CN110483757A - It is a kind of novel highly selective to click dissaving polymer and preparation method and application - Google Patents
It is a kind of novel highly selective to click dissaving polymer and preparation method and application Download PDFInfo
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Abstract
The present invention provides it is a kind of it is novel it is highly selective click dissaving polymer and the preparation method and application thereof, belong to biomedical material and polymeric material field.The present invention sufficiently combines the advantages of click chemistry, different number and polymer of different nature or functional molecular are grafted on a molecular backbone of polymer, realize that polymer ends branched structure and quantity are adjustable, hyperbranched amphipathic multi-block polymer material is prepared, in terms of can be applied to multifunctional biomaterials such as medicine antifouling and antibiosis material and pharmaceutical carrier and metal nano material, surfactant, each field of membrane material；On the other hand, hyperbranched amphipathic multi-block polymer material provided by the invention also has enhancing ground by the ability of cellular uptake, is used as the suitable material in the fields such as antibacterial, target medicine carrier and tissue engineering bracket when containing phosphatidyl choline base head.
Description
Technical field
The invention belongs to biomedical materials and polymeric material field, are related to a kind of bio-medical polymer material, tool
Body what is involved is it is a kind of it is novel have highly selective click dissaving polymer and the preparation method and application thereof.
Background technique
With the development of polymer science and synthetic technology, one kind possesses the highly branched polymer of stereoscopic three-dimensional structure
Structure is prepared by exploitation, such as dendrimer and dissaving polymer.This kind of macromolecular or polymer have highly branched
Three-dimensional globular molecular structure, to make strand without entanglement, stability and mechanical strength with higher；And with identical
Traditional linear macromolecule of molecular weight is compared, and has more active reaction end groups, it is easier to be introduced functional group, be adjusted parent
Hydrophobicity and carrier surface property, meet the different demands of every field.Such material has been widely used in drug load at present
The multiple fields such as body, metal nano material, surfactant, membrane material.
Dendrimer has the molecular structure of high degree of symmetry, molecular size controllability strong, generally by core, constantly
Spherical three-dimensional structure is presented with the increase of algebra in outside branch, and surface has the functional group of very high-density, intramolecular
There are a large amount of cavitys, possess fabulous reactivity and contain ability.However dendrimer need considerably complicated synthesis and
Purification process, during lengthy and tedious preparation and purification, the active group and structure of carrier are subject to destroy, and are not able to satisfy green
The requirement of colour chemistry and atom economy；More perplex, the active group of end passes through chemical reaction grafting functional group
Quantity is uncontrollable with position, and selectivity is poor.In addition, dendrimer mostly non-degradable or biocompatibility is bad,
Such as the terminals amination such as PAMAM, PPI dendrimer cytotoxicity with higher and haemolysis behavior mostly.
Dissaving polymer alternatively has the non-linear polymer of high density functional end-group, though in structure not
Such as dendrimer perfection, but preparation process is relatively easy, at low cost, is convenient for industrialized production, has also obtained a large amount of concerns.So
And the research about dissaving polymer selectivity grafting functional group is still less, first is that functional end-group is mostly single, only
There is a kind of reactive group, leads to graft reaction non-selectivity；Second is that the reactivity of polymer segment is low, it is difficult to fully achieve and connect
Branch.
Click chemistry is as a kind of new synthetic method, and because its is highly selective, reaction condition is mild, and yield is high, meets atom
The characteristic superiorities such as economy are shown one's talent in numerous synthesizing means, are become a kind of ideal chemical modification means and are applied to respectively
In the multifunction research of kind biomaterial.It can be more convenient more safely using click chemistry by various functional groups and molecule
It is introduced into polymer architecture.Currently, the feature and advantage using click chemistry prepare multi-functional drug carriers, antibacterial decontamination material
Material, tissue engineering bracket etc. have been achieved for some progress to attract people's attention.
Therefore, if can be prepared new in conjunction with the high-activity high-selectivity of hyperbranched polymer structure advantage and click chemistry
Type clicks dissaving polymer, and to realize that polymer ends active group quantity and position are controllable, alternative is at one
Different number and polymer of different nature or functional molecular are grafted on molecular backbone, it will be in the research of multifunctional biomaterials
In, there is important value and extensive use.The problem becomes the technical issues of field is thirsted for solution and realized at present.
Summary of the invention
The object of the invention is in order to solve the above-mentioned technical problem, and provides and a kind of novel highly selective click over-expense
Fluidized polymer and the preparation method and application thereof.The present invention sufficiently combines the advantages of click chemistry, connects on polymer molecule backbone
Branch different number clicks active reactive group with of different nature, so that click chemistry be utilized to be grafted various polymer or function
Energy molecule realizes that polymer ends branched structure quantity is adjustable, prepares multifunctional material, can be applied to multifunctional biomaterials example
In terms of medicine antifouling and antibiosis material and pharmaceutical carrier and metal nano material, surfactant, each field of membrane material；It is another
Aspect, hyperbranched amphipathic multi-block polymer material provided by the invention also have and increase when containing phosphatidyl choline base head
It is the suitable material in the fields such as target medicine carrier and tissue engineering bracket by force by the ability of cellular uptake.
An object of the present invention be to provide it is a kind of it is highly selective it is novel click dissaving polymer, the polymer
Structural formula I is expressed as follows:
Wherein, P is any polymer (polymer such as polyethers, copolyether, polyester, copolyesters or polyethers and polyester), number
Average molecular weight is 1000~20000；X is polymer ends functional group or H；Y is the grafted moiety for being linked at polymer one end,
1 or 2 active reactive groups are had on Y, can be linked with that can click small molecule and carry out chemical reaction, by different number difference
The click chemistry reactive group of type introduces polymer to obtain highly selective novel clicking dissaving polymer；Z1 to Z6
The branch's segment introduced after small molecule can be clicked to introduce, end, which has, carries out a functional group for chemical reaction, has as follows
Structural formula II:
Wherein, 0≤m≤6,2≤n≤6, B are any click chemistry key, Ri(i=1,2,3,4,5,6), respectively correspond Z1,
Z2, Z3, Z4, Z5With Z6。R1, R2, R3, R4, R5, R6It can be the same or different, Ri(i=1,2,3,4,5,6) it include having such as
One of compound of flowering structure: hydrogen atom, alkynyl or thiol group, azido or double bond, wherein R1, R2, R3Or R4,
R5, R6It cannot all simultaneously be hydrogen atom, RiAlkynyl and azido cannot be contained simultaneously in (i=1,2,3,4,5,6) group, or
Person's mercaptan and double bond.When n is 0, B key is not present, and R mono- is set to hydrogen atom.
Further, the grafted moiety Y can be alanine, phenylalanine, the various amino acid such as glutamic acid or
Phe-Glu synthesizes one of dipeptides and other amino acid derivativges, and the active reactive group on Y can be
Carboxyl, hydroxyl, amino etc..
It polymerize further, the polymer P can be selected from polyethers, copolyether, polyester, copolyesters or polyethers and polyester etc.
Object, the number-average molecular weight of polymer P are 1000~20000.
Further, the polymer P can be selected from PLA, PLGA, PCL, PHA, number-average molecular weight is 1000~
20000。
Further, the polymer ends functional group includes-OH ,-COOH etc..Preferably, the polymerization
Object has the following structure one of formula:
Or
Or
Or
Or
Or
The second object of the present invention is to provide the above-mentioned highly selective novel preparation method for clicking dissaving polymer,
Including following preparation step:
(1) compound with a functional group or Liang Ge functional group is chosen, is protected in functional group by blocking group
Under the conditions of, as initiator, by ring-opening reaction, free radical polymerization or anionic polymerisation prepare polymer；
(2) after obtaining polymer, the blocking group of functional group is removed, active reactive group is exposed, and with not
Small molecule of clicking with click chemistry group carries out chemical reaction link, thus obtain it is novel it is highly selective click it is hyperbranched
Polymer.
Above-mentioned reaction mechanism is summarized as follows:
(1) Y initiated polymerization obtains x-P-Y；
(2) in x-P-Y Y functional group, from synthesis carry it is different click chemical reaction functional group small molecule reactions, obtain
To it is highly selective it is novel click dissaving polymer, end has heterogeneity, and different number can click-reaction functional group.
About the synthesis that can click small molecule, citing can be chosen small with multiple hydroxy functional groups and other functional groups
Molecule, hydroxyl carry out WILLIAMS-DARLING Ton with bromo alkynes and react at ether, to introduce alkynyl, obtain the small molecule that can be clicked.Example
Such as: after serinol amino is protected with Boc, being reacted by WILLIAMS-DARLING Ton at ether and reacted with propargyl bromide, introduce alkynyl on double hydroxyls；
Trishydroxymethylaminomethane (Tris) is reacted at ether by WILLIAMS-DARLING Ton and is reacted with the bromo- 1- butine of 4-, is introduced on three hydroxyls
Alkynyl.In addition citing can choose the small molecule with multiple functional groups, and certain functional groups react with mercaptan compound, thus
Introduce the sulfydryl that can be clicked.For example, alanine of amido protecting glutamic acid or amido protecting etc. is with multiple carboxylic groups
The amino group of small molecule, the small molecules such as carboxyl and cysteine or amineothiot reacts, and introduces mercapto in the molecular structure
Base, it is also available to click small molecule.
The third object of the present invention is to provide the above-mentioned novel highly selective application for clicking dissaving polymer.The polymerization
Object can be applied to multifunctional biomaterials such as medicine antifouling and antibiosis material and pharmaceutical carrier and metal nano material, surface is lived
Property each field of agent, membrane material in terms of.
In terms of antifouling and antibiosis material, by the change of the different click chemistry group of polymer ends and its quantity,
The property of can choose access has the sulfonate of anti-pollution function or the quaternary ammonium salt of sterilizing function, and both adjustable ratio, thus
Obtain the adjustable material of antifouling and antibiosis function.
In terms of pharmaceutical carrier, such as the polymer can be grafted phosphatide, pass through click chemistry on polymer ends alkynyl
Grafting has the phosphatidylcholine molecules of azido group, obtains the amphipathic multi-branch polymer with different graft numbers, uses
When making anti-cancer medicament carrier, it can make the micella of the polymer self assembles that there is excellent cancer cell endocytosis efficiency, there is raising
Cellular uptake.
The structural formula of the amphipathic multi-branch polymer as obtained by grafting phosphatidylcholine molecules is as follows:
The structural formula of the amphipathic multi-branch polymer is as follows:
Or
Or
Compared with prior art, beneficial effects of the present invention are as follows:
(1) hyperbranched polymer structure provided by the invention, end active reactive group combine click chemistry, have a little
Hit the advantage of chemistry；
(2) hyperbranched polymer structure provided by the invention, branched structure quantity is adjustable, and the property of can choose is at one point
Different number and polymer of different nature or functional molecular are grafted on sub- main chain；
(3) after grafted by super branched polymer phosphatide provided by the invention, it is phosphorous to obtain amphipathic multi-block polymer material
When phosphatidylcholine base head, have be remarkably reinforced by the ability of cellular uptake, be used as antibacterial and target medicine carrier field
It is suitble to material；
(4) preparation method of the invention is simple, and technical maturity is easily controllable.
Detailed description of the invention
Fig. 1 is the cell endocytic comparative result figure of different structure chemical combination object in experimental example 1；
Fig. 2 is the structure chart of PCL-SerPC4 in experimental example 1；
Fig. 3 is the structure chart of PCL-SerPC2 in experimental example 1；
Fig. 4 is the structure chart of control sample PUEPC in experimental example 1.
Specific embodiment
In order to make the objectives, technical solutions, and advantages of the present invention clearer, with reference to embodiments to the present invention
It is specifically described, it is necessary to, it is noted that following embodiment is used only for that the present invention is explained and illustrated, be not used to
Limit the present invention.Some nonessential modifications and adaptations that those skilled in the art are made according to foregoing invention content, still belong to
In protection scope of the present invention.
Embodiment 1
6-caprolactone vacuumizes dehydration 1h at 60 DEG C, and tert-butyl ester protection alanine and catalyst are added under nitrogen protection
Stannous octoate is warming up to 120 DEG C of reactions for 24 hours.After the reaction was completed, using the trifluoroacetic acid removing tert-butyl ester obtain one end be hydroxyl, it is another
One end is the polycaprolactone of carboxyl；Using serinol and propargyl bromide as raw material, by the boc-protected serinol of aminoterminal and propargyl bromide into
Row WILLIAMS-DARLING Ton reacts to obtain the compound (Boc-AP-alk) with double alkynyl functionalities at ether.Boc-AP-alk is dissolved in full
Amino is exposed with Boc blocking group is removed in hydrogen chloride acetate solution, and the carboxyl of amino and polycaprolactone is in DCC and NHS
In the presence of generate amido bond, obtain the polycaprolactone with double alkynyls, structural formula is as follows:
Double alkynyls in above structure can be reacted with the polymer or functional molecular for having azido, be obtained with Y
The polymer of type branched structure.
Embodiment 2
6-caprolactone vacuumizes dehydration 1h at 60 DEG C, and tert-butyl ester protection glycine and catalyst are added under nitrogen protection
Stannous octoate is warming up to 120 DEG C of reactions for 24 hours.After the reaction was completed, using the trifluoroacetic acid removing tert-butyl ester obtain one end be hydroxyl, it is another
One end is the polycaprolactone of carboxyl；Using serinol and propargyl bromide as raw material, aminoterminal is protected, c-terminus also protected silk ammonia
Acid carries out WILLIAMS-DARLING Ton with propargyl bromide and reacts to obtain the compound (Boc-AP-alk) with alkynyl functionality at ether.Remove carboxyl
Blocking group, serine carboxyl and 6- amino -1- hexyl mercaptan carry out DCC condensation reaction and introduce sulfydryl.Finally remove serine ammonia
The carboxyl of base blocking group, amino and polycaprolactone generates amido bond in the presence of DCC and NHS, obtains with an alkynyl, a mercapto
The polycaprolactone of base, structural formula are as follows:
Above-mentioned double alkynyls can be reacted with the polymer or functional molecular for having azido, be obtained with Y type branching knot
The polymer of structure.
Embodiment 3
According to molecular weight demand, weighs alanine and levorotatory lactide (L-LA) is added in round-bottomed flask, then burning
A small amount of toluene, 60 DEG C of rotary evaporation 0.5h are added in bottle.After being azeotroped off toluene and water, flask is removed, is added 1 ‰
Octoate catalyst stannous and magnetic stir bar start to vacuumize, and lead to nitrogen, then vacuumize, and flask is put into 100 after 3 times repeatedly
2h is persistently vacuumized in DEG C oil bath, to remove toluene and water remaining in oxygen and reactant in bottle.Bottle is evacuated shape
After state, close vacuum valve, flask is totally immersed into oil bath and is warming up to 140 DEG C, under magnetic agitation start polymerization reaction for 24 hours, not between
It is disconnected.Colourless transparent liquid is obtained in flask after reaction, is white solid after cooling, after adding chloroform to dissolve, slowly adds
Enter a large amount of ether stirrings, has white flock precipitate appearance, topple over upper layer ether, then washed 3 times with ether.40 DEG C of rotary evaporations remove
Ether is removed, 60 DEG C of vacuum drying ovens are dry for 24 hours, to remove wherein remaining ether and chloroform, obtain product ala-PLA.With
Serinol and propargyl bromide are raw material, and the boc-protected serinol of aminoterminal is carried out WILLIAMS-DARLING Ton with propargyl bromide and reacts to obtain at ether
With double alkynyl functionality's compounds (Boc-AP-alk).Boc-AP-alk is dissolved in saturation hydrogen chloride acetate solution and is removed
Boc blocking group exposes amino (AP-alk)；Using boc-protected glutamic acid and double alkynyl compounds AP-alk as raw material, lead to
Overactivation ester condensation reacts two carboxyls of glutamic acid with the amino of AP-alk to obtain four alkynyl compounds (Boc-GA-
alk).Boc-GA-alk is dissolved in removing Boc blocking group in saturation Hydrochloride/ethyl acetate and exposes amino, amino with
Activation ester condensation in the presence of DCC and NHS of the carboxyl of ala-PLA generates amido bond, obtains the polylactic acid that one end has four alkynyls:
Alkynyl can be reacted with the polymer or functional molecular for having azido, obtain having the poly- of umbellate form branched structure
Object is closed, there are four branched chains for polymer.
Embodiment 4
6-caprolactone vacuumizes dehydration 1h at 60 DEG C, and tert-butyl ester protection phenylalanine and catalysis are added under nitrogen protection
Agent stannous octoate is warming up to 120 DEG C of reactions for 24 hours.After the reaction was completed, using trifluoroacetic acid removing the tert-butyl ester obtain one end be hydroxyl,
The other end is the polycaprolactone of carboxyl；Using serinol and propargyl bromide as raw material, by the boc-protected serinol of aminoterminal and propargyl bromide
It carries out WILLIAMS-DARLING Ton and reacts to obtain with double alkynyl functionality's compounds (Boc-AP-alk) at ether.Boc-AP-alk is dissolved in full
Amino (AP-alk) is exposed with Boc blocking group is removed in hydrogen chloride acetate solution；With boc-protected glutamic acid and double alkynes
Based compound AP-alk is raw material, makes two carboxyls of glutamic acid react to obtain with the amino of AP-alk by activating ester condensation
To four alkynyl compounds (Boc-GA-alk).Boc-GA-alk is dissolved in removing Boc in saturation Hydrochloride/ethyl acetate to protect
Shield group exposes amino, and activation ester condensation in the presence of DCC and NHS of the carboxyl of amino and polycaprolactone generates amido bond, obtains
The polycaprolactone of four alkynyls is had to one end.
Alkynyl can be reacted with the polymer or functional molecular for having azido, obtain having the poly- of umbellate form branched structure
Object is closed, there are four branched chains for polymer.It reacts, obtains with umbellate form branched structure with the phosphatide with azido if it is alkynyl
Polycaprolactone-phosphatide amphipathic nature block polymer, the copolymer preparation nanoscale carrier micelle have rapidly enters tumour
The ability of cell.
Embodiment 5
PCLH is synthesized by the method for anionic polymerisation.Design the weight that 30 caprolactones (- CL) are introduced in synthetic molecules chain
Multiple unit.First phenylalanine is placed in front of reaction drying for one day in drier.Phenylalanine is weighed in three-necked bottle, is protected in N2
Add anhydrous THF with syringe under shield, after phenylalanine dissolution completely, n-BuLi (n-BuLi) is added with syringe, to shape
At caprolactone (- CL) is added with syringe again after macromole evocating agent, 1.5h is reacted.After completion of the reaction, it is concentrated under reduced pressure and removes
THF is added water sedimentation product, is dried in vacuo to obtain solid product PCLH.Using serinol and propargyl bromide as raw material, by aminoterminal
Boc-protected serinol carries out WILLIAMS-DARLING Ton with propargyl bromide and reacts to obtain with double alkynyl functionality's compound (Boc-AP- at ether
alk)。
Boc-AP-alk is dissolved in removing Boc blocking group in saturation hydrogen chloride acetate solution and exposes amino (AP-
alk)；Amino is protected with Boc, the protected glutamic acid of another carboxyl and double alkynyl compounds AP-alk are raw material, pass through work
Changing ester condensation makes glutamic acid be that exposed carboxyl reacts to obtain the compound with diynyl with the amino of AP-alk；Later
The blocking group for removing another carboxyl in glutamic acid structure reacts amino reaction with 2- amineothiot, draws in the molecular structure
Enter sulfydryl, finally removes Boc blocking group and expose amino, the carboxyl of amino and polycaprolactone activates in the presence of DCC and NHS
Ester condensation generates amido bond, obtains the polycaprolactone that one end has double alkynyls and a sulfhydryl structure；
Alkynyl is reacted with the phosphatide with azido, and mercaptan is reacted with the taxol with double bond, obtains having double-branched
The prodrugs of paclitaxel polymer of phosphatide chain.
Embodiment 6
According to molecular weight demand, weighs phenylalanine and levorotatory lactide (L-LA) is added in round-bottomed flask, then exist
A small amount of toluene, 60 DEG C of rotary evaporation 0.5h are added in flask.After being azeotroped off toluene and water, flask is removed, is added 1 ‰
Octoate catalyst stannous and magnetic stir bar, start to vacuumize, lead to nitrogen, then vacuumize, be put into flask after 3 times repeatedly
2h is persistently vacuumized in 100 DEG C of oil baths, to remove toluene and water remaining in oxygen and reactant in bottle.Bottle is evacuated
After state, vacuum valve is closed, flask is totally immersed into oil bath and is warming up to 140 DEG C, starts polymerization reaction for 24 hours under magnetic agitation, no
Interruption.Colourless transparent liquid is obtained in flask after reaction, is white solid after cooling, after adding chloroform to dissolve, slowly
A large amount of ether stirrings are added, has white flock precipitate appearance, topples over upper layer ether, then washed 3 times with ether.40 DEG C of rotary evaporations
Ether is removed, 60 DEG C of vacuum drying ovens are dry for 24 hours, to remove wherein remaining ether and chloroform, obtain product phe-PLA.
The boc-protected serine of aminoterminal is carried out WILLIAMS-DARLING Ton with propargyl bromide to react to obtain with alkynyl functionality at ether
Compound；Then carboxyl and 2- amineothiot carry out activation ester condensation reaction and obtain the chemical combination with one sulfydryl of an alkynyl
Object.Amino accesses in two carboxyls of glutamic acid after removing Boc blocking group, and obtaining end is alternately alkynyl-sulfydryl-alkynyl-
There are four the compounds of click functional group for sulfydryl tool, the amino of Boc blocking group exposure glutamic acid are finally removed, with polylactic acid
Carboxyl DCC and in the presence of NHS activation ester condensation generate amido bond, obtaining end alternately is double alkynyls and double sulfhydryl structures
Polylactic acid:
Alkynyl and the sulfonic acid reactant salt for having azido, mercaptan and the quaternary ammonium reactant salt for having double bond, obtain antifouling and antibiosis
Material.Furthermore in this structure, the ratio of sulfydryl and alkynyl can also be changed, so that the ratio of sulfonate and quaternary ammonium salt is adjusted,
Obtain the adjustable material of antifouling and antibiosis function.
Embodiment 7
Using serinol and propargyl bromide as raw material, by the boc-protected serinol of aminoterminal and propargyl bromide carry out WILLIAMS-DARLING Ton at
Ether reacts to obtain with double alkynyl functionality's compounds (Boc-AP-alk).Boc-AP-alk is dissolved in saturation chlorination hydroacetic acid second
Boc blocking group is removed in ester solution exposes amino；Using the amino-terminated polyurethane of this compound, obtains end and have
The polyurethane of double alkynyl structures is reacted with the phosphatide with azido by click chemistry, is obtained with double phosphatide branched chains
Polyurethane.
Application examples 1
The PCL-SerPC2 of the PCL-SerPC4 and double phosphatide branched chains that choose four phosphatide branched chains are research object, with
The PUEPC with multiple phospholipid side chains of laboratory synthesis is control sample, and the cell endocytic for having studied this patent protection structure is taken the photograph
Ability is taken, as a result as shown in Figure 1.
The result shows that: after co-culturing 3 as a child with tumour cell HELA cell, observed by laser co-focusing, and make
Fluorescence intensity in picture is calculated with software I mageJ, it is found that HELA cell takes the photograph PCL-SerPC4 and PCL-SerPC2
Degree is taken to be significantly larger than PUEPC, it was demonstrated that the polymer micelle of this patent protection structure is easier to enter HELA cell, has stronger
Cell internalizing ability.
Claims (10)
1. novel highly selective dissaving polymer is clicked a kind of, which is characterized in that the structural formula I of the polymer indicates such as
Under:
Wherein, P is any polymer (polymer such as polyethers, copolyether, polyester, copolyesters or polyethers and polyester), and number is divided equally
Son amount is 1000~20000；X is polymer ends functional group or H；Y is the grafted moiety for being linked at polymer one end, on Y
With 1 or 2 active reactive groups, the active reactive group can be linked with that can click small molecule and carry out chemical reaction,
(the different types of click chemistry reactive group of different number is introduced into polymer to obtain highly selective novel clicking over-expense
Fluidized polymer)；Z1 to Z6 is that link can click the branch's segment introduced after small molecule, and end has the official of click chemistry reaction
It can roll into a ball, the Z1To Z6Have the following structure formula II:
Wherein, 0≤m≤6,0≤n≤6, B key are any click chemistry key (ester bond, amido bond, ehter bond etc.), RiMiddle number i is
1,2,3,4,5,6, respectively correspond Z1, Z2, Z3, Z4, Z5With Z6, R1, R2, R3, R4, R5, R6It can be the same or different, Ri(i=
1,2,3,4,5,6) include one of the compound having the following structure: hydrogen atom, alkynyl or thiol group, azido or
Double bond；
Wherein, R1, R2, R3Or R4, R5, R6It cannot all simultaneously be hydrogen atom；
It cannot be simultaneously containing alkynyl and azido or mercaptan and double bond in R group；
When n is 0, B key is not present, and R mono- is set to hydrogen atom.
2. novel highly selective dissaving polymer is clicked according to claim 1, which is characterized in that the grafting base
Group Y can be alanine, phenylalanine, and the various amino acid such as glutamic acid or Phe-Glu synthesize dipeptides, Yi Jiqi
One of his amino acid derivativges, the active reactive group on Y can be carboxyl, hydroxyl, amino.
3. novel highly selective dissaving polymer is clicked according to claim 1, which is characterized in that the polymer
P can be selected from the mixture of polyethers, copolyether, polyester, copolyesters or polyethers and polyester, and the number-average molecular weight of polymer P is 2000
~10000.
4. novel highly selective dissaving polymer is clicked according to claim 1, which is characterized in that the linkization
Learning key B can be ester bond, amido bond or ehter bond.
5. novel highly selective dissaving polymer is clicked according to claim 3, which is characterized in that the polymer
P can be selected from PLA, PLGA, PCL, PHA, and molecular weight is 2000~10000.
6. novel highly selective dissaving polymer is clicked according to claim 1, which is characterized in that the polymer
Functional end-group X can be-OH ,-COOH.
7. novel highly selective dissaving polymer is clicked according to claim 1, which is characterized in that the polymer
Have the following structure one of formula:
8. any one of -7 novel highly selective preparation method for clicking dissaving polymer according to claim 1, special
Sign is that the preparation method includes the following steps:
(1) compound with a functional group or Liang Ge functional group is chosen, in the condition that functional group is protected by blocking group
Under, as initiator, by ring-opening reaction, free radical polymerization or anionic polymerisation are prepared polyethers, copolyether, are gathered
The polymer such as ester, copolyesters or polyethers and polyester.
(2) after obtaining polymer, remove the blocking group of functional group, expose active reactive group, with have difference
The small molecule of clicking for hitting chemical group carries out chemical reaction link, to obtain novel highly selective clicking hyperbranched polymerization
Object.
9. novel highly selective dissaving polymer of clicking according to claim 1-7 is in pharmaceutical carrier, gold
Application in terms of each field of metal nanometer material, surfactant, membrane material.
10. the novel highly selective application for clicking dissaving polymer in terms of pharmaceutical carrier according to claim 7,
It is characterized in that, the application is to be grafted phosphatidylcholine molecules by click chemistry in polymer ends, obtain that there is difference
The amphipathic multi-branch polymer of graft numbers when being used as anti-cancer medicament carrier, can make the micella of the polymer self assembles
With excellent cancer cell endocytosis efficiency, the structural formula of the amphipathic multi-branch polymer is as follows:
Or
Or
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| CN114920917A (en) * | 2021-12-30 | 2022-08-19 | 康辉新材料科技有限公司 | Low-melting-index high-crystallization-temperature branched poly (butylene terephthalate-adipate) and preparation method thereof |
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