Molecular scaffolds for di-metallic complexation: The synthesis, characterisation and complexation properties of tetrakis-terpyridinyl-calix[4]arene

Article abstract of DOI:10.1016/S0040-4039(02)01386-2

The ligand tetrakis-terpyridinyl-calix[4]arene is used as a rigid scaffold and pre-organiser of supramolecular assemblies by complexation of the Ni(II), Cu(II) and Co(II) cations. The ligand synthesis was carried out using peptide synthesis conditions by coupling 4′-(2-aminoethoxy)-2,2′/6′,2′′-terpyridine to the tetra-succinimidoyl activated ester of p-tert-butylcalix[4]arene. The studies on complexation by UV show the existence of M₂L-type complexes.

Full text of DOI:10.1016/S0040-4039(02)01386-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 6355–6358
Molecular scaffolds for di-metallic complexation: the synthesis,
characterisation and complexation properties of
tetrakis-terpyridinyl-calix[4]arene
Yann Molard and H e´ l e` ne Parrot-Lopez*
Synth e` se, Reconnaissance et Organisation Mol e´ culaire et Biomol e´ culaire, UMR CNRS 5078, Universit e´ Claude Bernard-Lyon I,
Domaine Scientifique de la Doua, B aˆ t. J. Raulin, 43 Bd du 11 Novembre 1918, 69622 Villeurbanne cedex, France
Accepted 5 July 2002
Abstract—The ligand tetrakis-terpyridinyl-calix[4]arene is used as a rigid scaffold and pre-organiser of supramolecular assemblies
by complexation of the Ni(II), Cu(II) and Co(II) cations. The ligand synthesis was carried out using peptide synthesis conditions
by coupling 4%-(2-aminoethoxy)-2,2%/6%,2%%-terpyridine to the tetra-succinimidoyl activated ester of p-tert-butylcalix[4]arene. The
studies on complexation by UV show the existence of M L-type complexes. © 2002 Elsevier Science Ltd. All rights reserved.
2
The terpyridine fragment (tpy) is a highly versatile
terdentate ligand, of considerable interest in transition
metal coordination chemistry. A wide range of appli-
In view of the above, it seemed of interest to us to
couple multiple terpyridine functions to a rigid scaffold.
This presents multiple complexation sites with a pre-
defined but somewhat flexible geometry so as to allow
complexation to proceed accompanied by energy relax-
ation and hence eliminate too highly sterically con-
strained stereochemistries. The use of p-tert-butyl-
calix[4]arene as the rigid skeleton to which four ter-
pyridinyl units are coupled via short flexible spacer
functions appeared an interesting prospect for the con-
struction of such a molecular edifice. In this paper we
report the synthesis of the p-tert-butylcalix[4]arene
tetra-terpyridine system and the study by UV spec-
troscopy of the complexation of metal cations Ni(II),
Cu(II), Co(II).
1
cations have appeared in the literature; for example in
therapeutical applications they have been used to
1
99
109
2
chelate Au and Pd radioisotopes. In this case the
terpyridine units act as bifunctional chelates and are
linked in a covalent manner to transport molecules
for specific targeting. Investigation in the biomimetic
area has been concentrated in the complexation of
3
–6
metals
; the Cu(II)–tpy complexes are highly active
4
for the transesterification of phosphodiesters. In order
to improve the catalytic hydrolysis of RNA, Hamilton
et al. have used dinuclear complexes containing a
5
Cu(II)-bis-terpyridine system. Suh et al. used Cu(II)-
tpy or Ni(II)-tpy functionality couples to the synthetic
poly(ethylenimine) (PEI) to hydrolyse polyadenylic
In view of previous work and given our own compe-
6
1
0
acid. Research has focused on increasing the number
tence in the lower rim modification of calix[4]arene 1
of catalytic metal sites and also on modifying the local
hydrophobic environment.
we have chosen to use the calix[4]arene tetra-acid 3
prepared via the tetraester 2 as the base unit for the
construction of a novel supramolecular system: tetrakis-
terpyridinyl-p-tert-butylcalix[4] arene 6 (Scheme 1). The
presence of the carboxylate functions on the macrocycle
allows the use of a covalent amide linkage with the
terpyridine ligand substituted at the position 4%. The tpy
derivative may be synthesised using two routes, depend-
ing on whether the spacer arm between the calix[4]arene
and the tpy is coupled at the tpy by a C–C linkage or
by an ether functionality. The 4%-thiomethyl-2,2%/6%,2%%-
The calix[4]arenes are an attractive system on which to
construct spacer recognition sites for cations at the
7
8
upper rim, or anions at the lower rim. Reinhoudt has
reported model complexes based on di- and tri-nuclear
Zn(II) calix[4]arene systems. In this case, the 2,6-
bis(aminomethyl)pyridyl group was attached at the
9
upper rim of the calix[4]arene.
11
terpyridine available via a literature method was cou-
pled with the Grignard of benzyloxycarbonylamino
ethylbromide in a nickel-catalysed reaction. However,
*
0
Corresponding author. E-mail: h.parrot@cdlyon.univ-lyon1.fr
040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01386-2

6
356
Y. Molard, H. Parrot-Lopez / Tetrahedron Letters 43 (2002) 6355–6358
Scheme 1. Synthesis of tetrakis-terpyridinyl p-tert-butylcalix[4]arene 6; (i) NaH, BrCH CO Et, THF, 60°C, 1 h; (ii) NaOH,
2
2
EtOH, H O, 40°C, 48 h; (iii) N-hydroxy-succinimide (NHS), DCC, CH CO Et, 25°C, 48 h; (iv) 2-aminoethanol, KOH, DMSO,
2
3
2
1
h at 25°C and 40 h at 50°C; (v) compound 5, DIEA, CH Cl , 5 days at 25°C.
2 2
1
13
this versatile starting material and Grignard reagent did
by H, C NMR, electrospray mass spectrometry and
13 14
12
not couple efficiently. The terpyridine moiety 5 was
obtained in 71% yield at 50°C for 40 h by substitution
of 4%-chloro-2,2%/6%,2%%-terpyridine (1 g, 3.74 mmol) with
elemental analyses. The cone conformation is con-
firmed by the presence of an AB (J=13.2 Hz) system
characteristic of methylene bridges (ArCH Ar) and by
the position of the carbon atoms of the methylene
2
1
.2 equiv. of
a
solution of the alkoxide (2-
13
bridges in the C NMR: 31.90 ppm.
aminoethanol/KOH) (0.25 mL, 4.12 mmol/0.26 g, 4.53
mmol) in dry DMSO (30 mL) to give an ether linkage.
Purification of 5 was carried out by step gradient
column chromatography (Al O ; eluent CHCl then
The complexation of cations in solution was investi-
gated by UV spectroscopy between u=300–400 nm.
The stoichiometry of the complexes 7 and 8 prepared,
respectively, from Ni(NO ) , 6H O and Cu(NO ) ,
2
3
3
9
0% CHCl /10% MeOH). The grafting of four tpy
3
3
2
2
3 2
O-alkylated in the position 4% (0.61 g, 2.09 mmol) to the
2
.5H O and the ligand tetra-tpy-calix[4]arene 6 in a
2
10
tetra-succinimidoyl activated tetraester 4 of the tetra-
acid of calix[4]arene 3 (0.60 g, 0.47 mmol) is realised in
basic conditions in the presence of DIEA (diisopropyl-
CH Cl /EtOH (1/1) solution were calculated using a
2
2
15
continuous variation method.
MLCT) are permitted for the six coordinated nickel
complex and the three bands at 900, 540 and 330 nm
Three transitions
(
ethylamine) (0.4 mL, 2.09 mmol) in CH Cl (20 mL).
2
2
16
The new ligand tetrakis-terpyridinyl-p-tert-butyl-
calix[4]arene 6 was obtained by precipitation from a
CH Cl /n-hexane mixture and isolated in the 55% yield.
are displayed. The formation of complex 7 is followed
by the appearance of bands at umax=327 nm (m=34 000
3
3
−1
−1
2
2
dm mol cm ) and umax=314 nm (m=44 800 dm
−
1
−1
The novel calix[4]arene ligand 6 has been characterised
mol cm ) (Fig. 1a). Fig. 1b presents the evolution of

Y. Molard, H. Parrot-Lopez / Tetrahedron Letters 43 (2002) 6355–6358
6357
complex 9, the concentration of cobalt (CoCl ) and
2
−
4
15
ligand 6 is 5×10 M. The formation of the two
entities is characterised by the appearance of two
isobestic points at 550 and 668 nm. Three species are
present in solution, in equilibrium, as free CoCl , a
2
tetrahedral complex and an octahedral complex. Analy-
sis of the absorption at 450 nm indicates an M L
2
stoichiometry in accordance with the molar ratio of 0.5
whereas the same follow-up at 693 nm gives an M L
4
stoichiometry with the molar ratio of 0.25. With CoCl2,
in solution we have revealed the existence of an equi-
librium between the M L and M L type complexes
2
4
where chlorine intervenes in the coordination.
The use of terpyridine and of calixarene group is a
good way of obtaining structures by the complexation
of metal cations. We have shown that the pre-organisa-
tion of the calixarene ligand around metal illustrates its
Figure 1. (a) UV spectra of the complexation of Ni(II) and
−
5
the ligand 6 (2.5×10 M) in CH Cl /EtOH (1/1). (b) Mea-
2
2
surement of the variation of the absorption maximum at 327
nm as a function of the molar ratio n /(n +n ) according to
M
M
L
the continuous variation method. The stoichiometry is M L
2
(
the maximum obtained is at 0.65).
the absorbance of metal:ligand mixtures versus the
ratio n /(n +n ). Analysis of the absorptions at 327
M
M
L
and 314 nm yields a stoichiometry 0.65 in accordance
with octahedral geometry around Ni(II) i.e.
[
(Ni(NO ) ) (ttpy-calix)]. Similar experiments were car-
3 2 2
ried out with hydrated copper nitrate (Cu(NO ) , 2.5
H O). The UV spectra are given in Fig. 2a. The bands
situated at umax=314 nm (m=40 000 dm mol cm )
and umax=325 nm (m=40 000 dm mol cm ) corres-
3
2
1
5
2
3
−1
−1
3
−1
−1
pond to the s “p* and p“p* transitions centred on
L
the ligand. The formation of complex 8 is followed by
the decreasing of the intensity of these bands as soon as
the stoichiometry (0.65) of the mixture is exceeded. The
studies of Ni(II) and Cu(II) complexation by UV show
Figure 2. (a) UV spectra of the complexation of Cu(NO ) ,
3
2
−
5
2.5H O and the ligand 6 (5.1×10 M) in CH Cl /EtOH (1/1).
2
2
2
(b) Measurement of the variation of the absorption maximum
the existence of M L-type complexes and allow the
at 325 nm as a function of the molar ratio n /(n +n )
2
M
M
L
determination of stability constants of, respectively:
according to the continuous variation method. The stoi-
chiometry of the complex is M L [(ttpy-calix)(Cu(NO ) ) ].
Log K =13.4 and 12.8. In the case of the formation of
2
1
2
3 2 2

6
358
Y. Molard, H. Parrot-Lopez / Tetrahedron Letters 43 (2002) 6355–6358
aptitude to gather and to form new supramolecular
edifices by intermolecular interaction.
H tpy), 8.03 (s, 2H, H +H tpy), 8.62 (d, 2H, H +
4 3% 5% 3
%%
+
H tpy), 8.68 (d, 2H, H +H tpy); ES MS (+) m/z: [M]
3%% 6 6%%
+
2
93, [M+Na] 315; Anal. calcd for C H ON : C, 69.85;
15 16 4
H, 5.52; N, 19.16. Found: C, 70.07; H, 5.27, N, 18.67.
13. 5,11,17,23-Tetra-(tert-butyl)-25,26,27,28-tetrakis[N-(4%-
ethoxy-2,2%/6%,2%%terpyridinyl)amido-methoxy] calix[4]arene
Acknowledgements
−
1
6
. Yield 55%. mp 176°C; IR (KBr disc) wmax (cm )
1406–1600 (CꢀC, CꢀN stretches); 1669 (amide CꢀO
stretch)); 3317 (NH); UV umax (CH Cl /C OH) 278.5
nm (m=46 300); H NMR (CDCl3, 500MHz) l (ppm) 0.98
The authors wish to thank Professor M. Petit-Ramel
for comments and suggestions on the work. We are
grateful to the MRET for financial support. We thank
Mrs. N. Marshall for correcting the manuscript.
H
2 5
2
2
1
2
(s, 36H, tert-butyl-CH
CH -Ar ), 3.83 (m, 8H, N-CH ), 4.28 (t, 8H, J=5.15,
), 3.20 (d, J=13.2 Hz, 4H, Ar-
3
3
2
eq
2
2
O-CH -CH ), 4.51 (d, J=13.2 Hz, 4H, Ar-CH -Ar ),
2
2
2
ax
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4.67 (s, 8H, O-CH ), 6.69 (s, 8H, H-Ar), 7.21 (m, 8H,
2
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5
5%%tpy
1
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13
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), 8.56 (d, J=4.46, 8H, H +H6%%tpy);
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3
3%%tpy
6
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(ArCH Ar), 34.18 (tert-butyl-C-CH s), 39.275 (CH -
2
2
3%
2
NH), 67.23 (O-CH2tpy), 74.84 (O-CH ), 107.74 (C +
2
3%
C5%tpy), 121.61 (C +C
), 124.09 (C /C -Ar), 126.13
5
5%%tpy
3 5
(C +C
), 133.12 (C /C -Ar), 136.98 (C +C3%%tpy), 145.94
4
4%%tpy
2
6
3
(C -Ar), 149.33 (C +C
), 149.86 (C -Ar), 156.22 (C +
4
6
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4
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+
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+
2+/2
2+/2
[M+H] 1979, [M+2Na]
1012, [M+H+K]
1009, [M+
2+/2
2+/2
7
H+Na]
1001, [M+2H]
990; Anal. calcd for
C120H120N O +H O: C, 71.87; H, 6.03; N, 11.17.
16
12
2
1
Found: C, 71.85; H; 6.03; N, 11.13.
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15. Preparation of the solution of complexes 7, 8 and 9 for UV
investigation: Y ml (10-0 ml) of the Ni (NO ) , 6H O in a
3
2
2
−
5
CH Cl /EtOH (1/1) solution (2.5×10 M) or Cu(NO3)2,
2.5 H O solution (5.1×10 M) were added to the X ml
2 2
−
5
2
(0–10 ml) of the solution of the ttpy-calix[4]arene 6
−
5
−5
1
0. (a) Molard, Y.; Bureau, C.; Parrot-Lopez, H.; Lamartine,
(2.5×10 M or 5.1×10 M). The formation of the com-
plexes 7 and 8 is followed by UV. For the solution studies
of the complex 9, the cation concentration was constant.
To this effect, small quantities (5 ml at a time) of parent
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6
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−
2
1
1. Potts, K. T.; Usifer, K. T.; Guadalupe, A.; Abruna, H.
solution of ligand 6 of 10 M concentration are added to
−
4
D. J. Am. Chem. Soc. 1987, 109, 3961–3963.
the solution of CoCl 5×10 M in CH Cl /EtOH (1/1).
2
2
2
1
1
2. 4%-(2-Aminoethoxy)-2,2%/6,2%%-terpyridine 5. mp 136°C, H
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Wilkinson, G.; Gillard, R. D.; McCleverty, J. A., Eds.;
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NMR (CDCl3, 300 MHz) l (ppm) 3.16 (t, 2H, CH ), 4.26 (t,
2
2
H, CH ), 7.33 (m, 2H, H +H tpy), 7.85 (dt, 2H, H +
2 5 5%% 4