CN118344605A - Method for rapidly preparing polyrotaxane based on shaking induction - Google Patents
Method for rapidly preparing polyrotaxane based on shaking induction Download PDFInfo
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- CN118344605A CN118344605A CN202410509678.6A CN202410509678A CN118344605A CN 118344605 A CN118344605 A CN 118344605A CN 202410509678 A CN202410509678 A CN 202410509678A CN 118344605 A CN118344605 A CN 118344605A
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- polyethylene glycol
- cyclodextrin
- polyrotaxane
- block polymer
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- 238000000034 method Methods 0.000 title claims abstract description 22
- 230000006698 induction Effects 0.000 title claims abstract description 7
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 118
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 claims abstract description 94
- 229960003180 glutathione Drugs 0.000 claims abstract description 60
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 59
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 54
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims abstract description 38
- 239000011780 sodium chloride Substances 0.000 claims abstract description 27
- 229920000642 polymer Polymers 0.000 claims abstract description 26
- 108010024636 Glutathione Proteins 0.000 claims abstract description 24
- 238000006243 chemical reaction Methods 0.000 claims abstract description 19
- 229920000858 Cyclodextrin Polymers 0.000 claims abstract description 18
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000007864 aqueous solution Substances 0.000 claims abstract description 10
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims abstract description 6
- GJKGAPPUXSSCFI-UHFFFAOYSA-N 2-Hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone Chemical compound CC(C)(O)C(=O)C1=CC=C(OCCO)C=C1 GJKGAPPUXSSCFI-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 3
- HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 claims description 11
- 229920001450 Alpha-Cyclodextrin Polymers 0.000 claims description 7
- 229940043377 alpha-cyclodextrin Drugs 0.000 claims description 7
- GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 claims description 4
- 239000001116 FEMA 4028 Substances 0.000 claims description 3
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 claims description 3
- 235000011175 beta-cyclodextrine Nutrition 0.000 claims description 3
- 229960004853 betadex Drugs 0.000 claims description 3
- 229940080345 gamma-cyclodextrin Drugs 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 239000000203 mixture Substances 0.000 abstract description 16
- 238000002360 preparation method Methods 0.000 abstract description 8
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 230000001988 toxicity Effects 0.000 abstract 1
- 231100000419 toxicity Toxicity 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 35
- 239000000047 product Substances 0.000 description 27
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 26
- 238000005481 NMR spectroscopy Methods 0.000 description 25
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 23
- 239000000843 powder Substances 0.000 description 23
- 238000012512 characterization method Methods 0.000 description 17
- 230000015572 biosynthetic process Effects 0.000 description 16
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 16
- 238000005160 1H NMR spectroscopy Methods 0.000 description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 15
- 230000008878 coupling Effects 0.000 description 15
- 238000010168 coupling process Methods 0.000 description 15
- 238000005859 coupling reaction Methods 0.000 description 15
- 239000008367 deionised water Substances 0.000 description 15
- 229910021641 deionized water Inorganic materials 0.000 description 15
- 229910052739 hydrogen Inorganic materials 0.000 description 15
- 239000001257 hydrogen Substances 0.000 description 15
- 230000010354 integration Effects 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- 239000000126 substance Substances 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 14
- 239000012043 crude product Substances 0.000 description 14
- 238000002441 X-ray diffraction Methods 0.000 description 13
- 239000012467 final product Substances 0.000 description 13
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 10
- 239000012535 impurity Substances 0.000 description 8
- 238000000967 suction filtration Methods 0.000 description 8
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 7
- 240000001414 Eucalyptus viminalis Species 0.000 description 7
- 125000000304 alkynyl group Chemical group 0.000 description 7
- 238000003776 cleavage reaction Methods 0.000 description 7
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 239000005457 ice water Substances 0.000 description 7
- 239000012299 nitrogen atmosphere Substances 0.000 description 7
- JFNLZVQOOSMTJK-KNVOCYPGSA-N norbornene Chemical compound C1[C@@H]2CC[C@H]1C=C2 JFNLZVQOOSMTJK-KNVOCYPGSA-N 0.000 description 7
- 238000002390 rotary evaporation Methods 0.000 description 7
- 230000007017 scission Effects 0.000 description 7
- -1 2-hydroxyethoxy Chemical group 0.000 description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 238000002329 infrared spectrum Methods 0.000 description 5
- FYGUSUBEMUKACF-UHFFFAOYSA-N bicyclo[2.2.1]hept-2-ene-5-carboxylic acid Chemical compound C1C2C(C(=O)O)CC1C=C2 FYGUSUBEMUKACF-UHFFFAOYSA-N 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- HVAMZGADVCBITI-UHFFFAOYSA-N pent-4-enoic acid Chemical compound OC(=O)CCC=C HVAMZGADVCBITI-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- YWAKXRMUMFPDSH-UHFFFAOYSA-N pentene Chemical compound CCCC=C YWAKXRMUMFPDSH-UHFFFAOYSA-N 0.000 description 2
- JKANAVGODYYCQF-UHFFFAOYSA-N prop-2-yn-1-amine Chemical compound NCC#C JKANAVGODYYCQF-UHFFFAOYSA-N 0.000 description 2
- 238000001338 self-assembly Methods 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- PQHKBJOUOHLCCV-UHFFFAOYSA-N CC1(C=CC=CC1C(=O)C2=CC=C(C=C2)OCCO)O Chemical compound CC1(C=CC=CC1C(=O)C2=CC=C(C=C2)OCCO)O PQHKBJOUOHLCCV-UHFFFAOYSA-N 0.000 description 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical class ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N Valeric acid Natural products CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000012650 click reaction Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- CCGKOQOJPYTBIH-UHFFFAOYSA-N ethenone Chemical compound C=C=O CCGKOQOJPYTBIH-UHFFFAOYSA-N 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- UORVCLMRJXCDCP-UHFFFAOYSA-N propynoic acid Chemical compound OC(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-N 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229940005605 valeric acid Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G83/00—Macromolecular compounds not provided for in groups C08G2/00 - C08G81/00
- C08G83/007—Polyrotaxanes; Polycatenanes
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0009—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid alpha-D-Glucans, e.g. polydextrose, alternan, glycogen; (alpha-1,4)(alpha-1,6)-D-Glucans; (alpha-1,3)(alpha-1,4)-D-Glucans, e.g. isolichenan or nigeran; (alpha-1,4)-D-Glucans; (alpha-1,3)-D-Glucans, e.g. pseudonigeran; Derivatives thereof
- C08B37/0012—Cyclodextrin [CD], e.g. cycle with 6 units (alpha), with 7 units (beta) and with 8 units (gamma), large-ring cyclodextrin or cycloamylose with 9 units or more; Derivatives thereof
- C08B37/0015—Inclusion compounds, i.e. host-guest compounds, e.g. polyrotaxanes
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Polymers & Plastics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Materials Engineering (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Polyethers (AREA)
Abstract
The invention discloses a method for rapidly preparing polyrotaxane based on shaking induction, which comprises the steps of preparing polyethylene glycol or polyethylene glycol block polymer with a terminal group containing a carbon-carbon double bond or a carbon-carbon triple bond from polyethylene glycol or polyethylene glycol block polymer; preparing an aqueous solution of polyethylene glycol or polyethylene glycol block polymer with an unsaturated bond at the end group and cyclodextrin, shaking uniformly to form gel, adding a capping agent glutathione and 2-hydroxy-4' - (2-hydroxyethoxy) -2-methyl propiophenone, and carrying out ultraviolet irradiation reaction; after the reaction is finished, the mixture is dissolved by dimethyl sulfoxide, heated in sodium chloride aqueous solution, cooled, separated and purified to obtain the polyrotaxane. The invention greatly simplifies the preparation process, shortens the preparation time, reduces the preparation cost and is suitable for industrial mass production; and the raw materials used in the invention are polyethylene glycol or polyethylene glycol block polymer and cyclodextrin, and the invention is degradable, low in biological toxicity and environment-friendly.
Description
Technical Field
The invention relates to the technical field of polyrotaxane mechanical interlocking polymer materials, in particular to a method for rapidly preparing polyrotaxane based on shaking induction.
Background
Mechanically interlocking polymers (MECHANICALLY INTERLOCKEDPOLYMERS, MIPs) are a novel class of polymers that have been favored by scientists in recent years due to the unique mechanical properties they possess due to their unique topology. Among them, polyrotaxane (polyrotaxane, PR) obtained by passing a linear polymer guest molecule through a plurality of macrocyclic host molecules and introducing bulky end capping groups at both ends of the polymer is a typical representative of MIPs. Since the nineties of the last century, it was discovered by the japanese chemist Harada et al that PR could be synthesized efficiently from polyethylene glycol (polyethylene glycol, PE) and Cyclodextrin (CD), and PR has been rapidly developed, and various types of cyclic molecules and shaft polymers have been used to prepare PR today, and have been greatly applied in the fields of sensors, stimulus-responsive materials, self-repairing materials, and the like.
Typically, the synthesis of PR is accomplished in two stages, in the first stage, the linear polymer and the cyclic molecule are mixed together under suitable conditions, forming a poly-pseudo-rotaxane (poly-pseudorotaxane) under certain interactions, which is a necessary precursor for the synthesis of PR; in stage two, PR is formed by the end group reaction of the PPR obtained in stage one, wherein the linear polymer backbone is covered with large end groups to prevent ring dislocation. However, the interpenetrating structure of the polypseudorotaxane is formed based on hydrophilic-hydrophobic interaction, but the capping reaction usually requires the presence of an organic reagent, which results in a decrease in the success rate of the capping reaction and an increase in the preparation time. Therefore, the limitation of long self-assembly time and end capping in most organic phases of the existing polyrotaxane system is broken through, the polyrotaxane synthesis step is simplified, and the method is a problem to be solved in the research of the current polyrotaxane polymer field.
Disclosure of Invention
The invention aims to solve the problems of long self-assembly time and low end-capping reaction efficiency of a polyrotaxane system in the prior art, and provides a method for rapidly preparing polyrotaxane based on shaking induction.
In order to solve the technical problems, the invention adopts the following technical scheme: a method for rapidly preparing polyrotaxane based on shaking induction comprises the following steps:
S1, preparing polyethylene glycol or polyethylene glycol block polymer with unsaturated bond at the end group from polyethylene glycol or polyethylene glycol block polymer;
S2, preparing an aqueous solution of polyethylene glycol or polyethylene glycol block polymer with an unsaturated bond at the end group and cyclodextrin, shaking uniformly to form gel, and then adding end capping agent glutathione and 2-hydroxy-4' - (2-hydroxyethoxy) -2-methyl propiophenone to perform ultraviolet irradiation reaction;
S3, after the ultraviolet irradiation reaction is finished, dissolving the obtained product by using dimethyl sulfoxide, heating the obtained product in sodium chloride aqueous solution, cooling the obtained product, and separating and purifying the obtained product to obtain the polyrotaxane.
Preferably, the end groups of the polyethylene glycol or polyethylene glycol block polymer are carbon-carbon double bonds or carbon-carbon triple bonds.
Preferably, the molecular weight of the polyethylene glycol is 2000-35000.
Preferably, the cyclodextrin is one of alpha-cyclodextrin, beta-cyclodextrin or gamma-cyclodextrin.
Preferably, the mass concentration of the polyethylene glycol or the polyethylene glycol block polymer with the end group containing unsaturated bonds in the S2 is 2-12wt%.
Further preferably, the mass concentration of the cyclodextrin is 25-66wt%.
Further preferably, the shaking-up time in the step S2 is 2min; the time of the ultraviolet irradiation reaction is 6 hours.
Further preferably, the volume ratio of the dimethyl sulfoxide to the sodium chloride aqueous solution is 1:40.
Still more preferably, the sodium chloride aqueous solution has a mass concentration of 15%.
The invention has the beneficial effects that:
1. The invention accelerates the process by shaking in the synthesis process of the polyrotaxane, and then directly carries out click reaction in situ to prepare the polyrotaxane, thereby greatly simplifying the preparation process, shortening the preparation time, reducing the preparation cost and being suitable for industrial mass production.
2. The raw materials used in the invention are polyethylene glycol or polyethylene glycol block polymer and cyclodextrin, and the invention has low cost, degradability, low biotoxicity and environmental friendliness.
Drawings
FIG. 1 is a schematic representation of the synthetic route to polyrotaxane terminated with a single glutathione.
FIG. 2 is a schematic representation of the synthetic route to a polyrotaxane terminated with four glutathione.
FIG. 3 is a schematic representation of the synthetic route to polyrotaxane terminated with a single glutathione after changing the type of PEG terminal double bond.
FIG. 4 is a schematic representation of the synthetic route to a two-terminal glutathione polyrotaxane
FIG. 5 is a nuclear magnetic resonance spectrum of polyethylene glycol terminated with norbornene of different molecular weights.
FIG. 6 is a nuclear magnetic resonance spectrum of polyrotaxane terminated with single glutathione at different molecular weight.
FIG. 7 is an infrared spectrum of polyethylene glycol terminated with norbornene, cyclodextrin and polyrotaxane terminated with single glutathione of different molecular weights.
FIG. 8 is an X-ray diffraction pattern of a polyrotaxane terminated with a single glutathione at different molecular weights.
FIG. 9 is a nuclear magnetic resonance spectrum of a carboxyl terminated polyethylene glycol.
FIG. 10 is a nuclear magnetic resonance spectrum of an alkynyl terminated polyethylene glycol.
FIG. 11 is a nuclear magnetic resonance spectrum of a four-glutathione terminated polyrotaxane.
FIG. 12 is a nuclear magnetic resonance spectrum of a polyethylene glycol with pentene end groups.
FIG. 13 is a nuclear magnetic resonance spectrum of polyrotaxane prepared using polyethylene glycol having a pentene end.
FIG. 14 is a nuclear magnetic resonance spectrum of an alkynyl terminated polyethylene glycol block polymer F-127.
FIG. 15 is a nuclear magnetic resonance spectrum of polyrotaxane prepared using polyethylene glycol block polymer F-127 having an alkynyl end group.
Detailed Description
The invention will be further described with reference to the drawings and the specific examples.
FIG. 1 is a schematic representation of the synthetic route for polyrotaxane terminated with a single glutathione in examples 1 to 4.
Example 1
(1) Dry polyethylene glycol PEG (5 g,2.5 mmol) having a molecular weight of 2000 was dissolved in 20ml of anhydrous methylene chloride under a nitrogen atmosphere, 5-norbornene-2-carboxylic acid (0.765 ml,6.25 mmol) and 4-dimethylaminopyridine (0.611 g,5 mmol) were added, and the mixture was stirred at room temperature for 15min to dissolve the components sufficiently, and then the mixture was changed to an ice water bath, diisopropylcarbodiimide (0.986 ml,6.25 mmol) was added, and the reaction was stirred for 24 hours. The filtrate is filtered and collected, the crude product is obtained by rotary evaporation and concentration, and a large amount of diethyl ether is added into the crude product to obtain polyethylene glycol with the end group of the compound being norbornene, which is white powder. The white powder was collected by suction filtration and dried overnight in a vacuum desiccator at 40℃and designated as compound PEG 2k-(Nor)2.
The structure of PEG 2k-(Nor)2 is characterized, a proper amount of the final product is weighed into a nuclear magnetic tube, and is dissolved by deuterated chloroform, and is tested by a nuclear magnetic resonance apparatus at 25 ℃. As can be seen from the nuclear magnetic resonance spectrum (figure 5A), the chemical shift, integration and coupling cleavage conditions of each hydrogen are consistent with those of the target molecules, which indicates that the target products are obtained. PEG 2k-(Nor)2 characterization data were as follows:
compounds of formula (I) PEG2k-(Nor)2 1H NMR(400MHz,298K,CDCl3,ppm)δ＝5.90–6.18(m,CH＝CH ofnorbornyl,endo protons at 5.90and 6.18,exo protons at 6.07–6.12),4.18(m)3.62(m,CH2O ofPEG),3.20(s,CHCO ofnorbornyl),2.97(m,CH2 bridge ofnorbornyl)1.90(m,CH ofnorbornyl)1.42and 1.26(m,CH2 ofnorbornyl).
(2) PEG 2k-(Nor)2 (180 mg,0.09 mmol) and alpha-cyclodextrin (990 mg,1.02 mmol) were added to 3ml of deionized water, shaken well in a shaking machine at 3000 rpm for 2min, glutathione (138.3 mg,0.45 mmol) and 2-hydroxy-4' - (2-hydroxyethoxy) -2-methylpropionacetone (10.1 mg,0.045 mmol) were added, and after shaking well in a shaking machine at 3000 rpm for 2min, direct UV irradiation was performed for 6h to give a white gum, the gum was dissolved in dimethyl sulfoxide, and then was added to an aqueous NaCl solution with a mass concentration of 15% aqueous NaCl solution, the ratio of solvent dimethyl sulfoxide to aqueous precipitant sodium chloride was 1:40, then observing floccules, centrifuging and collecting the floccules, and washing with deionized water to obtain polyrotaxane with compound end groups of single glutathione as white gel. The white gel was dried in a freeze dryer to give a white powder, designated PR 2k-(GSH)2.
The structure of PR 2k-(GSH)2 is characterized, a proper amount of the final product is weighed into a nuclear magnetic tube, and is dissolved by deuterated dimethyl sulfoxide, and is tested by a nuclear magnetic resonance instrument at 25 ℃. As can be seen from the nuclear magnetic resonance spectrogram (figure 6A), the chemical displacement, integration and coupling split conditions of each hydrogen are consistent with those of target molecules, which shows that the target product is obtained, and the spectrogram has no impurity peak, thus proving that the product has higher purity. PR 2k-(GSH)2 characterization data are as follows:
Compounds of formula (I) PR-(GSH)2 1H NMR(400MHz,298K,DMSO-d6,ppm)δ＝6.79(-NH-CO-),5.66(OH-2ofα-CD),5.50(OH-3ofα-CD),4.79(H-1ofα-CD),4.43(OH-6ofα-CD),3.9-3.4(H-3,H-5,H-6ofα-CD and-CH2-ofPEG),3.4-3.2(H-2and H-4fromα-CD ofα-CD),1.23(-CH2-ofGSH).
FIG. 7A is an infrared spectrum of PEG 2k-(Nor)2, alpha-CD and PR 2k-(GSH)2 prepared by the post-shaking Click method, showing that the broad peak at 3330cm -1 is the stretching vibration peak of the hydroxyl group on the alpha-CD, and the peak near 1750cm -1 is the stretching vibration peak of the carbonyl group on PEG 2k-(Nor)2 and the carbonyl group on glutathione; PEG 2k-(Nor)2 prepared by example 1 exhibited a characteristic peak near 1750cm -1, indicating the presence of a carbonyl group in PEG 2k-(Nor)2, a characteristic peak at 960cm -1, indicating successful introduction of a double bond, confirming the formation of PEG 2k-(Nor)2; the transfer of the methylene peak on polyethylene glycol at 2890cm -1 to the lower wavenumber 2879cm -1 demonstrates successful synthesis of polyrotaxane.
The X-ray diffraction pattern of PR 2k-(GSH)2 is shown in FIG. 8A: from the X-ray diffraction analysis, new crystallization peaks appear in the X-ray diffraction pattern of the polyrotaxane, which indicates the appearance of new ordered structures in PR, and which indicates the successful synthesis of the polyrotaxane.
Example 2
(1) Dry polyethylene glycol PEG (5 g,1.25 mmol) having a molecular weight of 4000 was dissolved in 20ml of anhydrous methylene chloride under a nitrogen atmosphere, 5-norbornene-2-carboxylic acid (0.765 ml,6.25 mmol) and 4-dimethylaminopyridine (0.305 g,2.5 mmol) were added, and the mixture was stirred at room temperature for 15min to dissolve the components sufficiently, and then the mixture was changed to an ice water bath, diisopropylcarbodiimide (0.986 ml,6.25 mmol) was added, and the reaction was stirred for 24 hours. The filtrate is filtered and collected, the crude product is obtained by rotary evaporation and concentration, and a large amount of diethyl ether is added into the crude product to obtain polyethylene glycol with the end group of the compound being norbornene, which is white powder. The white powder was collected by suction filtration and dried overnight in a vacuum desiccator at 40℃and designated as compound PEG 4k-(Nor)2.
The structure of PEG 4k-(Nor)2 is characterized, a proper amount of the final product is weighed into a nuclear magnetic tube, and is dissolved by deuterated chloroform, and is tested by a nuclear magnetic resonance apparatus at 25 ℃. As can be seen from the nuclear magnetic resonance spectrum (figure 5B), the chemical shift, integration and coupling cleavage conditions of each hydrogen are consistent with those of the target molecules, which indicates that the target products are obtained. PEG 4k-(Nor)2 characterization data were as follows:
Compounds of formula (I) PEG4k-(Nor)2 1H NMR(400MHz,298K,CDCl3,ppm)δ＝5.90–6.18(m,CH＝CH of norbornyl,endo protons at 5.90and 6.18,exo protons at 6.07–6.12),4.18(m)3.62(m,CH2O ofPEG),3.20(s,CHCO ofnorbornyl),2.97(m,CH2 bridge ofnorbornyl)1.90(m,CH ofnorbornyl)1.42and 1.26(m,CH2 ofnorbornyl).
(2) PEG 4k-(Nor)2 (180 mg,0.045 mmol) and alpha-cyclodextrin (990 mg,1.02 mmol) were added to 3ml of deionized water, shaken well in a shaking machine at 3000 rpm for 2min, glutathione (138.3 mg,0.45 mmol) and 2-hydroxy-4' - (2-hydroxyethoxy) -2-methylpropionacetone (10.1 mg,0.045 mmol) were added, and after shaking well in a shaking machine at 3000 rpm for 2min, direct UV irradiation was performed for 6h to give a white gum, the gum was dissolved in dimethyl sulfoxide, and then was added to an aqueous NaCl solution with a mass concentration of 15% aqueous NaCl solution, the ratio of solvent dimethyl sulfoxide to aqueous precipitant sodium chloride was 1:40, then observing floccules, centrifuging and collecting the floccules, and washing with deionized water to obtain polyrotaxane with compound end groups of single glutathione as white gel. The white gel was dried in a freeze dryer to give a white powder, designated PR 4k-(GSH)2.
The structure of PR 4k-(GSH)2 is characterized, a proper amount of the final product is weighed into a nuclear magnetic tube, and is dissolved by deuterated dimethyl sulfoxide, and is tested by a nuclear magnetic resonance instrument at 25 ℃. As can be seen from the nuclear magnetic resonance spectrogram (figure 6B), the chemical shift, integration and coupling split conditions of each hydrogen are consistent with those of target molecules, which shows that the target product is obtained, and the spectrogram has no impurity peak, thus proving that the product has higher purity. PR 4k-(GSH)2 characterization data are as follows:
Compounds of formula (I) PR4k-(GSH)2 1H NMR(400MHz,298K,DMSO-d6,ppm)δ＝6.79(-NH-CO-),5.66(OH-2ofα-CD),5.50(OH-3ofα-CD),4.79(H-1ofα-CD),4.43(OH-6ofα-CD),3.9-3.4(H-3,H-5,H-6ofα-CD and-CH2-ofPEG),3.4-3.2(H-2and H-4fromα-CD ofα-CD),1.23(-CH2-ofGSH).
FIG. 7B is an infrared spectrum of PEG 4k-(Nor)2, alpha-CD and PR 4k-(GSH)2 prepared by the post-shaking Click method, showing that the broad peak at 3330cm -1 is the stretching vibration peak of the hydroxyl group on the alpha-CD, and the peak near 1750cm -1 is the stretching vibration peak of the carbonyl group on PEG 4k-(Nor)2 and the carbonyl group on glutathione; PEG 4k-(Nor)2 prepared by this example exhibited a characteristic peak near 1750cm -1, indicating the presence of a carbonyl group in PEG 4k-(Nor)2, a characteristic peak at 960cm -1, indicating successful introduction of a double bond, confirming the formation of PEG 4k-(Nor)2; the transfer of the methylene peak on polyethylene glycol at 2890cm -1 to the lower wavenumber 2879cm -1 demonstrates successful synthesis of polyrotaxane.
The X-ray diffraction pattern of the polyrotaxane with a single glutathione end group prepared in the embodiment is shown in fig. 8B: from the X-ray diffraction analysis, new crystallization peaks appear in the X-ray diffraction pattern of the polyrotaxane, which indicates the appearance of new ordered structures in PR, and which indicates the successful synthesis of the polyrotaxane.
Example 3
(1) Dry polyethylene glycol PEG (10 g,0.5 mmol) having a molecular weight of 20000 was dissolved in 50ml of anhydrous methylene chloride under a nitrogen atmosphere, 5-norbornene-2-carboxylic acid (1.224 ml,10 mmol) and 4-dimethylaminopyridine (0.122 g,1 mmol) were added, and the mixture was stirred at room temperature for 15min to dissolve the components sufficiently, and then the mixture was changed to an ice water bath, diisopropylcarbodiimide (1.578 ml,10 mmol) was added, and the reaction was stirred for 24 hours. The filtrate is filtered and collected, the crude product is obtained by rotary evaporation and concentration, and a large amount of diethyl ether is added into the crude product to obtain polyethylene glycol with the end group of the compound being norbornene, which is white powder. The white powder was collected by suction filtration and dried overnight in a vacuum desiccator at 40℃and designated as compound PEG 20k-(Nor)2.
The structure of PEG 20k-(Nor)2 is characterized, a proper amount of the final product is weighed into a nuclear magnetic tube, and is dissolved by deuterated chloroform, and is tested by a nuclear magnetic resonance apparatus at 25 ℃. As can be seen from the nuclear magnetic resonance spectrum (figure 5C), the chemical shift, integration and coupling cleavage conditions of each hydrogen are consistent with those of the target molecules, which indicates that the target products are obtained. PEG 20k-(Nor)2 characterization data were as follows:
Compounds of formula (I) PEG20k-(Nor)2 1H NMR(400MHz,298K,CDCl3,ppm)δ＝5.90–6.18(m,CH＝CH ofnorbornyl,endo protons at 5.90and 6.18,exo protons at 6.07–6.12),4.18(m)3.62(m,CH2O ofPEG),3.20(s,CHCO ofnorbornyl),2.97(m,CH2 bridge ofnorbornyl)1.90(m,CH ofnorbornyl)1.42and 1.26(m,CH2 ofnorbornyl).
(2) PEG 20k-(Nor)2 (180 mg, 0.09 mmol) and alpha-cyclodextrin (990 mg,1.02 mmol) were added to 3ml of deionized water, shaken well in a shaking machine at 3000 rpm for 2min, glutathione (138.3 mg,0.45 mmol) and 2-hydroxy-4' - (2-hydroxyethoxy) -2-methylpropionacetone (10.1 mg,0.045 mmol) were added, and after shaking well in a shaking machine at 3000 rpm for 2min, direct UV irradiation was performed for 6h to give a white gum, the gum was dissolved in dimethyl sulfoxide, and then was added to an aqueous NaCl solution with a mass concentration of 15% aqueous NaCl solution, the ratio of solvent dimethyl sulfoxide to aqueous precipitant sodium chloride was 1:40, then observing floccules, centrifuging and collecting the floccules, and washing with deionized water to obtain polyrotaxane with compound end groups of single glutathione as white gel. The white gel was dried in a freeze dryer to give a white powder, designated PR 20k-(GSH)2.
The structure of PR 20k-(GSH)2 is characterized, a proper amount of the final product is weighed into a nuclear magnetic tube, and is dissolved by deuterated dimethyl sulfoxide, and is tested by a nuclear magnetic resonance instrument at 25 ℃. As can be seen from the nuclear magnetic resonance spectrogram (figure 6C), the chemical shift, integration and coupling split conditions of each hydrogen are consistent with those of target molecules, which shows that the target product is obtained, and the spectrogram has no impurity peak, thus proving that the product has higher purity. PR 20k-(GSH)2 characterization data are as follows:
compounds of formula (I) PR20k-(GSH)2 1H NMR(400MHz,298K,DMSO-d6,ppm)δ＝6.79(-NH-CO-),5.66(OH-2ofα-CD),5.50(OH-3ofα-CD),4.79(H-1ofα-CD),4.43(OH-6ofα-CD),3.9-3.4(H-3,H-5,H-6ofα-CD and-CH2-ofPEG),3.4-3.2(H-2and H-4fromα-CD ofα-CD),1.23(-CH2-ofGSH).
FIG. 7C is an infrared spectrum of PEG 20k-(Nor)2, α -CD and PR 20k-(GSH)2 by the post-shaking Click method, showing that the broad peak at 3330cm -1 is the stretching vibration peak of the hydroxyl group on α -CD, and the peak near 1750cm -1 is the stretching vibration peak of the carbonyl group on PEG 20k-(Nor)2 and the carbonyl group on glutathione; PEG 20k-(Nor)2 prepared by example 1 exhibited a characteristic peak near 1750cm -1, indicating the presence of a carbonyl group in PEG 20k-(Nor)2, a characteristic peak at 960cm -1, indicating successful introduction of a double bond, confirming the formation of PEG 20k-(Nor)2; the transfer of the methylene peak on polyethylene glycol at 2890cm -1 to the lower wavenumber 2879cm -1 demonstrates successful synthesis of polyrotaxane.
The X-ray diffraction pattern of PR 20k-(GSH)2 in this example is shown in fig. 8C: from the X-ray diffraction analysis, new crystallization peaks appear in the X-ray diffraction pattern of the polyrotaxane, which indicates the appearance of new ordered structures in PR, and which indicates the successful synthesis of the polyrotaxane.
Example 4
(1) Dry polyethylene glycol PEG (10 g,0.29 mmol) having a molecular weight of 35000 was dissolved in 50ml of anhydrous methylene chloride under a nitrogen atmosphere, 5-norbornene-2-carboxylic acid (1.224 ml,10 mmol) and 4-dimethylaminopyridine (0.122 g,1 mmol) were added, and the mixture was stirred at room temperature for 15min to dissolve the components sufficiently, and then the mixture was changed to an ice water bath, diisopropylcarbodiimide (1.578 ml,10 mmol) was added, and the reaction was stirred for 24 hours. The filtrate is filtered and collected, the crude product is obtained by rotary evaporation and concentration, and a large amount of diethyl ether is added into the crude product to obtain polyethylene glycol with the end group of the compound being norbornene, which is white powder. The white powder was collected by suction filtration and dried overnight in a vacuum desiccator at 40℃and designated as compound PEG 35k-(Nor)2.
The structure of PEG 35k-(Nor)2 is characterized, a proper amount of the final product is weighed into a nuclear magnetic tube, and is dissolved by deuterated chloroform, and is tested by a nuclear magnetic resonance apparatus at 25 ℃. As can be seen from the nuclear magnetic resonance spectrum (figure 5D), the chemical shift, integration and coupling cleavage conditions of each hydrogen are consistent with those of the target molecules, which indicates that the target products are obtained. PEG 35k-(Nor)2 characterization data were as follows:
compounds of formula (I) PEG35k-(Nor)2 1H NMR(400MHz,298K,CDCl3,ppm)δ＝5.90–6.18(m,CH＝CH ofnorbornyl,endo protons at 5.90and 6.18,exo protons at 6.07–6.12),4.18(m)3.62(m,CH2O ofPEG),3.20(s,CHCO ofnorbornyl),2.97(m,CH2 bridge ofnorbornyl)1.90(m,CH ofnorbornyl)1.42and 1.26(m,CH2 ofnorbornyl).
(2) PEG 35k-(Nor)2 (180 mg, 0.09 mmol) and alpha-cyclodextrin (990 mg,1.02 mmol) were added to 3ml of deionized water, shaken well in a shaking machine at 3000 rpm for 2min, glutathione (138.3 mg,0.45 mmol) and 2-hydroxy-4' - (2-hydroxyethoxy) -2-methylpropionacetone (10.1 mg,0.045 mmol) were added, and after shaking well in a shaking machine at 3000 rpm for 2min, direct UV irradiation was performed for 6h to give a white gum, the gum was dissolved in dimethyl sulfoxide, and then was added to an aqueous NaCl solution with a mass concentration of 15% aqueous NaCl solution, the ratio of solvent dimethyl sulfoxide to aqueous precipitant sodium chloride was 1:40, then observing floccules, centrifuging and collecting the floccules, and washing with deionized water to obtain polyrotaxane with compound end groups of single glutathione as white gel. The white gel was dried in a freeze dryer to give a white powder, designated PR 35k-(GSH)2.
The structure of PR 35k-(GSH)2 is characterized, a proper amount of the final product is weighed into a nuclear magnetic tube, and is dissolved by deuterated dimethyl sulfoxide, and is tested by a nuclear magnetic resonance instrument at 25 ℃. As can be seen from the nuclear magnetic resonance spectrogram (figure 6D), the chemical shift, integration and coupling split conditions of each hydrogen are consistent with those of target molecules, which shows that the target product is obtained, and the spectrogram has no impurity peak, thus proving that the product has higher purity. PR 35k-(GSH)2 characterization data are as follows:
Compounds of formula (I) PR35k-(GSH)2 1H NMR(400MHz,298K,DMSO-d6,ppm)δ＝6.79(-NH-CO-),5.66(OH-2ofα-CD),5.50(OH-3ofα-CD),4.79(H-1ofα-CD),4.43(OH-6ofα-CD),3.9-3.4(H-3,H-5,H-6ofα-CD and-CH2-ofPEG),3.4-3.2(H-2and H-4fromα-CD ofα-CD),1.23(-CH2-ofGSH).
FIG. 7D is an infrared spectrum of PEG 35k-(Nor)2, α -CD and PR 35k-(GSH)2 by the post-shaking Click method, showing that the broad peak at 3330cm -1 is the stretching vibration peak of the hydroxyl group on α -CD, and the peak near 1750cm -1 is the stretching vibration peak of the carbonyl group on PEG 35k-(Nor)2 and the carbonyl group on glutathione; the formation of PEG 35k-(Nor)2 was confirmed by PEG 35k-(Nor)2 exhibiting a characteristic peak near 1750cm -1, indicating the presence of a carbonyl group in PEG 35k-(Nor)2, exhibiting a characteristic peak at 960cm -1, indicating successful introduction of a double bond; the transfer of the methylene peak on polyethylene glycol at 2890cm -1 to the lower wavenumber 2879cm -1 demonstrates successful synthesis of polyrotaxane.
The X-ray diffraction pattern of PR 35k-(GSH)2 is shown in FIG. 8D: from the X-ray diffraction analysis, new crystallization peaks appear in the X-ray diffraction pattern of the polyrotaxane, which indicates the appearance of new ordered structures in PR, and which indicates the successful synthesis of the polyrotaxane.
Example 5
FIG. 2 is a route to alkynyl terminated PEG and further to poly rotaxane with gamma-CD, as follows:
(1) PEG (5 g,0.25 mmol) with molecular weight 20000 was dissolved in 50ml deionized water, TEMPO (86 mg,0.55 mmol), naBr (0.5 g,5 mmol) and 5ml NaClO solution were added sequentially and stirred at room temperature for 15min (maintaining pH between 10-11). The reaction was quenched by adding 10ml of ethanol, adjusted to pH < 2 by adding 1M hydrochloric acid solution, extracted with DCM, and added with a large amount of diethyl ether to give the carboxyl terminated polyethylene glycol as a white powder. The white powder was collected by suction filtration and dried overnight in a vacuum desiccator at 40℃and designated as compound PEG 20k-(COOH)2.
The structure of the synthesized PEG with the end group of carboxyl is characterized, a proper amount of end product is weighed and put in a nuclear magnetic tube, deuterated trichloromethane is used for dissolution, and a nuclear magnetic resonance instrument is used for testing at 25 ℃. As shown in the nuclear magnetic resonance spectrogram (figure 9), the chemical shift, integration and coupling split conditions of each hydrogen are consistent with those of the target molecules, which shows that the target product is obtained, and the spectrogram has no impurity peak, which proves that the product has higher purity. PEG 20k-(COOH)2 characterization data were as follows:
Compounds of formula (I) PEG20k-(COOH)2 1H NMR(400MHz,298K,CDCl3,ppm)δ＝4.13(-CH2COOH),3.8-3.3(-CH2-ofPEG).
(2) PEG 20k-(COOH)2 (1 g,0.05 mmol) was dissolved in 5ml of anhydrous dichloromethane under nitrogen atmosphere, propargylamine (0.064 ml,1 mmol) and 4-dimethylaminopyridine (0.122 g,1 mmol) were added, the mixture was stirred at room temperature for 15min to dissolve the components sufficiently, then the mixture was replaced into an ice-water bath, diisopropylcarbodiimide (0.126 ml,1 mmol) was added, and the reaction was stirred for 24h. The filtrate is filtered and collected, the crude product is obtained by rotary evaporation and concentration, and a large amount of diethyl ether is added into the crude product to obtain polyethylene glycol with alkynyl end groups, which is white powder. The white powder was collected by suction filtration and dried overnight in a vacuum desiccator at 40℃and designated as compound PEG 20k-(≡)2.
The structure of PEG 20k-(≡)2 was characterized by weighing the appropriate amount of the final product in a nuclear magnetic resonance tube, dissolving with deuterated dimethyl sulfoxide, and testing at 25deg.C with a nuclear magnetic resonance instrument. As can be seen from the nuclear magnetic resonance spectrum (figure 10), the chemical shift, integration and coupling cleavage conditions of each hydrogen are consistent with those of the target molecules, which indicates that the target products are obtained. PEG 20k-(≡)2 characterization data were as follows:
compounds of formula (I) PEG20k-(≡)2 1H NMR(400MHz,298K,DMSO-d6,ppm)δ＝3.90(-CH2COOH),3.8-3.3(-CH2-of PEG),8.10(-NH of Propargylamine),3.90-3.87(-CH2-ofPropargylamine),3.07(≡CH ofPropargylamine).
(3) PEG 20k-(≡)2 (180 mg,0.09 mmol) and gamma-cyclodextrin (1320 mg,1.02 mmol) were added to 3ml of deionized water, shaken well in a shaking machine at 3000 rpm for 2min, glutathione (276.6 mg,0.9 mmol) and 2-hydroxy-4' - (2-hydroxyethoxy) -2-methylpropionacetone (20 mg,0.09 mmol) were added, and after shaking well in a shaking machine at 3000 rpm for 2min, direct UV irradiation was performed for 6h to obtain a white gum, the gum was dissolved in dimethyl sulfoxide, and then added with aqueous NaCl solution at a mass concentration of 15% aqueous NaCl solution, the ratio of solvent dimethyl sulfoxide to aqueous precipitant sodium chloride was 1:40, then observing floccules, centrifuging and collecting the floccules, and washing with deionized water to obtain the polyrotaxane with the compound end group of glutathione as a white gel. The white gel was dried in a freeze dryer to give a white powder, designated PR 20k-(GSH)8.
Characterization is carried out on the structure of the synthesized polyrotaxane with four glutathione end groups, a proper amount of end products are weighed in a nuclear magnetic tube, and are dissolved by deuterated dimethyl sulfoxide, and a nuclear magnetic resonance instrument is adopted for testing at 25 ℃. As can be seen from a nuclear magnetic resonance spectrogram (figure 11), the chemical displacement, integration and coupling split conditions of each hydrogen are consistent with those of target molecules, which shows that the target product is obtained, and the spectrogram has no impurity peak, so that the product is proved to reach higher purity. PR- (GSH) 8 characterization data are as follows:
Compounds of formula (I) PR-(GSH)8 1H NMR(400MHz,298K,DMSO-d6,ppm)δ＝5.81(OH-2ofγ-CD),5.76(OH-3ofγ-CD),4.89(H-1ofγ-CD),4.59(OH-6ofγ-CD),3.72-3.48(H-3,H-5,H-6ofγ-CD and-CH2-ofPEG),3.48-3.2(H-2and H-4ofγ-CD),1.23(-CH2-ofGSH).
Example 6
FIG. 3 is a synthetic scheme for the preparation of polyrotaxane using PEG having pentene as terminal group
(1) Dry polyethylene glycol PEG (2 g,0.1 mmol) with molecular weight of 20000 was dissolved in 10ml of anhydrous dichloromethane under nitrogen atmosphere, 4-allyl valeric acid (0.204 ml,2 mmol) and 4-dimethylaminopyridine (0.025 g,0.2 mmol) were added, the mixture was stirred at room temperature for 15min to dissolve the components sufficiently, and then the mixture was replaced in ice water bath, diisopropylcarbodiimide (0.204 ml,2 mmol) was added, and the mixture was stirred for 24h. The filtrate is filtered and collected, the crude product is obtained by rotary evaporation and concentration, and a large amount of diethyl ether is added into the crude product to obtain polyethylene glycol with the end group of the compound being norbornene, which is white powder. The white powder was collected by suction filtration and dried overnight in a vacuum desiccator at 40℃and designated as compound PEG 20k-(PA)2.
The structure of PEG 20k-(PA)2 is characterized, a proper amount of the final product is weighed into a nuclear magnetic tube, and is dissolved by deuterated chloroform, and is tested by a nuclear magnetic resonance apparatus at 25 ℃. As can be seen from the nuclear magnetic resonance spectrum (figure 12), the chemical shift, integration and coupling cleavage conditions of each hydrogen are consistent with those of the target molecules, which indicates that the target products are obtained. PEG 20k-(PA)2 characterization data were as follows:
Compounds of formula (I) PEG20k-(PA)2 1H NMR(400MHz,298K,CDCl3,ppm)δ＝5.76–5.86(m,CH ofPent-4-enoic acid),4.97-5.06(dd,CH2 ofCH2＝CH on Pent-4-enoic acid),3.20(t,CH2CO of Pent-4-enoic acid),3.63(m,CH2O of PEG)2.18(m,CH2 of Pent-4-enoic acid).
(2) PEG 20k-(PA)2 (180 mg,0.045 mmol) and alpha-cyclodextrin (990 mg,1.02 mmol) were added to 3ml of deionized water, shaken well in a shaking machine at 3000 rpm for 2min, glutathione (138.3 mg,0.45 mmol) and 2-hydroxy-4' - (2-hydroxyethoxy) -2-methylpropionacetone (10.1 mg,0.045 mmol) were added, and after shaking well in a shaking machine at 3000 rpm for 2min, direct UV irradiation was performed for 6h to give a white gum, the gum was dissolved in dimethyl sulfoxide, and then was added to an aqueous NaCl solution with a mass concentration of 15% aqueous NaCl solution, the ratio of solvent dimethyl sulfoxide to aqueous precipitant sodium chloride was 1:40, then observing floccules, centrifuging and collecting the floccules, and washing with deionized water to obtain polyrotaxane with compound end groups of single glutathione as white gel. The white gel was dried in a freeze dryer to give a white powder, designated PR 20kp-(GSH)2.
The structure of PR 20kp-(GSH)2 is characterized, a proper amount of the final product is weighed into a nuclear magnetic tube, and is dissolved by deuterated dimethyl sulfoxide, and is tested by a nuclear magnetic resonance instrument at 25 ℃. As can be seen from the nuclear magnetic resonance spectrogram (figure 13), the chemical shift, integration and coupling split conditions of each hydrogen are consistent with those of the target molecules, which shows that the target product is obtained, and the spectrogram has no impurity peak, thus proving that the product has higher purity. PR 20kp-(GSH)2 characterization data are as follows:
Compounds of formula (I) PR20kp-(GSH)2 1H NMR(400MHz,298K,DMSO-d6,ppm)δ＝6.79(-NH-CO-),5.66(OH-2ofα-CD),5.50(OH-3ofα-CD),4.79(H-1ofα-CD),4.43(OH-6ofα-CD),3.9-3.4(H-3,H-5,H-6ofα-CD and-CH2-ofPEG),3.4-3.2(H-2and H-4fromα-CD ofα-CD),1.23(-CH2-ofGSH).
Example 7
FIG. 4 shows a synthetic route for preparing polyrotaxane using F-127 having terminal group as alkynyl group
(1) Polyethylene glycol block polymer F-127 (2.52 g,0.2 mmol) was dissolved in 15ml of anhydrous methylene chloride under nitrogen atmosphere, propiolic acid (0.248 ml,4 mmol) and 4-dimethylaminopyridine (0.05 g,0.4 mmol) were added, and the mixture was stirred at room temperature for 15min to dissolve the components sufficiently, and then the mixture was changed to ice water bath, diisopropylcarbodiimide (0.62 ml,4 mmol) was added, and the reaction was stirred for 24 hours. The filtrate is filtered and collected, the crude product is obtained by rotary evaporation and concentration, and a large amount of diethyl ether is added into the crude product to obtain F-127 with the end group of the compound being alkynyl, which is white powder. The white powder was collected by suction filtration and dried overnight in a vacuum drier at 40℃and designated compound F-127- (≡) 2.
Characterization of the structure of F-127- (≡) 2), weighing a proper amount of the final product in a nuclear magnetic tube, dissolving with deuterated chloroform, and testing at 25 ℃ by using a nuclear magnetic resonance apparatus. As can be seen from the nuclear magnetic resonance spectrum (figure 14), the chemical shift, integration and coupling cleavage conditions of each hydrogen are consistent with those of the target molecules, which indicates that the target products are obtained. F-127- (≡) 2 characterization data are as follows:
Compounds of formula (I) F-127-(≡)2 1H NMR(400MHz,298K,CDCl3,ppm)δ＝3.30–3.70(m,CH2O ofPEG and PPG,CHO ofPPG)2.97(s,CH ofPropiolicAcid)1.12(d,CH3 of PPG).
(2) F-127- (≡) 2 (70 mg,0.0056 mmol) and beta-cyclodextrin (266 mg,0.235 mmol) were added to 0.7ml of deionized water, shaken in a shaking machine at 3000 rpm for 2min, glutathione (172.1 mg,0.56 mmol) and 2-hydroxy-4' - (2-hydroxyethoxy) -2-methylbenzophenone (12.5 mg,0.056 mmol) were added, and after shaking in a shaking machine at 3000 rpm for 2min, direct ultraviolet irradiation was performed for 6h to give a white gum, the gum was dissolved in dimethyl sulfoxide, and then added with an aqueous NaCl solution at a mass concentration of 15% in a ratio of dimethyl sulfoxide to aqueous sodium chloride as a precipitant of 1:40, and dialyzing in 1L deionized water for three days to obtain floccules, and freeze-drying to collect floccules as brown powder. Designated as F-127- (GSH) 4.
The structure of F-127- (GSH) 4 is characterized, a proper amount of the final product is weighed into a nuclear magnetic resonance tube, and is dissolved by deuterated dimethyl sulfoxide, and is tested by a nuclear magnetic resonance instrument at 25 ℃. As can be seen from the nuclear magnetic resonance spectrogram (figure 15), the chemical shift, integration and coupling split conditions of each hydrogen are consistent with those of the target molecules, which shows that the target product is obtained, and the spectrogram has no impurity peak, thus proving that the product has higher purity. Characterization data for F-127- (GSH) 4 are as follows:
Compounds of formula (I) F-127-(GSH)4 1H NMR(400MHz,298K,DMSO-d6,ppm)δ＝6.79(-NH-CO-),5.66(OH-2ofα-CD),5.50(OH-3ofα-CD),4.79(H-1ofα-CD),4.43(OH-6ofα-CD),3.9-3.4(H-3,H-5,H-6ofα-CD and-CH2-ofPEG and PPG,CH of PPG),3.4-3.2(H-2and H-4fromα-CD ofα-CD),1.23(-CH2-of GSH),1.04(d,CH3 ofPPG).
The specification and figures are to be regarded in an illustrative rather than a restrictive sense, and one skilled in the art, in light of the teachings of this invention, may make various substitutions and alterations to some of its features without the need for inventive faculty, all being within the scope of this invention.
Claims (9)
1. The method for rapidly preparing the polyrotaxane based on shaking induction is characterized by comprising the following steps of:
S1, preparing polyethylene glycol or polyethylene glycol block polymer with unsaturated bond at the end group from polyethylene glycol or polyethylene glycol block polymer;
S2, preparing an aqueous solution of polyethylene glycol or polyethylene glycol block polymer with an unsaturated bond at the end group and cyclodextrin, shaking uniformly to form gel, and then adding end capping agent glutathione and 2-hydroxy-4' - (2-hydroxyethoxy) -2-methyl propiophenone to perform ultraviolet irradiation reaction;
S3, after the ultraviolet irradiation reaction is finished, dissolving the obtained product by using dimethyl sulfoxide, heating the obtained product in sodium chloride aqueous solution, cooling the obtained product, and separating and purifying the obtained product to obtain the polyrotaxane.
2. The method of claim 1, wherein the polyethylene glycol or polyethylene glycol block polymer has end groups of carbon-carbon double bonds or carbon-carbon triple bonds.
3. The method of claim 1, wherein the polyethylene glycol has a molecular weight of 2000 to 35000.
4. The method of claim 1, wherein the cyclodextrin is one of α -cyclodextrin, β -cyclodextrin, or γ -cyclodextrin.
5. The method according to claim 1, wherein the mass concentration of the polyethylene glycol or polyethylene glycol block polymer having an unsaturated bond at the end group in S2 is 2 to 12wt%.
6. The method according to claim 1, wherein the cyclodextrin is present in a mass concentration of 25-66wt%.
7. The method according to claim 1, wherein the shaking-up time in S2 is 2min; the time of the ultraviolet irradiation reaction is 6 hours.
8. The method according to claim 1, wherein the volume ratio of dimethyl sulfoxide to sodium chloride aqueous solution is 1:40 .
9. The method according to claim 1, wherein the mass concentration of the sodium chloride aqueous solution is 15% .
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