CN105330703B - A kind of ten core terbiums substitution arsenic tungsten oxygen silicate nanometer cluster compound and its preparation method and application - Google Patents
A kind of ten core terbiums substitution arsenic tungsten oxygen silicate nanometer cluster compound and its preparation method and application Download PDFInfo
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Abstract
The present invention relates to a kind of ten core terbiums substitution arsenic tungsten oxygen silicate nanometer cluster compound, the chemical formula of the cluster compound is [H2N(CH3)2]6Na24H16{[Tb10W16(H2O)30O50](B‑α‑AsW9O33)8}·97H2O, belong to anorthic system,P- 1 space group, cell parameter area=18.940 (4),b=24.333 (5),c=29.920 (6),α=104.699 (4) °,ß=101.781 (4) °,γ=95.444 (4) °,V=12900(4)Å3,Z=1,R 1=0.1515,wR 2=0.3596.Research finds that the cluster compound has obvious growth inhibition effect to human cervical carcinoma cell HeLa and human breast cancer cell MCF 7, available for preparing anti-cervical cancer and anti-breast cancer medicines.
Description
Technical field
The invention belongs to poly-tungstate technical field of chemical material preparation, and in particular to a kind of ten core terbiums substitution arsenic tungsten oxygen acid
Salt nanometer cluster compound, preparation method and its application in terms of active anticancer.
Background technology
It is well known that cancer is to threaten one of important diseases of human health, deterioration recently as ecological environment and
The diversification of diet causes the incidence of disease of cancer in ascendant trend, the harm to the mankind are on the rise year by year.Although chemotherapy has been made
For a kind of important medical procedure for the treatment of cancer, but also make because of the shortcomings of its toxic side effect is big, costly its application by
Greatly limitation.Therefore the broad spectrum type cancer therapy drug for finding high-efficiency low-toxicity is extremely urgent.Polyoxometallate is by before high price
Transition metal ions（Usually MoV, MoVI, WVI, VV, NbV Or TaV）A kind of multinuclear to be formed is connected by oxygen atom to coordinate
Thing, its unique oxygen-enriched surface, controllable structure and preferable redox active impart them in catalysis, magnetic, medicine
The fields such as thing have significant application value.It is worthy of note that more metal salt anions can be possible with some special biomolecule
The redox of generation and the effect of relatively strong statcoulomb make it in the synthesis of medicine, separation, identification etc.
Has advantage.From last century the seventies, polyoxometallate has been used for antiviral, antitumor etc. research.Example
Such as 1971, French Raynaud etc. took the lead in reporting [SiW12O40]4–Studied in the pharmaceutical activity of anti-virus aspect（Referring to M.
Raynaud, J. C. Chermann, F. Plata, et al.C. R. Acad. Sci. Ser. D. 1971,272,
347）.1985, French Domont etc. have studied (NH4)17Na[NaSb9W21O86]·14H2O (HPA-23) is suppressing AIDS
Effect in sick viral reverse transcriptase（Referring to D. Domont, B. Spire, F. Barre-Sinoussi, et al.Ann Inst Pastear / Virol1985,136E, 75).The first has the polymolybdote (NH of anti HIV-1 virus activity4)12H2
[Eu4Mo29O100(H2O)16]·13H2O (PM-104) was reported by Inouye etc. in 1991（Referring to Y. Inouye, Y.
Tokutake, T. Yoshida,Chem. Pharm. Bull.1991,39, 1638）.1996, Yamase etc. had found saturation
Keggin, vacant Keggin, Wells-Dawson and the isostructural poly-tungstate of Keggin interlayer types are in anti-Staphylococcus aureus
It is active in terms of bacterium（Referring to T. Yamase, N. Fukuda, Y. Tajima,Biol. Pharm. Bull.1996,19,
459）.The beginning of this century, a new stage is entered again for the research in terms of polyoxometallate pharmaceutical chemistry.2001,
Hill etc. uses interaction of the study of computer simulation between the-Dawson of Wells containing niobium structures and HIV-1 albumen first
Situation（Referring to D. A. Judd, J. H. Nettles, C. L. Hill, et al.J. Am. Chem. Soc.2001,123,886）.2005, Wang Enbo etc. synthesized Vanadotungstic acid salt Pr using metathesis reaction and ion exchange first2H
[NiV13O38], the growth of the compound oral cancer cell shows very efficient inhibitory action（Referring to Y. Liu, S.
Tian, S. Liu, E. Wang.Transition Met. Chem.2005,30, 113）.2010, Dolbecq etc. have studied
Pharmaceutical activity of the polyoxometallate containing Diphosphonate part in terms of tumour cell is suppressed（Referring to J.-D. Compain,
P. Mialane, A. Dolbecq, et al.Chem. Eur. J2010,16,13741）.At present on polyoxometallic acid
The Anticancer Activities of salt are concentrated mainly on the more tungsten oxygen hydrochlorate transition metal derivatives and molybdenum oxygen of small-molecular-weight and small size
On hydrochlorate organic derivative, but polyoxometallate Anticancer Activities are substituted almost to the high core rare earth with nanoscale
It is blank out.
The content of the invention
Present invention aims at provide a kind of ten core terbiums substitution arsenic tungsten oxygen silicate nanometer cluster compound and preparation method thereof and answer
With.
To achieve the above object, the present invention adopts the following technical scheme that：
Ten core terbiums substitute arsenic tungsten oxygen silicate nanometer cluster compound, and its chemical formula is：[H2N(CH3)2]6Na24H16{[Tb10W16
(H2O)30O50](B-α-AsW9O33)8}·97H2O。
The preparation method of above-mentioned ten core terbium substitution arsenic tungsten oxygen silicate nanometer cluster compound, it comprises the following steps：
Under agitation, by Na2WO4·2H2O and (CH3)2NHHCl is dissolved into distilled water, and NaAsO is added dropwise dropwise2
Solution, Tb (NO are added after pH is adjusted into 4.0-4.53)3·6H2O, then pH is adjusted to 4.0-4.5 with hydrochloric acid, it is stirred at room temperature 30
More than min, then filter, filtrate is stood to colourless prism-shaped crystal is separated out, and is filtered again, crystal room temperature is dried as targeted
Compound；
The Na2WO4·2H2O、(CH3)2NH·HCl、NaAsO2、Tb(NO3)3·6H2The mol ratio of O and distilled water is
The ︰ 2222 of 8.5-10 ︰, 12.3-35.5 ︰, 1.0-2.3 ︰ 0.9-4.1.
Application of the above-mentioned ten core terbiums substitution arsenic tungsten oxygen silicate nanometer cluster compound in cancer therapy drug is prepared, is especially making
Application in standby anti-cervical cancer or anti-breast cancer medicines.
The advantages of present invention is using simple normal temperature aqua-solution method, in condition existing for organic solubilized agent dimethylamine hydrochloride
Under, sodium tungstate, terbium nitrate and sodium arsenite are reacted to obtain a kind of ten novel core terbiums by certain mol ratio substituted
Arsenic tungsten oxygen silicate nanometer cluster compound.In the reaction, the As of arsenous anionIIIElement has the three-dimensional effect of lone pair electrons chemical space
Should, the formation of the saturation structure with Keggin of classics on the one hand can be prevented, another aspect arsenous anion group introduces sodium tungstate reaction
The changeable arsenic tungsten oxygen hydrochlorate fragment of structure can be not only formed after system, and can effectively increase the carrying of arsenic tungsten oxygen hydrochlorate fragment
Negative electrical charge, this is advantageous to arsenic tungsten oxygen hydrochlorate fragment and is bonded more rare earth ions, and then assembles high core rare earth substitution arsenic tungsten oxygen
Silicate nanometer cluster.Rare earth ion with larger ionic radius and high ligancy is further assembled into arsenic tungsten oxygen hydrochlorate constructing block
Nano-cluster plays structure induction and stabilization.Slow evaporation, stand still for crystals process for high core rare earth substitute arsenic tungsten oxygen hydrochlorate receive
The formation of rice cluster provides advantage.
The present invention uses X-ray single crystal diffraction technology（Referring to Sheldrick G. M.SHELXTL−97, Program for Crystal Structure SolutionUniversity of G ttingen, Germany, 1997）To target
The crystal structure of compound is determined and characterized, and its cell parameter is as follows：
Compound [H2N(CH3)2]6Na24H16{[Tb10W16(H2O)30O50](B-α-AsW9O33)8}·97H2It is oblique that O belongs to three
Crystallographic system,P- 1 space group, cell parametera =18.940 (4),b =24.333 (5),c =29.920 (6),α =
104.699 (4) °,ß=101.781 (4) °,γ=95.444 (4) °,V = 12900(4) Å3,Z =1,R 1=0.1515,wR 2= 0.3596.The tungsten oxygen cluster fragment [Tb that its symmetrical molecule unit is included by ten core terbiums of 1 rectangle10W16(H2O)30O50
]26+Connect eight three omission [B- α-AsW9O33]9–Eight poly- the subunit { [Tb that constructing block is formed10W16(H2O)30O50](B-α-
AsW9O33)8}46–（See Fig. 1 a, Fig. 1 b）, 6 [H2N(CH3)2]+, 24 Na+Ion, 16 H+Ion and 97 crystalline water molecules
Form.Eight ten poly- core terbium arsenic tungsten oxygen hydrochlorate cluster anions { [Tb10W16(H2O)30O50](B-α-AsW9O33)8}46–It is by 8 three
Omission [B- α-AsW9O33]9–Constructing block is connected with the help of 50 external oxygen atoms by 10 terbium ions and 16 tungsten atoms
Form.In { [Tb10W16(H2O)30O50] (B-α-AsW9O33)8}46–Skeleton in, eight three omission [B- α-AsW9O33]9–Structure
Build block and be symmetrically distributed in the tungsten oxygen cluster fragment [Tb that ten core terbiums of rectangle include10W16(H2O)30O50]26+Around.According to we institute
Know, the tungsten oxygen cluster fragment [Tb that ten core terbiums of this rectangle include10W16(H2O)30O50]26+It is to be observed first.Closed in the cluster
In thing, all tungsten atoms use hexa-coordinate octahedral coordination pattern.[the Tb in rectangular metal center10W16(H2O)30O50]26+
Terbium atom uses two kinds of coordination modes：A kind of is the anti-prism geometric configuration in eight-coordinate four directions of distortion, and another kind is seven coordination lists
Cap triangular prism geometric configuration.It is worth mentioning that from { [Tb10W16(H2O)30O50](B-α-AsW9O33)8}46–Skeleton in by institute
Some terbium atoms can obtain a kind of eight ten eight nuclear tungsten clusters similar with the skeleton structure after removing（See Fig. 1 c）, this phenomenon enters
One step demonstrates terbium atom and substitutes the Stability Analysis of Structures of arsenic tungsten oxygen silicate nanometer cluster compound to act on for the ten core terbium.
The present invention substitutes the infrared spectrum of arsenic tungsten oxygen silicate nanometer cluster compound to ten core terbiums（See Fig. 2）With heat analysis behavior
（See Fig. 3）Characterize and analyzed.Its infrared spectrum is in 1100 600cm−1In the range of occur polyacid characteristic peak 950,867,
786 and 711 cm−1, they are respectively belonging toν(W–Ot)、ν(As–Oa)、ν(W–Ob) andν(W–Oc) asymmetric stretch of key shakes
It is dynamic.Means organic balance ion [H in cluster compound2N(CH3)2]+In N-H and the flexural vibrations peaks of C-H keys respectively appear in 1633 Hes
1467 cm−1Place, and the stretching vibration of N-H and C-H keys respectively appears in 3163 and 2810 cm–1Place.In addition, in 3438 cm–1
Strong absorption band, which occurs, in place to be proved in the cluster compound containing crystallization or water of coordination molecule；Ten core terbiums substitute arsenic tungsten oxygen silicate nanometer
The thermal stability analysis of cluster compound is as follows：On thermogravimetric curve, the first step between 25 to 200 DEG C is slowly weightless for 6.47%（Reason
By value：6.59%）, mainly losing corresponding to 97 crystalline water molecules；Second step weightlessness between 200 to 650 DEG C is
4.08%（Theoretical value：3.80%）, correspond mainly to 30 water of coordination molecule, 6 dimethylamine, 22 Hydrogen Protons lose；650 arrive
The 3rd step between 900 DEG C is weightless for 3.21%（Theoretical value：2.99%）, mainly due to losing 4 As2O3Caused by molecule.
In the present invention, ten core terbiums are substituted with the stabilization of arsenic tungsten oxygen silicate nanometer cluster compound in the solution by ultraviolet spectra
Property is studied.In its ultraviolet spectra, the strong absworption peak at 194 nm, O is attributed tot→ W p π-d π electric charges turn
Shifting transition, and the weak absorbing peak gone out at 248 nm, are attributed to Ob(c)→ W p π-d π charge transfer transitions（See Fig. 4）.In addition,
It has studied the feelings that the stability of ten core terbiums substitution arsenic tungsten oxygen silicate nanometer cluster compound in aqueous changes with time and acid-base value
Condition（As shown in Figure 5）, the results showed that target compound can be stablized 8 days or so in aqueous, the pH models stablized in aqueous
Enclose for 3.90-7.50（Cover blood of human body pH value range：7.30–7.50）.These results of study are lived for the anticancer of the cluster compound
Journal of Sex Research is laid a good foundation.
Substitute arsenic tungsten oxygen silicate nanometer cluster compound to human cervical carcinoma cell HeLa and human breast cancer cell to inquire into ten core terbiums
MCF-7 growth inhibition effect, using MTT（Tetramethyl azo azoles salt）Method is analyzed the cytotoxicity of target compound.
Active succinic dehydrogenase in the mitochondria of living cells can reduce MTT, form insoluble bluish violet first a ceremonial jade-ladle, used in libation
（Formazan）Crystal is deposited in living cells.On the contrary, dead cell can not then reduce MTT, produced into the cell without royal purple color substance
It is raw.Through dimethyl sulfoxide（DMSO）After cracking, the first a ceremonial jade-ladle, used in libation in living cells is dissolved, and its light is determined at 490 nm wavelength with ELIASA
Absorption value can reflect the number of living cells quantity in sample indirectly.Target compound is to human cervical carcinoma cell HeLa and people's mammary gland
Cancer cell MCF-7 has obvious growth inhibition effect while is in dose dependent（See Fig. 6）, its half-inhibition concentration (i.e. IC50
Value) it is shown in Table 1.Result of study shows that ten core terbiums substitution arsenowolframic acid salt nanometer cluster compound is formed such that target compound to people palace
Neck cancer cell HeLa（IC50 = 1.51 µM）And human breast cancer cell line Bcap-37（IC50 = 1.52 µM）Growth have preferably suppression
Make and use, significantly surmounted arsenowolframic acid salt precursor body K14[As2W19O67(H2O)]（To human cervical carcinoma cell HeLa：IC50 =
5.22 µM；To human breast cancer cell line Bcap-37：IC50 = 6.06 µM）.
In order to which goal in research compound is to human cervical carcinoma cell HeLa and apoptosis in breast cancer cell line MCF-7 process, use
Calcein-AM/PI lives the double dye test combination Annexin V-FITC/PI double fluorescence labelings experiments of dead cell to assess
Target compound induces the apoptosis degree of human cervical carcinoma cell HeLa and human breast cancer cell line Bcap-37, using light microscope come
Pattern change during tracker's cervical cancer cell HeLa and apoptosis in breast cancer cell line MCF-7.
The double dye tests of Calcein-AM/PI work dead cells：Calcein-AM（calcein acetoxymethy）Ester
It is a kind of cytoplasmic fluorescent marker, itself and unstressed configuration, but when it is penetrated into cell, by the lactonase in living cells
After catalysis, the water miscible green fluorescence material that can be generated is trapped in into the cell.So Calcein-AM is living thin commonly used to mark
Born of the same parents.And propidium iodide（PI）It can enter as fluorescent dye in the dead cell that has been destroyed of cell membrane, and in its nucleus
Chromosome combine, dead cell will be marked as red.So cell is marked jointly with Calcein-AM and PI, can be in fluorescence
Living cells and dead cell are observed under microscope simultaneously.It can be clearly seen that from Fig. 7 thin to human cervical carcinoma with target compound
Born of the same parents HeLa and human breast cancer cell line Bcap-37 handle part cancer cell dead after 6 h.
Annexin V-FITC/PI fluorescence labelings are tested：Under normal circumstances, the phosphatidylserine in normal cell
（phosphatidyl serine, PS）It is distributed on the inside of the double-layer of lipoid of cell membrane.But when there is apoptosis in cell, cell membrane
PS on the inside of double-layer of lipoid will turn over the outside to cell membrane.Annexin V are a kind of cardiolipin binding proteins, energy and Apoptosis
During be turned to PS outside cell membrane and specifically bound with higher affinity.Therefore, Annexin V fluoresceins can be passed through
FITC （Thiocyanic acid fluorescein）Annexin V-FITC after mark by and PS combination, mark in the apoptosis stage
Cell.And PI is a kind of DNA dyestuffs, the cell membrane in apoptosis mid-term, late period or dead cell can be passed through, and then make its cell
Core presents red.Can be clearly seen that from Fig. 8 can induce human cervical carcinoma cell HeLa and human breast carcinoma is thin with target compound
Born of the same parents MCF-7 handles part cancer cell-apoptosis after 6 h.
Cell can be rounded in apoptotic process along with form, volume reduction, karyopycnosis, chromatin condensation, karyorrhexis etc.
A series of changes.Using light microscope it can be seen that pattern change of the cell in apoptotic process.Display targeted in Fig. 9
Compound to human cervical carcinoma cell HeLa and human breast cancer cell line Bcap-37 processing after cancer cell in apoptotic process by primary morphology by
Gradual change circle, reduce, to 11 h after whole apoptosis.
The invention provides the preparation method and its active anticancer of a kind of ten core terbium substitution arsenic tungsten oxygen silicate nanometer cluster compound
Research, in terms of its advantage is concentrated mainly on following four：
1）The crystal structure characteristic of ten core terbium substitution arsenic tungsten oxygen silicate nanometer cluster compound provided by the invention can be penetrated by X-
Line single crystal diffraction technology accurately determines；
2）Ten core terbium substitution arsenic tungsten oxygen silicate nanometer cluster compound provided by the invention is synthesized using conventional aqueous method, system
Standby technique is simple, and cost is relatively low, and yield is higher, and application prospect is preferable；
3）Ten core terbium provided by the invention substitutes arsenic tungsten oxygen silicate nanometer cluster compound to human cervical carcinoma cell HeLa（IC50 =
1.51 µM）And human breast cancer cell line Bcap-37（IC50 = 1.52 µM）Growth there is better inhibition effect, significantly more than
Arsenowolframic acid salt precursor body K14[As2W19O67(H2O)]（To human cervical carcinoma cell HeLa：IC50 = 5.22 µM；It is thin to human breast carcinoma
Born of the same parents MCF-7：IC50 = 6.06 µM）；
4）Result of study provided by the invention is the first ten core terbiums substitution arsenic tungsten oxygen silicate nanometer cluster compound pharmaceutical activity
Research, Research foundation is provided as the feasibility of new cancer therapy drug to high core rare earth substitution polyoxometallate.
Brief description of the drawings
In Fig. 1, the molecular unit structure figure of arsenic tungsten oxygen silicate nanometer cluster compound, b a) are substituted for ten core terbiums) taken for ten core terbiums
For the simplification figure of arsenic tungsten oxygen silicate nanometer cluster compound, c) it is to substitute arsenic tungsten oxygen silicate nanometer cluster compound to go from ten core terbiums in terbium atom
88 core tungsten oxygen cluster compound figures after removing；
Fig. 2 be ten core terbiums substitute arsenic tungsten oxygen silicate nanometer cluster compound infrared spectrogram, show W-O in the cluster compound,
As-O, N-H, the eigen vibration absorption band of C-H and hydrone；
Fig. 3 be ten core terbiums substitute arsenic tungsten oxygen silicate nanometer cluster compound thermogravimetric curve, show weightless process Master Home in
Crystallize losing for water of coordination, water of coordination, dimethylamine, proton and arsenic trioxide；
Fig. 4 is the ultraviolet spectra that ten core terbiums substitute arsenic tungsten oxygen silicate nanometer cluster compound, wherein the strong absworption peak at 194 nm,
It is attributed to Ot→ W p π-d π charge transfer transitions, and the weak absorbing peak gone out at 248 nm, are attributed to Ob(c)→ W p π-d π electricity
Lotus shifts transition；
Fig. 5 is that ten core terbiums substitute arsenic tungsten oxygen silicate nanometer cluster compound in aqueous with the time（a）And pH（B, c）Stability
Research, the results showed that stabilization time is about 8 days to the cluster compound in the solution, and the pH scopes that the cluster compound is stablized in the solution are
3.90–7.50；
Fig. 6 be target compound to human cervical carcinoma cell HeLa and the inhibiting rate block diagram of human breast cancer cell line Bcap-37, this
Figure illustrates that there is target compound obvious growth inhibition to make to human cervical carcinoma cell HeLa and human breast cancer cell line Bcap-37
With；
In Fig. 7, upper figure is ten core terbiums substitution arsenic tungsten oxygen silicate nanometer cluster compound（1 mg/mL）To human cervical carcinoma cell HeLa
Calcein-AM/PI of effect double dyeing 6 h experiments, figure below are that ten core terbiums substitute arsenic tungsten oxygen silicate nanometer cluster compound（1 mg/
mL）Calcein-AM/PI double dyeing 6 h experiments to human breast cancer cell line Bcap-37 effect；
In Fig. 8, upper figure is ten core terbiums substitution arsenic tungsten oxygen silicate nanometer cluster compound（1 mg/mL）To human cervical carcinoma cell HeLa
The h of Annexin V-FITC/PI double fluorescence labelings 6 experiments of effect, figure below are that ten core terbiums substitute arsenic tungsten oxygen silicate nanometer cluster to close
Thing（1 mg/mL）The h of Annexin V-FITC/PI double fluorescence labelings 6 of human breast cancer cell line Bcap-37 effect is tested；
Fig. 9 is target compound to human cervical carcinoma cell HeLa and the light of human breast cancer cell line Bcap-37 growth inhibition process
Learn microscope figure.
Specific implementation method
Below by way of specific embodiment, the invention will be further described, but illustrates protection scope of the present invention herein not
It is confined to herein below.
Embodiment 1：
A kind of ten core terbiums substitution arsenic tungsten oxygen silicate nanometer cluster compound, its chemical formula are：[H2N(CH3)2]6Na24H16
{[Tb10W16 (H2O)30O50](B-α-AsW9O33)8}·97H2O。
Above-mentioned ten core terbiums substitution arsenic tungsten oxygen silicate nanometer cluster compound synthesizes to obtain using traditional normal temperature aqua-solution method, its
Preparation method is specific as follows：
Under agitation by 1.400 g (4.240 mmol) Na2WO4·2H2O and 0.502 g (6.156 mmol)
(CH3)2NHHCl is dissolved into 20 mL distilled water, and 0.5 mL is added dropwise dropwise（1 mol·L–1）NaAsO2Solution.With 6
mol·L–1Hydrochloric acid above-mentioned solution ph is adjusted to 4.0 after add 0.199 g (0.439 mmol) Tb (NO3)3·6H2O, then
With 0.5 molL–1Hydrochloric acid pH is adjusted to 4.0, be stirred at room temperature 30 min, stand filtering, separated out after filtrate standing for several weeks colourless
Prism-shaped crystal, is filtered again, and crystal room temperature dries to obtain 0.35 g target compounds（By Tb (NO3)3·6H2O calculates yield about
For 30%）.
Embodiment 2：
A kind of ten core terbiums substitution arsenic tungsten oxygen silicate nanometer cluster compound, its chemical formula are：[H2N(CH3)2]6Na24H16
{[Tb10W16 (H2O)30O50](B-α-AsW9O33)8}·97H2O。
Above-mentioned ten core terbiums substitution arsenic tungsten oxygen silicate nanometer cluster compound synthesizes to obtain using traditional normal temperature aqua-solution method, its
Preparation method is as follows：
Under agitation by 1.400 g (4.240 mmol) Na2WO4·2H2O and 0.502 g (6.156 mmol)
(CH3)2NHHCl is dissolved into 20 mL distilled water, and 0.5 mL is added dropwise dropwise（1 mol·L–1 ）NaAsO2Solution.With 6
mol·L–1Hydrochloric acid above-mentioned solution ph is adjusted to 4.0 after add 0.212 g (0.439 mmol) Tb (NO3)3·6H2O, then
With 0.5 molL–1 Hydrochloric acid pH is adjusted to 4.0, be stirred at room temperature 30 min, stand filtering, nothing is separated out after filtrate standing for several weeks
Color prism-shaped crystal, is filtered again, and crystal room temperature dries to obtain 0.41 g target compounds（By Tb (NO3)3·6H2O calculates yield
About 35%）.
Embodiment 3：
A kind of ten core terbiums substitution arsenic tungsten oxygen silicate nanometer cluster compound, its chemical formula are：[H2N(CH3)2]6Na24H16
{[Tb10W16 (H2O)30O50](B-α-AsW9O33)8}·97H2O。
Above-mentioned ten core terbiums substitution arsenic tungsten oxygen silicate nanometer cluster compound synthesizes to obtain using traditional normal temperature aqua-solution method, its
Preparation method is specific as follows：
Under agitation by 1.400 g (4.240 mmol) Na2WO4·2H2O and 0.502 g (6.156 mmol)
(CH3)2NHHCl is dissolved into 20 mL distilled water, and 0.5 mL is added dropwise dropwise（1 mol·L–1）NaAsO2 Solution.With 6
mol·L–1Hydrochloric acid above-mentioned solution ph is adjusted to 4.5 after add 0.212 g (0.439 mmol) Tb (NO3)3·6H2O, then
With 0.5 molL–1 Hydrochloric acid pH is adjusted to 4.5, be stirred at room temperature 30 min, stand filtering, nothing is separated out after filtrate standing for several weeks
Color prism-shaped crystal, is filtered again, and crystal room temperature dries to obtain 0.31 g target compounds（By Tb (NO3)3·6H2O calculates yield
About 27%）.
Application test 1
Human cervical carcinoma cell HeLa and human breast cancer cell line Bcap-37 are being aided with 10% heat-inactivated fetal bovine serum liquid respectively
The Dulbecco of (FBS, GIBCO) improves to be cultivated in Iger (DMEM, GIBCO) culture medium（37 ℃、5%CO2's
Cultivated in incubator）, culture medium replacing daily is once.Cytotoxicity is determined using mtt assay.Experiment is using cell number in every hole as 2
× 103It is individual to be inoculated in 96 hole plastic culture plates, next day, the difference that 100 μ L are dissolved in nutrient solution is added in each hole
The H of concentration2N(CH3)2]6Na24H16{[Tb10W16(H2O)30O50](B-α-AsW9O33)8}·97H2O and K14[As2 W19O67
(H2O)] solution.After 48 h, the concentration that 20 μ L are dissolved in phosphate buffered saline is added into often for 5 mg/mL MTT
In individual culture hole.Continue to cultivate 4 h at 37 DEG C, then the cell culture fluid comprising MTT is removed, sequentially adds 150 μ L bis-
Methyl sulfoxide crystallizes first a ceremonial jade-ladle, used in libation in each culture hole, to dissolve the bluish violet for the MTT being reduced.96 orifice plates are detected with ELIASA to shake
Absorbance (OD values) after dynamic 5 min at 490 nm wavelength, inhibitory rate of cell growth and inhibiting rate are calculated according to formula
For 50% when concentration (half-inhibition concentration IC50), as a result see Fig. 6 and table 1.
Inhibitory rate of cell growth=[(the OD values of blank control OD values-administration group)/blank control OD values] × 100%.
Table 1
Table 1 is target compound and arsenowolframic acid salt precursor body K14[As2W19O67(H2O)] to human cervical carcinoma cell HeLa and
Half-inhibition concentration (the i.e. IC of human breast cancer cell line Bcap-3750 Value), data show the compound to human cervical carcinoma cell Hela
（IC50 = 1.51 µM）And human breast cancer cell line Bcap-37（IC50 = 1.52 µM）Growth there is obvious inhibitory action, it is excellent
In arsenowolframic acid salt precursor body K14[As2W19O67(H2O)]（To human cervical carcinoma cell HeLa：IC50 = 5.22 µM；To people's mammary gland
Cancer cell MCF-7：IC50 = 6.06 µM）.
As shown in Figure 6：The formation of ten core terbiums substitution arsenic tungsten oxygen silicate nanometer cluster compound makes it to human cervical carcinoma cell HeLa
(IC50 =1.51 μM) and human breast cancer cell line Bcap-37 (IC50 =1.52 μM) growth there is better inhibition effect, and
Significantly more than arsenowolframic acid salt precursor body K14[As2W19O67(H2O)]（To human cervical carcinoma cell HeLa：IC50 = 5.22 µM；
To human breast cancer cell line Bcap-37：IC50 = 6.06 µM）.
Application test 2
By the human cervical carcinoma cell HeLa and human breast cancer cell line Bcap-37 of logarithmic growth with 105The concentration in/hole assigns to 12
It is incubated overnight in orifice plate, next day replaced with fresh medium and the target compound for adding final concentration of 1 mg/mL, and is trained in cell
Support and cultivated 6 hours in case, with PBS gently rinse 3 times, added containing Calcein-AM (2 μM) and PI (8 μM)
PBS is incubated at room temperature 30 minutes.Finally, fluorescence imaging is carried out to cell with fluorescence microscope.As a result Fig. 7 is seen.Can be clear from Fig. 7
Find out clearly：After target compound handles 6 h to human cervical carcinoma cell HeLa and human breast cancer cell line Bcap-37, part cancer cell
Dead.
Application test 3
By the human cervical carcinoma cell HeLa and human breast cancer cell line Bcap-37 of logarithmic growth with 105The concentration in/hole assigns to 12 holes
It is incubated overnight in plate, next day replaced with fresh medium and the target compound for adding final concentration of 1 mg/mL, and in cell culture
Cultivated 6 hours in case, with PBS gently rinse 3 times, add 500 μ L and contain 5 μ L Annexin V-FITC and 5 μ L PI
The combination buffer of solution.At room temperature, fluorescence imaging is carried out to cell with fluorescence microscope after lucifuge is incubated 5 minutes.As a result
See Fig. 8.As seen from Figure 8：Target compound induces human cervical carcinoma cell HeLa and human breast cancer cell line Bcap-37 to handle 6 h
Afterwards, part cancer cell-apoptosis.
Application test 4
By the human cervical carcinoma cell HeLa and human breast cancer cell line Bcap-37 of logarithmic growth with 2 × 105The concentration in/hole assigns to 6
It is incubated overnight in orifice plate, next day replaced with fresh medium and the target compound for adding final concentration of 1 mg/mL, and is trained in cell
Support and cultivated in case, cell morphology changes when recording the h of different time 0,2 h, 4 h, 6 h, 8 h and 11 h with light microscope.Knot
Fruit sees Fig. 9.It can be clearly seen that from Fig. 9：With the passage of time, human cervical carcinoma cell HeLa and human breast cancer cell MCF-
7 are gradually tapered up, and pattern is gradually rounded.The phenomenon further demonstrates that target compound can promote human cervical carcinoma cell HeLa and people
Apoptosis occurs for breast cancer cell MCF-7.
Claims (4)
1. ten core terbiums substitute arsenic tungsten oxygen silicate nanometer cluster compound, its chemical formula is：[H2N(CH3)2]6Na24H16{[Tb10W16
(H2O)30O50](B-α-AsW9O33)8}·97H2O。
2. the preparation method of ten core terbiums substitution arsenic tungsten oxygen silicate nanometer cluster compound described in claim 1, it is characterised in that including such as
Lower step：
Under agitation, by Na2WO4·2H2O and (CH3)2NHHCl is dissolved into distilled water, and NaAsO is then added dropwise2It is molten
Liquid, Tb (NO are added after pH is adjusted into 4.0-4.53)3·6H2O, then pH is adjusted to 4.0-4.5,30 more than min are stirred at room temperature,
Then filter, filtrate is stood to colourless prism-shaped crystal is separated out, and is filtered again, and crystal room temperature is dried as the core of target compound ten
Terbium substitutes arsenic tungsten oxygen silicate nanometer cluster compound；
The Na2WO4·2H2O、(CH3)2NH·HCl、NaAsO2、Tb(NO3)3·6H2The mol ratio of O and distilled water be 8.5-
The ︰ 2222 of 10 ︰, 12.3-35.5 ︰, 1.0-2.3 ︰ 0.9-4.1.
3. application of the ten core terbiums substitution arsenic tungsten oxygen silicate nanometer cluster compound in cancer therapy drug is prepared described in claim 1.
4. application of the ten core terbium substitution arsenic tungsten oxygen silicate nanometer cluster compound as claimed in claim 3 in cancer therapy drug is prepared, its
It is characterised by, the cancer therapy drug is medicament for resisting cervical cancer or anti-breast cancer medicines.
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| Title |
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| Assembly of a large cerium(III)-containing tungstotellurites(IV) nanocluster:[Ce10Te8W88O298(OH)12(H2O)40]18−;Wei-Chao Chen等，;《Dalton Transactions》;20150520;第44卷;第11290–11293页 * |
| Rectangle versus Square Oxalate-Connective Tetralanthanide Cluster Anchored in Lacunary Lindqvist Isopolytungstates: Syntheses,Structures, and Properties;Junwei Zhao等，;《Cryst. Growth Des. 》;20141003;第14卷;第5495−5505页 * |
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