CN103342790A - Preparation method for in-situ synthesis of phthalocyanine polymer - Google Patents
Preparation method for in-situ synthesis of phthalocyanine polymer Download PDFInfo
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- CN103342790A CN103342790A CN2013102526110A CN201310252611A CN103342790A CN 103342790 A CN103342790 A CN 103342790A CN 2013102526110 A CN2013102526110 A CN 2013102526110A CN 201310252611 A CN201310252611 A CN 201310252611A CN 103342790 A CN103342790 A CN 103342790A
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- phthalocyanine
- macromole
- preparation
- polymer
- original position
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- IEQIEDJGQAUEQZ-UHFFFAOYSA-N phthalocyanine Chemical compound N1C(N=C2C3=CC=CC=C3C(N=C3C4=CC=CC=C4C(=N4)N3)=N2)=C(C=CC=C2)C2=C1N=C1C2=CC=CC=C2C4=N1 IEQIEDJGQAUEQZ-UHFFFAOYSA-N 0.000 title claims abstract description 26
- 229920000642 polymer Polymers 0.000 title claims abstract description 18
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 6
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 5
- 238000011065 in-situ storage Methods 0.000 title abstract 3
- 238000000034 method Methods 0.000 claims abstract description 12
- 238000006116 polymerization reaction Methods 0.000 claims abstract description 8
- 230000002441 reversible effect Effects 0.000 claims abstract description 5
- 238000012546 transfer Methods 0.000 claims abstract description 4
- 239000000126 substance Substances 0.000 claims description 11
- 239000003153 chemical reaction reagent Substances 0.000 claims description 9
- 239000003999 initiator Substances 0.000 claims description 9
- 239000000178 monomer Substances 0.000 claims description 9
- 150000003254 radicals Chemical class 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 6
- 238000010189 synthetic method Methods 0.000 claims description 4
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 claims description 3
- ZLYSPLLEHZXBSX-UHFFFAOYSA-N 4-octoxybenzene-1,2-dicarbonitrile Chemical compound CCCCCCCCOC1=CC=C(C#N)C(C#N)=C1 ZLYSPLLEHZXBSX-UHFFFAOYSA-N 0.000 claims description 3
- FCMCSZXRVWDVAW-UHFFFAOYSA-N 6-bromo-1-hexanol Chemical compound OCCCCCCBr FCMCSZXRVWDVAW-UHFFFAOYSA-N 0.000 claims description 3
- OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 claims description 3
- -1 dithio naphthoic acid isopropyl cyanide ester Chemical class 0.000 claims description 3
- 238000006266 etherification reaction Methods 0.000 claims description 3
- VHRYZQNGTZXDNX-UHFFFAOYSA-N methacryloyl chloride Chemical compound CC(=C)C(Cl)=O VHRYZQNGTZXDNX-UHFFFAOYSA-N 0.000 claims description 3
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical group CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 claims description 3
- 238000010526 radical polymerization reaction Methods 0.000 claims description 3
- BEAZKUGSCHFXIQ-UHFFFAOYSA-L zinc;diacetate;dihydrate Chemical compound O.O.[Zn+2].CC([O-])=O.CC([O-])=O BEAZKUGSCHFXIQ-UHFFFAOYSA-L 0.000 claims description 3
- 239000003504 photosensitizing agent Substances 0.000 abstract description 11
- 238000006862 quantum yield reaction Methods 0.000 abstract description 6
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 abstract description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 4
- 229910052725 zinc Inorganic materials 0.000 abstract description 4
- 239000011701 zinc Substances 0.000 abstract description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 abstract description 3
- 229940098773 bovine serum albumin Drugs 0.000 abstract description 3
- 238000002428 photodynamic therapy Methods 0.000 abstract description 2
- 239000007853 buffer solution Substances 0.000 abstract 2
- 238000001308 synthesis method Methods 0.000 abstract 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 abstract 1
- 238000013467 fragmentation Methods 0.000 abstract 1
- 238000006062 fragmentation reaction Methods 0.000 abstract 1
- 238000013016 damping Methods 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 150000003384 small molecules Chemical class 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- BUMGIEFFCMBQDG-UHFFFAOYSA-N dichlorosilicon Chemical compound Cl[Si]Cl BUMGIEFFCMBQDG-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000010559 graft polymerization reaction Methods 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000012925 reference material Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
The invention discloses a preparation method of in-situ synthesis phthalocyanine polymer, which comprises the steps of firstly preparing a water-soluble macromolecular polymer with functional side chains by using a reversible addition-fragmentation chain transfer (RAFT) polymerization method, and then preparing a macromolecular photosensitizer zinc phthalocyanine polymer for photodynamic therapy by using the in-situ synthesis method. The synthesis method is simple and low in cost, can improve the water solubility of the photosensitizer carrier, has good stability in PBS buffer solution and bovine serum albumin buffer solution PBS-BSA, and has good singlet oxygen quantum yield as the photosensitizer carrier.
Description
Technical field
The invention belongs to chemical synthesis process, that be specifically related to is a kind of preparation method of original position synthetic phthalocyanine polymkeric substance.
Background technology
The polymer support of at present relevant optical dynamic therapy mostly uses the method for physical load photosensitizers.The similar prior art of utilizing chemical bond for before our patent of invention " the photodynamic therapy polymer support design of multiple Targeting Performance is synthetic ", what macromolecule medicament carrier adopted in the patent is the method for small molecules and high polymer graft polymerization, we at first use reversible addition fracture to connect the polymkeric substance that the method that shifts (RAFT) polymerization has prepared water-soluble temperature sensitive property, then the small molecules photosensitizers is grafted to and has prepared the temperature sensitive water-soluble photosensitizers phthalocyanine polymer of macromole on the polymkeric substance, the weak point of this method is: on the one hand, phthalocyanine silicon dichloride as general two generation the small molecules photosensitizers, its solvability is relatively poor; On the other hand, the purchase cost of small molecules photosensitizers is higher, causes the cost of integral experiment research higher.
Summary of the invention
The objective of the invention is to overcome the above problem that prior art exists, a kind of preparation method of original position synthetic phthalocyanine polymkeric substance is provided, improve the water-soluble of photosensitizers carrier.
For realizing above-mentioned technical purpose, reach above-mentioned technique effect, the present invention is achieved through the following technical solutions:
A kind of preparation method of original position synthetic phthalocyanine polymkeric substance may further comprise the steps:
Step 1) adopts compound
Obtain compound through the etherificate with 6-bromo-1-hexanol
Step 2) obtains monomer through the etherification reaction with methacrylic chloride
Step 3) adopts the method for reversible addition fracture transfer polymerization to carry out active free radical polymerization to prepare aggressiveness before the macromole
, the preceding aggressiveness of described macromole
M nBe 44800 g/mol, molecular weight distribution is 1.3;
Step 4) and 4-(octyloxy) phthalonitrile, Zinc diacetate dihydrate use the synthetic method of original position to prepare the macromole phthalocyanine polymer under the katalysis of DBU, and the phthalocyanine content of described macromole phthalocyanine polymer is 9.2wt%;
The synthesis technique reaction formula of step (1), (2), (3), (4) is:
Further, polymerization system comprises monomer, RAFT reagent, radical initiator; Described monomer is MAHE and PEG
475Described RAFT reagent is dithio naphthoic acid isopropyl cyanide ester (CPDN); Described radical initiator is Diisopropyl azodicarboxylate (AIBN), wherein, and in molar ratio, [MAHE]
0: [PEG
475]
0: [RAFT reagent]
0: [radical initiator]
0=25:100:1:0.5.
The invention has the beneficial effects as follows:
Synthetic method of the present invention is simple and cost is low, can improve simultaneously the water dissolution performance of photosensitizers carrier, it has good stability in PBS damping fluid and bovine serum albumin damping fluid PBS-BSA simultaneously, the most important thing is, as the photosensitive drug carrier, it has good single line oxygen quantum yield.
Description of drawings
Fig. 1 is the stability test figure of water soluble metal phthalocyanine polymkeric substance in PBS and PBS-BSA buffered soln;
Fig. 2 is the singlet quantum yield test pattern of water-soluble zinc phthalocyanine polymer.
Embodiment
Below with reference to the accompanying drawings and in conjunction with the embodiments, describe the present invention in detail.
A kind of preparation method of original position synthetic phthalocyanine polymkeric substance may further comprise the steps:
Step 1) adopts compound
Obtain compound through the etherificate with 6-bromo-1-hexanol
Step 2) obtains monomer through the etherification reaction with methacrylic chloride
Step 3) adopts the method for reversible addition fracture transfer polymerization to carry out active free radical polymerization to prepare aggressiveness before the macromole
, the preceding aggressiveness of described macromole
M nBe 44800 g/mol, molecular weight distribution is 1.3;
Step 4) and 4-(octyloxy) phthalonitrile, Zinc diacetate dihydrate use the synthetic method of original position to prepare the macromole phthalocyanine polymer under the katalysis of DBU, and the phthalocyanine content of described macromole phthalocyanine polymer is 9.2wt%;
The synthesis technique reaction formula of step (1), (2), (3), (4) is:
Further, polymerization system comprises monomer, RAFT reagent, radical initiator; Described monomer is MAHE and PEG
475Described RAFT reagent is dithio naphthoic acid isopropyl cyanide ester (CPDN); Described radical initiator is Diisopropyl azodicarboxylate (AIBN), wherein, and in molar ratio, [MAHE]
0: [PEG
475]
0: [RAFT reagent]
0: [radical initiator]
0=25:100:1:0.5.
With reference to Fig. 1, shown in Figure 2, described macromole phthalocyanine polymer photosensitizers, good water solubility, simultaneously its content at PBS damping fluid and bovine serum albumin damping fluid PBS-BSA(BSA is 0.05 wt%) in have good stability.The most important thing is that as the photosensitive drug carrier, it has good single line oxygen quantum yield, the singlet quantum yield of reference material zinc phthalocyanine ZnPc in the document
Φ (Δ)=0.56, the singlet quantum yield of the zinc phthalocyanine polymer ZnPc-Polymer of preparation is
Φ (Δ)=0.49.
Claims (2)
1. the preparation method of an original position synthetic phthalocyanine polymkeric substance is characterized in that, may further comprise the steps:
Step 1) adopts compound
Obtain compound through the etherificate with 6-bromo-1-hexanol
Step 2) obtains monomer through the etherification reaction with methacrylic chloride
Step 3) adopts the method for reversible addition fracture transfer polymerization to carry out active free radical polymerization to prepare aggressiveness before the macromole
, the preceding aggressiveness of described macromole
M nBe 44800 g/mol, molecular weight distribution is 1.3;
Step 4) and 4-(octyloxy) phthalonitrile, Zinc diacetate dihydrate use the synthetic method of original position to prepare the macromole phthalocyanine polymer under the katalysis of DBU, and the phthalocyanine content of described macromole phthalocyanine polymer is 9.2wt%;
The synthesis technique reaction formula of step (1), (2), (3), (4) is:
2. the preparation method of original position synthetic phthalocyanine polymkeric substance according to claim 1, it is characterized in that: polymerization system comprises monomer, RAFT reagent, radical initiator; Described monomer is MAHE and PEG
475Described RAFT reagent is dithio naphthoic acid isopropyl cyanide ester (CPDN); Described radical initiator is Diisopropyl azodicarboxylate (AIBN), wherein, and in molar ratio, [MAHE]
0: [PEG
475]
0: [RAFT reagent]
0: [radical initiator]
0=25:100:1:0.5.
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| CN103342790A true CN103342790A (en) | 2013-10-09 |
| CN103342790B CN103342790B (en) | 2015-11-18 |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109704989A (en) * | 2019-01-24 | 2019-05-03 | 大连理工大学 | A kind of synthetic method of O-phthalic nitrilic type acrylic ester monomer |
| CN110317291A (en) * | 2018-03-30 | 2019-10-11 | 长春理工大学 | Phthalocyanine high molecular polymer and its synthetic method containing aphthopyrans |
| WO2020150969A1 (en) * | 2019-01-24 | 2020-07-30 | 大连理工大学 | Diallyl phtalate monomer synthesis method |
| CN111875736A (en) * | 2020-07-29 | 2020-11-03 | 苏州大学 | Active free radical polymerization method using phthalocyanine zinc dye as near infrared light catalyst |
| WO2024080925A3 (en) * | 2022-10-10 | 2024-05-30 | Nanyang Technological University | Method of precision 3d printed glassy carbon |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101985352A (en) * | 2010-12-07 | 2011-03-16 | 电子科技大学 | Method for preparing multi-walled carbon nanotubes from phthalocyanine iron polymer by high temperature solid-phase cracking |
-
2013
- 2013-06-24 CN CN201310252611.0A patent/CN103342790B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101985352A (en) * | 2010-12-07 | 2011-03-16 | 电子科技大学 | Method for preparing multi-walled carbon nanotubes from phthalocyanine iron polymer by high temperature solid-phase cracking |
Non-Patent Citations (1)
| Title |
|---|
| 刘宏等: "芳氧基取代酞菁锌的合成及光物理化学性质", 《无机化学学报》, vol. 29, no. 3, 31 March 2013 (2013-03-31), pages 486 - 492 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110317291A (en) * | 2018-03-30 | 2019-10-11 | 长春理工大学 | Phthalocyanine high molecular polymer and its synthetic method containing aphthopyrans |
| CN110317291B (en) * | 2018-03-30 | 2021-06-08 | 长春理工大学 | Phthalocyanine high molecular polymer containing naphthopyran and its synthesis method |
| CN109704989A (en) * | 2019-01-24 | 2019-05-03 | 大连理工大学 | A kind of synthetic method of O-phthalic nitrilic type acrylic ester monomer |
| WO2020150969A1 (en) * | 2019-01-24 | 2020-07-30 | 大连理工大学 | Diallyl phtalate monomer synthesis method |
| CN111875736A (en) * | 2020-07-29 | 2020-11-03 | 苏州大学 | Active free radical polymerization method using phthalocyanine zinc dye as near infrared light catalyst |
| CN111875736B (en) * | 2020-07-29 | 2021-05-04 | 苏州大学 | Active free radical polymerization method using phthalocyanine zinc dye as near infrared light catalyst |
| WO2024080925A3 (en) * | 2022-10-10 | 2024-05-30 | Nanyang Technological University | Method of precision 3d printed glassy carbon |
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| CN103342790B (en) | 2015-11-18 |
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Granted publication date: 20151118 Termination date: 20180624 |