is also supported
1
by H NMR studies described below. The two signals
observed for the 1:1 [Tl(calix 4)]þ complex at -367 and
-415 ppm are most possibly related to the Tlþ ion located
in 18-crwon-6 and benzo-18-crown-6 units of calix 4,
respectively.
It is interesting to note that, according to the thallium-
203 NMR spectra shown in Figure 5, the relative intensity
of the -367 ppm signal-to- -415 ppm signal is also 3:1,
which implies that the ionophoricity of the former cavity
(i.e., cavity related to the -367 ppm signal) is 3 times
larger than that of the latter cavity (i.e., cavity related to
the -415 ppm signal). These observations demonstrate
the ability of thallium-203 NMR to distinguish the Tlþ
ion binding sites in macromolecules and to investigate
how specific the monovalent sites respond to the ligand
binding.
1
Proton NMR Study. Figure 6 shows the H NMR
spectra of the aromatic region of calix 4 at various Tlþ/
ligand molar ratios (R0) in CD3CN/CDCl3 (4:1 v/v) at 298 K.
Because of the asymmetry of calix 4 with respect to calix 2
and 3, its 1H NMR pattern is more complicated; however,
from the 1H NMR spectra of calix 4, some results similar to
those for calix 2 and 3 can be obtained. From Figure 6, it
seems that at a molar ratio of R0 = 2, one of the doublet of
Figure 4. Proton NMR spectra of the aromatic unit of calix 2 at various
Tlþ/ligand molar ratios and different temperatures in CD3CN/CDCl3
(4:1 v/v): (A) R0 = 1.0; (B) R0 = 1.3; (C) R0 = 1.5; (D) R0 = 2.0.
environment would greatly affect the thallium(I) resonance,
so that a clear and direct observation of the complexation
process can be made.5 Here, because of some asymmetry
in the structure of the two crown units of calix 4, the
resulting [Tl2(calix 4)]2þ complex gives two thallium(I)
resonances related to binding of a Tlþ ion in each of the
two different crown units of the ligand, which can be
observed separately in a slow exchange regime on the
thallium-203 NMR time scale.
triplets for the p-H of aryl (corresponding to [Tl2(calix4)]2þ
)
is overlapped with protons of the benzo group at the top of
the 18-crown-6 loop.
The inset of Figure 6 shows 1H NMR spectra of the p-H
of aryl of calix 4 at a molar ratio of R0 = 3 decoupled with
203Tl. Because of a lesser abundance of 203Tl relative to
205Tl (i.e., 29.5% to 70.5%), the decoupling cannot be
applied quantitatively. This observation can help to prove
the hypothesis of the presence of two types of aryl protons
in the resulting 1:1 and 2:1 complexs. The tallium(I) ion
As is obvious from Figure 5, upon further addition of
the ligand at molar ratios of R > 0.5 to the thallium(I) ion

Article
Inorganic Chemistry, Vol. 49, No. 15, 2010 6881
Figure 6. Proton NMR spectra of the aromatic region of calix 4 at various Tlþ/ligand molar ratios in CD3CN/CDCl3 (4:1 v/v) at 298 K. Inset shows the
1H NMRspectrumofthe p-Hofthe arylregionofcalix4ata Tlþ/ligandmolarratio of3.0:(top)203TldecoupledNMR;(bottom) 1H NMR203Tlcoupledfor
comparison.
can coordinate to four arene rings at a time, and if these
ligands can support two Tlþ ions at one time in distinct
coordination environments, then both Tlþ ions cannot
both interact with all four arene rings.
X-Ray Crystal Structure of [Tl(3)(MeCN)(H2O)]ClO4.
The crystal structure consists of discrete [Tl(3)(MeCN)-
(H2O)]þ cations and perchlorate anions. Figure 7 shows
the [Tl(calx 3)(MeCN)]þ cation with atom labeling.
Due to the two polyoxa chains, the calixarene adopts a
1,3-alternate conformation. As shown in Figure 7, two
CH π interactions are formed between the aromatic
rings of the calixarene and the catechol rings of the
3 3 3
˚
polyoxa chains. In fact, the C6 atom is 3.633(8) A from
˚
the plane defined by the nearest catechol ring (3.103(7) A
˚
˚
for C13) and 4.63(1) A from its centroid (4.38(1) A for
C13). This disposition of the calix[4]arene moiety and of
the two polyoxa chains defines two cavities located on
opposite sides of the calix[4]arene rim.
As shown in Figure 7, one of these cavities is occupied
by a thallium(I) ion which is coordinated by three oxygen
atoms from the polyoxa chain and by a water molecule.
˚
˚
The Tl-O distances range from 2.739(9) A to 2.949(4) A,
as expected for this kind of bond.45 The coordination
sphere is completed by the two aromatic rings bearing
the polyoxa chain not coordinated to the metal. Each
aromatic ring interacts with the metal center via π-
cation interactions involving three of the six carbon
atoms, with metal to carbon distances falling in the
range 3.095-3.317 A.
Included cations forming polyhapto aromatic interac-
tions are very common in calixarene complexes, mainly in
Figure 7. ORTEP drawing of the [Tl(3)(MeCN)(H2O)]þ cation with
labeling scheme adopted. H atoms and counteranions are omitted for
clarity. Selected bond distances: Tl-O12 = 2.945(4), Tl-O7 = 2.949(4),
Tl-O8 = 2.926(5), Tl-O140 = 2.739(9), Tl C5 = 3.310(7), Tl C6 =
3 3 3 3 3 3
˚
3.155(8), Tl C7 = 3.259(8), Tl C19 = 3.319(7), Tl C20 =
3 3 3 3 3 3 3 3 3
˚
3.095(7), Tl C21 = 3.273(7) A.
3 3 3
the case of alkali metal cations,46 but to the best of our
knowledge, only one crystal structure was previously
reported containing calixarene, including a thallium(I)
ion π-interacting with the aromatic rings of the calixarene
(42) Hinton, J. F. Magn. Reson. Chem. 1987, 25, 659.
(43) Kimura, K.; Tatsumi, K.; Yokoyama, M.; Ouchi, M.; Mocerino, M.
Anal. Commun. 1999, 36, 229.

6882 Inorganic Chemistry, Vol. 49, No. 15, 2010
Haddadi et al.
moiety.5 Also in that structure, the Tl C distances were
the methyl group of the MeCN interacts with one of the
aromatic rings bearing the polyoxa chain coordinated to
the Tlþ cation, giving rise to carbon to plane and carbon
to centroid of the ring distance values of 3.229(6) and
3 3 3
þ
about 3.2-3.3 A. Due to the similarity of Tl and Kþ
˚
cations, a close comparison can be done between the
Tl C distances found in these crystal structures and
3 3 3
˚
the K C distances observed in analogous complexes of
the potassium ion, which are slightly longer and generally
3.68(1) A, respectively.
3 3 3
47
˚
fall in the range 3.2-3.6 A. Additional information
could also be obtained by analyzing the Tl C distances
Conclusion
3 3 3
We have used 1H NMR and direct detection of 203Tl NMR
to characterize the binding of Tlþ to some calix[4]arene crown
ether derivatives 1-4 in a site-specific manner. The power of
direct detection 203Tl NMR is demonstrated by the observation
of a previously unobserved complexity in the association of
monovalent cations with the calixarene systems. Also, succes-
sive formation of mononuclear and dinuclear species, alterna-
tion of thallium(I) between two binding sites of calix derivatives
2-4 by migration through the π-basic hole.
in complexes featuring Tlþ ions involved in poly hapto
aromatic interactions with phenyl or cyclopentadienyl
groups. Actually, a search of the CSD database has evi-
denced that most of the metal to carbon distances in
complexes where the Tlþ is located near the normal to an
aromatic ring (angle between the Tl-centroid vector and
the normal to the aromatic plane being less than 20°) are
˚
about 3.2-3.3 A, in good agreement with distances ob-
served in the crystal structure of [Tl(3)(MeCN)(H2O)]þ.45
As shown in Figure 7, the second cavity defined by the
ligand is partially occupied by a MeCN molecule. Actually,
Acknowledgment. This work has been supported by
grants from the Tarbiat Modares University Research
Council, which is hereby gratefully acknowledged.
(44) Ramirez, F. D. M.; Charbonniere, L. J.; Muller, G.; Bunzli, J. C. G.
Eur. J. Inorg. Chem. 2004, 2, 2348.
(45) Data were retrieved from CSD using CCDC software (2009, v.5.30).
(46) Dalgarno, S. J.; Claudio-Bosque, K. M.; Warren, J-.E.; Glass, T. E.;
Atwood, J. L. Chem Commun. 2008, 1410 and references therein.
(47) Liu, L.; Zacharov, L. N.; Golen, J. A.; Rheingold, A. L.; Watson,
W. H.; Hanna, T. A. Inorg. Chem. 2006, 45, 4247.
Supporting Information Available: Crystallographic file in
CIF format. This material is available free of charge via the
Internet at http://pubs.acs.org.