Catalytic cyanosilylation application and antitumor activity in osteosarcoma of a porous Gd(III)-based coordination polymer

Article abstract of DOI:10.1016/j.molstruc.2019.126919

Solvothermal reactions of 1, 3, 5-tris (4-carboxyphenyl)-benzene (H₃BTB) with Gd(NO₃)·6H₂O gave rise to a new highly porous coordination polymer {[Gd(BTB)(H₂O)](DMF)(H₂O)}_n (1) having three

Full text of DOI:10.1016/j.molstruc.2019.126919

Journal of Molecular Structure 1198 (2019) 126919
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: http://www.elsevier.com/locate/molstruc
Catalytic cyanosilylation application and antitumor activity in
osteosarcoma of a porous Gd(III)-based coordination polymer
a
b, *
Lei Wang , Gui-Bin Xue
a
Department of Orthopedics, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, Jiangsu, China
Department of Orthopedics, Lianshui County People ‘s Hospital of Jiangsu Province, Lianshui, Jiangsu, China
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 12 June 2019
Received in revised form
Solvothermal reactions of 1, 3, 5-tris (4-carboxyphenyl)-benzene (H BTB) with Gd(NO )$6H O gave rise
3
3
2
to a new highly porous coordination polymer {[Gd(BTB)(H
2
2 n
O)](DMF)(H O)} (1) having three dimen-
sional structure. In light of its highly rigid framework as well as the large one-dimensional triangular
channel configuration that has abundant open metal sites, we can utilize the resulting activated 1a as
effective Lewis catalysts for the acetaldehyde's cyanosilylation at room temperature. The comparison
25 July 2019
Accepted 9 August 2019
Available online 10 August 2019
experiments reflect that the open Gd2 sites, as catalytic activation sites, played a crucial part in het-
erogeneous catalysis. In connection to these, the possible catalysis mechanism has also been discussed in
detail. Compound 1a inhibition against the cancer cell viability was detected by the CCK-8 assay. Besides,
the cell colony formation assay was also carried out for the cell proliferation assay. Next, we further
explored the mechanism of compound 1a against cancer cells, so the Annexin V-FITC/PI double staining
assay was performed to determine the cell apoptosis.
þ
Keywords:
Coordination polymers
Open metal sites
Solvothermal reaction
Cyanosilylation reaction
Anticancer activity
© 2019 Elsevier B.V. All rights reserved.
1. Introduction
as well as laborious separation procedures, among other disad-
vantages. Therefore, an efficient, mild and environmentally friendly
Cyanohydrins are industrially valuable substrates and important
intermediates for the preparation of -aminonitriles, -hydrox-
yketones, -hydroxyacids, -hydroxyamines, and -aminoalcohols,
among others [1]. The main synthetic route for the synthesis of
cyanohydrins is the catalytic addition of the cyano group to a
solution for cyanosilylation of carbonyl compounds with TMSCN is
continue highly needed.
a
a
a
b
b
Coordination polymers (CPs) are a group of compounds that are
characterized by having pores of needed size and shape as molec-
ular reactors, thus permitting the specific molecules' encapsulation.
CPs have discovered many promising applications which include in
sensing, gas sorption, heterogeneous catalysis as well as drug de-
livery [7e10]. The CPs' application as heterogeneous catalysts have
a lot of benefits, including insolubility in common organic solvents,
easy crystallization in high yields, high thermal stability and pores'
fine tuning via ligand design, when compared with discrete mo-
lecular containers. In order to obtain high-density sites of catalytic
activity in CPs, an attractive way is to decorate the pore walls in CPs
which have catalytically active centers, and thus providing CP-
based nanoreactors. Such nanoreactor can not only show active
sites that have high density in the confined nano-space, but also
can permit the active sites to orient toward the cage's core, hence
promoting the mutual effects among the substrates and the active
sites, with the prospects of effectively catalyzing the cyanosilylation
under mind conditions [11e14]. To build the CP-based nano-
reactors, the selection of suitable organic ligand and metal ion are
two most important factors should be considered. Recent
carbonyl compounds. Trimethylsilyl cyanide (TMSCN) is
a
frequently explored substrate for catalytic cyanation reaction since
it is easy to handle, it has a high atom economy without providing
side reactions, and its SieC bond has low dissociation energy,
therefore, contrasting with the toxic nature of other cyanide sour-
ces such as HCN, NaCN, KCN, etc [2e4]. For the sake of preparing
cyanohydrins, a catalyst with base character or Lewis acid that can
activate the cyanide precursor and substrate is utilized to obtain a
highly versatile cyanohydrin trimethylsilane. Numerous catalysts,
including Lewis acids, Lewis bases and oxazaborolidinium ion have
been used in the cyanosilylation reactions [5,6]. Despite wide-
spread development, most of the displayed solutions offer fairly
modest yields, harmful solvents, demand prolonged reaction times
*
Corresponding author.
E-mail address: guibin_xue66@126.com (G.-B. Xue).
https://doi.org/10.1016/j.molstruc.2019.126919
022-2860/© 2019 Elsevier B.V. All rights reserved.
0

2
L. Wang, G.-B. Xue / Journal of Molecular Structure 1198 (2019) 126919
literatures have revealed that the nano-sized tricarboxylate ligand
, 3, 5-tris (4-carboxyphenyl)-benzene (H BTB) is a good choice for
2014/6 to refine them through fullematrix leastesquare ap-
proaches on F [20]. The whole H atoms were produced in their
2
1
3
building CPs with robust framework and high inner spaces [15e17].
On the other hand, the Gd(III)-based coordination polymers have
been widely studied as the heterogeneous catalyst due to the strong
coordination bonds and easy generation of Lewis acid site [18]. In
this study, solvothermal reactions of 1, 3, 5-tris (4-carboxyphenyl)-
desired positions, and the whole nonehydrogen atoms were
refined anisotropically. Due to the highly disordered nature of the
lattice DMF and water solvents, they could not be figured out from
the electron density map via the structural refinement, so the
SQUEEZE option embedded in PLATON was used to remove the
contribution of the highly disordered lattice guests [21]. Table 1
summarized the refinement details and crystallographic data, and
the compound 1's chosen bond angles and bond distances are
displayed in there too.
benzene (H
porous coordination polymer {[Gd(BTB)(H
3
BTB) with Gd(NO
3
)$6H
2
O gave rise to a new highly
O)](DMF)(H O)} (1)
2
2
n
having three dimensional structure. In light of its highly rigid
framework as well as the large one-dimensional triangular
channel-type configuration that has abundant open metal sites, we
can utilized the resulting activated 1a as effective Lewis catalysts
for the acetaldehyde's cyanosilylation at room temperature and
solvent free conditions. The comparison experiments reflect that
2.4. CCK-8 assay
After treated with compound 1a, the viability of MG63 human
the open Gd2 sites, as catalytic activation sites, played a crucial
part in heterogeneous catalysis. In connection to these, the possible
catalysis mechanism has also been discussed in detail. In the
pharmacodynamics research section, we firstly evaluate the anti-
viability and anti-proliferation activity of compound 1a MG63 hu-
man osteosarcoma cells. All data demonstrated that compound
could remarkably reduce MG63 cells' proliferation and viability.
Besides, Annexin V-FITC/PI assay convinced the mechanism of the
compound activity, which is mediated by inducing cancer cell
apoptosis.
þ
osteosarcoma cells was identified by Cell Counting Kit-8 assay in
accordance with the instructions of manufacturer [22]. In short, the
MG63 cancer cells with 70e80% confluence was harvested, washed,
suspended and then seeded into 96-well plates at the final density
4
of 1 ꢂ 10 cells/well. The MG63 cancer cells were incubated at
2
thirty-seven centigrade degree in the incubator, 5% CO all night,
they were added with a certain dilutions of compound 1a (80, 40,
0, 10, 8, 4, 2, 1 M) for 24 h treatment in the incubator. After
2
m
treatment, the culture medium was discarded and further incu-
bated with fresh medium which contains CCK-8 reagent and
cultured for another 2 h at thirty-seven centigrade degree, 5% CO
2
2
. Experimental
in the dark. In the end, we measured absorbance of every group at
the wavelength is 450 nm utilizing the multifunctional microplate
reader. We repeated the experiment three times.
2.1. Materials and instrumentation
The whole solvents and reagents utilized in the study were
commercially available, and they can be utilized with no farther
purification. Elemental analyses (N, H as well as C) were measured
through utilizing PerkinElmer 240 elemental analyzer. Utilizing the
NETSCHZ STAe449C thermo-analyzer to perform thermogravi-
2.5. Colony formation assay
We also conducted the plate colony formation assay to explore
the compound 1a's inhibitory impact on MG63 cancer cell prolif-
eration in line with the protocols of manufacturer [23]. In short, the
ꢀ
metric analysis when the heating rate is 10 C/min and at a nitrogen
3
atmosphere. We measured infrared spectra on the Nicolet Magna
MG63 cancer cells with 1 ꢂ 10 cell/well were initially seeded into
ꢁ
1
7
50 FT-IR spectrometer between 400 cm to 4000 through uti-
each well of a six-well plate and maintained in DMEM culture
lizing the KBr pellets, and we recorded the PXRD analyses on the
Bruker AXS D8 advanced automated diffractometer which has Cu-
medium has added with 10% FBS. We refreshed the medium ac-
ꢀ
cording the cells' growth. After incubated at 37 C, 5% CO
2
for
Ka
radiation.
fourteen days, the cells were fixed with methanol and then stained
2.2. Synthesis of compound {[Gd(BTB)(H O)](DMF)(H O)} (1)
2 2 n
Table 1
Crystal data and structure refinements for 1.
We added the mixture of H
3
BTB (0.062 mmol, 35 mg) and
O (1 mL)
Empirical formula
Formula weight
Temperature/K
Crystal system
Space group
a/Å
27 7
C H14GdO
607.63
293(2)
hexagonal
P6 22
5
18.06392(11)
18.06392(11)
21.9636(15)
90
90
120
6206.7(4)
Gd(NO $6H O (0.1 mmol, 46 mg) into a solution of H
3
)
3
2
2
and DMF (4 mL). After joining 3 drops of 2,6-lutidine, sealing the
mixture in the Pyrex tube, and then heated them for three days at
one hundred twenty centigrade degree. Since they were cooled to
room temperature, we filtered the light yellow polyhedral-shaped
crystals formed, and washed them with H
in the air. Compound 1's analytical found (C30
H, 3.19%; C, 51.66%. Calculate: N, 2.00%; H, 3.32%; C, 51.57%.
b/Å
2
O, last, we dried them
c/Å
H
23GdNO ): N, 2.24%;
9
ꢀ
ꢀ
a
b
g
/
/
ꢀ
/
3
Volume/Å
Z
2
.3. X-ray crystallography
6
r
calcg/cm3
0.975
10.592
Compound 1's single crystal X-ray crystal data was gathered
ꢁ1
m
/mm
under the room temperature on the computerecontrolled Oxford
Xcalibu E diffractometer by utilizing graphiteemonochromated
Reflections collected
14298
Independent reflections
Data/restraints/parameters
Goodness-of-fit on F2
3721 [Rint ¼ 0.0449, Rsigma ¼ 0.0364]
3721/175/202
1.081
MoeK
and reduction were operated using the CrysAlisPro (version: 38.41)
19]. Empirical absorption correction was carried out using spher-
a radiation when l equals to 0.71073 Å. The data collection
Final R indexes [I ꢃ 2
s
(I)]
R
1
¼ 0.0422,
u
u
R
2
¼ 0.1261
[
Final R indexes [all data]
Largest diff. peak/hole/e Å
Flack parameter
R1 ¼ 0.0446,
0.81/-0.45
0.307(8)
R2 ¼ 0.1294
ꢁ
3
ical harmonics implemented in SCALE3 ABSPACK scaling algorithm.
The configurations were figured out through direct approaches by
utilizing SHELXS-2014 package, and then utilizing the SHELXL-
CCDC
1912933

L. Wang, G.-B. Xue / Journal of Molecular Structure 1198 (2019) 126919
3
with 1% crystal violet for 15 min. The MG63 cancer cell colonies
were counted, pictured and also visualized.
hexagonal and highly symmetric space group P6
1
22 and its three-
dimensional coordination network is established by the connec-
3
ꢁ
tion of the BTB ligands and infinite one-dimensional helical chain
construction units. The compound 1's asymmetric coordination
unit is composed of one crystallographically independent Gd(III)
ion which is located in a symmetric position ad occupied half of the
2.6. Cell apoptosis assay
The commercial Annexin V-FITC/PI Apoptosis Detection Kit I
was applied to measure apoptotic MG63 cancer cells’ level after
compound 1a treatment in accordance with the protocol of
3
ꢁ
space, one coordinated water molecule, a half BTB ligand, one
lattice water along with one disordered DMF molecules as reflected
via the TGA analysis, which all are conductive to the neutral
framework configuration. As Fig. 1a displayed, the Gd(III) ion is
seven-coordinated by one coordinated water molecule and six
manufacturer [24]. In brief, the MG63 cancer cells were seeded into
5
6
-well plates with destiny of 5 ꢂ 10 cells/well and incubated in an
ꢀ
incubator at 37 C, 5% CO
2
overnight. Next, the compound 1a was
3
ꢁ
carboxylate O atoms that from six varying BTB ligands, and the
pentagonal bipyramid geometry is obtained by it with the depar-
ture parameter of 1.62 as revealed via the SHAP software. The
Gd(III)eO bond distances are in between 2.206(3) and 2.596(5) Å,
which are similar to those observed in other Gd(III)-based coordi-
nation polymers constructed from the polycarboxylate ligands.
Each Gd(III) atom is linked to a neighboring atom by three car-
added into wells at a certain concentration for 24 h treatment. Since
4 h incubation, the cells were collected, washed and suspended. In
the dark, 5 L of PI dyes as well as FITC-Annexin V were added into
2
m
cell suspension to label the cells. Finally, we measured the apoptotic
cells in flow cytometry at 488 nm and 525/625 nm. We carried out
this experiment at least three times.
3
ꢁ
boxylic groups and every BTB ligand is bound to six Gd(III) ions.
Thus, this connection mode results in the formation of a one-
3
. Results and discussion
1
dimensional right-handed chain which is along the 6 axis and
3
.1. Crystal structure of complex 1
show a rare Ln-based helical chain construction units in line with
the CCDC database. The helical chain's pitch is 21.836(3) Å. The
3
ꢁ
H
3
BTB and Gd(NO
mixed solvent of H O and DMF, and complex 1 as light yellow
crystals was obtained. What calls for special attention is that the
BTB ligand couldn't be dissolved in common organic solvents
including CH CN, MeOH, EtOH, as well as water, but could be dis-
3 3 2
) $6H O are solvothermally reacted in the
three carboxylate groups of the BTB ligand are full deprotonated
1
1
1
1
2
6
and connects with six different Gd(III) atom in the m -h : h : h : h :
1
1
h
:
h
mode (Fig. 1b). In addition, such one-dimensional helical
H
3
chain construction units are farther connected by its three
3
ꢁ
3
carboxylate groups through BTB
ligand to provide a three-
solved in DMA and DMF. Hence, the DMF was selected as primary
solvent in the reaction with water which act as assistant solvent.
The complex 1's chemical formula was constructed through the
combination of TGA, the elemental analysis as well as single-crystal
dimensional non-interpenetrating framework that has one-
dimensional triangular channels, and its coordinated water mole-
cule pointed to the channel center (Fig. 1c). On the basis of the
crystallographic data and also in the consideration of the atoms'
van der Waals radii, the triangular channel's pore size is 8.8 Å,
which are filled with the disordered DMF molecules (Fig. 1d). From
the perspective of network topology, this three-dimensional
X-ray
[Gd(BTB)(H
tural solution on the basis of the crystal data under the room
temperature indicates that complex crystallizes in chiral
diffraction
study,
which
was
formulated
as
{
2
O)](DMF)(H
2
n
O)} . The refinement results and struc-
1
Fig. 1. (a) View of the Gd(III) ion's coordination environments and the 1D helical chain in 1 (b) The BTB3ꢁ ligand's coordination mode. (c) The compound 1's three-dimensional
framework. (d) The compound 1's one-dimensional trigonal channels with water occupied Gd(III) sites.

4
L. Wang, G.-B. Xue / Journal of Molecular Structure 1198 (2019) 126919
ꢀ
ꢀ
framework that has one-dimensional helical chain construction
units could be predigested to the 2-nodal (6,6)-connected network
whose point symbol is (4 .6 )(4 .6 ), and the point symbol can't be
observed in the MOF chemistry (Fig. 1d). Every Gd(III) ion acts as a
stability under 410 C. PXRD researches forecast that under 80 C
high vacuum for one day, the activated 1a was produced that
contain the highly-crystalline feature, and its pattern matches with
its as-synthesized pattern which demonstrate 1a is robust. We
10
5
7 8
6
-connected node and every BTB ligand connects six Gd(III) ions in
carried out N
the compound 1a's surface area and permanent porosity. As Fig. 2c
displayed, the compound 1a's N gas adsorption shows a reversible
type-I isotherm. The Langmuir surface areas and calculated BET are
2
adsorption on the activated samples at 77 K to study
the work. Through utilizing PLATON software, we calculated and
found that the compound 1's effective free volume with no coor-
dinated water molecules was 58.3% of the crystal volume, that is
2
3
3
2
ꢁ1
2 ꢁ1
3
569 Å of the 6126 Å unit cell volume.
1075 m g
and 784 m g , separately, ranking highly in the
Gd(III)-based coordination polymers. The micropore volume ac-
quired through the experiments which approaching to the theo-
retical value of 0.45 cm g is 0.38 cm g . Compliance with
measurements from the crystal structure, DFT analysis indicates
that the compound 1a's pore size is about 8.6 Å (displayed in
Fig. 2d).
3
.2. PXRD and thermogravimetric analysis for compound 1
3
ꢁ1
3 ꢁ1
In order to check the as-prepared 1's phase purity in different
reaction systems, the corresponding PXRD patterns were collected
under the room temperature. As Fig. 2a displayed, the compound
1
's PXRD pattern shows sharp peaks which is similar to the one
simulated from the crystal data, indicating the high crystallinity of
the as-prepared samples. The slight different peaks in reflection
intensity between experimental and simulated PXRD patterns
might be due to the following reason: In the as-prepared samples of
3.3. Catalytic activity
The benzaldehyde's cyanosilylation was chosen as the model
reaction to optimize the reaction conditions as well as to confirm
the compound 1a's catalytic activity. Several results are gathered in
Table 1. In the presence of 1a, excessive TMSCN whose molar ratio is
1:2 was utilized for the test reaction to obatin 2-phenyl-2-(trime-
thylsilyloxy)ethanenitrile which is the unique detectable outcome.
The conversion rate of benzaldehyde on 10mol % 1a enhanced with
time step by step, reaching 96% within 12 h (Table 2, entry 4).
Conversely, a blank reaction under identical conditions but without
any catalyst resulted in only 12% transformation after 12 h (entry 1).
The results evidently confirm the compound 1a's catalytic activity
for cyanosilylation. On order to determine whether the noticed
catalytic activity was related with the leached species or solid MOF,
the reaction with 10 mol% 1a was performed under identical
1, there exist a lot of DMF solvents in the lattice, but their electronic
contribution was removed from the crystal data by the SQUEEZE
option in PLATON. Even if the DMF crystal solvents in the voids are
disordered, their electron density still contributes to diffraction,
thus resulting in the additional peaks in the patterns of the as-
prepared samples [25]. Then, we performed TGA at the atmo-
spheric environment to evaluate the as-prepared 1's thermal sta-
bility and the pore volume which guest molecules might occupy
(
Fig. 2b). Results display that the framework revealed approxi-
ꢀ
mately 16.2% weight loss occurred before 248 C on account of the
release of one lattice DMF, coordinated H
2
O as well as one lattice
water solvent molecules (calcd: 15.6%), also, the framework
2
Fig. 2. (a) The compound 1's PXRD pattern (b) The compound 1's TGA curves, MeOH exchanged 1 and 1a. (c) The 77 K N sorption isotherm for 1a. (d) The compound 1a's pore size
distribution on the basis of the Horvath-Kawazoe model.

L. Wang, G.-B. Xue / Journal of Molecular Structure 1198 (2019) 126919
5
Table 2
Table 3
Optimization of conditions for catalyst 1a and contrast test of 1.
The results for the aldehydes’ catalytic cyanosilylation in the presence of compound
a.
1
Entry
Cat
Quant.a (mol%)
Time
Conv.(%)b
Entry
R
1
R
2
Time (h)
conversiona
1
2
3
e
e
12
12
12
12
12
12
12
12
12
12
70
85
96
94
28
34
90
88
1a
1a
1a
1a
Gd(NO
GdCl
1a
1a
2
5
1
2
3
4
5
6
Ph
H
H
H
H
H
H
12
12
12
12
12
30
96%
94%
96%
92
73%
32%
2-CH
3-CH
4-CH
1-naphth
9-nathra
3
3
3
C
C
C
6
6
6
H
H
H
4
4
4
c
4
10
20
10
10
10
10
5
6
7
8
9
3
)
3
$6H
2
O
3
$6H
2
O
d
a
e
Conversion determined by GC.
a
The quantity refers to the molar amount of Gd(III) compared with that of
benzaldehyde.
the complex 1a after the first cycle of catalytic application has been
checked via the PXRD measurements, which shows a similar PXRD
patterns with that of the freshly prepared 1a, indicating its robust
framework structure in the catalytic process (Fig. 2a).
b
Conversion of benzaldehyde determined by GC using n-dodecane as the internal
standard. Because only the addition product is formed in this reaction, the yield of
the product is equal to the conversion of benzaldehyde.
c
The first cycle.
The second cycle.
The third cycle.
d
e
conditions. After 5 h, we filtered the solid while hot, and then we
stirred and refluxed the filtrate again. The filtrate's GC analysis
demonstrated that nearly no farther reaction taken place even after
4
8 h. The control experiment evidently forcasts that no active
substance was immersed in the liquid phase and that the 1a's
catalytic properties were heterogeneous in essence.
We also researched the catalyst's effect dosage on cyanosilyla-
tion conversion. As Table 1 displayed (entries 2e5), as the catalyst's
amount raised from 2 mol% to 10 mol%, the conversion rate raises,
but farther enhancing the amount more than 10 mol% no longer
results in significant improvement in the conversion rate. We
compared the catalyst with two readily available Gd(III) reagents,
On the basis of the former reported results as well as the
experimental results, a reasonable reaction mechanism was put
forward to explain the cyanosilylation reaction process catalyzed by
that is GdCl
3
$6H
2
O and Gd(NO
3
)
3
$6H
2
O. The reaction carried out in
$6H O resulted in
the presence of 10 mol% GdCl
3
$6H
2
O or Gd(NO
3
)
3
2
the much lower conversion (displayed in the entries 6 and 7),
indicating that 1a was more effective in facilitating the reaction
than the simple Gd(III) compounds. This can give the credit to the
compound 1a's microporous configuration as well as the homo-
geneously distributed metal sites. We carried out many experi-
ments to examine the compound 1a's recyclability (displayed in
Table 2, entries 4, 8, 9). While the catalyst which was filtered out
since the first run was diametrically utilized for the second run, the
benzaldehyde conversion rate was 71% in 12 h. The reduced activity
might be mostly owing to the pores' partial blocking as well as the
ꢀ
open metal sites' occupancy. Through 2 h calcination under 200 C,
we can remove the guest molecules. When we calcined the catalyst
after every run and then reemployed them in the following run, the
benzaldehyde conversion rate remains high (90% at the second run
and 88% at the third run, separately). A slight reduce in the con-
version rate may be due to repeated reaction, and the calcination
procedures may bring about the minor damage to the frame. With
regard to benzaldehyde substituted under the identical conditions,
the 3-methylbenzaldehyde's conversion rate was very alike to the
benzaldehyde's conversion, while that of 2-methylbenzaldehyde
was a little lower and that of 4-nitrobenzaldehyde was a little
higher (Table 3). The results demonstrated the substituent groups'
(
weak) electronic impacts. Strong electron absorption of the nitro
group can remarkably enhance the aldehyde group's reactivity. The
nitro's rather weak impact that observed in the research could be in
the account of the strong Lewis acidity's leveling effect that in the
center of Gd(III). The large substrate 1-naphthaldehyde demon-
strated a lower conversion rate, while the larger 9-anthraldehyde
dementrted
a
conversion that lower than that of 1-
naphthaldehyde (32%). Size effect indicated that catalytic reaction
takes place at least in the MOF's pores. In addition, the stability of
Scheme 1. Proposed mechanism for the carbonyl compounds' cyanosilylation reaction
which are catalyzed by 1a.

6
L. Wang, G.-B. Xue / Journal of Molecular Structure 1198 (2019) 126919
1
a [11e14]. In order to pre-expose unsaturated metal sites, heating
compound 1a for 24 h, the cell viability curves of MG63 cells was
significantly reduced after compound 1a treatment, with the IC50 of
1.88 ± 0.04 mM, which is obviously lower than that of the control
the compound to remove unstable water molecules from the
compound 1a's channels is necessary. In order to react the alde-
hydes with TMSCN, we activated the aldehydes through the coor-
dinatively unsaturated Gd(III) centers (Scheme 1). Then the
isomerization of TMSCN to TMSNC occurs (to facilitate the subse-
quent nucleophilic addition of the isocyano group), which has been
reported in a previous computational study on the Strecker reac-
tion of TMSCN and benzaldehyde N-benzhydrylimine [26]. After
the nucleophilic addition of the isocyano group to the aldehydes,
the products leave from the catalyst and the MOF was used in the
next catalytic cycle.
drug (Fig. 3A). This result indicated the stronger anti-cancer activity
of compound on MG63 cancer cells in vitro. In accordance to the
previous study, the colony formation assay illustrated the com-
pound 1a's anti-proliferation ability on MG63 cancer cells. And the
results demonstrated that the numbers of colonies were reduced
obviously compared with the control group, which is shown in
pictures (Fig. 3B). These data indicated the compound 1a exhibited
remarkable anti-cancer activity in vitro.
3.5. Compound 1a induces apoptosis of MG63 cells
3.4. Compound 1a inhibits viability and proliferation of MG63 cells
The previous data revealed the compound 1a has remarkable
To detect the synthesized compound 1a's anti-cancer activity on
MG63 cells, the cell viability and proliferation was measured. We
carried out the CCK-8 assay to evaluate the compound 1a's anti-
anti-proliferation and anti-viability activity on MG63 cancer cells.
Then, we further explored the Annexin v-fitc/PI double staining
method to detect the impact of compound on MG63 cancer cells
apoptosis in flow cytometry. As Fig. 4 displayed, we can see that the
viability after treatment with
a certain concentration of
Fig. 3. Compound 1a constrains proliferation and viability of MG63 cells. MG63 cancer cells were treatment with compound 1a at a certain concentration compound and treated for
different time. (A) CCK-8 assayw was used to assay viability of MG63 cancer cells and the cell survival curves was plotted. (B) Numbers of cell colonies formation of MG63 cancer
cells with or without compound treatment. Data were showed as average ± three separate experiments' standard derivation.

L. Wang, G.-B. Xue / Journal of Molecular Structure 1198 (2019) 126919
7
Fig. 4. Compound 1a induces MG63 cancer cell apoptosis. The MG63 cancer cells that in the logarithmic growth stage were cultured with compound 1a for 24 h. We measured the
apoptotic cells after compound treatment by utilizing Annexin V-FITC/PI kit in flow cytometry.
positive control groups contain 43.44% apoptotic cells and the
negative control groups contain 0.19% apoptotic cells. As we ex-
pected, after treated with compound 1a, the apoptotic cells’ per-
centage was increased into 38.06%, which is close to the level of
positive group. This experiment indicated the compound 1a could
induce MG63 cancer cell apoptosis and exert anti-cancer activity
in vitro.
Conflicts of interest
The author(s) declare(s) that there is no conflict of interest
regarding the publication of this paper.
Acknowledgements
4
. Conclusion
The research did not receive any specific funding.
All in all, a novel porous coordination polymer which has per-
manent porosity was successfully made through the self-assemble
of Gd(III) ion and 1, 3, 5-tris (4-carboxyphenyl)-benzene in the
mixed solvent of water and DMF. The as-synthesized MOF 1 is
composed of the helical chain secondary construction units and has
one-dimensional nano-sized channels that operating along c axis
which are functionalized with high-density open metal sites.
Furthermore, in light of its highly rigid framework as well as the
large one-dimensional triangular channel configuration that has
abundant open metal sites, we can utilized the resulting activated
References
[1] R.J.H. Gregory, Chem. Rev. 99 (1999) 3649.
[2] Y. Yu, Y. Chen, W. Wu, H. Jiang, Chem. Commun. 53 (2017) 640.
[
[
3] L. Kang, L. Zhao, S. Yao, C. Duan, Ceram. Int. 45 (2019) 16717.
4] Y. Hamachi, M. Katano, Y. Ogiwara, N. Sakai, Org. Lett. 18 (2016) 1634.
[5] N.H. Khan, R.I. Kureshy, S.H.R. Abdi, S. Agrawal, R.V. Jasra, Coord. Chem. Rev.
252 (2008) 593.
[
[
6] D.H. Ryu, E.J. Corey, J. Am. Chem. Soc. 127 (2005) 5384.
7] C. Duan, F. Li, M. Yang, H. Zhang, Y. Wu, H. Xi, Ind. Eng. Chem. Res. 57 (2018)
1
5385.
[8] Y.Y. Yang, L. Kang, H. Li, Ceram. Int. 45 (2019) 8017.
9] Q. Sui, Y. Yuan, N.N. Yang, X. Li, T. Gong, E.Q. Gao, L. Wang, J. Mater. Chem. C. 5
2017) 12400.
10] B. Mu, F. Li, K.S. Walton, Chem. Commun. 47 (2009) 2493.
1
a as effective Lewis catalysts for the acetaldehyde's cyanosilylation
[
at room temperature. The comparison experiments reflect that the
(
open Gd2 sites, as catalytic activation sites, played a crucial part in
heterogeneous catalysis. Besides, the CCK-8 results forcasted the
compound 1a can restrain the MG63 cancer cells viability signifi-
cantly, and the colony formation assay demonstrated the com-
pound 1a has inhibitory effect on MG63 cancer cells. Then, we
carried out the cell apoptosis assay and discovered that compound
þ
[
[11] L. Kang, H.L. Du, X. Du, H.T. Wang, W.L. Ma, M.L. Wang, F.B. Zhang, Desalin.
Water Treat. 125 (2018) 296.
[
[
12] C. Duan, J. Huo, F. Li, M. Yang, H. Xi, J. Mater. Sci. 53 (2018) 16276.
13] P. Phuengphai, S. Youngme, P. Gamez, J. Reedijk, Dalton Trans. 39 (2010) 7936.
[14] M.K. Sharma, P.P. Singh, P.K. Bharadwaj, J. Mol. Catal.
42e343, 6.
15] M.L. Foo, S. Horike, S. Kitagawa, Inorg. Chem. 50 (2011) 11853.
16] C. Volkringer, T. Loiseau, J. Marrot, G. F eꢀ rey, CrystEngComm 11 (2009) 58.
A Chem. (2011)
3
[
[
1
a has impact on MG63 cancer cells apoptosis production. Results
manifested that the compound 1a exert anti-cancer effect through
inducing cancer cell apoptosis in vitro. Above all, the compound has
the potential to be a candidate anti-cancer compound for human
cancer therapy.
[17] D.M. Chen, J.Y. Tian, Z.W. Wang, C.S. Liu, M. Chen, M. Du, Chem. Commun. 53
(2017) 10668.
[18] Z. Xue, J. Jiang, M.G. Ma, M.F. Li, T. Mu, ACS Sustain. Chem. Eng. 5 (2017) 2623.
[19] O.D. Rigaku, CrysAlis PRO, Rigaku Oxford Diffraction, Yarnton, England, 2015.
[20] G.M. Sheldrick, Acta Crystallogr. Sect. C Struct. Chem. 71 (2015) 3.
[21] A.L. Spek, Acta Crystallogr. Sect. C Struct. Chem. 71 (2015) 9.
[22] S. Yuan, Y. Han, M. Ma, K. Rao, Z. Wang, R. Yang, Y. Liu, X. Zhou, Environ.
Pollut. 250 (2019) 58.
Supplementary material
[
[
[
23] P. Han, J.W. Li, B.M. Zhang, J.C. Lv, Y.M. Li, X.Y. Gu, Z.W. Yu, Y.H. Jia, X.F. Bai,
L. Li, Y.L. Liu, B.B. Cui, Mol. Cancer 16 (2017) 9.
24] H.D. Zhang, L.H. Jiang, J.C. Hou, S.L. Zhong, S.Y. Zhou, L.P. Zhu, J. Li, D.D. Wang,
D.W. Sun, Z.L. Ji, J.H. Tang, Biomed. Pharmacother. 107 (2018) 1342.
25] M.Y. Sun, D.M. Chen, Polyhedron 147 (2018) 80.
CCDC No.1912933 possesses additional crystallographic data for
this thesis. The data is available free of charge from The Cambridge
Crystallographic data Center via http://www.ccdc.cam.ac.uk/data_
request/cif.
[26] J. Tao, Y. Guo, S. Li, J. Mol. Struct. Theochem 899 (2009) 61.