CN115385968B - 一种高荧光量子产率的半三明治结构铱(iii)吡啶配合物及其制备方法和应用 - Google Patents
一种高荧光量子产率的半三明治结构铱(iii)吡啶配合物及其制备方法和应用 Download PDFInfo
- Publication number
- CN115385968B CN115385968B CN202211088251.0A CN202211088251A CN115385968B CN 115385968 B CN115385968 B CN 115385968B CN 202211088251 A CN202211088251 A CN 202211088251A CN 115385968 B CN115385968 B CN 115385968B
- Authority
- CN
- China
- Prior art keywords
- formula
- sodium acetate
- compound
- triphenylamine
- complex
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 238000006862 quantum yield reaction Methods 0.000 title abstract description 10
- ICTDFNDNVXCQFN-UHFFFAOYSA-N iridium(3+);pyridine Chemical compound [Ir+3].C1=CC=NC=C1 ICTDFNDNVXCQFN-UHFFFAOYSA-N 0.000 title description 4
- 239000003446 ligand Substances 0.000 claims abstract description 40
- -1 triphenylamine modified iridium (III) pyridine Chemical class 0.000 claims abstract description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 105
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 105
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 62
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 60
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 60
- 239000001632 sodium acetate Substances 0.000 claims description 60
- 235000017281 sodium acetate Nutrition 0.000 claims description 60
- 150000001875 compounds Chemical class 0.000 claims description 35
- NBIKPJUOLNNQLF-UHFFFAOYSA-N n,n-diphenylaniline;pyridine Chemical compound C1=CC=NC=C1.C1=CC=CC=C1N(C=1C=CC=CC=1)C1=CC=CC=C1 NBIKPJUOLNNQLF-UHFFFAOYSA-N 0.000 claims description 35
- 229910052757 nitrogen Inorganic materials 0.000 claims description 35
- 238000001914 filtration Methods 0.000 claims description 34
- 150000002503 iridium Chemical class 0.000 claims description 33
- 239000000047 product Substances 0.000 claims description 33
- 239000002904 solvent Substances 0.000 claims description 32
- 239000002244 precipitate Substances 0.000 claims description 30
- 238000000034 method Methods 0.000 claims description 28
- 239000002243 precursor Substances 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 229910052741 iridium Inorganic materials 0.000 claims description 8
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 claims description 8
- 239000002246 antineoplastic agent Substances 0.000 claims description 2
- 229940041181 antineoplastic drug Drugs 0.000 claims description 2
- 229910052728 basic metal Inorganic materials 0.000 claims description 2
- 238000011282 treatment Methods 0.000 claims description 2
- 238000009792 diffusion process Methods 0.000 claims 9
- 239000001257 hydrogen Substances 0.000 abstract description 35
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 35
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 32
- 210000004027 cell Anatomy 0.000 abstract description 17
- 210000003470 mitochondria Anatomy 0.000 abstract description 12
- 230000000259 anti-tumor effect Effects 0.000 abstract description 10
- 102000004169 proteins and genes Human genes 0.000 abstract description 8
- 108090000623 proteins and genes Proteins 0.000 abstract description 8
- 230000006907 apoptotic process Effects 0.000 abstract description 5
- 230000002438 mitochondrial effect Effects 0.000 abstract description 5
- 150000002431 hydrogen Chemical class 0.000 abstract description 3
- 125000006617 triphenylamine group Chemical group 0.000 abstract description 3
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 abstract description 2
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 abstract description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 abstract description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 abstract 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 abstract 1
- 101710179684 Poly [ADP-ribose] polymerase Proteins 0.000 abstract 1
- 102100023712 Poly [ADP-ribose] polymerase 1 Human genes 0.000 abstract 1
- 230000002222 downregulating effect Effects 0.000 abstract 1
- 201000005202 lung cancer Diseases 0.000 abstract 1
- 208000020816 lung neoplasm Diseases 0.000 abstract 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 abstract 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 47
- 238000001228 spectrum Methods 0.000 description 39
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 36
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 20
- 229910052799 carbon Inorganic materials 0.000 description 20
- 238000001819 mass spectrum Methods 0.000 description 20
- 238000012544 monitoring process Methods 0.000 description 20
- 238000005259 measurement Methods 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- MILUBEOXRNEUHS-UHFFFAOYSA-N iridium(3+) Chemical compound [Ir+3] MILUBEOXRNEUHS-UHFFFAOYSA-N 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 230000008685 targeting Effects 0.000 description 6
- 239000013078 crystal Substances 0.000 description 5
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 210000004881 tumor cell Anatomy 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 238000002441 X-ray diffraction Methods 0.000 description 4
- 230000001093 anti-cancer Effects 0.000 description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 230000005284 excitation Effects 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- ODHXBMXNKOYIBV-UHFFFAOYSA-N triphenylamine Chemical compound C1=CC=CC=C1N(C=1C=CC=CC=1)C1=CC=CC=C1 ODHXBMXNKOYIBV-UHFFFAOYSA-N 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 description 3
- 108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 3
- 229960004316 cisplatin Drugs 0.000 description 3
- 239000000539 dimer Substances 0.000 description 3
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 241000283707 Capra Species 0.000 description 2
- 102000004225 Cathepsin B Human genes 0.000 description 2
- 108090000712 Cathepsin B Proteins 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 102100035133 Lysosome-associated membrane glycoprotein 1 Human genes 0.000 description 2
- 101710116782 Lysosome-associated membrane glycoprotein 1 Proteins 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000000862 absorption spectrum Methods 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 230000008045 co-localization Effects 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- YOLNUNVVUJULQZ-UHFFFAOYSA-J iridium;tetrachloride Chemical compound [Cl-].[Cl-].[Cl-].[Cl-].[Ir] YOLNUNVVUJULQZ-UHFFFAOYSA-J 0.000 description 2
- 210000003712 lysosome Anatomy 0.000 description 2
- 230000001868 lysosomic effect Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 238000000120 microwave digestion Methods 0.000 description 2
- 230000004898 mitochondrial function Effects 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 2
- WQIQNKQYEUMPBM-UHFFFAOYSA-N pentamethylcyclopentadiene Chemical compound CC1C(C)=C(C)C(C)=C1C WQIQNKQYEUMPBM-UHFFFAOYSA-N 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- BGUWFUQJCDRPTL-UHFFFAOYSA-N pyridine-4-carbaldehyde Chemical compound O=CC1=CC=NC=C1 BGUWFUQJCDRPTL-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 238000009210 therapy by ultrasound Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- ARUAYSANQMCCEN-UHFFFAOYSA-N 2,3,4,5-tetramethylcyclopent-2-en-1-one Chemical compound CC1C(C)C(=O)C(C)=C1C ARUAYSANQMCCEN-UHFFFAOYSA-N 0.000 description 1
- IWTFOFMTUOBLHG-UHFFFAOYSA-N 2-methoxypyridine Chemical compound COC1=CC=CC=N1 IWTFOFMTUOBLHG-UHFFFAOYSA-N 0.000 description 1
- BSDGZUDFPKIYQG-UHFFFAOYSA-N 4-bromopyridine Chemical compound BrC1=CC=NC=C1 BSDGZUDFPKIYQG-UHFFFAOYSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- UQOKZDUUBVGFAK-UHFFFAOYSA-N 4-nitro-n,n-diphenylaniline Chemical compound C1=CC([N+](=O)[O-])=CC=C1N(C=1C=CC=CC=1)C1=CC=CC=C1 UQOKZDUUBVGFAK-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 108091006146 Channels Proteins 0.000 description 1
- 102000018832 Cytochromes Human genes 0.000 description 1
- 108010052832 Cytochromes Proteins 0.000 description 1
- 101710088172 HTH-type transcriptional regulator RipA Proteins 0.000 description 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- BAWFJGJZGIEFAR-NNYOXOHSSA-N NAD zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-N 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 108010090931 Proto-Oncogene Proteins c-bcl-2 Proteins 0.000 description 1
- 102000013535 Proto-Oncogene Proteins c-bcl-2 Human genes 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- NCOIBEMYOFIJHW-UHFFFAOYSA-M [Br-].C1=CC(OC)=CC=C1N(C=1C=CC(OC)=CC=1)C(C=C1)=CC=C1C[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 Chemical compound [Br-].C1=CC(OC)=CC=C1N(C=1C=CC(OC)=CC=1)C(C=C1)=CC=C1C[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 NCOIBEMYOFIJHW-UHFFFAOYSA-M 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004103 aerobic respiration Effects 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 238000011319 anticancer therapy Methods 0.000 description 1
- 230000005775 apoptotic pathway Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- WTEPWWCRWNCUNA-UHFFFAOYSA-M benzyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)CC1=CC=CC=C1 WTEPWWCRWNCUNA-UHFFFAOYSA-M 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000000006 cell growth inhibition assay Methods 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 238000004624 confocal microscopy Methods 0.000 description 1
- 150000004696 coordination complex Chemical class 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Natural products C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000002189 fluorescence spectrum Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- OXECIMIMUOWVJU-UHFFFAOYSA-N iridium;pyridine Chemical compound [Ir].C1=CC=NC=C1.C1=CC=NC=C1 OXECIMIMUOWVJU-UHFFFAOYSA-N 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 210000001700 mitochondrial membrane Anatomy 0.000 description 1
- 230000006677 mitochondrial metabolism Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229950006238 nadide Drugs 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 238000010814 radioimmunoprecipitation assay Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- CMSYDJVRTHCWFP-UHFFFAOYSA-N triphenylphosphane;hydrobromide Chemical compound Br.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 CMSYDJVRTHCWFP-UHFFFAOYSA-N 0.000 description 1
- 208000024719 uterine cervix neoplasm Diseases 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 System
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
-
- 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
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
-
- 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
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/645—Specially adapted constructive features of fluorimeters
- G01N21/6456—Spatial resolved fluorescence measurements; Imaging
- G01N21/6458—Fluorescence microscopy
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Physics & Mathematics (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Optics & Photonics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
Abstract
本发明公开了一种三苯胺修饰的高荧光量子产率的半三明治结构铱(III)吡啶配合物及其制备方法和应用。其结构式如式(I)所示,R1为氢、苯基;R2为氢、甲基、甲氧基;吡啶配体与三苯胺衍生物之间的连接方式为单键、碳碳双键、碳氮双键。三苯胺衍生物的引入赋予配合物优异的荧光特性,在溶液中的绝对荧光量子产率高达77.75%。目标配合物均表现出潜在的抗肿瘤活性。配合物可以在A549肺癌细胞的线粒体内积累,通过下调Bcl‑2和PARP蛋白,上调Bax和Cyt‑c蛋白表达,证实了线粒体凋亡通道的存在。
Description
技术领域:
本发明涉及有机金属配合物,具体为一种高荧光量子产率的半三明治结构铱(III)吡啶配合物及其制备方法和应用,属于化学制药领域。
背景技术:
线粒体被称为“动力车间”,是一种双层膜包裹的细胞器。除了通过有氧呼吸给细胞提供能量外,线粒体还可以调节膜电位、控制细胞的凋亡。在缺乏能量的情况下,线粒体会通过改变自身结构将细胞色素C(Cyt-C)从线粒体释放到细胞质,从而打开线粒体介导的细胞凋亡途径。文献表明,线粒体靶向型药物通常表现出两个特征:正电性和较强的亲脂性。由于表现出无限增殖和旺盛的代谢,癌细胞拥有比正常细胞更多的线粒体,又因线粒体代谢和功能在肿瘤发生和癌症进展中不可或缺,这使得线粒体和线粒体功能成为抗癌治疗的理想靶点。半三明治结构金属铱(III)配合物具有潜在抗癌活性且不同于顺铂(传统化疗药物)的抗肿瘤机制,包括参与细胞的氧化还原过程(催化烟酰胺腺嘌呤二核苷酸的氧化,诱导细胞内活性氧的过量积累)和抑制Bcl-2蛋白的抗凋亡功能,形成跨线粒体外膜通道,导致线粒体膜电位降低,最终导致细胞凋亡。但是,半三明治结构铱(III)配合物很难形成有效的共轭结构,所以发光性能较差,不便于研究其抗癌机制。本发明选择将三苯胺及其衍生物荧光基团引入到半三明治结构铱(III)吡啶配合物中,通过简单的配位反应制备了十种高荧光量子产率的半三明治结构铱(III)配合物。三苯胺的引入导致有效改善配合物的脂溶性,方便于目标配合物靶向肿瘤细胞中的线粒体。
发明内容:
一种半三明治结构金属铱(III)化合物,其特征在于,三苯胺-吡啶单齿配体与金属铱(III)配位,其结构式如式(I)所示:
;其中,R1为氢、苯,R2为氢、甲基、甲氧基,吡啶与三苯胺之间的连接方式为单键、碳碳双键、碳氮双键。
进一步的,本发明所有目标配合物的化学结构式如下:
。
本发明提供了上述化合物的制备方法:三苯胺-吡啶单齿配体(III)与基础金属铱二聚体(II)反应得到式(I)所示目标化合物,具体反应路线如下:
。
进一步的,所述化合物为式1时,通过以下方法制备而成:
63.68 mg基础铱二聚体(II,R1=氢),61.15 mg三苯胺吡啶前配体(L1),65.6 mg乙酸钠和甲醇(60.0 mL)在室温、氮气保护环境下搅拌过夜(TLC监测)。减压除去溶剂,然后加入二氯甲烷(5.0 mL),过滤除去沉淀物(醋酸钠),加入正己烷扩散得到最终的目标产物1。
进一步的,所述化合物为式2时,通过以下方法制备而成:
73.60 mg基础铱二聚体(II,R1=苯),61.15 mg三苯胺吡啶前配体(L1),65.6 mg乙酸钠和甲醇(60.0 mL)在室温、氮气保护环境下搅拌过夜(TLC监测)。减压除去溶剂,然后加入二氯甲烷(5.0 mL),过滤除去沉淀物(醋酸钠),加入正己烷扩散得到最终的目标产物2。
进一步的,所述化合物为式3时,通过以下方法制备而成:
63.68 mg基础铱二聚体(II, R1=氢),51.54 mg三苯胺吡啶前配体(L2),65.6 mg乙酸钠和甲醇(60.0 mL)在室温、氮气保护环境下搅拌过夜(TLC监测)。减压除去溶剂,然后加入二氯甲烷(5.0 mL),过滤除去沉淀物(醋酸钠),加入正己烷扩散得到最终的目标产物3。
进一步的,所述化合物为式4时,通过以下方法制备而成:
73.60 mg基础铱二聚体(II,R1=苯),51.54 mg三苯胺吡啶前配体(L2),65.6 mg乙酸钠和甲醇(60.0 mL)在室温、氮气保护环境下搅拌过夜(TLC监测)。减压除去溶剂,然后加入二氯甲烷(5.0 mL),过滤除去沉淀物(醋酸钠),加入正己烷扩散得到最终的目标产物4。
进一步的,所述化合物为式5时,通过以下方法制备而成:
63.68 mg基础铱二聚体(II,R1=氢),60.19 mg三苯胺吡啶前配体(L3),65.6 mg乙酸钠和甲醇(60.0 mL)在室温、氮气保护环境下搅拌过夜(TLC监测)。减压除去溶剂,然后加入二氯甲烷(5.0 mL),过滤除去沉淀物(醋酸钠),加入正己烷扩散得到最终的目标产物5。
进一步的,所述化合物为式6时,通过以下方法制备而成:
73.60 mg基础铱二聚体(II,R1=苯),60.19 mg三苯胺吡啶前配体(L3),65.6 mg乙酸钠和甲醇(60.0 mL)在室温、氮气保护环境下搅拌过夜(TLC监测)。减压除去溶剂,然后加入二氯甲烷(5.0 mL),过滤除去沉淀物(醋酸钠),加入正己烷扩散得到最终的目标产物6。
进一步的,所述化合物为式7时,通过以下方法制备而成:
63.68 mg基础铱二聚体(II,R1=氢),65.31 mg三苯胺吡啶前配体(L4),65.6 mg乙酸钠和甲醇(60.0 mL)在室温、氮气保护环境下搅拌过夜(TLC监测)。减压除去溶剂,然后加入二氯甲烷(5.0 mL),过滤除去沉淀物(醋酸钠),加入正己烷扩散得到最终的目标产物7。
进一步的,所述化合物为式8时,通过以下方法制备而成:
73.60 mg基础铱二聚体(II,R1=苯),65.31 mg三苯胺吡啶前配体(L4),65.6 mg乙酸钠和甲醇(60.0 mL)在室温、氮气保护环境下搅拌过夜(TLC监测)。减压除去溶剂,然后加入二氯甲烷(5.0 mL),过滤除去沉淀物(醋酸钠),加入正己烷扩散得到最终的目标产物8。
进一步的,所述化合物为式9时,通过以下方法制备而成:
63.68 mg基础铱二聚体(II,R1=氢),55.87 mg三苯胺吡啶前配体(L5),65.6 mg乙酸钠和甲醇(60.0 mL)在室温、氮气保护环境下搅拌过夜(TLC监测)。减压除去溶剂,然后加入二氯甲烷(5.0 mL),过滤除去沉淀物(醋酸钠),加入正己烷扩散得到最终的目标产物9。
进一步的,所述化合物为式10时,通过以下方法制备而成:
73.60 mg基础铱二聚体(II,R1=苯),55.87 mg三苯胺吡啶前配体(L5),65.6 mg乙酸钠和甲醇(60.0 mL)在室温、氮气保护环境下搅拌过夜(TLC监测)。减压除去溶剂,然后加入二氯甲烷(5.0 mL),过滤除去沉淀物(醋酸钠),加入正己烷扩散得到最终的目标产物10。
本发明提供了一种通过上述方法制备的半三明治结构金属铱吡啶配合物在抗肿瘤药物中的应用。富含电子的芳香配体(环戊二烯基及衍生物)与铱(III)配位,可以稳定铱(III)的高氧化态。三苯胺及其衍生物可以调控配合物的亲脂性,促进配合物与酶的受体或特定靶向位点之间的相互作用,进而调节细胞的组织靶向,影响抗肿瘤活性;另外,可以调控配合物的电子特性,赋予配合物优异的荧光特性。
本发明的有益效果为:
(1)本发明合成的半三明治结构铱(III)配合物表现出潜在的抗癌活性;
(2)本发明合成的配合物具有高的绝对荧光量子产率,可作为线粒体荧光探针。
附图内容:
图1为本发明配合物1的核磁共振氢谱;
图2为本发明配合物1的核磁共振碳谱;
图3为本发明配合物1的质谱;
图4为本发明配合物1的x-衍射单晶结构图;
图5为本发明配合物2的核磁共振氢谱;
图6为本发明配合物2的核磁共振碳谱;
图7为本发明配合物2的质谱;
图8为本发明配合物3的核磁共振氢谱;
图9为本发明配合物3的核磁共振碳谱;
图10为本发明配合物3的质谱;
图11为本发明配合物3的x-衍射单晶结构图;
图12为本发明配合物4的核磁共振氢谱;
图13为本发明配合物4的核磁共振碳谱;
图14为本发明配合物4的质谱;
图15为本发明配合物5的核磁共振氢谱;
图16为本发明配合物5的核磁共振碳谱;
图17为本发明配合物5的质谱;
图18为本发明配合物6的核磁共振氢谱;
图19为本发明配合物6的核磁共振碳谱;
图20为本发明配合物6的质谱;
图21为本发明配合物7的核磁共振氢谱;
图22为本发明配合物7的核磁共振碳谱;
图23为本发明配合物7的质谱;
图24为本发明配合物8的核磁共振氢谱;
图25为本发明配合物8的核磁共振碳谱;
图26为本发明配合物8的质谱;
图27为本发明配合物9的核磁共振氢谱;
图28为本发明配合物9的核磁共振碳谱;
图29为本发明配合物9的质谱;
图30为本发明配合物10的核磁共振氢谱;
图31为本发明配合物10的核磁共振碳谱;
图32为本发明配合物10的质谱;
图33为本发明配合物6的紫外-可见吸收光谱图(a)和荧光光谱图(b);
图34为本发明配合物1-6的绝对荧光量子产率图;
图35为本发明配合物6的细胞组织靶向图;
图36为本发明配合物6与A549细胞作用24 h后,Western blot检测5种线粒体凋亡蛋白的表达水平图(a)和蛋白表达的直方图(b)。
具体实施方式:
本发明在下文描述的一些代表性化合物的实施方案上进一步阐述,但这些描述并不限制本发明。
在化合物中,起始化合物用于合成商业产品或可以通过已知的合成方法制备,所有有机化合物的制备都可以从文献中获得,而合成化学家的方法是一种基本而明显的方法。因此,以下对合成方法的描述可以视为详细和具体的。
实施例1
称取1.2 g三氯化铱水合物、1.8 mL 1,2,3,4,5-五甲基环戊二烯,然后将35 mL无水甲醇加入到混合体系中,超声5 min。加入氮气,放入微波消解仪中反应。倒出上清液,冰甲醇洗涤罐中固体,加入二氯甲烷溶解,过滤,滤液中加入20 mL无水乙醚,冷却结晶得到金属铱二聚体产物(II,R1=氢),1.98 g(产率:72.4%)。1H NMR (500 MHz, CDCl3) δ 1.60 (s,J = 1.4 Hz, 30H)。
实施例 2
量取4.4 mL 2,3,4,5-四甲基-2-环戊烯酮,加入35 mL无水四氢呋喃,搅拌下加入12.8 mL苯基溴化镁。加热回流4 h后,倒入60 mL冰水中,缓慢加入40 mL浓盐酸,搅拌0.5h。无水乙醚萃取2次,无水碳酸钠干燥,真空浓缩得粗产物。柱层析提纯得二聚体前配体。取1.2 g三氯化铱水合物、2.1 g二聚体前配体依次加入微波消解罐中,然后加入35 mL无水甲醇,超声5 min。加入氮气保护,完成消解后取出,上清液倒出,冰甲醇洗涤罐中固体。加入二氯甲烷溶解剩余晶体,过滤,加入20 mL无水乙醚,冷藏后可得金属铱二聚体产物(II,R1=苯),2.02 g(产率:62.8%)。1H NMR (500 MHz, CDCl3) δ 7.58 (m, 4H), 7.35 (m, 6H),1.72 (s, 12H), 1.63 (s, 12H)。
实施例 3
称取2.16 g 4-[(双(4-甲氧基苯基)]苯基硼酸,或称取1.72 g 4-[(二苯基氨基)]苯基硼酸,0.64 g 4-溴代吡啶、0.48 g四(三苯基膦)钯三种试剂溶于水:甲苯体积比为1:5的混合溶剂中,氮气环境中加热回流15 h。反应完成后乙酸乙酯萃取三次,柱层析(乙酸乙酯:石油醚=15:1(v/v))提纯,分别得到L1和L2。L1:2.16 g(产率:77.0%)。1H NMR (500MHz, CDCl3) δ 8.58 (d, J = 5.2 Hz, 2H), 7.45 (dd, J = 10.0, 7.3 Hz, 4H), 7.10(d, J = 8.8 Hz, 4H), 6.97 (d, J = 8.6 Hz, 2H), 6.86 (d, J = 8.8 Hz, 4H), 3.81(s, 6H)。ESI-MS (m/z): C25H22N2O2,计算值:383.17813 [M+H]+, 实测值:383.17470。L2:1.75 g(产率:74.2%)。1H NMR (500 MHz, CDCl3) δ 8.61 (d, J = 5.6 Hz, 2H), 7.54-7.51 (m, 2H), 7.47 (dd, J = 4.6, 1.5 Hz, 2H), 7.32-7.27 (m, 5H), 7.16-7.12(m, 5H), 7.08 (t, J = 7.4 Hz, 2H)。ESI-MS (m/z): C23H18N2,计算值:323.15700;[M+H]+,实测值:323.15389。
实施例 4
称取1.51 g 4-[N,N’-二(对甲苯基)氨基]苯甲醛,或称取1.5 g 4-[双(4-甲氧基苯基)氨基]苯甲醛溶于无水甲醇:二氯甲烷体积比为1:2的混合溶剂中,称取0.81 g硼氢化钠分批加入上述溶液中,常温、氮气环境中搅拌24 h。减压除去溶剂后,加入二氯甲烷溶解,缓慢加水、搅拌,去离子水反复冲洗两到三次,取适量的无水硫酸镁进行干燥,得到4-[N,N-二(对甲苯基)氨基]苯甲醇,或得到4-[双(4-甲氧基苯基)氨基]苯甲醇。三苯基膦氢溴酸盐分别与上述产物在三氯甲烷中加热回流21 h后可以得到4-[N,N'-二-(对甲苯基)氨基]苄基(三苯基)溴化磷,或得到[4-(双(4-甲氧基苯基)氨基]苄基(三苯基)溴化磷,将其溶于30mL四氢呋喃中,0℃下搅拌,注入20 mL 2.12 g叔丁醇钾的四氢呋喃溶液,反应0.5 h。称取0.51g 4-吡啶甲醛,缓慢注入上述溶液中,室温下搅拌6 h。反应完成后乙酸乙酯萃取,无水硫酸镁干燥,抽滤、旋干,再加入80 mL四氢呋喃和少许单质碘,加热回流10 h,加入100 mL的10%的氢氧化钠搅拌30 min,乙酸乙酯萃取三次,无水硫酸镁干燥,抽滤、旋干,得到配体L3和L4。L3:1.87 g(产率:56.7%)。1H NMR (500 MHz, CDCl3) δ 8.80 (d, J = 5.5 Hz,2H), 7.34 (dd, J = 15.4, 7.0 Hz, 4H), 7.28-7.25 (d, 1H), 7.06 (dd, J = 37.9,7.8 Hz, 8H), 6.97 (d, J = 8.2 Hz, 2H), 6.83 (d, J = 16.2 Hz, 1H), 2.33 (s,6H)。ESI-MS (m/z): C27H24N2,计算值:377.20395;[M+H]+,实测值:377.20089。L4:1.69 g(产率:53.5%)。1H NMR (500 MHz, CDCl3) δ 8.52 (dd, J = 4.7, 1.4 Hz, 2H), 7.54(ddd, J = 5.5, 5.0, 1.4 Hz, 4H), 7.35-7.30 (m, 4H), 7.08 (d, J = 9.0 Hz, 4H),6.85 (d, J = 8.9 Hz, 4H), 3.80 (s, 6H)。ESI-MS (m/z): C27H24N2O2,计算值:409.1938;[M+H]+,实测值:409.1946。
实施例 5
称取4.2 g 4-硝基三苯胺溶于40 mL无水乙醇中,加入2.5 g钯碳催化剂,加热回流5 min,量取17 mL水合肼(80%)缓慢滴加到反应烧瓶中,回流反应8 h。趁热抽滤,将滤液冷却至室温,过滤,得粗产品4-氨基三苯胺溶于70 mL乙醇中,加热搅拌,待全部溶解之后,缓慢滴加1.2 g 4-吡啶甲醛,回流24 h。减压蒸馏,用二氯甲烷溶解,再加入约10 mL的石油醚,挥发结晶得到配体L5, 2.63 g(产率:53.1%)。1H NMR (500 MHz, CDCl3) δ 8.74 (d, J= 5.9 Hz, 2H), 8.49 (s, 1H), 7.74 (d, J = 5.9 Hz, 2H), 7.28 (d, J = 8.3 Hz,4H), 7.22 (d, J = 8.8 Hz, 2H), 7.12 (dd, J = 8.2, 4.4 Hz, 6H), 7.05 (t, J =7.3 Hz, 2H)。ESI-MS (m/z): C24H19N3,计算值:350.16790;[M+H]+,实测值:350.16454。
实施例6
63.68 mg基础铱二聚体(II,R1=氢),61.15 mg三苯胺吡啶前配体(L1),65.6 mg乙酸钠和甲醇(60.0 mL)在室温、氮气保护环境下搅拌过夜(TLC监测)。减压除去溶剂,然后加入二氯甲烷(5.0 mL),过滤除去沉淀物(醋酸钠),加入正己烷扩散得到最终的目标产物1。95.2 mg(产率:97.2%)。核磁共振氢谱、核磁共振碳谱、质谱和x-射线衍射单晶结构分别如图1、2、3和4所示:1H NMR (500 MHz, CDCl3) δ 8.85 (d, J = 6.7 Hz, 2H), 7.45 (d, J= 7.1 Hz, 4H), 7.11 (d, J = 8.8 Hz, 4H), 6.95 (d, J = 8.7 Hz, 2H), 6.87 (d, J= 8.9 Hz, 4H), 3.81 (s, 6H), 1.56 (s, 15H)。13C NMR (126 MHz, CDCl3) δ 156.72,153.03, 150.84, 149.32, 139.69, 127.69, 127.43, 126.06, 121.72, 119.09,114.95, 85.64, 55.54, 8.60。HRMS (m/z): C35H37Cl2N2O2Ir,计算值:745.2173;[M-Cl]+,实测值:745.2007。
实施例7
73.60 mg基础铱二聚体(II,R1=苯),61.15 mg三苯胺吡啶前配体(L1),65.6 mg乙酸钠和甲醇(60.0 mL)在室温、氮气保护环境下搅拌过夜(TLC监测)。减压除去溶剂,然后加入二氯甲烷(5.0 mL),过滤除去沉淀物(醋酸钠),加入正己烷扩散得到最终的目标产物2。93.4 mg(产率:95.7%)。核磁共振氢谱、核磁共振碳谱和质谱分别如图5、6和7所示:1H NMR(500 MHz, CDCl3) δ 8.81 (d, J = 5.0 Hz, 2H), 7.73 (s, 2H), 7.38 (d, J = 11.5Hz, 7H), 7.09 (d, J = 7.6 Hz, 4H), 6.91 (d, J = 7.6 Hz, 2H), 6.86 (d, J = 7.5Hz, 4H), 3.81 (s, 6H), 1.72 (s, 6H), 1.52 (s, 6H)。13C NMR (126 MHz, CDCl3) δ156.72, 153.15, 150.82, 149.30, 139.68, 130.93, 130.26, 128.75, 128.21,127.65, 127.43, 125.99, 121.66, 119.04, 114.94, 94.01, 83.84, 80.49, 55.52,9.69, 8.72。HRMS (m/z): C40H39Cl2N2O2Ir,计算值:807.2229;[M-Cl]+,实测值:807.2137。
实施例8
63.68 mg基础铱二聚体(II,R1=氢),51.54 mg三苯胺吡啶前配体(L2),65.6 mg乙酸钠和甲醇(60.0 mL)在室温、氮气保护环境下搅拌过夜(TLC监测)。减压除去溶剂,然后加入二氯甲烷(5.0 mL),过滤除去沉淀物(醋酸钠),加入正己烷扩散得到最终的目标产物3。94.3 mg(产率:96.4%)。核磁共振氢谱、核磁共振碳谱、质谱和x-射线衍射单晶结构分别如图8、9、10和11所示:1H NMR (500 MHz, CDCl3) δ 8.90 (d, J = 6.7 Hz, 2H), 7.49 (dd,J = 9.5, 7.8 Hz, 4H), 7.31 (t, J = 7.8 Hz, 4H), 7.13 (dd, J = 16.3, 8.0 Hz,8H), 1.57 (s, 15H)。13C NMR (126 MHz, CDCl3) δ 153.18, 150.04, 148.28, 146.86,129.56, 128.15, 127.82, 125.42, 124.15, 122.14, 122.03, 85.67, 8.59。HRMS (m/ z): C33H33Cl2N2Ir,计算值:685.1962;[M-Cl]+, 实测值:685.1816。
实施例9
73.60 mg基础铱二聚体(II,R1=苯),51.54 mg三苯胺吡啶前配体(L2),65.6 mg乙酸钠和甲醇(60.0 mL)在室温、氮气保护环境下搅拌过夜(TLC监测)。减压除去溶剂,然后加入二氯甲烷(5.0 mL),过滤除去沉淀物(醋酸钠),加入正己烷扩散得到最终的目标产物4。95.4 mg(产率:97.6%)。核磁共振氢谱、核磁共振碳谱和质谱分别如图12、13和14所示:1HNMR (500 MHz, CDCl3) δ 8.86 (d, J = 6.8 Hz, 2H), 7.74 (dd, J = 7.2, 2.1 Hz,2H), 7.45 (d, J = 8.8 Hz, 2H), 7.41 – 7.39 (m, 5H), 7.30 (t, J = 7.9 Hz, 4H),7.15 – 7.07 (m, 8H), 1.73 (s, 6H), 1.52 (s, 6H)。13C NMR (126 MHz, CDCl3) δ153.30, 150.00, 149.22, 146.84, 130.89, 130.25, 129.55, 128.77, 128.24,128.06, 127.80, 125.40, 124.14, 122.08, 121.98, 94.07, 83.88, 80.52, 9.70,8.73。HRMS (m/z): C38H35Cl2N2Ir,计算值:747.1818;[M-Cl]+,实测值:747.1935。
实施例10
63.68 mg基础铱二聚体(II,R1=氢),60.19 mg三苯胺吡啶前配体(L3),65.6 mg乙酸钠和甲醇(60.0 mL)在室温、氮气保护环境下搅拌过夜(TLC监测)。减压除去溶剂,然后加入二氯甲烷(5.0 mL),过滤除去沉淀物(醋酸钠),加入正己烷扩散得到最终的目标产物5。92.3 mg(产率:93.4%)。核磁共振氢谱、核磁共振碳谱和质谱分别如图15、16和17所示:1HNMR (500 MHz, CDCl3) δ 8.80 (d, J = 5.5 Hz, 2H), 7.34 (dd, J = 15.4, 7.0 Hz,4H), 7.13 – 6.95 (m, 12H), 2.33 (s, 6H), 1.55 (s, 15H)。13C NMR (126 MHz,CDCl3) δ 152.95, 149.57, 147.06, 144.48, 135.63, 133.66, 130.09, 128.39,127.77, 125.42, 121.90, 121.04, 120.96, 85.65, 20.89, 8.58。HRMS (m/z):C37H39Cl2N2Ir,计算值:739.2431;[M-Cl]+,实测值:739.2419。
实施例11
73.60 mg基础铱二聚体(II,R1=苯),60.19 mg三苯胺吡啶前配体(L3),65.6 mg乙酸钠和甲醇(60.0 mL)在室温、氮气保护环境下搅拌过夜(TLC监测)。减压除去溶剂,然后加入二氯甲烷(5.0 mL),过滤除去沉淀物(醋酸钠),加入正己烷扩散得到最终的目标产物6。96.7 mg(产率:98.0%)。核磁共振氢谱、核磁共振碳谱和质谱分别如图18、19和20所示:1HNMR (500 MHz, CDCl3) δ 8.76 (d, J = 5.8 Hz, 2H), 7.84 – 7.65 (m, 2H), 7.39(d, J = 5.1 Hz, 3H), 7.32 (d, J = 8.3 Hz, 2H), 7.23 (dd, J = 20.9, 14.9 Hz,2H), 7.05 (dd, J = 39.4, 7.9 Hz, 8H), 6.95 (d, J = 8.2 Hz, 2H), 6.77 (d, J =16.2 Hz, 1H), 2.33 (s, 6H), 1.72 (s, 6H), 1.51 (s, 6H)。13C NMR (126 MHz,CDCl3) δ 153.06, 149.57, 147.04, 144.47, 135.66, 133.66, 130.91, 130.24,130.09, 128.76, 128.36, 128.22, 127.73, 125.42, 121.85, 120.96, 120.93,94.06, 83.83, 80.45, 20.89, 9.68, 8.70。HRMS (m/z): C42H41Cl2N2Ir,计算值:801.2588;[M-Cl]+,实测值:801.2565。
实施例12
63.68 mg基础铱二聚体(II,R1=氢),65.31 mg三苯胺吡啶前配体(L4),65.6 mg乙酸钠和甲醇(60.0 mL)在室温、氮气保护环境下搅拌过夜(TLC监测)。减压除去溶剂,然后加入二氯甲烷(5.0 mL),过滤除去沉淀物(醋酸钠),加入正己烷扩散得到最终的目标产物7。95.5 mg(产率:97.4%)。核磁氢谱、核磁碳谱和质谱分别如图21、22和23所示:1H NMR (500MHz, CDCl3) δ 8.79 (s, 2H), 7.32 (s, 5H), 7.13–7.03 (m, 4H), 6.83 (dd, J =29.6, 12.5 Hz, 7H), 3.81 (d, J = 3.1 Hz, 6H), 1.55 (s, 15H)。13C NMR (126 MHz,CDCl3) δ 156.53, 152.91, 150.06, 147.15, 139.97, 135.71, 128.42, 127.25,126.85, 121.83, 120.54, 119.17, 114.86, 85.64, 55.51, 8.57。 HRMS (m/z):C37H39Cl2N2O2Ir,计算值:771.2329;[M-Cl]+,实测值:771.2313。
实施例13
73.60 mg基础铱二聚体(II,R1=苯),65.31mg三苯胺吡啶前配体(L4),65.6 mg乙酸钠和甲醇(60.0 mL)在室温、氮气保护环境下搅拌过夜(TLC监测)。减压除去溶剂,然后加入二氯甲烷(5.0 mL),过滤除去沉淀物(醋酸钠),加入正己烷扩散得到最终的目标产物8。91.9 mg(产率:92.8%)。核磁共振氢谱、核磁共振碳谱和质谱分别如图24、25和26所示:1HNMR (500 MHz, CDCl3) δ 8.75 (d, J = 6.6 Hz, 2H), 7.72 (dd, J = 6.6, 2.5 Hz,2H), 7.39 (dd, J = 5.1, 1.6 Hz, 3H), 7.30 (d, J = 8.7 Hz, 2H), 7.21 (dd, J =14.4, 11.5 Hz, 3H), 7.08 (d, J = 8.9 Hz, 4H), 6.88 – 6.83 (m, 6H), 6.74 (d, J= 16.2 Hz, 1H), 3.80 (s, 6H), 1.71 (s, 6H), 1.51 (s, 6H)。13C NMR (126 MHz,CDCl3) δ 156.52, 153.01, 150.04, 147.13, 139.95, 135.74, 130.92, 130.25,128.75, 128.41, 128.21, 127.24, 126.83, 121.80, 120.47, 119.15, 114.86,94.06, 83.81, 80.44, 55.52, 9.68, 8.70。HRMS (m/z): C42H41Cl2N2O2Ir,计算值:833.2486;[M-Cl]+,实测值:833.2487。
实施例14
63.68 mg基础铱二聚体(II,R1=氢),55.87 mg三苯胺吡啶前配体(L5),65.6 mg乙酸钠和甲醇(60.0 mL)在室温、氮气保护环境下搅拌过夜(TLC监测)。减压除去溶剂,然后加入二氯甲烷(5.0 mL),过滤除去沉淀物(醋酸钠),加入正己烷扩散得到最终的目标产物9。94.5 mg(产率:96.7%)。核磁共振氢谱、核磁共振碳谱和质谱分别如图27、28和29所示: 1HNMR (500 MHz, CDCl3) δ 9.06 (d, J = 6.4 Hz, 2H), 8.52 (s, 1H, CH=N), 7.77 (d,J = 6.5 Hz, 2H), 7.30 (d, J = 8.1 Hz, 3H), 7.27 (s, 1H), 7.25 (s, 1H), 7.12(m, 5H), 7.08 (dd, J = 12.4, 4.9 Hz, 3H), 1.56 (s, 15H)。13C NMR (126 MHz,CDCl3) δ 153.8, 152.49, 148.20, 147.29, 144.76, 143.48, 129.43, 124.86,123.56, 123.43, 123.30, 122.83, 85.93, 8.58。HRMS (m/z): C34H34Cl2N3Ir,计算值:712.2070;[M-Cl]+,实测值:712.2057。
实施例15
73.60 mg基础铱二聚体(II, R1=苯),55.87 mg三苯胺吡啶前配体(L5),65.6 mg乙酸钠和甲醇(60.0 mL)在室温、氮气保护环境下搅拌过夜(TLC监测)。减压除去溶剂,然后加入二氯甲烷(5.0 mL),过滤除去沉淀物(醋酸钠),加入正己烷扩散得到最终的目标产物10。 96.1 mg(产率:97.4%)。核磁共振氢谱、核磁共振碳谱和质谱分别如图30、31和32所示:1HNMR (500 MHz, CDCl3) δ 9.03 (d, J = 6.5 Hz, 2H), 8.49 (s, 1H), 7.77 – 7.69(m, 4H), 7.42 (dd, J = 5.1, 1.5 Hz, 3H), 7.33 – 7.27 (m, 3H), 7.24 (d, J =8.8 Hz, 2H), 7.17 – 7.08 (m, 8H), 1.74 (s, 6H), 1.53 (s, 6H)。 13C NMR (126MHz, CDCl3) δ 153.99, 152.36, 148.21, 147.27, 144.71, 143.41, 130.65, 130.17,129.43, 128.83, 128.35, 124.87, 123.57, 123.47, 123.25, 122.77, 94.40, 84.04,80.61, 9.69, 8.71。HRMS (m/z): C39H36Cl2N3Ir,计算值:774.2227;[M-Cl]+,实测值:774.2244。
实施例16
具有抗肿瘤活性的配合物1-10对A549和HeLa肿瘤细胞株的增殖抑制活性实验:
(1) 待测配合物原液的配制:将配合物溶解在二甲基亚砜中。用细胞培养液进一步稀释至工作浓度,孵育24 h;
(2) 细胞生长抑制实验(MTT法):
1) 96孔板,每孔铺5000个肿瘤细胞,配制成细胞悬液;
2) 培养基预培养细胞(5% CO2,310 K,24 h),加入待测配合物原液,孵育24 h;
3) 加入MTT溶液(15 μL 5 mg mL-1),继续孵育4 h;
4) 终止培养。洗去孔内的培养液,加入二甲基亚砜(100 μL),振荡器混匀,使用酶标仪测定各孔的光密度值(激发波长570 nm);
5) 每个实验至少重复三次。引用的IC50值为平均值±SEM。
目标化合物(I,1-10)、基础铱二聚体(II)、三苯胺-吡啶单齿配体(III,L1-L5)及顺铂对人类肺泡基底上皮肿瘤细胞(A549)和子宫颈肿瘤细胞(Hela)生长抑制率见表1。
表1
通过实施例11可以看出,相比于基础铱的二聚体(II)和配体L1-L5(IC50:>100 μM),目标配合物的抗肿瘤活性更占明显优势,这说明三苯胺-吡啶配体与铱(III)的结合具有良好的协同效果。其中,配合物6表现出对A549细胞最好的抗增殖活性,这几乎与顺铂的活性类似。本系列配合物中2、4、6、8、10比对应配体(L)的1、3、5、7、9显示出相对更高的抗肿瘤活性,这说明在五甲基环戊二烯上引入苯基可有助于提高此类配合物的抗肿瘤活性。但是,三苯胺基团上的取代基对此类配合物的抗肿瘤活性影响较小。
实施例17
用TU-1901紫外分光光度计在1 cm径程石英比色管(3.0 mL)上记录了配合物6的紫外-可见吸收光谱。用Origin软件对光谱进行处理。除非另有说明,实验是在298 K下进行的。从吸收曲线中可以看出6出现了两处主要的吸收峰,278 nm和402 nm(图33)。
实施例18
用FLS 1000-stm(Edinburgh Instruments, UK)瞬态荧光光度计对配合物的荧光强度和绝对荧光量子产率进行了测试,激发波长为440 nm。如图33所示,配合物6的最大发射峰在547 nm处。配合物1-6在溶液状态下(二甲亚砜作为溶剂)的绝对荧光量子产率分别为77.75%、44.45%、10.35%、39.85%、24.65%和42.99%(图34)。这说明了本发明配合物具备优异的荧光性能,这为探索药物的作用靶点和抗肿瘤机制提供了有利的条件。
实施例19
用双光子激光共聚焦扫描显微镜(*/LSM/880NLO)观察并记录了配合物6进入A549细胞后的靶向情况。Lyso Tracker Red DND-99(LTDR)和Mito Tracker Deep Red(MTDR)分别作为溶酶体和线粒体的荧光探针。A549细胞与配合物6(10 μM)在310 K下孵育1 h后加入LTDR(500 nM)和MTDR(500 nM)染色30 min,用磷酸盐生理盐水缓冲溶液(PBS)冲洗细胞板3次,激光共聚焦显微镜观察。目标化合物的激发波长为488 nm,收集波长为550±30 nm;LTRD的激发波长为630±30 nm,收集波长为493~630 nm;MTDR在644 nm处激发,发射波长为690±30 nm。如图35所示,配合物6在线粒体中的皮尔森共定位系数为0.95,而在溶酶体中的共定位系数为0.07,证实了配合物6可有效靶向于细胞内的线粒体。
实施例20
A549细胞在六孔板中培养,加入配合物6孵育48 h。收集细胞,PBS洗2次,用放射免疫沉淀测定缓冲液(RIPA)孵育,紫外-可见分光光度计(Meriton,SMA4000)测定蛋白浓度。等量的细胞总蛋白被sds-聚丙烯酰胺凝胶电泳分离并转移到硝化纤维膜。用5%脱脂牛奶在室温下封闭膜7 h,然后在4 ℃下与一抗孵育过夜,然后在室温下与酶标二抗体孵育4 h。Western blotting抗体为:兔抗人Cathepsin B(CB)、兔抗人LAMP-1(溶酶体相关膜蛋白1)、兔抗人β-actin、鼠抗人Cyt-c和鼠抗人PARP(聚adp核糖聚合酶)蛋白。二抗包括山羊抗兔抗体β-肌动蛋白、山羊抗小鼠抗体β-肌动蛋白。采用增强型化学发光试剂盒,使用Image Lab软件(Bio-Rad Gel Doc XR+)进行检测。实验重复三次。蛋白表达水平如图36所示,随着配合物6浓度的升高,Bcl-2和PARP蛋白表达明显降低,Bax和Cyt-c蛋白表达增加。这些结果证实了配合物6的线粒体抗癌通道的存在,并与共定位实验结果是一致的(靶向线粒体)。
Claims (8)
1.一种半三明治结构金属铱(I)化合物,其特征在于,其结构式为:
2.一种权利要求1所述半三明治结构金属铱配合物(I)的制备方法,其特征在于,步骤如下:三苯胺吡啶单齿配体(III)与基础金属铱二聚体(II)反应得到式(I)所示目标配合物,具体反应路线如下:
3.根据权利要求2所述的半三明治结构金属铱配合物的制备方法,其特征在于,所述化合物为式1时,通过以下方法制备而成:
63.68mg式(II)所示基础铱二聚体,其中R1为甲基,61.15mg式L1所示三苯胺吡啶前配体,65.6mg乙酸钠和60.0mL甲醇在室温、氮气保护环境下搅拌过夜;减压除去溶剂,然后加入5.0mL二氯甲烷,过滤除去沉淀物醋酸钠,加入正己烷扩散得到最终的目标产物1;所述化合物为式2时,通过以下方法制备而成:
73.60mg式(II)所示基础铱二聚体,其中R1为苯基,61.15mg式L1所示三苯胺吡啶前配体,65.6mg乙酸钠和60.0mL甲醇在室温、氮气保护环境下搅拌过夜;减压除去溶剂,然后加入5.0mL二氯甲烷,过滤除去沉淀物醋酸钠,加入正己烷扩散得到最终的目标产物2。
4.根据权利要求2所述的制备方法,其特征在于,所述化合物为式3时,通过以下方法制备而成:
63.68mg式(II)所示基础铱二聚体,其中R1为甲基,51.54mg式L2所示三苯胺吡啶前配体,65.6mg乙酸钠和60.0mL甲醇在室温、氮气保护环境下搅拌过夜;减压除去溶剂,然后加入5.0mL二氯甲烷,过滤除去沉淀物醋酸钠,加入正己烷扩散得到最终的目标产物3;所述化合物为式4时,通过以下方法制备而成:
73.60mg式(II)所示基础铱二聚体,其中R1为苯基,51.54mg式L2所示三苯胺吡啶前配体,65.6mg乙酸钠和60.0mL甲醇在室温、氮气保护环境下搅拌过夜;减压除去溶剂,然后加入5.0mL二氯甲烷,过滤除去沉淀物醋酸钠,加入正己烷扩散得到最终的目标产物4。
5.根据权利要求2所述的制备方法,其特征在于,所述化合物为式5时,通过以下方法制备而成:
63.68mg式(II)所示基础铱二聚体,其中R1为甲基,60.19mg式L3所示三苯胺吡啶前配体,65.6mg乙酸钠和60.0mL甲醇在室温、氮气保护环境下搅拌过夜;减压除去溶剂,然后加入5.0mL二氯甲烷,过滤除去沉淀物醋酸钠,加入正己烷扩散得到最终的目标产物5;
所述化合物为式6时,通过以下方法制备而成:
73.60mg式(II)所示基础铱二聚体,其中R1为苯基,60.19mg式L3所示三苯胺吡啶前配体,65.6mg乙酸钠和60.0mL甲醇在室温、氮气保护环境下搅拌过夜;减压除去溶剂,然后加入5.0mL二氯甲烷,过滤除去沉淀物醋酸钠,加入正己烷扩散得到最终的目标产物6。
6.根据权利要求2所述的制备方法,其特征在于,所述化合物为式7时,通过以下方法制备而成:
63.68mg式(II)所示基础铱二聚体,其中R1为甲基,65.31mg式L4所示三苯胺吡啶前配体,65.6mg乙酸钠和60.0mL甲醇在室温、氮气保护环境下搅拌过夜;减压除去溶剂,然后加入5.0mL二氯甲烷,过滤除去沉淀物醋酸钠,加入正己烷扩散得到最终的目标产物7;
所述化合物为式8时,通过以下方法制备而成:
73.60mg式(II)所示基础铱二聚体,其中R1为苯基,65.31mg式L4所示三苯胺吡啶前配体,65.6mg乙酸钠和60.0mL甲醇在室温、氮气保护环境下搅拌过夜;减压除去溶剂,然后加入5.0mL二氯甲烷,过滤除去沉淀物醋酸钠,加入正己烷扩散得到最终的目标产物8。
7.根据权利要求2所述的制备方法,其特征在于,所述化合物为式9时,通过以下方法制备而成:
63.68mg式(II)所示基础铱二聚体,其中R1为甲基,55.87mg式L5所示三苯胺吡啶前配体,65.6mg乙酸钠和60.0mL甲醇在室温、氮气保护环境下搅拌过夜;减压除去溶剂,然后加入5.0mL二氯甲烷,过滤除去沉淀物醋酸钠,加入正己烷扩散得到最终的目标产物9;
所述化合物为式10时,通过以下方法制备而成:
73.60mg式(II)所示基础铱二聚体,其中R1为苯基,55.87mg式L5所示三苯胺吡啶前配体,65.6mg乙酸钠和60.0mL甲醇在室温、氮气保护环境下搅拌过夜;减压除去溶剂,然后加入5.0mL二氯甲烷,过滤除去沉淀物醋酸钠,加入正己烷扩散得到最终的目标产物10。
8.一种权利要求2-7任一项所述的制备方法制备的半三明治结构铱配合物在制备抗肿瘤药物中的应用。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202211088251.0A CN115385968B (zh) | 2022-09-07 | 2022-09-07 | 一种高荧光量子产率的半三明治结构铱(iii)吡啶配合物及其制备方法和应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202211088251.0A CN115385968B (zh) | 2022-09-07 | 2022-09-07 | 一种高荧光量子产率的半三明治结构铱(iii)吡啶配合物及其制备方法和应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN115385968A CN115385968A (zh) | 2022-11-25 |
CN115385968B true CN115385968B (zh) | 2023-12-08 |
Family
ID=84126120
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202211088251.0A Active CN115385968B (zh) | 2022-09-07 | 2022-09-07 | 一种高荧光量子产率的半三明治结构铱(iii)吡啶配合物及其制备方法和应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN115385968B (zh) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108250250A (zh) * | 2018-01-25 | 2018-07-06 | 曲阜师范大学 | 含1,1,1-三苯基-n-(1-(吡啶-2-亚甲基)甲胺的配合物及制备方法、应用 |
CN113754701A (zh) * | 2021-09-22 | 2021-12-07 | 曲阜师范大学 | 一种半三明治结构铱二茂铁吡啶配合物及其制备方法和应用 |
-
2022
- 2022-09-07 CN CN202211088251.0A patent/CN115385968B/zh active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108250250A (zh) * | 2018-01-25 | 2018-07-06 | 曲阜师范大学 | 含1,1,1-三苯基-n-(1-(吡啶-2-亚甲基)甲胺的配合物及制备方法、应用 |
CN113754701A (zh) * | 2021-09-22 | 2021-12-07 | 曲阜师范大学 | 一种半三明治结构铱二茂铁吡啶配合物及其制备方法和应用 |
Non-Patent Citations (3)
Title |
---|
Lysosome-targeted iridium(III) compounds with pyridine-triphenylamine Schiff base ligands: syntheses, antitumor applications and mechanisms;Shujiao Chen等;《Inorg. Chem. Front.》;第7卷;第91-100页 * |
Triphenylamine and carbazole‐modified iridiumIII 2‐ phenylpyridine complexes: Synthesis, anticaner application and targeted research;Shujiao Chen等;Appl Organometal Chem. 》;第33卷;第e5053页 * |
Triphenylamine-Appended Half-Sandwich Iridium(III) Complexes and Their Biological Applications;Xiangdong He等;《Chem. Asian J. 》;第13卷;第1500-1509页 * |
Also Published As
Publication number | Publication date |
---|---|
CN115385968A (zh) | 2022-11-25 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Sun et al. | Exploiting Incommensurate Symmetry Numbers: Rational Design and Assembly of M2M3′ L6 Supramolecular Clusters with C3h Symmetry | |
Sharma et al. | DNA-binding behavior of ruthenium (II) complexes containing both group 15 donors and 2, 2′: 6′, 2 ″-terpyridine | |
Stolzenberg et al. | Structure, reactivity, and electrochemistry of free-base. beta.-oxoporphyrins and metallo-. beta.-oxoporphyrins | |
CN110305146B (zh) | 一种链状席夫碱铜配合物及其制备方法和应用 | |
CN113512068B (zh) | 一种双配体的亚硝酰钌配合物及其制备方法和应用 | |
CN103012401B (zh) | 蒽醌多吡啶配体及钌-蒽醌配合物的制备方法和应用 | |
CN115385968B (zh) | 一种高荧光量子产率的半三明治结构铱(iii)吡啶配合物及其制备方法和应用 | |
CN114524853B (zh) | 一种全反式维甲酸-芳基金属配合物、制备方法及应用 | |
Zhang et al. | Selective Construction of Trefoil knots and a Molecular Borromean Ring Induced by Steric Hindrance of Thioether Ligands | |
Gayathri et al. | Convenient synthesis of symmetrical azines from alcohols and hydrazine catalyzed by ruthenium (II) hydrazone complex in air | |
CN107827934B (zh) | 具有抗癌活性的四价铂配合物、制备方法及应用 | |
Gupta et al. | Mononuclear Complexes of Platinum Group Metals Containing η6‐and η5‐Cyclic Π‐Perimeter Hydrocarbon and Pyridylpyrazolyl Derivatives: Syntheses and Structural Studies | |
CN115057893A (zh) | 一种三明治构型的靶向线粒体的有机金属铱配合物及其制备方法、应用 | |
CN103467497B (zh) | 以水杨醛缩牛磺酸和咪唑为配体的双配体铜配合物及其合成方法和其用途 | |
CN113072593A (zh) | 一种具有抗癌活性的金属有机铱配合物及其制备方法、应用 | |
CN106632421A (zh) | 1‑(2‑吡啶)‑9‑(4‑甲基苄基)‑β‑咔啉的硝酸铜配合物及其合成方法和应用 | |
CN106478687B (zh) | 以1-(2-吡啶)-9-乙基-β-咔啉为配体的氯化铜配合物及其合成方法和应用 | |
CN113735915B (zh) | 一种异核金属铱-铼配合物及其制备方法与应用 | |
CN106478691B (zh) | 1-(2-吡啶)-9-(2-苯基乙基)-β-咔啉的氯化铜配合物及其合成方法和应用 | |
CN108822038B (zh) | 一种高活性的离子型比生群衍生物及其合成方法和应用 | |
CN106478685B (zh) | 以1-(2-吡啶)-9-丙基-β-咔啉为配体的氯化铜配合物及其合成方法和应用 | |
CN106478675B (zh) | 1‑(2‑吡啶)‑9‑(2‑苄氧基乙基)‑β‑咔啉的氯化铜配合物及合成方法和应用 | |
CN106632416B (zh) | 以1-(2-吡啶)-9-异戊基-β-咔啉为配体的氯化铜配合物及其合成方法和应用 | |
CN106632423B (zh) | 1-(2-吡啶)-9-(2-苯基乙基)-β-咔啉的硝酸铜配合物及其合成方法和应用 | |
CN106478683B (zh) | 以1-(2-吡啶)-9-异丁基-β-咔啉为配体的氯化铜配合物及其合成方法和应用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |