Two Cu(II)-organic frameworks: Effective CO2 fixation and protective activity on the motor function after stroke by increasing neural stem cells differentiation

Article abstract of DOI:10.1016/j.ica.2020.119880

In the present research, two novel metal–organic frameworks (MOFs) containing Cu(II) ions as nodes {[Cu(L)]·2DMF·2H₂O}_n (1) and {[(CH₃)₂NH₂][Cu₂(L)(H₂O)PO₄]·2DMF}

Full text of DOI:10.1016/j.ica.2020.119880

Journal Pre-proofs
Research paper
Two Cu(II)-organic frameworks: effective CO fixation and protective activi‐
2
ty on the motor function after stroke by increasing neural stem cells differen‐
tiation
Qing Ye, Li Zhang, Zhou-Li Shao, Wei Zhang, Chao Li, Xiang-Ming Ye
PII:
DOI:
Reference:
S0020-1693(20)31079-3
https://doi.org/10.1016/j.ica.2020.119880
ICA 119880
To appear in:
Inorganica Chimica Acta
Received Date:
Revised Date:
Accepted Date:
24 May 2020
3 July 2020
3 July 2020
Please cite this article as: Q. Ye, L. Zhang, Z-L. Shao, W. Zhang, C. Li, X-M. Ye, Two Cu(II)-organic
frameworks: effective CO fixation and protective activity on the motor function after stroke by increasing neural
2
stem cells differentiation, Inorganica Chimica Acta (2020), doi: https://doi.org/10.1016/j.ica.2020.119880
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Two Cu(II)-organic frameworks: effective CO fixation and protective activity
2
on the motor function
differentiation
after stroke by increasing neural stem cells
Qing Ye, Li Zhang, Zhou-Li Shao, Wei Zhang, Chao Li, Xiang-Ming Ye*
Department of Rehabilitation Medicine, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou
Medical College, Hangzhou, Zhejiang, China
E-mail: xm_ye01@126.com
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Abstract
In the present research, two novel metal-organic frameworks (MOFs) containing Cu(II) ions as nodes
{[Cu(L)]·2DMF·2H O} (1) and {[(CH ) NH ][Cu (L)(H O)PO ]·2DMF} (2) have been constructed by using 5-
2
n
3 2
2
2
2
4
n
(1H-imidazol-1-yl)isophthalic acid (H L), the dual-functional organic ligand featuring an imidazole part to
2
isophthalic acid 5-position. Because of its robust framework structure and the high density of open metal positions,
the activated 1 (denoted as 1a) could adsorb CO and efficiently convert them into cyclic carbonates under the
2
mild conditions. Their treatment activity on the recovery of motor function after stroke in rats was evaluated.
Firstly, the beam walking assay was implemented to determine rats motor function after treated with compounds.
Next, the differentiation levels of the neural stem cells were also determined with western bot.
Keywords: Metal-organic framework, CO fixation, motor function
2
Introduction
Stroke is one of the diseases that seriously endanger human health. Due to the lack of a total understanding of
the cellular and molecular mechanisms that cause neuronal cell death after ischemia, there is no effective method
for the stroke treatment [1]. Current research indicates that the possible mechanisms of stroke involve apoptosis,
excitotoxicity, oxidative and nitrifying stress, inflammatory response, innate and adaptive immune cells, intestinal
flora, and intracranial atherosclerosis [2, 3]. Studying the pathophysiology of ischemic stroke and revealing its
intertwined signal pathway mechanisms will help us find targets that can effectively treat ischemic stroke and lay
the foundation for the development of treatment options for ischemic stroke.
Metal-organic frameworks (MOFs) are the porous materials with adjustable structure, which are constructed
by integrating organic connectors and secondary building units (SBUs). The diversity of their two components of
structure endows MOF with flexible design in channel size and type, open metal positions as well as surface non-
metallic active pendant group, making MOFs excellent functional porous materials from carbon dioxide capture to
the chemical fixation by the heterogeneous catalysis [4-9]. For the given application, synthetic MOF chemists
1

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have proposed classical design principles and constructed SBUs with distinct attraction from different metal
centers. The SBUs could not only define the final structural features of the as-prepared MOFs, but could also
bring new functionalities into the targeted frameworks [10-15]. On the other hand, polycarboxylic ligands have
different structural topologies due to their different coordination patterns, and are often chose as multifunctional
organic connectors. The 5-(1H-imidazol-1-yl) isophthalic acid, (H L), contains two carboxylatea and a N donor,
2
has attracted chemists' attention in recent years. Its coordination polymers contain an extensive structural
diversities and latent applications as magnetic and porous materials; in addition, polycarboxylic ligands also have
the function of hydrogen bond acceptors and/or donors [16, 17]. In this study, H L was selected as the ligand to
2
prepare the functional coordination polymers containing transition metal ions Cu(II) and this resulted in two novel
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metal-organic
frameworks
(MOFs)
containing
Cu(II)
of
{[Cu(L)]·2DMF·2H O}
(1)
and
2
n
{[(CH ) NH ][Cu (L)(H O)PO ]·2DMF} (2). Because of its robust framework structure and the high density of
3
2
2
2
2
4
n
open metal positions, the activated 1 (denoted as 1a) could adsorb CO and efficiently convert them into cyclic
2
carbonates under mild conditions. In biological research, for the recovery of the motor function of the rats after
stroke, serious experiments were performed for evaluation and the mechanism was evaluated as well. The results
of the beam walking assay indicated that the motor function of the rats after stroke was significantly improved,
especially compound 1. In addition to this, the differentiation levels of the neural stem cells were also increased
after treated by compound 1, but compound 2 did not. In conclusion, compound 1 showed better protective
activity than compound 2 on the motor function after stroke by increasing neural stem cells differentiation.
Experimental
Chemicals and measurements
Unless the otherwise specified, materials were acquired from the suppliers and could be used with no in-
depth purification. Nitrogen, hydrogen and carbon elements were analyzed with the analyzer of Perkin Elmer
2400. The data of FTIR were acquired utilizing the FTIR spectrometer of Nicolet Impact 410. The analysis of GC
− MS was implemented by the Shimadzu GCMS-QP 2010 plus contains DB-5MS capillary column (30 m ×0.25
mm × 0.25 μm; J&W Scientific, Folsom, CA, USA). The measurements of nitrogen and carbon dioxide
adsorption were performed utilizing ASAP 2020 Micromeritics.
Preparation
and
characterization
for
{[Cu(L)]·2DMF·2H O}
(1)
and
2
n
{[(CH ) NH ][Cu (L)(H O)PO ]·2DMF} (2)
3
2
2
2
2
4
n
For the complex 1, we mixed 0.13 mmol and 30 mg H L and 0.2 mmol and 48 mg Cu(NO ) ·6H O with
2
3 2
2
DMF of 5 mL and H O (0.5 mL) in the Teflon vessel 25 mL and then heated them for three days at 90 ℃. After
2
cooling the mixture to the ambient temperature, the resulting blue crystals with block-shape were collected and
then cleaned repeatedly by the DMF, and then by the acetone, and dried in the air, and the yield was 72% (on the
2

1
2
3
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5
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0
1
2
3
4
5
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basis of the ligand). Anal. Calcd for C H N O Cu: C, 42.90; H, 5.08; N, 11.77; %. Found: C, 42.98; H, 5.21; N,
17 24 4 8
−
1
11.69%. IR (KBr pellet, cm ): 3416br, 3328m, 3170w, 2131m, 1609s, 1456m, 831m, 738m, 699m, 608m
For the complex 2, we mixed 0.13 mmol and 30 mg H L and 0.2 mmol and 48 mg Cu(NO ) ·6H O, and 20
2
3 2
2
μL of H PO (85%) with DMF of 3 mL and H O (0.5 mL) in the Teflon vessel 25 mL and then heated them for
3
4
2
three days at 120 ℃. After cooling the mixture to the ambient temperature, the resulting blue crystals with block-
shape were collected and then cleaned repeatedly by the DMF, and then by the acetone, and dried in the air, and
the yield was 83% (on the basis of the ligand). Anal. Calcd for C H N O PCu : C, 34.55; H, 4.27; N, 10.60%.
1
9
28
5
11
2
−
1
Found: C, 34.53; H, 4.39; N, 10.61%. IR (KBr pellet, cm ): 3442m, 3176w, 3054w, 2965m, 2875w, 1598w,
1540s, 1456m, 1397s, 792m, 740s.
1
1
1
1
1
1
1
1
1
The software of crysalispro was applied for the analysis of strength data and then to convert strength data
into the HKL files. We utilized diffractometer of Oxford XcaliburE to get the data of X-ray. The program of
SHELXS in accordance with the direct method was applied to establish the initial skeleton pattern for the
compound 1, and the program of SHELXL-2014 in accordance with least square means was modified. All the
non-hydrogen atoms were refined using the anisotropic parameters. All hydrogen atoms were treated via applying
the command of AFIX to fix on the C atom geometrically they are connected to. The refinement along with the
crystallographic parameters for these two complexes are described in detail in Table 1.
Table 1 The parameters of crystallography as well as the refinement for the complex 1 and complex 2.
Identification code
1
2
Empirical formula
C H CuN O
C H Cu N O P
1
1
6
2
4
11
8
2
2
9
Formula weight
293.72
273.15
470.24
298(2)
trigonal
R-3
Temperature/K
Crystal system
monoclinic
Space group
P2 /c
1
a/Å
10.6291(10)
12.6642(10)
13.5792(13)
90
33.624(3)
33.624(3)
b/Å
c/Å
10.4960(10)
90
α/°
β/°
108.863(2)
90
90
γ/°
120
Volume/Å3
Z
1729.7(3)
4
10277(2)
18
ρcalcg/cm3
μ/mm-1
1.128
1.368
1.968
1.267
3

Goodness-of-fit on F2
1.091
1.091
Final R indexes [I>=2σ (I)]
Final R indexes [all data]
R = 0.0860, ωR = 0.2185 R = 0.0399, ωR = 0.1055
1
2
1
2
R = 0.0925, ωR = 0.2220 R = 0.0540, ωR = 0.1163
1
2
1
2
Largest diff. peak/hole / e Å-3 1.68/-2.35
0.63/-0.68
CCDC
2003681
2003682
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Beam walking assay
To determine the recovery of the motor function of the rats after stroke, compounds 1 and 2 were synthesized
and used in the stroke mice for indicated treatment. All of the preparation in this research was under instructions'
guidance with slight modification. Briefly, the SD rats used in this research were obtained from Tianjin University
(Tianjin, China). All the preformation was conducted in the study were authorized via Tianjin University Animal
Ethics Committee. The cerebral infarction was made in the left middle cerebral artery to induce the stroke model,
then the compound 1 or the compound 2 was injected for the treatment at 5 mg/kg concentration. Afterward, the
beam walking method was carried out and the animals behaver were recorded. All the preformation in this
experiment were repeated at least three times. (0=balance in the stable position; 1=grasp one beam side; 2=hug the
beam and one limb, fall off the beam; 3=hug the beam and two limbs, fall off from beam, or rotate on the beam
for more than 60 seconds; 4=try to balance on the beam but fall off for more than 40 seconds; 5=try to balance on
the beam but fall off for more than 20 seconds; and 6=fall off, do not try to balance or hang on the beam for less
than 20 seconds). This experiment was repeated at least three times.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
Western blot
The western blot method was utilized to determine the differentiation levels of the neural stem cells after
treated with the compound 1 or compound 2 by measuring the expression of the β-tubulin III. This research was
implemented on the basis of the instructions with some modification. Briefly, the cerebral infarction was made in
the left middle cerebral artery of the rats to induce the stroke model, then the compound 1 or the compound 2 was
injected for the treatment at 5 mg/kg concentration. Subsequently, we isolated neural stem cells in brain and
overall protein was extracted. BCA detection kit was used for the protein concentration determination, and the
samples were loaded onto the gel of SDS-PAGE and then transferred into the 0.22 mm PVDF membrane. After
blocked by the nonfat milk solution of 5% for two hours at the ambient temperature, the primary antibody was
used to incubate the PVDF membrane at 4℃ overnight. After washed twice by the PBST, the membranes were
incubated by using the suitable secondary antibody and the horseradish peroxidase for two hours. In this research,
GAPDH was recommended as the internal control. Finally, ChemiDoc™ Touch Imaging System was used to
capture the images.
Results and discussion
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Crystal structures
In the water and DMF mixed solvent, the solvothermal reaction between Cu(NO ) ·3H O and the ligand of
3
2
2
H L was carried out at 90 ℃ to form the blue crystals with block-shape of 1. In accordance with the data of
2
crystal which harvested at ambient temperature, the structural solution as well as refinement results indicated that
complex 1 was crystallized in monoclinic P2 /c space group and reveals a three-dimensional channel-type
1
framework on the basis of the impeller cluster-based unit. Its asymmetric unit is composed of a Cu(II) ion, a
2
–
ligand of L , 2 DMF, as well as two lattice molecules of water. As reflected in the Fig 1a, the center of Cu1 has a
–
penta-coordinated geometry, which is composed of four oxygen atoms of 2 COO groups in a ligand and a
nitrogen atom in another ligand imidazole part to generate Cu (COO) N , the paddle-wheel SBU. It is found that
2
4
2
2
-
1
1
1
1
1
1
1
1
1
1
the distance between these two ions of Cu···Cu was 3.032 Å. The ligand L acts as a 5-connected node utilizing
its four carboxylic acid oxygen atoms and a imidazole nitrogen atom to bind with five adjacent Cu(II) ions (Fig
1b). The obtained coordination arrangement of the ligand and Cu(II) ion formed a three-dimensional porous
skeleton with one-dimensional open channels along the axis a of crystallography, and the channel dimensions is
2
about 12 × 7 Å (Fig 1c). The channels in skeleton are full of water solvent molecules as well as DMF. When we
removed water solvent molecules and the DMF from lattice, the total volume of void that the solvent of
3
3
compound 1 can enter is 51.8% (1847.3 Å / 956.1 Å ). The analysis of topology (Fig 1d) by the TOPOS reflected
that the paddle-wheel SBU of Cu (COO) N could be regarded as a 6-linked node and the L ligand can be
2
4
2
considered a 3-linked node. This made skeleton a three, six-linked binodal network with the point symbol of
2
2
10
3
{4.6 } {4 .6 .8 }, which can be assigned to be a topological mode of rtl rutile 3,6-conn (topos&RCSR.ttd).
2
2
0
1
2
-
2
Fig. 1 (a) Complex 1's asymmetry unit view. (b) The coordination diagram view for the ligand L . (c) Complex
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3
1's three-dimensional skeleton. (d) Complex 1's 3,6-linked binodal network.
In the presence of phosphoric acid at 120 ℃, the solvothermal reaction between Cu(NO ) ·3H O and ligand
3
2
2
H L resulted in the formation of anionic skeleton 2 contains large open hexagonal pores and double-walled rosette
2
architecture. The anionic skeleton 2 based on phosphate was crystallized in rhombohedral R-3 space group. And
its asymmetric unit contains a PO43– anion, two ions of Cu(II), a coordinated water, a ligand of L, as well as the
disordered solvent molecules, (CH ) NH cations and DMF (Fig 2a). It is found that these two carbon atoms inthe
3
2
2
imidazole were disordered at two designated positions. Due to the disorder of DMA cations and solvent, it is
impossible to model, thus, they were removed by SQUEEZE [18, 19]. The single crystal X-ray diffraction studies
show that both Cu1 and Cu2 are five coordinated but possess different coordination surroundings. The Cu1 was
coordinated by two oxygen atoms in a group of COO , two oxygen atoms in the anion of PO43–, and a nitrogen
1
1
1
1
1
1
1
1
1
1
2
2
2
2
–
–
atom in imidazole group, whereas the Cu2 was coordinated by two oxygen atoms in a group of COO , two oxygen
atoms in the anion of PO43–, as well as a coordination molecule of water. The calculations of charge balance
reflected that there are 4+ charge from 2 Cu(II) ions and 5– charge from a PO43– and 2 COO . Ultimately, another
positive charge that needs to be balanced from one H NMe cation produced by DMF solvent decomposition in
–
2
2
the process of solvothermal reaction. The analysis of structure for the complex 2 exhibited that the ions of PO43–
and Cu(II) generated a continuous one-dimensional chain along crystallographic c-axis linked via L ligand,
2
generating the double-walled hexagonal channels, and the window size is about 15 × 16 Å and (Fig 2b and Fig
2c), in addition, generated a fascinating three-dimensional skeleton of rosette architecture (Fig 2d). The large
channels of hexagon were full of H NMe cations and DMF molecules. The total volume of void that the solvent
2
2
3
3
of compound 2 can enter is 42.5% (10532 Å /4477 Å ). Complex 2 possessed coordinated water molecules on the
channels walls. In the heating process, the coordinated water molecules can be removed to acquire the active
skeleton contains open metal positions, which is a latent candidate for heterogeneous catalysis and gas adsorption.
6

1
2
Fig. 2 (a) Complex 2's asymmetry unit. (b) The one-dimensional chain-like SBU view in the complex 2. (c) The
one-dimensional channels generated via connecting the one-dimensional SBUs and the ligands. (d) Complex 2's
three-dimensional skeleton revealing double-walled hexagonal channels along axis c.
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
To check the phase purity of the products, powder X-ray diffraction (PXRD) experiments have been carried
out for these complexes (Fig 3a and 3b). The peak positions of the experimental and simulated PXRD patterns are
in good agreement with each other, indicating that the crystal structures are truly representative of the bulk crystal
products [20]. The differences in intensity may be owing to the preferred orientation of the crystal samples.
Considering the channel-type frameworks as well as large solvent accessible voids in the complexes 1 and 2, they
1
1
1
1
1
1
1
1
1
1
might be potentially applied for the CO sorption and conversion. To get the activated phases of complexes 1 and
2
2, about 200 mg of the freshly as-prepared samples were soaked in the anhydrous methanol for five days, during
which the fresh MeOH was added to replace the old one every day. The solvent-exchanged samples were heated
in high vacuum for eight hours at 150 ℃ to generate the guest-free samples (denoted as 1a and 2a). The PXRD
experiments were used to study the framework robustness after the activation. As shown in the Fig 3a and Fig 3b,
the PXRD patterns of complex 1 after the activation are totally different with those of as-prepared samples with
most of the peaks disappearing, indicating its framework collapses after the activation. For complex 2, the PXRD
patterns of the samples after activation match well with those of the as-prepared ones, reflecting its good
robustness in the activation process. The different framework robustness of complexes 1 and 2 might be attributed
7

3
–
1
2
to their different structural features. Compared with the binuclear {Cu (CO ) } cluster, the PO bridged 1D rod-
2 2 4 4
like chains might contribute better to the framework stability of MOFs.
3
4
Fig 3. The PXRD patterns for complex 1 (a) and complex 2 (b).
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Gas adsorption and catalytic Studies
The thermally robust nature and considerable porosity of the complex 2 as well as the existence of open
metal positions encourage us to investigate it gas sorption properties. The adsorption of N on guest-free skeletons
2
was investigated at 77 K. Complex 2a revealed a relatively higher intake, and the maximum intake is 214.7
3
–1
1
1
1
1
1
1
1
1
1
1
cm ·g (Fig 4a). The surface areas of Brunauer–Emmett–Teller (BET) for the complex 2a were estimated as 750
2
–1
m ·g (based on the adsorption isotherms of N ). The pore volume derived from the N sorption isotherm is 0.29
2
2
3
–1
3
–1
cm ·g , which is near to the calculated value from the crystal data (0.31 cm ·g ) [21-23]. In addition, the studies
of CO adsorption on 2a exhibited that the isotherms were very similar, they were completely reversible and
2
without hysteresis, and the adsorption curve is type I (Fig 4b). The complex 2a at 298 K and 1 bar can adsorb 58
–
1
–1
cc·g , while the adsorption value at 273 K and 1 bar was 111.7 cc·g . To have a better knowledge of the CO -
2
framework, we calculated the CO sorption heats based on the CO sorption isotherms at 273 K and 298 K using
2
2
the Virial equation (Fig S1). The sorption heats of 2a were plotted in the Fig S2, which gave a value of 37.9
kJ/mol at zero loading, indicating there is a strong interaction between the framework of 2a and the guest CO2
molecules.
8

1
2
Fig 4. The data of N sorption at 77 K for the complex 2a (left); (b) The sorption isotherms of CO for the
2
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
complex 2a around the ambient temperature.
Due to the complex 2a have high stability, Lewis acid positions and excellent CO , all the sample can be
2
used as the efficient heterogeneous catalyst for the cycloaddition reaction of CO with epoxy as the substrate.
2
Before this reaction of catalysis, 100.0 mg complex 2a dried in the air was added into the system of catalysis for
0.15 g TBABr and 20.0 mmol propylene oxide. The reaction of catalysis was carried out at CO of 0.5 MPa and
2
80℃ for five hours; at the same time, using the n-dodecane as an internal standard, the yield of catalysis can be
calculated accurately via gas chromatography. Table 2 summarizes all the catalytic yields of different epoxides
and carbon dioxide. As reflected in the entry 1, in the simultaneous existence of 2a and TBAB, the catalytic yield
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
for the propylene carbonate synthesis from CO and propylene oxide is over 99%. Nevertheless, under the same
2
conditions of reaction, the catalytic yields for only TBAB or compound 2a are 10.8% and 7.5%, respectively, with
almost no obvious reaction (entry 2 and entry 3). The results show that 2a is used as the catalyst and TBABr is
used as the cocatalyst, both of them are essential for the reaction of CO fixation. In addition, the epoxy
2
compounds with distinct substituents were used as the substrates for chain extension reaction at CO of 0.5 MPa
2
and 80℃ with TBAB and 2a. As reflected in the entry 4, the catalytic yield for the 2-(chloromethyl)oxirane is
similar to the catalytic yield of propylene oxide (>99%). Nevertheless, the relevant catalytic yields for the target
cyclic carbonates reduced gradually to 53.7%, 81.9%, 86.5%, 93.2% and 96.8% for the cyclohexene oxide (entry
9), tert-butyl glycidyl ether (entry 8), benzyl phenylglycidyl ether (entry 7), 1,2-epoxy-3-allyloxypropane (entry 6)
and styrene oxide (entry 5), respectively. Different functional groups have distinct catalytic properties for the
epoxides, which may be due to different electronic and barrier effects for the functional groups. As revealed in the
Figure 5a, the catalytic yields of kinetics show that the reaction can only be induced by TBAB and 2a. On the
other hand, 2a can easily be recovered and then reproduced via the centrifugation and repeated cleaning with
methanol. After reusing 2a catalyst for four times, its catalytic property remains the major catalytic performance
(Fig 5b). In addition, the PXRD measurement results show that the structure of 2a does not change after the
catalytic reaction, reflecting its excellent catalytic stability.
9

O
O
O
O
+
CO2
1
2
3
Table 2 The cycloaddition reaction between CO and distinct epoxides.
2
Entry
1
Substrate
Product
Yield (%)
>99
O
O
O
O
O
O
O
O
O
O
O
2
3
4
7.5
10.8
>99
O
O
O
Cl
O
O
Cl
O
O
5
O
O
96.8
O
O
6
7
93.2
86.5
O
O
O
O
O
O
O
O
O
O
O
O
8
9
81.9
53.7
O
O
O
O
O
O
O
O
4
5
6
Fig. 5 (a) The catalytic yields of kinetics with no catalyst (blue), filtering 2a (red) and 2a + TBAB (black); and
7
8
(b) the recyclability for the cycloaddition reaction of CO with the propylene oxide as substrate.
2
1
0

1
2
3
4
5
6
7
8
Compound improved the motor function of the rats after stroke
The occurrence of the stroke would damage the motor function of the patients. Thus, in this research, the
motor function of the stroke rats was assessed for the evaluation of the rat motor function. The cerebral infarction
was made in the left middle cerebral artery to induce stroke model, then the compound 1 or the compound 2 was
injected for the treatment at 5 mg/kg concentration. The motor function of the rats after stroke was evaluated with
beam walking method. According to the results in the Fig. 6, in the model group, the motor function of the rats
was serious damaged with a lowest score of the motor function evaluation. While, after compounds treatment the
scores were increased, and the compound 1 revealed a stronger effect than the compound 2.
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Fig. 6 Improved motor effect of the stroke rats after compound treatment. The cerebral infarction was made in the
left middle cerebral artery to induce stroke model, then the compound 1 or the compound 2 was injected for the
treatment at 5 mg/kg concentration. The motor function of the rats after stroke was evaluated with beam walking
assay.
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Compound stimulated the expression of the β-tubulin III on the neural stem cells
In the former research, we can find that the compound 1 revealed much stronger promotion against the motor
function of the rats with stroke. So, in this experiment the mechanism of the compound was still needed to be
explored. The β-tubulin III was the indicator the differentiation the neural stem cells ability into the neural cells.
The western results showed in Fig. 7 suggested that there a reduced of expression of β-tubulin III in model group.
Whereas, after treated by the compound 1, the β-tubulin III expression level on neural stem cells was obviously
enhanced, but the compound 2 revealed nearly no influence against the differentiation of neural stem cells.
1
1

1
2
Fig. 7 Stimulated expression of the β-tubulin III on neural stem cells after treated with compound. The cerebral
infarction was made in the left middle cerebral artery to induce stroke model, then the compound 1 or the
compound 2 was injected for the treatment at 5 mg/kg concentration. The western blot was used in this research
for the β-tubulin III expression evaluation.
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Conclusion
To sum up, we have shown the synthesis and structural diversity of two Cu(II)-organic frameworks by using
the 5-(1H-imidazol-1-yl)isophthalic acid ligand. The structural determination studies reveal that complex 1 is a
3D framework structure based on the {Cu (CO ) } paddle-wheel clusters while complex 2 shows a 3D channel-
1
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type framework based on the 1D rod-like SBUs. The structural differences results in their different framework
robustness, and the complex 2 with better framework stability could adsorb CO and efficiently convert them into
2
cyclic carbonates under the mild conditions. The results of the beam walking assay indicated that the motor
function of the rats after stroke was significantly improved, especially compound 1. In addition to this, the
differentiation levels of the neural stem cells were also increased after treated with the compound 1, but
compound 2 did not. Furthermore, compound 1 revealed stronger promotion activity on the recovery of the motor
function of the rats after stroke by stimulating the neural stem cells differentiation. At the end of the research, we
draw this conclusion, compound 1 exhibited much more excellent protective activity than compound 2 on the
motor function after stroke by increasing neural stem cells differentiation.
Conflicts of Interest
The author(s) declare(s) that there is no conflict of interest regarding the publication of this paper.
Data Availability
The data used to support the findings of this study are included within the article.
Acknowledgments
Not applicable.
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Two Cu(II)-organic frameworks: effective CO fixation and protective activity
2
on the motor function
differentiation
after stroke by increasing neural stem cells
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5
In the present research, two novel metal-organic frameworks (MOFs) containing Cu(II) ions as nodes of and
{[Cu(L)]·2DMF·2H O} (1) and {[(CH ) NH ][Cu (L)(H O)PO ]·2DMF} (2) have been constructed by using 5-
2
n
3 2
2
2
2
4
n
(1H-imidazol-1-yl)isophthalic acid (H L), the dual-functional organic ligand featuring an imidazole part to
2
1
4

1
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3
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5
isophthalic acid 5-position. Because of its robust framework structure and the high density of open metal positions,
the activated 1 (denoted as 1a) could adsorb CO and efficiently convert them into circulating carbonates under
2
the mild conditions. Their treatment activity on the recovery of motor function after stroke in rats was evaluated.
Firstly, the beam walking assay was implemented to determine rats motor function after treated with compounds.
Next, the differentiation levels of the neural stem cells were also determined with western bot.
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24.
1. Two novel metal-organic frameworks (MOFs) containing Cu(II) ions have been constructed.
2. The activated 1 (denoted as 1a) could adsorb CO and efficiently convert them into circulating carbonates.
3. Their treatment activity on the recovery of motor function after stroke in rats was evaluated.
2
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1
1
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1
1
1
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25.
Two Cu(II)-organic frameworks: effective CO fixation and protective activity
2
on the motor function
differentiation
after stroke by increasing neural stem cells
Qing Ye, Li Zhang, Zhou-Li Shao, Wei Zhang, Chao Li, Xiang-Ming Ye*
Department of Rehabilitation Medicine, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou
Medical College, Hangzhou, Zhejiang, China
E-mail: xm_ye01@126.com
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Qing Ye and Li Zhang synthesized and characterized the compounds;
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5

1
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Zhou-Li Shao and Wei Zhang performed the activity assay experiments;
Chao Li and Xiang-Ming Ye designed the study and prepared the manuscript.
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26.
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