CN105315289A - Zinc phthalocyanine hydriodate photosensitizer, as well as preparation method and application thereof - Google Patents
Zinc phthalocyanine hydriodate photosensitizer, as well as preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses a 2,9,16,23-tetra-((4-aminomethyl) phenoxy) zinc phthalocyanine hydroiodide, as well as a preparation method and application thereof to a photodynamic therapy method, and relates to a 2,9,16,23-tetra-((4-aminomethyl) phenoxy) zinc phthalocyanine hydroiodide photosensitizer. The 2,9,16,23-tetra-((4-aminomethyl) phenoxy) zinc phthalocyanine hydroiodide photosensitizer not only is simple in synthetic method, excellent in solubility (based on the protonation principle) in water, high in anti-tumor activity (based on the heavy atom effect) and low in dark toxicity, but also has a good application prospect in the field of photodynamic therapy methods.
Description
Technical field
The invention belongs to the photosensitizers technical field with photodynamic activity, relate to a kind of ZnPc hydriodate photosensitizers, and its synthetic method and the application in photodynamic therapy thereof.
Background technology
The known molecule containing the large ring of phthalocyanine can produce active oxygen, such as singlet oxygen, and by being characterized as being high fluorescence with the interaction of visible ray.Due to these characteristics, phthalocyanine compound has been employed for some time in order to therapeutic treatment with in order to diagnostic object in photodynamic therapy (representing with abbreviation " PDT " below).As what describe in European patent EP 0906758, EP1164135, EP1381611 and EP1883641, prove that phthalocyanine is effective photosensitizers in the PDT treatment of tumour and infected by microbes.
PDT comprises three fundamentals: light source, oxygen and photosensitizers.Wherein along with the development to treatment light source progress of research and oxygenerating technology, the light source in optical dynamic therapy process and the problem of oxygen are resolved to a certain extent.Compared to light source and oxygen, although the key element photosensitizers of PDT there has also been very large progress and development, but still face a lot of problem and challenge.First the photosensitizers entering clinical application is Porphyrin-Based Sensitizer, is called as first-generation photosensitizers.Since last century the eighties, with phthalocyanines photosensitizers for representative, have that composition is single, structure clear and definite, active oxygen productive rate high to tumor-selective uptake ratio become compared with the s-generation photosensitizers of advantages of higher the object that numerous researcher studies.
Although phthalocyanines photosensitizers has many good qualities, but also there is a lot of bottleneck problem in the application of phthalocyanines photosensitizers in PDT, and main manifestations is the problem how obtaining water-soluble good phthalocyanine, how to strengthen its photosensitive activity further.In order to solve the water solubility problems of Phthalocyanines, researcher both domestic and external has carried out large quantifier elimination, also achieves the achievement that some are considerable.People introduce negatively charged ion or cationic groups by the method for structural modification on phthalocyanine, thus make it have water-soluble by phthalocyanine ionization or formation quaternary ammonium salt; Or by building drug delivery system, under the prerequisite not changing phthalocyanine structure, make it have water-soluble by the effect of carrier and phthalocyanine.This is all that the application of Phthalocyanines in PDT serves certain pushing effect, but the phthalocyanines photosensitizers simultaneously at present with highly water-soluble and anti-tumor activity still extremely lacks.
Recent study shows, the tight demand to aminocompound produced because tumor tissues rises in value fast, amido modified medicine often shows certain tumor-targeting, amido modified phthalocyanine also therefore reason be subject to extensive concern, but amido modified phthalocyanine does not often have good water-soluble, photodynamic activity is also desirable not to the utmost.In order to synchronously increase the water-soluble of amido modified phthalocyanine and photosensitive activity, investigator prepares the quaternary ammonium salt product of amino phthalocyanine often through the method for organic synthesis, and the method can effectively increase the water-soluble of amino phthalocyanine and targeting.But synthesis quaternary ammonium salt phthalocyanine relates to complicated organic reaction and separating-purifying process.Therefore, simpler method is sought to improve the water-soluble of amido modified phthalocyanine and photosensitive activity becomes the key promoting amino phthalocyanine clinical application process.
Summary of the invention
The object of the invention is to overcome existing phthalocyanines derivates as photosensitizers Problems existing, a kind of novel ZnPc hydriodate photosensitizers for photodynamic therapy is provided, amino phthalocyanine is improved based on protonated principle and heavy atoms effect, strengthen the water-soluble and photosensitive anti-tumor activity of amino phthalocyanines photosensitizers, the solvability that described ZnPc hydriodate photosensitizers has not only had in water, and there is high anti-tumor activity and low dark toxicity.
Another object of the present invention is to the synthetic method that described ZnPc hydriodate photosensitizers is provided.
Another object of the present invention is also to provide the application of described ZnPc hydriodate photosensitizers in photodynamic therapy.
For achieving the above object, the present invention by the following technical solutions: a kind of novel photosensitizer compounds ZnPc hydriodate for photodynamic therapy, its structural formula is as shown in the formula shown in I:
Wherein R is
m is Zn.
Described ZnPc hydriodate chemistry 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydriodate by name.Compared with general phthalocyanine derivates, ZnPc hydriodate photosensitizer molecule of the present invention comprises photosensitizers active part and hydrophilic parts, these two portions are combined into hydrophilic photosensitive immunomodulator compounds 2 by ionic linkage, 9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydriodate.
The invention still further relates to a kind of preparation method of described ZnPc hydriodate photosensitizers, comprise the following steps:
1), under basic catalyst catalytic condition, gumbix and 4-nitro phthalic nitrile are obtained by reacting intermediate 4-((4-aminomethyl) phenoxy group) phthalic nitrile (3);
2) under basic catalyst catalytic condition, 4-((4-aminomethyl) phenoxy group) phthalic nitrile (3) and triphenylmethyl chloride react, generate intermediate 4-(4-((triphen methylamino-) methyl) phenoxy group) phthalic nitrile (4), amino is protected;
tr is trityl
3) 4-(4-((triphen methylamino-) methyl) phenoxy group) phthalic nitrile (4) and zinc acetate adopt DBU catalysis to carry out cyclization, obtain nonionic phthalocyanine (5);
4) nonionic phthalocyanine (5) and trifluoroacetic acid react and slough protecting group, generate 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc (6);
5) 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc (6) and HI react, and after recrystallization, obtain 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydriodate (I).
6) 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc (6) and HCl react, and after recrystallization, obtain 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydrochloride (II).
In aforementioned preparation process, DBU is 1,8-diazacyclo [5,4,0] hendecene-7.
Preparation method and the reaction scheme of described ZnPc hydriodate are as follows.
More specifically, in aforesaid method,
The reaction conditions of step (1) is: the mol ratio of 4-nitro phthalic nitrile, gumbix and basic catalyst is 1:1 ~ 5:2 ~ 4; Above-mentioned reaction preferred solvent is DMF (DMF), and protective atmosphere is nitrogen, and temperature of reaction is preferably 20 ~ 100 DEG C.
The reaction conditions of step (2) is: 4-((4-aminomethyl) phenoxy group) phthalic nitrile, triphenylmethyl chloride and basic catalyst mol ratio are 1:1 ~ 5:2 ~ 4; solvent is preferably methylene dichloride; protective atmosphere is nitrogen, normal-temperature reaction.
The reaction conditions of step (3) is: the mol ratio of 4-(4-((triphen methylamino-) methyl) phenoxy group) phthalic nitrile, zinc acetate and DBU is 1:0.5 ~ 2:1 ~ 4; protective atmosphere is nitrogen; solvent is preferably Pentyl alcohol, and temperature of reaction is 120 ~ 160 DEG C.
The reaction conditions of step (4) is: the mol ratio of nonionic phthalocyanine and trifluoroacetic acid is 1:4 ~ 16, and temperature of reaction is 0 ~ 30 DEG C, and solvent is chloroform or methylene dichloride etc.
The reaction conditions of step (5) is: 2,9,16,23-, tetra--((4-aminomethyl) phenoxy group) ZnPc and excessive HI react, and solvent is preferably water, and temperature of reaction is 25 DEG C ~ reflux temperature.Recrystallization solvent is preferably acetone.
The reaction conditions of step (6) is: 2,9,16,23-, tetra--((4-aminomethyl) phenoxy group) ZnPc and excessive HCl react, and solvent is preferably water, and temperature of reaction is 25 DEG C ~ reflux temperature.Recrystallization solvent is preferably acetone.
Described basic catalyst is inorganic base catalyst or organic alkali catalyst, and wherein inorganic base catalyst is preferably Na
2cO
3, K
2cO
3or LiOH, organic alkali catalyst is preferably triethylamine.
The invention still further relates to aforesaid 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydriodates and prepare the application in photo-dynamical medicine as photosensitizers.
The ultra-violet absorption spectrum of 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydriodates of the present invention as shown in Figure 1, has strong absorption at phototherapy window (600-900nm); Described ZnPc hydriodate has higher singlet oxygen quantum yield and reactive oxygen species productive rate, 2,9,16, the singlet oxygen of 23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydriodate in water produces speed as shown in Figure 2, and reactive oxygen species productive rate as shown in Figure 3.And ZnPc hydriodate of the present invention has good anti tumor activity in vitro, and dark toxicity is low, and the dark toxicity under its In vitro cell experiment and anti-tumor activity are respectively as shown in Figure 4, Figure 5.
Photosensitizers 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) the ZnPc hydriodate of the present invention's synthesis, it has good solvability in the solvent of water or biocompatibility.Not only effectively can improve water-soluble (based on the protonated principle) of amino phthalocyanine, and effectively can strengthen the photosensitive anti-tumor activity (based on heavy atoms effect principle) of amino phthalocyanine.Amino phthalocyanine method that is water-soluble and anti-tumor activity is improved not only effective by synthesis hydriodate, and very simple, do not relate to complicated synthesis and sepn process, have a good application prospect.
2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydriodates of the present invention have following advantages:
(1) of the present invention 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydriodate can not only be soluble in water, and long-time stable can to exist in water.
(2) 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydriodates of the present invention have strong absorption at phototherapy window (600-900nm), can be dissolved in multi-solvents.
(3) 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydriodates of the present invention have higher singlet oxygen quantum yield and reactive oxygen species productive rate.
(4) In vitro cell experiment shows, 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydriodates of the present invention have good anti tumor activity in vitro, and dark toxicity is low.
Describe the present invention below in conjunction with specific embodiment.Protection scope of the present invention is not limited with embodiment, but is limited by claim.
Accompanying drawing explanation
Fig. 1 is 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydriodate (I) and 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydrochloride (II) ultra-violet absorption spectrum in water.
Fig. 2 is the Linear Fit Chart that the singlet oxygen of 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydriodate in water produces speed.With 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydrochloride (II) is compared, and 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydriodate shows higher singlet oxygen productive rate.
Fig. 3 is that 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydriodate produces speed at intracellular active oxygen.As seen from the figure, 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydriodate shows higher reactive oxygen species productive rate, imply that it has higher anti-tumor activity.
Fig. 4 is the dark toxicity (under lucifuge condition cell survival rate) of 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydriodates under different pharmaceutical concentration.As seen from the figure, 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydriodate has lower dark toxicity, shows that its security is high.
Fig. 5 is the anti-tumor activity of 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydriodates under different pharmaceutical concentration.As seen from the figure, 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydriodate shows higher anti-tumor activity.
Embodiment
In following examples, DBU is 1,8-diazacyclo [5,4,0] hendecene-7, Tr is trityl, and DMF is DMF.Basic catalyst adopts mineral alkali as K
2cO
3, LiOH, Na
2cO
3deng and organic bases as triethylamine etc.
The synthesis of embodiment 12,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydriodate
(1) synthesis of 4-((4-aminomethyl) phenoxy group) phthalic nitrile
Reaction formula is shown below:
Under nitrogen protection, 4-nitro phthalic nitrile, gumbix and K
2cO
31:1:2 joins in DMF in molar ratio, then adds 10mL methylene dichloride as solvent, reacts 6h at 60 DEG C, obtain intermediate 3;
(2) synthesis of 4-(4-((triphen methylamino-) methyl) phenoxy group) phthalic nitrile
Reaction formula is shown below:
Under nitrogen protection, triphenylmethyl chloride methylene dichloride dissolves, and instills in the dichloromethane solution of intermediate 3 and salt of wormwood with constant pressure funnel slowly, intermediate 3 is 1:1.2:2.5 with triphenylmethyl chloride and salt of wormwood mol ratio, titration is about 5h, then normal-temperature reaction 4h, obtains intermediate 4;
(3) 2,9,16, the 23-tetra--(synthesis of (4-(((trityl) is amino) methyl) phenoxy group) ZnPc
Reaction formula is shown below:
Under nitrogen protection, intermediate 4, metal-salt and DBU in molar ratio 4:2.5:6 add in Pentyl alcohol, and back flow reaction 24h obtains the nonionic phthalocyanine 5 containing trityl as protecting group;
The synthesis of (4) 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPcs
Reaction formula is shown below:
Under ice-water bath, the trifluoroacetic acid of 8 equivalents adds in the dichloromethane solution of nonionic phthalocyanine 5 of trityl as protecting group, stirring reaction 1h, rise to room temperature and continue stirring reaction 2h, regulate pH to be about 9-10 with the aqueous sodium hydroxide solution of 10% afterwards, obtain 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc 6;
The synthesis of (5) 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydriodates
Reaction formula is shown below:
By 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc 6 is suspended in distilled water, adds the hydroiodic acid HI of 5% of 30 equivalents, stirs until 2 under normal temperature, 9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc 6 dissolves completely.Concentration of reaction solution, in impouring 50mL acetone, has blue-greenish colour fluffy solid to separate out.Filter, obtain described ZnPc hydriodate I.
Embodiment 2
The synthetic method of 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydriodate, step is as follows:
(1) synthesis of 4-((4-aminomethyl) phenoxy group) phthalic nitrile
Under nitrogen protection, 4-nitro phthalic nitrile, gumbix and LiOH in molar ratio 1:1.5:2 join in DMF, then add 10mL methylene dichloride and react 6h as at solvent 80 DEG C, obtain intermediate 3;
(2) synthesis of 4-(4-((triphen methylamino-) methyl) phenoxy group) phthalic nitrile
Under nitrogen protection, triphenylmethyl chloride methylene dichloride dissolves, and constant pressure funnel instills in the dichloromethane solution of intermediate 3 and LiOH slowly, intermediate 3 is 1:1.5:2 with triphenylmethyl chloride and LiOH in molar ratio, titration is about 5h, then normal-temperature reaction 4h, obtains intermediate 4;
(3) 2,9,16, the 23-tetra--(synthesis of (4-(((trityl) is amino) methyl) phenoxy group) ZnPc
Under nitrogen protection, intermediate 4, metal-salt and DBU in molar ratio 1:1.6:4 add in Pentyl alcohol, and back flow reaction 24h obtains the nonionic phthalocyanine 5 containing trityl as protecting group;
The synthesis of (4) 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPcs
Under ice-water bath, 12 equivalent trifluoroacetic acids add in the dichloromethane solution of nonionic phthalocyanine 5 of trityl as protecting group, stirring reaction 1h, rise to room temperature and continue stirring reaction 2h, regulate pH to be about 9-10 with the aqueous sodium hydroxide solution of 10% afterwards, obtain 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc 6;
The synthesis of (5) 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydriodates
By 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc 6 is suspended in distilled water, adds the hydroiodic acid HI of 5% of 40 equivalents, stirs until 2 under normal temperature, 9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc 6 dissolves completely.Concentration of reaction solution, in impouring 50mL acetone, has blue-greenish colour fluffy solid to separate out.Filter, obtain described ZnPc hydriodate I.
Embodiment 3
The synthesis of 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydrochloride (II), step is as follows:
(1) according to embodiment 1 step (1) ~ (4), obtained 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc;
The synthesis of (2) 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydrochlorides
By 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc 6 is suspended in distilled water, adds the hydrochloric acid of 5% of 30 equivalents, stirs until 2 under normal temperature, 9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc 6 dissolves completely.Concentration of reaction solution, in impouring 50mL acetone, has blue-greenish colour fluffy solid to separate out.Filter, obtain 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydrochloride II.
Embodiment 4
(1) by phthalocyanine solution and ADPA aqueous solution, the LED of 665nm is irradiated, the ultraviolet absorption peak at a per minute record 378nm place.
(2) the generation speed of singlet oxygen is obtained by following formulae discovery:
ln([ADPA]
t/[ADPA]
0)＝-kt
Wherein [ADPA]
t[ADPA]
0be the concentration of ADPA before and after illumination, k is the generation speed of singlet oxygen, and t is the time of illumination.
(3) velocity fitting value is produced from the singlet oxygen of two phthalocyanines in water, 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydriodate (I) is compared to 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydrochloride (II) singlet oxygen produces ability obvious enhancing.
Embodiment 5
(1) hatch 4h after cell administration, add non-blooming DCFH-DA (dichlorofluorescin-acetylacetic ester).By the LED that wavelength is 665nm, 5min is irradiated to it.The active oxygen oxidizes that non-blooming DCFH-DA can be produced by medicine is the DCF (dichlorofluorescein) having fluorescence, detects reactive oxygen species generation ability by surveying intracellular fluorescence intensity.
(2) produce the ability of active oxygen in cell, namely relative intensity of fluorescence FL value is obtained by following formulae discovery:
FL＝DCF
treated/DCF
untreated
Wherein, DCF
treatedfor administration group produces the fluorescence intensity of DCF, DCF
untreatedfor blank group produces the fluorescence intensity of DCF.
(3) by more known with blank group, two kinds of phthalocyanines all have good active oxygen and produce ability, and 2,9, the reactive oxygen species of 16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydriodate (I) produces ability and is obviously better than 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydrochloride (II).
Embodiment 6
(1) with tetrazolium bromide (MTT) method research 2,9,16, the anti tumor activity in vitro of 23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydriodate, 24h is hatched after cell administration, by carrying out the phototoxicity of detection of drugs to its illumination 5min by LED (665nm), the experimental group of not illumination is used for detecting dark toxicity.
(2) cell survival rate is the absorbance decision measured by administration group and blank group cell, and cell survival rate V can be obtained by following formulae discovery:
V＝A
1/A
2×100％
Wherein, A
1for administration group absorbance, A
2for blank group absorbance.
(3) 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydriodate has good cell security, in addition, 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydriodate (I) is compared to 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydrochloride (II) has better photosensitive activity.
Claims (9)
1. a ZnPc hydriodate photosensitizers, is characterized in that, has the structure of following formula I:
In formula,
m=Zn.
2. a preparation method for ZnPc hydriodate photosensitizers according to claim 1, comprises the following steps:
1), under basic catalyst catalytic condition, gumbix and 4-nitro phthalic nitrile are obtained by reacting intermediate 4-(4-aminomethyl) phenoxy group) phthalic nitrile (3);
2) under basic catalyst catalytic condition, 4-((4-aminomethyl) phenoxy group) phthalic nitrile and triphenylmethyl chloride react, generate intermediate 4-(4-((triphen methylamino-) methyl) phenoxy group) phthalic nitrile (4), amino is protected;
tr is trityl
3) 4-(4-((trityl-amino) methyl) phenoxy group) phthalic nitrile and zinc acetate adopt DBU catalysis to carry out cyclization, obtain nonionic phthalocyanine (5);
4) nonionic phthalocyanine (5) and trifluoroacetic acid react and slough trityl-protecting group, generate 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc (6);
5) 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc (6) and hydroiodic acid HI react, and after recrystallization, obtain 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc hydriodate.
3. the preparation method of ZnPc hydriodate photosensitizers according to claim 2, it is characterized in that: described basic catalyst is inorganic base catalyst or organic alkali catalyst, wherein inorganic base catalyst is Na
2cO
3, K
2cO
3or LiOH, organic alkali catalyst is triethylamine.
4. the preparation method of ZnPc hydriodate photosensitizers according to claim 2, is characterized in that: in step (1), the mol ratio of described 4-nitro phthalic nitrile, gumbix and basic catalyst is 1:1 ~ 5:2 ~ 4; Reaction solvent is DMF (DMF); Temperature of reaction, between 20 ~ 100 DEG C, is carried out under protective atmosphere is condition of nitrogen gas.
5. the preparation method of ZnPc hydriodate photosensitizers according to claim 2, it is characterized in that: in step (2), described 4-((4-aminomethyl) phenoxy group) phthalic nitrile (3), triphenylmethyl chloride and basic catalyst mol ratio are 1:1 ~ 5:2 ~ 4; Solvent is methylene dichloride, and protective atmosphere is nitrogen, reacts under normal temperature.
6. the preparation method of ZnPc hydriodate photosensitizers according to claim 2; it is characterized in that: in step (3); the mol ratio of described 4-(4-((triphen methylamino-) methyl) phenoxy group) phthalic nitrile (4), zinc acetate and DBU is 1:0.5 ~ 2:1 ~ 4; protective atmosphere is nitrogen; solvent is Pentyl alcohol, and temperature of reaction is 120 ~ 160 DEG C.
7. the preparation method of ZnPc hydriodate photosensitizers according to claim 2, it is characterized in that: in step (4), nonionic phthalocyanine (5) is 1:4 ~ 16 with the mol ratio of trifluoroacetic acid, and temperature of reaction is 0 ~ 30 DEG C, and solvent is chloroform or methylene dichloride.
8. the preparation method of ZnPc hydriodate photosensitizers according to claim 2, it is characterized in that: in step (5), described 2,9,16,23-tetra--((4-aminomethyl) phenoxy group) ZnPc (6) and excessive HI react, and solvent is water, temperature of reaction is 25 DEG C ~ reflux temperature, and recrystallization solvent is acetone.
9. ZnPc hydriodate according to claim 1 is preparing the application in photo-dynamical medicine as photosensitizers.
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| CN105968117A (en) * | 2016-05-16 | 2016-09-28 | 河北工业大学 | Tetra-substituted phenoxyl zinc phthalocyanine and preparation method thereof |
| CN109996801A (en) * | 2016-11-17 | 2019-07-09 | 坦佩林大学注册基金会 | Photosensitizer |
| CN113880849A (en) * | 2021-08-31 | 2022-01-04 | 南京师范大学 | Chiral lysine modified zinc phthalocyanine and preparation method and application thereof |
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| CN104262350A (en) * | 2014-10-09 | 2015-01-07 | 福州大学 | Phthalocyanine metal complex as well as preparation method and application thereof |
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| CN104003993A (en) * | 2014-06-03 | 2014-08-27 | 南京师范大学 | Polyamine phthalocyanine and derivative thereof as well as preparation and application of polyamine phthalocyanine and derivative thereof |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105968117A (en) * | 2016-05-16 | 2016-09-28 | 河北工业大学 | Tetra-substituted phenoxyl zinc phthalocyanine and preparation method thereof |
| CN109996801A (en) * | 2016-11-17 | 2019-07-09 | 坦佩林大学注册基金会 | Photosensitizer |
| CN109996801B (en) * | 2016-11-17 | 2022-03-22 | 等离子体光学有限公司 | Photosensitizers |
| CN113880849A (en) * | 2021-08-31 | 2022-01-04 | 南京师范大学 | Chiral lysine modified zinc phthalocyanine and preparation method and application thereof |
| CN113880849B (en) * | 2021-08-31 | 2022-12-16 | 南京师范大学 | Chiral lysine modified zinc phthalocyanine and preparation method and application thereof |
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