CN104402940A - Rhodium complex as well as preparation method and application thereof - Google Patents
Rhodium complex as well as preparation method and application thereof Download PDFInfo
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- CN104402940A CN104402940A CN201410657963.9A CN201410657963A CN104402940A CN 104402940 A CN104402940 A CN 104402940A CN 201410657963 A CN201410657963 A CN 201410657963A CN 104402940 A CN104402940 A CN 104402940A
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- rhodium complex
- methyl
- rhodium
- methoxybenzaldehyde
- thiosemicarbazide
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- 229910052703 rhodium Inorganic materials 0.000 title claims abstract description 69
- 239000010948 rhodium Substances 0.000 title claims abstract description 69
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 title claims abstract description 68
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 238000010668 complexation reaction Methods 0.000 title 1
- -1 monochloride o-mono-methoxy benzaldehyde acetal Chemical class 0.000 claims abstract description 13
- 239000003814 drug Substances 0.000 claims abstract description 10
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 8
- PKZJLOCLABXVMC-UHFFFAOYSA-N 2-Methoxybenzaldehyde Chemical compound COC1=CC=CC=C1C=O PKZJLOCLABXVMC-UHFFFAOYSA-N 0.000 claims description 58
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 30
- PTVZQOAHCSKAAS-UHFFFAOYSA-N 4-methyl-3-thiosemicarbazide Chemical compound CNC(=S)NN PTVZQOAHCSKAAS-UHFFFAOYSA-N 0.000 claims description 25
- 239000000243 solution Substances 0.000 claims description 21
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 20
- 239000011259 mixed solution Substances 0.000 claims description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 10
- 239000007787 solid Substances 0.000 claims description 9
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 claims description 8
- 239000012074 organic phase Substances 0.000 claims description 8
- SMQUZDBALVYZAC-UHFFFAOYSA-N salicylaldehyde Chemical compound OC1=CC=CC=C1C=O SMQUZDBALVYZAC-UHFFFAOYSA-N 0.000 claims description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 7
- 239000000460 chlorine Substances 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 7
- 125000003963 dichloro group Chemical group Cl* 0.000 claims description 7
- WQIQNKQYEUMPBM-UHFFFAOYSA-N pentamethylcyclopentadiene Chemical compound CC1C(C)=C(C)C(C)=C1C WQIQNKQYEUMPBM-UHFFFAOYSA-N 0.000 claims description 7
- 239000000843 powder Substances 0.000 claims description 7
- PZSJYEAHAINDJI-UHFFFAOYSA-N rhodium(3+) Chemical class [Rh+3] PZSJYEAHAINDJI-UHFFFAOYSA-N 0.000 claims description 7
- 238000005481 NMR spectroscopy Methods 0.000 claims description 6
- 230000000844 anti-bacterial effect Effects 0.000 claims description 6
- 230000002141 anti-parasite Effects 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- 201000011510 cancer Diseases 0.000 claims description 4
- 239000002775 capsule Substances 0.000 claims description 4
- 239000000839 emulsion Substances 0.000 claims description 4
- 238000002347 injection Methods 0.000 claims description 4
- 239000007924 injection Substances 0.000 claims description 4
- 239000006187 pill Substances 0.000 claims description 4
- 239000000375 suspending agent Substances 0.000 claims description 4
- 239000003826 tablet Substances 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 claims description 3
- 239000013078 crystal Substances 0.000 claims description 3
- 239000002223 garnet Substances 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 230000001225 therapeutic effect Effects 0.000 claims description 3
- 238000004821 distillation Methods 0.000 claims description 2
- 238000010992 reflux Methods 0.000 claims description 2
- 229940079593 drug Drugs 0.000 abstract description 4
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 abstract 1
- 239000000047 product Substances 0.000 description 11
- 150000001875 compounds Chemical class 0.000 description 8
- 239000002609 medium Substances 0.000 description 8
- 210000004881 tumor cell Anatomy 0.000 description 8
- 230000000694 effects Effects 0.000 description 7
- 229910052751 metal Inorganic materials 0.000 description 7
- 239000002184 metal Substances 0.000 description 7
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 6
- 238000000034 method Methods 0.000 description 5
- 230000001954 sterilising effect Effects 0.000 description 5
- 239000002246 antineoplastic agent Substances 0.000 description 4
- 229940041181 antineoplastic drug Drugs 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 229910052697 platinum Inorganic materials 0.000 description 4
- 241000224016 Plasmodium Species 0.000 description 3
- 230000000259 anti-tumor effect Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- 241000193830 Bacillus <bacterium> Species 0.000 description 2
- 244000063299 Bacillus subtilis Species 0.000 description 2
- 235000014469 Bacillus subtilis Nutrition 0.000 description 2
- 241000222122 Candida albicans Species 0.000 description 2
- 230000004543 DNA replication Effects 0.000 description 2
- 241000191967 Staphylococcus aureus Species 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 229940095731 candida albicans Drugs 0.000 description 2
- 238000010224 classification analysis Methods 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 230000006837 decompression Effects 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000011275 oncology therapy Methods 0.000 description 2
- 230000000590 parasiticidal effect Effects 0.000 description 2
- 239000002297 parasiticide Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 235000015320 potassium carbonate Nutrition 0.000 description 2
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- FZGHWGNQHDJBME-UHFFFAOYSA-N C(C=1C(C(=O)OC)=CC=CC1)(=O)OC.[S] Chemical compound C(C=1C(C(=O)OC)=CC=CC1)(=O)OC.[S] FZGHWGNQHDJBME-UHFFFAOYSA-N 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 239000003972 antineoplastic antibiotic Substances 0.000 description 1
- 239000003096 antiparasitic agent Substances 0.000 description 1
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 238000012136 culture method Methods 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 238000013016 damping Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- DBLXOVFQHHSKRC-UHFFFAOYSA-N ethanesulfonic acid;2-piperazin-1-ylethanol Chemical compound CCS(O)(=O)=O.OCCN1CCNCC1 DBLXOVFQHHSKRC-UHFFFAOYSA-N 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229960001756 oxaliplatin Drugs 0.000 description 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 230000003071 parasitic effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 150000003284 rhodium compounds Chemical class 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 201000000498 stomach carcinoma Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F17/00—Metallocenes
- C07F17/02—Metallocenes of metals of Groups 8, 9 or 10 of the Periodic Table
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
Abstract
The invention discloses a rhodium complex as well as a preparation method and application thereof. The rhodium complex is monochloride o-mono-methoxy benzaldehyde acetal 4-methyl-3-thiosemicarbazide-pentamethylcyclopetadienyl-rhodium (III), and the rhodium complex can serve as the application for preparing drugs for treating cancers. The structural formula of the rhodium complex is shown in the Specification.
Description
Technical field
The present invention relates to chemical medicine field, especially a kind of rhodium complex and its production and use.
Technical background
Since Rosenberg in 1967 finds that cis-platinum has antitumor action, cis-platinum has become and has been used for the treatment of cancer one of 3 kinds of medicines the most widely in the world.Through the research of researcher decades, the several generations such as carboplatin, oxaliplatin platinum complex is synthesized out and is applied to clinical.But, apply to clinical chemotherapy or tens of kinds of auxiliary antitumor drugs at present, only to the treatment of Partial tumors, there is good curative effect.Therefore, prepare new metal complexes antitumor drug, for the treatment of tumor disease can provide how better selection, become current study hotspot.The present invention attempts using rhodium metal to replace traditional platinum, does not also find the report of being correlated with at present.
Summary of the invention
The object of the invention is to the deficiency for general chemicals, a kind of rhodium complex and its production and use is provided, by utilizing heavy metal rhodium compound can the feature of inhibition tumor cell DNA replication dna and thiosemicarbazide compound feature cheap and easy to get, formed after making their coordinate a kind of newly there is rhodium complex that is anticancer, antibacterial and parasiticide effect.
Technical scheme provided by the invention is:
A kind of rhodium complex, wherein:
The chemical name of described rhodium complex is: a chlorine one o-methoxybenzaldehyde contracting 4-methyl-3-thiosemicarbazide First Five-Year Plan methyl cyclopentadienyl closes rhodium (III);
The structural formula of described rhodium complex is:
Preferably, in described rhodium complex, described compound is garnet crystal and is soluble in organic solvent, and its hydrogen nuclear magnetic resonance modal data is
1h NMR (CDCl
3solvent): δ=8.92 (s, 1H), 8.55 (d, J=9Hz, 1H), 7.69 (t, J=7.1Hz, 1H), 7.13 (t, J=7.5, Hz 1H), 7.03 (d, J=8.93Hz, 1H), 5.59 (d, J=5.7Hz, 1H), 4.95 (d, J=5.8Hz, 1H), 4.86 (d, J=5.7Hz, 1H), 4.57 (d, J=5.7Hz, 1H), 3.14 (d, J=4.2Hz, 3H), (2.70-2.63 m, J=6.9Hz, 1H).
A preparation method for rhodium complex, wherein, comprises the following steps:
Step one, by salicylic aldehyde, acetone and K
2cO
3put into container and be mixed to get the first mixed solution, stirring and refluxing at a certain temperature, and after a certain time a certain amount of methyl-sulfate is mixed with the first mixed solution, the second mixed solution is mixed to get with dilute hydrochloric acid after reaction certain hour, add the layering of saturated NaCl solution to the second mixed solution again, get organic phase, organic phase is mixed with NaOH solution, bottom dark red oil is o-methoxybenzaldehyde, and structural formula is as follows:
Step 2, o-methoxybenzaldehyde and dehydrated alcohol to be mixed, after becoming yellow solution, described yellow solution and 4-methyl-3-thiosemicarbazide are dissolved each other, return stirring at a certain temperature, there is a large amount of pale yellow powder to separate out after certain hour, described pale yellow powder is leached, obtains white solid, for o-methoxybenzaldehyde contracting 4-methyl-3-thiosemicarbazide, structural formula is as follows:
Step 3, take a certain amount of o-methoxybenzaldehyde contracting 4-methyl-3-thiosemicarbazide and dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer and CH
2cl
2be mixed to get the 3rd mixed solution, after stirring certain hour, by the 3rd mixed solution underpressure distillation to 1-3ml, leave standstill and separate out yellow solid, namely product one chlorine one o-methoxybenzaldehyde contracting 4-methyl-3-thiosemicarbazide First Five-Year Plan methyl cyclopentadienyl of the present invention closes rhodium (III).
Preferably, in the preparation method of described rhodium complex, in step one, each amounts of components used is respectively: salicylic aldehyde 4-8g, acetone 30-60ml, K
2cO
30.1-1g, methyl-sulfate 3-6ml, dilute hydrochloric acid 2-5ml and NaOH 30-60ml; Wherein said K
2cO
3for anhydrous K
2cO
3, acetone concentration is 90-100%, and dimethyl sulfate ester concentration is 90-100%, and dilute hydrochloric acid concentration is 0.5-2mol/L, NaOH concentration is 1.5-3mol/L.
Preferably, in the preparation method of described rhodium complex, in step 2, each amounts of components used is respectively: o-methoxybenzaldehyde 3-5g, dehydrated alcohol 20-50ml and 4-methyl-3-thiosemicarbazide 1-2g; Described temperature is 70-90 DEG C, and the described time is 1-2 hour.
Preferably, in the preparation method of described rhodium complex, churning time described in step 3 is 5-8 hour, whipping temp is 15-35 DEG C, each amounts of components used is respectively: o-methoxybenzaldehyde contracting 4-methyl-3-thiosemicarbazide 20-25mg, dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer 30-35mg and CH
2cl
25-10ml, wherein said CH
2cl
2concentration be 90-100%.
A purposes for rhodium complex, wherein, described rhodium complex is for the preparation of the application of Therapeutic cancer, antibacterial and antiparasitic medicine.
A purposes for rhodium complex, wherein, described rhodium complex can be made into the form of injection, tablet, pill, capsule, suspension agent or emulsion.
The present invention has following beneficial effect: first, rhodium complex of the present invention to the medium effective concentration of tumour cell between 15-40umol/mL, showing that it has good inhibition tumor cell active effect, providing new thinking for researching and developing new antitumor drug.Its form that can be made into injection, tablet, pill, capsule, suspension agent or emulsion uses as cancer therapy drug.
Secondly, rhodium complex of the present invention has good sterilization effect, it all has very strong bactericidal properties to streptococcus aureus (ATCC 6538), colon bacillus (ATCC 25922), Candida albicans (ATCC 10231), Bacillus subtilis endophyticus (ATCC 9372), and its sterilizing rate reaches more than 99.9%.
Again, rhodium metal title complex of the present invention is 7.2 ± 2.6umol/mL to plasmodial medium effective concentration, illustrates that this compound has strong Antiparasitic Activity.
The preparation method of last rhodium complex of the present invention is simple, and raw material is easy to get, and has the advantage that cost is low, compares traditional anticancer antibiotic medicine, and cost reduces by 50%.
Embodiment
Below in conjunction with embodiment, the present invention is elaborated, can implement according to this after consulting this specification sheets to make those of ordinary skill in the art.
A kind of rhodium complex, wherein:
The chemical name of described rhodium complex is: a chlorine one o-methoxybenzaldehyde contracting 4-methyl-3-thiosemicarbazide First Five-Year Plan methyl cyclopentadienyl closes rhodium (III);
The structural formula of described rhodium complex is:
In described rhodium complex, rhodium metal and compound thereof can act on the DNA replication dna process of tumour cell, the reproduction process of the RNA of tumour cell can also be acted on when the concentration of rhodium metal and compound thereof is enough large, and damage its cytolemma, thus reach the object of tumors destroyed cell, and thiosemicarbazide compound, it is the intermediate of medicine synthesis, very cheap and easy to get, use thiosemicarbazide compound as the ligand of rhodium metal, significantly can reduce cost, thus provide a thinking for solving the expensive problem of cancer therapy drug.
In described rhodium complex, described compound is garnet crystal and is soluble in organic solvent, and its hydrogen nuclear magnetic resonance modal data is
1h NMR (CDCl
3solvent): δ=8.92 (s, 1H), 8.55 (d, J=9Hz, 1H), 7.69 (t, J=7.1Hz, 1H), 7.13 (t, J=7.5, Hz 1H), 7.03 (d, J=8.93Hz, 1H), 5.59 (d, J=5.7Hz, 1H), 4.95 (d, J=5.8Hz, 1H), 4.86 (d, J=5.7Hz, 1H), 4.57 (d, J=5.7Hz, 1H), 3.14 (d, J=4.2Hz, 3H), (2.70-2.63 m, J=6.9Hz, 1H).
A preparation method for rhodium complex, wherein, comprises the following steps:
Step one, by salicylic aldehyde, acetone and anhydrous K
2cO
3put into round-bottomed flask to mix, 50-60 DEG C of magnetic agitation backflow, preferably 55 DEG C, and drip in described round-bottomed flask in the methyl-sulfate that concentration is 90-100% by 20-30min, wherein preferred 15min and bright sulfur dimethyl phthalate, react and drip dilute hydrochloric acid after 10-13 hour salt of wormwood complete for unreacted is dissolved, wherein preferably 12 hours, add saturated NaCl solution again to solution layering, take out organic phase, in organic phase, add NaOH solution, bottom dark red oil is o-methoxybenzaldehyde, and structural formula is as follows:
Step 2, o-methoxybenzaldehyde is dissolved in after in dehydrated alcohol becomes yellow solution, 4-methyl-3-thiosemicarbazide is added in yellow solution, 70-90 DEG C of return stirring wherein preferably 80 DEG C, a large amount of pale yellow powder is had to separate out after 1-2 hour, wherein return time preferably 1.5 hours, filters pale yellow powder, obtains white solid, for o-methoxybenzaldehyde contracting 4-methyl-3-thiosemicarbazide, structural formula is as follows:
Step 3, title 20-40mg o-methoxybenzaldehyde contracting 4-methyl-3-thiosemicarbazide and dichloro (pentamethylcyclopentadiene base) close rhodium (III) dimer and add pure CH
2cl
2, stirring at normal temperature 5-8 hour, wherein preferably 6 hours, solution decompression is distilled to 1-3ml, wherein preferred 3ml, leaves standstill and separates out yellow solid, and namely product one chlorine one o-methoxybenzaldehyde contracting 4-methyl-3-thiosemicarbazide First Five-Year Plan methyl cyclopentadienyl of the present invention closes rhodium (III).
In the preparation method of described rhodium complex, the used each amounts of components in step one is respectively: 4-8g salicylic aldehyde, 30-60ml acetone, 0.1-1g anhydrous K
2cO
3, 3-6ml methyl-sulfate, the NaOH 30-60ml of dilute hydrochloric acid 2-5ml and 1.5-3mol/L of 0.5-2mol/L, preferably, 6g salicylic aldehyde, 40ml acetone, 0.5g anhydrous K
2cO
3, 4ml methyl-sulfate, the NaOH 40ml of dilute hydrochloric acid 3ml and 2mol/L of 1mol/L.
In the preparation method of described rhodium complex, in step 2, each amounts of components used is respectively: 4g o-methoxybenzaldehyde, 30ml dehydrated alcohol and 1.5g 4-methyl-3-thiosemicarbazide.
In the preparation method of described rhodium complex, in step 3, each amounts of components used is respectively: 20mg o-methoxybenzaldehyde contracting 4-methyl-3-thiosemicarbazide, 30mg dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer and 6mlCH
2cl
2.
A purposes for rhodium complex, wherein, described rhodium complex is for the preparation of the application of Therapeutic cancer medicine.
A purposes for rhodium complex, wherein, described rhodium complex can be made into the form of injection, tablet, pill, capsule, suspension agent or emulsion.Final product of the present invention is solid, also can make liquor or spraying use.
Embodiment 1
One, product preparation
Get 5g salicylic aldehyde, 40ml acetone, 0.1g anhydrous K
2cO
3put into round-bottomed flask, 55 DEG C of magnetic agitation backflows, and in 20-30min, 4ml methyl-sulfate is dripped down in reaction flask, react and drip 3ml after 12 hours, salt of wormwood complete for unreacted dissolves by 1mol/L dilute hydrochloric acid, mix with saturated NaCl solution again, solution layering, gets organic phase, in organic phase, add 50ml, 2mol/L NaOH solution, bottom dark red oil is o-methoxybenzaldehyde; 3g o-methoxybenzaldehyde is dissolved in 30ml dehydrated alcohol, become yellow solution, and add 4-methyl-3-thiosemicarbazide 1.2g, 80 DEG C of return stirrings, a large amount of pale yellow powder is had to separate out after 1 hour, filter, obtaining white solid, is o-methoxybenzaldehyde contracting 4-methyl-3-thiosemicarbazide; Take o-methoxybenzaldehyde contracting 4-methyl-3-thiosemicarbazide 21mg and dichloro (pentamethylcyclopentadiene base) to close rhodium (III) dimer 31.5mg and add pure CH
2cl
26ml, stirring at normal temperature 6 hours, is distilled to about 1ml by solution decompression, leaves standstill and separates out yellow solid, and namely product one chlorine one o-methoxybenzaldehyde contracting 4-methyl-3-thiosemicarbazide First Five-Year Plan methyl cyclopentadienyl closes rhodium (III).
Two, anti tumor activity in vitro experiment
Experimentation: adopt MTT method, carry out vitro cytotoxicity mensuration.By rhodium complex obtained above and cancer of the stomach SGC 7901 cell strain and liver cancer BEL-7404 cell strain 72 hours action time respectively, then measure rhodium complex to the medium effective concentration (IC of tumor cell line
50).Wherein, medium effective concentration (IC
50) be limit value with 100umol/mL, be less than 100umol/mL and illustrate that there is effect, be greater than 100umol/mL and illustrate there is no effect.
Experimental result:
Table 1 product of the present invention is to the medium effective concentration (IC of tumor cell line
50) (umol/mL)
| Cell strain | SGC-7901 | BEL-7404 |
| IC 50(umol/mL) | 16.5±5.8 | 16.2±5.9 |
From the results shown in Table 1, rhodium complex of the present invention shows through anticancer experiment in vitro, and this compound has strong anti-tumor activity, and the medium effective concentration of the compound on tumor cell of gained of the present invention is at 10-45umol/mL, and description effect is obvious.The present invention is that the new antitumor drug of research and development provides new thinking.
Three, antibacterial experiment
Experimentation: adding 1mL concentration in sterilizing test tubes is 10
6the bacterium liquid of/ml, adds 1mg product of the present invention, cultivates 24h for 37 DEG C.Cultivate after time point, substratum collects with doubling dilution, and extension rate is 10 times and spread plate method detection viable count.
Experimental result:
The sterilizing rate of table 2 product of the present invention
| ATCC 6538 | ATCC 25922 | ATCC 10231 | ATCC 9372 | |
| Product of the present invention | 99.92％ | 99.97％ | 99.95％ | 99.99％ |
Test-results is as shown in table 2, result shows: the product obtained by the present invention all has very strong bactericidal properties to streptococcus aureus (ATCC 6538), colon bacillus (ATCC 25922), Candida albicans (ATCC 10231), Bacillus subtilis endophyticus (ATCC 9372), and its sterilizing rate reaches more than 99.9%.
Four, parasiticide experiment
Experimentation: adopt fluorocyte classification analysis (FACS) quantitative erythrocytic plasmodium culture method to assess the Antiparasitic Activity of product of the present invention.Rhodium metal title complex embodiment 1 obtained is dissolved in 1mlDMSO, then with by 25mmol/L 4-hydroxyethyl piperazine ethanesulfonic acid damping fluid, and 32mmol/LNaHCO
3200 times are diluted with RPMI 1640 cell culture medium that 10% human plasma is made into.Sample solution is made into 11 kinds of different concns by the method for 2 times of dilutions subsequently successively, by 1ml, and 2 × 10
6the plasmodium of/ml adds in solution, is put in 5%CO at 37 DEG C
248h is cultivated in incubator.Add 1ml 3% DAPI solution, then cultivate 18h, measure RBC number with fluorocyte classification analysis instrument, can show that different concns sample is to plasmodial inhibiting rate, calculates IC
50value.
Experimental result:
Table 3 product of the present invention is to parasitic medium effective concentration (IC
50)
| Parasite | Plasmodium |
| IC 50(umol/mL) | 7.2±2.6 |
From the results shown in Table 3, rhodium complex of the present invention is 7.2 ± 2.6umol/mL to plasmodial medium effective concentration, illustrates that this compound has strong Antiparasitic Activity.
Although embodiment of the present invention are open as above, but it is not restricted to listed in specification sheets and embodiment utilization, it can be applied to various applicable the field of the invention completely, for those skilled in the art, can easily realize other amendment, therefore do not deviating under the universal that claim and equivalency range limit, the present invention is not limited to specific details and illustrates here and the example described.
Claims (8)
1. a rhodium complex, is characterized in that:
The chemical name of described rhodium complex is: a chlorine one o-methoxybenzaldehyde contracting 4-methyl-3-thiosemicarbazide First Five-Year Plan methyl cyclopentadienyl closes rhodium (III);
The structural formula of described rhodium complex is:
2. rhodium complex as claimed in claim 1, it is characterized in that, described rhodium complex is garnet crystal and is soluble in organic solvent, and described rhodium complex hydrogen nuclear magnetic resonance modal data is
1h NMR (CDCl
3solvent): δ=8.92 (s, 1H), 8.55 (d, J=9Hz, 1H), 7.69 (t, J=7.1Hz, 1H), 7.13 (t, J=7.5, Hz 1H), 7.03 (d, J=8.93Hz, 1H), 5.59 (d, J=5.7Hz, 1H), 4.95 (d, J=5.8Hz, 1H), 4.86 (d, J=5.7Hz, 1H), 4.57 (d, J=5.7Hz, 1H), 3.14 (d, J=4.2Hz, 3H), (2.70-2.63 m, J=6.9Hz, 1H).
3. a preparation method for rhodium complex as claimed in claim 1, is characterized in that, comprises the following steps:
Step one, by salicylic aldehyde, acetone and K
2cO
3put into container and be mixed to get the first mixed solution, stirring and refluxing at a certain temperature, and after a certain time a certain amount of methyl-sulfate is mixed with the first mixed solution, reaction certain hour after after and dilute hydrochloric acid be mixed to get the second mixed solution, add the layering of saturated NaCl solution to the second mixed solution again, get organic phase, organic phase is mixed with NaOH solution, bottom dark red oil is o-methoxybenzaldehyde, and structural formula is as follows:
Step 2, o-methoxybenzaldehyde and dehydrated alcohol to be mixed, after becoming yellow solution, described yellow solution and 4-methyl-3-thiosemicarbazide are dissolved each other, return stirring at a certain temperature, there is a large amount of pale yellow powder to separate out after certain hour, described pale yellow powder is leached, obtains white solid, for o-methoxybenzaldehyde contracting 4-methyl-3-thiosemicarbazide, structural formula is as follows:
Step 3, take a certain amount of o-methoxybenzaldehyde contracting 4-methyl-3-thiosemicarbazide and dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer and CH
2cl
2be mixed to get the 3rd mixed solution, after stirring certain hour, by the 3rd mixed solution underpressure distillation to 1-3ml, leave standstill and separate out yellow solid, namely product one chlorine one o-methoxybenzaldehyde contracting 4-methyl-3-thiosemicarbazide First Five-Year Plan methyl cyclopentadienyl of the present invention closes rhodium (III).
4. the preparation method of rhodium complex as claimed in claim 3, it is characterized in that, in step one, each amounts of components used is respectively: salicylic aldehyde 4-8g, acetone 30-60ml, K
2cO
30.1-1g, methyl-sulfate 3-6ml, dilute hydrochloric acid 2-5ml and NaOH 30-60ml; Wherein said K
2cO
3for anhydrous K
2cO
3, acetone concentration is 90-100%, and dimethyl sulfate ester concentration is 90-100%, and dilute hydrochloric acid concentration is 0.5-2mol/L, NaOH concentration is 1.5-3mol/L.
5. the preparation method of rhodium complex as claimed in claim 3, it is characterized in that, in step 2, each amounts of components used is respectively: o-methoxybenzaldehyde 3-5g, dehydrated alcohol 20-50ml and 4-methyl-3-thiosemicarbazide 1-2g; Described temperature is 70-90 DEG C, and the described time is 1-2 hour.
6. the preparation method of rhodium complex as claimed in claim 3, it is characterized in that, churning time described in step 3 is 5-8 hour, whipping temp is 15-35 DEG C, each amounts of components used is respectively: o-methoxybenzaldehyde contracting 4-methyl-3-thiosemicarbazide 20-25mg, dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer 30-35mg and CH
2cl
25-10ml, wherein said CH
2cl
2concentration be 90-100%.
7. a purposes for rhodium complex as claimed in claim 1, is characterized in that, described rhodium complex is for the preparation of the application of Therapeutic cancer, antibacterial and anti-parasite medicine.
8. a purposes for rhodium complex as claimed in claim 7, is characterized in that, described rhodium complex can be made into the form of injection, tablet, pill, capsule, suspension agent or emulsion.
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| CN105288727A (en) * | 2015-11-17 | 2016-02-03 | 广西中医药大学 | Method for preparing antibacterial and anti-cancer titanium dioxide nano-tubes by using rhodium coordination compound |
| CN105396173A (en) * | 2015-11-20 | 2016-03-16 | 广西中医药大学 | Method for preparing stainless steel with antibacterial and anti-cancer properties by means of rhodium complex |
| CN105463439A (en) * | 2015-11-17 | 2016-04-06 | 广西中医药大学 | Rhodium-complex-modified titanium material and preparing method and application of rhodium-complex-modified titanium material |
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| CN117003626A (en) * | 2023-08-07 | 2023-11-07 | 浙江宏达化学制品有限公司 | Method for synthesizing o-methoxy benzaldehyde based on dimethyl sulfate, reflux device and recycling system |
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