Journal of Molecular Structure 1101 (2015) 14e20

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Journal of Molecular Structure

journal homepage: http://www.elsevier.com/locate/molstruc

Synthesis and structure of new carbohydrate metaleorganic

frameworks and inclusion complexes
Jing-Quan Sha, Lian-He Wu, Shu-Xian Li, Xiao-Ning Yang, Yu Zhang*, Qian-Nan Zhang,
Pei-Pei Zhu
The Provincial Key Laboratory of Biological Medicine Formulation, School of Pharmacy, Jiamusi University, Jiamusi, 154007, PR China

a r t i c l e i n f o

a b s t r a c t

Article history:
Received 3 June 2015
Received in revised form
7 August 2015
Accepted 7 August 2015
Available online 13 August 2015

Two new metaleorganic framework compounds based on natural b-cyclodextrin molecules (b-CD) and
alkali metals (Na/K) were synthesized and characterized by elemental analyses, IR, XPRD and 1HNMR.
Single-crystal X-ray diffraction analysis reveals that compounds 1 and 2 possess the bowl-like pore and
the 8 type double channels conguration. Due to the [blow channel] double conguration, 5Fluorouracil (5-FU) and Quercetin inclusion complexes of compound 1 are studied, and the results
show that the two kinds of drug with different structure and size can be included into the compound at
the same time, which is expected to become a new type of multi-functional green crystalline solid
material.
2015 Elsevier B.V. All rights reserved.

Keywords:
Carbohydrate
Metaleorganic framework
b-Cyclodextrin
Inclusion complexes

1. Introduction
Green chemistry has become a central issue in both academic
and industrial research in 21st century, involving organic synthesis,
material chemistry and biochemistry. The metaleorganic frameworks (MOFs), a new class of crystalline solid materials consisting
of metal ions and organic ligands, are being evaluated for diverse
potential applications, such as gas adsorption [1e8], storage of
clean gas fuels [9,10], separations [11e13], and drug delivery
[14e16]. However, the vast majority of MOFs reported to date are
composed of organic subunits derived from non-renewable
petrochemical feedstocks and transition metals. Once these MOFs
are applied to the industrialization, some urgent problems may
appear as follow: 1) High costs make it difcult to large-scale applications in the industry; 2) Pollution control during the synthesis;
3) Non-renewable ingredients. Therefore, it is necessary that the
preparing MOFs from natural products derive environmentally
benign, clean synthetic procedures, and renewable materials.
As a special class of carbohydrates [17,18], cyclodextrin (CD)
consists of six, seven or eight a-1,4-linked D-glucopyranosyl
repeating units and displays the eOCCO- binding motif on both their
primary and secondary faces auguring well for forming extended

* Corresponding author.
http://dx.doi.org/10.1016/j.molstruc.2015.08.020
0022-2860/ 2015 Elsevier B.V. All rights reserved.

structures with Group IA and IIA metal. These characteristics of CDs

can merge into metaleorganic frameworks (named as CD-MOFs)
with alkali metals as organic candidates to contribute the natural
porous materials [19e23]. More importantly, CD-MOFs are inexpensive and green in the sense, because they can be synthesized
from renewable sources that are themselves derived from water,
CO2, and nontoxic metal salts. On the other hand, the hosteguest
complexes of CDs have been studied extensively over a long period
depending on their natural exible porosities, and such complexes
are used in the pharmaceutical and food industries [24e26].
Although many CD-MOFs assembled form a-, b-, and g- CD were
reported, and their structures exhibit the barrel, the cage, the independent double CD and three-leaf oar, and so on, but the 2D bowllike structure was rarely reported.
On the basis of the above considerations, to seek the green
natural porous material, and to isolate the suitable crystals of CDMOF with different structure, herein, we report the unprecedented and rapid formation of a well-dened porous materials
constituted by natural b-cyclodextrin (b-CD) molecules and alkali
metals (Na/K) via a pollution-free method. Our success owes to
the C7 symmetric of b-CD with causing the asymmetric coordinating mode with alkali metals. Due to the interesting
[blow channel] double conguration of CD-MOF, the drug (5-FU
and Quercetin) inclusion complexes of CD-MOFs are studied
(shown in Scheme 1).

J.-Q. Sha et al. / Journal of Molecular Structure 1101 (2015) 14e20

15

Scheme 1. Schematic representation of CD-MOF with double conguration and the drug inclusion complexes of CD-MOFs.

2. Experimental section

2.4. X-ray single crystal diffraction analysis

2.1. General information

Structural measurements for Na/K-CD-MOF were performed on

a Rigaku RAXIS RAPID IP diffractometer with Mo-Ka monochromatic radiation (l 0.71069 ) at 293 K. The structures were
solved by the directed methods and rened by full matrix leastsquares on F2 using the SHELXTL crystallographic software package [27]. All non-hydrogen atoms in 1 and 2 were rened anisotropically. The positions of hydrogen atoms on carbon atoms were
calculated theoretically. The crystal data for 1 and 2 are summarized in Table 1. Since the metrical parameters associated with
these structures are unexceptional, full listings of bond lengths and
angles for the M sites and for the CD are given in the supplementary
tables only. Crystallographic data for the structure reported in this
paper have been deposited in the Cambridge Crystallographic Data
Center with CCDC Number 1041731 for 1 and 1041782 for 2.

All reagents were purchased commercially and used with

further purication. Elemental analyses (C and H) were performed
on a PerkineElmer 2400 CHN Elemental Analyzer. The IR spectra
were obtained on an Alpha Centaurt FT/IR spectrometer with KBr
pallet in the 400e4000 cm1 region. Chromatography work was
performed using the HPLC-1100 system (Agilent, CA, USA). Thermal
Analysis DSC-Q100 differential scanning calorimeter was performed on a Thermal Analysis Ltd Co, USA. The X-ray powder
diffraction (XRPD) patterns were obtained with a Rigaku D/max
2500 V PC diffractometer with Cu-Ka radiation, the scanning rate is
4 /s, 2q ranging from 5 to 40 . The 1HNMR spectra obtained on a
Bruker AV400 instrument with deuterate dimethyl sulphoxide
(DMSO) as solvent.

3. Results and discussion

2.2. Synthesis
3.1. Crystal structures of compounds 1 and 2
2.2.1. Synthesis of NaOH (C42H70O35)9H2O (Na-CD-MOF)
b-Cyclodextrin (1.135 g, 1 mmol) and NaOH (0.32 g, 8 mmol)
were dissolved in deionized H2O (15 ml) and C2H5OH (5 ml), and
the resulting solution was stirred for 1 h. The solution was ltered
through PTFE membrane. After two week, colorless crystals were
isolated, washed with C2H5OH, and dried at room temperature.
Yield: ca. 76%. Elemental analysis (%) calcd. for Na(C42H70O35)$
OH$9H2O: C 37.69, H 6.71; found: C 37.59; H 6.75.
2.2.2. Synthesis of KOH (C42H70O35)9H2O (K-CD-MOF)
b-Cyclodextrin (1.135 g, 1 mmol) and KOH (0.448 g, 8 mmol)
were dissolved in deionized H2O (15 ml) and C2H5OH (5 ml), and
the resulting solution was stirred for 1 h. The solution was ltered
through PTFE membrane. After two week, colorless crystals were
isolated, washed with EtOH, and dried at room temperature. Yield:
ca. 74%. Elemental analysis (%) calcd. for K(C42H70O35)$OH$9H2O: C
37.27, H 6.58; found: C 37.24; H 6.61.
2.3. Preparation of drug-CD-MOF inclusion complexes
Drug-CD-MOF inclusion complexes were prepared by grinding
method at room temperature. In brief, 5-FU, Quercetin and CD-MOF
were accurately weighted at a molar ration of 1:1:1, respectively.
The result compounds were grinded with absolute alcohol as
wetter. After grinding for 1 h, the products were rinsed 3 times by
using certain amount of absolute alcohol. The inclusion complexes
were desiccated at 60  C until constant weight was obtained.

Single crystal X-ray diffraction analysis reveals that compounds

1 and 2 are isostructural, and each consists of one b-CD, one Na ion
for 1 and one K ion for 2 and nine lattice waters and one OH ion
(Fig. 1a). Here, the structure of compound 1 is discussed as an
example. There is a crystallographically independent Na ion,
which is six-coordinated by six oxygen atoms from four contiguous
CD molecules, namely, four secondary hydroxyls, one primary hydroxyl and one ring oxygen atom. The NaeO bond distances are in
range of 2.730 e2.985 (Fig. 1b). The b-CD adopts four coordinated mode linking with four Na ions via a-, b- and D-glucopyranosyl (Fig. 1c). . To the best of our knowledge, the coordinated
mode of CD has never been found in the other CD based compound.
The prominent structure feature of compound 1 is the presence
of the bowl-like pore (size ca.6.0  5.8 ) via T arrangements of bCDs and the 8 type double channels (size ca.5.6  5.4 ), which
can be understood from Fig. 2. Two adjacent b-CDs link with Na
ions forming the T shape structure with unique bowl-like pore, in
which one b-CD uses its 2, 3eOH groups from a- and D-glucopyranosyl and another uses its 6-OH and 2, 3-OH groups from b- and Dglucopyranosyl (Fig. 2a). Furthermore, these T shape structure
units array along the b-axis forming the 8 type double channels
(Fig. 2b). Note that such an unusual coordination mode has not
been found in CD chemistry hitherto. Finally, each of the double
channels units held together along the a-axis via interactions of
NaeO leading to the formation of 2D layers in ab plans (Fig. 3). The
solvent-accessible volume of the unit cell is estimated, (PLATON

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J.-Q. Sha et al. / Journal of Molecular Structure 1101 (2015) 14e20

Table 1
Crystallographic and structural renement data of 1 and 2.
Compounds

Na-CD-MOF

K-CD-MOF

Empirical formula
Formula weight
Temperature
Wavelength
Crystal system
space group
a()
b()
c()
a( )
b( )
g( )
Volume (3)
Z, Calculated density
Absorption coefcient
F (000)
Crystal size (mm)
Reections collected/unique
Data/restraints/parameters
Goodness-of-t on F2
Final R indices [I > 2sigma(I)]
R indices (all data)

NaC42H70 O35
1157.99
293(2) K
0.71069
Monoclinic
P21
15.2371(5)
10.5956(5)
20.2018(5)
90.000
108.223
90.000
3098.0(19)
2, 1.236
0.115 mm1
1392
0.46  0.39  0.28
15607/7707 [R(int) 0.0238]
7707/1/802
1.043
R1 0.0619, wR2 0.1843
R1 0.0717, wR2 0.1948

K1C42H70O35
1174.10
293(2) K
0.71069
Monoclinic
P21
15.235(5)
10.549(5)
20.241(5)
90.000
108.180
90.000
3103.8(19)
2, 1.250
0.198
1406
0.43  0.37  0.25
15634/7597 [R(int) 0.0278]
7597/31/802
1.063
R1 0.0493, wR2 0.1360
R1 0.0572, wR2 0.1426

R1 S(jjF0jjFcjj)/SjF0j, wR2 Sw(jF0j2jFcj2)2/Sw(jF0j2)2]1/2.

program) to be 589.2 3, which is approximately 19.5% of the unitcell volume (3027 3). Additionally, to obtain the information about
surface area of the CD-MOFs, the N2 adsorption/desorption was
performed, and the results shows poor uptakes of N2. Maybe
because the 2D layer in CD-MOF are stacked in parallel staggering
fashion, the vacancies in a layer are covered by CD of adjacent layers
in this stack style, which is of disadvantage for gas absorption
(Fig. S1). The XRPD pattern undergoes partial after experiment

(Fig. S2), suggesting that phase transition or framework collapse

happens during N2 absorption process.
As is known to all, the formation of the barrel or three leaf
blade structures are easy when cyclodextrins are connected between the tail and end via the secondary hydroxyls. But the
asymmetric coordination modes of the b-CD in Na/K-CD-MOF,
namely, a-, b- and D-glucopyranosyl coordination mode concentrate in the side of the ring, not only lead to the above structure

Fig. 1. Ball and stick representation of the asymmetric of Na-CD-MOF (a); the coordination environment of Na ions (b) and b-CD(c).

J.-Q. Sha et al. / Journal of Molecular Structure 1101 (2015) 14e20

17

Fig. 2. Ball and stick representation of the T shape structure with unique bowl-like pore (a) and the 8 type double channels (b).

feature, but also prevent the formation of the 3D framework. As a

result, Na/K-CD-MOF contains [blow channel] double conguration, which allows for the enclosing two types of small molecular drugs at the same time.

3.2. Spectroscopic properties

The IR spectra (Fig. S3) of compounds 1 and 2 show prominent
characteristic absorption bands at 3392 cm1 (for eOH stretching

Fig. 3. Stick representation of 2D layers (left) and schematic of [blow channel] double conguration for the enclosing two types of small molecular drug (right).

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J.-Q. Sha et al. / Journal of Molecular Structure 1101 (2015) 14e20

vibrations of multi-association body), 2930 cm1 (for CeH

stretching vibrations of eCH3 and eCH2), 1419, 1157 cm1 (for eOH
bending vibration), 1080, 1030 cm1 (for CeC, CeO or CeCeO
stretching vibrations), which indicates that Na-CD-MOF and K-CDMOF keep the skeleton structure of the b-CD. By comparison, the
spectra of two compounds are very similar except for the CeO and
OeH stretching vibration region with a slight difference perhaps
due to the formation of MeO bond.
3.3. XRPD pattern analyses
The X-ray powder diffraction (XRPD) pattern for compounds 1
and 2 is presented in Fig. S4. The diffraction peaks of both simulated
and experimental patterns match well, thus indicating that the
phase purity of the compounds is good. The difference in reection
intensities between the simulated and the experimental patterns is
due to the different orientation of the crystals in the powder
samples.
3.4. Study about drug-b-CD-MOF inclusion compounds
To study inclusion properties of compounds 1 and 2, we use
them as inclusion materials to include drug molecules, owing to
their special cavity structure. On the one hand, compound 1 is
isomorphous with compound 2, therefore their inclusion properties are explored using compound 1 as an example. On the other
hand, the structure of compounds 1 and 2 possesses
[blow channel] double conguration, which is favor of inclusion
and loading two types of small molecular drugs at the same time.
As a result, compounds 1 and 2 are expected to become a new type
of multi-functional green materials in drug delivery.
3.4.1. HPLC assay
The Quercetin and 5-Fu content of the inclusion complexes was
determined by HPLC shown in Fig. 4. The HPLC system consisted of
a water1525 Binary HPLC Pump with a Water 2487 Dual l Absorbance Detector, and a C18 Phenomenex column (5 mm,
4.60 mm  250 mm). The mobile phase included methanol: water
(50:50/V:V), running at a ow rate of 1.0 mL min1. The injected
volume was 10 mL and the detection wavelength was 270 nm, while
the column temperature was set at 25  C. The standard 5-FU,
Quercetin and inclusion complexes were detected by this condition. The results show that the pure 5-FU retention time was
3.12 min, and the pure Quercetin retention time was 16.42 min. The
inclusion complexes have two absorption peaks in 2.71 min and
15.40 min, which belong to that of 5-FU and Quercetin, respectively.
The change of retention time of 5-FU and Quercetin in the inclusion

Fig. 4. HPLC chromatograms of 5-FU (1), Quercetin (2) and inclusion complexes (3).

complex indicates that there is a force between the host and guest
and the formation of inclusion complexes.
3.4.2. Spectroscopic properties
Fig. 5 shows the spectra of Quercetin, 5-FU, b-CD, Na-CD-MOF,
and their physical mixture and inclusion complexes, respectively.
The IR spectra of 5-FU and Quercetin show their prominent characteristic absorption, respectively. And the spectrum of physical
mixture shows correspondence to superposition of its parent
products with relatively weak absorption, however, compared with
its parent products, the spectrum of inclusion complexes shows a
relatively large difference, namely, for 5-FU, the NeH stretching
vibration peak (3010 cm1) disappeared, the CeF peak (1699 cm1)
is weakened; for Quercetin, the eOH stretching vibrations peak
(3388 cm1) is weakened and the stretching vibrations peak of
benzene skeleton (1151 cm1) shift. The changes further indicate
that 5-FU and Quercetin interact with Na-CD-MOF and formed inclusion complexes.
The 1HNMR spectra of CD-MOF, 5-FU, Quercetin, physical mixtures and inclusion complexes are shown in Fig. 6 and Fig. S5, and
1
HNMR chemical shift are listed Table S3eS5. The glucopyranosyl
residues of CD-MOF in the 1HNMR spectrum produce ve distinct
signals for the protons. It is clearly found that the chemical shift of
protons is only a superposition of three substances in the 1HNMR
spectra of physical mixture, but the chemical shift of protons have
changed signicantly in the 1HNMR spectrum of the inclusion
complexes. More specically, the chemical shift of H-3 and H-5
localized within the cyclodextrin cavity changed due to the
screening effect, which demonstrates 5-FU as guest molecules
enter the CD-MOF cavity. On the other hand, when Quercetin
molecule and CD-MOF interaction, hydrogen bonds between 6-OH
of Quercetin and 7-OH of CD-MOF result in changing of chemical
shift of 6-OH of Quercetin and 7-OH of CD-MOF (shown in Fig. S6).
This data further indicate that 5-FU, Quercetin and CD-MOF form
inclusion complexes.
3.4.3. Differential scanning calorimetry (DSC)
Fig. 7 shows the DSC curve of Quercetin, 5-FU, b-CD, NaeCDMOF, and their physical mixture and inclusion complexes, respectively. Na-CD-MOF has one endothermic peak at 86  C and one melt
peak at 315  C; 5-FU has one sharp endothermic peak at 283  C;
Quercetin has one endothermic peak at 130  C and a melt peak at
315  C; In DSC curve of physical mixture, all endothermic peak was

Fig. 5. IR spectra of (1) CD-MOF; (2) 5-FU; (3) Quercetin; (4) Physical mixture; (5)
Inclusion complexes.

J.-Q. Sha et al. / Journal of Molecular Structure 1101 (2015) 14e20

19

Fig. 6. 1HNMR spectra of CD-MOF, Quercetin, 5-FU; mixture product and inclusion complexes.

Acknowledgments

found and weakened, which suggest the weak interaction between

three components without a formation of a new phase; For the
inclusion complexes, the endothermic peak of 5-FU and Quercetin
completely disappeared, which indicates that the inclusion complexes has been formed.

This work is nancially supported by the National Natural Science Foundation (Grant Nos. 21271089) and the Education Ofce
Foundation (12511575) in Heilongjiang Province.

4. Conclusion

Appendix A. Supplementary information

In summary, two new carbohydrate metaleorganic frameworks

(CD-MOF) with [blow channel] double conguration have been
synthesized, and their unique structure and inclusion properties
were characterized and studied. It is interesting that this kind of
CD-MOF is favor of inclusion and loading the drug molecules with
different structure, different size, or different charges at the same
time, which are expected to become a new type of multi-functional
green material. The successfully isolation of the suitable crystals of
CD-MOF can lead to a new generation of the carbohydrate metaleorganic frameworks with different structures.

Supplementary data related to this article can be found at http://

dx.doi.org/10.1016/j.molstruc.2015.08.020.

Fig. 7. Differential scanning calorimetry curves of (1) CD-MOF; (2) 5-FU; (3) Quercetin;
(4) Physical mixture; (5) Inclusion complexes.

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