CN113248503B - Perylene diimide shoulder tetra-substituted derivative and preparation method and application thereof - Google Patents
Perylene diimide shoulder tetra-substituted derivative and preparation method and application thereof Download PDFInfo
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- CN113248503B CN113248503B CN202110626841.3A CN202110626841A CN113248503B CN 113248503 B CN113248503 B CN 113248503B CN 202110626841 A CN202110626841 A CN 202110626841A CN 113248503 B CN113248503 B CN 113248503B
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- dichloromethane
- perylene diimide
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- KJOLVZJFMDVPGB-UHFFFAOYSA-N perylenediimide Chemical compound C=12C3=CC=C(C(NC4=O)=O)C2=C4C=CC=1C1=CC=C2C(=O)NC(=O)C4=CC=C3C1=C42 KJOLVZJFMDVPGB-UHFFFAOYSA-N 0.000 title claims abstract description 47
- 238000002360 preparation method Methods 0.000 title claims abstract description 34
- 150000001875 compounds Chemical class 0.000 claims abstract description 73
- 238000006243 chemical reaction Methods 0.000 claims abstract description 45
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 24
- 239000003504 photosensitizing agent Substances 0.000 claims abstract description 13
- 238000000926 separation method Methods 0.000 claims abstract description 11
- 239000012221 photothermal agent Substances 0.000 claims abstract description 7
- 238000000746 purification Methods 0.000 claims abstract description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 102
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 51
- 239000000243 solution Substances 0.000 claims description 50
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 48
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 46
- 238000004440 column chromatography Methods 0.000 claims description 31
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 26
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 26
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 24
- 239000012065 filter cake Substances 0.000 claims description 24
- 239000003480 eluent Substances 0.000 claims description 23
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 claims description 18
- -1 silver hexafluoroantimonate Chemical compound 0.000 claims description 17
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 16
- 239000012295 chemical reaction liquid Substances 0.000 claims description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 14
- 229910052799 carbon Inorganic materials 0.000 claims description 14
- 229940125782 compound 2 Drugs 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 13
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 13
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 12
- 238000001035 drying Methods 0.000 claims description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 10
- 229940125904 compound 1 Drugs 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 10
- QVLTVILSYOWFRM-UHFFFAOYSA-L CC1=C(C)C(C)([Rh](Cl)Cl)C(C)=C1C Chemical class CC1=C(C)C(C)([Rh](Cl)Cl)C(C)=C1C QVLTVILSYOWFRM-UHFFFAOYSA-L 0.000 claims description 9
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims description 9
- 238000001914 filtration Methods 0.000 claims description 9
- 239000011259 mixed solution Substances 0.000 claims description 9
- CLYVDMAATCIVBF-UHFFFAOYSA-N pigment red 224 Chemical compound C=12C3=CC=C(C(OC4=O)=O)C2=C4C=CC=1C1=CC=C2C(=O)OC(=O)C4=CC=C3C1=C42 CLYVDMAATCIVBF-UHFFFAOYSA-N 0.000 claims description 9
- 239000002244 precipitate Substances 0.000 claims description 9
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 8
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims description 8
- 239000012298 atmosphere Substances 0.000 claims description 8
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 8
- SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 claims description 8
- 238000002156 mixing Methods 0.000 claims description 8
- 229940057499 anhydrous zinc acetate Drugs 0.000 claims description 7
- 239000012044 organic layer Substances 0.000 claims description 7
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 claims description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 7
- DJWUNCQRNNEAKC-UHFFFAOYSA-L zinc acetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O DJWUNCQRNNEAKC-UHFFFAOYSA-L 0.000 claims description 7
- 235000019270 ammonium chloride Nutrition 0.000 claims description 6
- 239000012153 distilled water Substances 0.000 claims description 6
- 229910052763 palladium Inorganic materials 0.000 claims description 5
- 239000000047 product Substances 0.000 claims description 5
- 238000004659 sterilization and disinfection Methods 0.000 claims description 5
- ZZPNDIHOQDQVNU-UHFFFAOYSA-N 2-hydroxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound CC1(C)OB(O)OC1(C)C ZZPNDIHOQDQVNU-UHFFFAOYSA-N 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- 238000004140 cleaning Methods 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 230000004614 tumor growth Effects 0.000 claims description 3
- ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims description 2
- 239000000376 reactant Substances 0.000 claims description 2
- 238000010992 reflux Methods 0.000 claims description 2
- 238000007789 sealing Methods 0.000 claims description 2
- 229960000314 zinc acetate Drugs 0.000 claims description 2
- 239000004246 zinc acetate Substances 0.000 claims description 2
- 239000000417 fungicide Substances 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract description 16
- 239000001301 oxygen Substances 0.000 abstract description 16
- 206010028980 Neoplasm Diseases 0.000 abstract description 11
- 230000005283 ground state Effects 0.000 abstract description 9
- 239000000463 material Substances 0.000 abstract description 7
- 230000001808 coupling effect Effects 0.000 abstract description 6
- 230000031700 light absorption Effects 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 5
- 230000001443 photoexcitation Effects 0.000 abstract description 3
- 230000007704 transition Effects 0.000 abstract description 3
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 12
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- 238000010521 absorption reaction Methods 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 239000000370 acceptor Substances 0.000 description 7
- 201000011510 cancer Diseases 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 241000894006 Bacteria Species 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 238000000605 extraction Methods 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- ZKSVYBRJSMBDMV-UHFFFAOYSA-N 1,3-diphenyl-2-benzofuran Chemical compound C1=CC=CC=C1C1=C2C=CC=CC2=C(C=2C=CC=CC=2)O1 ZKSVYBRJSMBDMV-UHFFFAOYSA-N 0.000 description 5
- 229910052786 argon Inorganic materials 0.000 description 5
- 239000012300 argon atmosphere Substances 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 229920001971 elastomer Polymers 0.000 description 5
- 239000012299 nitrogen atmosphere Substances 0.000 description 5
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- 229940123973 Oxygen scavenger Drugs 0.000 description 3
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- 230000005764 inhibitory process Effects 0.000 description 3
- 230000001678 irradiating effect Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- PQPFFKCJENSZKL-UHFFFAOYSA-N pentan-3-amine Chemical compound CCC(N)CC PQPFFKCJENSZKL-UHFFFAOYSA-N 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000003642 reactive oxygen metabolite Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 230000001954 sterilising effect Effects 0.000 description 3
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 2
- IICCLYANAQEHCI-UHFFFAOYSA-N 4,5,6,7-tetrachloro-3',6'-dihydroxy-2',4',5',7'-tetraiodospiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C(C(=C(Cl)C(Cl)=C2Cl)Cl)=C2C21C1=CC(I)=C(O)C(I)=C1OC1=C(I)C(O)=C(I)C=C21 IICCLYANAQEHCI-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 2
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- 229940081623 rose bengal Drugs 0.000 description 2
- STRXNPAVPKGJQR-UHFFFAOYSA-N rose bengal A Natural products O1C(=O)C(C(=CC=C2Cl)Cl)=C2C21C1=CC(I)=C(O)C(I)=C1OC1=C(I)C(O)=C(I)C=C21 STRXNPAVPKGJQR-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
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- GBHRGHJTZFOAKE-UHFFFAOYSA-N 2-anthracen-9-yl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound O1C(C)(C)C(C)(C)OB1C1=C(C=CC=C2)C2=CC2=CC=CC=C12 GBHRGHJTZFOAKE-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
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- XLHBQRJOHIHZGQ-UHFFFAOYSA-N heptadecan-9-amine Chemical compound CCCCCCCCC(N)CCCCCCCC XLHBQRJOHIHZGQ-UHFFFAOYSA-N 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
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- GFBRYGJZWXLRFR-UHFFFAOYSA-N undecan-6-amine Chemical compound CCCCCC(N)CCCCC GFBRYGJZWXLRFR-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/06—Peri-condensed systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- C02—TREATMENT OF WATER, WASTE WATER, SEWAGE, OR SLUDGE
- C02F—TREATMENT OF WATER, WASTE WATER, SEWAGE, OR SLUDGE
- C02F1/00—Treatment of water, waste water, or sewage
- C02F1/02—Treatment of water, waste water, or sewage by heating
- C02F1/04—Treatment of water, waste water, or sewage by heating by distillation or evaporation
- C02F1/048—Purification of waste water by evaporation
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- C02—TREATMENT OF WATER, WASTE WATER, SEWAGE, OR SLUDGE
- C02F—TREATMENT OF WATER, WASTE WATER, SEWAGE, OR SLUDGE
- C02F1/00—Treatment of water, waste water, or sewage
- C02F1/02—Treatment of water, waste water, or sewage by heating
- C02F1/04—Treatment of water, waste water, or sewage by heating by distillation or evaporation
- C02F1/14—Treatment of water, waste water, or sewage by heating by distillation or evaporation using solar energy
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- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A20/00—Water conservation; Efficient water supply; Efficient water use
- Y02A20/20—Controlling water pollution; Waste water treatment
- Y02A20/208—Off-grid powered water treatment
- Y02A20/212—Solar-powered wastewater sewage treatment, e.g. spray evaporation
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Abstract
The invention discloses a perylene diimide shoulder position tetrasubstituted derivative, a preparation method and application thereof, and a conjugated molecular system with a plurality of electron donors and a single electron acceptor which are covalently connected is constructed, namely the perylene diimide shoulder position tetrasubstituted derivative. The extremely strong electron coupling action between the electron donor and the electron acceptor leads to the broadening of the light absorption range of the compound, and at the same time, the charge separation state formed under the photoexcitation condition can reach a triplet state through intersystem crossing or return to the ground state in a non-radiative transition form. This is the origin of the excellent active oxygen generation efficiency and photothermal conversion efficiency of the derivative. The derivative has high active oxygen yield and remarkable photo-thermal conversion effect, is a photosensitizer with excellent performance and an organic micromolecule photo-thermal material, and is expected to be applied to the fields of solar water purification engineering and clinical photo-thermal/photodynamic tumor treatment. Provides a new idea for designing photosensitizer and photo-thermal agent with excellent performance.
Description
Technical Field
The invention belongs to the technical field of preparation of micromolecular photosensitizers and photo-thermal materials in organic synthesis, and particularly relates to a perylene diimide shoulder position tetrasubstituted derivative and a preparation method and application thereof.
Background
According to the estimation of the world health organization, one sixth of the deaths worldwide are caused by cancer at present, and as cancer becomes one of the main factors endangering human health and influencing human quality of life, effective treatment of cancer becomes a formidable challenge. Photodynamic therapy and photothermal therapy are increasingly used in the treatment of cancer as a non-invasive and low-toxicity treatment technique. Photodynamic therapy mainly relies on photosensitizers to generate Reactive Oxygen Species (ROS) under the irradiation of excitation light of corresponding wave bands to eliminate bacteria or tumor cells. Photothermal therapy relies on the powerful absorption of photothermal agents on the irradiation light intensity to reach an excited state, and returns to a ground state in a non-radiative transition mode, so that light energy is converted into heat energy, and the tumor part is rapidly heated to kill cancer cells.
Conventional photosensitizer molecular designs often incorporate heavy atoms to enhance spin-orbit coupling and thereby promote intermolecular cross-talk processes to increase singlet oxygen yield, but such photosensitizers containing heavy atoms often lead to dark toxicity, high cost, low solubility, and other unexpected additional problems. Organic photothermal therapeutic agents generally exhibit biodegradable properties that will reduce their potential long-term toxicity and increase their safety after systemic administration. However, organic photothermal therapeutics with narrow energy gaps and near-infrared biological window absorption are not readily achievable.
The common strategy is to construct a large conjugate with electron donor and electron acceptor groups, which requires great skill and effort to design and synthesize. Therefore, the development of novel photosensitizers and photothermal agents is of great importance in enhancing the therapeutic effect of cancer. In addition to the above challenges, the light absorption capability of organic photosensitizers and photothermal agents is also an important consideration, which is closely related to the properties of the materials obtained by later preparation.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention aims to provide a perylene diimide shoulder tetra-substituted derivative, and a preparation method and application thereof.
In order to achieve the purpose, the invention adopts the following technical scheme to realize the purpose:
the invention discloses a perylene diimide shoulder position tetrasubstituted derivative, which has the following structural formula:
wherein X is selected from C or O; n is 0 to 3; r is1、R2、R3、R4Each independently selected from electron-donating groups.
Preferably, the electron-donating group has the following structure:
and the position of the bond of the substituent group is represented.
Preferably, the perylene diimide shouldered four-substituted derivative specifically comprises a compound with the following structure:
in compounds P1, P2, P3, P4 and P5, X is selected from C, O; n is 0 to 3.
The invention also discloses a preparation method of the perylene diimide shoulder position tetrasubstituted derivative, which comprises the following steps:
1) preparation of Compound 1
Mixing reactants including perylene tetracarboxylic anhydride, amine, anhydrous zinc acetate and imidazole, heating until the imidazole is dissolved and fully stirring for reaction for 5-8 hours under the protection of inert atmosphere, dissolving by using tetrahydrofuran after the reaction liquid is cooled to room temperature, adding the reaction system into a mixed solution of hydrochloric acid and methanol to form a precipitate, filtering and collecting the precipitate, cleaning, drying a filter cake, and performing column chromatography separation to obtain a compound 1;
wherein the structural formula of the compound 1 is as follows:
wherein X is selected from C, O; n is 0 to 3.
2) Preparation of Compound 2
Mixing dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer, silver hexafluoroantimonate and dichloroethane, stirring and reacting at room temperature for 0.5-1 hour under the protection of inert atmosphere, then adding a compound 1, N-iodosuccinimide, copper acetate and dichloroethane, sealing, stirring and reacting at 80-100 ℃ for 120-135 hours, adding dichloromethane after the reaction liquid is cooled to room temperature, extracting by using saturated sodium thiosulfate solution and saturated saline solution in sequence, drying an organic layer, concentrating under reduced pressure, and separating by column chromatography to obtain a compound 2;
wherein the structural formula of the compound 2 is as follows:
wherein X is selected from C, O; n is 0 to 3.
3) Preparation of the target compounds P1, P2, P3, P4 and P5
Mixing the compound 2, an aryl heterocyclic compound, cuprous iodide, phenanthroline, potassium carbonate and N, N-dimethylformamide, stirring and refluxing for 8-10 hours under the protection of inert atmosphere, cooling the reaction liquid to room temperature, pouring into an ammonium chloride solution, filtering, cleaning a filter cake with distilled water, drying the filter cake, and performing column chromatography to obtain target products P2, P4 and P5;
or,
mixing the compound 2, an aryl compound containing boric acid pinacol ester, tetratriphenylphosphine palladium, potassium carbonate, toluene, water and ethanol, heating to 80-90 ℃ under the protection of inert atmosphere, stirring for reaction for 20-24 hours, adding water after the reaction liquid is cooled to room temperature, extracting with dichloromethane, decompressing, removing the solvent, and performing column chromatography separation to obtain target products P1 and P3.
Preferably, in step 1), the molar ratio of perylene tetracarboxylic anhydride, the corresponding amine, zinc acetate and imidazole is 1: (3-4): (0.7-0.9): (250-300), the concentration of the used hydrochloric acid is 2mol/L, and the ratio of the hydrochloric acid to the methanol in the mixed solution of the hydrochloric acid and the methanol is 2:1 volume is mixed;
in step 2), the molar ratio of the compound 1, dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer, silver hexafluoroantimonate, N-iodosuccinimide, copper acetate and dichloroethane is 1: (0.1-0.2): (0.8-1): (160-200): (1-1.1): (500-600);
in the step 3), when the compounds P2, P4 and P5 are prepared, the molar ratio of the compound 2, the aryl heterocyclic compound, cuprous iodide, phenanthroline, potassium carbonate and N, N-dimethylformamide is 1: (6-7): (0.4-0.6): (0.4-0.6): (4.5-5): (50-60);
when the compounds P1 and P3 are prepared, the molar ratio of the compound 2, the aryl compound containing the boric acid pinacol ester, the tetratriphenylphosphine palladium, the potassium carbonate, the toluene, the water and the ethanol is 1 (1-1.2) to 0.1-0.2 to 6-8): (200-250): (200-250): (60-80).
Preferably, in the step 1), the column chromatography is performed by taking a dichloromethane-n-hexane system as an eluent, wherein the volume ratio of dichloromethane to n-hexane is 1: 1;
in the step 2), the column chromatography separation is performed by taking a dichloromethane-n-hexane system as an eluent, wherein the volume ratio of dichloromethane to n-hexane is 1: 2;
in the step 3), when the compounds P2, P4 and P5 are prepared, a dichloromethane-n-hexane system is taken as an eluent for column chromatography, wherein the volume ratio of dichloromethane to n-hexane is 1: 1; in the preparation of compounds P1 and P3, the column chromatography was carried out using the dichloromethane-n-hexane system as eluent, wherein the volume ratio of dichloromethane to n-hexane was 2: 1.
The invention also discloses application of the perylene diimide shoulder position tetrasubstituted derivative in preparation of a photo-thermal agent.
Preferably, the photothermal agent is used for solar water purification, photothermal sterilization or tumor growth inhibition.
The invention also discloses application of the perylene diimide shoulder position tetrasubstituted derivative in preparation of a photosensitizer.
Preferably, the photosensitizer is used for photodynamic disinfection or inhibition of tumor growth.
Compared with the prior art, the invention has the following beneficial effects:
the invention discloses a perylene diimide shoulder position tetrasubstituted derivative, which constructs a conjugated molecular system formed by covalent connection of a plurality of electron donors and a single electron acceptor, wherein the strong electron coupling action between the electron donors and the electron acceptors leads to the widening of the light absorption range of the compound. The formed charge separation state returns to the ground state by two routes: firstly, the oxygen reaches a triplet state through intersystem crossing, and returns to a ground state after energy transfer with oxygen, and singlet oxygen is generated in the process; secondly, the energy returns to the ground state in the form of thermal energy release through a charge recombination process. The two excited state attenuation channels are the origin of the derivative with excellent active oxygen generation efficiency and photothermal conversion efficiency. Therefore, the derivative exhibits excellent singlet oxygen generation efficiency in a small polar solvent and in a thin film state. In addition, the derivative has high photo-thermal conversion capability in a monomer state and an aggregation state due to the strong absorption property in a visible light region.
The invention also discloses a synthesis method of the perylene diimide shoulder tetra-substituted derivative, and the preparation method is simple and convenient to operate and mild in reaction conditions.
The perylene diimide shoulder position tetrasubstituted derivative disclosed by the invention is high in active oxygen yield and remarkable in photothermal conversion effect, so that the perylene diimide shoulder position tetrasubstituted derivative is a photosensitizer with excellent performance and an organic micromolecule photothermal material, and is expected to be applied to the fields of solar water purification engineering and clinical photothermal/photodynamic tumor treatment.
Drawings
FIG. 1 is a high-resolution mass spectrum of a target compound P2a prepared by the invention;
FIG. 2 is a nuclear magnetic hydrogen spectrum of a target compound P2a prepared by the invention;
FIG. 3 is a nuclear magnetic carbon spectrum of a target compound P2a prepared by the invention;
FIG. 4 is a crystal structure diagram of a target compound P2a prepared by the present invention;
FIG. 5 is a diagram showing the absorption of the target compound P2a in solution;
FIG. 6 is a powder state absorption diagram of a target compound P2a prepared by the invention;
FIG. 7 is a reactive oxygen species monitoring graph of target compound P2 a;
FIG. 8 is a test chart of photothermal conversion of the target compound P2 a;
FIG. 9 is a graph of photothermal inhibition of tumor cell growth by the compound of interest P2 a.
Detailed Description
In order to make the technical solutions of the present invention better understood, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
It should be noted that the terms "first," "second," and the like in the description and claims of the present invention and in the drawings described above are used for distinguishing between similar elements and not necessarily for describing a particular sequential or chronological order. It is to be understood that the data so used is interchangeable under appropriate circumstances such that the embodiments of the invention described herein are capable of operation in other sequences than those illustrated or described herein. Moreover, the terms "comprises," "comprising," and "having," and any variations thereof, are intended to cover a non-exclusive inclusion, such that a process, method, system, article, or apparatus that comprises a list of steps or elements is not necessarily limited to those steps or elements expressly listed, but may include other steps or elements not expressly listed or inherent to such process, method, article, or apparatus.
The invention is described in further detail below with reference to the accompanying drawings:
example 1
Preparation of compound P2a (carbazole is used as electron donating group in this example, X is selected from C, n ═ 0)
1) Synthesis of Compound P2a-1
0.4g of perylenetetracarboxylic anhydride, 0.3g of 3-aminopentane, 0.14g of anhydrous zinc acetate and 4.0g of imidazole are sequentially added into a 50mL flask, heated until the imidazole is dissolved (130 ℃) under the protection of nitrogen atmosphere and stirred vigorously for 5 hours, the reaction solution is dissolved by 20mL of tetrahydrofuran after being cooled to room temperature, and then added into 300mL of a 2mol/L mixed solution of hydrochloric acid and methanol (the volume ratio is 2:1) to form a precipitate. Filtering, washing the filter cake with water and methanol in sequence, and drying the filter cake, wherein the weight ratio of dichloromethane: separating with column chromatography using n-hexane (volume ratio, 1:1) as eluent to obtain compound P2 a-1;
the reaction equation is as follows:
2) preparation of Compound P2a-2
0.15g of dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer, 1.37g of silver hexafluoroantimonate and 10mL of dichloroethane were charged into a 250mL Schlenk flask and stirred at room temperature for 30 minutes under argon. Then 2.65g of the compound P2a-1, 9.8g N-iodosuccinimide, 0.91g of copper acetate and 90mL of dichloroethane were added, and the bottle was sealed with a rubber stopper. The mixture was stirred at 80 ℃ for 120 hours. After the reaction solution was cooled to room temperature, an appropriate amount of dichloromethane was added, extraction was sequentially performed with a saturated sodium thiosulfate solution and a saturated common salt solution, and the organic layer was dried and concentrated under reduced pressure to obtain a reaction product of dichloromethane: separating with column chromatography using n-hexane (volume ratio, 1:2) as eluent to obtain compound P2 a-2;
the reaction equation is as follows:
3) preparation of the target Compound P2a
0.52g of the compound P2a-2, 0.50g of carbazole, 38mg of cuprous iodide, 35mg of phenanthroline, 0.3g of potassium carbonate and 3mL of N, N-dimethylformamide are added to a 25mL round-bottom flask, and the mixture is stirred and refluxed at 120 ℃ for 8 hours under the protection of argon atmosphere. After the reaction liquid is cooled to room temperature, the reaction liquid is poured into an ammonium chloride solution, filtered and the filter cake is washed by distilled water. The filter cake was dried, washed with dichloromethane: performing column chromatography with n-hexane (volume ratio, 1:1) as eluent to obtain target compound P2 a;
the reaction equation is as follows:
the results of the structural characterization data of the target compound P2a prepared by the method are shown in FIGS. 1-4.
Example 2
Production of target compound P3a (anthracene is used as electron donating group in this example, X is selected from C, n is 0)
1) Synthesis of Compound P3a-1
0.4g of perylenetetracarboxylic anhydride, 0.3g of 3-aminopentane, 0.14g of anhydrous zinc acetate and 4.0g of imidazole are sequentially added into a 50mL flask, heated until the imidazole is dissolved (130 ℃) under the protection of nitrogen atmosphere and stirred vigorously for 5 hours, the reaction solution is dissolved by 20mL of tetrahydrofuran after being cooled to room temperature, and then added into 300mL of a 2mol/L mixed solution of hydrochloric acid and methanol (the volume ratio is 2:1) to form a precipitate. Filtering, washing the filter cake with water and methanol in sequence, and drying the filter cake, wherein the weight ratio of dichloromethane: separating with column chromatography using n-hexane (volume ratio, 1:1) as eluent to obtain compound P3 a-1;
the reaction equation is as follows:
2) preparation of Compound P3a-2
0.15g of dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer, 1.37g of silver hexafluoroantimonate and 10mL of dichloroethane were charged into a 250mL Schlenk flask and stirred at room temperature for 30 minutes under argon. Then 2.65g of the compound P2a-1, 9.8g N-iodosuccinimide, 0.91g of copper acetate and 90mL of dichloroethane were added, and the bottle was sealed with a rubber stopper. The mixture was stirred at 80 ℃ for 120 hours. After the reaction solution was cooled to room temperature, an appropriate amount of dichloromethane was added, extraction was sequentially performed with a saturated sodium thiosulfate solution and a saturated common salt solution, and the organic layer was dried and concentrated under reduced pressure to obtain a reaction product of dichloromethane: separating with column chromatography using n-hexane (volume ratio, 1:2) as eluent to obtain compound P3 a-2;
the reaction equation is as follows:
5) preparation of the target product P3a
0.52g of the compound P3a-2, 0.18g of 9-anthraceneboronic acid pinacol ester, 58mg of tetratriphenylphosphine palladium, 0.42g of potassium carbonate, 15mL of toluene, 15mL of water and 5mL of ethanol are placed in a 100mL round-bottom flask and stirred under an argon atmosphere at 85 ℃ for 24 hours. After the reaction solution was cooled to room temperature, an appropriate amount of water was added, and after 3 times of extraction with dichloromethane, the solvent was removed under reduced pressure, and the reaction mixture was cooled to room temperature in the following ratio of dichloromethane: separating with n-hexane (volume ratio, 2:1) as eluent by column chromatography to obtain target compound P3 a;
the reaction equation is as follows:
example 3
Production of target Compound P5a (phenothiazine as an electron donating group in this example, and X is selected from C, n ═ 0)
1) Synthesis of Compound P5a-1
0.4g of perylenetetracarboxylic anhydride, 0.3g of 3-aminopentane, 0.14g of anhydrous zinc acetate and 4.0g of imidazole are sequentially added into a 50mL flask, heated until the imidazole is dissolved (130 ℃) under the protection of nitrogen atmosphere and stirred vigorously for 5 hours, the reaction solution is dissolved by 20mL of tetrahydrofuran after being cooled to room temperature, and then added into 300mL of a 2mol/L mixed solution of hydrochloric acid and methanol (the volume ratio is 2:1) to form a precipitate. Filtering, washing the filter cake with water and methanol in sequence, and drying the filter cake, wherein the weight ratio of dichloromethane: separating with column chromatography using n-hexane (volume ratio, 1:1) as eluent to obtain compound P5 a-1;
the reaction equation is as follows:
2) preparation of Compound P5a-2
0.15g of dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer, 1.37g of silver hexafluoroantimonate and 10mL of dichloroethane were charged into a 250mL Schlenk flask and stirred at room temperature for 30 minutes under argon. Then 2.65g of the compound P2a-1, 9.8g N-iodosuccinimide, 0.91g of copper acetate and 90mL of dichloroethane were added, and the bottle was sealed with a rubber stopper. The mixture was stirred at 80 ℃ for 120 hours. After the reaction solution was cooled to room temperature, an appropriate amount of dichloromethane was added, extraction was sequentially performed with a saturated sodium thiosulfate solution and a saturated common salt solution, and the organic layer was dried and concentrated under reduced pressure to obtain a reaction product of dichloromethane: separating with n-hexane (volume ratio, 1:2) as eluent by column chromatography to obtain compound P5 a-2;
the reaction equation is as follows:
3) preparation of the target Compound P5a
0.52g of compound P5a-2, 0.6g of phenothiazine, 38mg of cuprous iodide, 35mg of phenanthroline, 0.3g of potassium carbonate and 3mL of N, N-dimethylformamide are added to a 25mL round-bottomed flask, and the mixture is stirred and refluxed at 120 ℃ for 8 hours under an argon atmosphere. After the reaction liquid is cooled to room temperature, the reaction liquid is poured into an ammonium chloride solution, filtered and the filter cake is washed by distilled water. The filter cake was dried, washed with dichloromethane: performing column chromatography with n-hexane (volume ratio, 1:1) as eluent to obtain target compound P5 a;
the reaction equation is as follows:
example 4
Production of target compound P2b (in this example, carbazole is used as electron-donating group, and X is selected from C, n ═ 1)
1) Synthesis of Compound P2b-1
0.4g of perylenetetracarboxylic anhydride, 0.52g of 6-aminoundecane, 0.14g of anhydrous zinc acetate and 4.0g of imidazole are sequentially added into a 50mL flask, heated until the imidazole is dissolved (130 ℃) under the protection of nitrogen atmosphere and stirred vigorously for 5 hours, the reaction solution is dissolved by 16mL of tetrahydrofuran after being cooled to room temperature, and then added into 300mL of a mixed solution of 2mol/L hydrochloric acid and methanol (the volume ratio is 2:1) to form a precipitate. Filtering, washing the filter cake with water and methanol in sequence, and drying the filter cake, wherein the weight ratio of dichloromethane: separating with column chromatography using n-hexane (volume ratio, 1:1) as eluent to obtain compound P2 b-1;
the reaction equation is as follows:
2) preparation of Compound P2b-2
0.15g of dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer, 1.37g of silver hexafluoroantimonate and 10mL of dichloroethane were charged into a 250mL Schlenk flask and stirred at room temperature for 30 minutes under argon. Then 3.5g of compound P2b-1, 9.8g N-iodosuccinimide, 0.91g of copper acetate and 90mL of dichloroethane were added, and the bottle was sealed with a rubber stopper. The mixture was stirred at 80 ℃ for 120 hours. After the reaction solution was cooled to room temperature, an appropriate amount of dichloromethane was added, extraction was performed with a saturated sodium thiosulfate solution and a saturated brine in this order, and the organic layer was dried and concentrated under reduced pressure, and the reaction mixture was cooled to room temperature using dichloromethane: separating with column chromatography using n-hexane (volume ratio, 1:2) as eluent to obtain compound P2 b-2;
the reaction equation is as follows:
3) preparation of the target Compound P2b
0.7g of the compound P2b-2, 0.5g of carbazole, 38mg of cuprous iodide, 35mg of phenanthroline, 0.30g of potassium carbonate and 3mL of N, N-dimethylformamide are added to a 25mL round-bottom flask, and the mixture is stirred and refluxed at 120 ℃ for 8 hours under the protection of argon atmosphere. After the reaction liquid is cooled to room temperature, the reaction liquid is poured into an ammonium chloride solution, filtered and the filter cake is washed by distilled water. The filter cake was dried, washed with dichloromethane: performing column chromatography with n-hexane (volume ratio, 1:1) as eluent to obtain target compound P2 b;
the reaction equation is as follows:
example 5
Production of target compound P2C (in this example, carbazole is used as electron-donating group, and X is selected from C, n ═ 2)
1) Synthesis of Compound P2c-1
0.4g of perylenetetracarboxylic anhydride, 0.77g of 9-aminoheptadecane, 0.14g of anhydrous zinc acetate and 4.0g of imidazole are sequentially added into a 50mL flask, heated until the imidazole is dissolved (130 ℃) under the protection of nitrogen atmosphere and stirred vigorously for 5 hours, the reaction solution is dissolved by 12mL of tetrahydrofuran after being cooled to room temperature, and then added into 300mL of a mixed solution of 2mol/L hydrochloric acid and methanol (the volume ratio is 2:1) to form a precipitate. Filtering, washing the filter cake with water and methanol in sequence, and drying the filter cake, wherein the weight ratio of dichloromethane to methanol is as follows: separating with column chromatography using n-hexane (volume ratio, 1:1) as eluent to obtain compound P2 c-1;
the reaction equation is as follows:
2) preparation of Compound P2c-2
0.15g of dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer, 1.37g of silver hexafluoroantimonate and 10mL of dichloroethane were charged into a 250mL Schlenk flask and stirred at room temperature for 30 minutes under argon. Then 3.5g of the compound P2c-1, 9.8g N-iodosuccinimide, 0.91g of copper acetate and 90mL of dichloroethane were added, and the bottle was sealed with a rubber stopper. The mixture was stirred at 80 ℃ for 120 hours. After the reaction solution was cooled to room temperature, an appropriate amount of dichloromethane was added, extraction was sequentially performed with a saturated sodium thiosulfate solution and a saturated common salt solution, and the organic layer was dried and concentrated under reduced pressure to obtain a reaction product of dichloromethane: separating with column chromatography using n-hexane (volume ratio, 1:2) as eluent to obtain compound P2 c-2;
the reaction equation is as follows:
3) preparation of the target Compound P2c
0.85g of the compound P2c-2, 0.5g of carbazole, 38mg of cuprous iodide, 35mg of phenanthroline, 0.30g of potassium carbonate and 3mL of N, N-dimethylformamide are added to a 25mL round-bottom flask, and the mixture is stirred and refluxed at 120 ℃ for 8 hours under the protection of argon atmosphere. After the reaction liquid is cooled to room temperature, the reaction liquid is poured into an ammonium chloride solution, filtered and the filter cake is washed by distilled water. The filter cake was dried, washed with dichloromethane: separating with n-hexane (volume ratio, 1:1) as eluent by column chromatography to obtain target compound P2 c;
the reaction equation is as follows:
example 6
Active oxygen generation efficiency determination based on perylene diimide shoulder tetra-substituted derivative
1) Taking perylene diimide shoulder tetra-substituted derivative P2a, adding toluene solvent to prepare the solution with the concentration of 7.5 multiplied by 10-6～2×10-5Adding a solution of a mol/L perylene diimide shoulder tetra-substituted derivative P2a into the solution, and adding a singlet oxygen scavenger 1, 3-diphenyl isobenzofuran (DPBF) to ensure that the concentration of the solution is 7.5 multiplied by 10-5～1×10-4mol/L. Standing the solution in dark place, and storing under sealed condition for no more than 3 days;
2) taking 3mL of the perylene diimide shouldered tetra-substituted derivative P2a solution prepared in the step 1) to be placed in a quartz cuvette with the optical path width of 1cm, irradiating the cuvette for 1 minute by using laser with the wavelength of 520nm and constant power, and recording the change of the absorbance.
3) The rose bengal is selected as a standard reference substance, the same operation as that of the solution of the perylene diimide shouldered tetra-substituted derivative P2a is carried out, the change of the absorbance is recorded and the two are compared.
Example 7
Active oxygen generation efficiency determination based on perylene diimide shoulder tetra-substituted derivative
1) Taking perylene diimide shoulder tetra-substituted derivative P2a, adding dichloromethane solvent to prepare the solution with the concentration of 7.5 multiplied by 10-6～2×10-5Adding a solution of a mol/L perylene diimide shoulder tetra-substituted derivative P2a into the solution, and adding a singlet oxygen scavenger 1, 3-diphenyl isobenzofuran (DPBF) to ensure that the concentration of the solution is 7.5 multiplied by 10-5～1×10-4mol/L. Standing the solution in dark place, and storing under sealed condition for no more than 3 days;
2) taking 3mL of the perylene diimide shouldered tetra-substituted derivative P2a solution prepared in the step 1) to be placed in a quartz cuvette with the optical path width of 1cm, irradiating the cuvette for 1 minute by using laser with the wavelength of 520nm and constant power, and recording the change of the absorbance.
3) The rose bengal is selected as a standard reference substance, the same operation as that of the solution of the perylene diimide shouldered tetra-substituted derivative P2a is carried out, the change of the absorbance is recorded and the two are compared.
Example 8
Photo-thermal conversion efficiency determination method based on perylene diimide shoulder tetra-substituted derivative
1) Weighing 5mg of perylene diimide shouldered tetra-substituted derivative P2a in a watch glass, adjusting the position of a sample to align to laser, and adjusting the laser power to be 1W/cm2Recording a temperature rise and temperature reduction curve of the surface of the sample after the laser irradiation is carried out for 90 seconds and the laser is turned off by the thermal imager;
2) repeating the step 1) for five times and recording a temperature rising and reducing curve.
Example 9
Photo-thermal sterilization experiment based on perylene diimide shoulder tetra-substituted derivative
Centrifuging the enriched bacteria at 8000r/min, pouring out the culture medium, adding 5mL of 0.9% NaCl solution for dispersion, centrifuging again, repeating for 3 times to wash off excessive cultureAnd (5) culturing, and finally dispersing into 0.9% NaCl solution to obtain a primary bacterial liquid. Diluting the original bacterial liquid with 0.9% NaCl to working concentration of 2X 109And (3) preparing CFU/mL for later use, adding 10 mu L of bacterial liquid and 10 mu L of perylene diimide shouldered tetrasubstituted derivative DMSO solutions with different concentrations into a centrifugal tube, adding 0.9% NaCl to complement 1mL, incubating for 10min to ensure that the perylene diimide shouldered tetrasubstituted derivative DMSO solution is fully contacted with bacteria, irradiating the experimental groups for 2min and 4min by using laser respectively, not applying laser to the control group, and reading the bacterial death rate after the polymer treatment under different concentrations.
In order to verify the effect of the present invention, a large number of laboratory research experiments were conducted on the perylene diimide shouldered tetra-substituted derivative P2a synthesized in example 1, and the experimental conditions were as follows:
1. basic optical behavior characterization
The absorption of the perylene diimide shouldered tetra-substituted derivative P2a in chloroform and solid powder was characterized using hiti U-3900/3900H uv-vis spectrophotometer and us Perkin-Elmer lamb 1050 uv-vis near-infrared spectrophotometer, respectively, and the results are shown in fig. 5 and fig. 6. As can be seen from fig. 5 and 6, the compound has a greatly widened light absorption range in the solution state and the solid state due to the extremely strong electron coupling effect between the electron donor and the electron acceptor, and substantially achieves full coverage of the ultraviolet visible region. We selected the maximum absorption wavelength of 520nm for the active oxygen productivity determination experiment. In consideration of the fact that the biological tissue penetration capability of long-wavelength laser is stronger, 630nm is selected as an excitation light source to perform photothermal conversion related experiments.
2. Active oxygen generation assay
In the active oxygen yield determination experiment, the characteristic absorption of the singlet oxygen scavenger DPBF at 414nm is continuously reduced along with the increase of the illumination time, and the relevant test result is shown in FIG. 6. Test results show that the perylene diimide shoulder position tetrasubstituted derivative can efficiently generate active oxygen under the irradiation of 520nm laser.
3. Photothermal conversion experiment
The perylene diimide shoulder tetra-substituted derivative solid powder is rapidly heated up under 630nm laser irradiation, the temperature is raised to 70 ℃ within 90 seconds, through five-cycle experiments, the photothermal conversion performance of the material is not faded, and related test results are shown in fig. 8. The result shows that the material has excellent photo-thermal stability, and lays a foundation for further exploring photo-thermal related applications in the later period.
4. Photothermal sterilization experiment
Fig. 9 is a statistical graph of the survival rate of bacteria under the conditions of light addition and no light addition in the presence of perylene diimide shouldered tetrasubstituted derivatives with different concentrations, and the results show that the bacteria growth inhibition effect can be achieved under the presence of the perylene diimide shouldered tetrasubstituted derivatives, and the bacteria are expected to be used for clinical photothermal treatment of cancer at a later stage.
In conclusion, the perylene diimide shoulder position tetrasubstituted derivative disclosed by the invention constructs a conjugated molecular system formed by covalently connecting a plurality of electron donors and a single electron acceptor, and the extremely strong electron coupling effect between the electron donors and the electron acceptors leads to the broadening of the light absorption range of the compound. The derivative shows excellent singlet oxygen generation efficiency in a small polar solvent and in a thin film state. In addition, the derivative has high photo-thermal conversion capability in a monomer state and an aggregation state due to the strong absorption property in a visible light region. The research shows that the strong electron coupling effect between the perylene diimide and the electron-donating substituent causes the derivative to be easy to form a non-luminous charge separation state under the photoexcitation condition. The formed charge separation state returns to the ground state by two routes: firstly, the oxygen reaches a triplet state through intersystem crossing, and returns to a ground state after energy transfer with oxygen, and singlet oxygen is generated in the process; secondly, it returns to the ground state in the form of thermal energy release through a charge recombination process. The two excited state attenuation channels (the strong electron coupling action between an electron donor and an electron acceptor leads the light absorption range of the compound to be widened, and meanwhile, a charge separation state formed under the photoexcitation condition can reach a triplet state through intersystem crossing or return to a ground state in a non-radiative transition mode) are the origin of the derivative with excellent active oxygen generation efficiency and photothermal conversion efficiency. The derivative has high active oxygen yield and remarkable photo-thermal conversion effect, is a photosensitizer with excellent performance and an organic micromolecule photo-thermal material, and is expected to be applied to the fields of solar water purification engineering and clinical photo-thermal/photodynamic tumor treatment.
The above-mentioned contents are only for illustrating the technical idea of the present invention, and the protection scope of the present invention is not limited thereby, and any modification made on the basis of the technical idea of the present invention falls within the protection scope of the claims of the present invention.
Claims (8)
1. A perylene diimide shoulder position tetrasubstituted derivative is characterized in that the structural formula is as follows:
wherein X is selected from C or O; n is 0 to 3; r is1、R2、R3、R4Each independently selected from electron donating groups;
the electron donating group has the following structure:
and the position of the bond of the substituent group is represented.
2. The perylene diimide shouldered tetra-substituted derivative according to claim 1, wherein the perylene diimide shouldered tetra-substituted derivative specifically comprises a compound having the following structure:
in compounds P1, P2, P3, P4 and P5, X is selected from C, O; n is 0 to 3.
3. The method for preparing the perylene diimide shouldered tetrasubstituted derivative according to claim 2, comprising the steps of:
1) preparation of Compound 1
Mixing reactants including perylene tetracarboxylic anhydride, amine, anhydrous zinc acetate and imidazole, heating until the imidazole is dissolved and fully stirring for reaction for 5-8 hours under the protection of inert atmosphere, dissolving by using tetrahydrofuran after the reaction liquid is cooled to room temperature, adding the reaction system into a mixed solution of hydrochloric acid and methanol to form a precipitate, filtering and collecting the precipitate, cleaning, drying a filter cake, and performing column chromatography separation to obtain a compound 1;
wherein the structural formula of the compound 1 is as follows:
wherein X is selected from C, O; n is 0 to 3;
2) preparation of Compound 2
Mixing dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer, silver hexafluoroantimonate and dichloroethane, stirring and reacting at room temperature for 0.5-1 hour under the protection of inert atmosphere, then adding a compound 1, N-iodosuccinimide, copper acetate and dichloroethane, sealing, stirring and reacting at 80-100 ℃ for 120-135 hours, adding dichloromethane after the reaction liquid is cooled to room temperature, extracting by using saturated sodium thiosulfate solution and saturated saline solution in sequence, drying an organic layer, concentrating under reduced pressure, and separating by column chromatography to obtain a compound 2;
wherein the structural formula of the compound 2 is as follows:
wherein X is selected from C, O; n is 0 to 3;
3) preparation of the target compounds P1, P2, P3, P4 and P5
Mixing the compound 2, an aryl heterocyclic compound, cuprous iodide, phenanthroline, potassium carbonate and N, N-dimethylformamide, stirring and refluxing for 8-10 hours under the protection of inert atmosphere, cooling the reaction liquid to room temperature, pouring into an ammonium chloride solution, filtering, cleaning a filter cake with distilled water, drying the filter cake, and performing column chromatography to obtain target products P2, P4 and P5;
or,
mixing the compound 2, an aryl compound containing boric acid pinacol ester, tetratriphenylphosphine palladium, potassium carbonate, toluene, water and ethanol, heating to 80-90 ℃ under the protection of inert atmosphere, stirring and reacting for 20-24 hours, adding water after the reaction liquid is cooled to room temperature, extracting with dichloromethane, decompressing and removing the solvent, and performing column chromatography separation to obtain target products P1 and P3;
in the step 1), the molar ratio of the perylene tetracarboxylic anhydride to the corresponding amine to the zinc acetate to the imidazole is 1: (3-4): (0.7-0.9): (250-300), the concentration of the used hydrochloric acid is 2mol/L, and the ratio of the hydrochloric acid to the methanol in the mixed solution of the hydrochloric acid and the methanol is 2:1 volume is mixed;
in step 2), the molar ratio of the compound 1, dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer, silver hexafluoroantimonate, N-iodosuccinimide, copper acetate and dichloroethane is 1: (0.1-0.2): (0.8-1): (160-200): (1-1.1): (500-600);
in the step 3), when the compounds P2, P4 and P5 are prepared, the molar ratio of the compound 2, the aryl heterocyclic compound, cuprous iodide, phenanthroline, potassium carbonate and N, N-dimethylformamide is 1: (6-7): (0.4-0.6): (0.4-0.6): (4.5-5): (50-60);
when the compounds P1 and P3 are prepared, the molar ratio of the compound 2, the aryl compound containing the boric acid pinacol ester, the tetratriphenylphosphine palladium, the potassium carbonate, the toluene, the water and the ethanol is 1 (1-1.2) to 0.1-0.2 to 6-8): (200-250): (200-250): (60-80).
4. The preparation method of the perylene diimide derivatives substituted on the shoulder four as described in claim 3, wherein in the step 1), the column chromatography is performed by using dichloromethane-n-hexane system as eluent, wherein the volume ratio of dichloromethane to n-hexane is 1: 1;
in the step 2), the column chromatography separation is performed by taking a dichloromethane-n-hexane system as an eluent, wherein the volume ratio of dichloromethane to n-hexane is 1: 2;
in the step 3), when preparing the compounds P2, P4 and P5, performing column chromatography by taking a dichloromethane-n-hexane system as an eluent, wherein the volume ratio of dichloromethane to n-hexane is 1: 1; in the preparation of compounds P1 and P3, the column chromatography was carried out using the dichloromethane-n-hexane system as eluent, wherein the volume ratio of dichloromethane to n-hexane was 2: 1.
5. Use of the perylene diimide shouldered tetrasubstituted derivative according to claim 1 or 2 for the preparation of a photothermal agent for solar water purification.
6. The use of the perylene diimide derivatives substituted on the shoulder four as defined in claim 1 or 2 for preparing photo-thermal fungicides.
7. The use of the perylene diimide shouldered tetrasubstituted derivative according to claim 1 or 2 in the preparation of a medicament for inhibiting tumor growth.
8. The use of the perylene diimide shouldered tetrasubstituted derivative according to claim 1 or 2 in the preparation of a photosensitizer for photodynamic disinfection.
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