A water-soluble calix[4]arene-based podand incorporating 4,4′-dicarboxy-2,2′-bipyridine chelating units - Synthesis and complexation properties towards copper ions

Article abstract of DOI:10.1002/ejic.200300690

A water-soluble calix[4]arene-based podand has been prepared by incorporation, at the lower rim, of two 4,4′-dicarboxy-2,2′- bipyridine units in opposite positions. The association between its coordination and hydrophilic properties were beneficial to the complexation and solubilization of copper(i) in water, even in the presence of bovine serum albumin. The ligand and its corresponding Cu^I complex have been fully characterized, but attempts to crystallize them have been unsuccessful so far. For this reason, the dinuclear ZnCl₂ complex of the organic solvent soluble tetraester intermediate has been crystallized, and subjected to X-ray diffraction analysis, confirming the expected podand-like structure of the ligand. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

Full text of DOI:10.1002/ejic.200300690

FULL PAPER
A Water-Soluble Calix[4]arene-Based Podand Incorporating 4,4Ј-Dicarboxy-
2,2Ј-bipyridine Chelating Units ؊ Synthesis and Complexation Properties
towards Copper Ions
Nicolas Psychogios,[a] Jean-Bernard Regnouf-de-Vains,*[a] and Helen M. Stoeckli-Evans[b]
Keywords: Calix[4]arene / Bipyridine / Podand / Copper / Zinc
A water-soluble calix[4]arene-based podand has been pre-
pared by incorporation, at the lower rim, of two 4,4Ј-dicar-
boxy-2,2Ј-bipyridine units in opposite positions. The associ-
ation between its coordination and hydrophilic properties
were beneficial to the complexation and solubilization of
have been unsuccessful so far. For this reason, the dinuclear
ZnCl2 complex of the organic solvent soluble tetraester inter-
mediate has been crystallized, and subjected to X-ray dif-
fraction analysis, confirming the expected podand-like struc-
ture of the ligand.
copper(I) in water, even in the presence of bovine serum al-
bumin. The ligand and its corresponding CuI complex have
been fully characterized, but attempts to crystallize them
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2004)
Introduction
portionation in water, and thus limiting investigations on
its properties in aqueous media. The fact that the copper()
complexes are diamagnetic and colored (metal-to-ligand
charge transfer band at ca. 450 nm) should allow a con-
venient analysis of the complexation processes by NMR
and UV spectroscopy.
In this report, we describe (a) the multi-step synthesis of
the water-soluble calix[4]arene-based heterocyclic podand 6
in which the 2,2Ј-bipyridine arms exhibit both chelating and
hydrophilic behavior, (b) its complexation properties
towards CuI and CuII ions in water, and (c) the synthesis
and characterization of the copper() complex 7. Attempts
to obtain crystals of 6 and 7 suitable for X-ray analysis did
not succeed, but were successful for the dinuclear ZnCl2
complex of the organic-solvent soluble tetraester intermedi-
ate 4, allowing a preliminary structural investigation.
The transition from organic to aqueous solubility of the
calixarenes, and their corresponding properties, is gaining
attention as demonstrated by a rapid on-line survey on
water-soluble calixarenes, and recent review literature.[1] The
introduction of carboxylic acid functionalities at the
lower[2] and upper rims,[3,4] or sulfonyl,[5,6] phosphonate,[7]
and alkylamino groups[8] at the upper rim have been the
main routes for making calixarenes water soluble. Many
structural modifications have been carried out on these
water-soluble structures, leading to new ligands for various
metal cations.
With the aim of conducting, in water, some complexation
experiments, that we have previously developed with lipo-
philic calixarene-based heterocyclic podands,[9Ϫ17] and in
anticipation of future biological investigations, we at-
tempted to synthesize a hydrophilic ligand able to complex
the relatively unstable CuI cation in this medium. A number
of very rare examples of water-soluble copper() coordi-
nation complexes have been described involving a sulfon-
Results and Discussion
Ligand Syntheses
ated
phosphane
ligand,[18]
or
calix[6]-[19]
and
The calixarene podand species 4Ϫ7 were prepared ac-
cording to Scheme 1. The starting calix[4]arenetetrol was
synthesized as described previously.[23Ϫ26]
calix[4]arene[20Ϫ22] heterocyclic derivatives illustrating, in
part, the difficulty of protecting this cation from dispro-
The bipyridine arms were introduced to the calixarene
platform via the bromomethyl intermediate 3, which was
prepared according to Scheme 2 The starting bipyridine 1
was prepared following the Ni0-mediated procedure of Al-
pha et al.,[27] from methyl 2-methyl-6-[(p-tolylsulfonyl)oxy]-
pyridine-4-carboxylate. For the latter, the toxic and expens-
ive pyridine generally used as base and solvent for the tosyl-
ation reaction was replaced by triethylamine and
[a]
´
´
GEVSM, UMR 7565 CNRS-Universite Henri Poincare,
´
Faculte de Pharmacie,
5, rue Albert Lebrun, BP 403, 54001 Nancy Cedex, France
Fax: (internat.) ϩ33-3-83682345
E-mail: jean-bernard.regnouf@pharma.uhp-nancy.fr
[b]
´
Laboratoire de Cristallographie, Institut de Chimie, Universite
ˆ
de Neuchatel,
ˆ
51, C.P. 2, 2007 Neuchatel, Switzerland
Fax: (internat.) ϩ41-32-7182511
E-mail: Helen.Stoeckli-Evans@unine.ch
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DOI: 10.1002/ejic.200300690
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Synthesis of a Water-Soluble Calix[4]arene-Based Podand
FULL PAPER
Scheme 1. i) 3, MeCN, K2CO3, reflux, 83%; ii) a) NaOH, H2O, EtOH, reflux; b) HCl, pH 3Ϫ4, 80%; iii) NaOH, H2O, pH 7, 100%; iv)
Cu(MeCN)4PF6, MeCN, H2O
Scheme 2. i) mCPBA, CH2Cl2, 90%; ii) a) (CF3CO)2O; b) LiBr, THF, DMF, 55%
CH2Cl2.[28] This safe and economical procedure afforded With acetic anhydride, this leads to an acetate-protected
the tosyl derivative in a yield of 90%.
hydroxymethyl functionality, a key compound for further
The introduction of a single active bromomethyl func- transformations. This reaction was employed successfully to
tionality at the 6-position of 1 was performed via a three prepare more sophisticated activated heterocyclic systems,
step process including a controlled N-oxidation, a Boeck- notably with 6,6Ј-dimethyl-2,2Ј-bipyridine and its
elheide rearrangement, and a pseudo-halogen exchange. analogues.[27,31Ϫ35]
Compound 1 was initially treated in CH2Cl2 with 1 equiv.
The presence of the two ester functions in 1, both of
of mCPBA at 0 °C, then at room temperature to afford the which are prone to hydrolysis, led us to employ a more sen-
mono-N-oxide 2, mixed with ca. 5% of the corresponding sitive pathway involving a labile trifluoroacetate derivative,
di-N-oxide, and ca. 5% of unchanged bipyridine 1. An ana- which exhibits, in the alkyl[36] and arylalkyl series,[32,34] the
lytical sample of 2 was obtained by chromatography on interesting characteristic of being directly substituted by
Al2O3 (CH2Cl2) but, unstable on this support, and in order bromine in polar aprotic solvent, and at room temperature
to avoid dismutation, the above-mentioned raw mixture was via a pseudo-halogen exchange with LiBr.
frozen or directly transformed.
Thus, the raw mono-N-oxide 2 was heated to reflux in
The second step was a modified Boekelheide rearrange- CH2Cl2 in the presence of an excess of trifluoroacetic anhy-
ment. This process initially described with picoline N- dride. After evaporation of the solvent the solid residue,
oxides[29Ϫ30] allows the functionalization, by an active car- which contains the dimethyl 6-trifluoroacetyl-6Ј-methyl-
bonyl compound via a radical or ionic mechanism, of the 2,2Ј-bipyridine-4,4Ј-dicarboxylate, was dissolved in dry
methyl group in the α-position of the N-oxide function. DMF and dry THF in the presence of an excess of anhy-
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FULL PAPER
drous LiBr, itself dried under vacuum at 150 °C. The result- of CuCl2 by UV-visible spectroscopy in water (Figure 2).
ant monobromide 3 was obtained pure in a yield of 55%. The presence of two isosbestic points at 304 nm (0 to 1
The dibromomethyl analogue[27] was also isolated in a yield equiv.) and 316 nm (1 to 2 equiv.) revealed the formation
of 12%, and the bipyridine 1 (ca. 15%) was recovered. Their of two consecutive complex species, namely [CuCl2/6] and
formation was explained by the partial dismutation of 2 [(CuCl2)2/6]. In order to prepare a sample of the corre-
under the given conditions of the reaction.[35]
sponding final complex, the addition of 2 equiv. of CuCl2
A similar but longer process involving the consecutive in water to an aqueous solution of 6 resulted in a brown-
formation of the trifluoroacetate, the alcohol, the mesylate, green coloration, nevertheless immediately followed by for-
and then the bromide was also described for the tert-butyl mation of a gel then precipitation. The solvent was removed
ester analogue of 3,[37] as well as another procedure involv- by filtration and the residue was dried under high vacuum
ing a radical bromination.[38]
to give 8 as a green-brown powder. Surprisingly, the solid
Following the procedure previously reported by Beer et thus obtained remained insoluble in common solvents, even
al.[39] for the unsubstituted bipyridine, the monobromide 3, in DMSO. This behavior led us to believe that the water
calix[4]arenetetrol, and K2CO3 were heated to reflux in solubilizing carboxylate groups were in fact engaged in a
MeCN to give the podand 4 in a yield of 83% after chroma- chelating interaction with copper(), giving oligomeric or
tography (SiO2, CH2Cl2). The four ester functions of 4 were polymeric chelate species resulting in loss of solubility of
saponified in an aqueous alcoholic NaOH solution at re- the material. No relevant mass analysis has been obtained.
flux. Acidification to pH 3Ϫ4 resulted in the precipitation
An elemental analysis of the copper() complex 8 was
of the tetraacid 5, which was recovered in a yield of 80%.
A controlled neutralization of 5 with NaOH afforded the
tetrasodium carboxylate 6 in almost quantitative yield
(Scheme 1).
consistent with the formula C56H40ClCu2N4NaO12·4.5H2O,
corresponding to the loss of 3 equiv. of NaCl thus suggest-
ing an ionic interaction between copper and the carboxylate
groups. Such an interaction should involve a bridging mode
of the copper ions between two calixarene moieties, in a
linear polymeric network. Nevertheless, IR spectroscopy
(KBr) did not show relevant modifications in the carbonyl
region with regards to the ligand 6. Attempts to improve
this structure are under current investigation.
Complexation Studies
The formation of the copper() complex 7 was initially
studied by UV-visible spectroscopy in water (Figure 1). The
addition of [Cu(MeCN)4]PF6 to a solution of 6 resulted in
the immediate appearance of the expected MLCT band at
470 nm (red color), characteristic of tetrahedral copper()
complexes. The evolution of this band, as well as the new
ligand-centered band at ca. 300 nm, was complete upon ad-
dition of 1 equiv. of metal, confirming the formation of a
mononuclear complex.
The bimetallic copper() complex [(CuCl2)2 ʚ 6] formed
during the UV titration experiment was subjected to re-
duction by ascorbate (Figure 3). The complex was fully re-
duced after the addition of 0.5 equiv. of ascorbate, as de-
duced by the appearance of the expected MLCT band at
470 nm, characterized by an ε value of 5500 mol·LϪ1·cmϪ1
,
similar to that of complex 7. The addition of more ascorb-
ate did not result in any further change in the absorption
pattern.
In order to make a biological assessment of the complex
7, competition experiments with bovine serum albumin
were monitored by UV-visible spectroscopy (Figure 4). The
results show that the presence of 1 equiv. or 10 equiv. of
BSA relative to 7 did not change the absorption profile of
the latter, the MLCT band being conserved even after 24
or 48 hours. Under the same conditions, the copper() com-
plex of the corresponding free bipyridine decomposed. In
parallel, we have verified that no absorption band of the
MLCT type was generated by the interaction between BSA
and [Cu(MeCN)4]PF6. This confirmed that the copper()
ion is strongly maintained in a tetrahedral coordination by
6 under these conditions.
Figure 1. UV-visible titration of 6 with [Cu(MeCN)4]PF6: a) 6,
[2 mL; 1.71 ϫ 10Ϫ5  in H2O]; from b) to k): addition of 1 equiv.
of [Cu(MeCN)4]PF6 [10 ϫ 4µL; 9.98 ϫ 10Ϫ4  in MeCN]
In contrast to, a similar test carried out with [(CuCl2)2 ʚ
6] (Figure 5) resulted in the loss of the ligand-centered band
at 322 nm, which was concomitant with the appearance of
a new band at 312 nm (1 equiv. BSA), the latter being found
again as a shoulder with 10 equiv. of BSA. After 1 day, the
absorption pattern was found to be similar to the free li-
gand 6 (λmax. ϭ 304 nm). No specific absorption bands
were observed during the reaction between BSA and CuCl2.
The air-stable red complex 7 was prepared quantitatively
by addition of 1 equiv. of [Cu(MeCN)4]PF6 in acetonitrile
to an aqueous solution of 6, followed by evaporation to
dryness. Attempts to crystallize 7 for an X-ray structural
analysis were unsuccessful.
Since the redox properties of copper are favorable for the
doubly charged species, we have followed the complexation
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Synthesis of a Water-Soluble Calix[4]arene-Based Podand
FULL PAPER
Figure 2. UV-visible titration of 6 by CuCl2·2H2O: a) 6, [2 mL; 2.0 ϫ 10Ϫ5  in H2O]; from b) to k): addition of 2 equiv. of CuCl2·2H2O
[10 ϫ 8 µL; 1.00 ϫ 10Ϫ3  in H2O]
(cut-off mol. wt. ϭ 100) on aqueous solutions of 6 and 7
did not result in satisfactory removal of sodium chloride,
the residual solutions giving precipitates of silver chloride
upon addition of silver nitrate. Attempts to evaluate the
water content in 6 and 7 by mass-coupled thermogravi-
metric analysis were not successful, the loss of water being
observed over a wide range of temperatures (20Ϫ250 °C).
Nevertheless, 6 showed a clean loss of four CO2 molecules
between 420 and 540 °C.
NMR Analyses
According to de Mendoza et al,[40,41] 13C NMR spectro-
scopic analyses showed that 4, 5 and 6 exist in the cone con-
formation.
The cone conformation of 6 was also demonstrated by
1H NMR spectroscopy in D2O, with the Ar-CH2-Ar AB
system located at δ ϭ 3.18Ϫ3.96 ppm (JAB ϭ 15 Hz). 2D-
COSY experiments allowed the full assignment of reson-
Figure 3. UV-visible titration of [(CuCl2)2 ʚ 6] by ascorbic acid: a)
[(CuCl2)2 ʚ 6], [2 mL; 2.0 ϫ 10Ϫ5  in H2O]; from b) to f): addition
of 0.5 equiv. of ascorbic acid [5 ϫ 4µL; 1.00 ϫ 10Ϫ3  in H2O]
ance signals. In the aromatic region, the ligand exhibits four
perfectly well resolved bipyridyl singlets together with two
doublets and two triplets for the calixarene moiety, which
confirmed the expected structure. The terminal methyl
Compounds 2Ϫ7 gave satisfactory elemental, IR, MS groups and the methoxy linkers appear as singlets at δ ϭ
and NMR analyses.
In particular, a preliminary elemental analysis performed
2.53 and 5.33 ppm, respectively.
The H NMR spectrum of the copper() complex 7 in
1
on 6 dried with P2O5 showed the presence of 2 molecules D2O (Figure 6) exhibits broad resonance signals in all the
of NaCl and 3 molecules of H2O, but the instability of the relevant frequency domains, except for the aromatic calixar-
mass during the weighing process suggested logically that 6 ene protons, which appear as well resolved doublets and
was hygroscopic. After equilibration under ambient con- triplets. The presence of more than the four expected bipyri-
ditions, the analysis of 6 was consistent with the presence dyl resonance signals is in accordance with the probable
of 2 molecules of NaCl and 6 molecules of H2O. Argon presence of more than one species under these conditions.
plasma emission spectrophotometric analyses were consist- Addition of [D6]DMSO to the aqueous solution resulted in
ent with the presence of 5 sodium ions for one ligand 6, the increasing of one of the signals, and a general sharpen-
5 sodium, and 1 copper ion for one complex 7. Dialysis ing of all signals. At the concentration used in the NMR
experiments performed with cellulose ester membranes experiments, it is possible to suggest that oligomeric or
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N. Psychogios, J.-B. Regnouf-de-Vains, H. M. Stoeckli-Evans
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Figure 4. UV-visible analysis of 7 in the presence of bovine serum albumin: a) 7, [1.6 ϫ 10Ϫ5  in H2O]; b) 1 equiv. of BSA; c) 10 equiv.
of BSA
Figure 5. UV-visible analysis of [(CuCl2)2 ʚ 6] in the presence of bovine serum albumin: a) [(CuCl2)2 ʚ 6], [1.6 ϫ 10Ϫ5  in H2O];
b) 1 equiv. of BSA; c) 10 equiv. of BSA; d) 10 equiv. of BSA, one day; e) 6 [1.6 ϫ 10Ϫ5  in H2O]
polymeric complex species can be formed involving, due to firmed the complexation of copper() in a prohelicoidal
the lack of steric hindrance at the upper rim, conic or non- tetrahedral mode.
conic calixarene platforms, that could correspond to the
presence of multiple signals. The addition of DMSO may
modify the solvation of these flexible species, resulting in
Mass Spectrometry
the recovery of a conic conformer. Finally, pure [D6]DMSO
The mass analyses of ligand 6 and complex 7 were per-
gave a well resolved NMR spectrum resulting in the pres- formed with the electrospray technique in the positive or
ence of the expected cone conformer as the major com- negative mode. In the positive mode, 6 exhibited the mono-
pound with, notably, the presence of the four bipyridyl sing- (sodium) and the doubly charged bis(sodium) derivatives at
lets, the aromatic succession of calixarene doublets and trip- 1076.0 and 549.3 a.m.u. (base peak), respectively, ac-
lets, and the appearance of two AB systems at δ ϭ 3.27 and companied by other entities, which were not well analyzed.
4.24 ppm (JAB ϭ 12 Hz), and 5.31 and 6.27 ppm (JAB
ϭ
Conversely, the negative mode analysis resulted in the exhi-
11 Hz), which can be attributed to the Ar-CH2-Ar and bition of three groups of doubly charged (481.2, 492.2 and
OCH2-bpy spin systems, respectively. According to the re- 503.2 a.m.u.), triply charged (327.8 and 320.5 a.m.u.), and
sults obtained with parent hydrophobic complexes ,[11,13] tetra-charged (240.0 a.m.u.) species resulting from the loss
the presence of the Ar-CH2-Ar AB system confirmed the of 2, 3 or 4 sodium ions compensated, when necessary, by
cone conformation, and the OCH2-bpy AB system con- replacement with 1 or 2 protons. The base peak appearing
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Synthesis of a Water-Soluble Calix[4]arene-Based Podand
FULL PAPER
1
Figure 6. H NMR spectrum of the copper() complex 7 (a: D2O, b: D2O ϩ [D6]DMSO, c: [D6]DMSO; 400 MHz, room temp.)
in this case at 320.5 a.m.u. was attributed to the triply
charged species [6؊4Naϩ ϩ Hϩ]3Ϫ/3
.
The copper() complex 7 gave no relevant information in
the positive mode. In the negative mode, three groups of
signals were observed. As for the ligand, the loss of 1, 3,
and 4 sodium ions compensated by addition of protons
when necessary, resulted in doubly charged species located
at 544.1, 523.2, and 512.2 a.m.u. The loss of 4 sodium ions
resulted in a triply charged species located at 341.3 a.m.u.
Finally, the hexafluorophosphate anion appeared as a pure
entity at 144.9 a.m.u. (base peak), and as an adduct with
NaPF6 at 312.9 a.m.u.
X-ray Crystallography
Attempts to obtain single crystals of the ligand 6, its CuI
complex 7, and other transition metal complexes of 6 suit-
able for X-ray diffraction analyses were unsuccessful. In or-
der to ascertain the podand structure, and considering that
on the basis of NMR results, the general structure of 6
should not be different from the organic-solvent soluble
tetraester intermediate 4, we tried to prepare various metal
complexes of the latter and good results were obtained with
zinc(). In particular, the reaction of 4 with ZnCl2 gave the
conic complex 9 which was characterized by 1D and 2D 1H
NMR spectroscopic experiments, mass spectrometry, and
elemental analysis. Crystals of 9 suitable for X-ray diffrac-
Figure 7. ORTEP side-view of complex 9, molecule C
As expected, the calixarene subunit of 9 is in the cone
tion analysis were obtained as yellow plates by slow dif- conformation and substituted in alternate positions of the
fusion of hexane into a dichloromethane solution of the lower rim by two dimethyl 6-methyl-2,2Ј-bipyridyl-4,4Ј-di-
complex.
carboxylate arms tethered to the platform by a 6Ј-methyl-
Compound 9 crystallizes with 2 independent molecules, eneoxy linker. Each bipyridyl unit coordinates via its nitro-
C and D, per asymmetric unit, hence the molecular formula gen atoms to a tetrahedral ZnII cation, with the two remain-
is [Cl2Zn6ZnCl2]·2.25CH2Cl2.
ing coordination positions occupied by two chloride anions,
The molecular structure without the solvent is illustrated as already observed.[43]
in the PLATON[42] drawing (Figure 7) along with a partial
crystallographic numbering scheme.
In the two independent molecules C and D, the
[bpyZnCl2] units are opposed to each other, facing outward
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N. Psychogios, J.-B. Regnouf-de-Vains, H. M. Stoeckli-Evans
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Table 1. Selected torsion angles [°] around the zinc center in complex 9
N2ϪZn1ϪN1ϪC6
N1ϪZn1ϪN2ϪC7
N1ϪC6ϪC7ϪN2
N22ϪZn21ϪN21ϪC66
N21ϪZn21ϪN22ϪC67
N21ϪC66ϪC67ϪN22
1.5(5)
2.1(5)
6.4(10)
4.5(8)
Ϫ1.0(8)
6.5(17)
N4ϪZn2ϪN3ϪC50
N3ϪZn2ϪN4ϪC49
N3ϪC50ϪC49ϪN4
N24ϪZn22ϪN23ϪC111
N23ϪZn22ϪN24ϪC110
N24ϪC110ϪC111ϪN23
Ϫ10.8(5)
ϩ8.0(5)
Ϫ4.9(10)
Ϫ7.9(6)
7.7(6)
Ϫ0.3(12)
˚
Table 2. Selected bond lengths [A] and angles [°] around the zinc center in complex 9
Zn1ϪN1
Zn1ϪN2
Zn1ϪCl2
Zn1ϪCl1
Zn2ϪN3
Zn2ϪN4
Zn2ϪCl4
Zn2ϪCl3
Zn21ϪN21
Zn21ϪN22
Zn21ϪCl21
Zn21ϪCl22
Zn22ϪN23
Zn22ϪN24
Zn22ϪCl23
Zn22ϪCl24
2.059(7)
2.083(7)
2.197(3)
2.204(3)
2.048(7)
2.074(6)
2.196(2)
2.201(2)
2.065(12)
2.134(16)
2.174(3)
2.190(4)
2.036(7)
2.100(9)
2.179(3)
2.214(4)
N1ϪZn1ϪN2
N1ϪZn1ϪCl2
N2ϪZn1ϪCl2
N1ϪZn1ϪCl1
N2ϪZn1ϪCl1
Cl2ϪZn1ϪCl1
80.5(3)
116.2(2)
108.07(18)
114.61(19)
113.4(2)
N3ϪZn2ϪN4
N3ϪZn2ϪCl4
N4ϪZn2ϪCl4
N3ϪZn2ϪCl3
N4ϪZn2ϪCl3
Cl4ϪZn2ϪCl3
80.3(3)
119.0(2)
114.00(19)
108.8(2)
110.02(18)
118.47(10)
117.88(13)
N21ϪZn21ϪN22
N21ϪZn21ϪCl21
N22ϪZn21ϪCl21
N21ϪZn21ϪCl22
N22ϪZn21ϪCl22
Cl21ϪZn21ϪCl22
81.4(6)
114.5(3)
113.0(4)
110.5(3)
106.1(3)
123.32(16)
N23ϪZn22ϪN24
N23ϪZn22ϪCl23
N24ϪZn22ϪCl23
N23ϪZn22ϪCl24
N24ϪZn22ϪCl24
Cl23ϪZn22ϪCl24
79.8(4)
115.0(3)
114.8(3)
110.0(2)
108.9(2)
120.9(2)
from the calixarene main axis, and orienting the chlorine crystalline dinuclear complex 9 which was characterized by
atoms in the direction of the calixarene platform. A rotation X-ray diffraction, thus confirming the expected podand-like
of 90 ° around the C2 axis shows that these two units are structure of the ligand. The evaluation of the complexing
quasi parallel.
ability of 6 with various transition metal cations in water
Looking more precisely at the complex subunits of mol- and biological media, as well as their potent antimicrobial
ecules C and D, shows that the bipyridine units are planar, activities are under current investigation.
with NϪCϪCϪN torsion angles between Ϫ4.9 and 6.5 °
(Table 1). The zinc() centers are in strongly distorted tetra-
Experimental Section
hedral coordination environments, with NϪZnϪN angles
of ca. 80 °, ClϪZnϪCl angles of ca. 120 °, and NϪZnϪCl
between 106 and 119° (Table 2).
The ZnϪN and ZnCl distances (Table 2) are consistent
with those measured in a non-carboxylated analogue,[43]
suggesting a poor influence of the electroactive ester sub-
stituents on the complex geometry.
General Remarks: Melting points (°C, uncorrected) were deter-
mined with an Electrothermal 9200 Capillary apparatus. 1H, 13C
and 15ⁿ NMR spectra were recorded with a Bruker DRX 400
(chemical shifts in ppm) instrument. Mass spectra (electronic ioniz-
ation Ϫ EI, and electrospray Ϫ ES) were recorded with a Nermag
R-1010C apparatus or a Micromass Platform II apparatus, respec-
´
tively, at the Service Commun de Spectrometrie de Masse Or-
ganique, Nancy. Infrared spectroscopy was performed with a Matt-
son 5000 FT apparatus (KBr, ν˜ in cmϪ1) and UV spectra were
recorded using a SAFAS UV mc2 apparatus, λmax. in nm, ε in
Conclusion
A new water-soluble calix[4]arene-based bipyridyl pod- dm3·molϪ1·cmϪ1. Elemental analyses were performed at the Service
de Microanalyse, Nancy. Merck TLC plates were used for chroma-
tographic analyses (SiO2, ref 1.05554; Al2O3, ref 1.05581). Sodium
and copper concentrations were determined by argon plasma emis-
sion spectrophotometry on a Spectrascan 7 Spectrametrics appar-
atus. Mass-coupled thermogravimetric analyses were performed
with a Netzch STA 409 C apparatus.
and 6 has been synthesized and subjected to complexation
studies with copper() and copper() species in water. The
copper() complex 7 exhibits considerable stability, even in
the presence of bovine serum albumin, promising interest-
ing behavior in biological media. It was fully characterized
as a mononuclear species, involving probably a pro-heli-
coidal pseudo-tetrahedral complexation mode between the
chelating bipyridines and the metallic center, as already ob-
served for organic-solvent soluble analogues. No crystals of
either water-soluble ligand 6 or the copper() complex 7
could be obtained, but the lipophilic tetra methyl ester in-
All commercially available products were used without further
purification unless otherwise specified.
N-Oxide 2: To a solution of dimethyl 6,6Ј-dimethyl-2,2Ј-bipyridine-
4,4Ј-dicarboxylate (1) (1 g, 3.30 mmol) in CH2Cl2 (20 mL) at 0 °C
under argon, was added dropwise a solution of m-chloroperbenzoic
termediate 4 reacted with zinc() chloride to give a mono- acid (0.685 g, 3.96 mmol; from 0.975 g of 70% commercial
2520  2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim www.eurjic.org
Eur. J. Inorg. Chem. 2004, 2514Ϫ2523

Synthesis of a Water-Soluble Calix[4]arene-Based Podand
mCPBA) in CH2Cl2 (10 mL). The mixture was then stirred at room 133.52, 139.06, 139.82, 152.26, 153.88, 156.18, 156.25, 158.73,
FULL PAPER
temp. for 2.5 h (TLC monitoring; Al2O3, CH2Cl2/hexane, 90:10).
The solvent was evaporated to dryness at 25 °C, and the residue
was triturated with Et2O to remove mCBA and unchanged
mCPBA. The resultant solid, which contained 90% of the mono N-
oxide, traces of di-N-oxide, and unchanged bipyridine was retained
at Ϫ20 °C. (1.025 g). A small analytical sample of 2 was obtained
by rapid chromatography (Al2O3; CH2Cl2). 1H NMR (CDCl3): δ ϭ
2.62 (s, 3 H, Mebpy), 2.74 (s, 3 H, Mebpy), 3.98 (s, 3 H, COOMe),
3.99 (s, 3 H, COOMe), 7.82 (s, 1 H), 7.94 (d, J ϭ 2.7 Hz, 1 H),
8.61 (d, J ϭ 2.7 Hz, 1 H), 9.05 (s, 1 H) (3-H, 3Ј-H, 5-H, 5Ј-H)
ppm. 13C NMR (CDCl3): δ ϭ 18.80 (Mebpy), 24.99 (Mebpy), 53.22
(ϪOMe), 122.00, 123.75, 126.00, 126.38 (C3, C3Ј, C5, C5Ј), 125.74,
138.45, 147.61, 150.53, 150.77, 159.82 (C2, C2Ј, C4, C4Ј, C6, C6Ј),
164.96, 166.11 (COOMe) ppm. C16H16N2O5·0.1H2O (318.11):
calcd. C 60.41, H 5.13, N 8.80; found C 60.17, H 4.98, N 8.57.
159.82 (C2, C2Ј, C4, C4Ј, C6, C6Ј of bpy; Ci,o,p of Ar), 165.58,
166.43 (COOMe) ppm. MS (ES, positive mode): m/z ϭ 1020 [4]ϩ,
703 [4 Ϫ OCH2Bpy(COOMe)2]ϩ. C60H52N4O12 (1021.07): calcd. C
70.58, H 5.13, N 5.49; found C 70.48, H 5.45, N 5.34.
Calixarene Tetraacid 5 and Calixarene Tetraacid Sodium Salt 6: A
suspension of 4 (1 g; 0.98 mmol) in a solution of NaOH (0.4 g;
10 mmol) in MeOH (110 mL) and H2O (90 mL) was heated to re-
flux under argon for 24 h. After cooling to room temp., the solu-
tion was acidified to pH 3Ϫ4 with 1  HCl. The resultant precipi-
tate of tetraacid 5 was filtered, washed with H2O (4 ϫ 30 mL), then
dispersed in H2O (50 mL) and dissolved by careful addition of 1 
NaOH up to pH 7.0. The resultant solution was evaporated to
dryness to give 6 (0.97 g; 80%). 6: White powder, m.p. 270Ϫ280 °C
(dec.). IR: ν˜ ϭ 1555.8 (CϭN), 1604.3 (COONa). UV (H2O): λ ϭ
302 nm (21600). 1H NMR (D2O): δ ϭ 2.54 (s, 6 H, Mebpy),
3.18Ϫ3.96 (‘‘q’’, JAB ϭ 15 Hz, 8 H, Ar-CH2-Ar), 5.34 (s, 4 H,
ϪOCH2bpy), 6.41 (t, J ϭ 7.5 Hz, 2 H, 4-H of Ar1), 6.63 (d, J ϭ
7.4 Hz, 4 H, 3-H and 5-H of Ar1), 6.66 (t, J ϭ 7.4 Hz, 2 H, 4-H
of Ar2), 7.03 (d, J ϭ 7.7 Hz, 4 H, 3-H and 5-H of Ar2), 7.53 (s, 2
H, 3Ј-H or 5Ј-H of bpy), 7.65 (s, 2 H, 5Ј-H or 3Ј-H of bpy), 7.96
(s, 2 H, 3-H or 5-H of bpy), 8.22 (s, 2 H, 5-H or 3-H of bpy) ppm.
13C NMR (D2O): δ ϭ 23.29 (Mebpy), 30.79 (Ar-CH2-Ar), 78.25
(ϪOCH2), 119.24, 120.59, 121.68, 123.32, 124.07, 126.18 (C3, C3Ј,
C5, C5Ј of bpy; Cp of Ar), 128.46, 133.71 (Coof Ar), 129.40 (Cmof
Ar), 147.49, 147.64, 150.87, 152.09, 155.42, 156.00, 156.38, 159.68
(C2, C2Ј, C4, C4Ј, C6, C6Ј of bpy; Cp of Ar), 172.93, 173.60
(COOϪ) ppm. ES-MS: (positive mode, 30 V): m/z ϭ 1075.98 [6 ϩ
Naϩ]ϩ, 549.27 [6 ϩ 2 Naϩ]2ϩ/2; (negative mode, 20 V): m/z ϭ
503.24 [6 Ϫ 2 Naϩ]2Ϫ/2, 492.23 [6 Ϫ 3 Naϩ ϩ Hϩ]2Ϫ/2, 481.22 [6
Ϫ 4 Naϩ ϩ 2 Hϩ]2Ϫ/2, 327.87 [6 Ϫ 3 Naϩ]3Ϫ/3, 320.53 [6 Ϫ 4 Naϩ
ϩ Hϩ]3Ϫ/3, 240.04 [6 Ϫ 4 Naϩ]4Ϫ/4. C56H40N4Na4O12·2NaCl·6H2O
(1277.87): calcd. C 52.63, H 4.10, N 4.38; found C 52.88, H 3.82,
N 4.24.
Bromide 3: Compound 2 (1 g, 5.0 mmol) was dissolved at room
temp. in dry CH2Cl2 (10 mL), and trifluoroacetic anhydride
(10 mL) was added. The solution was brought to reflux under ar-
gon over 1.5 h, during which time it became orange. The solvents
were then evaporated to dryness. The raw material containing the
trifluoroacetic ester was dissolved at room temp. in a 1:1 mixture
of dry DMF and dry THF (15 mL), then anhydrous LiBr (2 g,
23 mmol, dried at 180 °C over 1 h) was added. The resultant yellow
mixture was stirred under argon for 4 h (TLC monitoring, SiO2,
CH2Cl2), and the solvents were evaporated to dryness (2 torr, 70
°C). The residue was washed with water (3 ϫ 20 mL) then chroma-
tographed (SiO2, CH2Cl2) to give the monobromide 3 (1 g, 55%),
the dibromide (0.25 g, 12%), and unchanged 1. White powder, m.p.
160Ϫ162 °C. IR: ν˜ ϭ 1565.8 (CϭN), 1731.3 (COOMe). UV-vis
1
(CH2Cl2): λ ϭ 310 nm (16700). H NMR (CDCl3): δ ϭ 2.75 (s, 3
H, Mebpy), 4.02 (s, 3 H, COOMe), 4.03 (s, 3 H, COOMe), 4.72 (s,
2 H, CH2Br), 7.79 (d, J ϭ 0.5 Hz, 1 H), 8.06 (d, J ϭ 1.1 Hz, 1 H),
8.79 (d, J ϭ 0.5 Hz, 1 H), 8.91 (d, J ϭ 1.3 Hz, 1 H, 3-H, 3Ј-H, 5-H,
5Ј-H) ppm. 13C NMR (CDCl3): δ ϭ 24.99 (Mebpy), 33.78 (BrCH2),
53.12, 53.25 (OMe), 118.25, 120.32, 123.37, 123.46 (C3, C3Ј, C5,
C5Ј), 139.16, 140.63, 155.83, 157.02, 157.97, 159.75 (C2, C2Ј, C4,
C4Ј, C6, C6Ј), 165.79, 166.38 (COOMe) ppm. MS (EI): m/z ϭ
A solution of 6 (0.925 g, 0.724 mmol) in water (50 mL) (pH ϭ 7.38)
was carefully acidified to pH ϭ 3.11 with 1  HCl. The resultant
yellow suspension was washed with CH2Cl2 (4 ϫ 30 mL) before the
residual organic solvent was removed under vacuum. The yellow
precipitate was filtered off, washed with H2O, CH3OH and CH2Cl2,
then dried under vacuum. (5; 0.65 g, 93%). M.p. 235 °C (dec.). IR:
380Ϫ378 [3]ϩ, 322Ϫ320 [3
Ϫ Ϫ
COOMe]ϩ; 299 [3 Br]ϩ.
C16H15BrN2O4·0.1CH2Cl2 (387.7): calcd. C 49.88, H 3.95, N 7.23;
found C 50.00, H 3.95, N 7.23.
1
ν˜ ϭ 1568.1 (CϭN), 1720.6 (COOH). H NMR ([D6]DMSO): δ ϭ
2.67 (s, 6 H, Mebpy), 3.48Ϫ4.27 (‘‘q’’, JAB ϭ 13 Hz, 8 H, Ar-CH2-
Ar), 5.41 (s, 4 H, CH2O), 6.61 (t, J ϭ 7.5 Hz, 2 H, Hp of Ar), 6.86
(t, J ϭ 7.5 Hz, 2 H, Hp of Ar), 7.09 (d, J ϭ 7.6 Hz, 4 H, Hmof Ar),
7.17 (d, J ϭ 7.6 Hz, 4 H, Hmof Ar), 7.73 (d, J ϭ 1 Hz, 2 H), 8.47
(s, 2 H), 8.62 (s, 4 H), 8.93 (s, 2 H, 3-H, 3Ј-H, 5-H, 5Ј-H of bpy
and ArOH) ppm. 13C NMR ([D6]DMSO): δ ϭ 25.03 (Mebpy),
31.59 (Ar-CH2-Ar), 78.78 (ϪOCH2), 118.02, 119.64, 119.81,
122.61, 123.74, 126.50 (C3, C3Ј, C5, C5Ј of bpy, Cp of Ar), 128.13,
134.43 (Co of Ar), 129.46, 129.99 (Cm of Ar), 140.49, 140.91,
152.75, 153.87, 155.77, 155.86, 158.79, 159.89 (C2, C2Ј, C4, C4Ј,
C6, C6Ј of bpy; Cipso of Ar), 166.65, 167.19 (COOH) ppm. ES-
Calixarene Tetraester 4:
A suspension of calix[4]arene (1 g;
2.35 mmol) and K2CO3 (0.305 g; 2.35 mmol) in anhydrous CH3CN
(50 mL) was heated to reflux under argon for 30 min. The bromide
3 (1.88 g; 4.95 mmol) was then added and reflux was continued for
4 h (TLC monitoring; SiO2, CH2Cl2/MeOH, 95:5). The solvent was
evaporated to dryness, and the residue was washed with Et2O and
water before being chromatographed (SiO2, CH2Cl2) to give 4 (2 g;
83%). White powder, m.p. 268Ϫ270 °C (dec.). IR: ν˜ ϭ 1567.9 (Cϭ
N), 1732.1 (COOMe). UV (CH2Cl2): λ ϭ 310 nm (23200). 1H
NMR (CDCl3): δ ϭ 2.77 (s, 6 H, Mebpy), 3.48Ϫ4.43 (‘‘q’’, AB,
JAB ϭ 13 Hz, 8 H, Ar-CH2-Ar), 3.55 (s, 6 H, ϪOMe), 3.99 (s, 6 H,
Ms (pos. mode): m/z ϭ 965.35 [5 ϩ Hϩ]ϩ, 483.30 [5 ϩ 2 Hϩ]2ϩ/2
.
ϪOMe), 5.47 (s, 4 H, ϪOCH2bpy), 6.71 (t, J ϭ 7.4 Hz, 2 H, 4-H
of Ar-OH), 6.86 (t, J ϭ 7.8 Hz, 2 H, 4-H of Ar), 7.00 (d, J ϭ
7.6 Hz, 4 H, 3-H and 5-H of Ar), 7.12 (d, J ϭ 7.4 Hz, 4 H, 3-H
and 5-H of Ar-OH), 7.77 (d, J ϭ 1 Hz, 2 H, 3Ј-H or 5Ј-H of bpy),
C56H44N4O12·2.5H2O (1010.01): calcd. C 66.59, H 4.89, N 5.55;
found C 66.89, H 4.83, N 5.10.
Copper(I) Complex 7: A solution of [Cu(MeCN)4]PF6 (0.076 g,
8.18 (s, 2 H, ArOH), 8.71 (d, J ϭ 1.0 Hz, 2 H, 5Ј-H or 3Ј-H of 0.205 mmol) in MeCN was added to a solution of 6 (0.3 g,
bpy), 8.84 (d, J ϭ 1.1 Hz, 2 H, 3-H or 5-H of bpy), 9.12 (d, J ϭ 0.204 mmol) in H2O (10 mL). The resultant deep red solution was
1 Hz, 2 H, 5-H or 3-H of bpy) ppm. 13C NMR (CDCl3): δ ϭ 25.04 stirred at room temp. for 10 min, and the solvents were evaporated
(Mebpy), 31.98 (Ar-CH2-Ar), 52.63 (ϪOMe), 53.05 (ϪOMe), 78.77 to dryness to give 7 as a brown-red powder. (0.34 g, 100%). IR:
(ϪOCH2bpy), 117.95, 119.50, 120.11, 121.98, 123.28, 126.24 (C3,
C3Ј, C5, C5Ј of bpy, Cp of Ar), 128.98, 129.69 (Cm of Ar), 128.12, (22780), 470 nm (5210; MLCT). H NMR ([D6]DMSO): δ ϭ 1.76
ν˜ ϭ 855 (PF6Ϫ), 1555.4 (CϭN), 1608.7 (COOϪ). UV: λ ϭ 320
1
Eur. J. Inorg. Chem. 2004, 2514Ϫ2523
www.eurjic.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2521

N. Psychogios, J.-B. Regnouf-de-Vains, H. M. Stoeckli-Evans
(s, 6 H, Mebpy), 3.27Ϫ4.24 (‘‘q’’, JAB ϭ 12 Hz, 4 H, Ar-CH2-Ar), Details for the experimental conditions, cell data, structure, and
FULL PAPER
5.31Ϫ6.27 (‘‘q’’, JAB ϭ 11.0 Hz, 4 H, CH2O), 6.42 (t, J ϭ 7.0 Hz,
2 H, Hp of Ar1), 6.80 (d, J ϭ 7.4 Hz, 2 H, Hm of Ar1), 6.87 (t, J ϭ
7.0 Hz, 2 H, Hp of Ar2), 6.92 (d, J ϭ 7.6 Hz, 2 H, Hm of Ar1),
7.16 (d, J ϭ 7.0 Hz, 2 H, Hm of Ar2), 7.28 (d, Jϭ 7.0 Hz, 4 H, Hm
of Ar2), 7.78 (s, 2 H, 5-H or 3-H bpy), 8.04 (s, 2 H, 5Ј-H or 3Ј-H
bpy), 8.67 (s, 2 H, 3-H or 5-H bpy), 8.87 (s, 2 H, 3Ј-H or 5Ј-H bpy)
refinement data are given in Table 3.
Table 3. Crystal data and structural refinement of 9
Empirical formula
C62.25H56.5Cl8.5N4O12Zn2
[Cl4Zn2(C60H52N4O12)]·
2.25(CH2Cl2)]
1484.68
ppm. ES-MS (neg. mode, 30 V): m/z ϭ 544.4 [6 ϩ Cuϩ Ϫ Naϩ
2 Hϩ]2Ϫ/2, 523.20 [6 ϩ Cuϩ Ϫ 3 Naϩ]2Ϫ/2, 512.19 [6 ϩ Cuϩ
Ϫ
Formula mass
Temperature
Ϫ
4 Naϩ ϩ Hϩ]2Ϫ/2, 341.25 [6 ϩ Cuϩ Ϫ 4 Naϩ]3Ϫ/3, 312.83 [NaPF6
ϩ PF6 Ϫ]Ϫ, 144.87 [PF6Ϫ]Ϫ. C56H40N4Na4O12·CuPF6·NaCl·4H2O
(1391.91): calcd. C 48.32, H 3.48, N 4.03; found C 48.18, H 3.71,
N 4.00.
153(2) K
triclinic, P1
¯
Crystal system, Space group
Unit cell dimensions
˚
a [A]
11.6265(9)
16.3888(13)
36.039(3)
80.222(6)
89.128(6)
84.924(6)
6740.7(9)
4
˚
b [A]
˚
c [A]
Copper(ii) Complex 8: A solution of ligand 6 (0.1 g; 0.0783 mmol)
in H2O (3 mL) was mixed with a solution of CuCl2(H2O)2
(0.0267 g; 0.156 mmoles) in H2O (2 mL) at room temp., resulting
in the immediate formation of a green-brown gelatinous precipitate.
The solvent was evaporated to dryness under high vacuum without
heating. The resultant solid was then triturated with H2O (3 ϫ
2 mL) and filtered to give 8. (0.094 g; 98%). Deep-brown solid.
α [°]
β [°]
γ [°]
3
˚
V [A ]
Z
Dcalcd. [g·cmϪ3
]
1.463
1.110
Linear absorption coefficient
IR: ν˜ ϭ 1559.20 (CϭN), 1611.12 (COOϪ). C56H40Cu2ClN4Na- [mmϪ1
]
F(000)
Crystal size [mm]
θ Range for data collection [°]
Limiting indices
2656
O12·4.5H2O (1227.54): calcd. C 54.79, H 4.02, N 4.56; found
C 54.70, H 3.83, N 4.65.
0.50 ϫ 0.24 ϫ 0.10
1.15 to 24.10
Ϫ12 Յ h Յ 13
Ϫ18 Յ k Յ 18
Ϫ41 Յ l Յ 41
43707/20350
8602
0.550 and 0.091
20350/0/1468
Zinc(ii) Complex 9: A solution of ligand 4 (0.05 g; 0.045 mmol) in
CH2Cl2 (5 mL) was mixed with ZnCl2 (0.06 g; 0.44 mmol) at room
temp. under Ar. The resultant solvents were evaporated to dryness,
twice dissolved in CH2Cl2 and filtered then evaporated to dryness.
The residue was dissolved in CH2Cl2 (5 mL) and precipitated in an
excess of Et2O to give 9 as a light yellow powder (0.056 g; 95%).
UV: λ ϭ 338 nm (34650). 1H NMR (CD2Cl2): δ ϭ 3.11 (s, 6 H,
Mebpy), 3.57 (s, 6 H, COOMe), 3.67, 4.36 (AB, JAB ϭ 13.5 Hz, 8
H, Ar-CH2-Ar), 4.14 (s, 6 H, COOMe), 5.83 (s, 4 H, OCH2bpy),
6.77 (t, J ϭ 7.4 Hz, 2 H, Hp of Ar1), 6.99 (t, J ϭ 7.4 Hz, 2 H, Hp
of Ar2), 7.12 (d, J ϭ 7.6 Hz, 4 H, Hm of Ar2), 7.20 (d, J ϭ 7.6 Hz,
4 H, Hm of Ar1), 7.90 (s, 2 H, OH), 8.24 (s, 2 H, 3-H or 5-H of
Mepy), 8.77 (s, 2 H, 3-H or 5-H of OCH2py), 8.89 (s, 2 H, 3-H or
5-H of CH3py), 9.90 (s, 2 H, 3-H or 5-H of OCH2py) ppm. ES-
MS (pos. mode, 100 V): m/z ϭ 1315.3 [4 ϩ 2 ZnCl2 ϩ Naϩ]ϩ,
1257.3 [4 ϩ ZnCl2 ϩ ZnCl]ϩ, 1179.4 [4 ϩ ZnCl2 ϩ Naϩ]ϩ, 1043.4
[4 ϩ Naϩ]ϩ, base peak. C60H52Cl2N4O12Zn2 (1293.63): calcd. C
55.71, H 4.05, N 4.39; found C 55.76, H 4.08, N 4.37.
Reflections collected/unique
Number of observed reflections
Max./min. transmission
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I Ͼ 2σ(I)]
R indices (all data)
1.022
R1 ϭ 0.0854, wR2 ϭ 0.2138
R1 ϭ 0.1575, wR2 ϭ 0.2493
0.465/Ϫ0.865
3
˚
Densities (max./min.) [e·A ]
CCDC-213363 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge at
www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge
Crystallographic Data Center, 12 Union Road, Cambridge
CB2 1EZ, UK; Fax: (internat.) ϩ44-1223/336-033; E-mail:
deposit@ccdc.cam.ac.uk].
X-ray Crystallographic Study: The intensity data were collected at
153 K (Ϫ120 °C) with a Stoe Mark II-Image Plate Diffraction Sys-
tem[44] equipped with a two-circle goniometer using Mo-Kα graph-
ite-monochromated radiation. Image plate distance 100 mm, ω ro-
tation scans 0Ϫ180° at ϕ 0°, and 0Ϫ21° at ϕ 90°, step ∆ω ϭ 1.2°,
Acknowledgments
We are grateful to the MRES and CNRS for financial support,
and to SAFAS (Monaco) for UV spectroscopy facilities. N. P. is
˚
2θ range 2.29Ϫ59.53°, dmax. Ϫ dmin. ϭ 17.799Ϫ0.716 A.
´
grateful to the Fondation pour la Recherche Medicale, Paris, for a
The structure was solved by direct methods using the program
SHELXS-97.[45] The refinement and all further calculations were
carried out using SHELXL-97.[46] The H-atoms were either located
from Fourier difference maps and refined isotropically or included
in calculated positions, and treated as riding atoms using SHELXL
default parameters. The non-H atoms were refined anisotropically,
using weighted full-matrix least-squares on F2.
`
Fin de These grant. The authors thank Mr. J.-M. Ziegler and Mrs.
E. Eppiger for mass spectrometry, and NMR spectrometric meas-
urements, respectively.
[1]
A. Casnati, D. Sciotto, G. Arena, in Calixarene 2001 (Eds.: Z.
Asfari, V. Böhmer, J. Harrowfield, J. Vicens), Kluwer, Dord-
recht, The Netherlands, 2001, pp. 440Ϫ456.
A. Arduini, A. Pochini, S. Reverberi, R. Ungaro, J. Chem. Soc.,
[2]
An empirical absorption correction was applied using the DIFABS
routine in PLATON.[42] Transmission factors Tmin./Tmax. were 0.091
and 0.550, respectively. A considerable amount of disordered sol-
vent was present and the SQUEEZE routine in PLATON revealed
Chem. Commun. 1984, 981.
[3]
C. D. Gutsche, P. F. Pagoria, J. Org. Chem. 1985, 50, 5795.
[4]
C. D. Gutsche, I. Alam, Tetrahedron 1988, 4689.
[5]
S. Shinkai, S. Mori, T. Tsukabi, T. Sone, O. Manabe, Tetra-
3
˚
the presence of 380 electrons for a volume of 1559 A . This could
be equated to 9 molecules of CH2Cl2 per unit cell and the hkl file
was modified accordingly.
hedron Lett. 1984, 25, 5315.
S. Shinkai, K. Araki, T. Tsubaki, T. Arimura, O. Manabe, J.
Chem. Soc., Perkin Trans. 1 1987, 2297.
[6]
2522
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjic.org
Eur. J. Inorg. Chem. 2004, 2514Ϫ2523

Synthesis of a Water-Soluble Calix[4]arene-Based Podand
FULL PAPER
B. Alpha, E. Anklam, R. Deschenaux, J.-M. Lehn, M. Pietras-
kiewicz, Helv. Chim. Acta 1988, 71, 1042.
L. Motta, J.-B. Regnouf de Vains, C. Bavoux, M. Perrin, J.
Chem. Crystallogr. 1995, 25, 401.
V. Boekelheide, D. L. Harrington, Chem. Ind. 1955, 1423.
V. J. Traynelis, R. F. Martello, J. Am. Chem. Soc. 1958, 80,
6590.
G. R. Newkome, W. E. Puckett, G. E. Kiefer, V. K. Gupta, Y.
Xia, M. Coreil, M. A. Hackney, J. Org. Chem. 1982, 47, 4116.
J.-M. Lehn, J.-B. Regnouf de Vains, Tetrahedron Lett. 1989,
30, 2209.
G. R. Newkome, K. J. Theriot, V. K. Gupta, F. R. Fronczek,
G. R. Baker, J. Org. Chem. 1989, 54, 1766.
J.-M. Lehn, J.-B. Regnouf de Vains, Helv. Chim. Acta 1992,
75, 1221.
[7]
[27]
[28]
M. Almi, A. Arduini, A. Casnati, A. Pochini, R. Ungaro,
Tetrahedron 1989, 45, 2177.
D. Gutsche, K. C. Nam, J. Am. Chem. Soc. 1988, 110, 6153.
J.-B. Regnouf-de-Vains, R. Lamartine, Helv. Chim. Acta 1994,
77, 1817.
[8]
[9]
[29]
[30]
[10]
J.-B. Regnouf-de-Vains, S. Pellet-Rostaing, R. Lamartine,
Tetrahedron Lett. 1995, 36, 5745.
J.-B. Regnouf-de-Vains, R. Lamartine, B. Fenet, C. Bavoux, A.
[31]
[32]
[33]
[34]
[35]
[11]
Thozet, M. Perrin, Helv. Chim. Acta 1995, 78, 1607.
S. Pellet-Rostaing, J.-B. Regnouf-de-Vains, R. Lamartine,
[12]
Tetrahedron Lett. 1996, 37, 5889.
S. Pellet-Rostaing, J.-B. Regnouf-de-Vains, R. Lamartine, P.
[13]
Meallier, S. Guittonneau, B. Fenet, Helv. Chim. Acta 1997,
80, 1229.
[14]
J.-B. Regnouf de Vains, A.-L. Papet, A. Marsura, J. Hetero-
cyclic Chem. 1994, 31, 1069.
J.-B. Regnouf-de-Vains, R. Lamartine, B. Fenet, Helv. Chim.
Acta 1998, 81, 661.
S. Pellet-Rostaing, J.-B. Regnouf-de-Vains, R. Lamartine, B.
[36]
[37]
[15]
F. Camps, V. Gasol, A. Guerrero, Synthesis 1987, 5, 511.
M. Harding, U. Koert, J.-M. Lehn, A. Marquis-Rigault, C.
Piguet, J. Siegel, Helv. Chim. Acta 1991, 74, 594.
R. Ziessel, J.-M. Lehn, Helv. Chim. Acta 1990, 73, 1149.
P.-D. Beer, J.-P. Martin, M. G. B. Drew, Tetrahedron 1992, 48,
9917.
C. Jaime, J. de Mendoza, P. Prados, P. M. Nieto, C. Sanchez,
J. Org. Chem. 1991, 56, 3372.
J. O. Magrans, J. de Mendoza, M. Pons, P. Prados, J. Org.
Chem. 1997, 62, 4518.
‘‘PLATON/PLUTON version Jan. 1999’’, A. L. Spek, Acta
Crystallogr., Sect. A 1990, 46, C-34.
J.-O. Dalbavie, J.-B. Regnouf-de-Vains, R. Lamartine, M. Per-
rin, S. Lecocq, B. Fenet, Eur. J. Inorg. Chem. 2002, 901.
Stoe & Cie, X-Area V1.17 & X-RED32 V1.04 Software, Stoe &
Cie GmbH, Darmstadt, Germany, 2002.
Fenet, Inorg. Chem. Commun. 1999, 2, 4.
Y. Molard, C. Bureau, H. Parrot-Lopez, R. Lamartine, J.-B.
[16]
[38]
[39]
Regnouf-de-Vains, Tetrahedron Lett. 1999, 40, 6383.
J.-O. Dalbavie, J.-B. Regnouf-de-Vains, R. Lamartine, S. Lec-
[17]
ocq, M. Perrin, Eur. J. of Inorg. Chem. 2000, 4, 683.
F. Tisato, F. Refosco, G. Bandoli, G. Pilloni, B. Corain, Inorg.
[40]
[41]
[42]
[43]
[44]
[45]
[46]
[18]
Chem. 2001, 40, 1394.
Y. Rondelez, G. Bertho, O. Reinaud, Angew. Chem. Int. Ed.
[19]
2002, 41, 1044.
[20]
N. Psychogios, J.-B. Regnouf-de-Vains, Tetrahedron Lett. 2001,
42, 2799.
N. Psychogios, J.-B. Regnouf-de-Vains, Tetrahedron Lett. 2002,
43, 77.
N. Psychogios, J.-B. Regnouf-de-Vains, Tetrahedron Lett. 2002,
43, 7691.
C. D. Gutsche, J. A. Levine, J. Am. Chem. Soc. 1982, 104, 2652.
C. D. Gutsche, J. A. Levine, P. K. Sujeeth, J. Org. Chem. 1985,
50, 5802.
H. M. Chawla, K. Srinivas, Indian J. Chem. 1993, 32B, 1162.
B. Yao, J. Bassus, R. Lamartine, An. Quim. 1997, 93, 165.
[21]
[22]
G. M. Sheldrick, ‘‘SHELXS-97 Program for Crystal Structure
Determination’’, Acta Crystallogr., Sect. A 1990, 46, 467.
G. M. Sheldrick, ‘‘SHELXL-97’’, University Göttingen, Ger-
many, 1999.
[23]
[24]
Received September 30, 2003
Early View Article
Published Online April 20, 2004
[25]
[26]
Eur. J. Inorg. Chem. 2004, 2514Ϫ2523
www.eurjic.org
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