CN1315855C - Molybdenum, wolfram, molybdenum and wolfram complex, method for making and use in preparing anticancer, antitumor medicament - Google Patents
Molybdenum, wolfram, molybdenum and wolfram complex, method for making and use in preparing anticancer, antitumor medicament Download PDFInfo
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- CN1315855C CN1315855C CNB2004100964944A CN200410096494A CN1315855C CN 1315855 C CN1315855 C CN 1315855C CN B2004100964944 A CNB2004100964944 A CN B2004100964944A CN 200410096494 A CN200410096494 A CN 200410096494A CN 1315855 C CN1315855 C CN 1315855C
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- 238000000034 method Methods 0.000 title claims abstract description 33
- 229910052750 molybdenum Inorganic materials 0.000 title claims abstract description 30
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 title claims abstract description 27
- 239000011733 molybdenum Substances 0.000 title claims abstract description 24
- WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 title claims abstract description 17
- 239000003814 drug Substances 0.000 title claims abstract description 7
- 230000001093 anti-cancer Effects 0.000 title description 6
- 230000000259 anti-tumor effect Effects 0.000 title description 3
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 29
- 239000013256 coordination polymer Substances 0.000 claims abstract description 23
- 229920001795 coordination polymer Polymers 0.000 claims abstract description 23
- 229910052721 tungsten Inorganic materials 0.000 claims abstract description 21
- 239000010937 tungsten Substances 0.000 claims abstract description 15
- MGRWKWACZDFZJT-UHFFFAOYSA-N molybdenum tungsten Chemical compound [Mo].[W] MGRWKWACZDFZJT-UHFFFAOYSA-N 0.000 claims abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 21
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 20
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 20
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 18
- 125000003118 aryl group Chemical class 0.000 claims description 17
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 14
- HNXQXTQTPAJEJL-UHFFFAOYSA-N 2-aminopteridin-4-ol Chemical compound C1=CN=C2NC(N)=NC(=O)C2=N1 HNXQXTQTPAJEJL-UHFFFAOYSA-N 0.000 claims description 12
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 10
- -1 aromatic dithiol Chemical class 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 9
- 229910021645 metal ion Inorganic materials 0.000 claims description 9
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- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 8
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 claims description 8
- 125000005605 benzo group Chemical class 0.000 claims description 8
- 229910052751 metal Inorganic materials 0.000 claims description 8
- 239000002184 metal Substances 0.000 claims description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 8
- YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical compound C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims description 8
- MEFBJEMVZONFCJ-UHFFFAOYSA-N molybdate Chemical compound [O-][Mo]([O-])(=O)=O MEFBJEMVZONFCJ-UHFFFAOYSA-N 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- PBYZMCDFOULPGH-UHFFFAOYSA-N tungstate Chemical compound [O-][W]([O-])(=O)=O PBYZMCDFOULPGH-UHFFFAOYSA-N 0.000 claims description 7
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- 201000011510 cancer Diseases 0.000 claims description 6
- 239000012046 mixed solvent Substances 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
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- 150000004984 aromatic diamines Chemical class 0.000 claims description 5
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- 229920000768 polyamine Chemical class 0.000 claims description 5
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- 229920006295 polythiol Chemical class 0.000 claims description 5
- XKZQKPRCPNGNFR-UHFFFAOYSA-N 2-(3-hydroxyphenyl)phenol Chemical compound OC1=CC=CC(C=2C(=CC=CC=2)O)=C1 XKZQKPRCPNGNFR-UHFFFAOYSA-N 0.000 claims description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000003277 amino group Chemical group 0.000 claims description 4
- 239000008346 aqueous phase Substances 0.000 claims description 4
- 239000012074 organic phase Substances 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 239000000376 reactant Substances 0.000 claims description 4
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 3
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 3
- 229910052761 rare earth metal Inorganic materials 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 150000001340 alkali metals Chemical class 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000001453 quaternary ammonium group Chemical group 0.000 claims description 2
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- 125000001424 substituent group Chemical group 0.000 claims 12
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- 229910001431 copper ion Inorganic materials 0.000 description 7
- ZKKLPDLKUGTPME-UHFFFAOYSA-N diazanium;bis(sulfanylidene)molybdenum;sulfanide Chemical compound [NH4+].[NH4+].[SH-].[SH-].S=[Mo]=S ZKKLPDLKUGTPME-UHFFFAOYSA-N 0.000 description 7
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- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 4
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- 229910021581 Cobalt(III) chloride Inorganic materials 0.000 description 3
- 102000016680 Dioxygenases Human genes 0.000 description 3
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- AOHJOMMDDJHIJH-UHFFFAOYSA-N propylenediamine Chemical compound CC(N)CN AOHJOMMDDJHIJH-UHFFFAOYSA-N 0.000 description 3
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 238000001308 synthesis method Methods 0.000 description 3
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- 229910015234 MoCo Inorganic materials 0.000 description 2
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- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
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- VVRQVWSVLMGPRN-UHFFFAOYSA-N oxotungsten Chemical compound [W]=O VVRQVWSVLMGPRN-UHFFFAOYSA-N 0.000 description 2
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- LJRDOKAZOAKLDU-UDXJMMFXSA-N (2s,3s,4r,5r,6r)-5-amino-2-(aminomethyl)-6-[(2r,3s,4r,5s)-5-[(1r,2r,3s,5r,6s)-3,5-diamino-2-[(2s,3r,4r,5s,6r)-3-amino-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-hydroxycyclohexyl]oxy-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl]oxyoxane-3,4-diol;sulfuric ac Chemical compound OS(O)(=O)=O.N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)N)O[C@@H]1CO LJRDOKAZOAKLDU-UDXJMMFXSA-N 0.000 description 1
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- JRNGUTKWMSBIBF-UHFFFAOYSA-N naphthalene-2,3-diol Chemical compound C1=CC=C2C=C(O)C(O)=CC2=C1 JRNGUTKWMSBIBF-UHFFFAOYSA-N 0.000 description 1
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Abstract
The present invention relates to molybdenum, tungsten and molybdenum-tungsten coordination polymers, a preparing method thereof and an application of the coordination polymers in preparing medicine for preventing and curing cancers and tumors. The coordination polymers have a general formula disclosed in a general formula I or a general formula II.
Description
Technical Field
The invention relates to molybdenum, tungsten and molybdenum-tungsten coordination polymers and a preparation method thereof, and the coordination polymers can prevent and inhibit generation and growth of cancers and tumors and can be used for preparing medicaments for preventing and treating cancers and tumor diseases. The invention also relates to the application of the compounds in preparing medicaments for preventing and treating the diseases and medicaments containing the compounds.
Background
Molybdenum is a trace element of life needed by organisms. The lack of molybdenum in human body can cause a series of diseases. Such as keshan disease, kidney stone, Kaschin-Beck disease, hypertension, diabetes, etc. In particular, molybdenum deficiency can lead to increased cancer and tumor incidence. For example, the data reports that in the high-incidence areas of cancers such as esophagus cancer, digestive tract cancer, stomach cancer, liver cancer, rectal cancer, lung cancer, breast cancer and the like, the content of molybdenum in resident serum, urine sample and hair is obviously lower than that in the low-incidence areas. After the molybdenum-deficient animals and normal animals receive a certain dose of nitroso compound, the incidence rate of the forestomach carcinoma of the molybdenum-deficient animals is obviously higher than that of the normal animals.
In vivo, the fact that molybdenum metal is an antagonistic element of copper metal has long been accepted. Since 1991, the study of ammonium tetrathiomolybdate for anticancer and antitumor angiogenesis was initiated. The growth and metastasis of malignant tumors are closely related to the blood vessels in the tumor region, new blood vessels are required to form and metabolize oxygen and nutrients required for the growth of tumors as they grow to about 2 mm, and copper is a nutrient necessary for the formation and growth of new blood vessels, that is, the formation of new blood vessels depends on copper. Since the reduction of the copper ion content in a tumor region can prevent the formation and growth of blood vessels in the region, the treatment of tumors with a target of new blood vessels has become a very active research focus in recent years. The molybdenum-containing compound can antagonize copper ions in organisms, and the ammonium tetrathiomolybdate can antagonize the copper ions and can complex the metal copper ions to reduce the concentration of the copper ions in cancer and tumor areas, so that tumors are in a no-growth, chronic growth or dormancy state, the anti-tumor angiogenesis is achieved, and the life of people is prolonged. The mixed use of other antitumor drugs can also eradicate tumor cells from the source. Currently, the drugs used for clinically inhibiting the concentration of copper ions to achieve the aim of resisting the angiogenesis of cancer cells include penicillamine, zinc sulfate and the like, but have great side effects and are often accompanied with symptoms of nervous disorder, fever, rash, arthralgia and the like. The ammonium tetrathiomolybdate is safe, and the normal cell growth is not influenced after the concentration of copper ions is reduced. Meanwhile, the ammonium tetrathiomolybdate can also antagonize the treatment and absorption of copper elements in food. At present, the treatment of tumors by using ammonium tetrathiomolybdate and taking new vessels as targets enters second-stage clinical treatment, and the effects of resisting cancers and tumors and prolonging the service life of patients are achieved.
Ammonium tetrathiomolybdate, however, is very unstable and extremely sensitive to light, water and oxygen. Therefore, the glass needs to be placed in an anhydrous, dry, light-proof and oxygen-free environment and is generally stored in inert argon. Only 90% of the efficacy of the ammonium tetrathiomolybdate placed in the capsules was retained within 8 weeks. Therefore, it is imperative to find new anticancer and antitumor drugs with high efficiency and low toxicity, which are superior to or specific to the existing clinical drugs and have certain stability.
Tungsten is a family element of molybdenum and is also the active center of tungsten oxygen transferase. In many organisms, tungsten oxygen transferase coexists with molybdenum oxygen transferase, and has similar biochemical functions.
Disclosure of Invention
The invention aims to design a molybdenum, tungsten and molybdenum-tungsten coordination polymer and a preparation method thereof, and relates to application of the molybdenum-tungsten coordination polymer in preparation of anti-cancer and anti-tumor drugs.
The structural general formula of the coordination polymer is shown as formula I or formula II:
wherein: m is Mo, W or MoxW1-x；
n is 4, 5 or 6, x is a positive number less than 1;
z is alkali metal ion, alkaline earth metal, transition metal ion, rare earth metal ion;
q is an integer ranging from 1 to 6;
m is an integer of 1 or more;
L1is ortho-substituted aromatic diphenol, polyphenol and substituted derivatives thereof, ortho-substituted aromatic diamine, polyamine and substituted derivatives thereof, ortho-substituted aromatic dithiol, polythiol and substituted derivatives thereof, ortho-amino aromatic phenol and substituted derivatives thereof, ortho-hydroxy aromatic thiophenol and substituted derivatives thereof, alpha-substituted (substituted by hydroxyl, amino and sulfhydryl) five-membered monoheterocycle and substituted derivatives thereof, alpha-substituted (substituted by hydroxyl, amino and sulfhydryl) six-membered monoheterocycle and substituted derivatives thereof, alpha-substituted (substituted by hydroxyl, amino and sulfhydryl) benzo five-membered monoheterocycle and substituted derivatives thereof, alpha-substituted (substituted by hydroxyl, amino and sulfhydryl) benzo six-membered monoheterocycle and substituted derivatives thereof, purine and substituted derivatives thereof, pterin and substituted derivatives thereof or flavin and substituted derivatives thereof, wherein the aromatic parent is benzene, naphthalene, anthracene or phenanthrene;
L2、L3and L4Is an organic compound containing one or more amino groups, one or more hydroxyl groups, and one or more mercapto groups, L2、L3And L4May be the same or different.
The complex can be used for preparing high-efficiency anticancer and antitumor drugs.
The synthesis method of the coordination polymer of the present invention is as follows:
the preparation route 1 is as follows:
the coordination polymer of the present invention is formed by compounding an inorganic salt or an inorganic salt hydrate containing mononuclear molybdenum and tungsten with an aromatic ring, a heterocyclic ring and an aliphatic cluster compound containing a coordinating atom such as O, N, S in an aqueous phase and an organic phase.
Wherein:
m is Mo, W or MoxW1-xN is 4, 5 or 6, x is a positive number less than 1;
z is a metal ion and q is an integer ranging from 1 to 6;
m is an integer of 1 or more;
the solvent is water and/or an organic solvent.
The preparation route 2 is as follows:
A. in the aqueous phase, molybdate and/or tungstate is mixed with a compound carrying a quaternary ammonium group [ R ]1R2R3R4N]+To obtain an intermediate [ R ]1R2R3R4N]PMXOY；
B. In the organic phase, the above intermediate is complexed with an organic compound containing O, N, S to form the coordination polymer of the present invention.
Wherein:
QP[MXOY]is [ (R)1R2R3R4)N]PMXOY；
P is a positive integer from 1 to 60; x is a positive integer from 1 to 36; y is a positive integer from 1 to 160;
R1-R4is C, which may be the same or different1-20An alkyl group;
m is Mo, W or MoxW1-xN is 4, 5 or 6, x is a positive number less than 1;
q is an inorganic ammonium ion and a protonated organic amine ion;
z is a metal ion and q is an integer ranging from 1 to 6;
m is an integer of 1 or more;
the solvent is water and/or an organic solvent.
In the above two preparation methods, the molybdate and the tungstate may also be hydrates of molybdate and tungstate. The Z metal ions are alkali metal, alkaline earth metal, transition metal or rare earth metal, and the Z metal ions in the reactants exist in the form of salt or alkali. The organic solvent can be methanol, acetonitrile, acetone or ethanol single solvent or mixed solvent composed of the methanol, the acetonitrile, the acetone or the ethanol single solvent.
The coordination polymer and the synthesis method thereof have the following advantages:
1. the synthesis method of the complex has the advantages of easily available raw materials, low cost, crystal precipitation of the product, high purity and high yield;
2. the complex can stably exist in a natural state;
3. the complex has good water solubility and fat solubility;
4. the complex of the invention is used for treating mouse sarcoma S180Excellent inhibitory effect has been exhibited.
Drawings
FIG. 1: the chemical structure diagram of Lu 1;
FIG. 2: the chemical structure diagram of Lu 2;
FIG. 3: the chemical structure diagram of Lu 3;
lu4 obtained in example 4 has the same chemical structure as that of FIG. 3 except that W in FIG. 3 is replaced by 0.5Mo and 0.5W; the chemical structure of Lu1 obtained in example 5 is the same as that of FIG. 1.
Detailed Description
The following examples are intended to further illustrate the invention, but it is to be understood that the invention is not limited in scope by the following detailed description.
Example 1
Weighing 0.3g Na2MoO4·H2O and 1.0g of catechol were added to a mixed solvent of 20ml of equal volume of water and methanol, 8ml of 1, 2-propanediamine was added to obtain a red solution, which was magnetically stirred for 6 hours, filtered, the filtrate was diffused with ether, and after standing at room temperature for one week, red flaky crystals (called Lu1) were formed.
Elemental analysis (%) was (theoretical value in parentheses): c: 41.52 (41.48); h: 5.26 (5.42); n: 10.83 (10.75); na: 4.39 (4.41); mo: 18.48(18.40). Infrared Spectrum data (cm)-1) Comprises the following steps: N-H: 3413 m; Ar-H: 3052 m; R-H: 2962 w; C-O: 1479s, 1253 s; Mo-O: 873s, 805m, 736 s.
And (3) resolving an X-ray crystal structure: C18H28N 4O6Na Mo, molecular weight 521.18, chemical formula (eta [. eta. ])2-OC6H4O)(μ2-O)2(μ2-(η2-OC6H4O))MoNa(η2-NH2CH2CHNH2CH3)(η1-NH2CH2CHNH2CH3) Orthorhombic system, belonging to Pbca space group. Unit cell parameters: a-1.3373 (2) nm, b-1.5134 (2) nm, c-2.2680 (3) nm, and V-4.590 nm3，Z＝8，Dc＝1.463g/cm-3R is 0.0465 and Rw is 0.0975. The structure of Lu1 is shown in figure 1.
Example 2
Weighing 0.2g Na2MoO4·H2O and 0.2g of 2, 3-dihydroxynaphthalene were added to a mixed solvent of 20ml of water having the same volume as that of acetonitrile, 1ml of ethylenediamine was added to obtain a red solution, the mixture was magnetically stirred for 6 hours, filtered, the filtrate was diffused with ether, and after standing at room temperature for one week, red flaky crystals (called Lu2) were formed.
Elemental analysis (%) was (theoretical value in parentheses): c: 48.78 (48.69); h: 5.26 (5.39); n: 9.76 (9.84); na: 3.65 (3.59); mo: 15.02(14.97). Infrared Spectrum data (cm)-1) Comprises the following steps: N-H: 3355 m; Ar-H: 3048 m; R-H: 2930 w; C-O: 1462s, 1262 s; Mo-O: 902m, 866s, 753 m.
And (3) resolving an X-ray crystal structure: C25H 31N 4O 7NaMo, the molecular weight is 602.50, and the chemical formula is (eta)2-OC10H6O)(μ2-O)2(μ2-(η2-OC10H6O))MoNa(η1-NH2CH2CH2NH2)2(OCH3) Orthorhombic system, belonging to Pbca space group. Unit cell parameters: a-1.4562 (4) nm, b-1.5320 (5) nm, c-2.7135 (8) nm, and V-6.054 (3) nm3，Z＝8，Dc＝1.322g/cm-3R is 0.0573, and Rw is 0.1625. The structure of Lu2 is shown in figure 2.
Example 3
Weighing 0.3g Na2WO4·H2O1.0 g and catechol 1.0g were added to a mixed solvent of methanol and water of equal volume of 20ml, 1, 2-propanediamine 8ml was added to obtain an orange solution, which was magnetically stirred for 6 hours, filtered, the filtrate was diffused with ether and allowed to stand at room temperature for one week to form yellow flaky crystals (called Lu 3).
Elemental analysis (%) was (theoretical value in parentheses): c: 35.84 (35.78); h: 4.76 (4.84); n: 9.27 (9.31); na: 3.75 (3.80); w: 30.50(30.42). Infrared Spectrum data (cm)-1) Comprises the following steps: N-H: 3413 m; Ar-H: 3053 m; R-H: 2962w；C-O：1483s、1263s；Mo-O：874m、808s、754m。
And (3) resolving an X-ray crystal structure: C18H28N4NaO6W, molecular weight 609.29, (eta.) (II)2-OC6H4O)(μ2-O)2(μ2-(η2-OC6H4O))MoNa(η2-N2CH2CH2NH2CH3)(η1-N2CH2CH2NH2CH3) Orthorhombic system, belonging to Pbca space group. Unit cell parameters: a-1.3368 (5) nm, b-1.5170 (5) nm, c-2.2625 (8) nm, and V-4.588 (3) nm3，Z＝8，Dc＝1.764g/cm-3R is 0.0544, and Rw is 0.1306. The structure of Lu3 is shown in FIG. 3.
Example 4
Weighing 0.3g Na2MoO4·H2O、0.3gNa2WO4·H2O1.0 g and catechol 1.0g were added to a mixed solvent of methanol and acetonitrile of 20ml in the same volume, 8ml of 1, 2-propanediamine was added to obtain a red solution, which was magnetically stirred for 6 hours, filtered, the filtrate was diffused with ether, and after standing at room temperature for one week, red flaky crystals (called Lu4) were formed.
Elemental analysis (%) was (theoretical value in parentheses): c: 38.42 (38.38); h: 5.47 (5.01); n: 9.91 (9.95); na: 4.15 (4.08); mo: 8.58 (8.52); w: 16.29(16.32). Infrared Spectrum data (cm)-1) Comprises the following steps: N-H: 3413 m; Ar-H: 3052 m; R-H: 2962 w; C-O: 1479s, 1257 s; Mo-O: 873s, 806m, 748 s.
And (3) resolving an X-ray crystal structure: C18H28N4NaO6Mo0.5W0.5Molecular weight of 563.34 and chemical formula of [ (. eta. ])2-OC6H4O)(μ2-O)2(μ2-(η2-OC6H4O))MoNa(η2-N2CH2CH2NH2CH3)(η1-N2CH2CH2NH2CH3) Orthorhombic system, belonging to Pbca space group. CellParameters are as follows: a-1.3371 (2) nm, b-1.5152 (2) nm, c-2.2667 (3) nm, and V-4.5890 nm3，Z＝8，Dc＝1.589g/cm-3R is 0.0468 and Rw is 0.0997. Lu4 has the same structure as in FIG. 3, except that W in FIG. 3 is replaced by 0.5Mo and 0.5W.
Example 5
Will contain 13gNa2MoO4·2H240ml of aqueous O solution are adjusted to pH 3.5 with HCl (1: 1) and 8g (C) are added4H9)4NBr, stirring for one hour, filtering to obtain white powder, washing with distilled water and ether for three times, and air drying.
The above-mentioned 0.6 g white powder product and 0.8 g pyrocatechol are dissolved in a suitable amount of a mixed solution of 15ml acetonitrile and 15ml methanol, 0.2g NaCl and 6ml ethylenediamine are added, stirred at room temperature for 6 hours, filtered, the dark red filtrate is diffused with diethyl ether, and after standing at room temperature for one week, red block crystals (called L1) are precipitated.
Elemental analysis (%) was (theoretical value in parentheses): c: 41.52 (41.48); h: 5.26 (5.42); n: 10.83 (10.75); na: 4.39 (4.41); mo: 18.48(18.40). Infrared Spectrum data (cm)-1) Comprises the following steps: N-H: 3413 m; Ar-H: 3052 m; R-H: 2962 w; C-O: 1479s, 1253 s; Mo-O: 873s, 805m, 736 s.
And (3) resolving an X-ray crystal structure: C18H28N 4O6Na Mo, molecular weight 521.18, chemical formula (eta [. eta. ])2-OC6H4O)(μ2-O)2(μ2-(η2-OC6H4O))MoNa(η2-NH2CH2CHNH2CH3)(η1-NH2CH2CHNH2CH3) Orthorhombic system, belonging to Pbca space group. Unit cell parameters: a-1.3373 (2) nm, b-1.5134 (2) nm, c-2.2680 (3) nm, and V-4.590 nm3，Z＝8，Dc＝1.463g/cm-3R is 0.0465 and Rw is 0.0975. The structure of Lu1 is shown in figure 1.
Example 6 the same procedure as in example 1 was used except that purine was used instead of o-benzeneDiphenol to give (. eta.)2-C5H5N4)(μ2-O)2(μ2-(η2-C5H5N4))MoNa(η2-NH2CH2CHNH2CH3)(η1-NH2CH2CHNH2CH3)。
Example 7 the same procedure as in example 3 was used, except that purine was used instead of catechol, to give ((η [. eta. ])2-C5H5N4)(μ2-O)2(μ2-(η2-C5H5N4))WNa(η2-NH2CH2CHNH2CH3)(η1-NH2CH2CHNH2CH3)。
Example 8 the same procedure as in example 4 was used, except that purine was used instead of catechol, to give ((η [. eta. ])2-C5H5N4)(μ2-O)2(μ2-(η2-C5H5N4))MoxW1-xNa(η2-NH2CH2CHNH2CH3)(η1-NH2CH2CHNH2CH3) Wherein x is a positive number less than 1.
Example 9 Using the same procedure as in example 1, except that pteridine was used instead of catechol, the compound (. eta.2-C6H3N4)(μ2-O)2(μ2-(η2-C6H3N4))MoNa(η2-NH2CH2CHNH2CH3)(η1-NH2CH2CHNH2CH3)。
Example 10 Using the same procedure as in example 3, except that pteridine was used instead of catechol, ((η) was obtained2-C6H3N4)(μ2-O)2(μ2-(η2-C6H3N4))WNa(η2-NH2CH2CHNH2CH3)(η1-NH2CH2CHNH2CH3)。
Example 11 the same procedure as in example 4 was used, except that pteridine was used instead of catechol, to give ((η)2-C6H3N4)(μ2-O)2(μ2-(η2-C6H3N4))MoxW1-xNa(η2-NH2CH2CHNH2CH3)(η1-NH2CH2CHNH2CH3) Wherein x is a positive number less than 1.
Example 12 the same procedure as in example 1 was used, except that pyridine was used instead of catechol, to obtain (. eta.) (eta.)2-C5H6N)(μ2-O)2(μ2-(η2-C5H6N))MoNa(η2-NH2CH2CHNH2CH3)(η1-NH2CH2CHNH2CH3)。
Example 13 Using the same procedure as in example 3 except that pyridine was used instead of catechol, (η)2-C5H6N)(μ2-O)2(μ2-(η2-C5H6N))WNa(η2-NH2CH2CHNH2CH3)(η1-NH2CH2CHNH2CH3)。
Example 14 the same procedure as in example 4 was used, except that pyridine was used instead of catechol, to obtain (. eta.) (eta.)2-C5H6N)(μ2-O)2(μ2-(η2-C5H6N))MoxW1-xNa(η2-NH2CH2CHNH2CH3)(η1-NH2CH2CHNH2CH3) Wherein x is a positive number less than 1.
Example 15 Using the same procedure as in example 1 except that flavin (denoted by F) was used instead of catechol, (. eta. eta.2-F)(μ2-O)2(μ2-(η2-F))MoNa(η2-NH2CH2CHNH2CH3)(η1-NH2CH2CHNH2CH3)。
Example 16 the same procedure as in example 3, except that flavin (denoted by F) was used in place of catechol, was used to obtain (. eta.) (2-F)(μ2-O)2(μ2-(η2-F))WNa(η2-NH2CH2CHNH2CH3)(η1-NH2CH2CHNH2CH3)。
Example 17 the same procedure as in example 4 was followed, except that flavin (denoted by F) was used instead of catechol, to give (. eta. eta.2-F)(μ2-O)2(μ2-(η2-F))MoxW1-xNa(η2-NH2CH2CHNH2CH3)(η1-NH2CH2CHNH2CH3) Wherein x is a positive number less than 1.
Example 18 the same procedure as in example 1 was used except that (Bu)4N)4Mo8O26And FeCl3In place of Na2MoO4·H2O, to obtain (eta)2-OC6H4O)(μ2-O)2(μ2-(η2-OC6H4O))MoFe(η2-NH2CH2CHNH2CH3)(η1-NH2CH2CHNH2CH3)。
Example 19 the same procedure as in example 2 was used, except that (Bu)4N)4W10O32And FeCl3In place of Na2MoO4·H2O, to obtain (eta)2-OC6H4O)(μ2-O)2(μ2-(η2-OC6H4O))WFe(η2-NH2CH2CHNH2CH3)(η1-NH2CH2CHNH2CH3)。
Example 20 the same procedure as in example 2 was used, except that (Bu)4N)2Mo3W3O19And FeCl3In place of Na2MoO4·H2O, to obtain (eta)2-OC6H4O)(μ2-O)2(μ2-(η2-OC6H4O))MoxW1-xFe(η2-NH2CH2CHNH2CH3)(η1-NH2CH2CHNH2CH3) Wherein x is a positive number less than 1.
Example 21 the same procedure as in example 1 was used except that (Bu)4N)4Mo8O26And Ce (NO)3)3In place of Na2MoO4·H2O, to obtain (eta)2-OC6H4O)(μ2-O)2(μ2-(η2-OC6H4O))MoCe(η2-NH2CH2CHNH2CH3)(η1-NH2CH2CHNH2CH3)。
Example 22 the same procedure as in example 1 was used, except that (Bu)4N)4W10O32And Ce (NO)3)3In place of Na2MoO4·H2O, to obtain (eta)2-OC6H4O)(μ2-O)2(μ2-(η2-OC6H4O))WCe(η2-NH2CH2CHNH2CH3)(η1-NH2CH2CHNH2CH3)。
Example 23 the same procedure as in example 1 was used, except that (Bu)4N)2Mo3W3O19And Ce (NO)3)3In place of Na2MoO4·H2O, to obtain (eta)2-OC6H4O)(μ2-O)2(μ2-(η2-OC6H4O))Mo0.6W0.4Ce(η2-NH2CH2CHNH2CH3)(η1-NH2CH2CHNH2CH3) Wherein x is a positive number less than 1.
Example 24 the same procedure as in example 2 was used except that Na was used2WO4·H2O instead of Na2MoO4·H2O, to obtain (eta)2-OC10H6O)(μ2-O)2(μ2-(η2-OC10H6O))MoNa(η1-NH2CH2CH2NH2)2(OCH3)。
Example 25 the same procedure as in example 2 was used, except that Na was used2WO4·H2O and Na2MoO4·H2O instead of Na2MoO4·H2O, to obtain (eta)2-OC10H6O)(μ2-O)2(μ2-(η2-OC10H6O))Mo0.5W0.5Na(η1-NH2CH2CH2NH2)2(OCH3)。
Example 26 the same procedure as in example 2 was used, except that (Bu)4N)4Mo8O26And CoCl3In place of Na2MoO4·H2O, to obtain (eta)2-OC10H6O)(μ2-O)2(μ2-(η2-OC10H6O))MoCo(η1-NH2CH2CH2NH2)2(OCH3)。
Example 27 the same procedure as in example 2 was used, except that (Bu)4N)4W10O32And CoCl3In place of Na2MoO4·H2O, to obtain (eta)2-OC10H6O)(μ2-O)2(μ2-(η2-OC10H6O))MoCo(η1-NH2CH2CH2NH2)2(OCH3)。
Example 28 the same procedure as in example 2 was used, except that (Bu)4N)2Mo3W3O19And CoCl3In place of Na2MoO4·H2O, to obtain (eta)2-OC10H6O)(μ2-O)2(μ2-(η2-OC10H6O))Mo0.5W0.5Co(η1-NH2CH2CH2NH2)2(OCH3)。
Example 29 the same procedure as in example 2 was used, except that (Bu)4N)4Mo8O26And Ce (NO)3)3In place of Na2MoO4·H2O, to obtain (eta)2-OC10H6O)(μ2-O)2(μ2-(η2-OC10H6O))MoCe(η1-NH2CH2CH2NH2)2(OCH3)。
Example 30 the same procedure as in example 2 was used, except that (Bu)4N)4W10O32And Ce (NO)3)3In place of Na2MoO4·H2O, to obtain (eta)2-OC10H6O)(μ2-O)2(μ2-(η2-OC10H6O))WCe(η1-NH2CH2CH2NH2)2(OCH3)。
Example 31 the same procedure as in example 2 was used, except that (Bu)4N)2Mo3W3O19And Ce (NO)3)3In place of Na2MoO4·H2O, to obtain (eta)2-OC10H6O)(μ2-O)2(μ2-(η2-OC10H6O))WCe(η1-NH2CH2CH2NH2)2(OCH3)。
Example 32 Lu1 on mouse sarcoma S180The inhibiting effect of (1): 10 Kunming mice are used as one group, tumor cells are taken from the abdominal cavity of the mice, and the cells are diluted to 5 multiplied by 10 after being treated6And/ml, inoculating 0.2 ml/mouse left forelimb axilla under aseptic condition, and administering by groups after 24 hours of inoculation, and performing intraperitoneal injection once a day for 10 days. Tumors were removed and weighed on day 12, and the mean tumor weight per group was calculated as the P value. Cyclophosphamide was used as a positive control. LuI 100mg/kg, 50mg/kg and positive control against mouse sarcoma S180Has inhibiting effect with inhibiting rate of 68.7(P < 0.01), 32.2(P < 0.01) and 64.5 (0.01).
Example 33 Lu2 vs. mouse sarcoma S180The inhibiting effect of (1): 10 Kunming mice are used as one group, liver cancer cells are taken from the abdominal cavity of the mice, and the treated liver cancer cells are diluted to 5 multiplied by 106And/ml, inoculating 0.2 ml/mouse left forelimb axilla under aseptic condition, and administering by groups after 24 hours of inoculation, and performing intraperitoneal injection once a day for 10 days. Tumors were removed and weighed on day 12, and the mean tumor weight per group was calculated as the P value. Cyclophosphamide was used as a positive control. Lu 2100 mg/kg, 50mg/kg and positive control for mouse liver cancer H22All have inhibiting effect and inhibiting rateRespectively 62.6(P < 0.01), 21.3(P < 0.01) and 67.1 (0.01).
Example 34 Lu3 vs. mouse sarcoma S180The inhibiting effect of (1): 10 Kunming mice are used as one group, tumor cells are taken from the abdominal cavity of the mice, and the cells are diluted to 5 multiplied by 10 after being treated6And/ml, inoculating 0.2 ml/mouse left forelimb axilla under aseptic condition, and administering by groups after 24 hours of inoculation, and performing intraperitoneal injection once a day for 10 days. Tumors were removed and weighed on day 12, and the mean tumor weight per group was calculated as the P value. Cyclophosphamide was used as a positive control. Lu 3100 mg/kg, 50mg/kg and positive control all have inhibitory effects on mouse sarcoma 180, and the inhibitory rates are 46.3(P < 0.01), 14.2(P < 0.01) and 64.58(0.01), respectively.
Example 35 Lu4 on mouse sarcoma S180The inhibiting effect of (1): 10 Kunming mice are used as one group, tumor cells are taken from the abdominal cavity of the mice, and the cells are diluted to 5 multiplied by 10 after being treated6And/ml, inoculating 0.2 ml/mouse left forelimb axilla under aseptic condition, and administering by groups after 24 hours of inoculation, and performing intraperitoneal injection once a day for 10 days. Tumors were removed and weighed on day 12, and the mean tumor weight per group was calculated as the P value. Cyclophosphamide was used as a positive control. Lu 4100 mg/kg, Lu 4100/kg, Lu 50mg/kg and positive control all have inhibitory effects on mouse sarcoma 180, and the inhibitory rates are 49.8P < 0.01), 17.8(P < 0.01), and 64.58(0.01), respectively.
Example 36 toxicity LD of Lu1 to mice50The determination of (1): 50 Kunming mice are taken, 10 mice are taken, and the total number of the mice is 5. Respectively injecting Lu1 with different concentrations into abdominal cavity, observing general behavior and death condition of mice after administration, continuously observing for 7-10 days, and measuring LD50470.2mg/kg, with a 95% confidence limit of 470.2. + -. 12.56 mg/kg.
Claims (7)
1. The general formula of the molybdenum, tungsten and molybdenum-tungsten coordination polymer is shown as formula I or formula II:
wherein:
m is Mo, W or MoxW1-xN is 4, 5 or 6, x is a positive number less than 1;
z is a metal ion and q is an integer ranging from 1 to 6;
m is an integer of 1 or more;
L1is ortho-substituted aromatic diphenol, polyphenol and substituted derivatives thereof, ortho-substituted aromatic diamine, polyamine and substituted derivatives thereof, ortho-substituted aromatic dithiol, polythiol and substituted derivatives thereof, ortho-amino aromatic phenol and substituted derivatives thereof, ortho-hydroxy aromatic thiophenol and substituted derivatives thereof, alpha-substituted five-membered mono-heterocyclic ring and substituted derivatives thereof with a substituent group of hydroxyl, amino or sulfhydryl, alpha-substituted six-membered mono-heterocyclic ring and substituted derivatives thereof with a substituent group of hydroxyl, amino or sulfhydryl, alpha-substituted benzo five-membered mono-heterocyclic ring and substituted derivatives thereof with a substituent group of hydroxyl, amino or sulfhydryl, alpha-substituted benzo six-membered mono-heterocyclic ring and substituted derivatives thereof with a substituent group of hydroxyl, amino or sulfhydryl, purine and substituted derivatives thereof, pterin which the aromatic parent body is benzene, polyphenol, substituted derivatives thereof, o-substituted aromatic diamine, polyamine and substituted derivatives thereof, o-substituted aromatic dithiol, polythiol and, Naphthalene, anthracene or phenanthrene;
L2、L3and L4Is one of organic compounds containing one or more amino groups, one or more hydroxyl groups and one or more mercapto groups, L2、L3And L4May be the same or different.
2. A method for synthesizing the molybdenum, tungsten, molybdenum-tungsten coordination polymer of claim 1, which is characterized by comprising the following preparation routes:
in the aqueous or organic phase, tungstate and/or molybdate containing Z ions of the metal are reacted with the following reactants: 1) ortho-substituted aromatic diphenol, polyphenol and substituted derivatives thereof, ortho-substituted aromatic diamine, polyamine and substituted derivatives thereof, ortho-substituted aromatic dithiol, polythiol and substituted derivatives thereof, ortho-amino aromatic phenol and substituted derivatives thereof, ortho-hydroxy aromatic thiophenol and substituted derivatives thereof, alpha-substituted five-membered mono-heterocyclic ring and substituted derivatives thereof with a substituent of hydroxyl, amino or sulfhydryl, alpha-substituted six-membered mono-heterocyclic ring and substituted derivatives thereof with a substituent of hydroxyl, amino or sulfhydryl, alpha-substituted benzo five-membered mono-heterocyclic ring and substituted derivatives thereof with a substituent of hydroxyl, amino or sulfhydryl, alpha-substituted benzo six-membered mono-heterocyclic ring and substituted derivatives thereof with a substituent of hydroxyl, amino or sulfhydryl, purine and substituted derivatives thereof, pterin which the aromatic parent is benzene, flavin and substituted derivatives thereof, pterin the presence of a compound having a structure of a structure represented by formula, Naphthalene, anthracene or phenanthrene; 2) an organic compound containing one or more amine groups and/or one or more hydroxyl groups and/or one or more mercapto groups; the ligand of the coordination polymer forms a ring or chain with metal molybdenum, tungsten, molybdenum tungsten and metal Z ions through coordination atoms and adjacent C-C, C-N, C-S, C-O, N-O or N-S bonds to form the coordination polymer,
wherein,
m is Mo, W or MoxW1-x；
n is 4, 5 or 6, x is a positive number less than 1;
z is a metal ion and q is an integer ranging from 1 to 6;
m is an integer of 1 or more;
the solvent is water and/or an organic solvent.
3. A method for synthesizing the molybdenum, tungsten, molybdenum-tungsten coordination polymer of claim 1, which is characterized by comprising the following preparation routes:
the first step is as follows: in the aqueous phase, molybdate and/or tungstate is mixed with a compound carrying a quaternary ammonium group [ R ]1R2R3R4N]+To obtain an intermediate [ R ]1R2R3R4N]PMXOY；
The second step is that: in organic phase or organic-inorganic mixed phaseIn (1), the intermediate [ R ]1R2R3R4N]PMXOYAnd a salt or base containing a metal Z ion, with the following reactants: 1) ortho-substituted aromatic diphenol, polyphenol and substituted derivatives thereof, ortho-substituted aromatic diamine, polyamine and substituted derivatives thereof, ortho-substituted aromatic dithiol, polythiol and substituted derivatives thereof, ortho-amino aromatic phenol and substituted derivatives thereof, ortho-hydroxy aromatic thiophenol and substituted derivatives thereof, alpha-substituted five-membered mono-heterocyclic ring and substituted derivatives thereof with a substituent of hydroxyl, amino or sulfhydryl, alpha-substituted six-membered mono-heterocyclic ring and substituted derivatives thereof with a substituent of hydroxyl, amino or sulfhydryl, alpha-substituted benzo five-membered mono-heterocyclic ring and substituted derivatives thereof with a substituent of hydroxyl, amino or sulfhydryl, alpha-substituted benzo six-membered mono-heterocyclic ring and substituted derivatives thereof with a substituent of hydroxyl, amino or sulfhydryl, purine and substituted derivatives thereof, pterin which the aromatic parent is benzene, flavin and substituted derivatives thereof, pterin the presence of a compound having a structure of a structure represented by formula, Naphthalene, anthracene or phenanthrene; 2) an organic compound containing one or more amine groups and/or one or more hydroxyl groups and/or one or more mercapto groups; the ligand of the coordination polymer forms a ring or chain with metal molybdenum, tungsten, molybdenum tungsten and metal Z ions through coordination atoms and adjacent C-C, C-N, C-S, C-O, N-O or N-S bonds to form the coordination polymer,
wherein,
QP[MXOY]is [ (R)1R2R3R4)N]PMXOY；
P is a positive integer from 1 to 60;
x is a positive integer from 1 to 36;
y is a positive integer from 1 to 160;
R1-R4is C, which may be the same or different1-20An alkyl group;
m is Mo, W or MoxW1-xN is 4, 5 or 6, x is a positive number less than 1;
q is an inorganic ammonium ion and a protonated organic amine ion;
z is a metal ion and q is an integer ranging from 1 to 6;
m is an integer of 1 or more;
the solvent is water and/or an organic solvent.
4. The method for synthesizing molybdenum, tungsten, molybdenum-tungsten coordination polymer according to claim 2 or 3, characterized in that molybdate and tungstate can also be hydrate of molybdate and hydrate of tungstate.
5. The method for synthesizing the molybdenum, tungsten, molybdenum-tungsten coordination polymer according to claim 2 or 3, characterized in that the Z metal ion is alkali metal, alkaline earth metal, transition metal or rare earth metal, and the Z metal ion in the reactant exists in the form of salt or alkali.
6. The method for synthesizing the molybdenum, tungsten, molybdenum-tungsten coordination polymer according to claim 2 or 3, characterized in that the selected organic solvent is methanol, acetonitrile, acetone or ethanol single solvent or a mixed solvent composed of the same.
7. Use of the molybdenum, tungsten, molybdenum tungsten coordination polymer of claim 1 in the preparation of a medicament for the prevention and treatment of cancer and tumors.
Priority Applications (1)
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| CN100384860C (en) * | 2006-07-04 | 2008-04-30 | 首都师范大学 | Process for preparing tungsten complex crystal with multiple channel structure characteristic |
| CN101891898B (en) * | 2009-05-19 | 2012-09-26 | 首都师范大学 | Organic nano molybdenum-sodium metal compound polymer and preparation method and application thereof |
| CN103145759B (en) * | 2011-12-06 | 2016-04-27 | 首都师范大学 | Alizarin molybdenum match and method for making thereof are being prevented and the application in treatment cancer with it |
| CN104628699B (en) * | 2013-11-12 | 2016-09-28 | 首都师范大学 | 15 hats 5 and MoO2cl2(H2o)2molybdenum compound and preparation method and application |
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| CN1321644A (en) * | 2001-04-06 | 2001-11-14 | 鲁晓明 | Chiral octahedral Mo-W complexes, their synthesis method and application for preparing anticancer medicine |
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Non-Patent Citations (5)
| Title |
|---|
| [(n-Bu)_4N]_2[X_2Mo_4O_(10)(OCH_3)_2]的合成与表征 鲁晓明，屠淑洁，刘顺诚，毛希安，首都师范大学学报(自然科学版)，第18卷第4期 1997 * |
| 2,3-二羟基萘钼多酸有机衍生物的合成及~1H NMR和IR谱学研究 鲁晓明，朱惠菊，袁汉珍，毛希安，光谱学与光谱分析，第22卷第1期 2002 * |
| 2,3-二羟基萘钼多酸有机衍生物的合成及~1H NMR和IR谱学研究 鲁晓明，朱惠菊，袁汉珍，毛希安，光谱学与光谱分析，第22卷第1期 2002;Synthesis,Crystal Structure,UV-visandEPRStudiesof(NH_3CH_2CH_2NH_2)_(2.5)[Mo_(0.5)~(V)W_(0.5)~(VI)O_2(OC_6H_4O)_2] 鲁晓明，宋富根，娄福艳，毛希安，叶朝辉，卢景芬,Chinese Journal of Chemistry,Vol.21 No.11 2003;[(n-Bu)_4N]_2[X_2Mo_4O_(10)(OCH_3)_2]的合成与表征 鲁晓明，屠淑洁，刘顺诚，毛希安，首都师范大学学报(自然科学版)，第18卷第4期 1997;邻苯二酚合W、Mo手性金属配合物的合成与研究 鲁晓明，刘顺诚，卜显和，毛希安，化学通报，第10期 2000 * |
| Synthesis,Crystal Structure,UV-visandEPRStudiesof(NH_3CH_2CH_2NH_2)_(2.5)[Mo_(0.5)~(V)W_(0.5)~(VI)O_2(OC_6H_4O)_2] 鲁晓明，宋富根，娄福艳，毛希安，叶朝辉，卢景芬,Chinese Journal of Chemistry,Vol.21 No.11 2003 * |
| 邻苯二酚合W、Mo手性金属配合物的合成与研究 鲁晓明，刘顺诚，卜显和，毛希安，化学通报，第10期 2000 * |
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