The structure of inclusion complex of β-cyclodextrin with p-nitrophenoxyacetic acid in solution and the solid state

Article abstract of DOI:10.1007/s10847-009-9721-8

The inclusion complex (1) of with β-cyclodextrin-p-nitrophenoxyacetic acid was synthesized and characterized. Its inclusion behavior was investigated by means of X-ray crystallography and NMR spectroscopy in solution and in the solid state. The crystallog

Full text of DOI:10.1007/s10847-009-9721-8

J Incl Phenom Macrocycl Chem (2010) 67:393–398
DOI 10.1007/s10847-009-9721-8
ORIGINAL ARTICLE
The structure of inclusion complex of b-cyclodextrin
with p-nitrophenoxyacetic acid in solution and the solid state
•
Min-Jie Guo Chun-Hua Diao Zuo-Liang Jing
•
•
•
Bin Dong Zhi Fan Min Wang
•
Received: 16 June 2009 / Accepted: 3 December 2009 / Published online: 18 December 2009
ꢀ Springer Science+Business Media B.V. 2009
Abstract The inclusion complex (1) of with b-cyclodex-
trin-p-nitrophenoxyacetic acid was synthesized and char-
acterized. Its inclusion behavior was investigated by means
of X-ray crystallography and NMR spectroscopy in solution
and in the solid state. The crystallographic study shows that
one b-cyclodextrin co-crystallize with one p-nitrophen-
oxyacetic acid, and 17 water molecules in the Monoclinic
system with unit cell constants: a = 18.6864(16), b =
an apolar cavity that can include a wide variety of guest
molecules into the host CD cavity to form supramolecular
inclusion complexes without formation of covalent bonds in
solution and/or in solid state [1–4]. The unique structural
features and fascinating properties enable these molecules to
be ideal prototypes for examining intermolecular interactions
associated with molecular recognition and assembly [5–8].
Therefore, there has been increasing interest in the inclusion
complexes formed by CD and all kinds of guest molecules in
order to understand the weak interactions associated with the
inclusion process. The large numbers of investigations indi-
cate that several factors contribute to the stabilization of the
inclusion complexes: hydrogen bonding and polar interac-
tions between the guest and host molecules, and the shape and
size of the guest [9–19]. However, the mechanisms of
molecular recognition and inclusion are still complicated.
To get insight into the conformation and mechanism of the
noncovalent interactions of inclusion complexes at the
molecular level, in present study, we prepared the inclusion
complex of b-CD with p-nitrophenoxyacetic acid (b-CD-p-
NPOAA), and investigated its binding behavior by means of
X-ray crystallography and NMR spectroscopy in the solid
state and in solution. It is of our particular interest to eluci-
date the weak interaction and the binding behavior of the
inclusion complexation on b-CD complexes.
˚
24.961(2), c = 16.6644(14) A, b = 105.129(5)ꢁ. Two
b-cyclodextrins are held together by hydrogen bonds to
form head-to-head dimers. The disordered guest molecule
molulates itself to attain the most stable accommodation
into the cavity in which the nitro group is located at the
dimer interface while the carboxyl group buried in the
primary hydroxyl groups of b-CD. The further 2D NMR
spectroscopy investigation in solution supports the inclu-
sion mode of the solid state.
Keywords b-Cyclodextrin ꢀ Inclusion complex ꢀ
Crystal structure ꢀ p-Nitrophenoxyacetic acid
Introduction
Cyclodextrins (CDs) are a unique family of naturally occur-
ringorganic compounds. These macrocyclic compounds have
M.-J. Guo ꢀ C.-H. Diao ꢀ Z.-L. Jing ꢀ B. Dong ꢀ Z. Fan (&)
College of Sciences, Tianjin University of Science
and Technology, Tianjin 300222, People’s Republic of China
e-mail: zhifan@tust.edu.cn
Experimental
Reagents
M. Wang
b-CD of reagent grade was recrystallized twice from water
and dried in vacuo at 95 ꢁC for 24 h prior to use,
p-NPOAA was commercially available and used without
further purification.
Key Laboratory of Industrial Microbiology, Ministry
of Education, School of Biological Engineering, Tianjin
University of Science and Technology, Tianjin 300222,
People’s Republic of China
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Apparatus
Crystals of 1 was obtained from aqueous solution. A
small amount of 1 was dissolved in hot water to make a
saturated solution, which was then cooled to room tem-
perature. After removal of the precipitates by filtration, the
resultant solution was kept at room temperature for 1 week.
The crystal formed was collected along with its mother
liquor for X-ray crystallographic analysis.
Elemental analyses was performed on a Perkin-Elmer
1
2400C instrument. H NMR spectra were recorded in D2O
on a Varian Mercury VX300 spectrometer. The X-ray
intensity data were collected on a Saturn-70 Rigaku CCD
Area Detector System equipped with a micro focus
molybdenum target of Micro-Max-007 rotating anode (Mo
˚
Ka radiation k = 0.71073 A) operated at 50 kV and
16 mA and a confocal monochromator. During data col-
lection, no intensity decay was observed. Data collection,
reduction and absorption correct were performed by pro-
gram Crystalclear [20]. The structure was eventually
solved employing SHELXD [21].
Results and discussion
The crystal structure of 1. The crystal data, experimental
and refinement parameters of 1 are shown in Table 1. In the
b-CD and p-NPOAA complex, b-CD forms a 1:1 complex
with p-NPOAA, as shown in Fig. 1. Every glucose residue
of b-CD has a 4C1 chair conformation, and seven glycosidic
Synthesis of complex 1
˚
oxygen atoms make up a plane (O4-plane) within 0.0540 A.
The ethanol solution of p-NPOAA (0.5 mmol, 30 mL) was
added dropwise to an aqueous solution of b-CD (0.5 mmol,
40 mL) and stirred at 60 ꢁC for 6 h. Then the solution was
cooled to room temperature, and the precipitate was
obtained by slow evaporation of the solution. The crude
product was recrystallized from water to give white solid 1
in 76% yield. Data for 1: 1H NMR (D2O, ppm) d 8.07–8.10
(d, 2H), 6.92–6.95 (d, 2H), 4.89–4.90 (m, 7H), 4.60 (s, 2H),
3.40–3.80 (m, 42H). Anal. Calcd for C50H77NO40ꢀ18H2O:
C, 36.25; H, 6.88, N, 0.85. Found: C, 36.40; H, 6.67, N,
0.63.
No disordered atom has been found in the host molecule.
The primary hydroxyl groups having a gauche-gauche
orientation point outward from the cavity, except atoms
O62, O64 and O65 which have gauche-trans orientation
point to the cavity. The parameters describing the macro-
cyclic conformation of 1 are presented in Table 2, the
sevenfold symmetry of the b-CD appears to be well main-
tained. This is also reflected in the O4(n)ꢀꢀꢀO4(n - 1) dis-
˚
tances [average 4.38 A] and O4(n ? 1)ꢀꢀꢀO4(n)ꢀꢀꢀO4
(n - 1) angles [128.5428ꢁ]. The latter is equal to the angle
of the regular heptagon (128.5714…ꢁ).
Table 1 The crystal data,
experimental and refinement
parameters of 1
Crystal 1
Molecular formula
Mr (g mol-1
C50 H111.25 N O57.13
)
1640.65
Crystal system
Space group
Z
Monoclinic
C2
4
˚
a (A)
18.6864(16)
˚
b (A)
24.961(2)
˚
c (A)
16.6644(14)
b (ꢁ)
V(A )
105.129(5)
3
˚
7503.3(11)
qcalcd (g cm-3
)
1.452
F (000)
3501
Absorption coefficient (mm-1
Crystal size (mm)
Correction method
Range scanned h (ꢁ)
Index range
)
0.134
0.40 9 0.38 9 0.20
Multi-scan
2.07 to 27.79
-24 B h B 24, -31 B k B 32, -21 B l B 21
16902/263/1143
Data/restraints/parameters
Final R indices [I [ 2sigma(I)]
R indices (all data)
R1 = 0.0498, wR2 = 0.1300
R1 = 0.0548, wR2 = 0.1347
0.589 and -0.671
-3
)
˚
Largest diff. peak and hole (e A
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J Incl Phenom Macrocycl Chem (2010) 67:393–398
395
Fig. 1 An diagram showing the
b-CD and p-NPOAA molecule
and the numbering scheme:
a Top and b side views of the
complex
Table 2 Geometrical data
describing the b-CD unit of the
compound
O4(n)–O4
˚
(n - 1) (A)
O4(n)–O4
(n ? 1)–O4(n ? 2) (ꢁ)
C4(n)–O4
(n)–C1(n ? 1) (ꢁ)
Tilt
angle (ꢁ)a
Deviation
of O(4)
atom (A)
b
˚
G1
G2
G3
G4
G5
G6
G7
4.431
4.343
4.247
4.563
4.362
4.297
4.432
130.1
122.3
132.9
131.0
123.2
129.4
130.8
117.5
119.0
116.6
118.0
119.4
117.3
117.9
21.9
25.9
30.0
23.2
23.2
29.2
27.7
0.0342
-0.0691
-0.0159
0.0954
a
The tilt angle is defined as an
angle made by the O4 plane and
the plane through C1, C2, O4
and O40
-0.0458
-0.0582
0.0594
b
The deviation of each O4
atom from the plane through O4
atoms
The disordered guest is included into the b-CD cavity in
which the nitro group points to the second hydroxyl groups.
The angle between the molecular axis of the disordered
guest and the perpendicular axis to the O4 plane of b-CD is
32.9ꢁ and 35.4ꢁ, respectively. And the aromatic ring center
of p-NPOAA are shifted from the O4 plane center to the
the occurrence of host–guest interaction and stabilize the
inclusion complex.
Two b-CD molecules form a head-to-head dimer which
the secondary hydroxyl sides face each other and are linked
by means of hydrogen-bonds producing a barrel-like
structure in the interior of which a pair of guest molecules
is accommodated, as shown in Fig. 2.
˚
second sides of b-CD by 1.54 and 1.31 A, respectively.
Which show that the guest molecule could adjust position
of itself to occupy most of the available space in the cavity,
and that the structural active adjustability would facilitate
In the dimeric structure, the both p-NPOAA molecules
are placed in the central cavities of b-CD molecules, with
the nitro group protruding from the region of the second
Fig. 2 Stereoscopic view of the
b-CD dimer with the guest
molecules inside the cavity.
Intermolecular hydrogen bond
interactions are drawn by dotted
lines
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hydroxyl groups and the carboxyl group buried in the
primary hydroxyl groups of b-CD. The aromatic ring enters
the cavity of the b-CD and makes van der Waals contacts
with the atoms constructing the inside wall of the b-CD
cavity, while the two oxygen atoms in the nitro group,
Showing that the guest molecule can adjust it’s position
and the orientation in b-CD cavity to some extent
according to it’s size/shape. So we think that the study will
further our understanding of the molecuar recognition of
substrate receptors together with published reports.
O4 and O5, is hydrogen bonded to the adjacent b-CD
Crystal structures of the b-CD inclusion complexes are
classified into three types according to the host–guest
interactions and the chemical nature of b-CD and the guest
molecule. In this inclusion complex, as shown in Fig. 3, the
b-CD molecules complexed to p-NPOAAs form a layer-
type structure in which the primary hydroxyl sides are open
to the intermolecular space of the adjacent layer. Adjacent
layers are shifted by half a molecule. The interspace
between the adjacent layers is filled with water molecules.
It should be noted that the water molecules filled with the
layer interspace participate in interactions with b-CD to
form the hydrogen bonds, typically bridging hydroxyl
groups of b-CD molecules of the next layer, which con-
tribute to stabilization of the layer-type structure.
˚
(d[O4BꢀꢀꢀH35B-C35A] = 3.488(8) A, U[O4BꢀꢀꢀH35B-C35A]
169.5(17)ꢁ, d[O5BꢀꢀꢀH36B-C36A] = 3.350(3) A, U[O5BꢀꢀꢀH36B-C36A]
156.4(18)ꢁ). In addition, the carboxyl oxygen atom, O1,
=
˚
=
and the methylene form the hydrogen bond with the adja-
˚
cent b-CD (d[O1BꢀꢀꢀH66E-C66C] = 3.246(3) A, U[O1BꢀꢀꢀH66E-C66C]
=
=
˚
115.5ꢁ, d[O65CꢀꢀꢀH2A-C2B] = 3.141(3) A, U[O65CꢀꢀꢀH2A-C2B]
132.0(17)ꢁ). Although the ether oxygen atom (O3) does not
have any hydrogen bonds with hydroxyl groups, it seems to
form weak electrostatic interactions with the hydrogen
atoms attached to the C-5 atoms. Since all of the C-5
hydrogen atoms in the b-CD direct to the center of the
torus, the center of the C-5 plane is very much suited for an
electronegative ether oxygen atom (O3). The distance
˚
between O3 and H54 and H55 are 2.914 and 3.340 A,
The inclusion behavior of 1 in aqueous solution. In order
to understand the formation mechanism of the inclusion
complex from solution to the solid state, 1H ROESY
experiments have been performed on a Varian Mercury
VX300 spectrometer. As shown in Fig. 4, the ROESY
spectrum of 1 exhibits clear NOE cross-peaks (peaks A–E)
between the protons of b-CD and p-NPOAA in complex 1,
which demonstrates that the p-NPOAA molecule is deeply
included into the cavity of b-CD. Further information about
the orientation of the guest molecule in the cavity of the
b-CD moiety may be reasonably deduced according to the
relative intensity of these cross-peaks. As illustrated in
Fig. 4, the clear correlation between Hm and H3 (peaks A)
suggesting that the weak electrostatic interaction certainly
exists between O3 and the C5 hydrogen atoms. As a result,
These interactions between the host and guest are thought
to determine the position and the orientation of the guest in
the cavity, giving rise to the inclusion mode.
Comparing the title complex with the inclusion com-
plexes of b-CD and p-nitro-benzoic acid, they show the
similar inclusion geometries. In the dimeric struture of
p-nitro-benzoic acid [22], the distance between aromatic
˚
ring centroids is 4.86 A, and the dihedral angle is 0.3ꢁ. In
the present study, the distance between aromatic ring
˚
centroids is 4.56 A, and the dihedral angle is 26.5ꢁ.
Fig. 3 The layer-type
molecular packing structure of
the inclusion complex 1.
Intermolecular hydrogen bond
interactions are drawn by dotted
lines
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J Incl Phenom Macrocycl Chem (2010) 67:393–398
397
Fig. 4 1H ROESY spectra
(300 MHz) of 1 ([1])
1.04 9 10-3 M) with a mixing
time of 300 ms in D2O at 298 K
is stronger than that between Hm and H5 (peaks B), which
imply that Hm must be close to H3, while the correlation
between Ho and H5 (peaks C) is weaker than that between
Ho and H3 (peaks D), implying that Ho must be close to
H3. Furthermore, the correlation of H-CH2 with H5 (peaks
E) indicates that the methylene in the p-NPOAA must be
close to the primary hydroxyl side of b-CD. These results
unequivocally indicate that the solution conformation is
consistent with the solid state structure.
p-NPOAA molecules are maintained in positions to form
hydrogen bonding with the surrounding hydroxyl groups
and water molecules which stabilize the layer structure. We
suggest that this system provides a data for the study of the
inclusion mechanism and the interrelationship between
steric effects and weak binding interactions.
Supplementary data
Complete crystallographic data for the structural analyses for
compound 1 has been deposited with the Cambridge Crys-
tallographic Data Centre, CCDC No. 664798. Copies of this
information may be obtained free of charge from the
Director, Cambridge Crystallographic Data Centre, 12 Union
Road, Cambridge, CB2 1EZ, UK (fax: ?44 1223 336033,
deposit@ccdc.cam.ac.uk or http://www.ccdc.cam.ac.uk).
Conclusion
The inclusion behavior of b-CD with p-NPOAA was studied
in solution and in the solid state. In the crystal structure, the
b-CD molecules form dimers and these dimers are arranged
like coins in a roll constructing infinite linear supramolec-
ular architecture along the crystallographic c-axis in which
the p-NPOAA molecules are embedded. The p-NPOAA
molecules prefer to occupy most of the available space in the
cavity, and prefer to protrude with their polar COOH and
NO2 groups at hydroxyl group sides. On the other hand, the
Acknowledgment This work was supported by NNSFC (No.
20704031 and 20776111), Tinajin Natural Science Fund (Grant No.
09JCYBJC06300), Science Fund of Tianjin Education Committee
(No. 20060515), and Science Fund of Tianjin University of Science
and Technology (No. 20060420), which are gratefully acknowledged.
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