CN101580506B - 1-3 generation arylene ether dendritic phthalocyanine complex and polymer nano-particle thereof - Google Patents

1-3 generation arylene ether dendritic phthalocyanine complex and polymer nano-particle thereof Download PDF

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CN101580506B
CN101580506B CN2009101118461A CN200910111846A CN101580506B CN 101580506 B CN101580506 B CN 101580506B CN 2009101118461 A CN2009101118461 A CN 2009101118461A CN 200910111846 A CN200910111846 A CN 200910111846A CN 101580506 B CN101580506 B CN 101580506B
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mpc
phthalocyanine
methionin
polyethylene glycol
aryl oxide
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CN101580506A (en
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彭亦如
张宏
黄宝铨
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Fujian Normal University
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Fujian Normal University
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Abstract

The invention discloses a 1-3 generation arylene ether-substituted dendritic phthalocyanine zinc complex, a preparation method and an application thereof. The method comprises the following steps of adopting a Frechet synthesis method to synthesize the first to third generation alcohol molecules which take the 1-3 generation cyan as an end group; leading the first to third generation alcohols to react with 4-nitrophthalonitrile respectively, thus synthesizing corresponding phthalocyanine precursor of dendrimer taking the 1-3 generation cyan as the end group; subsequently, leading the phthalocyanine precursor ring of dendrimer taking the 1-3 generation cyan as the end group to synthesize corresponding arylene ether dendritic phthalocyanine taking the first to third generation cyan as the end group and the arylene ether dendritic phthalocyanine taking the first to third generation carboxyl as the end group generated by hydrolysis. The 1-3 generation arylene ether dendritic phthalocyaninecomplex and the amphiphilic block copolymer are automatically dissolved to form the polymer nano-particle loading the 1-3 generation arylene ether dendritic phthalocyanine complex. The 1-3 generation diaryl ether dendritic phthalocyanine zinc complex and the loaded polymer nano-particle thereof are used as photosencitizers for photodynamic therapy.

Description

1-3 is for aryl oxide dendritic phthalocyanine complex and polymer nano-particle thereof
Technical field:
The invention belongs to the title complex field, especially belong to a kind of 1-3 for aryl oxide dendritic phthalocyanine Zn complex and polymer nano-particle and preparation method, this title complex is applied to optical dynamic therapy moist degeneration of macula class disease and cancer as photosensitizers.
Background technology:
(photodynamic therapy PDT) is a kind of treatment cancer to PDT, the novel method of HIV and moist degeneration of macula class disease.The key of optical dynamic therapy is a photosensitizers.Phthalocyanine complex is because of having the skeleton structure similar with porporino, and structure is more stable and be prone to modification, and maximum absorption wavelength is positioned at about 670nm, is prone to see through the ruddiness zone of tissue and can make pure article, is considered to one type of very potential photosensitizers.Because the intermolecular intensive π of phthalocyanine-π effect is assembled easily, thereby reduce the fluorescence quantum yield of molecule, shorten the triplet quantum life-span, thereby reduce photosensitization efficient.Therefore, be difficult for the goal in research that the accumulative photosensitizers is for we between the design synthetic molecules.
Dendritic polymer (dendrimer) is the one type of novel cpd with special construction that grows up nearly decades.This hyperbranched polymer with exquisite structure had caused scientist's attention immediately after people such as Tomalia and Newkome successfully synthesize first kind dendritic polymer first in 1985.Branch type polymkeric substance is made up of three parts, i.e. core, branching unit and peripheral functional group.Be characterized in compound with regular structure, controlledly synthesis, molecular scale is at nano level, and the internal cavity can comprise various molecules.Along with the growth of periphery functional group algebraically, functional group's number is Exponential growth to the periphery from core.The functional group surface can be made into the close quarters of being made up of the differing mol group.These molecular radicals can play the effect of hook, can combine with the multivalent molecule attachment point of virus and cell surface, thereby are used to adhere to various useful molecules.In addition, three-dimensional branch macromole is a non-biological material, can not bring out patient's immunoreation; So select the carrier of branch macromole as medicine; Carrying and carry medicine to get into the blood of human body circulation and be transported to diseased region, reach therapeutic purpose, is the development trend of Nano medication.Appearing in the newspapers with the phthalocyanine complex with optical dynamic therapy effect abroad is nuclear, only 5 types of the macromolecular dendroid photosensitizerss of around branch.Julien L.D etc. are through synthetic eight replacements of the method for dispersing 5 generation phosphorus hydrazine dendriform metal-free phthalocyanine.Mutsumi Kimura etc. replace polyethers-amino dendritic phthalocyanine zinc through the method for dispersing synthetic four.Mutsumi Kimura etc. have also synthesized four replacements through the method for dispersing and have contained the dendritic phthalocyanine cobalt of Behera ammonia.Casey A. etc. are through synthetic eight replacements of convergent synthesis 3 generation poly alkyl ether metal-free phthalocyanine.Dennis K.P.Ng is through the synthetic ester class end group four replacements 3 generation polyarylether Phthalocyanine Zinc that has of convergent synthesis.Result of study shows: compare with traditional phthalocyanine complex, these are nuclear with the phthalocyanine complex, and three-dimensional branch macromole is that substituent photosensitizers has the following advantages: along with periphery functional group algebraically increases, effectively penetrating wavelength increases; Because big sterically hindered of periphery functional group has the site centrifugation to phthalocyanine nucleus, cause phthalocyanine under high density, also to be difficult for forming aggregate, and the high point of the quantum yield of singlet oxygen.Also do not see with the end group to be the report of the 1-3 of carboxyl and cyanic acid both at home and abroad for the aryl oxide dendritic phthalocyanine complex.
Also have, all there is a common weakness in described phthalocyanine complex as the photosensitizers of the s-generation, and uptake ratio and inrichment in the cambium are lower.And the 3rd generation photosensitizers be the 2nd generation photosensitizers verivate, they are on the 2nd generation photosensitizers, to adhere to or introduce some molecular vehicles, utilize the selectivity identification of this carrier to cambium, and photosensitizers is transported to the right newborn position of target selectively.Agreed that by U.S. FDA the carrier that is used for clinical treatment has: polymer micelle and liposome and water-soluble polymers.Polymer micelle is the particulate that is self-assembled into hydrophobic core-wetting ability shell with the segmented copolymer of polyoxyethylene glycol and hydrophobic polymer such as polyamino acid, POLYACTIC ACID or polyoxytrimethylene structure; It dissolves the spontaneous formation macromolecule micelle in back in water, accomplish solubilising and parcel to medicine.Therefore, can the size of polymer micelle be reduced to below the 100nm through control.Because the unique undersized character of micella, permeability is high, can get into histoorgan that many macroparticles are difficult to get into or the biological barrier that is difficult to cross, and is detained at the cambium position, in the inner special enrichment of cambium.Therefore; The nanostructure of this nucleocapsid structure polymer particle can improve the penetration power of dendroid photosensitizers at cambium; The hydrophilic polymer segment can promote polymer particle in blood circulation and be transported near the cambium, hydrophobic segment makes polymer particle be prone to be absorbed by cambium.The quenching of fluorescence after the dendritic phthalocyanine photosensitizers aggregate load is avoided in the existence of polymkeric substance hydrophilic segment simultaneously.Therefore the nanometer polymer particle is expected stronger target to the ability of cambium, uptake ratio and high fluorescence quantum yield in cambium, thereby has stronger photodynamic activity.
Summary of the invention:
The object of the present invention is to provide a kind of 1-3 for aryl oxide dendritic phthalocyanine complex and polymer nano-particle and preparation method.
The present invention also proposes 1-3 for the application as photosensitizers of aryl oxide dendritic phthalocyanine complex and polymer nano-particle thereof.
The objective of the invention is to realize like this, 1-3 of the present invention is the compound of following structure for the aryl oxide dendritic phthalocyanine complex:
The compound of (1) first kind of structure:
Figure GSB00000821448700021
In the formula: M is hydrogen, silicon, iron, titanium, cobalt, zinc, aluminium or copper;
In the formula: R is a cyanic acid, nitro, carboxyl or ester.R in the structural formula is identical group, and described aryl oxide branch substituting group the position of substitution on the phthalocyanine phenyl ring is the β position.
The compound of (2) second kinds of structures:
In the formula: M is hydrogen, silicon, iron, titanium, cobalt, zinc, aluminium or copper;
In the formula: R is a cyanic acid, nitro, carboxyl or ester.R in the structural formula is identical group, and described aryl oxide branch substituting group the position of substitution on the phthalocyanine phenyl ring is the β position.
(3) compound of the third structure:
Figure GSB00000821448700041
In the formula: M is hydrogen, silicon, iron, titanium, cobalt, zinc, aluminium or copper;
In the formula: R is a cyanic acid, nitro, carboxyl or ester.R in the structural formula is identical group, and described aryl oxide branch substituting group the position of substitution on the phthalocyanine phenyl ring is the β position.
And the cyanic acid reaction generates carboxyl or ester group all is the technology that those skilled in the art can realize.
To cyanic acid benzyl bromine use to nitrobenzyl bromine replacement just can generate R in the said structure formula as the 1-3 of nitro for the aryl oxide dendritic phthalocyanine complex.
The preferred 1-3 of the present invention is for the aryl oxide dendritic phthalocyanine complex, and its structure is following:
1) chemical formula is four-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl] phthalocyanine (9) [G 1-MPc (CN) 8]
Structural formula is:
Figure GSB00000821448700051
In the formula: M is hydrogen, silicon, iron, titanium, cobalt, zinc, aluminium or copper.
Described aryl oxide branch substituting group the position of substitution on the phthalocyanine phenyl ring is the β position.
2) chemical formula is four-{ 3,5-two-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl } phthalocyanine (10) [G 2-MPc (CN) 16]
Structural formula is:
Figure GSB00000821448700052
In the formula: M is hydrogen, silicon, iron, titanium, cobalt, zinc, aluminium or copper.
In the formula: described aryl oxide branch substituting group the position of substitution on the phthalocyanine phenyl ring is the β position.
3) chemical formula is four-{ 3,5-two-{ 3,5-two-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl }-1-methylene oxygen phenyl } phthalocyanine (11) [G 3-MPc (CN) 32]
Structural formula is:
Figure GSB00000821448700061
In the formula: M is hydrogen, silicon, iron, titanium, cobalt, zinc, aluminium or copper.
In the formula: described aryl oxide branch substituting group the position of substitution on the phthalocyanine phenyl ring is the β position.
4) chemical formula is four-[3,5-two-(4-carboxyl benzyloxy)-1-methylene oxygen phenyl] phthalocyanine (12) [G 1-MPc (COOH) 8]
Structural formula is:
Figure GSB00000821448700071
In the formula: M is hydrogen, silicon, iron, titanium, cobalt, zinc, aluminium or copper.
In the formula: described aryl oxide branch substituting group the position of substitution on the phthalocyanine phenyl ring is the β position.
5) chemical formula is four-{ 3,5-two-[3,5-two-(4-carboxyl benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl } phthalocyanine (13) [G 2-MPc (COOH) 16]
Structural formula is:
Figure GSB00000821448700072
In the formula: M is hydrogen, silicon, iron, titanium, cobalt, zinc, aluminium or copper.
In the formula: described aryl oxide branch substituting group the position of substitution on the phthalocyanine phenyl ring is the β position.
6) chemical formula is four-{ 3,5-two-{ 3,5-two-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl }-1-methylene oxygen phenyl } phthalocyanine (14) [G 3-MPc (COOH) 32].
Structural formula is:
In the formula: M is hydrogen, silicon, iron, titanium, cobalt, zinc, aluminium or copper.
Aryl oxide branch substituting group the position of substitution on the phthalocyanine phenyl ring described in the formula is the β position.
The above-mentioned 1-3 of the present invention is to introduce bulky dendrimer at the phthalocyanine complex periphery for the aryl oxide dendritic phthalocyanine complex, realizes that " site " separate, and is expected to suppress aggregate and forms, and improves the photosensitive activity of photosensitizers.
1-3 of the present invention is for aryl oxide dendritic phthalocyanine complex preparation method, and concrete steps are following:
1) at first adopting the synthetic 1-3 of Fr é chet synthesis method is the dendrimer of end group for cyanic acid.Promptly with 3, the 5-dihydroxybenzyl alcohol is the branch monomeric unit, and to cyanic acid benzyl bromine and branch monomeric unit 3, the 5-dihydroxybenzyl alcohol synthesized for " 1 " generation in salt of wormwood and acetone soln pure: 3, and 5-two-(4-cyanic acid benzyloxy) phenylcarbinol (CN) 2-[G-1]-OH is called for short material (1).This material (1) and carbon tetrabromide and triphenylphosphine are synthesized " 1 " for the benzyl bromine: 3,5-two-(4-cyanic acid benzyloxy) benzyl bromine (CN) 2-[G-1]-Br is called for short material (2).With this material (2) and 3, it is pure that the coupling of 5-dihydroxybenzyl alcohol synthesized for " 2 " generation: 3, and 5-two-[3,5-two-(4-cyanic acid benzyloxy) benzyloxy] phenylcarbinol (CN) 4-[G-2]-OH is called for short material (3).This material (3) and carbon tetrabromide and triphenylphosphine are synthesized " 2 " for the benzyl bromine: 3,5-two-[3,5-two-(4-cyanic acid benzyloxy) benzyloxy] benzyl bromine (CN) 4-[G-2]-Br is called for short material (4).Repeat above synthetic route, above-mentioned material (4) and 3,5-dihydroxybenzyl alcohol synthetic " 3 " is for pure: 3,5-two-{ 3,5-two-[3,5-two-(4-cyanic acid benzyloxy) benzyloxy] } phenylcarbinol (CN) 8-[G-3]-OH is called for short material (5).
2) in the presence of salt of wormwood, in DMF solution, above-mentioned material (1) (is seen, material (3) for alcohol in " the 1st to the 3rd "; Material (5)) reacts with the 4-nitrophthalonitrile respectively, synthesize and contain the phthalocyanine presoma that " the 1st to the 3rd " is the dendrimer of end group for cyano-containing, be respectively: 3; 5-two-(4-cyanic acid benzyloxy) benzyloxy phthalonitrile is called for short material (6) and 3,5-two-[3; 5-two-(4-cyanic acid benzyloxy) benzyloxy] phthalonitrile, be called for short material (7) and 3,5-two-{ 3; 5-two-[3,5-two-(4-cyanic acid benzyloxy) benzyloxy] } phthalonitrile, be called for short material (8).
3) with DBU (1; 8-diazacyclo [5; 4,0] be catalyzer hendecene-7), lithium chloride, silicon tetrachloride, iron(ic)chloride, NSC 51149, zinc acetate, cupric chloride, titanium tetrachloride, aluminum chloride are template; To contain " the 1st to the 3rd " generation is phthalocyanine presoma (seeing above-mentioned material (6)-material (8)) the cyclization one-tenth corresponding " the 1st to the 3rd " of the dendrimer of end group aryl oxide dendritic phthalocyanine for the cyano-containing end group with cyanic acid; Be respectively: four-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl] phthalocyanines, be called for short material (9) [G 1-MPc (CN) 8], four-{ 3,5-two-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl } phthalocyanine (10) [G 2-MPc (CN) 16], be called for short material (10) and four-{ 3,5-two-{ 3,5-two-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl }-1-methylene oxygen phenyl } phthalocyanine [G 3-MPc (CN) 32], be called for short material (11).
In the above-mentioned steps to cyanic acid benzyl bromine use to nitrobenzyl bromine replacement just can generate contain the nitro end group 1-3 for the aryl oxide dendritic phthalocyanine complex, and other reaction conditions is the same, is the technology that the present technique personnel can realize.
4) with above-mentioned material (9), material (10) and material (11) are hydrolyzed in NaOH accordingly that " the 1st to the 3rd " is respectively with the aryl oxide branch phthalocyanine of carboxyl end groups: four-[3,5-two-(4-carboxyl benzyloxy)-1-methylene oxygen phenyl] phthalocyanine [G 1-MPc (COOH) 8], be called for short material (12) and four-{ 3,5-two-[3,5-two-(4-carboxyl benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl } phthalocyanine [G 2-MPc (COOH) 16], be called for short material (13) and four-{ 3,5-two-{ 3,5-two-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl }-1-methylene oxygen phenyl } phthalocyanine, be called for short material (14) [G 3-MPc (COOH) 32].
And cyanic acid reaction generation contains the technology that the 1-3 of carboxyl or ester group can realize for those skilled in the art for the aryl oxide dendritic phthalocyanine complex.
Another object of the present invention is achieved in that load 1-3 of the present invention comprises for the polymer nano-particle of aryl oxide dendritic phthalocyanine complex: 1) material (9) [G 1-MPc (CN) 8] and gather (N ε-carbobenzoxy-(Cbz) Methionin)-polyethylene glycol-(N ε-carbobenzoxy-(Cbz) Methionin) polymer nano-particle that constitutes, i.e. material (9) [G 1-MPc (CN) 8]/gather (N ε-carbobenzoxy-(Cbz) Methionin)-polyethylene glycol-(N ε-carbobenzoxy-(Cbz) Methionin) polymer nano-particle, described material (9) [G 1-MPc (CN) 8] and gather (N ε-carbobenzoxy-(Cbz) Methionin)-polyethylene glycol-(N ε-carbobenzoxy-(Cbz) Methionin) material (9) [G in the polymer nano-particle 1-MPc (CN) 8] and gather (N ε-carbobenzoxy-(Cbz) Methionin)-polyethylene glycol-(N ε-carbobenzoxy-(Cbz) Methionin) mol ratio is 8: 1, and promptly mol ratio is 8: 1 material (9) [G 1-MPc (CN) 8]/gather (N ε-carbobenzoxy-(Cbz) Methionin)-polyethylene glycol-(N ε-carbobenzoxy-(Cbz) Methionin) polymer nano-particle; 2) mol ratio is 5: 1 material (9) [G 1-MPc (CN) 8]/gather (N ε-carbobenzoxy-(Cbz) Methionin)-the polyethylene glycol polymer nanoparticle; 3) mol ratio is 6: 1 material (10) [G 2-MPc (CN) 16]/gather (N ε-carbobenzoxy-(Cbz) Methionin)-polyethylene glycol-(N ε-carbobenzoxy-(Cbz) Methionin) polymer nano-particle; 4) mol ratio is 4: 1 material (10) [G 2-MPc (CN) 16]/gather (N ε-carbobenzoxy-(Cbz) Methionin)-the polyethylene glycol polymer nanoparticle; 5) mol ratio is 5: 1 material (11) [G 3-MPc (CN) 32]/gather (N ε-carbobenzoxy-(Cbz) Methionin)-polyethylene glycol-(N ε-carbobenzoxy-(Cbz) Methionin) polymer nano-particle; 6) mol ratio is 2: 1 material (11) [G 3-MPc (CN) 32]/gather (N ε-carbobenzoxy-(Cbz) Methionin)-the polyethylene glycol polymer nanoparticle; 7) mol ratio is 4: 1 material (12) [G 1-MPc (COOH) 8]/polylysine-polyethylene glycol-Methionin polymer nano-particle; 8) mol ratio is 2: 1 material (12) [G 1-MPc (COOH) 8]/polylysine-polyethylene glycol polymer nanoparticle; 9) mol ratio is 2: 1 material (13) [G 2-MPc (COOH) 16]/polylysine-polyethylene glycol-Methionin polymer nano-particle; 10) mol ratio is 1: 1 material (13) [G 2-MPc (COOH) 16]/polylysine-polyethylene glycol polymer nanoparticle; 11) mol ratio is 1: 1 material (14) [G 3-MPc (COOH) 32]/polylysine-polyethylene glycol-Methionin polymer nano-particle; 12) mol ratio is 2: 1 material (14) [G 3-MPc (COOH) 32]/polylysine-polyethylene glycol polymer nanoparticle.
The amphiphilic of the above-mentioned indication of the present invention block polymer altogether is meant positively charged polylysine-polyethylene glycol-Methionin and polyethylene glycol-Methionin; With uncharged (N that gathers ε-carbobenzoxy-(Cbz) Methionin)-polyethylene glycol-(N ε-carbobenzoxy-(Cbz) Methionin) and gather (N ε-carbobenzoxy-(Cbz) Methionin)-polyoxyethylene glycol.Wherein the molecular weight of polyoxyethylene glycol is in the 500-20000 scope.
The solvent of 1-3 for the aryl oxide dendritic phthalocyanine complex dissolved in the present invention; Character to concrete phthalocyanine complex can be water, organic solvent (DMSO 99.8MIN., N, dinethylformamide, THF etc.); Buffered soln (phosphoric acid salt), trishydroxymethyl amine salt acid solution or other systems.
Load 1-3 of the present invention has following two kinds for the preparation method of the polymer nano-particle of aryl oxide dendritic phthalocyanine complex:
Method 1, amphiphilic block polymer carrier are altogether gathered (N ε-carbobenzoxy-(Cbz) Methionin)-polyethylene glycol-(N ε-carbobenzoxy-(Cbz) Methionin) and gather (N ε-carbobenzoxy-(Cbz) Methionin)-and polyoxyethylene glycol is dissolved among the DMF/DMSO, and the 1-3 that gets end group and be cyanic acid is for aryl oxide dendritic phthalocyanine material (9) [G 1-MPc (CN) 8], material (10) [G 2-MPc (CN) 16] and material (11) [G 3-MPc (CN) 32] one of be dissolved among the DMF, be made into certain density solution, both are mixed, add zero(ppm) water in the solution, place dialysis tubing to dialyse behind 48h～72h filtrating, take out micellar solution, use filtering with microporous membrane.Method 2:; Amphiphilic is the block polymer carrier altogether: polylysine-polyethylene glycol-Methionin and polyethylene glycol-Methionin are dissolved in the disodium phosphate soln respectively; Be made into certain density solution, the 1-3 that gets end group and be carboxyl is for aryl oxide dendritic phthalocyanine material (12) [G 1-MPc (COOH) 8], material (13) [G 2-MPc (COOH) 16] and material (14) [G 3-MPc (COOH) 32] a kind of being dissolved in the SODIUM PHOSPHATE, MONOBASIC, be made into certain density solution.Polymer support polylysine-polyethylene glycol-Methionin and polyethylene glycol-lysine solution and material (12) [G 1-MPc (COOH) 8], material (13) [G 2-MPc (COOH) 16] and material (14) [G 3-MPc (COOH) 32] one of solution according to a certain amount of than mixing, form polymer nano-particle.
Beneficial effect of the present invention: these are nuclear with the phthalocyanine complex for the present invention; The photosensitizers that three-dimensional branch macromole is a carrier is compared with traditional phthalocyanine complex; Has increase along with algebraically; The peripheral group of the dendritic polymer that increases strengthens the obvious red shift of absorption spectrum to the insulation blocking effect of core; Phthalocyanine nucleus does not form aggregate yet under high density, improve the photosensitive activity of photosensitizers, advantages such as the quantum yield of high singlet oxygen.In addition, the high negative charge density carboxyl substituent of phthalocyanine periphery, it is well water-soluble to give phthalocyanine complex, and easy and other drug carrier interaction.
The present invention is wrapped in the intrafascicular formation polymer nano-particle of polymer latex that amphipathic nature block polymer forms with 1-3 for aryl oxide dendritic phthalocyanine complex photosensitizers; On the one hand, 1-3 can to a certain degree further suppress again for the congregation of aryl oxide dendritic phthalocyanine complex photosensitizers.On the other hand; 1-3 forms the stable polymer nano-particle with nucleocapsid structure for aryl oxide dendritic phthalocyanine complex photosensitizers and amphipathic nature block polymer through the electrostatic interaction self-assembly, and the nanostructure of this nucleocapsid structure polymer particle can improve the penetration power of photosensitizers at cambium.Because the activation force that the nanometer polymer particle forms is the uncompatibility of hydrophobic segment and water and being separated of hydrophobic segment and hydrophilic segment; The hydrophilic polymer segment can promote polymer particle in blood circulation and be transported near the cambium, hydrophobic segment makes polymer particle be prone to be absorbed by cambium.The existence of polymkeric substance hydrophilic segment simultaneously, the quenching of fluorescence after avoiding 1-3 for aryl oxide dendritic phthalocyanine complex photosensitizers aggregate load.Therefore the nanometer polymer particle is expected effectively to improve 1-3 for the tissue penetration property of aryl oxide dendritic phthalocyanine metal complexes photosensitizers and the uptake ratio of cambium; Stronger target is arranged to the ability of cambium, uptake ratio and high fluorescence quantum yield in cambium, thereby have stronger photodynamic activity.
Embodiment:
Below in conjunction with embodiment the present invention is elaborated:
1) " 1 " generation alcohol: 3,5-two-(4-cyanic acid benzyloxy) phenylcarbinol (1) synthetic
In three-necked bottle, add 20g to cyanic acid benzyl bromine, 5.0g 3,5-dihydroxybenzyl alcohol, 15g Anhydrous potassium carbonate, 200mL acetone, 90 ℃ of back flow reaction 25h under nitrogen protection.With trichloromethane and water extraction.Crude product is used the normal hexane recrystallization, obtains white powder " 1 " generation alcohol: 3, and 5-two-(4-cyanic acid benzyloxy) phenylcarbinol (1) solid 15g, productive rate 89%.
2) " 1 " for the benzyl bromine: 3, and 5-two-(4-cyanic acid benzyloxy) benzyl bromine (2) synthetic
Material (1) 5g that in three-necked bottle, adds above-mentioned steps, carbon tetrabromide 10g, triphenylphosphine 3g and 40mL THF, 40 ℃ of reaction response 1h under nitrogen protection.Reaction solution is with trichloromethane and water extraction.Crude product is used the normal hexane recrystallization, obtains white powder solid (2) 5.2g, productive rate 82.5%.
3) " 2 " generation alcohol: 3,5-two-[3,5-two-(4-cyanic acid benzyloxy) benzyloxy] phenylcarbinol (3) synthetic
In three-necked bottle, add material (2) 5g, 3,5-dihydroxybenzyl alcohol 2g, Anhydrous potassium carbonate 2.5g and acetone 100mL, 30 ℃ of back flow reaction 48h under nitrogen protection.Product is with trichloromethane and water extraction, normal hexane recrystallization.Get white plates solid matter (3) 3.25g, productive rate 75%.
4) the " 2 " for the benzyl bromine: 3,5-two-[3,5-two-(4-cyanic acid benzyloxy) benzyloxy] benzyl bromine (4) synthetic
In three-necked bottle, add material (3) 5g, carbon tetrabromide 10g, triphenylphosphine 4g and THF 50mL, 40 ℃ of reaction response 4h under nitrogen protection.Reaction solution is with trichloromethane and water extraction.Crude product is used the normal hexane recrystallization, obtains white powder solid matter (4) 5.7g, productive rate 82.1%.
5) " 3 " generation alcohol: 3,5-two-{ 3,5-two-[3,5-two-(4-cyanic acid benzyloxy) benzyloxy] } phenylcarbinol (5) synthetic
In three-necked bottle, add material (4) 5g, carbon tetrabromide 20g, triphenylphosphine 8g and THF 200mL, 40 ℃ of reaction response 3h under nitrogen protection.Reaction solution is with trichloromethane and water extraction, and crude product is used the normal hexane recrystallization, obtains white powder solid matter (5) 5.7g, productive rate 89.1%.
6) presoma: 3,5-two-(4-cyanic acid benzyloxy) benzyloxy phthalonitrile (6) synthetic
With material (1) 2.0g, 4-nitrophthalonitrile 1g and K 2CO 32g is dissolved in the 40mL DMF solution, 60 ℃ of stirring reaction 6h.Cold filtration pours into filtrating in the frozen water, separates out deposition, filters collecting precipitation.Thick product is through recrystallizing methanol, and vacuum-drying gets faint yellow solid material (6) 0.76g, productive rate 50%.
7) presoma: 3,5-two-[3,5-two-(4-cyanic acid benzyloxy) benzyloxy)] phthalonitrile (7) synthetic
Material (3) 2g, 4-nitrophthalonitrile 1g, K 2CO 31g is dissolved among the 20mL DMF, and 70 ℃ of stirring reactions spend the night.After the question response liquid cooling but, filtrating pours in the frozen water, separates out deposition.Filter collecting precipitation.Deposition is used through recrystallizing methanol 2～3 times, vacuum-drying, faint yellow solid material (7) 1.19g, productive rate 60%.
8) presoma: 3,5-two-{ 3,5-two-[3,5-two-(4-cyanic acid benzyloxy) benzyloxy] } phthalonitrile (8) synthetic
Material (5) 1g, 4-nitrophthalonitrile 2g and K 2CO 33.0g be dissolved among the 30mL DMF 70 ℃ of stirred overnight reactions.After the question response liquid cooling but, filter, filtrating pours in the frozen water, separates out deposition, filters collecting precipitation.Deposition is used through recrystallizing methanol 2～3 times, vacuum-drying, faint yellow solid material (9) 2.13g, productive rate 62%.
9) " 1 " generation was the dendritic phthalocyanine photosensitizers of end group with cyanic acid: four-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl] Phthalocyanine Zinc (9) [G 1-ZnPc (CN) 8] synthetic
In the 100mL three-necked bottle, add 0.2g material (6) respectively, Zn (OAc) 20.04g with Pentyl alcohol 20mL, under nitrogen protection, drip DBU 1mL, 190 ℃ of stirring and refluxing reaction 5h.Reaction is cooled to room temperature after finishing, and crosses to filter green bullion.Bullion is with CHCl 3Be eluent,, get deep green solid matter (9) 0.12g, productive rate 60% through silica gel column chromatography separating purification.IR(KBr/cm -1)：3450，2920，2230，1600，1450，1165，1060，822，580。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.67(s，4H)，7.24-7.25(d，J＝4Hz，4H)，7.16～7.17(d，J＝4Hz，4H)，7.63～7.65(d，J＝8Hz，16H)，7.47～7.49(d，J＝8Hz，16H)，6.57(s，8H)，6.50(s，4H)，5.05(s，24H).MALDI-TOF-MS：m/z＝2068[M+H 3O +]。
10) " 2 " generation was the dendritic phthalocyanine photosensitizers of end group with cyanic acid: four-{ 3,5-two-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl } Phthalocyanine Zinc (10) [G 2-ZnPc (CN) 16] synthetic
In three-necked bottle, add material (7) 0.39g, Zn (OAc) 20.04g with Pentyl alcohol 20mL, under nitrogen protection, drip DBU 1mL, 200 ℃ of stirring and refluxing reaction 10h.Reaction is cooled to room temperature after finishing, and filters collecting precipitation, vacuum-drying.Bullion is with CH 3OH is an eluent, separates through silica gel column chromatography and purifies, and vacuum-drying gets deep green solid matter (10) 0.24g, productive rate 80%.IR(KBr/cm -1)：3450，2920，2230，1600，1450，1251，1153，1067，822，580。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.80～7.82(d，J＝8Hz，32H)，7.56～7.58(d，J＝8Hz，32H)，7.38(s，4H)，7.29(s，4H)，7.19～7.21(d，J＝8Hz，4H)，6.69(s，16H)；6.61(s，12H)，6.57(s，8H)，5.17(s，40H)，4.99(s，16H)。MALDI-TOF-MS：m/z＝3949[M+H 3O +].
11) " 3 " generation was the dendritic phthalocyanine photosensitizers of end group with cyanic acid: four-{ 3,5-two-{ 3,5-two-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl }-1-methylene oxygen phenyl } Phthalocyanine Zinc (11) [G 3-ZnPc (CN) 32] synthetic
In three-necked bottle, add material (8) 0.74g, Zn (OAc) 20.04g with Pentyl alcohol 20mL, under nitrogen protection, drip DBU 1mL, 220 ℃ of stirring and refluxing reaction 12h.Reaction is cooled to room temperature after finishing, filters, and collecting precipitation, vacuum-drying, bullion is with CH 3OH is an eluent, separates through silica gel column chromatography and purifies, and vacuum-drying gets deep green solid matter (11) 0.63g, productive rate 83%.IR(KBr/cm -1)：3450，2920，2230，1600，1450，1254，1155，1065，822，580。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.81～7.83(d，J＝8Hz，64H)，7.62～7.60(d，J＝8Hz，64H)，7.52(s，16H)，7.49(s，16H)，7.47(s，16H)，7.40(s，4H)，7.27(s，4H)，7.21～7.23(d，J＝8Hz，4H)，6.65(s，16H)；6.54(s，12H)，6.59(s，8H)，5.17(s，40H)，4.99(s，16H)，4.66(s，12H)。MALDI-TOF-MS：m/z＝7701[M+H 3O +]。
12) " 1 " generation was the dendritic phthalocyanine photosensitizers of end group with the carboxyl: four-[3,5-two-(4-carboxyl benzyloxy)-1-methylene oxygen phenyl] Phthalocyanine Zinc (12) [G 1-ZnPc (COOH) 8] synthetic
The NaOH solution that adds 50mL 6mol/L in the three-necked bottle that 0.5g material (9) are housed, 40 ℃ of reaction 7h.Be cooled to room temperature, filter, in filtrating, add dilute hydrochloric acid solution, separate out green solid.Vacuum-drying gets blue-greenish colour solid matter (12) 0.35g, productive rate 80%.IR(KBr/cm -1)：3445，2930，1690，1600，1450，1153，1067，822，580。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：6.92～6.93(d，J＝4Hz，4H)，7.04～7.06(d，J＝8Hz，4H)，7.18(s，4H)，7.90～7.92(d，J＝8Hz，16H)，7.50～7.52(d，J＝8Hz，16H)，6.71(s，8H)，6.55(s，4H)，5.23(s，8H)，5.14(s，8H)，5.08(s，8H)。MALDI-TOF-MS：m/z＝2203[M+H]。
13) " 2 " generation was the dendritic phthalocyanine photosensitizers of end group with the carboxyl: four-{ 3,5-two-[3,5-two-(4-carboxyl benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl } Phthalocyanine Zinc (13) [G 2-ZnPc (COOH) 16] synthetic
With the NaOH solution of 0.5g material (10) adding 100mL 6mol/L, 40 ℃ of reaction 30h.Filter, in filtrating, add dilute hydrochloric acid solution, separate out green solid, vacuum-drying gets green solid material (13) 0.55g, productive rate 82%.IR(KBr/cm -1)：3145，3040，1700，1600，1450，1400，1153，1067，822，580。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.78～7.80(s，4H)，7.31(s，4H)，7.11～7.14(d，J＝12Hz，4H)，7.94～7.96(d，J＝8Hz，32H)，7.53～7.55(d，J＝8Hz，32H)，6.73(s，16H)，6.72-6.71(d，J＝4Hz，12H)，6.66(s，8H)，5.18(s，32H)，5.12(s，8H)，5.02(s，16H)。MALDI-TOF-MS：m/z＝4253[M]。
14) " 3 " generation was the dendritic phthalocyanine photosensitizers of end group with the carboxyl: four-{ 3,5-two-{ 3,5-two-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl }-1-methylene oxygen phenyl } Phthalocyanine Zinc (14) [G 3-ZnPc (COOH) 32] synthetic
0.5g material (11) is added in the NaOH solution of 200mL 6mol/L 40 ℃ of reaction 20h.Filter, in filtrating, add dilute hydrochloric acid solution, separate out green solid, filter, vacuum-drying gets green solid material (14) 0.67g, productive rate 80%.IR(KBr/cm -1)：3200，3042，1695，1600，1453，1402，1155，1069，822，580。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.75(s，4H)，7.42(s，4H)，7.09～7.11(d，J＝12Hz，4H)，7.92-7.94(d，J＝8Hz，64H)，7.63-7.65(d，J＝8Hz，64H)，6.92(s，16H)，6.78(s，16H)，6.65(s，16H)，6.54(s，8H)，6.37(s，8H)，6.25(s，4H)，6.20(s，4H)，6.15(s，4H)，5.19(s，64H)，5.12(s，32H)，5.03(s，16H)，4.99s，8H)。MALDI-TOF-MS：m/z＝8252[M]。
Specific embodiment two:
Among the embodiment one, process 2) carbon tetrabromide changes 8g into, and triphenylphosphine changes 4g into and THF changes 20mL into, and the reaction times changes 2h into.Other reaction conditions is identical, obtains white powder solid matter (2) 4.0g, productive rate 65.0%.
Process 4) carbon tetrabromide changes 15g in, and triphenylphosphine changes 8g into and THF changes 35mL into, and the reaction times changes 2.5h into.Other reaction conditions is identical, obtains white powder solid matter (4) 5.04g, productive rate 80.0%.
Process 5) carbon tetrabromide changes 30g in, and triphenylphosphine changes 16g into and THF changes 60mL into, and the reaction times changes 3.0h into.Other reaction conditions is identical, gets white powder solid matter (5) 5.25g, productive rate 82%.
Specific embodiment three:
Among the embodiment one, process 6) temperature of reaction is 80 ℃, and other reaction conditions is identical, the material of acquisition (6) productive rate 45.0%.
Process 7) temperature of reaction is 80 ℃, and other reaction conditions is identical, material (7) productive rate 30.0%.
Process 8) temperature of reaction is 80 ℃, and other reaction conditions is identical, material (8) productive rate 22.0%.
Specific embodiment four:
Compound method is with embodiment one, process 9)-14) in, replacing zinc acetate with aluminum chloride, other processes are constant, obtain four-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl] aluminum phthalocyanine [G 1-AlPc (CN) 8], productive rate 65%.IR (KBr/cm -1): 3449,2921,2231,1601,1452,1168,1059,826,640. 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.68(s，4H)，7.25-7.26(d，J＝4Hz，4H)，7.18～7.19(d，J＝4Hz，4H)7.66～7.68(d，J＝8Hz，16H)，7.46～7.48(d，J＝8Hz，16H)，6.58(s，8H)，6.52(s，4H)，5.06(s，24H)。MALDI-TOF-MS：m/z＝2068[M+H 3O +]。Four-{ 3,5-two-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl } aluminum phthalocyanine [G 2-AlPc (CN) 16], productive rate 62%.IR(KBr/cm -1)：3450，2920，2230，1600，1450，1251，1153，1067，822，640。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.81～7.83(d，J＝8Hz，32H)，7.56～7.58(d，J＝8Hz，32H)，7.39(s，4H)，7.30(s，4H)，7.20～7.22(d，J＝8Hz，4H)，6.70(s，16H)，6.61(s，12H)，6.57(s，8H)，5.18(s，40H)，5.00(s，16H)。MALDI-TOF-MS：m/z＝3910[M+H 3O +]。Four-{ 3,5-two-{ 3,5-two-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl }-1-methylene oxygen phenyl } aluminum phthalocyanine [G 3-AlPc (CN) 32], productive rate 79%.IR(KBr/cm -1)：3450，2921，2229，1600，1450，1254，1155，1065，822，640。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.81～7.83(d，J＝8Hz，64H)，7.63～7.61ppm(d，J＝8Hz，64H)，7.53(s，16H)，7.50(s，16H)，7.48(s，16H)，7.41(s，4H)，7.27(s，4H)，7.21～7.23(d，J＝8Hz，4H)，6.66(s，16H)，6.55(s，12H)，6.60(s，8H)，5.18(s，40H)，4.99(s，16H)，4.66(s，12H)。MALDI-TOF-MS:m/z=7723 [M+H 3O +]. four-[3,5-two-(4-carboxyl benzyloxy)-1-methylene oxygen phenyl] aluminum phthalocyanine [G 1-AlPc (COOH) 8], productive rate 82%.IR(KBr/cm -1)：3446，2930，1691，1601，1451，1154，1067，822，640。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：6.92～6.93(d，J＝4Hz，4H)，7.04～7.06(d，J＝8Hz，4H)，7.18(s，4H)，7.90～7.92(d，J＝8Hz，16H)，7.50～7.52(d，J＝8Hz，16H)，6.72(s，8H)，6.55(s，4H)，5.23(s，8H)，5.14(s，8H)，5.08(s，8H)。MALDI-TOF-MS：m/z＝2125[M+H]。Four-{ 3,5-two-[3,5-two-(4-carboxyl benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl } aluminum phthalocyanine [G 2-AlPc (COOH) 16], productive rate 88%.IR(KBr/cm -1)：3145，3040，1700，1600，1450，1400，1153，1067，822，640。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.78～7.80(s，4H)，7.31(s，4H)，7.11～7.14(d，J＝12Hz，4H)，7.94～7.96(d，J＝8Hz，32H)，δ＝7.53～7.55(d，J＝8Hz，32H)，6.74(s，16H)，6.72-6.71(d，J＝4Hz，12H)，6.66(s，8H)，5.18(s，32H)，5.13(s，8H)，5.01(s，16H)。MALDI-TOF-MS：m/z＝4214[M]。Four-{ 3,5-two-{ 3,5-two-[3,5-two-(4-carboxyl benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl }-1-methylene oxygen phenyl } aluminum phthalocyanine [G 3-AlPc (COOH) 32] productive rate: 70%.IR(KBr/cm -1)：3200，3042，1695，1600，1453，1402，1155，1069，822，640. 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.75(s，4H)，7.42(s，4H)，7.09～7.11(d，J＝12Hz，4H)，7.92-7.94(d，J＝8Hz，64H)，7.63-7.65(d，J＝8Hz，64H)，6.92(s，16H)，6.78(s，16H)，6.65(s，16H)，6.54(s，8H)，6.37(s，8H)，6.25(s，4H)，6.20(s，4H)，6.15(s，4H)，5.19(s，64H)，5.11(s，32H)，5.03(s，16H)，4.99(s，8H)。MALDI-TOF-MS：m/z＝7780[M]。
Specific embodiment five:
Compound method is with embodiment one, process 9)-14) in, replacing zinc acetate with NSC 51149, other processes are constant, obtain four-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl] phthalocyanine cobalt [G 1-CoPc (CN) 8], productive rate 30%.IR(KBr/cm -1)：3449，2921，2231，1601，1452，1168，1059，826，655. 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.68(s，4H)，7.25-7.26(d，J＝4Hz，4H)，7.18～7.19(d，J＝4Hz，4H)，7.66～7.68(d，J＝8Hz，16H)，7.46～7.48(d，J＝8Hz，16H)，6.58(s，8H)，6.52(s，4H)，5.06(s，24H)。MALDI-TOF-MS：m/z＝2100[M+H 3O +]。Four-{ 3,5-two-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl } phthalocyanine cobalt [G 2-CoPc (CN) 16], productive rate 33%.IR(KBr/cm -1)：3450，2920，2230，1600，1450，1251，1153，1067，822，655. 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.81～7.83(d，J＝8Hz，32H)，7.56～7.58(d，J＝8Hz，32H)，7.39(s，4H)，7.30(s，4H)，7.20～7.22(d，J＝8Hz，4H)，6.70(s，16H)，6.61(s，12H)，6.57(s，8H)，5.18(s，40H)，5.00(s，16H)。MALDI-TOF-MS：m/z＝3942[M+H 3O +]。Four-{ 3,5-two-{ 3,5-two-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl }-1-methylene oxygen phenyl } phthalocyanine cobalt [G 3-CoPc (CN) 32], productive rate 37%.IR(KBr/cm -1)：3450，2921，2229，1600，1450，1254，1155，1065，822，655。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.81～7.83(d，J＝8Hz，64H)，7.63～7.61ppm(d，J＝8Hz，64H)，7.53(s，16H)，7.50(s，16H)，7.48(s，16H)，7.41(s，4H)，7.27(s，4H)，7.21～7.23(d，J＝8Hz，4H)，6.66(s，16H)，6.55(s，12H)，6.60(s，8H)，5.18(s，40H)，4.99(s，16H)，4.66(s，12H)。MALDI-TOF-MS：m/z＝7752[M+H 3O +]。Four-[3,5-two-(4-carboxyl benzyloxy)-1-methylene oxygen phenyl] phthalocyanine cobalt [G 1-CoPc (COOH) 8], productive rate 34%.IR(KBr/cm -1)：3446，2930，1691，1601，1451，1154，1067，822，655. 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：6.92～6.93(d，J＝4Hz，4H)，7.04～7.06(d，J＝8Hz，4H)，7.18(s，4H)，7.90～7.92(d，J＝8Hz，16H)，7.50～7.52(d，J＝8Hz，16H)，6.72(s，8H)，6.55(s，4H)，5.23(s，8H)，5.14(s，8H)，5.08(s，8H).MALDI-TOF-MS：m/z＝2147[M+H]。Four-{ 3,5-two-[3,5-two-(4-carboxyl benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl } phthalocyanine cobalt [G 2-CoPc (COOH) 16], productive rate 39%.IR(KBr/cm -1)：3145，3040，1700，1600，1450，1400，1153，1067，822，655。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.78～7.80(s，4H)，7.31(s，4H)，7.11～7.14(d，J＝12Hz，4H)，7.94～7.96(d，J＝8Hz，32H)，7.53～7.55(d，J＝8Hz，32H)，6.74(s，16H)，6.72-6.71(d，J＝4Hz，12H)，6.66(s，8H)，5.18(s，32H)，5.13(s，8H)，5.01(s，16H)。MALDI-TOF-MS：m/z＝4246[M]。Four-{ 3,5-two-{ 3,5-two-[3,5-two-(4-carboxyl benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl }-1-methylene oxygen phenyl } phthalocyanine cobalt [G 3-CoPc (COOH) 32], productive rate: 30%.IR(KBr/cm -1)：3200，3042，1695，1600，1453，1402，1155，1069，822，655。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.75(s，4H)，7.42(s，4H)，7.09～7.11(d，J＝12Hz，4H)，7.92-7.94(d，J＝8Hz，64H)，7.63-7.65(d，J＝8Hz，64H)，6.92(s，16H)，6.78(s，16H)，6.65(s，16H)，6.54(s，8H)，6.37(s，8H)，6.25(s，4H)，6.20(s，4H)，6.15(s，4H)，5.19(s，64H)，5.11(s，32H)，5.03(s，16H)，4.99(s，8H)。MALDI-TOF-MS：m/z＝7812[M]。
Specific embodiment six:
Compound method is with embodiment one, process 9)-14) in, replacing zinc acetate with cupric chloride, other processes are constant, obtain four-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl] CuPc [G 1-CuPc (CN) 8], productive rate 13%.IR(KBr/cm -1)：3449，2921，2231，1601，1452，1168，1059，826，650。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.68(s，4H)，7.25-7.26(d，J＝4Hz，4H)，7.18～7.19(d，J＝4Hz，4H)，7.66～7.68(d，J＝8Hz，16H)，7.46～7.48(d，J＝8Hz，16H)，6.58(s，8H)，6.52(s，4H)，5.06(s，24H)。MALDI-TOF-MS：m/z＝2105[M+H 3O +]。Four-{ 3,5-two-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl } CuPc [G 2-CuPc (CN) 16], productive rate 22%.IR(KBr/cm -1)：3450，2920，2230，1600，1450，1251，1153，1067，822，650. 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.81～7.83(d，J＝8Hz，32H)，7.56～7.58(d，J＝8Hz，32H)，7.39(s，4H)，7.30(s，4H)，7.20～7.22(d，J＝8Hz，4H)，6.70(s，16H)，6.61(s，12H)，6.57(s，8H)，5.18(s，40H)，5.00(s，16H)。MALDI-TOF-MS：m/z＝3947[M+H 3O +]。Four-{ 3,5-two-{ 3,5-two-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl }-1-methylene oxygen phenyl } CuPc [G 3-CuPc (CN) 32], productive rate 29%.IR(KBr/cm -1)：3450，2921，2229，1600，1450，1254，1155，1065，822，650。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.81～7.83(d，J＝8Hz，64H)，7.63～7.61ppm(d，J＝8Hz，64H)，7.53(s，16H)，7.50(s，16H)，7.48(s，16H)，7.41(s，4H)，7.27(s，4H)，7.21～7.23(d，J＝8Hz，4H)，6.66(s，16H)，6.55(s，12H)，6.60(s，8H)，5.18(s，40H)，4.99(s，16H)，4.66(s，12H)。MALDI-TOF-MS：m/z＝7760[M+H 3O +]。Four-[3,5-two-(4-carboxyl benzyloxy)-1-methylene oxygen phenyl] CuPc [G 1-CuPc (COOH) 8], productive rate 22%.IR(KBr/cm -1)：3446，2930，1691，1601，1451，1154，1067，822，650。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：6.92～6.93(d，J＝4Hz，4H)，7.04～7.06(d，J＝8Hz，4H)，7.18(s，4H)，7.90～7.92(d，J＝8Hz，16H)，7.50～7.52(d，J＝8Hz，16H)，6.72(s，8H)，6.55(s，4H)，5.23(s，8H)，5.14(s，8H)，5.08(s，8H)。MALDI-TOF-MS：m/z＝2162[M+H]。Four-{ 3,5-two-[3,5-two-(4-carboxyl benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl } CuPc [G 2-CuPc (COOH) 16], productive rate 28%.IR(KBr/cm -1)：3145，3040，1700，1600，1450，1400，1153，1067，822，650。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.78～7.80(s，4H)，7.31(s，4H)，7.11～7.14(d，J＝12Hz，4H)，7.94～7.96(d，J＝8Hz，32H)，7.53～7.55(d，J＝8Hz，32H)6.74(s，16H)，6.72-6.71(d，J＝4Hz，12H)，6.66(s，8H)，5.18(s，32H)，5.13(s，8H)，5.01(s，16H)。MALDI-TOF-MS：m/z＝4251[M]。Four-{ 3,5-two-{ 3,5-two-[3,5-two-(4-carboxyl benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl }-1-methylene oxygen phenyl } CuPc [G 3-CuPc (COOH) 32] productive rate: 20%.IR(KBr/cm -1)：3200，3042，1695，1600，1453，1402，1155，1069，822，650。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.75(s，4H)，7.42(s，4H)，7.09～7.11(d，J＝12Hz，4H)，7.92-7.94(d，J＝8Hz，64H)，7.63-7.65(d，J＝8Hz，64H)，6.92(s，16H)，6.78(s，16H)，6.65(s，16H)，6.54(s，8H)，6.37(s，8H)，6.25(s，4H)，6.20(s，4H)，6.15(s，4H)，5.19(s，64H)，5.11(s，32H)，5.03(s，16H)，4.99(s，8H)。MALDI-TOF-MS：m/z＝7817[M]。
Specific embodiment seven:
Compound method is with embodiment one, process 9)-14) in, replacing zinc acetate with iron(ic)chloride, other processes are constant, obtain four-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl] FePC [G 1-FePc (CN) 8], productive rate 12%.IR(KBr/cm -1)：3449，2921，2231，1601，1452，1168，1059，826，710. 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.68(s，4H)，7.25-7.26(d，J＝4Hz，4H)，7.18～7.19(d，J＝4Hz，4H)7.66～7.68(d，J＝8Hz，16H)，7.46～7.48(d，J＝8Hz，16H)，6.58(s，8H)，6.52(s，4H)5.06(s，24H)。MALDI-TOF-MS：m/z＝2097[M+H 3O +]。Four-{ 3,5-two-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl } FePC [G 2-FePc (CN) 16], productive rate 22%.IR(KBr/cm -1)：3450，2920，2230，1600，1450，1251，1153，1067，822，710。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.81～7.83(d，J＝8Hz，32H)，7.56～7.58(d，J＝8Hz，32H)，7.39(s，4H)，7.30(s，4H)，7.20～7.22(d，J＝8Hz，4H)，6.70(s，16H)，6.61(s，12H)，6.57(s，8H)，5.18(s，40H)，5.00(s，16H)。MALDI-TOF-MS：m/z＝3939[M+H 3O +]。Four-{ 3,5-two-{ 3,5-two-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl }-1-methylene oxygen phenyl } FePC [G 3-FePc (CN) 32], productive rate 29%.IR(KBr/cm -1)：3450，2921，2229，1600，1450，1254，1155，1065，822，710。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.81～7.83(d，J＝8Hz，64H)，7.63～7.61ppm(d，J＝8Hz，64H)，7.53(s，16H)，7.50(s，16H)，7.48(s，16H)，7.41(s，4H)，7.27(s，4H)，7.21～7.23(d，J＝8Hz，4H)，6.66(s，16H)，6.55(s，12H)，6.60(s，8H)，5.18(s，40H)，4.99(s，16H)，4.66(s，12H)。MALDI-TOF-MS：m/z＝7752[M+H 3O +]。Four-[3,5-two-(4-carboxyl benzyloxy)-1-methylene oxygen phenyl] FePC [G 1-FePc (COOH) 8], productive rate 22%.IR(KBr/cm -1)：3446，2930，1691，1601，1451，1154，1067，822，710。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：6.92～6.93(d，J＝4Hz，4H)，7.04～7.06(d，J＝8Hz，4H)7.18(s，4H)，7.90～7.92(d，J＝8Hz，16H)，7.50～7.52(d，J＝8Hz，16H)，6.72(s，8H)，6.55(s，4H)，5.23(s，8H)，5.14(s，8H)，5.08(s，8H)。MALDI-TOF-MS：m/z＝2164[M+H]。Four-{ 3,5-two-[3,5-two-(4-carboxyl benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl } FePC [G 2-FePc (COOH) 16], productive rate 28%.IR(KBr/cm -1)：3145，3040，1700，1600，1450，1400，1153，1067，822，710。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.78～7.80(s，4H)，7.31(s，4H)，7.11～7.14(d，J＝12Hz，4H)，7.94～7.96(d，J＝8Hz，32H)，7.53～7.55(d，J＝8Hz，32H)，6.74(s，16H)，6.72-6.71(d，J＝4Hz，12H)，6.66(s，8H)，5.18(s，32H)，5.13(s，8H)，5.01(s，16H)。MALDI-TOF-MS:m/z=4243 [M], four-{ 3,5-two-{ 3,5-two-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl }-1-methylene oxygen phenyl } FePC [G 3-FePc (COOH) 32] productive rate: 20%.IR(KBr/cm -1)：3200，3042，1695，1600，1453，1402，1155，1069，822，710。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.75(s，4H)，7.42(s，4H)，7.09～7.11(d，J＝12Hz，4H)，7.92-7.94(d，J＝8Hz，64H)，7.63-7.65(d，J＝8Hz，64H)，6.92(s，16H)，6.78(s，16H)，6.65(s，16H)，6.54(s，8H)，6.37(s，8H)，6.25(s，4H)，6.20(s，4H)，6.15(s，4H)，5.19(s，64H)，5.11(s，32H)，5.03(s，16H)，4.99(s，8H)。MALDI-TOF-MS：m/z＝7809[M]。
Specific embodiment eight:
Compound method is with embodiment one, process 9)-14) in, replacing zinc acetate with titanium tetrachloride, other processes are constant, obtain four-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl] titanyl phthalocyanine [G 1-TiOPc (CN) 8], productive rate 25%.IR(KBr/cm -1)：3449，2921，2231，1601，1452，1168，1059，961，826。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.68(s，4H)，7.25-7.26(d，J＝4Hz，4H)，7.18～7.19(d，J＝4Hz，4H)，7.66～7.68(d，J＝8Hz，16H)，7.46～7.48(d，J＝8Hz，16H)，6.58(s，8H)，6.52(s，4H)，5.06(s，24H)。MALDI-TOF-MS：m/z＝2105[M+H 3O +]。Four-{ 3,5-two-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl } titanyl phthalocyanine [G 2-TiOPc (CN) 16], productive rate 32%.IR(KBr/cm -1)：3450，2920，2230，1600，1450，1251，1153，1067，961，826。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.81～7.83(d，J＝8Hz，32H)，7.56～7.58(d，J＝8Hz，32H)，7.39(s，4H)，7.30(s，4H)，7.20～7.22(d，J＝8Hz，4H)，6.70(s，16H)；6.61(s，12H)，6.57(s，8H)，5.18(s，40H)，5.00(s，16H)。MALDI-TOF-MS：m/z＝3947[M+H 3O +]。Four-{ 3,5-two-{ 3,5-two-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl }-1-methylene oxygen phenyl } titanyl phthalocyanine [G 3-TiOPc (CN) 32], productive rate 29%.IR(KBr/cm -1)：3450，2921，2229，1600，1450，1254，1155，1065，822，640。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.81～7.83(d，J＝8Hz，64H)，7.63～7.61(d，J＝8Hz，64H)，7.53(s，16H)，7.50(s，16H)，7.48(s，16H)，7.41(s，4H)，7.27(s，4H)，7.21～7.23(d，J＝8Hz，4H)，6.66(s，16H)，6.55(s，12H)，6.60(s，8H)，5.18(s，40H)，4.99(s，16H)，4.66(s，12H)。MALDI-TOF-MS：m/z＝7750[M+H 3O +]。Four-[3,5-two-(4-carboxyl benzyloxy)-1-methylene oxygen phenyl] titanyl phthalocyanine [G 1-TiOPc (COOH) 8], productive rate 32%; IR (KBr/cm -1): 3446,2930,1691,1601,1451,1154,1067,961,826. 1H NMR (400MHz, DMSO-d 6, δ/ppm): 6.92～6.93 (d, J=4Hz, 4H), 7.04～7.06 (d, J=8Hz; 4H) 7.18 (s, 4H), 7.90～7.92 (d, J=8Hz, 16H), 7.50～7.52 (d; J=8Hz, 16H), 6.72 (s, 8H), 6.55 (s, 4H); 5.23 (s, 8H), 5.14 (s, 8H), 5.08 (s, 8H) .MALDI-TOF-MS:m/z=2152 [M+H].Four-{ 3,5-two-[3,5-two-(4-carboxyl benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl } titanyl phthalocyanine [G 2-TiOPc (COOH) 16], productive rate 88%.IR(KBr/cm -1)：3145，3040，1700，1600，1450，1400，1153，1067，822，640。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.78～7.80(s，4H)，7.31(s，4H)，7.11～7.14(d，J＝12Hz，4H)，7.94～7.96(d，J＝8Hz，32H)，7.53～7.55(d，J＝8Hz，32H)，6.74(s，16H)，6.72-6.71(d，J＝4Hz，12H)，6.66(s，8H)，5.18(s，32H)，5.13(s，8H)，5.01(s，16H)。MALDI-TOF-MS：m/z＝4251[M]。Four-{ 3,5-two-{ 3,5-two-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl }-1-methylene oxygen phenyl } titanyl phthalocyanine [G 3-TiOPc (COOH) 32] productive rate: 40%.IR(KBr/cm -1)：3200，3042，1695，1600，1453，1402，1155，1069，961，826。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.75(s，4H)，7.42(s，4H)，7.09～7.11(d，J＝12Hz，4H)，7.92-7.94(d，J＝8Hz，64H)，7.63-7.65(d，J＝8Hz，64H)，6.92(s，16H)，6.78(s，16H)，6.65(s，16H)，6.54(s，8H)，6.37(s，8H)，6.25(s，4H)，6.20(s，4H)，6.15(s，4H)，5.19(s，64H)，5.11(s，32H)，5.03(s，16H)，4.99(s，8H)。MALDI-TOF-MS：m/z＝7817[M]。
Specific embodiment nine:
Compound method is with embodiment one, process 9)-14) in, replacing zinc acetate with silicon tetrachloride, other processes are constant, obtain four-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl] silicon chlorine phthalocyanine [G 1-SiCl 2Pc (CN) 8], productive rate 46%.IR(KBr/cm -1)：3449，2921，2231，1601，1452，1168，1059，826，595。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.68(s，4H)，7.25-7.26(d，J＝4Hz，4H)，7.18～7.19(d，J＝4Hz，4H)，7.66～7.68(d，J＝8Hz，16H)，7.46～7.48(d，J＝8Hz，16H)，6.58(s，8H)，6.52(s，4H)，5.06(s，24H)。MALDI-TOF-MS：m/z＝2149[M+H 3O +]。Four-{ 3,5-two-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl } silicon chlorine phthalocyanine [G 2-SiCl 2Pc (CN) 16], productive rate 48%.IR(KBr/cm -1)：3450，2920，2230，1600，1450，1251，1153，1067，822，595。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.81～7.83(d，J＝8Hz，32H)，7.56～7.58(d，J＝8Hz，32H)，7.39(s，4H)，7.30(s，4H)，7.20～7.22(d，J＝8Hz，4H)，6.70(s，16H)；6.61(s，12H)，6.57(s，8H)，5.18(s，40H)，5.00(s，16H)。Four-{ 3,5-two-{ 3,5-two-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl }-1-methylene oxygen phenyl } silicon chlorine phthalocyanine [G 3-SiCl 2Pc (CN) 32], productive rate 50%.IR(KBr/cm -1)：3450，2921，2229，1600，1450，1254，1155，1065，822，595。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.81～7.83(d，J＝8Hz，64H)，7.63～7.61(d，J＝8Hz，64H)，7.53(s，16H)，7.50(s，16H)，7.48(s，16H)，7.41(s，4H)，7.27(s，4H)，7.21～7.23(d，J＝8Hz，4H)，6.66(s，16H)；6.55(s，12H)，6.60(s，8H)，5.18(s，40H)，4.99(s，16H)，4.66(s，12H)。MALDI-TOF-MS：m/z＝7804[M+H 3O +]。Four-[3,5-two-(4-carboxyl benzyloxy)-1-methylene oxygen phenyl] silicon chlorine phthalocyanine [G 1-SiCl 2Pc (COOH) 8], productive rate 51%.IR(KBr/cm -1)：3446，2930，1691，1601，1451，1154，1067，822，595。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：6.92～6.93(d，J＝4Hz，4H)，7.04～7.06(d，J＝8Hz，4H)7.18(s，4H)，7.90～7.92(d，J＝8Hz，16H)，7.50～7.52(d，J＝8Hz，16H)，6.72(s，8H)，6.55(s，4H)，5.23(s，8H)，5.14(s，8H)，5.08(s，8H)。MALDI-TOF-MS：m/z＝2206[M+H]。Four-{ 3,5-two-[3,5-two-(4-carboxyl benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl } silicon chlorine phthalocyanine [G 2-SiCl 2Pc (COOH) 16], productive rate 60%.IR(KBr/cm -1)：3145，3040，1700，1600，1450，1400，1153，1067，822，595。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.78～7.80(s，4H)，7.31(s，4H)，7.11～7.14(d，J＝12Hz，4H)，7.94～7.96(d，J＝8Hz，32H)，7.53～7.55(d，J＝8Hz，32H)6.74(s，16H)，6.72-6.71(d，J＝4Hz，12H)，6.66(s，8H)，5.18(s，32H)，5.13(s，8H)，5.01(s，16H)。MALDI-TOF-MS：m/z＝4295[M]。Four-{ 3,5-two-{ 3,5-two-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl }-1-methylene oxygen phenyl } silicon chlorine phthalocyanine [G 3-SiCl 2Pc (COOH) 32] 63%, IR (KBr/cm -1): 3200,3042,1695,1600,1453,1402,1155,1069,822,595.。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.75(s，4H)，7.42(s，4H)，7.09～7.11(d，J＝12Hz，4H)，7.92-7.94(d，J＝8Hz，64H)，7.63-7.65(d，J＝8Hz，64H)，6.92(s，16H)，6.78(s，16H)，6.65(s，16H)，6.54(s，8H)，6.37(s，8H)，6.25(s，4H)，6.20(s，4H)，6.15(s，4H)，5.19(s，64H)，5.11(s，32H)，5.03(s，16H)，4.99(s，8H)。MALDI-TOF-MS：m/z＝7861[M]。
Specific embodiment ten:
Compound method is with embodiment one, process 9)-14) in, replacing zinc acetate with lithium chloride, other processes are constant, obtain four-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl] metal-free phthalocyanine [G 1-H 2Pc (CN) 8], productive rate 45%.IR (KBr/cm -1): 3449,2921,2230,1601,1452,1168,1059,826,450. 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.69(s，4H)，7.25-7.26(d，J＝4Hz，4H)，7.19～7.20(d，J＝4Hz，4H)7.66～7.68(d，J＝8Hz，16H)，7.46～7.48(d，J＝8Hz，16H)，6.58(s，8H)，6.53(s，4H)，5.07(s，24H)。MALDI-TOF-MS：m/z＝2043[M+H 3O +]。Four-{ 3,5-two-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl } metal-free phthalocyanine [G 2-H 2Pc (CN) 16], productive rate 62%.IR(KBr/cm -1)：3452，2920，2230，1600，1450，1251，1155，1069，823，450。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.82～7.84(d，J＝8Hz，32H)，7.59～7.60(d，J＝8Hz，32H)，7.39(s，4H)，7.30(s，4H)，7.20～7.22(d，J＝8Hz，4H)，6.70(s，16H)，6.61(s，12H)，6.57(s，8H)，5.18(s，40H)，5.00(s，16H)。MALDI-TOF-MS：m/z＝3893[M+H 3O +]。Four-{ 3,5-two-{ 3,5-two-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl }-1-methylene oxygen phenyl } no metal [G 3-H 2Pc (CN) 32], productive rate 79%.IR(KBr/cm -1)：3450，2921，2229，1600，1450，1254，1155，1065，822，450。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.81～7.83(d，J＝8Hz，64H)，7.63～7.61ppm(d，J＝8Hz，64H)，7.53(s，16H)，7.50(s，16H)，7.48(s，16H)，7.41(s，4H)，7.27(s，4H)，7.21～7.23(d，J＝8Hz，4H)，6.66(s，16H)，6.55(s，12H)，6.60(s，8H)，5.18(s，40H)，4.99(s，16H)，4.66(s，12H)。MALDI-TOF-MS:m/z=7698 [M+H 3O +]. four-[3,5-two-(4-carboxyl benzyloxy)-1-methylene oxygen phenyl] metal-free phthalocyanine [G 1-H 2Pc (COOH) 8], productive rate 82%.IR(KBr/cm -1)：3446，2930，1691，1601，1451，1154，1067，822，640。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：6.92～6.93(d，J＝4Hz，4H)，7.04～7.06(d，J＝8Hz，4H)，7.18(s，4H)，7.90～7.92(d，J＝8Hz，16H)，7.50～7.52(d，J＝8Hz，16H)，6.72(s，8H)，6.55(s，4H)，5.23(s，8H)，5.14(s，8H)，5.08(s，8H)。MALDI-TOF-MS：m/z＝2125[M+H]。Four-{ 3,5-two-[3,5-two-(4-carboxyl benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl } metal-free phthalocyanine [G 2-AlPc (COOH) 16], productive rate 88%.IR(KBr/cm -1)：3145，3040，1700，1600，1450，1400，1153，1067，822，450。 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.78～7.80(s，4H)，7.31(s，4H)，7.11～7.14(d，J＝12Hz，4H)，7.94～7.96(d，J＝8Hz，32H)，δ＝7.53～7.55(d，J＝8Hz，32H)，6.74(s，16H)，6.72-6.71(d，J＝4Hz，12H)，6.66(s，8H)，5.18(s，32H)，5.13(s，8H)，5.01(s，16H)。MALDI-TOF-MS：m/z＝4189[M]。Four-{ 3,5-two-{ 3,5-two-[3,5-two-(4-carboxyl benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl }-1-methylene oxygen phenyl } metal-free phthalocyanine [G 3-H 2Pc (COOH) 32] productive rate: 70%.IR(KBr/cm -1)：3200，3042，1695，1600，1453，1402，1155，1069，822，450. 1H?NMR(400MHz，DMSO-d 6，δ/ppm)：7.75(s，4H)，7.42(s，4H)，7.09～7.11(d，J＝12Hz，4H)，7.92-7.94(d，J＝8Hz，64H)，7.63-7.65(d，J＝8Hz，64H)，6.92(s，16H)，6.78(s，16H)，6.65(s，16H)，6.54(s，8H)，6.37(s，8H)，6.25(s，4H)，6.20(s，4H)，6.15(s，4H)，5.19(s，64H)，5.11(s，32H)，5.03(s，16H)，4.99(s，8H)。MALDI-TOF-MS：m/z＝7765[M]。
Load 1-3 of the present invention comprises for the polymer nano-particle of aryl oxide dendritic phthalocyanine complex: 1) material (9) [G 1-MPc (CN) 8] and gather (N ε-carbobenzoxy-(Cbz) Methionin)-polyethylene glycol-(N ε-carbobenzoxy-(Cbz) Methionin) polymer nano-particle that constitutes, i.e. material (9) [G 1-MPc (CN) 8]/gather (N ε-carbobenzoxy-(Cbz) Methionin)-polyethylene glycol-(N ε-carbobenzoxy-(Cbz) Methionin) polymer nano-particle, described material (9) [G 1-MPc (CN) 8] and gather (N ε-carbobenzoxy-(Cbz) Methionin)-polyethylene glycol-(N ε-carbobenzoxy-(Cbz) Methionin) material (9) [G in the polymer nano-particle 1-MPc (CN) 8] and gather (N ε-carbobenzoxy-(Cbz) Methionin)-polyethylene glycol-(N ε-carbobenzoxy-(Cbz) Methionin) mol ratio is 8: 1, and promptly mol ratio is 8: 1 material (9) [G 1-MPc (CN) 8]/gather (N ε-carbobenzoxy-(Cbz) Methionin)-polyethylene glycol-(N ε-carbobenzoxy-(Cbz) Methionin) polymer nano-particle; 2) mol ratio is 5: 1 material (9) [G 1-MPc (CN) 8]/gather (N ε-carbobenzoxy-(Cbz) Methionin)-the polyethylene glycol polymer nanoparticle; 3) mol ratio is 6: 1 material (10) [G 2-MPc (CN) 16]/gather (N ε-carbobenzoxy-(Cbz) Methionin)-polyethylene glycol-(N ε-carbobenzoxy-(Cbz) Methionin) polymer nano-particle; 4) mol ratio is 4: 1 material (10) [G 2-MPc (CN) 16]/gather (N ε-carbobenzoxy-(Cbz) Methionin)-the polyethylene glycol polymer nanoparticle; 5) mol ratio is 5: 1 material (11) [G 3-MPc (CN) 32]/gather (N ε-carbobenzoxy-(Cbz) Methionin)-polyethylene glycol-(N ε-carbobenzoxy-(Cbz) Methionin) polymer nano-particle; 6) mol ratio is 2: 1 material (11) [G 3-MPc (CN) 32]/gather (N ε-carbobenzoxy-(Cbz) Methionin)-the polyethylene glycol polymer nanoparticle; 7) mol ratio is 4: 1 material (12) [G 1-MPc (COOH) 8]/polylysine-polyethylene glycol-Methionin polymer nano-particle; 8) mol ratio is 2: 1 material (12) [G 1-MPc (COOH) 8]/polylysine-polyethylene glycol polymer nanoparticle; 9) mol ratio is 2: 1 material (13) [G 2-MPc (COOH) 16]/polylysine-polyethylene glycol-Methionin polymer nano-particle; 10) mol ratio is 1: 1 material (13) [G 2-MPc (COOH) 16]/polylysine-polyethylene glycol polymer nanoparticle; 11) mol ratio is 1: 1 material (14) [G 3-MPc (COOH) 32]/polylysine-polyethylene glycol-Methionin polymer nano-particle; 12) mol ratio is 2: 1 material (14) [G 3-MPc (COOH) 32]/polylysine-polyethylene glycol polymer nanoparticle.
The solvent of substituted phthalocyanine title complex is dissolved in the present invention; Character to concrete phthalocyanine complex can be water, organic solvent (DMSO 99.8MIN., N, dinethylformamide, THF etc.); Buffered soln (phosphoric acid salt), trishydroxymethyl amine salt acid solution or other systems.
Load 1-3 of the present invention is following for the concrete preparation instance of the polymer nano-particle of aryl oxide dendritic phthalocyanine complex:
Be used for the gel that gel chromatography separation is used in the instance of the present invention, must possess following characteristic: (1) is stable in buffered soln, and (2) have suitable molecular weight separating ranges, can be that phthalocyanine and molecular weight between the 1000-10000 is in 2-10 * 10 with molecular weight 5Polymer nano-particle separate.The present invention recommends polydextran gel, Sephadex G-100 for example, Sephadex G-50.
Described in the following instance 1) material (9) is four-[3; 5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl] zinc phthalocyanine (9), certainly also can four-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl] copper phthalocyanines etc.; 2) material (10) is four-{ 3; 5-two-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl } zinc phthalocyanine (10), can be four-{ 3 certainly; 5-two-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl } the cobalt phthalocyanine etc.; 3) material (11) is four-{ 3; 5-two-{ 3,5-two-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl }-1-methylene oxygen phenyl } the zinc phthalocyanine; Also four-{ 3; 5-two-{ 3,5-two-[3,5-two-(4-cyanic acid benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl }-1-methylene oxygen phenyl } iron-phthalocyanine; 4) material (12) is four-[3,5-two-(4-carboxyl benzyloxy)-1-methylene oxygen phenyl] zinc phthalocyanines, certainly also can four-[3,5-(two-4-carboxyl benzyloxy)-benzyloxy] titanyl phthalocyanines etc.; 5) material (13) is four-{ 3,5-two-[3,5-two-(4-carboxyl benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl } zinc phthalocyanines; Also can be four-{ 3,5-two-[3,5-two-(4-carboxyl benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl } cobalt phthalocyanines etc.; 6) material (14) be four-3,5-two-3,5-two-[3; 5-two-(4-carboxyl benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl }-1-methylene oxygen phenyl } the zinc phthalocyanine, certainly also four-3,5-two-{ 3; 5-two-[3,5-two-(4-carboxyl benzyloxy)-1-methylene oxygen phenyl]-1-methylene oxygen phenyl }-1-methylene oxygen phenyl } the aluminium phthalocyanine etc.
Embodiment 1
Be 8: 1 in molar ratio, accurately take by weighing a certain amount of material (9) [G 1-MPc (CN) 8] and gather (N ε-carbobenzoxy-(Cbz) Methionin)-polyethylene glycol-(N ε-carbobenzoxy-(Cbz) Methionin) be dissolved among the DMF, under vigorous stirring, slowly add zero(ppm) water 100mL, filter, place dialysis tubing to dialyse behind 48h～72h filtrating, take out micellar solution, use filtering with microporous membrane, must material (9) [G 1-MPc (CN) 8]/gather (N ε-carbobenzoxy-(Cbz) Methionin)-polyethylene glycol-(N ε-carbobenzoxy-(Cbz) Methionin) in the polymers soln, the two mol ratio is 8: 1, and as in the test tube, 37 ℃ vibrated 5 hours with above-mentioned mixed solution.Measure solution turbidity with turbidometer, no longer change to solution turbidity, zeta-potential is 0.6522.
Is that the glass chromatography column of 100cm is vertically placed with diameter for 1.5cm length, has slowly added fully swollen polydextran gel (Sephadex G-50) (gel length is 50cm), is 7.4 NaH with pH 2PO 4/ Na 2HPO 4Buffered soln is eluent, separates above-mentioned mixing solutions, and mixed solution is separated into two blue color component, and collecting first component, to be mol ratio be 8: 1 material (9) [G 1-MPc (CN) 8]/gather (N ε-carbobenzoxy-(Cbz) Methionin)-polyethylene glycol-(N ε-carbobenzoxy-(Cbz) Methionin) polymer nano-particle.AFM figure (AFM) figure shows that it is spherical in shape, and the about 80nm of diameter, transmission electron microscope picture show that it presents nucleocapsid structure, good dispersivity.The dynamic Laser scattering shows that its micella diameter Distribution in solution is 78nm, dispersion index (μ 2/ Γ 2=0.135).
Embodiment 2
Repeat the process of embodiment 1, just making mol ratio into is 5: 1, and will gather (N ε-carbobenzoxy-(Cbz) Methionin)-polyethylene glycol-(N ε-carbobenzoxy-(Cbz) Methionin) change into and gather (N ε-carbobenzoxy-(Cbz) Methionin)-and polyoxyethylene glycol, finally obtain mol ratio and be 5: 1 material (9) [G 1-MPc (CN) 8]/polylysine-polyethylene glycol polymer nanoparticle.Zeta-potential is 1.120, and AFM figure (AFM) shows that it is spherical in shape, and the about 100nm of diameter, transmission electron microscope picture show that it presents nucleocapsid structure, good dispersivity.The dynamic Laser scattering shows that its micella diameter Distribution in solution is 100nm, dispersion index (μ 2/ Γ 2=0.141).
Embodiment 3
Repeat the process of embodiment 1, just making mol ratio into is 6: 1, with material (9) [G 1-MPc (CN) 8] change material (10) [G into 2-MPc (CN) 16], finally obtain mol ratio and be 6: 1 material (10) [G 2-MPc (CN) 16]/gather (N ε-carbobenzoxy-(Cbz) Methionin)-polyethylene glycol-(N ε-carbobenzoxy-(Cbz) Methionin) polymer nano-particle.Zeta-potential is 0.7258, and AFM figure (AFM) shows that it is spherical in shape, and the about 120nm of diameter, transmission electron microscope picture show that it presents nucleocapsid structure, good dispersivity.The dynamic Laser scattering shows that its micella diameter Distribution in solution is 110nm, dispersion index (μ 2/ Γ 2=0.141).
Embodiment 4
Repeat the process of embodiment 1, just making mol ratio into is 4: 1, with material (9) [G 1-MPc (CN) 8] change material (10) [G into 2-MPc (CN) 16], gather (N ε-carbobenzoxy-(Cbz) Methionin)-polyethylene glycol-(N ε-carbobenzoxy-(Cbz) Methionin) change into and gather (N ε-carbobenzoxy-(Cbz) Methionin)-and polyoxyethylene glycol, finally obtain mol ratio and be 4: 1 material (10) [G 2-MPc (CN) 16]/gather (N ε-carbobenzoxy-(Cbz) Methionin)-and the polyethylene glycol polymer nanoparticle, zeta-potential is 0.69, and AFM figure (AFM) shows that it is spherical in shape, and the about 110nm of diameter, transmission electron microscope picture show that it presents nucleocapsid structure, good dispersivity.The dynamic Laser scattering shows that its micella diameter Distribution in solution is 110nm, dispersion index (μ 2/ Γ 2=0.138).
Embodiment 5
Repeat the process of embodiment 1, just making mol ratio into is 5: 1, with material (9) [G 1-MPc (CN) 8] change material (11) [G into 3-MPc (CN) 32], finally obtain mol ratio and be 2: 1 material (11) [G 3-MPc (CN) 32]/gather (N ε-carbobenzoxy-(Cbz) Methionin)-polyethylene glycol-(N ε-carbobenzoxy-(Cbz) Methionin) polymer nano-particle, zeta-potential are-0.20, and AFM figure (AFM) shows that it is spherical in shape, and the about 150nm of diameter, transmission electron microscope picture show that it presents nucleocapsid structure, good dispersivity.The dynamic Laser scattering shows that its micella diameter Distribution in solution is 150nm, dispersion index (μ 2/ Γ 2=0.30).
Embodiment 6
Repeat the process of embodiment 1, just making mol ratio into is 2: 1, with material (9) [G 1-MPc (CN) 8] change material (11) [G into 3-MPc (CN) 32], gather (N ε-carbobenzoxy-(Cbz) Methionin)-polyethylene glycol-(N ε-carbobenzoxy-(Cbz) Methionin) change into and gather (N ε-carbobenzoxy-(Cbz) Methionin)-and polyoxyethylene glycol, finally obtain mol ratio and be 2: 1 load material (11) [G 3-MPc (CN) 32]/gather (N ε-carbobenzoxy-(Cbz) Methionin)-and the polyethylene glycol polymer nanoparticle, zeta-potential is 0.052, and AFM figure (AFM) shows that it is spherical in shape, and the about 130nm of diameter, transmission electron microscope picture show that it presents nucleocapsid structure, good dispersivity.The dynamic Laser scattering shows that its micella diameter Distribution in solution is 130nm, dispersion index (μ 2/ Γ 2=0.42).
Embodiment 7
Accurately take by weighing a certain amount of material (12) [G 1-MPc (COOH) 8] be dissolved in the aqueous solution, with polylysine-polyethylene glycol-Methionin polymer dissolution in NaH 2PO 4/ Na 2HPO 4In the buffered soln, buffer concentration is 1.0 * 10 -5Mol/L, pH are 7.4.With material (12) [G 1-MPc (COOH) 8] solution is added drop-wise in polylysine-polyethylene glycol-Methionin polymers soln gradually, the two mol ratio is 4: 1, with above-mentioned mixed solution as in the test tube, 37 ℃ of vibrations 5 hours.Measure solution turbidity with turbidometer, no longer change to solution turbidity, zeta-potential is 0.96.
Is that the glass chromatography column of 100cm is vertically placed with diameter for 1.5cm length, has slowly added fully swollen polydextran gel (Sephadex G-50) (gel length is 50cm), is 7.4 NaH with pH 2PO 4/ Na 2HPO 4Buffered soln is eluent, separates above-mentioned bout solution, and mixed solution is separated into two blue color component, and collecting first component, to be mol ratio be 4: 1 material (12) [G 1-MPc (COOH) 8]/polylysine-polyethylene glycol-Methionin polymer nano-particle.AFM figure (AFM) shows that it is spherical in shape, and the about 50nm of diameter, transmission electron microscope picture show that it presents nucleocapsid structure, good dispersivity.The dynamic Laser scattering shows that its micella diameter Distribution in solution is 60, dispersion index (μ 2/ Γ 2=0.132).
Embodiment 8
Repeat the process of embodiment 7, just changing mol ratio is 2: 1, changes polylysine-polyethylene glycol-Methionin polymkeric substance into polylysine-polyoxyethylene glycol, finally obtains mol ratio and be 2: 1 material (12) [G 1-MPc (COOH) 8]/polylysine-polyethylene glycol polymer nanoparticle, zeta-potential are 0.65.AFM figure (AFM) shows that it is spherical in shape, and the about 70nm of diameter, transmission electron microscope picture show that it presents nucleocapsid structure, good dispersivity.The dynamic Laser scattering shows that its micella diameter Distribution in solution is 70, dispersion index (μ 2/ Γ 2=0.145).
Embodiment 9
Repeat the process of embodiment 7, just changing mol ratio is 2: 1, with material (12) [G 1-MPc (COOH) 8] change material (13) into, finally obtain mol ratio and be material (13)/polylysine-polyethylene glycol-Methionin polymer nano-particle of 2: 1; Zeta-potential is 0.48.AFM figure (AFM) shows that it is spherical in shape, and the about 80nm of diameter, transmission electron microscope picture show that it presents nucleocapsid structure, good dispersivity.The dynamic Laser scattering shows that its micella diameter Distribution in solution is 90nm, dispersion index (μ 2/ Γ 2=0.249).
Embodiment 10
Repeat the process of embodiment 7, just changing mol ratio is 1: 1, with material (12) [G 1-MPc (COOH) 8] change material (13) [G into 2-MPc (COOH) 16], polylysine-polyethylene glycol-Methionin polymkeric substance changes polylysine-polyoxyethylene glycol into, finally obtains mol ratio and be 1: 1 material (13) [G 2-MPc (COOH) 16]/polylysine-polyethylene glycol polymer nanoparticle, zeta-potential are 0.52.AFM figure (AFM) shows that it is spherical in shape, and the about 80nm of diameter, transmission electron microscope picture show that it presents nucleocapsid structure, good dispersivity.The dynamic Laser scattering shows that its micella diameter Distribution in solution is 80nm, dispersion index (μ 2/ Γ 2=0.215).
Embodiment 11
Repeat the process of embodiment 7, just changing mol ratio is 1: 1, just with material (12) [G 1-MPc (COOH) 8] change material (14) [G into 3-MPc (COOH) 32], finally obtain mol ratio and be 1: 1 material (14) [G 3-MPc (COOH) 32]/polylysine-polyethylene glycol-Methionin polymer nano-particle; Zeta-potential is-0.10.AFM figure (AFM) shows that it is spherical in shape, and the about 50nm of diameter, transmission electron microscope picture show that it presents nucleocapsid structure, good dispersivity.The dynamic Laser scattering shows that its micella diameter Distribution in solution is 60nm, dispersion index (μ 2/ Γ 2=0.040).
Embodiment 12
Repeat the process of embodiment 7, just changing mol ratio is 2: 1, with material (12) [G 1-MPc (COOH) 8] change material (14) [G into 3-MPc (COOH) 32], polylysine-polyethylene glycol-Methionin polymkeric substance changes polylysine-polyoxyethylene glycol into, finally obtains mol ratio and be 2: 1 material (14) [G 3-MPc (COOH) 32]/polylysine-polyethylene glycol polymer nanoparticle, zeta-potential are-0.20.AFM figure (AFM) shows that it is spherical in shape, and the about 50nm of diameter, transmission electron microscope picture show that it presents nucleocapsid structure, good dispersivity.The dynamic Laser scattering shows that its micella diameter Distribution in solution is 50nm, dispersion index (μ 2/ Γ 2=0.030).
(1) normal people's Human umbilical vein endothelial cells (HUVEC) HUVEC picked-up 1-3 is for the pharmacokinetics of aryl oxide dendritic phthalocyanine Zn complex
Open the UV, visible light spectrophotometer; Return to zero with 2.0%TritionX-100 earlier; Add 10 μ g/mL1-3 respectively for aryl oxide dendritic phthalocyanine Zn complex 1mL, carry out absorption spectrum scanning, find absorption peak at 300nm-800nm; Do spot scan at this peak value then, make a typical curve respectively.With the people HUVEC cell that reaches the third generation, put 6 orifice plates and cultivate, every hole 1.0mL, cell density are 5 * 10 6/ mL, 6 kinds of phthalocyanine final concentrations are 20 μ g/mL, control group adds the PBS solution with volume, 37 ℃, 5%CO 2, the CO of saturated humidity 2Lucifuge is hatched in the incubator.0.5h, 1h, 2h, 3h, respectively collected one group of cell (each group establish 3 parallel holes) in 4 hours.Behind PBS washed cell 2 times, add 1mL cell pyrolysis liquid (2.0%TritionX-100), the piping and druming mixing, intact cell is not seen in detection under the opticmicroscope.Product of cell lysis is in 4 ℃ of refrigerated centrifuges, and high speed centrifugation 30min gets supernatant, detects the amount of 6 kinds of phthalocyanines in the cell with the UV, visible light sub-ray spectrometer.
The different incubation time HUVEC of table 1 cellular uptake 1-3 is for the amount of aryl oxide dendritic phthalocyanine Zn complex
Figure GSB00000821448700241
The different incubation time HUVEC of table 2 cellular uptake load 1-3 is for the amount of aryl oxide dendritic phthalocyanine zinc polymer nano-particle
The M I is for gathering (N ε-carbobenzoxy-(Cbz) Methionin)-polyethylene glycol-(N ε-carbobenzoxy-(Cbz) Methionin)
The different incubation time HUVEC of table 3 cellular uptake load 1-3 is for the amount of aryl oxide dendritic phthalocyanine zinc polymer nano-particle
M2 is polylysine-polyethylene glycol-Methionin
(2) the light power effect is estimated
1-3 handles for the PDT of the polymer nano-particle of aryl oxide dendritic phthalocyanine Zn complex for aryl oxide dendritic phthalocyanine Zn complex and load 1-3
With the resuspended HUVE cell of DMEM/F12 nutrient solution that contains 10% foetal calf serum, density is 1x10 6/ ml, the 1-3 that adds final concentration and be 10 μ g/mL be for aryl oxide dendritic phthalocyanine Zn complex and the load 1-3 polymer nano-particle for aryl oxide dendritic phthalocyanine Zn complex, hatches illumination behind the 4h; Illumination condition: by the 670nm laser of LD-670 semiconductor laser machine (by Medical University Of Tianjin laser medicine research department development) output with 600mW/cm 2Power density, be divided into 50J/cm by energy density 2Irradiation.Set up the light control group (not add photosensitizers simultaneously; Add equal volume PBS; Hatch illumination behind the 4h), contain 10 μ g/ml 1-3 for aryl oxide dendritic phthalocyanine Zn complex and load 1-3 polymer nano-particle for aryl oxide dendritic phthalocyanine Zn complex; Control group (only hatching 4h, not illumination) with photosensitizers.
The MTT colourimetry
Be the HUVEC cell after PDT handles, be inoculated in 96 well culture plates, establish 3 parallel holes for every group, experiment repetition 3 times.Put 37 ℃, 5%CO 2, the CO of saturated humidity 2Hatch 48h in the incubator, detect the multiplication capacity of HUVEC cell with nitroblue tetrazolium(NBT) salt (MTT) colourimetry.Step is following: inhale the nutrient solution remove to contain foetal calf serum, every hole adds 20 μ l MTT (5mg/ml), after adding serum free medium to 200 μ l and cultivating 4h, abandons supernatant, and it is dissolving crystallized to add 20 μ L DMSO.On ELIASA, survey the OD value, calculate inhibiting rate with wavelength 490nm.
Inhibiting rate=(untreated fish group OD value-experimental group OD value)/untreated fish group OD value * 100%.
The mtt assay detected result (n=9) of 48 hours HUVEC cells behind the table 2PDT
Figure GSB00000821448700251
Figure GSB00000821448700261
Compare difference between two groups of groups of ★ and significance is arranged, p＜0.01
The M I is for gathering (N ε-carbobenzoxy-(Cbz) Methionin)-polyethylene glycol-(N ε-carbobenzoxy-(Cbz) Methionin) (PLL (Z)-PEG-PLL (Z));
M2 is polylysine-polyethylene glycol-Methionin.
Gather (N ε-carbobenzoxy-(Cbz) Methionin)-polyoxyethylene glycol (PLL (Z)-PEG).Positive charge polylysine-polyoxyethylene glycol (PLL-PEG) that PLL (Z)-PEG obtains after going to protect.

Claims (9)

  1. One kind 1 generation the aryl oxide dendritic phthalocyanine complex, it is characterized in that: be the compound of following chemical structure:
    Figure FSB00000885019900011
    In the formula: M is hydrogen, silicon, iron, titanium, cobalt, zinc, aluminium or copper;
    In the formula: R is a cyanic acid, nitro, carboxyl or ester group; R in the structural formula is identical group, and described aryl oxide branch substituting group the position of substitution on the phthalocyanine phenyl ring is the β position.
  2. One kind 2 generation the aryl oxide dendritic phthalocyanine complex, it is characterized in that: be the compound of following chemical structure:
    Figure FSB00000885019900021
    In the formula: M is hydrogen, silicon, iron, titanium, cobalt, zinc, aluminium or copper;
    In the formula: R is a cyanic acid, nitro, carboxyl or ester group; R in the structural formula is identical group, and described aryl oxide branch substituting group the position of substitution on the phthalocyanine phenyl ring is the β position.
  3. One kind 3 generation the aryl oxide dendritic phthalocyanine complex, it is characterized in that: be the compound of following chemical structure:
    In the formula: M is hydrogen, silicon, iron, titanium, cobalt, zinc, aluminium or copper;
    In the formula: R is a cyanic acid, nitro, carboxyl or ester; R in the structural formula is identical group, and described aryl oxide branch substituting group the position of substitution on the phthalocyanine phenyl ring is the β position.
  4. 4. the described 1-3 of one of claim 1～3 independently adorns the polymer nano-particle of the load 1-3 of formation for the aryl oxide dendritic phthalocyanine complex for aryl oxide dendritic phthalocyanine complex and amphiphilic block copolymer.
  5. 5. the described 1-3 of one of claim 1～3 uses at the photosensitizers of preparation PDT for the aryl oxide dendritic phthalocyanine complex.
  6. 6. the described load 1-3 of claim 4 uses at the photosensitizers of preparation PDT for the polymer nano-particle of aryl oxide dendritic phthalocyanine complex.
  7. 7. load 1-3 according to claim 4 is characterized in that for the polymer nano-particle of aryl oxide dendritic phthalocyanine complex: described load 1-3 is following a kind of for aryl oxide dendritic phthalocyanine complex polymer nano-particle: 1) mol ratio is 8: 1 [G 1-MPc (CN) 8]/gather (N ε-carbobenzoxy-(Cbz) Methionin)-polyethylene glycol-(N ε-carbobenzoxy-(Cbz) Methionin) polymer nano-particle; 2) mol ratio is 5: 1 [G 1-MPc (CN) 8]/gather (N ε-carbobenzoxy-(Cbz) Methionin)-the polyethylene glycol polymer nanoparticle; 3) mol ratio is 6: 1 [G 2-MPc (CN) 16]/gather (N ε-carbobenzoxy-(Cbz) Methionin)-polyethylene glycol-(N ε-carbobenzoxy-(Cbz) Methionin) polymer nano-particle; 4) mol ratio is 4: 1 [G 2-MPc (CN) 16]/gather (N ε-carbobenzoxy-(Cbz) Methionin)-the polyethylene glycol polymer nanoparticle; 5) mol ratio is 5: 1 [G 3-MPc (CN) 32]/gather (N ε-carbobenzoxy-(Cbz) Methionin)-polyethylene glycol-(N ε-carbobenzoxy-(Cbz) Methionin) polymer nano-particle; 6) mol ratio is 2: 1 [G 3-MPc (CN) 32]/gather (N ε-carbobenzoxy-(Cbz) Methionin)-the polyethylene glycol polymer nanoparticle; 7) mol ratio is 4: 1 [G 1-MPc (COOH) 8]/polylysine-polyethylene glycol-Methionin polymer nano-particle; 8) mol ratio is 2: 1 [G 1-MPc (COOH) 8]/polylysine-polyethylene glycol polymer nanoparticle; 9) mol ratio is 2: 1 [G 2-MPc (COOH) 16]/polylysine-polyethylene glycol-Methionin polymer nano-particle; 10) mol ratio is 1: 1 [G 2-MPc (COOH) 16]/polylysine-polyethylene glycol polymer nanoparticle; 11) mol ratio is 1: 1 [G 3-MPc (COOH) 32]/polylysine-polyethylene glycol-Methionin polymer nano-particle; 12) mol ratio is 2: 1 [G 3-MPc (COOH) 32]/polylysine-polyethylene glycol polymer nanoparticle; The molecular weight of described polyoxyethylene glycol is 1500-10000;
    Wherein, [G 1-MPc (CN) 8] (compound 9) structural formula is:
    Figure FSB00000885019900041
    In the formula: M is hydrogen, silicon, iron, titanium, cobalt, zinc, aluminium or copper,
    In the formula: described aryl oxide branch substituting group the position of substitution on the phthalocyanine phenyl ring is the β position;
    [G 2-MPc (CN) 16] (compound 10) structural formula is:
    Figure FSB00000885019900051
    In the formula: M is hydrogen, silicon, iron, titanium, cobalt, zinc, aluminium or copper,
    In the formula: described aryl oxide branch substituting group the position of substitution on the phthalocyanine phenyl ring is the β position;
    [G 3-MPc (CN) 32] (compound 11) structural formula is:
    Figure FSB00000885019900061
    In the formula: M is hydrogen, silicon, iron, titanium, cobalt, zinc, aluminium or copper,
    In the formula: described aryl oxide branch substituting group the position of substitution on the phthalocyanine phenyl ring is the β position;
    [G 1-MPc (COOH) 8] (compound 12) structural formula is:
    Figure FSB00000885019900071
    In the formula: M is hydrogen, silicon, iron, titanium, cobalt, zinc, aluminium or copper,
    In the formula: described aryl oxide branch substituting group the position of substitution on the phthalocyanine phenyl ring is the β position;
    [G 2-MPc (COOH) 16] (compound 13) structural formula is:
    Figure FSB00000885019900072
    In the formula: M is hydrogen, silicon, iron, titanium, cobalt, zinc, aluminium or copper,
    In the formula: described aryl oxide branch substituting group the position of substitution on the phthalocyanine phenyl ring is the β position;
    [G 3-MPc (COOH) 32] (compound 14) structural formula is:
    Figure FSB00000885019900081
    In the formula: M is hydrogen, silicon, iron, titanium, cobalt, zinc, aluminium or copper,
    Aryl oxide branch substituting group the position of substitution on the phthalocyanine phenyl ring described in the formula is the β position.
  8. 8. the described load 1-3 of claim 7 is characterized in that: polymer support is gathered (N for the preparation method of the polymer nano-particle of aryl oxide dendritic phthalocyanine complex ε-carbobenzoxy-(Cbz) Methionin)-polyethylene glycol-(N ε-carbobenzoxy-(Cbz) Methionin) and gather (N ε-carbobenzoxy-(Cbz) Methionin)-and polyoxyethylene glycol is dissolved among the DMF/DMSO, and the 1-3 that gets end group and be cyanic acid is for aryl oxide dendritic phthalocyanine material [G 1-MPc (CN) 8], [G 2-MPc (CN) 16] and [G 3-MPc (CN) 32] a kind of being dissolved among the DMF; Be made into the solution of suitable concentration, behind both proportional mixing, add zero(ppm) water in the solution; Place dialysis tubing to dialyse behind 48h～72h filtrating; Take out micellar solution, use filtering with microporous membrane, promptly obtain the polymer nano-particle of load 1-3 for aryl oxide dendritic phthalocyanine photosensitizers.
  9. 9. the described 1-3 of claim 7 is for the preparation method of the polymer nano-particle of aryl oxide dendritic phthalocyanine complex; It is characterized in that: with polymer support: polylysine-polyethylene glycol-Methionin and polyethylene glycol-Methionin are dissolved in the disodium phosphate soln respectively; Be made into the solution of suitable concentration, getting end group is the material [G of the 1-3 of carboxyl for the aryl oxide dendritic phthalocyanine 1-MPc (COOH) 8], [G 2-MPc (COOH) 16] and [G 3-MPc (COOH) 32] a kind of being dissolved in the SODIUM PHOSPHATE, MONOBASIC, be made into the solution of suitable concentration, polymer support polylysine-polyethylene glycol-Methionin and polyethylene glycol-lysine solution and [G 1-MPc (COOH) 8], [G 2-MPc (COOH) 16] and [G 3-MPc (COOH) 32] in a kind of solution proportional mixing, form the polymer nano-particle of load 1-3 for aryl oxide dendritic phthalocyanine photosensitizers.
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