CN103242474B - Phosphorylcholine structure modified-perylene imide derivative and preparation method thereof - Google Patents

Abstract

The invention provides a phosphorylcholine structure modified-perylene imide derivative. The structural formula is as shown in the specification. The invention also provides a preparation method of the phosphorylcholine structure modified-perylene imide derivative. The phosphorylcholine structure modified-perylene imide derivative provided by the invention is grafted with a hydrophilic phosphorylcholine structure by a chemical method, and is good in water solubility, high in fluorescence quantum yield, and good in biocompatibility. According to the preparation method, two oligomers containing the phosphorylcholine structures are connected to perylene bisimide to form a segment of grafted oligomer chain by an atom transfer radical polymerization grafting method. The preparation method is simple and reliable in preparation technology, and easy to achieve.

Description

Perylene imide derivatives modified by phosphorylcholine structure and preparation method thereof

technical field

The invention belongs to the field of chemical synthesis, and in particular relates to a phosphorylcholine-modified peryleneimide derivative, and also relates to a preparation method of the phosphorylcholine-modified peryleneimide derivative.

Background technique

Perylene derivatives have superior photochemical, chemical and thermal stability, and have strong absorption of light from visible light to ultraviolet region. They are a class of molecular electronics materials with specific properties. It has a wide range of applications in batteries and photoluminescent devices. Perylene has high fluorescence quantum yield, high photostability, and chemical stability. Its absorption in the visible region can avoid the background fluorescence of organisms, and it is easy to modify. These properties lay the foundation for it to be used as a biomarker.

It is difficult to make perylene derivatives water-soluble while maintaining high fluorescence quantum yield, which has always been a very hot topic. In the existing research literature, the modification method to make the perylene derivatives have good water solubility is to introduce a solubilizing group on the nitrogen atom or Bay-position of the imide. Gao et al. (Gao B, et al. Water-soluble and fluorescent dendritic perylenebisimides for live-cell imaging. Chemical Communications. 2011; 47 (13): 3894-3896) grafted dendritic polyethylene glycol (PEG) onto perylene On the nitrogen atom of the imine, the obtained polyethylene glycol-modified perylene imide derivative (PEPBI) has good water solubility, low cytotoxicity and high fluorescence yield, and can be applied to the fluorescent labeling of cells . Xu et al. (Xu LQ, et al. Functionalization of reduced graphene oxide nanosheets via stacking interactions with the fluorescent and water-soluble perylenebisimide-containing polymers. Polymer. 2011; 52 (11): 2376-2383) used the ATRP method to polymerize glyceryl acrylate Branched on the perylene imide, the obtained perylene imide derivative (PBIPGA) has good water solubility and high fluorescence yield, and the product is used to modify graphene to obtain water-soluble graphene. The patent document with Chinese patent application number 200910229526.6 discloses a method for synthesizing water-soluble peryleneimide derivatives containing N-pyridine oxide groups. The reaction of a hydroxyl substitution reagent, followed by oxidation with hydrogen peroxide, the conditions of the preparation method are easy to control, the reaction is relatively mild, and the raw materials are economical. High rate. The patent document with the Chinese patent application number 200910204975.5 discloses a weather-resistant perylene imide dye and its preparation method. The naphthalene modified by the water-soluble group is reacted with the perylene imide, and the Bay-position modification of the perylene ring is water-soluble Reactive groups can be used to obtain perylene imide derivatives with excellent weather resistance, which can be used as colorants in materials.

It is difficult for perylene derivatives to maintain a high fluorescence quantum yield while being water-soluble, which has always been a problem for researchers to expand their application in biological systems.

Contents of the invention

Purpose of the invention: the first purpose of the present invention is to provide a kind of perylene imide derivative with good water solubility and high fluorescence quantum yield of phosphorylcholine structure modification, more specifically to provide a kind of (meth)acrylic Acyloxyalk(oxy)ylphosphorylcholine-modified peryleneimide derivatives.

The second object of the present invention is to provide a preparation method of the above-mentioned derivatives.

Technical solution: The phosphorylcholine structurally modified perylene imide derivative provided by the present invention has the following structural formula:

Wherein, R ₁ is H, CH ₃ ;

R ₂ is C _n H _2n , n=2, 3 or 4;

R ₃ is C _m H _2m , m=2, 3 or 4;

x≥1.

The present invention also provides a method for preparing the above-mentioned peryleneimide derivatives modified by phosphorylcholine structure, comprising the following steps:

(1) Preparation of N,N'-hydroxyalkylperyleneimide (PBI-OH): N,N'-hydroxyalkylperyleneimide is obtained from the reaction of perylenetetracarboxylic dianhydride and alkanolamine;

(2) Preparation of 2-bromo-2-methylpropionyl bromide modified perylene imide derivatives (PBI-Br): N,N'-hydroxyalkyl perylene imide and 2-bromo-2-methyl Propionyl bromide reaction to obtain 2-bromo-2-methyl propionyl bromide modified perylene imide derivatives;

(3) Preparation of perylene imide derivatives modified by phosphorylcholine structure: using atom transfer radical polymerization (ATRP) grafting method, in an inert atmosphere such as nitrogen or argon, 2-bromo-2-methyl The perylene imide derivative modified by propionyl bromide and the polymerizable compound containing phosphorylcholine structure undergo free radical polymerization under the induction of an initiating system to obtain the obtained product.

Wherein, in step (1), the amino alcohol amine is preferably one of ethanolamine, n-propanolamine and n-butanolamine.

Wherein, in step (1), the molar ratio of perylenetetracarboxylic dianhydride to alkanolamine is 1:2-1:100, preferably 1:60-1:80; the reaction temperature is 100-190°C, preferably 140-180°C; the reaction time is 3h-30h, preferably 12-24h.

Wherein, in step (2), the molar ratio of N,N'-hydroxyalkylperyleneimide (PBI-OH) to 2-bromo-2-methylpropionyl bromide is 1:3-1:10, preferably 1:3-1:6; the reaction temperature is 0-40°C, preferably 4-25°C; the reaction time is 1h-24h, preferably 4-12h.

Wherein, in step (2), the reaction solvent is halogenated alkanes, preferably one or more of chloroform, dichloromethane, monochloromethane, dichloroethane, trichloroethane, monochloroethane Composition; the ratio of reaction solvent to N,N'-hydroxyalkyl perylene imide (PBI-OH) is 100-250mL:1mmol, preferably 150-200mL:1mmol.

Wherein, in step (2), the reaction system also includes an acid-binding agent, the acid-binding agent is an organic base, preferably one or more of tributylamine, tripropylamine, triethylamine, trimethylamine, pyridine The composition, the molar ratio of the acid-binding agent to 2-bromo-2-methylpropionyl bromide is 1:1.

Wherein, in step (3), the peryleneimide derivative provided by the present invention is modified with a polymerizable compound containing a phosphorylcholine structure, and the structural formula of the polymerizable compound containing a phosphorylcholine structure is as follows:

Among them, the polymerizable compound containing phosphorylcholine structure is acryloyloxyethylphosphorylcholine, acryloyloxypropylphosphorylcholine, acryloyloxybutylphosphorylcholine, methacryloylphosphorylcholine A combination of one or more of oxyethyl phosphorylcholine, methacryloyloxypropyl phosphorylcholine or methacryloyloxybutyl phosphorylcholine.

Wherein, in step (3), the molar ratio of the polymerizable compound containing phosphorylcholine structure to the peryleneimide derivative (PBI-Br) modified by 2-bromo-2-methylpropionyl bromide is 20-60 :1, preferably 20-40:1; the reaction temperature is 30-100°C, preferably 50-80°C; the reaction time is 8-24h, preferably 10-16h; the reaction system adopts ultrasonic oscillation.

Wherein, in step (3), the initiating system is a combination of a transition metal salt and a ligand, and the transition metal salt is one of ferrous sulfate, ferrous chloride, cuprous chloride and cuprous bromide , the ligands are bipyridine (bpy), 4,4'-di-tert-butyl-2,2'-bipyridine (dTbpy), 4,4'-di-n-heptyl-2,2'-bipyridine One of pyridine (dHbpy), 4,4'-bis(5-nonyl)-2,2'-bipyridine (dNbpy), pentamethyldiethylenetriamine (PMDETA); the transition metal salt and The number of moles of the ligands is the same; the number of moles of the transition metal salt is more than twice, preferably twice, the number of moles of the peryleneimide derivative modified by 2-bromo-2-methylpropionyl bromide.

Wherein, in step (3), the reaction solvent is one or more compositions in benzene, xylene, cyclohexanone, anisole and tetrahydrofuran; the reaction solvent and 2-bromo-2-methylpropionyl bromide The dosage ratio of the modified peryleneimide derivative (PBI-Br) is 10-100mL:0.05mmol, preferably 10-20mL:0.05mmol.

Beneficial effects: the phosphorylcholine structure-modified perylene imide derivatives provided by the invention are grafted with a hydrophilic phosphorylcholine structure by a chemical method, and have good water solubility, high fluorescence quantum yield, and good biocompatibility .

Since the phosphorylcholine structure is a part of a class of compounds inherent in organisms such as phospholipids, the peryleneimide derivatives modified with the phosphorylcholine structure have good biocompatibility, and because the product has high fluorescence Therefore, the peryleneimide derivative has the potential use as a fluorescent label in the biomedical field.

The preparation method of perylene imide derivatives modified by phosphorylcholine structure provided by the present invention is to connect two oligomers containing phosphorylcholine structure to peryleneimide by means of atom transfer radical polymerization grafting A grafted oligomer chain is formed on the surface, and the preparation process is simple, reliable and easy to realize.

Description of drawings

Fig. 1 is the nuclear magnetic hydrogen ( ¹ H-NMR) spectrogram of the perylene imide derivative modified by phosphorylcholine structure;

Fig. 2 is the ultraviolet-visible spectrogram of the perylene imide derivative of phosphorylcholine structure modification;

Fig. 3 is the fluorescence emission spectrum of the perylene imide derivative modified by phosphorylcholine structure.

Detailed ways

The present invention can be better understood from the following examples. However, those skilled in the art will readily understand that the specific material ratios, process conditions and results described in the examples are only used to illustrate the present invention, and should not and will not limit the present invention described in detail in the claims .

Example 1

A perylene imide derivative modified by phosphorylcholine structure, its structural formula is:

Its preparation method comprises the following steps:

(1) Preparation of hydroxyethyl perylene imide: Weigh 0.8g of perylenetetracarboxylic dianhydride and place it in a polytetrafluoroethylene-lined hydrothermal reaction kettle, add 9.76g of ethanolamine, and place the reaction kettle at 180°C for reaction 24h. After the reaction, add 25 mL of distilled water, centrifuge after stirring, pour off the last solution, repeat this process 3 times, and obtain hydroxyethyl perylene imide after vacuum drying at 60°C.

(2) Preparation of 2-bromo-2-methylpropionyl bromide-modified peryleneimide derivatives (PBI-Br): Weigh 550mg of hydroxyethylperyleneimide into a 250mL three-necked bottle, add 150mL to dry of dichloromethane and 0.43mL of triethylamine, ultrasonically dispersed. The three-necked flask was placed in an ice-water bath, 0.69 g of 2-bromo-2-methylpropionyl bromide was added dropwise, and the stirring was continued for 1 h. Then, the three-necked flask was placed at room temperature and stirred for 24 h. The reacted product was filtered to remove unreacted hydroxyethyl perylene imide and triethylamine hydrobromide. The obtained filtrate was evaporated to dryness to obtain a 2-bromo-2-methylpropionyl bromide-modified peryleneimide derivative (PBI-Br).

(3) Free radical polymerization grafted phosphorylcholine structure: Weigh 43 mg of perylene imide derivative (PBI-Br) modified by 2-bromo-2-methylpropionyl bromide, 3 mmol of methacryloyloxyethyl Phosphorylcholine, 14.4mg of cuprous bromide, 8mL of tetrahydrofuran in a 25mL flask, magnetically stirred. Nitrogen was passed into the flask for 20 minutes. Add 17.3mg of pentamethyldiethylenetriamine (PMDETA) rapidly, seal the flask, and stir in an oil bath at 60°C for 8h. The obtained dispersion was passed through a 0.22 μm filter membrane and washed three times with tetrahydrofuran. Dry at 60°C to obtain a peryleneimide derivative grafted with a phosphorylcholine structure.

The final product PBI-PCn in this example was characterized and determined.

In the proton nuclear magnetic resonance spectrum of accompanying drawing 1, the two peaks between 8.0-8.5ppm are the peaks of 8 hydrogens on the perylene ring, and the peaks at 0.86, 1.05, and 1.11ppm on the figure are connected to the phosphorylcholine structure. The signal of the hydrogen on the two methyl groups on the double bond methyl and 2-bromo-2-methylpropionyl bromide, the peak at 1.82ppm is the signal of the hydrogen on the methylene connecting two carbon atoms in the final product, 3.2ppm The signal at 3.66ppm is the signal of hydrogen on the three methyl groups on the quaternary amine, the doublet at 3.66ppm is the signal of hydrogen on the methylene connecting the nitrogen atom and the carbon atom in the final product, and the multiplet at 4.18ppm is the final The signal of hydrogen on the methylene connecting the oxygen atom and the carbon atom in the product is the water peak at 4.7ppm. ^{The 1} H-NMR spectrum proves from the structure that the phosphorylcholine structure has been successfully grafted to the perylene On the amine, through the integral ratio of the two peaks at 8.0-8.5ppm and the single peak at 3.2ppm, the number of phosphorylcholine structural units grafted is calculated to be 32, so x≈16 here.

In the visible spectrum of accompanying drawing 2, three characteristic peaks of the perylene derivatives at 475nm, 501nm and 543nm all appear in the spectrogram, and the solution is uniform, which proves that the structure of phosphorylcholine is successfully connected to Branched onto the perylene imide.

In the ultraviolet fluorescence spectrum of accompanying drawing 3, the excitation light of 373nm wavelength is used to excite solutions of different concentrations. At a concentration of 5mg/mL, the fluorescence is mainly red light of 600nm, and the fluorescence intensity is lower than that of the solution of 2.5mg/mL , this is due to the self-quenching of the fluorescence of the peryleneimide derivative solution at a high concentration. The structurally modified perylene imide derivatives have good water solubility and high-intensity fluorescence.

Example 2

A perylene imide derivative modified by phosphorylcholine structure, its structural formula is:

Its preparation method comprises the following steps:

(1) Preparation of hydroxy n-propyl perylene imide: take 2mmol perylenetetracarboxylic dianhydride and place it in a polytetrafluoroethylene-lined hydrothermal reaction kettle, add 4mmol n-propanolamine, and place the reaction kettle at 190°C Reaction 3h. After the reaction, 25 mL of distilled water was added, stirred and centrifuged, and the last solution was poured off. This process was repeated 3 times, and the hydroxy-n-propylperyleneimide was obtained after vacuum drying at 60°C.

(2) Preparation of 2-bromo-2-methylpropionyl bromide-modified peryleneimide derivatives (PBI-Br): Take 1mmol of hydroxy-n-propylperyleneimide in a 250mL three-necked bottle, add 100mL to dry of chloroform and 3 mmol of tributylamine, ultrasonically dispersed. The three-necked flask was placed in an ice-water bath, and 3 mmol of 2-bromo-2-methylpropionyl bromide was added dropwise, and the stirring was continued for 1 h. Then, the three-necked flask was placed at 0° C. and stirred for 24 h. The reacted product was filtered to remove unreacted hydroxyethyl perylene imide and triethylamine hydrobromide. The obtained filtrate was evaporated to dryness to obtain a 2-bromo-2-methylpropionyl bromide-modified peryleneimide derivative (PBI-Br).

(3) Free radical polymerization grafted phosphorylcholine structure: take 0.05mmol 2-bromo-2-methylpropionyl bromide modified perylene imide derivative (PBI-Br), 1mmol methacryloyloxyethyl Phosphorylcholine, 0.1mmol ferrous sulfate, 10mL benzene in a 25mL flask, magnetically stirred. Nitrogen was passed through the flask for 20 minutes. Quickly add 0.1 mmol bipyridine (bpy), seal the flask, and stir in an oil bath at 70° C. for 13 h. The obtained dispersion was passed through a 0.22 μm filter membrane and washed three times with tetrahydrofuran. Dry at 60°C to obtain a peryleneimide derivative grafted with a phosphorylcholine structure.

Example 3

A perylene imide derivative modified by phosphorylcholine structure, its structural formula is:

Its preparation method comprises the following steps:

(1) Preparation of hydroxyisopropyl perylene imide: Weigh 2mmol perylenetetracarboxylic dianhydride and place it in a polytetrafluoroethylene-lined hydrothermal reaction kettle, add 200mmol isopropanolamine, and place the reaction kettle at 100 ℃ reaction 30h. After the reaction, 25 mL of distilled water was added, stirred and centrifuged, and the last solution was poured off. This process was repeated three times, and hydroxyisopropyl perylene imide was obtained after vacuum drying at 60°C.

(2) Preparation of 2-bromo-2-methylpropionyl bromide-modified peryleneimide derivatives (PBI-Br): Take 1mmol hydroxyisopropylperyleneimide in a 250mL three-necked bottle, add 250mL to dry Dichloroethane and 6mmol of tripropylamine, ultrasonic dispersion. Place the three-necked flask in an ice-water bath, add 6 mmol of 2-bromo-2-methylpropionyl bromide dropwise, and continue stirring for 1 h. Then, the three-necked flask was placed at 40° C. and stirred for 1 h. The reacted product was filtered to remove unreacted hydroxyethyl perylene imide and triethylamine hydrobromide. The obtained filtrate was evaporated to dryness to obtain a 2-bromo-2-methylpropionyl bromide-modified peryleneimide derivative (PBI-Br).

(3) Free radical polymerization grafted phosphorylcholine structure: Take 0.05mmol 2-bromo-2-methylpropionyl bromide modified perylene imide derivative (PBI-Br), 3mmol acryloyloxypropylphosphorus Acylcholine, 0.1mmol ferrous chloride, 100mL xylene in a 150mL flask, magnetically stirred. Nitrogen was passed into the flask for 20 minutes. Add 0.1 mmol 4,4'-di-tert-butyl-2,2'-bipyridine (dTbpy) rapidly, seal the flask, and stir in an oil bath at 80°C for 10 h. The obtained dispersion was passed through a 0.22 μm filter membrane and washed three times with tetrahydrofuran. Dry at 60°C to obtain a peryleneimide derivative grafted with a phosphorylcholine structure.

Example 4

A perylene imide derivative modified by phosphorylcholine structure, its structural formula is:

Its preparation method comprises the following steps:

(1) Preparation of hydroxy-n-butylperyleneimide: Weigh 2mmol perylenetetracarboxylic dianhydride and place it in a polytetrafluoroethylene-lined hydrothermal reaction kettle, add 120mmol n-butanolamine, and place the reaction kettle at 140 ℃ reaction 12h. After the reaction, add 25 mL of distilled water, centrifuge after stirring, pour off the last solution, repeat this process 3 times, and obtain hydroxy-n-butylperyleneimide after vacuum drying at 60°C.

(2) Preparation of 2-bromo-2-methylpropionyl bromide modified perylene imide derivatives (PBI-Br): Take 1 mmol of hydroxy n-butyl perylene imide in a 250 mL three-necked bottle, add 150 mL to dry of trichloroethane and 10 mmol of trimethylamine, ultrasonically dispersed. Place the three-necked flask in an ice-water bath, add 10 mmol of 2-bromo-2-methylpropionyl bromide dropwise, and continue stirring for 1 h. Then, the three-necked flask was placed at 4° C. and stirred for 12 h. The reacted product was filtered to remove unreacted hydroxyethyl perylene imide and triethylamine hydrobromide. The obtained filtrate was evaporated to dryness to obtain a 2-bromo-2-methylpropionyl bromide-modified peryleneimide derivative (PBI-Br).

(3) Free radical polymerization grafted phosphorylcholine structure: take 0.05mmol 2-bromo-2-methylpropionyl bromide modified perylene imide derivative (PBI-Br), 2mmol methacryloyloxypropane Base phosphorylcholine, 0.1mmol cuprous chloride, 20mL cyclohexanone in a 25mL flask, magnetically stirred. Nitrogen was passed into the flask for 20 minutes. Add 0.1 mmol 4,4'-di-n-heptyl-2,2'-bipyridine (dHbpy) rapidly, seal the flask, and stir in an oil bath at 50°C for 16h. The obtained dispersion was passed through a 0.22 μm filter membrane and washed three times with tetrahydrofuran. Dry at 60°C to obtain a peryleneimide derivative grafted with a phosphorylcholine structure.

Example 5

A perylene imide derivative modified by phosphorylcholine structure, its structural formula is:

Its preparation method comprises the following steps:

(1) Preparation of hydroxyisobutylperyleneimide: Weigh 2mmol perylenetetracarboxylic dianhydride and place it in a polytetrafluoroethylene-lined hydrothermal reaction kettle, add 40mmol isobutanolamine, and place the reaction kettle at 170 ℃ reaction 18h. After the reaction, 25 mL of distilled water was added, stirred and centrifuged, and the last solution was poured off. This process was repeated 3 times, and hydroxyisobutylperyleneimide was obtained after vacuum drying at 60°C.

(2) Preparation of 2-bromo-2-methylpropionyl bromide-modified peryleneimide derivatives (PBI-Br): Take 1mmol hydroxyisobutylperyleneimide in a 250mL three-necked bottle, add 200mL to dry Chloromethane and 5mmol of pyridine, ultrasonically dispersed. The three-necked flask was placed in an ice-water bath, and 5 mmol of 2-bromo-2-methylpropionyl bromide was added dropwise, and the stirring was continued for 1 h. Then, the three-necked flask was placed at 25°C and continued to stir for 4h. The reacted product was filtered to remove unreacted hydroxyethyl perylene imide and triethylamine hydrobromide. The obtained filtrate was evaporated to dryness to obtain a 2-bromo-2-methylpropionyl bromide-modified peryleneimide derivative (PBI-Br).

(3) Free radical polymerization grafted phosphorylcholine structure: take 0.05mmol 2-bromo-2-methylpropionyl bromide modified perylene imide derivative (PBI-Br), 1.5mmol acryloyloxypropyl Phosphorylcholine, 0.1mg cuprous bromide, 50mL anisole in a 100mL flask, magnetically stirred. Nitrogen was passed through the flask for 20 minutes. Add 0.1 mmol 4,4'-bis(5-nonyl)-2,2'-bipyridine (dNbpy) rapidly, seal the flask, and stir in an oil bath at 100°C for 8h. The obtained dispersion was passed through a 0.22 μm filter membrane and washed three times with tetrahydrofuran. Dry at 60°C to obtain a peryleneimide derivative grafted with a phosphorylcholine structure.

Example 6

A perylene imide derivative modified by phosphorylcholine structure, its structural formula is:

Its preparation method comprises the following steps:

(1) Preparation of hydroxymethylpropyl perylene imide: Weigh 2mmol of perylenetetracarboxylic dianhydride and place it in a polytetrafluoroethylene-lined hydrothermal reaction kettle, add 160mmol of 3-aminobutanol, and place the reaction kettle in Reaction at 180°C for 24h. After the reaction, add 25 mL of distilled water, centrifuge after stirring, pour off the last solution, repeat this process 3 times, and obtain hydroxymethyl perylene imide after vacuum drying at 60°C.

(2) Preparation of 2-bromo-2-methylpropionyl bromide-modified peryleneimide derivatives (PBI-Br): Take 1mmol of hydroxymethylperyleneimide in a 250mL three-necked bottle, add 175mL of dry Chloroethane and 8mmol of triethylamine, ultrasonic dispersion. Place the three-necked flask in an ice-water bath, add 8 mmol of 2-bromo-2-methylpropionyl bromide dropwise, and continue stirring for 1 h. Then, the three-necked flask was placed at 20°C and continued to stir for 8h. The reacted product was filtered to remove unreacted hydroxyethyl perylene imide and triethylamine hydrobromide. The obtained filtrate was evaporated to dryness to obtain a 2-bromo-2-methylpropionyl bromide-modified peryleneimide derivative (PBI-Br).

(3) Free radical polymerization grafted phosphorylcholine structure: take 0.05mmol 2-bromo-2-methylpropionyl bromide modified perylene imide derivative (PBI-Br), 2.5mmol methacryloyloxy Propylphosphorylcholine, 0.1mmol cuprous bromide, and 15mL tetrahydrofuran were placed in a 25mL flask, and magnetically stirred. Nitrogen was passed through the flask for 20 minutes. Quickly add 0.1 mmol of pentamethyldiethylenetriamine (PMDETA), seal the flask, and stir in an oil bath at 30°C for 24h. The obtained dispersion was passed through a 0.22 μm filter membrane and washed three times with tetrahydrofuran. Dry at 60°C to obtain a peryleneimide derivative grafted with a phosphorylcholine structure.

Example 7

The same as in Example 1, except that the amount of 2-bromo-2-methylpropionyl bromide in the second step was increased to 1.3 g to obtain a peryleneimide derivative grafted with a phosphorylcholine structure.

Example 8

Same as Example 1, except that the triethylamine in the second step is replaced by trimethylamine in an equimolar amount to obtain a peryleneimide derivative grafted with a phosphorylcholine structure.

Example 9

Same as Example 1, except that the initiation system of cuprous bromide and pentamethyldiethylenetriamine in the third step is replaced by ferrous chloride in an equimolar amount, and ultrasonically reacted at 60° C. for 12 hours to obtain grafted phosphorus Perylene imide derivatives of the acylcholine structure. Example 10

Same as Example 1, but the methacryloyloxyethylphosphorylcholine in the third step was replaced with 1g of acryloyloxyethylphosphorylcholine and stirred at 60°C for 8 hours to obtain the following Perylene imide derivatives of branched phosphorylcholine structure.

Example 11

Same as Example 1, but the methacryloyloxyethylphosphorylcholine in the third step was replaced with 2g of acryloyloxybutylphosphorylcholine, stirred and reacted for 12 hours in a nitrogen atmosphere at 60°C, and obtained Perylene imide derivatives grafted with phosphorylcholine structure.

Example 13

Same as Example 1, but the methacryloyloxyethyl phosphorylcholine in the third step was replaced with 2g methacryloyloxybutylphosphorylcholine and stirred and reacted for 8 hours in a nitrogen atmosphere at 30°C, Perylene imide derivatives grafted with phosphorylcholine structure were obtained.

Claims (8)

1. Phosphorylcholine structural modification perylene diimide derivative, its structural formula is as follows:

Wherein, R ₁for H, CH ₃;

R ₂for C _mh _2m, m=2,3 or 4;

R ₃for C _nh _2n, n=2,3 or 4;

x≥1。

2. the preparation method of Phosphorylcholine structural modification perylene diimide derivative according to claim 1, is characterized in that: comprise the following steps:

(1) the preparation: You perylene tetracarboxylic acid dianhydride of N, N'-Qiang Wan Ji perylene diimide and alkyl alcoholamine are obtained by reacting N, N'-Qiang Wan Ji perylene diimide;

(2) 2-bromo-2-methyl-prop acylbromide modifies the preparation of perylene diimide derivative: N, N'-Qiang Wan Ji perylene diimide and 2-bromo-2-methyl-prop acylbromide react, and obtains 2-bromo-2-methyl-prop acylbromide and modifies perylene diimide derivative;

(3) preparation of Phosphorylcholine structural modification perylene diimide derivative: the method utilizing atom transfer radical polymerization grafting, in an inert atmosphere, the perylene diimide derivative that 2-bromo-2-methyl-prop acylbromide is modified is induced at initiator system with the polymerizable compound containing Phosphorylcholine structure and is issued raw Raolical polymerizable, to obtain final product.

3. the preparation method of Phosphorylcholine structural modification perylene diimide derivative according to claim 2, is characterized in that: (mol ratio of 1) Zhong ， perylene tetracarboxylic acid dianhydride and alkyl alcoholamine is 1:2-1:100 to step; Temperature of reaction is 100-190 DEG C; Reaction times is 3h-30h.

4. the preparation method of Phosphorylcholine structural modification perylene diimide derivative according to claim 2, it is characterized in that: in step (2), the mol ratio of N, N'-Qiang Wan Ji perylene diimide and 2-bromo-2-methyl-prop acylbromide is 1:3-1:10, and temperature of reaction is 0-40 DEG C; Reaction times is 1h-24h.

5. the preparation method of Phosphorylcholine structural modification perylene diimide derivative according to claim 2, it is characterized in that: in step (2), also acid binding agent is comprised in reaction system, described acid binding agent is organic bases, and the mol ratio of described acid binding agent and 2-bromo-2-methyl-prop acylbromide is 1:1.

6. the preparation method of Phosphorylcholine structural modification perylene diimide derivative according to claim 2, it is characterized in that: in step (3), the polymerizable compound containing Phosphorylcholine structure is one or more the composition in acryloyl-oxyethyl Phosphorylcholine, acryloxypropyl Phosphorylcholine, acryloxy butyl Phosphorylcholine, methacryloxyethyl Phosphorylcholine, methacryloxypropyl Phosphorylcholine or methacryloxy butyl Phosphorylcholine.

7. the preparation method of Phosphorylcholine structural modification perylene diimide derivative according to claim 2, it is characterized in that: in step (3), the mol ratio of the perylene diimide derivative that polymerizable compound and 2-bromo-2-methyl-prop acylbromide containing Phosphorylcholine structure are modified is 20-60:1; Temperature of reaction is 30-100 DEG C; Reaction times is 8-24h; Reaction system adopts ultra-sonic oscillation.

8. the preparation method of Phosphorylcholine structural modification perylene diimide derivative according to claim 2, it is characterized in that: in step (3), described initiator system is the combination of transition metal salt and part, described transition metal salt is ferrous sulfate, iron protochloride, one in cuprous chloride and cuprous bromide, described part is bipyridine (bpy), 4, 4'-di-tert-butyl-2, 2'-dipyridyl (dTbpy), 4, 4'-bis-n-heptyl-2, 2'-dipyridyl (dHbpy), 4, 4'-bis-(5-nonyl)-2, 2'-dipyridyl (dNbpy), one in pentamethyl-diethylenetriamine.