CN105295898B - A kind of macromolecular optical probe and its preparation method and purposes to being acidified with weary oxygen continuous response - Google Patents
A kind of macromolecular optical probe and its preparation method and purposes to being acidified with weary oxygen continuous response Download PDFInfo
- Publication number
- CN105295898B CN105295898B CN201510594252.6A CN201510594252A CN105295898B CN 105295898 B CN105295898 B CN 105295898B CN 201510594252 A CN201510594252 A CN 201510594252A CN 105295898 B CN105295898 B CN 105295898B
- Authority
- CN
- China
- Prior art keywords
- optical probe
- polyethylene glycol
- reaction
- macromolecular optical
- thiophene
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- IPMBQGZVCDWBHA-UHFFFAOYSA-N O=Cc(cc1)cnc1-c1cc(cccc2)c2[s]1 Chemical compound O=Cc(cc1)cnc1-c1cc(cccc2)c2[s]1 IPMBQGZVCDWBHA-UHFFFAOYSA-N 0.000 description 1
Abstract
A kind of macromolecular optical probe, it has following structural formula：Wherein, the polymerization degree n of polyalkylene glycol moiety can regulate and control between 12-455.Above-mentioned macromolecular optical probe has the feature of continuous response to acidifying and weary oxygen, and launch wavelength is located at feux rouges near infrared light wave band, it is soluble in water, good biocompatibility, can apply to chemiluminescence assay, effective amplification of tumor microenvironment signal is realized, so as to reach the lesion detection of high s/n ratio.The invention discloses its preparation method.
Description
Technical field
Macromolecular probe the present invention relates to be used for Photobiology imaging, and in particular to one kind can connect to acidifying and weary oxygen
The macromolecular optical probe and its preparation method and purposes of continuous response.
Background technology
One of key technology of cancer diagnosis is to amplify tumor microenvironment signal, and the amplification strategy of tumor microenvironment signal
The feature of some tumor-markers is typically based on, for example, is acidified, tumor markers of weary oxygen and overexpression etc..However, these are marked
Difference of the feature of will in tumour and internal normal structure is often and little.For example, the extrace llular pH of entity tumor is big
About 6.5-6.9, and the pH value outside normal tissue cell is about 7.4, both difference is extremely limited.The tumor tissues of weary oxygen
In partial pressure of oxygen be about 0-3%O2, and the partial pressure of oxygen under physiological condition under normal oxygen environment is about>5%O2, both differences
It is limited.In addition, difference of many tumor markerses in the tumors subtypes of expression high and the hypotype of low expression is often also and little.
Difference of these tumor-marker features between tumour and normal structure can be used the probe of stimuli responsive to be amplified, so that
Reach the degree that can be detected.But as mentioned above, because these tumor-marker features are between tumour and normal structure
Original differences very little, and the response sensitivity of probe is limited, and tumor microenvironment is carried out using the probe of this kind of stimuli responsive
The signal to noise ratio that the method that one step is amplified is frequently resulted in lesion detection is very low.
The content of the invention
In order to solve above-mentioned problem, it is proposed that a kind of concept amplified of two-stage and method improve tumor microenvironment signal
Method.That is, probe is first converted into another form in the case where the first time of tumor microenvironment stimulates, and referred to as reports molecule；
Afterwards, the signal of report molecule is responded in a new passage, then to second stimulation of tumor microenvironment, so that reality
Two steps of existing tumor microenvironment signal are amplified.In order to realize this imagination, we pick the cell generation of tumour-specific first
Thank to the response object designed as probe.Compared with normal structure, tumour has the unusual accretion rate for accelerating, and result in acid
Change the tumor microenvironment with weary oxygen.This symbolic characteristic has fine popularity, is almost present in all types of tumours.
Then, for this response object, we have devised a kind of probe to it with two-stage response.Designed probe chemistry
It is made up of the complex of iridium of phosphorescent emissions and the polyethylene glycol of biocompatibility in structure, by a kind of acid-sensitive between two components
The imine linkage connection of sense.Under neutral pH conditions, the probe molecule structure remained stable.Under acidic pH, probe
Imine linkage fracture in chemical constitution, causes probe molecule complex of iridium to be separated with polyalkylene glycol moiety, the change of the chemical constitution
Changing can cause the change of probe molecule launch wavelength simultaneously.Thereafter, the long-life phosphorus of fracture separation complex of iridium part out
Light transmitting continues to show the sensitive property of weary oxygen, and its emissive porwer can strengthen with the raising of weary oxygen degree.Based on this
Principle, designed macromolecular optical probe can show the spy of continuous response to the acidifying caused by tumor metabolic and weary oxygen
Levy, two steps such that it is able to effectively realize tumor microenvironment signal are amplified.
It is an object of the invention to provide a kind of macromolecular optical probe and its preparation to acidifying and weary oxygen continuous response
Method and purposes.
Technical scheme is as follows：
A kind of macromolecular optical probe, it has following structural formula：
Above-mentioned macromolecular optical probe, the polymerization degree n of polyalkylene glycol moiety can regulate and control between 12-455 in its structure.
A kind of method for preparing above-mentioned macromolecular optical probe, it comprises the following steps：
Step 1. is by benzo [b] thiophene -2- boric acid, 6- chloropyridine formaldehydes, tetrakis triphenylphosphine palladium, tetrahydrofuran and carbon
Acid sodium aqueous solution is added in reaction vessel, benzo [b] thiophene -2- boric acid, 6- chloropyridine formaldehydes and tetrakis triphenylphosphine palladium
Mol ratio is 1.2:1:0.03, the concentration of described sodium carbonate liquor is the body of 2mol/L, tetrahydrofuran and aqueous sodium carbonate
Product is than being 3:1, mixture flows through night next time in argon gas protection, and room temperature is cooled to after reaction, and reactant mixture is poured into water,
Extracted using dichloromethane, dichloromethane mutually uses saturated common salt water washing, anhydrous magnesium sulfate is dried, filtering, and is concentrated under reduced pressure, and is produced
Thing is purified using column chromatography method, obtains 6- (benzo [b] thiophene -2- bases) pyridine carboxaldehyde；
Step 2. is by 6- (benzo [b] thiophene -2- bases) pyridine carboxaldehyde, double-[two (the 2- phenylpyridines) obtained by step 1
Close iridochloride], silver triflate and diethylene glycol dimethyl ether be placed in reaction vessel, 6- (benzo [b] thiophene -2-
Base) mol ratio of pyridine carboxaldehyde, double-[two (2- phenylpyridines) close iridochloride] and silver triflate is 5:1:2, mixing
Thing is heated to 150 DEG C of stirring reactions 24 hours under argon gas protection, after reaction, reactant mixture is cooled into room temperature, in ether
Middle sedimentation, is collected by filtration sediment, and is dissolved in dichloromethane, and insoluble matter is filtered to remove, and the decompression of gained dichloromethane solution is dense
After contracting, purified using column chromatography for separation, obtain the complex of iridium with aldehyde radical；
Be dissolved in dichloromethane for polyethylene glycol mono-methyl and triethylamine by step 3., and is cooled to 0 DEG C, and it is right to be slowly added to
Toluene sulfochloride, polyethylene glycol mono-methyl and tolysulfonyl cl molar ratio are 1:5, it is small that reactant mixture stirs 2 at 0 DEG C
When, then to react 2 days at room temperature, subsequent solvent removed by evaporation at reduced pressure dissolves the residue in chloroform, and use saturated carbon
Acid sodium aqueous solution is washed, and then chloroform is dried using anhydrous magnesium sulfate, is filtered, and is precipitated in ether, is deposited in true
Dried under Altitude, obtain the polyethylene glycol of p-methyl benzenesulfonic acid end group；
The polyethylene glycol of the p-methyl benzenesulfonic acid end group that step 4. obtains step 3, p-aminobenzoic acid and potassium carbonate are added
To in dimethylformamide, stirring reaction 24 hours at 50 DEG C, the polyethylene glycol of p-methyl benzenesulfonic acid end group, p-aminobenzoic acid
It is 1 with the mol ratio of potassium carbonate:5:5, after reaction terminates, reaction solution is cooled to room temperature, settled in ether, it is heavy to be collected by filtration
Starch, is dissolved in chloroform, is washed using saturated aqueous sodium carbonate, afterwards, chloroform is mutually used into anhydrous magnesium sulfate
Dry, after filtering and concentrating, settled in ether, vacuum drying obtains the amine-terminated polyethylene glycol of benzene, and its structure is：
Step 5. coordinates the iridium with aldehyde radical that the amine-terminated polyethylene glycol of benzene and step 2 obtained by step 4 are obtained
Thing is dissolved in methyl alcohol, and the amine-terminated polyethylene glycol of benzene and the complex of iridium mol ratio with aldehyde radical are 1:2, triethylamine is added,
By mixture heated overnight at reflux, after reaction, mixture then, is dissolved in neutrality by solvent removed by evaporation at reduced pressure and triethylamine
In water, filtered through cellulose acetate sheets, remove insoluble solid granule, obtained aqueous solution is freezed, obtain described right
Acidifying and the macromolecular optical probe of weary oxygen continuous response
Above-mentioned macromolecular optical probe, the application in the tumor imaging agent in organism is prepared.
Macromolecular optical probe prepared by the present invention, the feature to acidifying and weary oxygen with continuous response, and launch wavelength
Soluble in water positioned at feux rouges near infrared light wave band, good biocompatibility can apply to the optical imagery of live body, realize swollen
Effective amplification of knurl Micro-environmental cues, so as to reach the lesion detection of high s/n ratio.
Brief description of the drawings
Fig. 1 is the phosphorescent emissions light that macromolecular optical probe (number-average molecular weight 6000) prepared by the present invention is responded to acidifying
Spectrum test result.
Fig. 2 is the phosphorescent emissions light that macromolecular optical probe (number-average molecular weight 6000) prepared by the present invention is responded to weary oxygen
Spectrum test result.
Fig. 3 is optical imagery of the macromolecular optical probe (number-average molecular weight 6000) of present invention preparation in tumor-bearing mice
As a result.
Specific embodiment
With reference to the example content that the present invention is furture elucidated, but these examples are not intended to limit protection model of the invention
Enclose.
Embodiment 1
The preparation of the amine-terminated polyethylene glycol of benzene, comprises the following steps：
(1) preparation of the polyethylene glycol of p-methyl benzenesulfonic acid end group
Polyethylene glycol mono-methyl (0.4mmol, number-average molecular weight 500-20000) and triethylamine (0.4mL) are dissolved in two
In chloromethanes (20mL), and it is cooled to 0 DEG C, is slowly added to paratoluensulfonyl chloride (0.38g, 2mmol), reactant mixture is at 0 DEG C
Lower stirring 2 hours, then reacts 2 days at room temperature, and after reaction, solvent removed by evaporation at reduced pressure dissolves the residue in chloroform
(20mL) and washed using saturated aqueous sodium carbonate, each 10mL is washed 3 times, and then chloroform is done using anhydrous magnesium sulfate
Dry, filtering is precipitated in ether, and precipitation is dried under vacuum conditions, obtains product for a kind of white powder, and yield is 80%.
Product structure is characterized as below,1H NMR(400MHz,DMSO-d6):δ 7.77 (d, J=8.4Hz, 2H), 7.47
(d, J=8.4Hz, 2H), 4.11 (m, 2H), 3.49 (s, PEG), 3.22 (s, 3H), 2.41 (s, 3H).Infer that product is certain accordingly
It is the polyethylene glycol of p-methyl benzenesulfonic acid end group, its structure is as follows：
(2) preparation of the amine-terminated polyethylene glycol of benzene
By polyethylene glycol (0.4mmol, number-average molecular weight 500- of the p-methyl benzenesulfonic acid end group synthesized by step (1)
20000), p-aminobenzoic acid (0.27g, 2mmol) and potassium carbonate (0.27g, 2mmol) are added to dimethylformamide (15mL)
In, reaction solution after reaction terminates, is cooled to room temperature by stirring reaction 24 hours at 50 DEG C, is settled in ether, is collected by filtration
Sediment, is dissolved in chloroform (20mL), is washed using saturated aqueous sodium carbonate, and each 10mL is washed 3 times, afterwards, by trichlorine
Methane is dried using anhydrous magnesium sulfate, after filtering and concentrating, is settled in ether, and vacuum drying obtains a kind of white powder, receives
Rate 70%.
Product structure is characterized as below,1H NMR(400MHz,DMSO-d6):δ 7.62 (d, J=8.6Hz, 2H), 6.54
(d, J=8.7Hz, 2H), 5.97 (s, 2H), 4.25 (t, J=4.6Hz, 2H), 3.49 (s, PEG), 3.22 (s, 3H).Push away accordingly
Stopping pregnancy thing is the amine-terminated polyethylene glycol of benzene really, and its structure is as follows：
The reaction equation of above-mentioned reaction is as follows：
Embodiment 2
The preparation of the complex of iridium with aldehyde radical, comprises the following steps：
(1) preparation of 6- (benzo [b] thiophene -2- bases) pyridine carboxaldehyde
By benzo [b] thiophene -2- boric acid (1.28g, 7.2mmol), 6- chloropyridine formaldehydes (0.85g, 6mmol), four (triphens
Base phosphine) palladium (0.21g, 0.18mmol), tetrahydrofuran (30mL) and 2M aqueous sodium carbonates (10mL) be added to reaction vessel
In, night is flowed through next time in argon gas protection, room temperature is cooled to after reaction, reactant mixture is poured into (300mL) in water, use two
Chloromethanes is extracted, and each 50mL is extracted 3 times, and dichloromethane is washed using saturated common salt, and each 50mL washes 3 times, anhydrous slufuric acid
Magnesium is dried, filtering, and is concentrated under reduced pressure, and crude product is purified using column chromatography method, and solvent is dichloromethane/petroleum ether (gradient
Ratio 1:1 to 1:0) yellow powder 1.22g, yield 85%, are obtained.
The basic structure of product is characterized as below,1H NMR(400MHz,CDCl3):δ 10.11 (s, 1H), δ 9.06 (dd, J=
2.1,0.8Hz, 1H), δ 8.22 (dd, J=8.3,2.1Hz, 1H), δ 8.00 (s, 1H), δ 7.95 (d, J=8.4Hz, 1H), δ
7.91-7.89(m,1H),δ7.87-7.85(m,1H),δ7.43-7.38(m,2H)。ESI-MS(m/z):[M]+C14H9NOS is theoretical
Value 240, measured value 240.Infer that product is 6- (benzo [b] thiophene -2- bases) pyridine carboxaldehyde, the following institute of its structure really accordingly
Show：
(2) preparation of double-[two (2- phenylpyridines) close iridochloride]
Take three hydrated iridium trichlorides (390mg, 1.1mmol), 2- phenylpyridines (320 μ L, 2.2mmol) and be dissolved in 2- ethyoxyls
In the mixed solvent of ethanol (30mL) and water (10mL), by mixture heated overnight at reflux, after reaction, room temperature is cooled to, filtered
Sediment is collected, is washed using water and methyl alcohol successively, then be dried under vacuum, obtain yellow powder 560mg, yield 95%.
The structural characterization of product is as follows,1H NMR(400MHz,CDCl3):δ 9.24 (d, J=5.6Hz, 4H), 7.87 (d, J
=8.0Hz, 4H), 7.73 (t, J=7.8,4H), 7.48 (d, J=7.6,4H), 6.78-6.72 (m, 8H), 6.56 (t, J=
7.6,4H), 5.93 (d, J=7.8,4H).It is double-[two (2- phenylpyridines) close iridochloride] to infer product accordingly really, its
Structure is as follows：
(3) preparation of the complex of iridium with aldehyde radical
Take 6- (benzo [b] thiophene -2- bases) pyridine carboxaldehyde (360mg, 1.5mmol), the step (2) prepared by step (1)
Prepared double-[two (2- phenylpyridines) close iridochloride] (320mg, 0.3mmol), silver triflate (155mg,
0.6mmol) and diethylene glycol dimethyl ether (15mL) is placed in reaction vessel, under argon gas protection, 150 DEG C of stirrings are heated to anti-
Answer 24 hours, after reaction, reactant mixture is cooled to room temperature, settled in ether, sediment is collected by filtration, and be dissolved in dichloro
Methane, insoluble matter is filtered to remove, and after gained dichloromethane solution is concentrated under reduced pressure, using column chromatography for separation purified product, is launched
Agent is dichloromethane/petroleum ether (1:2) dark red powder 48mg, yield 11%, are obtained.
Product structure is characterized as below,1H NMR(400MHz,CDCl3):δ9.61(s,1H),7.94-7.89(m,2H),7.86
(d, J=8.3Hz, 1H), 7.76-7.66 (m, 5H), 7.61 (d, J=8.4Hz, 2H), 7.55 (d, J=5.9Hz, 1H), 7.46
(d, J=5.5Hz, 1H), 7.16 (t, J=7.1Hz, 1H), 7.01-6.68 (m, 10H).ESI-MS(m/z):[M+Na]+
IrC36H24ON3S calculated values 762, measured value 762.Infer that product is really the complex of iridium with aldehyde radical accordingly, its structure is as follows
It is shown：
The reaction equation of above-mentioned reaction is as follows：
Embodiment 3
To acidifying and the preparation of the macromolecular optical probe of weary oxygen continuous response
The amine-terminated polyethylene glycol of benzene (0.02mmol, number-average molecular weight 500-20000) obtained by Example 1 and
The complex of iridium (30mg, 0.04mmol) with aldehyde radical obtained by embodiment 2 is dissolved in methyl alcohol (10mL), adds triethylamine
(20 μ L), by mixture heated overnight at reflux, after reaction, solvent removed by evaporation at reduced pressure and triethylamine then, mixture are dissolved
In neutral water, filtered through 0.22 μm of cellulose acetate sheets, remove insoluble solid granule, obtained aqueous solution is freezed,
Product is obtained for a kind of crocus powder, yield 65%.
The structural characterization of product is as follows,1H NMR(400MHz,CDCl3):δ 7.96 (dd, J=8.4,1.8Hz, 1H), 7.89
(d, J=8.3Hz, 1H), 7.87-7.82 (m, 3H), 7.72 (d, J=8.0Hz, 1H), 7.66-7.49 (m, 9H), 7.11 (m,
1H), 6.97-6.74 (m, 11H), 6.64 (d, J=8.6Hz, 1H), 4.41 (t, J=4.8Hz, 2H), 3.64 (s, PEG), 3.38
(s,3H).Deduction product is the designed macromolecular optical probe to being acidified with weary oxygen continuous response, its structure really accordingly
It is as follows：
The reaction equation of above-mentioned reaction is as follows：
Embodiment 4
The obtained macromolecular optical probe (number-average molecular weight 6000) to acidifying and weary oxygen continuous response of embodiment 3 is to acid
The phosphorescence emission spectra test result for changing response is as shown in Figure 1.Under the conditions of pH value 7.4, the transmitting of the macromolecular optical probe
Peak is located at 610nm.(the 0%O in the case where partial pressure of oxygen is constant2), with solution ph reduction, peak intensity is launched at 610nm
Degree is gradually reduced, and is located at the transmitting peak intensity at 705nm and is gradually risen.The probe molecule of other molecular weight also shows to be similar to
Response characteristic.Phosphorescence emission spectra test result shows that the macromolecular optical probe has significant response characteristic to acidifying,
Can be by the red shift of probe emission wavelength come the acidifying situation in reaction environment.
Embodiment 5
The obtained macromolecular optical probe (number-average molecular weight 6000) to acidifying and weary oxygen continuous response of embodiment 3 is to weary
The phosphorescence emission spectra test result of oxygen response is as shown in Figure 2.In the case where pH value is constant (pH 5.5), with oxygen in solution
The reduction of partial pressure, the 705nm transmitting peak intensities produced by acidifying induction gradually strengthen.The probe molecule of other molecular weight is also showed
Go out similar response characteristic.This phosphorescence emission spectra test result shows that the macromolecular optical probe is responded to acidifying
Afterwards, moreover it is possible to which continuation is responded to weary oxygen.By the continuous response to acidifying and weary oxygen, can effectively to being not only acidified but also weary oxygen
Tumor microenvironment signal be amplified.
Embodiment 6
The obtained macromolecular optical probe (number-average molecular weight 6000) to acidifying and weary oxygen continuous response of embodiment 3 is in lotus
Living imaging result in knurl mouse is as shown in Figure 3.Mouse tumor model is inoculated in ICR mouse using hypodermic mode
(left side oxter injection mouse source HCC H22, every 106Individual H22 cells), plant one week after, selection gross tumor volume 100mm3It is left
Right mouse.Macromolecular optical probe is dissolved in PBS (0.01M) and is made into 5mg/mL solution, tail vein injection 0.2mL enters Mice Body
It is interior, tumor-bearing mice is imaged by near-infrared living imaging system.Result shows, 1 hour to 96 hours after probe injection,
The probe optical signal that tumor locus are detected will much be better than background signal.The probe molecule of other molecular weight also shows class
As imaging effect.Living imaging test result shows the obtained macromolecular light to being acidified with weary oxygen continuous response of embodiment 3
Learning probe can effectively amplify the signal of tumor microenvironment, realize the lesion detection of high s/n ratio.
Claims (3)
1. a kind of macromolecular optical probe, it is characterized in that it has following structural formula：
Described macromolecular optical probe, the polymerization degree n of polyalkylene glycol moiety is between 12-455 in its structure.
2. a kind of method for preparing macromolecular optical probe described in claim 1, it is characterized in that it comprises the following steps：
Step 1. is by benzo [b] thiophene -2- boric acid, 6- chloropyridine formaldehydes, tetrakis triphenylphosphine palladium, tetrahydrofuran and sodium carbonate
The aqueous solution is added in reaction vessel, benzo [b] thiophene -2- boric acid, 6- chloropyridine formaldehydes and tetrakis triphenylphosphine palladium mole
Than being 1.2:1:0.03, the concentration of described sodium carbonate liquor is the volume ratio of 2mol/L, tetrahydrofuran and aqueous sodium carbonate
It is 3:1, mixture flows through night next time in argon gas protection, and room temperature is cooled to after reaction, and reactant mixture is poured into water, uses
Dichloromethane is extracted, and dichloromethane mutually uses saturated common salt water washing, and anhydrous magnesium sulfate is dried, filtering, and is concentrated under reduced pressure, and product makes
Purified with column chromatography method, obtain 6- (benzo [b] thiophene -2- bases) pyridine carboxaldehyde；
Step 2. by 6- (benzo [b] thiophene -2- bases) pyridine carboxaldehyde obtained by step 1, it is double-[two (2- phenylpyridines) close two
Iridium chloride], silver triflate and diethylene glycol dimethyl ether be placed in reaction vessel, 6- (benzo [b] thiophene -2- bases) pyrrole
The mol ratio of pyridine formaldehyde, double-[two (2- phenylpyridines) close iridochloride] and silver triflate is 5:1:2, mixture exists
Under argon gas protection, 150 DEG C of stirring reactions are heated to 24 hours, after reaction, reactant mixture are cooled to room temperature, sunk in ether
Drop, is collected by filtration sediment, and is dissolved in dichloromethane, and insoluble matter is filtered to remove, after gained dichloromethane solution is concentrated under reduced pressure,
Purified using column chromatography for separation, obtain the complex of iridium with aldehyde radical；
Be dissolved in dichloromethane for polyethylene glycol mono-methyl and triethylamine by step 3., and is cooled to 0 DEG C, is slowly added to toluene
Sulfonic acid chloride, polyethylene glycol mono-methyl and tolysulfonyl cl molar ratio are 1:5, reactant mixture is stirred 2 hours at 0 DEG C, is connect
And react 2 days at room temperature, subsequent solvent removed by evaporation at reduced pressure dissolves the residue in chloroform, and use saturated sodium carbonate
The aqueous solution is washed, and then chloroform is dried using anhydrous magnesium sulfate, is filtered, and is precipitated in ether, is deposited in vacuum ring
Dried under border, obtain the polyethylene glycol of p-methyl benzenesulfonic acid end group；
The polyethylene glycol of the p-methyl benzenesulfonic acid end group that step 4. obtains step 3, p-aminobenzoic acid and potassium carbonate are added to two
In NMF, stirring reaction 24 hours at 50 DEG C, the polyethylene glycol of p-methyl benzenesulfonic acid end group, p-aminobenzoic acid and carbon
The mol ratio of sour potassium is 1:5:5, after reaction terminates, reaction solution is cooled to room temperature, settled in ether, precipitation is collected by filtration
Thing, is dissolved in chloroform, is washed using saturated aqueous sodium carbonate, afterwards, chloroform is done using anhydrous magnesium sulfate
It is dry, after filtering and concentrating, settled in ether, vacuum drying obtains the amine-terminated polyethylene glycol of benzene；
The complex of iridium with aldehyde radical that step 5. obtains the amine-terminated polyethylene glycol of benzene and step 2 obtained by step 4 is molten
In methyl alcohol, the amine-terminated polyethylene glycol of benzene and the complex of iridium mol ratio with aldehyde radical are 1:2, triethylamine is added, will be mixed
Compound heated overnight at reflux, after reaction, solvent removed by evaporation at reduced pressure and triethylamine then, mixture are dissolved in neutral water,
Filtered through cellulose acetate sheets, remove insoluble solid granule, obtained aqueous solution is freezed, obtain it is described to acidifying and
The macromolecular optical probe of weary oxygen continuous response：
3. application of the macromolecular optical probe described in claim 1 in the tumor imaging agent in organism is prepared.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510594252.6A CN105295898B (en) | 2015-09-17 | 2015-09-17 | A kind of macromolecular optical probe and its preparation method and purposes to being acidified with weary oxygen continuous response |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510594252.6A CN105295898B (en) | 2015-09-17 | 2015-09-17 | A kind of macromolecular optical probe and its preparation method and purposes to being acidified with weary oxygen continuous response |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105295898A CN105295898A (en) | 2016-02-03 |
| CN105295898B true CN105295898B (en) | 2017-07-07 |
Family
ID=55193750
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510594252.6A Active CN105295898B (en) | 2015-09-17 | 2015-09-17 | A kind of macromolecular optical probe and its preparation method and purposes to being acidified with weary oxygen continuous response |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105295898B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110818739B (en) * | 2018-08-12 | 2021-05-28 | 南京大学 | Metal iridium complex with synergistic response to tumor microenvironment pH/hypoxic and application thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5500594B2 (en) * | 2008-10-17 | 2014-05-21 | 国立大学法人群馬大学 | Novel compound and functional luminescent probe containing the same |
| CN101787054B (en) * | 2010-03-23 | 2013-04-17 | 上海师范大学 | Water-soluble cationic iridium complex phosphorescence probe and preparation method |
| CN103215031B (en) * | 2013-03-18 | 2015-07-08 | 南京大学 | Iridium complexe-polyvinylpyrrolidone hypoxic probe, its preparation method and application |
-
2015
- 2015-09-17 CN CN201510594252.6A patent/CN105295898B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN105295898A (en) | 2016-02-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109336909B (en) | Near-infrared two-region fluorescent compound with aggregation-induced emission property, preparation method thereof, nano-micelle and application thereof | |
| CN102516988B (en) | Polymerization fluorescent dye, preparation method and application thereof | |
| CN108892654B (en) | Near-infrared fluorescent dye containing 4-dicyanomethylbenzopyran unit, and preparation method and application thereof | |
| CN103214875B (en) | Preparation method of fluorescence dye using fluorescein as matrix and application thereof | |
| CN106977529A (en) | Modifiable area's fluorescence imaging probe of near-infrared two of one class and its production and use | |
| CN110862819B (en) | PH fluorescent probe based on near-infrared fluorescent dye and preparation method and application thereof | |
| CN102702090A (en) | Methyl pyridinium with organic two-photon absorption materia, and preparation method and application thereof | |
| CN107417737A (en) | A kind of ionic type iridium complex with double phosphorescent emissions properties and its preparation method and application | |
| Wang et al. | Precise design and synthesis of an AIE fluorophore with near-infrared emission for cellular bioimaging | |
| CN105295898B (en) | A kind of macromolecular optical probe and its preparation method and purposes to being acidified with weary oxygen continuous response | |
| CN113717089B (en) | Fluorinated Cy7 compound and synthetic method and application thereof | |
| CN103483275B (en) | The coupling compound of NSAID class anti-inflammatory analgesic medicine and EGFR kinase inhibitor and synthetic method thereof and application | |
| CN111662567A (en) | Heptamethine carboxyl indole cyanine dye and preparation method and application thereof | |
| CN105602276B (en) | Polymerizable near-infrared fluorescent dye monomer and preparation method and application thereof | |
| CN103215031B (en) | Iridium complexe-polyvinylpyrrolidone hypoxic probe, its preparation method and application | |
| CN116425739B (en) | Compound for tumor targeted imaging and photodynamic therapy and synthesis method and application thereof | |
| CN109970780B (en) | Near-infrared fluorescent compound, preparation method thereof, near-infrared fluorescent imaging probe and application thereof | |
| Huang et al. | Near-Infrared Hemicyanine Fluorophores with Optically Tunable Groups: A ‘Leap Forward’for in Vivo Sensing and Imaging | |
| CN113278036B (en) | Phenothiazine-containing iridium complex and preparation method and application thereof | |
| CN105295007B (en) | One kind conjugation water-soluble polymer tracer material and preparation method thereof | |
| CN104693258A (en) | Fluorescence labelled nucleotide based on molecular glue and use thereof in DNA sequencing | |
| CN114699539A (en) | Synthetic method of near-infrared fluorescent tracer for diagnosing metastatic lymph nodes | |
| CN111662565B (en) | Heptamethine nitroindole cyanine dye and preparation method and application thereof | |
| CN113845471B (en) | BSA (bovine serum albumin) -based pyridinium photosensitizer compound as well as preparation method and application thereof | |
| CN108676002B (en) | 9-nitrogen (6' -amino) hexyl heterobicyclo [3.3.1] nonane coupled rhodamine B compound and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |