One methylene too far: The solid state structure of the para-sulfonatomethylcalix[4]arene

Article abstract of DOI:10.1016/j.molstruc.2006.06.029

We report here, the first crystallographic structure of the new water soluble calixarene, para-sulfonatomethylcalix[4]arene. Anchoring a methylene group between the aromatic core of the calixarene and sulfonate groups extended the hydrophobic cavity but led to a more flexible macromolecule allowing formation of hydrogen bonds between vicinal sulfonate groups, causing the groups to point towards the cavity and effectively close it, with S ? S distances of 9.7 ? × 7.9 ?. The packing motif consists of bilayers of para-sulfonatomethylcalix[4]arene along both the a and b axis.

Full text of DOI:10.1016/j.molstruc.2006.06.029

Journal of Molecular Structure 830 (2007) 35–39
www.elsevier.com/locate/molstruc
One methylene too far: The solid state structure of the
para-sulfonatomethylcalix[4]arene
Florent Perret a,¤, Stéphanie Guéret a, Kinga Suwinska b, Anthony W. Coleman a
a Institut de Biologie et Chimie des Protéines (IBCP UMR 5086), CNRS, Université Lyon 1, IFR128 BioSciences Lyon-Gerland, 7 passage du Vercors,
F-69367 Lyon cedex 07, France
b Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka, 44/52, PL-01 224 Warszawa, Poland
Received 31 May 2006; received in revised form 27 June 2006; accepted 28 June 2006
Available online 1 August 2006
Abstract
We report here, the Wrst crystallographic structure of the new water soluble calixarene, para-sulfonatomethylcalix[4]arene. Anchoring
a methylene group between the aromatic core of the calixarene and sulfonate groups extended the hydrophobic cavity but led to a more
Xexible macromolecule allowing formation of hydrogen bonds between vicinal sulfonate groups, causing the groups to point towards the
cavity and eVectively close it, with S , S distances of 9.7 Å £ 7.9 Å. The packing motif consists of bilayers of para-sulfonatomethylca-
lix[4]arene along both the a and b axis.
© 2006 Elsevier B.V. All rights reserved.
Keywords: para-Sulfonatomethylcalix[4]arene; Calixarene; Crystal structure; X-ray crystallography
1. Introduction
both increase the Xexibility of the sulfonate group at the
upper rim of the calixarene and to extend the depth of the
hydrophobic cavity, we have inserted methylene groups
between the aromatic core and the ionisable functions,
leading to the para-sulfonatomethylcalix[4]arene 1 [19,20]
(Fig. 1). Here, we describe the Wrst crystallographic study of
this new water soluble calixarene, the results are cautionary
as eVectively the cavity is no longer open and hence inclu-
sion is blocked.
Water soluble calixarene derivatives have been well stud-
ied since 1984, when the Wrst one was synthesised.[1]
Among them, the para-sulfonatocalix[n]arenes are the most
widely studied, both in solution and in the solid state. A
large body of work has been carried out in aqueous media
on the biochemistry of the para-sulfonatocalix[n]arenes and
they have been found to have interesting bioactivities.[2]
Concerning the solid state, the Wrst structure of the sodium
salt of para-sulfonatocalix[4]arene was published by
Atwood et al. in 1988.[3] Since then, work has been carried
out to study the solid state complexation of these calixa-
renes with various molecules including organic ammonium
cations,[4–9] amino-acids [10–14], lanthanide cations,[15].
Depending on the nature of guest molecules, they can
adopt diVerent conformations leading to various kinds of
packing: classic bilayers [10,12,16], zig-zag bilayers [13],
stepped bilayers[17], capsules, and tubes [18]. In order to
2. Experimental
2.1. Synthesis
para-Sulfonatomethylcalix[4]arene, 1, has been synthe-
sised as previously reported [19,20].
The Wrst step consists of the synthesis of the 5,11,17,23-
tetrachloromethyl-25,26,27,28-tetrahydroxycalix[4]arene : to
a solution of p-H-calix[4]arene (3.0g; 7mmol) and chloro-
methyl-n-octylether (46.75mL; 240mmol) in 300 ml CHCl3,
cooled at ¡10°C, was added SnCl4 (14.1mL, 12mmol)
in about 15min. The cooling bath was removed and the
*
Corresponding author. Tel.: +33 4 72 72 26 40; fax: +33 4 72 72 26 90.
E-mail address: f.perret@ibcp.fr (F. Perret).
0022-2860/$ - see front matter © 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2006.06.029

36
F. Perret et al. / Journal of Molecular Structure 830 (2007) 35–39
Fig. 1. Structural formula of the p-sulfonatomethyl-calix[4]arene 1, and molecular structure of the complex.
Table 1
Table 2
Hydrogen bonds (Å and °)
Crystallographic data for para-sulfonatomethyl-calix[4]arene–triethylam-
monium complexes
D–H , A
d(D–H) d(H , A) d(D , A) <(DHA)
Empirical formula
C32H32O16S4·2CH3OH·C3H6O·4.5H2O
O1–H1 , O2
0.84
0.84
0.84
0.84
0.84
0.84
0.84
0.85
0.84
2.07
2.64
1.99
2.14
2.54
1.99
2.04
1.35
1.66
2.66(1)
3.22(1)
2.68(1)
2.69(1)
3.18(2)
2.66(1)
2.87(4)
2.17(3)
2.21(2)
126.6
127.3
138.7
123.3
134.6
136.1
168.8
160.2
120.4
Formula weight
Temperature (K)
Wavelength (Å)
Crystal system
Space group
Unit cell dimensions
a (Å)
b (Å)
c (Å)
ꢀ (°)
ꢁ (°)
1004.08
100(2)
0.71073
Triclinic
P-1
O1–H1 , O41
O2–H2 , O3
O3–H3A , O4
O3–H3A , O1A2
O4–H4 , O1
O11M–H11M , O6
O12M–H12M , O3W3
O2M–H2M , O73
10.866(2)
10.947(2)
18.245(2)
94.344(7)
97.722(8)
100.933(7)
2100.1(6)
2
Possible hydrogen bonds to water molecules
O5 , O3W3
2.50(1)
2.73(2)
2.72(2)
2.13(2)
3.03(1)
2.50(2)
3.05(2)
2.26(2)
2.68(2)
2.08(2)
2.67(2)
2.86(2)
2.25(2)
2.36(2)
2.82(2)
2.44(2)
2.84(2)
2.09(2)
1.99(2)
2.47(1)
2.24(1)
2.20(4)
2.40(3)
2.17(3)
1.95(3)
2.19(2)
2.14(2)
O6 , O3W3
ꢂ (°)
O6 , O5W3
Volume (Å3)
Z
O8 , O3W3
O9 , O2W4
Calculated density (Mg · m¡3
Absorption correction
F (000)
)
1.567
None
1032
O10 , O1W
O10 , O3W3
O10 , O4W3
O11 , O1W
Crystal size (mm3)
0.10 £ 0.10 £ 10
ꢃ range for data collection (°)
Limiting indices
2.98–20.30
O11 , O4W3
O12 , O1W5
O12 , O2W
¡10 6 h 6 10, ¡10 6 k 6 10,
¡17 6 l 6 17
7318 /3934 [Rint D 0.101]
96.8%
ReXections collected/unique
Completeness to ꢃ D 20.30°
ReWnement method
O13 , O5W
O14A , O5W
O14B , O1W3
O14B , O1W6
O15 , O1W3
O15 , O3W
Full-matrix least-squares on F2
3934/0/625
Data/restraint/parameters
Goodness-of-Wt on F2
0.980
Final R indices [I > 2ꢄ(I)]
Final R indices [all data]
R D 0.210, wR D 0.315
R D 0.114, wR D 0.267
O15 , O4W
O16 , O5W
O16 , O5W3
O11M , O3W3
O11M , O4W3
O12M , O3W3
O12M , O4W3
O1W , O4W3
O3W , O4W
reaction mixture stored at room temperature for additional
50min. Water was then added slowly and the two phases
separated. The organic layer was washed twice with distilled,
dried on Na2SO4 and evaporated to give a residue which
was treated with n-hexane and Wltered. A white powder is
obtained and dried. Yield 67%. H NMR (293K, CDCl3)
3.60 and 4.20ppm (2 bs, 8H, Ar-CH2-Ar); 4.43ppm (s, 8H,
Ar-CH2-Cl); 7.10ppm (s, 4H, Ar-H); 10.1ppm (s, 4H, Ar-
1
Symmetry transformations used to generate equivalent atoms: (1)
¡x + 1,¡y,¡z + 1; (2) ¡x + 1,¡y + 1,¡z + 1; (3) ¡x + 1,¡y,¡z; (4)
x,+y ¡ 1,+z; (5) ¡x + 2,¡y,¡z; (6) x ¡ 1,+y,+z.

F. Perret et al. / Journal of Molecular Structure 830 (2007) 35–39
37
Fig. 2. (a) Top view of para-sulfonatomethylcalix[4]arene 1 showing that its cavity is less accessible than the one of para-sulfonatocalix[4]arene 2 (b).
OH). 13C NMR (293K, CDCl3) 31.6 (t, Ar-CH2-Ar); 45.8 (t,
Ar-CH2-Cl); 128.3 (s, Ar-ortho); 129.5 (d, Ar-meta); 131.4 (s,
Ar-para); 148.9 (s, Ar-O).
To a solution of 5,11,17,23-tetrachloromethyl-25, 26,
27,28-tetrahydroxycalix[4]arene (1.54g, 2.5mmol) in EtOH
(10mL), an aqueous solution of Na2SO3 (2M, 11mmol) was
added. After reXuxing overnight, the solvent was evaporated
until the obtention of a precipitate which was then washed
with brine. After puriWcation on an Amberlit IR-120 col-
umn, the residue is recrystallised from methanol to give pure
compound 1 as a white powder. Yield 60%. 1H NMR
(293K, D2O) 3.70ppm (s, 8H, Ar-CH2-Ar); 4.60ppm (s, 8H,
Ar-CH2-SO3Na); 6.90ppm (s, 8H, Ar-H). ES-MS (negative
Weld, m/z): 865 (M-Na+), 421 ((M-2Na+)/2).
Crystals were obtained by recrystallisation of the crude
reaction product from an acetone/methanol mixture.
2.2. X-ray crystallography
X-ray data were collected on a Nonius KappaCCD
diVractometer. Data were corrected for Lorentz and polarisa-
Table 3
Comparison of the apparent stability constants K calculated for the com-
plexes formed between the p-sulfonatomethylcalix[4]arene 1 and p-sulfo-
natocalix[4]arene 2 with arginine and lysine in water at pH 7.5 (phosphate
buVer) and 298.15 Ka [23]
Compound
Kb
1
2
Arginine
Lysine
a
40 (§10)
100 (§20)
1780 (§220)
740 (§60)
Fig. 3. Calixarene packing via hydrogen bonds (blue lines) between phe-
nolic hydroxyl groups and short contacts (dark line) with acetone mole-
cules (purple). Hydrogen bonds with water molecules are not shown for
clarity. (For interpretation of the references to colour in this Wgure legend,
the reader is referred to the web version of this paper.)
K deduced from the non-linear least-squares Wt of the data using a 1:1
binding model.
b
Molar scale. c Shifts of the lysine.

38
F. Perret et al. / Journal of Molecular Structure 830 (2007) 35–39
Fig. 4. View along the a axis of the structural bilayer packing motif; acetone channels are marked in orange. Calixarene molecules are colored in dark and
light blue, methanol molecules in green, acetone in purple and water molecules as red spheres. (For interpretation of the references to colour in this Wgure
legend, the reader is referred to the web version of this paper.)
tion eVects but not for absorption. The structure was solved
by direct methods and Fourier techniques (SHELXS-86, [21])
and reWned, on ΗFΗ2 (SHELX-97, [22]). All non-hydrogen
atoms were reWned anisotropically. H-atoms were included in
geometric positions and reWned as ‘riding’ atoms with isotro-
pic thermal parameters based upon the corresponding bond-
ing carbon or oxygen atom [Uiso D1.2Ueq, Uiso D1.5Ueq for
CH3 and OH hydrogens]. Experimental details for the struc-
ture determination are presented in Table 1, hydrogen bond
lengths and cone angle are listed in Table 2.
ture of para-sulfonatocalix[4]arene – triethylamine complex
[17] (Fig. 2), it can be clearly seen that the hydrophobic
cavity is less accessible than that of the “traditional” para-
sulfonatocalix[4]arene; the size of the upper rim
(7.9 £ 9.2 Å) of the para-sulfonatomethylcalix[4]arene being
noticeably smaller compared to the sulfonatocalixarene 2
(8.6 £ 12.3Å). This observation is in agreement with the
results we obtained on the complexation of 1 with lysine
and arginine.[23] The association constants values were
three orders of magnitude lower than those obtained for
para-sulfonatocalix[4]arene 2 (Table 3), leading us to postu-
late that the cavity was not accessible for the lateral chains
of these aminoacids.
3. Result and discussion
para-Sulfonatomethylcalix[4]arene 1 adopts a very
slightly Xattened cone conformation (cone angles between
the opposite aromatic rings are 78.7° and 62.4°). Hydrogen
bonds occur not only between the four phenolic hydroxyl
groups at the lower rim as, usually seen in the structure of
para-sulfonatocalix[4]arene 2, but also between sulfonate
groups at the upper rim causing them to be directed
towards the interior of the cavity. Each sulfonate group
also forms hydrogen bonds with either water or methanol
molecules (for details see Table 2).
The stoichiometry of the crystal is 1:2:1:4.5 for calixa-
rene, methanol, acetone and water, respectively. Even
though we have started with the acidic form of para-sul-
fonatomethylcalix[4]arene, in the crystal, the sulfonate
groups are hydrated and probably deprotonated; four
water molecules are probably protonated as hydroxonium
cations to balance the charge.
The two methanol molecules found in the crystal are not
chemically equivalent. One, disordered over two positions,
is bound within the cavity and forms with the calixarene an
inclusion complex with the methyl group pointing inside
the cavity. The two partially occupied hydroxyl groups are
Comparing the structure of this water soluble calixarene
with that of one of para-sulfonatocalix[4]arene in the struc-

F. Perret et al. / Journal of Molecular Structure 830 (2007) 35–39
39
hydrogen bond donors; one to a sulfonate group and the
second to a water molecule. In both orientations those
hydroxyls may also act as the acceptors of hydrogen bonds
from water molecules (for details see Table 2). The second
methanol molecule, situated near the upper rim, interacts
only with one of the sulfonate groups of para-sul-
fonatomethylcalix[4]arene via a hydrogen bond.
Water molecules are involved in a number of hydrogen
bonds with calixarene sulfonate groups, methanol mole-
cules as described above, and other water molecules form-
ing a complex hydrogen bond network. The acetone
molecule, which is also partially disordered, is not involved
in this network.
The solid state structure is generated by a new kind of
bilayer structural motif, diVerent from typical bilay-
ers[10,12,16] or zig-zag bilayers [13]. The bilayer is assumed
by direct hydrogen bonds between phenolic hydroxyl
groups of two calixarenes and strong hydrogen bonds
between sulfonate groups and water molecules (Fig. 3).
Between bilayers along crystallographic a axis, a hydropho-
bic channel Wlled with acetone molecules is formed (Fig. 4).
the Polish Ministry of Science and High Education (Grant
4 T09A 068 25).
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4. Conclusion
The Wrst para-sulfonatomethylcalix[4]arene crystallo-
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5. Supplementary materials
Crystallographic data for this complex reported in this
paper have been deposited with the Cambridge Crystallo-
graphic Data Center as supplementary materials (CCDC
607951). Copies of available material can be obtained free
of charge on application to the director, CCDC. 12 Union
Road, Cambridge CB2 1EZ, UK (Fax: +44 1223 336033;
e-mail: deposit@ccdc.cam..ac.uk.
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Acknowledgements
F.P. acknowledges support of the CNRS for a postdoc-
toral fellowship. This research was partially supported by