CN108250250A - - the N- of triphenyl containing 1,1,1- (1- (pyridine -2- methylene) complexs of methylamine and preparation method, application - Google Patents
- the N- of triphenyl containing 1,1,1- (1- (pyridine -2- methylene) complexs of methylamine and preparation method, application Download PDFInfo
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- CN108250250A CN108250250A CN201810070816.XA CN201810070816A CN108250250A CN 108250250 A CN108250250 A CN 108250250A CN 201810070816 A CN201810070816 A CN 201810070816A CN 108250250 A CN108250250 A CN 108250250A
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- pyridine
- methylamine
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- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 title claims abstract description 24
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 title claims abstract description 22
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 title claims abstract description 12
- 238000002360 preparation method Methods 0.000 title claims description 9
- YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 title abstract description 5
- 230000001093 anti-cancer Effects 0.000 claims abstract description 20
- 239000003814 drug Substances 0.000 claims abstract description 8
- 239000000126 substance Substances 0.000 claims abstract description 8
- 238000003384 imaging method Methods 0.000 claims abstract description 7
- 229940079593 drug Drugs 0.000 claims abstract description 5
- 238000000034 method Methods 0.000 claims abstract description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 38
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 38
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 37
- 229910052751 metal Inorganic materials 0.000 claims description 30
- 239000002184 metal Substances 0.000 claims description 30
- 229910052739 hydrogen Inorganic materials 0.000 claims description 24
- 239000001257 hydrogen Substances 0.000 claims description 24
- 229910052741 iridium Inorganic materials 0.000 claims description 22
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical group [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 claims description 22
- 238000009792 diffusion process Methods 0.000 claims description 21
- 239000013078 crystal Substances 0.000 claims description 20
- 150000002431 hydrogen Chemical class 0.000 claims description 20
- 229910021135 KPF6 Inorganic materials 0.000 claims description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 19
- 239000000539 dimer Substances 0.000 claims description 19
- 235000019441 ethanol Nutrition 0.000 claims description 19
- 238000001914 filtration Methods 0.000 claims description 19
- 229910052757 nitrogen Inorganic materials 0.000 claims description 19
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical group [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 18
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical group [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 18
- 229910052707 ruthenium Inorganic materials 0.000 claims description 18
- 238000003756 stirring Methods 0.000 claims description 18
- 229910052697 platinum Inorganic materials 0.000 claims description 11
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 claims description 5
- 229930007927 cymene Natural products 0.000 claims description 5
- -1 1,1,1- triphenyl-N- (1- (pyridine -2-yl) ethylidene) methylamine Chemical compound 0.000 claims description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical group [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- NMGSDTSOSIPXTN-UHFFFAOYSA-N cyclohexa-1,2-diene Chemical compound C1CC=C=CC1 NMGSDTSOSIPXTN-UHFFFAOYSA-N 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 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
- 125000000352 p-cymenyl group Chemical group C1(=C(C=C(C=C1)C)*)C(C)C 0.000 claims description 3
- 239000012675 alcoholic extract Substances 0.000 claims description 2
- 150000004982 aromatic amines Chemical group 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 claims description 2
- 229910017052 cobalt Inorganic materials 0.000 claims description 2
- 239000010941 cobalt Chemical group 0.000 claims description 2
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical group [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 150000002503 iridium Chemical class 0.000 claims description 2
- 229910052742 iron Inorganic materials 0.000 claims description 2
- 229910052762 osmium Inorganic materials 0.000 claims description 2
- SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical group [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 claims description 2
- HFPZCAJZSCWRBC-UHFFFAOYSA-N p-cymene Chemical compound CC(C)C1=CC=C(C)C=C1 HFPZCAJZSCWRBC-UHFFFAOYSA-N 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 229910052703 rhodium Inorganic materials 0.000 claims description 2
- 239000010948 rhodium Chemical group 0.000 claims description 2
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical group [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims description 2
- 229910001873 dinitrogen Inorganic materials 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 12
- 206010028980 Neoplasm Diseases 0.000 abstract description 8
- 201000011510 cancer Diseases 0.000 abstract description 8
- 239000003446 ligand Substances 0.000 abstract description 6
- 238000011160 research Methods 0.000 abstract description 6
- 150000001450 anions Chemical class 0.000 abstract description 2
- 239000000470 constituent Substances 0.000 abstract description 2
- 230000008569 process Effects 0.000 abstract description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 abstract 1
- 230000010415 tropism Effects 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 25
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
- 150000004696 coordination complex Chemical class 0.000 description 8
- 230000005311 nuclear magnetism Effects 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- 238000001228 spectrum Methods 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- UGTJLJZQQFGTJD-UHFFFAOYSA-N Carbonylcyanide-3-chlorophenylhydrazone Chemical compound ClC1=CC=CC(NN=C(C#N)C#N)=C1 UGTJLJZQQFGTJD-UHFFFAOYSA-N 0.000 description 3
- 239000003005 anticarcinogenic agent Substances 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 229940041181 antineoplastic drug Drugs 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 description 2
- 206010008342 Cervix carcinoma Diseases 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 239000012327 Ruthenium complex Substances 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000009056 active transport Effects 0.000 description 2
- 201000010881 cervical cancer Diseases 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 229960003677 chloroquine Drugs 0.000 description 2
- WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 201000005296 lung carcinoma Diseases 0.000 description 2
- 210000003712 lysosome Anatomy 0.000 description 2
- 230000001868 lysosomic effect Effects 0.000 description 2
- 125000002524 organometallic group Chemical group 0.000 description 2
- WQIQNKQYEUMPBM-UHFFFAOYSA-N pentamethylcyclopentadiene Chemical compound CC1C(C)=C(C)C(C)=C1C WQIQNKQYEUMPBM-UHFFFAOYSA-N 0.000 description 2
- 238000002390 rotary evaporation Methods 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- PMJHHCWVYXUKFD-SNAWJCMRSA-N (E)-1,3-pentadiene Chemical compound C\C=C\C=C PMJHHCWVYXUKFD-SNAWJCMRSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000009876 antimalignant effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000012925 biological evaluation Methods 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- YAYRGNWWLMLWJE-UHFFFAOYSA-L carboplatin Chemical compound O=C1O[Pt](N)(N)OC(=O)C11CCC1 YAYRGNWWLMLWJE-UHFFFAOYSA-L 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 239000012930 cell culture fluid Substances 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000007248 cellular mechanism Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000012447 hatching Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 231100000417 nephrotoxicity Toxicity 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen(.) Chemical compound [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 150000002894 organic compounds Chemical class 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
- 229960001756 oxaliplatin Drugs 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 150000003057 platinum Chemical class 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 150000003303 ruthenium Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000000007 visual effect Effects 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
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0033—Iridium compounds
-
- 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
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0046—Ruthenium compounds
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Physics & Mathematics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
Abstract
The present invention is specially that containing 1,1,1 triphenyl N, (complex of 1 (2 methylene of pyridine) methylamine, belongs to chemical pharmacy field to one kind.The molecular structural formula of the complex is：, the complex for preparing of the present invention can assign entire complex with high anti-cancer activity, and Mitochondrially targeted property, core target tropism can have selectivity to cancer cell, be of great significance to the research of target-oriented drug；The anion ligand that the present invention is chelated using N^N as two teeth, synthesize it is a kind of it is novel have compared with high anti-cancer activity complex, complex effect in anticancer and cell imaging is good, and activity is high；The present invention has many advantages, such as that simple for process, of low cost, chemical constituent is easily controllable, reproducible and yield is high.
Description
Technical field
The present invention relates to metal complex, specially a kind of (1- (pyridine -2- methylene) first containing 1,1,1- triphenyl-N-
The complex and preparation method of amine, application, belong to chemical pharmacy field.
Background technology
In nineteen sixty-five, the synthesis of cis-platinum thoroughly changes the present situation for only carrying out treating cancer by radiotherapy, and spread out therefrom
The many cis-platinum derivatives born have also been carried out biological evaluation.With the research that deepens continuously of people, cis-platinum, carboplatin and
Three kinds of platinum class anticarcinogens of oxaliplatin become global range in ratify Metal Anticancer Drug, and be the whole world uniquely using metal as base
The anticarcinogen used in clinic of plinth.Metal complex is treated, but their use is often for about the 50% of all tumours
With toxic side effect, such as renal toxicity and medicament dependence, it is about the most important restrictive condition of platinum-containing anticancer drug
Pass through cell small molecule（Particularly glutathione）It inactivates and cell can be flowed out.In order to overcome these cis-platinums in pharmacy research
Limitation, constantly opening up new channel becomes the main policies that these is met to challenge, and is matched including seeking using the metal other than platinum
It closes object and changes basic skeleton structure of complex etc., and the various good bioactivity that iridium shows make it into masses
The visual field.Based on the chemical differences between these metals, the spectrum action of molecular mechanism and potential indication can expand significantly,
So as to which the influence to cancer cell is maximized and minimized the problem of making its adverse side effect.Therefore, transition metal medicine is studied extensively
Object to become current development trend to anti-malignant tumor.
In recent years about antitumor activity iridium（Ir）Complex reported successively, the discoveries such as Liu Zhe, Peter J. Saler
Pentamethylcyclopentadiene base IrIII organometallic complexs can be used as potential anticancer as the complex of new type anticancer activity
Drug.Synthesized pentamethylcyclopentadiene base IrIII organometallic complexs are mostly N^N, C^C or C^N ligand at present
Complex of iridium.Ruthenium class complex is the most potential antitumor drug generally acknowledged in the world, is most hopeful after platinum
As one of metal that toxicity is low, activity is high.The complex for having hundreds of ruthenium at present is synthesized.Keppler in 1987
The ICR for obtaining good effect in vivo is synthesized.Alessio synthesized NAMFA in 1998, it is that the 1st entrance is faced
The ruthenium complex of bed, KP1019 is the 2nd kind of nail complex for entering clinical test after NAMFA.It prepares in the prior art
Complex, active anticancer is still to be improved, and does not shine the research that is imaged in the cell about half sandwich structure itself.
Invention content
For problems of the prior art, the present invention provides one kind (1- (pyridine -2- containing 1,1,1- triphenyl-N-
Methylene) methylamine complex, the complex be half sandwich metal complex.
The present invention also provides a kind of-N- (systems of the complex of 1- (pyridine -2- methylene) methylamine of triphenyl containing 1,1,1-
Preparation Method.
The present invention also provides the applications of above-mentioned half sandwich metal complex.
The used to achieve these goals technical solution of the present invention is：
The present invention provides one kind, containing 1,1,1- triphenyl-N-, (complex of 1- (pyridine -2- methylene) methylamine, the metal are matched
Close object molecular structural formula be：
І
Formula（І）In, the R1 is aryl, aryl amine, fragrant and mellow base, cymene or halogenated aryl, cyclopentadienyl group, 1.2.3.4.5-
Pentamethylcyclopentadiene base and the cyclopentadienyl group replaced by halogenated cycloalkyl, halogenated aryl, aryl, halogen；R2 for hydrogen,
Alkyl, amino, alcoholic extract hydroxyl group, halogen or halogenated alkyl, halogenated cycloalkyl；M is platinum metal.
Further, the M is iron, ruthenium, osmium, platinum, cobalt, rhodium, iridium.
Further, the chemical structural formula of the optimization of complex that the present invention synthesizes is as follows：
The present invention also provides a kind of preparation method of above-mentioned complex, this method iridium dimer and formulas as shown in formula (II)
(III) complex shown in formula (I) is obtained by the reaction：
Further, it when the complex is complex 1-6, is as follows：
Complex 1：By 50.0mg iridium dimers（Formula（I）R1 is 1.2.3.4.5- pentamethylcyclopentadiene bases, and R2 is hydrogen, and M is
Metal iridium）, (1- (pyridine -2- methylene) methylamine is placed in 250mL and wishes Lake by 46.3mg 1,1,1- triphenyls-N-（Schlenk）
It in bottle, vacuumizes, with nitrogen three times, the analytically pure ethyl alcohol of 20mL is added in syringe needle, stir at room temperature for 24 hours, add in 60 mg
KPF6 is spin-dried for Rotary Evaporators, after dissolved with CH2Cl2, diatomite filtering, recrystallized with diffusion method, obtain red crystals.
Complex 2：By 50.0mg iridium dimers（Formula（I）R1 is 4-（2.3.4.5- tetramethyl-ring pentadiene）- 1 ' 1- biphenyl
Base, R2 are hydrogen, and M is metal iridium）, 43.6 mg, 1,1,1- triphenyl-N- (1- (pyridine -2-yl) ethylidene) methylamine is placed in
250mL wishes Lake（Schlenk）It in bottle, vacuumizes, with nitrogen three times, the analytically pure ethyl alcohol of 20mL, room temperature is added in syringe needle
It is lower stirring for 24 hours, add in 60 mg KPF6, be spin-dried for Rotary Evaporators, after dissolved with CH2Cl2, diatomite filtering, use diffusion method
Recrystallization, obtains red crystals.
Complex 3：By 50.0mg ruthenium dimers（Formula（III）R1 is phenyl, and R2 is hydrogen, and M is metal Ru）, 63.1mg 1,
1,1- triphenyls-N- (1- (pyridine -2-yl) ethylidene) methylamine is placed in 250mL and wishes Lake（Schlenk）In in bottle, vacuumize,
With nitrogen three times, the analytically pure ethyl alcohol of 20mL is added in syringe needle, stirs at room temperature for 24 hours, add in 60 mg KPF6, use rotary evaporation
Instrument is spin-dried for, after dissolved with CH2Cl2, diatomite filtering, recrystallized with diffusion method, obtain red crystals.
Complex 4：By 50.0mg ruthenium dimers（Formula（III）R1 is cymene, and R2 is hydrogen, and M is metal Ru）, 57.5mg
1,1,1- triphenyls-N- (1- (pyridine -2-yl) ethylidene) methylamine is placed in 250mL and wishes Lake（Schlenk）In in bottle, take out true
Sky with nitrogen three times, the analytically pure ethyl alcohol of 20mL is added in syringe needle, stirs at room temperature for 24 hours, 60 mg KPF6 are added in, with rotation
Evaporimeter is spin-dried for, after dissolved with CH2Cl2, diatomite filtering, recrystallized with diffusion method, obtain red crystals.
Complex 5：By 50.0mg ruthenium dimers（Formula（III）R1 is 4- (1.4- cyclohexadiene)-propyl alcohol, R2 is hydrogen, and M is
Metal Ru）, 60.0mg 1,1,1- triphenyls-N- (1- (pyridine -2-yl) ethylidene) methylamine is placed in 250mL and wishes Lake
（Schlenk）It in bottle, vacuumizes, with nitrogen three times, adds in the analytically pure ethyl alcohol of 20mL with syringe needle, stir for 24 hours, add at room temperature
Enter 60 mg KPF6, be spin-dried for Rotary Evaporators, after dissolved with CH2Cl2, diatomite filtering, recrystallized, obtained red with diffusion method
Color crystal.
Complex 6：By 50.0mg ruthenium dimers（Formula（III）4- (1.4- cyclohexadiene)-butanol, R2 are hydrogen, and M is metal
Ruthenium）, 51.9mg 1,1,1- triphenyls-N- (1- (pyridine -2-yl) ethylidene) methylamine is placed in 250mL and wishes Lake（Schlenk）Bottle
In in, vacuumize, with nitrogen three times, with syringe needle add in the analytically pure ethyl alcohol of 20mL, stir at room temperature for 24 hours, add in 60 mg
KPF6 is spin-dried for Rotary Evaporators, after dissolved with CH2Cl2, diatomite filtering, recrystallized with diffusion method, obtain red crystals.
The present invention also provides a kind of application of above-mentioned half sandwich metal complex in anticancer and cell imaging drug.
The coordination center atom of N^N ligands is an electronics unsymmetric structure in metal complex prepared by the present invention, nitrogen
Atom is very strong σ-electron donor, being capable of stable metal；And phenyl has certain conjugation, can be the change of complex
It learns and bioactivity provides changeability.Therefore, we have synthesized the neutral ligand that N^N is chelated as two teeth, a kind of novel tool
Have compared with high anti-cancer activity, while the metal complex that can be imaged in the cell.
Beneficial effects of the present invention are：
（1）Complex prepared by the present invention can assign entire complex with high anti-cancer activity, Mitochondrially targeted property, core target to
Property, there can be selectivity to cancer cell, be of great significance to the research of target-oriented drug.
（2）The anion ligand that the present invention is chelated using N^N as two teeth, synthesizing a kind of novel there is higher anticancer to live
Property complex, complex effect in anticancer and cell imaging is good, and activity is high.
（3）It is excellent that the present invention has that simple for process, of low cost, chemical constituent is easily controllable, reproducible and yield is high etc.
Point.
Description of the drawings
Fig. 1 is the nucleus magnetic hydrogen spectrum of complex 1 prepared by the embodiment of the present invention 1.
Fig. 2 is the mono-crystalline structures of complex 2 prepared by the embodiment of the present invention 2.
Fig. 3 is the nucleus magnetic hydrogen spectrum of complex 2 prepared by the embodiment of the present invention 2.
Fig. 4 is the mono-crystalline structures of complex 3 prepared by the embodiment of the present invention 3.
Fig. 5 is the nucleus magnetic hydrogen spectrum of complex 3 prepared by the embodiment of the present invention 3.
Fig. 6 is the mono-crystalline structures of complex 4 prepared by the embodiment of the present invention 4.
Fig. 7 is the nucleus magnetic hydrogen spectrum of complex 4 prepared by the embodiment of the present invention 4.
Fig. 8 is the nuclear-magnetism phosphorus spectrum of complex 5 prepared by the embodiment of the present invention 5.
Fig. 9 is the nuclear-magnetism carbon spectrum of complex 6 prepared by the embodiment of the present invention 6.
Figure 10 is the imaging of complex of the present invention target organelles in the cell.
Figure 11 is the research of complex of the present invention mechanism of absorption in the cell.
Specific embodiment
The present invention is expanded on further by the embodiment of some following representative compounds, but these explanations are not intended to limit
The present invention.
Initial compounds used are commercial prods or can be prepared from known synthetic method, institute in the synthesis of compound
The preparation method for having organic compound can be obtained from document, and these methods are basic and aobvious and easy to synthesis chemist
See.Therefore, the description of following synthetic method is regarded as detailed and specific.
Embodiment 1
By 50.0mg iridium dimers（Formula（I）R1 is 1.2.3.4.5- pentamethylcyclopentadiene bases, and R2 is hydrogen, and M is metal iridium）,
(1- (pyridine -2- methylene) methylamine is placed in 250mL and wishes Lake 46.3mg 1,1,1- triphenyls-N-（Schlenk）In in bottle, take out
Vacuum with nitrogen three times, the analytically pure ethyl alcohol of 20mL is added in syringe needle, stirs at room temperature for 24 hours, 60 mg KPF6 are added in, with rotation
Turn evaporimeter to be spin-dried for, after dissolved with CH2Cl2, diatomite filtering, recrystallized with diffusion method, obtain red crystals.Yield:52.48
mg(61.3%)。
As shown in Figure 1, nuclear-magnetism is characterized as：[(η5-Cp*)Ir(N^N)Cl]PF6 (1). 1H NMR (500 MHz,
DMSO) δ 8.61 (d, J = 4.7 Hz, 1H), 8.33 (d, J = 7.9 Hz, 1H), 7.98 (t, J = 7.0
Hz, 1H), 7.77 (s, 1H), 7.51 (ddd, J = 7.5, 4.8, 1.1 Hz, 1H), 7.37 (t, J = 7.5
Hz, 6H), 7.31 (t, J = 7.3 Hz, 3H), 7.24 – 7.21 (m, 6H), 1.75 (s, 15H). Anal.
Calcd. For [(η5- Cp*)Ir(N^N)Cl]PF6 (856.3): C, 49.09; H, 4.12; N, 3.27;
Found: C, 49.20; H, 4.02; N, 3.83. MS: m/z 711.34 [(η5-Cp*)Ir(N^N)Cl]+。
Embodiment 2
By 50.0mg iridium dimers（Formula（I）R1 is 4-（2.3.4.5- tetramethyl-ring pentadiene）- 1 ' 1- xenyls, R2 are hydrogen, M
For metal iridium）, 43.6 mg, 1,1,1- triphenyl-N- (1- (pyridine -2-yl) ethylidene) methylamine is placed in 250mL and wishes Lake
（Schlenk）It in bottle, vacuumizes, with nitrogen three times, adds in the analytically pure ethyl alcohol of 20mL with syringe needle, stir for 24 hours, add at room temperature
Enter 60 mg KPF6, be spin-dried for Rotary Evaporators, after dissolved with CH2Cl2, diatomite filtering, recrystallized, obtained red with diffusion method
Color crystal, the mono-crystalline structures of complex 2 are as shown in Figure 2.Yield:40.05 mg（40.3%）.
As shown in figure 3, nuclear-magnetism is characterized as：[(η5-Cpxbiph )Ir(N^N)Cl]PF6 (2). Yield: 40.05
mg, 40.3%.1H NMR (500 MHz, DMSO) δ 13.59 (d, J = 9.6 Hz, 2H), 9.54 (d, J =
9.7 Hz, 3H), 8.80 (d, J = 5.4 Hz, 2H), 8.57 – 8.13 (m, 5H), 8.05 – 7.65 (m,
8H), 7.64 – 7.23 (m, 8H), 1.83 (dd, J = 33.5, 10.8 Hz, 12H). Anal. Calcd. For
[(η5- Cpxbiph )Ir(N^N) Cl]PF6 (994.47): C, 55.56; H, 4.16; N, 2.82; Found: C,
54.20; H, 4.32; N, 2.73. MS: m/z 849.7 [(η5-Cpxbiph )Ir(N^N)Cl]+。
Embodiment 3
By 50.0mg ruthenium dimers（Formula（III）R1 is phenyl, and R2 is hydrogen, and M is metal Ru）, 63.1mg 1,1,1- triphenyls-N-
(1- (pyridine -2-yl) ethylidene) methylamine is placed in 250mL and wishes Lake（Schlenk）It in bottle, vacuumizes, with nitrogen three times, uses
Syringe needle adds in the analytically pure ethyl alcohol of 20mL, stirs at room temperature for 24 hours, adds in 60 mg KPF6, be spin-dried for Rotary Evaporators, rear to use
CH2Cl2 dissolves, and diatomite filtering is recrystallized with diffusion method, obtains red crystals, the mono-crystalline structures of complex 3 are as shown in Figure 4.
Yield:45.43 mg (61.3%).
As shown in figure 5, nuclear-magnetism is characterized as：[(η6-bz )Ru(N^N)Cl]PF6 (3). 1H NMR (500 MHz,
DMSO) δ 9.63 (d, J = 5.3 Hz, 1H), 8.78 (s, 1H), 8.32 (d, J = 7.9 Hz, 1H),
8.26 (t, J = 8.2 Hz, 1H), 7.89 – 7.86 (m, 1H), 7.45 (ddd, J = 27.3, 19.4, 7.3
Hz, 15H), 5.61 (s, 6H). Anal. Calcd. For [(η6- bz )Ir(N^N)Cl]PF6 (708.04): C,
52.59; H, 3.70; N, 3.96; Found: C, 50.20; H, 3.62; N, 3.86. MS: m/z 527.93[(η
6- bz )Ir(N^N)]+。
Embodiment 4
By 50.0mg ruthenium dimers（Formula（III）R1 is cymene, and R2 is hydrogen, and M is metal Ru）, 57.5mg 1,1,1- triphens
Base-N- (1- (pyridine -2-yl) ethylidene) methylamine is placed in 250mL and wishes Lake（Schlenk）In in bottle, vacuumize, with nitrogen three
It is secondary, the analytically pure ethyl alcohol of 20mL is added in syringe needle, is stirred at room temperature for 24 hours, is added in 60 mg KPF6, be spin-dried for Rotary Evaporators,
It is dissolved afterwards with CH2Cl2, diatomite filtering is recrystallized with diffusion method, obtains red crystals, mono-crystalline structures such as Fig. 6 of complex 4
It is shown.Yield:55.31 mg, 72.4%.
As shown in fig. 7, nuclear-magnetism is characterized as：[(η6 -p-cym)Ru(N^N)Cl]PF6 (4). 1H NMR (500 MHz,
CDCl3) δ 9.48 (s, 1H), 8.37 (s, 2H), 8.06 (s, 2H), 7.84 (d, J = 61.2 Hz, 3H),
7.47 (dd, J = 46.9, 7.3 Hz, 12H), 5.83 (s, 1H), 5.27 (s, 1H), 4.71 (s, 1H),
4.48 (s, 1H), 2.43 (s, 1H), 2.17 (s, 3H), 1.00 – 0.76 (m, 6H). Anal. Calcd.
For [(η6 - p-cym)Ir(N^N)Cl]PF6 (764.15): C, 55.01; H, 4.48; N, 3.67; Found:
C, 55.20; H, 4.52; N, 3.76. MS: m/z 584.75[(η6 - p-cym)Ir(N^N) + H]+。
Embodiment 5
By 50.0mg ruthenium dimers（Formula（III）R1 is 4- (1.4- cyclohexadiene)-propyl alcohol, R2 is hydrogen, and M is metal Ru）,
60.0mg 1,1,1- triphenyls-N- (1- (pyridine -2-yl) ethylidene) methylamine is placed in 250mL and wishes Lake（Schlenk）In bottle
In, it vacuumizes, with nitrogen three times, the analytically pure ethyl alcohol of 20mL is added in syringe needle, stir at room temperature for 24 hours, add in 60 mg KPF6,
Be spin-dried for Rotary Evaporators, after dissolved with CH2Cl2, diatomite filtering, recrystallized with diffusion method, obtain red crystals.Yield:
53.51 mg (69.8%)。
As shown in figure 8, nuclear-magnetism is characterized as：[(η6-bz-PA )Ru(N^N)Cl]PF6 (5). 1H NMR (500 MHz,
DMSO) δ 9.57 (d, J = 5.3 Hz, 1H), 8.76 (s, 1H), 8.35 – 8.21 (m, 3H), 7.92 –
7.81 (m, 2H), 7.45 (ddd, J = 26.9, 15.6, 7.3 Hz, 13H), 5.71 (t, J = 6.0 Hz,
1H), 5.66 (d, J = 6.3 Hz, 1H), 5.38 (t, J = 5.6 Hz, 1H), 5.03 – 4.96 (m, 2H),
4.55 (t, J = 5.0 Hz, 1H), 2.45 – 2.38 (m, 2H), 1.65 (ddd, J = 12.9, 8.8, 5.4
Hz, 2H), 1.53 (ddd, J = 13.5, 11.1, 6.7 Hz, 2H). Anal. Calcd. For [(η6- bz-PA
)Ir(N^N)Cl]PF6 (766.12): C, 53.30; H, 4.21; N, 3.66; O, 2.09; Found: C,
54.20; H, 4.32; N, 3.79; O, 2.12. MS: m/z 586.72 [(η6- bz-PA )Ir(N^N) + H]+。
Embodiment 6
By 50.0mg ruthenium dimers（Formula（III）4- (1.4- cyclohexadiene)-butanol, R2 are hydrogen, and M is metal Ru）, 51.9mg 1,
1,1- triphenyls-N- (1- (pyridine -2-yl) ethylidene) methylamine is placed in 250mL and wishes Lake（Schlenk）In in bottle, vacuumize,
With nitrogen three times, the analytically pure ethyl alcohol of 20mL is added in syringe needle, stirs at room temperature for 24 hours, add in 60 mg KPF6, use rotary evaporation
Instrument is spin-dried for, after dissolved with CH2Cl2, diatomite filtering, recrystallized with diffusion method, obtain red crystals.Yield:50.72 mg
(65.0%)。
As shown in figure 9, nuclear-magnetism is characterized as：[(η6-bz-BA)Ru(N^N)Cl]PF6 (6). 1H NMR (500 MHz,
DMSO) δ 9.56 (d, J = 5.4 Hz, 1H), 8.76 (s, 1H), 8.31 (d, J = 6.5 Hz, 1H),
8.26 (t, J = 7.7 Hz, 1H), 7.88 (t, J = 5.8 Hz, 1H), 7.45 (ddd, J = 26.8,
14.7, 7.3 Hz, 13H), 5.73 (dd, J = 13.6, 7.7 Hz, 2H), 5.64 (d, J = 5.9 Hz,
1H), 5.40 (t, J = 5.6 Hz, 1H), 5.02 (t, J = 6.0 Hz, 1H), 4.96 (d, J = 6.5 Hz,
1H), 2.38 – 2.29 (m, 2H), 1.64 – 1.27 (m, 6H). Anal. Calcd. For [(η6- bz-BA
Ir(N^N)Cl]PF6 (780.14): C, 53.88; H, 4.39; N, 3.59; O, 2.05;Found: C, 54.70;
H, 4.42; N, 3.79; O, 2.16. MS: m/z 600.35 [(η6- bz-BA Ir(N^N) + H]+。
Comparative example 1
[(η 5-C5Me5) Ir (L1) Cl] PF6 (7) of synthetic compound 7 are by 50.0mg iridium dimers（Formula（I）R1 is
1.2.3.4.5- pentamethylcyclopentadiene base, structural formula such as L1, M are metal iridium）, 40.2 mg L1 are placed in 250mL and wish Lake
（Schlenk）It in bottle, vacuumizes, with nitrogen three times, adds in the analytically pure ethyl alcohol of 20mL with syringe needle, stir for 24 hours, add at room temperature
Enter 60 mg KPF6, be spin-dried for Rotary Evaporators, after dissolved with CH2Cl2, diatomite filtering, recrystallized, obtained red with diffusion method
Color crystal.Yield: 37.5 mg, 52.2%.
1H NMR (500 MHz, DMSO-d6) δ 9.52 (s, 1H), 9.05 (d, J = 5.5 Hz, 1H),
8.37 (dt, J = 15.2, 6.4 Hz, 2H), 8.00 – 7.97 (m, 1H), 7.38 – 7.35 (m, 1H),
7.30 (dd, J = 8.0, 5.5 Hz, 2H), 2.29 (s, 3H), 2.09 (s, 3H), 1.42 (s, 15H).
13C NMR (126 MHz, DMSO-d6) δ 174.30 (s), 155.37 (s), 152.99 (s), 147.10 (s),
141.17 (s), 132.28 (s), 131.32 (s), 130.53 (d, J = 15.4 Hz), 129.72 (s),
129.15 (s), 128.87 (s), 90.98 (s), 19.93 (s), 19.11 (s). Anal. Calcd. for [(η
5-C5Me5)Ir(L1)Cl]PF6 (718.13): C, 40.14; H, 4.07; N, 3.90; Found: C, 40.02;
H, 4.02; N, 3.83. MS: m/z 538.61 [(η5-C5Me5)Ir(L2) + H]+。
The cell imaging effect of complex 7 prepared by the comparative example is poor.
Effect example
（One）The proliferation inhibition activity experiment of 1 ~ 6 pair of tumor cell line of complex with anticancer activity：
(1) preparation of untested compound：
Solid complexes 1 ~ 5 are dissolved in DMSO respectively, are made into certain density storing solution, it is further dilute with cell culture fluid
Storing solution is released until reaching working concentration, culture is for 24 hours；
(2) cell growth inhibition test (mtt assay)：
1) 5000 cervical cancer cells (HeLa) or lung carcinoma cell are taken（A549）, cell suspension is configured to, is inoculated in the training of 96 holes
It supports in plate；
2) with no medicine culture medium pre-cultured cell, 5%CO2,310K are incubated 24 hours, add in prepared untested compound, train
Support 24 h；
3) the MTT solution of 15 μ L, 5 mg/mL is added in per hole, continues culture 4 hours, forms purple crystal substance first a ceremonial jade-ladle, used in libation；
4) culture is terminated, carefully sucks culture solution in hole, the DMSO that 100 μ L are added in per hole fully dissolves first a ceremonial jade-ladle, used in libation precipitation, oscillator
After mixing, the microplate reader OD value that wavelength is that 570nm measures each hole；
5) it is each to test in triplicate, IC50=average value ± SEM
Complex 1 ~ 6 and cis-platinum are to cervical cancer cell (HeLa) and lung carcinoma cell（A549）The inhibiting rate of growth is shown in Table 1.
Table 1
It can be seen from Table 1 that the change of 1 ~ 6 cyclopentadienyl ring R1 of complex and metal all shows very greatly two kinds of cancer cells
Influence, for A549 cells, the active anticancer of complex 2 and 3 maintains an equal level outer, complex with commercialized cis-platinum anticarcinogen substantially
5 active anticancer is slightly weaker than cis-platinum, and the active anticancer of complex 1 is 4 times of cis-platinum or so.In addition, when M is metal iridium
R1 is by 4-（2.3.4.5- tetramethyl-ring pentadiene）When -1 ' 1- xenyls become 1.2.3.4.5- pentamethylcyclopentadiene bases, resist
Cancer activity improves 5 times or so；4- (1.4- cyclohexadiene)-propyl alcohol of R1 positions is changed into 4- (1.4- hexamethylenes when M is metal Ru
Diene)-butanol when, active anticancer reduce；Comparison for ruthenium and iridium, the active anticancer of metal iridium complex are apparently higher than metal
Ruthenium complex.(the metal complex active anticancer of 1- (pyridine -2- methylene) methylamine ligand is apparent by the-N- of triphenyl containing 1,1,1-
Better than complex 7, this illustrates that the modification of substituent group can produce a very large impact active anticancer.
（Two）Cell imaging experiments experiment step：
A549 cells, which are placed in 6 orifice plates, hatches 24 hours, adds in MTDR (mitochondrial stain)/LTDR（Lysosome coloring agent）
100nM, 37 degree hatch 30 minutes, add in 1/3 10 μM of complex, after hatching 30 minutes altogether, are washed three times with cold PBS, immediately
It is observed under two-photon laser Laser Scanning Confocal Microscope.
Experimental result obtains：It can be seen from fig. 10 that complex just enters nucleus for 1 30 minutes, and complex 3 is first
First in cytoplasm, there is good common location with mitochondria and lysosome, after 8 hours into nucleus, match with cytotoxicity
3 IC50=32.0 ± 1.2 of ± 0.6 complex of 1 IC50=6.5 of object are closed, relatively understand that being directly targeted nucleus can more promote cancer thin
Born of the same parents' apoptosis, the reason of leading to this phenomenon are that nucleus is the center for controlling all metabolic activities.
（Three）Cell mechanism of absorption is tested
A549 cells, which are placed in 6 orifice plates, hatches 24 hours, is separately added into 50 μM of chloroquine/CCCP, hatches 60 minutes, adds in cooperation
1/3 10 μM of object, 37 degree altogether hatch 30 minutes after, while 4 degree it is parallel with 37 degree carry out be total to hatch 30 minutes after, with cold PBS
It washes three times, is observed under two-photon laser Laser Scanning Confocal Microscope immediately.
Chloroquine is that packet gulps down inhibitor, and CCCP is inhibitor of energy, can must be wrapped by Figure 11 gulp down to cell absorb always not
Significantly, however when adding in CCCP substantially completely cell is inhibited to absorb, this illustrates that complex is entered by the mode of energy
Cell, small molecule enters cell main energetic dependent form（Active transport, packet gulp down）Non-energy dependent form（Diffusion is assisted, freely
Diffusion）It can thus be appreciated that complex 1 and 3, which is all active transport, enters cell.
Claims (6)
1. a kind of (complex of 1- (pyridine -2- methylene) methylamine, which is characterized in that the complex containing 1,1,1- triphenyl-N-
Molecular structural formula be：
І
Formula（І）In, the R1 is aryl, aryl amine, fragrant and mellow base, cymene or halogenated aryl, cyclopentadienyl group, 1.2.3.4.5-
Pentamethylcyclopentadiene base and the cyclopentadienyl group replaced by halogenated cycloalkyl, halogenated aryl, aryl, halogen；R2 for hydrogen,
Alkyl, amino, alcoholic extract hydroxyl group, halogen or halogenated alkyl, halogenated cycloalkyl；M is platinum metal.
2. complex according to claim 1, which is characterized in that the M is iron, ruthenium, osmium, platinum, cobalt, rhodium, iridium.
3. complex according to claim 1 or 2, which is characterized in that the chemical structural formula of the complex is as follows：
。
It is 4. a kind of such as the preparation method of claim 1-3 any one of them complexs, which is characterized in that this method is by formula (II)
Complex shown in formula (I) is obtained by the reaction with formula (III) in shown iridium dimer：
。
5. preparation method according to claim 4, which is characterized in that when the complex is complex 1-6, specific steps
It is as follows：
Complex 1：By 50.0mg iridium dimers（Formula（I）R1 is 1.2.3.4.5- pentamethylcyclopentadiene bases, and R2 is hydrogen, and M is
Metal iridium）, (1- (pyridine -2- methylene) methylamine is placed in 250mL and wishes Lake by 46.3mg 1,1,1- triphenyls-N-（Schlenk）
It in bottle, vacuumizes, with nitrogen three times, the analytically pure ethyl alcohol of 20mL is added in syringe needle, stir at room temperature for 24 hours, add in 60 mg
KPF6 is spin-dried for Rotary Evaporators, after dissolved with CH2Cl2, diatomite filtering, recrystallized with diffusion method, obtain red crystals；
Complex 2：By 50.0mg iridium dimers（Formula（I）R1 is 4-（2.3.4.5- tetramethyl-ring pentadiene）- 1 ' 1- xenyls,
R2 is hydrogen, and M is metal iridium）, 43.6 mg, 1,1,1- triphenyl-N- (1- (pyridine -2-yl) ethylidene) methylamine is placed in 250mL and wishes
Lake（Schlenk）It in bottle, vacuumizes, with nitrogen three times, adds in the analytically pure ethyl alcohol of 20mL with syringe needle, stir at room temperature
For 24 hours, add in 60 mg KPF6, be spin-dried for Rotary Evaporators, after dissolved with CH2Cl2, diatomite filtering, recrystallized with diffusion method,
Obtain red crystals；
Complex 3：By 50.0mg ruthenium dimers（Formula（III）R1 is phenyl, and R2 is hydrogen, and M is metal Ru）, 63.1mg 1,1,1-
Triphenyl-N- (1- (pyridine -2-yl) ethylidene) methylamine is placed in 250mL and wishes Lake（Schlenk）In in bottle, vacuumize, same to nitrogen
Gas adds in the analytically pure ethyl alcohol of 20mL three times, with syringe needle, stirs at room temperature for 24 hours, adds in 60 mg KPF6, revolved with Rotary Evaporators
It is dry, after dissolved with CH2Cl2, diatomite filtering is recrystallized with diffusion method, obtains red crystals；
Complex 4：By 50.0mg ruthenium dimers（Formula（III）R1 is cymene, and R2 is hydrogen, and M is metal Ru）, 57.5mg 1,1,
1- triphenyls-N- (1- (pyridine -2-yl) ethylidene) methylamine is placed in 250mL and wishes Lake（Schlenk）In in bottle, vacuumize, together
Nitrogen adds in the analytically pure ethyl alcohol of 20mL three times, with syringe needle, stirs at room temperature for 24 hours, adds in 60 mg KPF6, use Rotary Evaporators
Be spin-dried for, after dissolved with CH2Cl2, diatomite filtering, recrystallized with diffusion method, obtain red crystals；
Complex 5：By 50.0mg ruthenium dimers（Formula（III）R1 is 4- (1.4- cyclohexadiene)-propyl alcohol, R2 is hydrogen, and M is metal
Ruthenium）, 60.0mg 1,1,1- triphenyls-N- (1- (pyridine -2-yl) ethylidene) methylamine is placed in 250mL and wishes Lake（Schlenk）Bottle
In in, vacuumize, with nitrogen three times, with syringe needle add in the analytically pure ethyl alcohol of 20mL, stir at room temperature for 24 hours, add in 60 mg
KPF6 is spin-dried for Rotary Evaporators, after dissolved with CH2Cl2, diatomite filtering, recrystallized with diffusion method, obtain red crystals；
Complex 6：By 50.0mg ruthenium dimers（Formula（III）4- (1.4- cyclohexadiene)-butanol, R2 are hydrogen, and M is metal Ru）,
51.9mg 1,1,1- triphenyls-N- (1- (pyridine -2-yl) ethylidene) methylamine is placed in 250mL and wishes Lake（Schlenk）In bottle
In, it vacuumizes, with nitrogen three times, the analytically pure ethyl alcohol of 20mL is added in syringe needle, stir at room temperature for 24 hours, add in 60 mg KPF6,
Be spin-dried for Rotary Evaporators, after dissolved with CH2Cl2, diatomite filtering, recrystallized with diffusion method, obtain red crystals.
It is 6. a kind of such as application of the claim 1-3 any one of them complex in anticancer and cell imaging drug.
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| CN115385968B (en) * | 2022-09-07 | 2023-12-08 | 曲阜师范大学 | Iridium (III) pyridine complex with high fluorescence quantum yield and semi-sandwich structure, and preparation method and application thereof |
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