CN107286197B - A kind of complex of iridium and its preparation method and application with phosphorescence ion-pair structure - Google Patents
A kind of complex of iridium and its preparation method and application with phosphorescence ion-pair structure Download PDFInfo
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- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic System
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic System compounds of the platinum group
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- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
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- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic System
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic System compounds of the platinum group
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Abstract
The invention discloses a kind of complex of iridium and its preparation method and application with phosphorescence ion-pair structure.Such complex is the soft salt complex of iridium of phosphorescence anion and cation being combined by terpyridyl cationic complexes and the anionic complex formed with cyclic metal complexes, metal center and cyanogen root as assistant ligand, and general structure is as follows；Phosphorescence ion pair complex of iridium of the invention can generate singlet oxygen under white light illumination, and can apply to photodynamic therapy field.Phosphorescence ion pair complex of iridium of the present invention has extraordinary application prospect in terms of optical dynamic therapy.
Description
Technical field
The present invention relates to a kind of complex of iridium and its preparation method and application with phosphorescence ion-pair structure, belongs to organic
Photoelectric functional material technology field.
Background technique
Photodynamic therapy (photodynamic therapy, PDT) is a kind of noninvasive or minimal invasive, nonthermal, is utilized
The treatment method of photochemical reaction target tissue and targets neoplastic cells.PDT is a kind of cold light chemical reaction, and fundamental is
Oxygen, photosensitizer and visible light (common laser).Tumor tissues selectively intake photosensitizer first, then selects swashing for appropriate wavelength
Light can absorb the energy of the light source photon and reach excitation state singlet state to local irradiation, photosensitizer, and photosensitizer is single by excitation
Weight state is by traversing to photosensitizer excited triplet state between gap.Since photosensitizer is sent out in the level-density parameter of excited triplet state and oxygen
Raw energy transfer, photosensitizer transfer energy to the ground state oxygen molecule of surrounding, and ground state oxygen molecule occurs photooxidation reaction and generates list
Line state oxygen or oxygen radical etc..Oxidation reaction occurs for singlet oxygen and adjacent large biological molecule such as nucleic acid, protein, generates thin
Cytotoxicity and lead to cell damage or even death.With traditional operation, chemotherapy, the big oncotherapy means of radiotherapy three
Compare, photodynamic therapy have toxicity is humble, applicability is wide, it is traumatic it is small, can cooperate with operation improve therapeutic effect, selectivity
High, repeatable treatment, to the injury tumor tissues small, that hiding can be eliminated of vitals the features such as.
The yield for being conducive to improve singlet oxygen using the energy transmission between two components of zwitterion, such as Wang
It works (J.Am.Chem.Soc., 2009,131,13117-13124).But this work be based on Cationic organic dyes and yin from
Sub- conjugated polymer, structure is complex, is unfavorable for synthesis and preparation.Metal iridium complex is dynamic in light as photosensitizer at present
Power therapy field plays important role.Since heavy atom iridium atom can induce strong spin inductance in metal iridium complex
To enhance excited singlet state to more efficiency is altered between the gap between excited triplet state, the metal iridium for reaching excited triplet state is matched for coupling
The energy for closing object is released in the form of phosphorescence on one side, generates activity to ground state oxygen by energy transfer or electric charge transfer on one side
Oxygen or singlet oxygen, the application range of metal iridium complex is extended to photodynamic therapy field by this.However, at present about
It is had not been reported using phosphorescence ion pair complex of iridium as photosensitizer applied to field of photodynamic.Usual zwitterion is matched
Energy transmission can be had by closing between object improves singlet oxygen yield, therefore designs composite structure and be more simply based on phosphorescence ion
It is necessary to the photosensitizer of complex.
Summary of the invention
Technical problem solved by the present invention is proposing a kind of complex of iridium with ion-pair structure, their system is provided
Preparation Method, and propose application of this kind of complex in field of photodynamic.
In order to solve the above-mentioned technical problem, technical solution proposed by the present invention is: a kind of with phosphorescence ion-pair structure
Complex of iridium, the ion pair complex of iridium have the following structure formula:
R1、R2Can be one kind of having structure:
In order to solve the above-mentioned technical problem, technical solution proposed by the present invention is: a kind of with phosphorescence ion-pair structure
The synthetic route of complex of iridium preparation method, this method is as follows:
Specifically: step 1, as above by aldehyde compound and 2- acetylpyridine, sodium hydroxide and ammonia shown in figure reaction I
Water 25 DEG C of reactions in ethanol solution obtain terpyridyl derivative in 12 hours；
Step 2 as above shown in figure reaction II, will react the obtained terpyridyl derivative of I and three hydrated iridium trichlorides exists
In ethylene glycol ethyl ethers ethereal solution lower 160 DEG C of nitrogen protection it is closed be protected from light 15 minutes, after being cooled to room temperature, filter, with water, cold second
Pure and mild ether washs respectively, obtains terpyridyl complex of iridium；
Step 3 as above shown in figure reaction III, will react the terpyridyl complex of iridium and another three pyrrole that ii is obtained
Piperidine derivatives in ethylene glycol ethyl ethers ethereal solution under nitrogen protection 180 DEG C it is closed be protected from light 20 minutes, be added after being cooled to room temperature
The reaction was continued 5 minutes for hexafluorophosphoric acid aqueous solutions of potassium, filters washing and obtains cationic terpyridyl iridium cooperation symmetrically or non-symmetrically
Object；
Step 4, as above shown in figure reaction IV, under nitrogen protection, C^N ligand and three hydrated iridium trichlorides are in ethylene glycol
Ether/water volume ratio is to obtain iridium dichloro bridge within confined reaction 24 hours for 110 DEG C in the mixed liquor of 3:1；
Step 5, as above shown in figure reaction V, will react the obtained dichloro bridge of iv and tetrabutyl cyanamide methylene chloride/
Methanol volume ratio is to react 4 hours for lower 25 DEG C of nitrogen protection in 2:1 mixed liquor, and chromatographic column separating-purifying obtains the cooperation of anion iridium
Object；
Step 6, will react the anion complex of iridium that v is obtained and the cationic terpyridyl iridium that step iii is obtained cooperates
Object reacts 4 hours for 25 DEG C in acetone soln, adds water and stirs suction filtration, and precipitating is purified to obtain final ion pair complex of iridium.
In order to solve the above-mentioned technical problem, technical solution proposed by the present invention is: the phosphorescence ion pair complex of iridium
Application, it is characterised in that the ion pair complex of iridium can be applied to the photosensitizer of the diagnosing and treating purpose of non-disease,
Singlet oxygen is generated under white light.
In order to solve the above-mentioned technical problem, technical solution proposed by the present invention is: the phosphorescence ion pair complex of iridium
Application, it is characterised in that the ion pair complex of iridium can be applied to by the energy transmission between zwitterion complex
The raising singlet oxygen yield of the diagnosing and treating purpose of non-disease.
Beneficial effects of the present invention:
There are energy transmission between phosphorescence ion pair complex of iridium zwitterion of the invention, it is allowed to singlet under illumination and produces
Rate is improved.
Phosphorescence ion pair complex of iridium of the invention has lower dark toxicity and higher phototoxicity, is to be applied to well
The photosensitizer of optical dynamic therapy.
Detailed description of the invention
Of the invention is described further with reference to the accompanying drawing.
The uv-visible absorption spectra of Fig. 1 complex of iridium Ir-1, Ir-2 and Ir-3；
The singlet oxygen yield of Fig. 2 complex of iridium Ir-1, complex of iridium Ir-2 and complex of iridium Ir-3 compare；
The singlet yield of Fig. 3 complex of iridium Ir-1, complex of iridium Ir-2 different proportion；
Fig. 4 complex of iridium Ir-3 generates the test experience of singlet oxygen in cell；
The Flow cytometry experiments of Fig. 5 complex of iridium Ir-3 optical dynamic therapy effect.
Specific embodiment
The content of patent for a better understanding of the present invention further illustrates of the invention below by specific example
Technical solution.But these embodiments are not intended to limit the present invention.
Embodiment 1:
The preparation of cationic complex of iridium Ir-1:
As shown above, as shown in reaction I, benzaldehyde (1mmol), 2- acetylpyridine (4mmol), sodium hydroxide are weighed
(4.2mmol), ammonium hydroxide (3mmol) put into reaction flask in, be added ethyl alcohol, 25 DEG C magnetic agitation 12 hours.It filters after reaction
Precipitating, and be phenyl terpyridyl with the recrystallized product that ethyl alcohol recrystallization obtains, it can be direct plungeed into after drying anti-in next step
It answers.1H NMR(400MHz,CDCl3) δ 8.76-8.71 (m, 4H), 8.67 (t, J=6.4Hz, 2H), 7.94-7.85 (m, 4H),
7.49 (dt, J=20.0,4.9Hz, 3H), 7.35 (dt, J=10.8,5.2Hz, 2H).
If reacted shown in II, phenyl terpyridyl (1mmol) and IrCl are weighed3·3H2O (1mmol) mixing investment three-necked bottle
In, nitrogen-is vacuumized-protected on biexhaust pipe and is vacuumized, is moved in circles three times, and the entire reaction system of nitrogen protection is finally used.
Ethylene glycol ethyl ether is injected into reaction system, is warming up to 160 DEG C, magnetic agitation is reacted 15 minutes.After reaction, by system
It is cooled to room temperature, filters, washed respectively with water, cold ethyl alcohol and ether, the phenyl three that obtained solid product as singly cooperates
Pyridine complex of iridium can be direct plungeed into after drying and be reacted in next step.
If reacted shown in III, phenyl terpyridyl complex of iridium (1mmol) and three pyrrole of 9- hexyl carbazole -3- phenyl are weighed
In pyridine (1mmol) mixing investment three-necked bottle, nitrogen-is vacuumized-protected on biexhaust pipe and is vacuumized, moves in circles three times, finally adopts
With the entire reaction system of nitrogen protection.Ethylene glycol ethyl ether is injected into reaction system, is warming up to 180 DEG C, magnetic agitation reaction
20 minutes.After reaction, system is cooled to room temperature, the aqueous solution injection that will contain 2 (mmol) chlorine fluorophosphoric acid potassium enters reaction
System, magnetic agitation 5 minutes, filtering precipitating and was washed respectively with water, cold ethyl alcohol and ether, obtained solid product with acetonitrile/
Diethyl ether recrystallization, obtained orange/yellow solid product are cationic complex of iridium Ir-1.1H NMR(400MHz,DMSO-d6)δ
9.68 (s, 2H), 9.61 (s, 2H), 9.30 (s, 1H), 9.27-9.18 (m, 4H), 8.59 (d, J=8.5Hz, 1H), 8.44 (d, J
=7.6Hz, 2H), 8.37 (dt, J=14.5,7.4Hz, 5H), 8.05 (d, J=8.9Hz, 1H), 7.99 (d, J=5.1Hz,
2H), 7.95 (d, J=5.3Hz, 2H), 7.84 (t, J=7.7Hz, 2H), 7.76 (dd, J=12.8,7.9Hz, 2H), 7.59
(dt, J=12.6,7.0Hz, 5H), 7.40 (t, J=7.6Hz, 1H), 4.58 (t, J=7.0Hz, 2H), 1.94-1.74 (m,
2H), 1.50-1.17 (m, 6H), 0.82 (t, J=7.1Hz, 3H).
Embodiment 2:
The preparation of anion complex of iridium Ir-2:
If reacted shown in IV, phenylpyridine (2.5mmol) and IrCl are weighed3·3H2O (1mmol) mixing investment three-necked bottle
In, nitrogen-is vacuumized-protected on biexhaust pipe and is vacuumized, is moved in circles three times, and the entire reaction system of nitrogen protection is finally used.
The mixture of ethylene glycol ethyl ether and water that volume ratio is 3:1 is injected into reaction system, is warming up to 110 DEG C, magnetic agitation is anti-
It answers 24 hours.After reaction, system is cooled to room temperature, filtering precipitating, and with ethyl alcohol and washing, obtained solid product is i.e.
For phenylpyridine iridium dichloro bridge, it can direct plunge into after dry and react in next step.
If reacted shown in V, phenylpyridine iridium dichloro bridge (1mmol) is weighed with tetrabutyl cyanamide (2.3mmol) and mixes addition
Into reaction flask, by the mixture injection system of methylene chloride and methanol that volume ratio is 2:1, temperature is controlled at 25 DEG C,
It is stirred to react 4 hours.It is separated after reaction with the method that column chromatographs, rotation is except solvent and is dried in vacuo to get anionic
Complex of iridium Ir-2.
Embodiment 3:
The preparation of phosphorescence ion pair complex of iridium Ir-3:
Cationic iridium complex Ir-1 (1mmol) and anionic complex of iridium Ir-2 are weighed shown in VI as reacted
(3mmol) mixing is added into reaction flask, and by acetone injection system, temperature is controlled at 25 DEG C, after being stirred to react 4 hours,
It will stir 1 minute, filter in a small amount of water injection system, solid product obtains solid product i.e. through acetone and Diethyl ether recrystallization
For complex of iridium Ir-3.1H NMR(400MHz,DMSO-d6)δ9.68(s,2H),9.61(s,2H),9.30(s,1H),9.27–
9.18 (m, 4H), 8.59 (d, J=8.5Hz, 1H), 8.44 (d, J=7.6Hz, 2H), 8.37 (dt, J=14.5,7.4Hz, 5H),
8.05 (d, J=8.9Hz, 1H), 7.99 (d, J=5.1Hz, 2H), 7.95 (d, J=5.3Hz, 2H), 7.84 (t, J=7.7Hz,
2H), 7.76 (dd, J=12.8,7.9Hz, 2H), 7.59 (dt, J=12.6,7.0Hz, 5H), 7.40 (t, J=7.6Hz, 1H),
4.58 (t, J=7.0Hz, 2H), 1.94-1.74 (m, 2H), 1.50-1.17 (m, 6H), 0.82 (t, J=7.1Hz, 3H).
Ibid Ir1 preparation process, we are prepared for following cationic complex of iridium Ir-4 to Ir-7:
Ir-4:1H NMR(400MHz,DMSO-d6) δ 9.59 (d, J=8.0Hz, 4H), 9.20 (d, J=8.2Hz, 4H),
8.48-8.30 (m, 9H), 7.93 (t, J=4.5Hz, 4H), 7.83 (t, J=7.6Hz, 2H), 7.63 (d, J=8.5Hz, 2H),
7.59–7.49(m,4H),1.21(s,3H)。
Ir-5:1H NMR(400MHz,DMSO-d6) δ 9.58 (s, 2H), 9.42 (s, 2H), 9.18 (dd, J=8.1,
3.0Hz, 4H), 8.41 (dd, J=8.0,6.5Hz, 4H), 8.33 (td, J=8.3,1.1Hz, 4H), 7.96 (d, J=5.5Hz,
2H), 7.90 (d, J=5.4Hz, 2H), 7.82 (t, J=7.6Hz, 1H), 7.74 (t, J=7.4Hz, 4H), 7.53 (ddd, J=
16.5,10.3,4.1Hz,2H),3.16(s,6H)。
Ir-6:1H NMR(400MHz,DMSO-d6) δ 9.68 (s, 2H), 9.61 (s, 2H), 9.20 (t, J=7.5Hz, 4H),
8.62 (d, J=8.2Hz, 2H), 8.44 (d, J=7.5Hz, 2H), 8.37 (td, J=8.0,1.3Hz, 4H), 8.24 (d, J=
8.4Hz, 2H), 7.94 (t, J=6.5Hz, 4H), 7.83 (t, J=7.6Hz, 2H), 7.75 (t, J=7.4Hz, 1H), 7.60-
7.51(m,4H)。
Ir-7:1H NMR(400MHz,DMSO-d6)δ9.68(s,2H),9.59(s,2H),9.30(s,1H),9.23(t,J
=8.1Hz, 4H), 8.59 (d, J=8.8Hz, 1H), 8.37 (ddd, J=20.0,8.0,4.1Hz, 7H), 8.05 (d, J=
8.7Hz, 1H), 7.97 (dd, J=13.4,5.7Hz, 4H), 7.77 (d, J=8.3Hz, 1H), 7.66-7.51 (m, 7H), 7.39
(t, J=7.3Hz, 1H), 4.58 (t, J=6.8Hz, 2H), 2.07 (s, 3H), 1.42-1.17 (m, 8H), 0.82 (t, J=
7.1Hz,3H)。
Ibid Ir3 preparation process, using corresponding cation complex of iridium Ir-4 to Ir-7 we be prepared for following phosphorescence from
Son is to complex of iridium Ir-8 to Ir-11:
Ir-8:1H NMR(400 MHz,DMSO-d6) δ 9.59 (d, J=8.0 Hz, 4H), 9.20 (d, J=8.2 Hz,
4H), 8.48-8.30 (m, 9H), 7.93 (t, J=4.5 Hz, 4H), 7.83 (t, J=7.6 Hz, 2H), 7.63 (d, J=8.5
Hz,2H),7.59–7.49(m,4H),1.21(s,3H)。
Ir-9:1H NMR(400 MHz,DMSO-d6) δ 9.58 (s, 2H), 9.42 (s, 2H), 9.18 (dd, J=8.1,3.0
Hz, 4H), 8.41 (dd, J=8.0,6.5 Hz, 4H), 8.33 (td, J=8.3,1.1 Hz, 4H), 7.96 (d, J=5.5 Hz,
2H), 7.90 (d, J=5.4 Hz, 2H), 7.82 (t, J=7.6 Hz, 1H), 7.74 (t, J=7.4 Hz, 4H), 7.53 (ddd, J
=16.5,10.3,4.1 Hz, 2H), 3.16 (s, 6H).
Ir-10:1H NMR(400 MHz,DMSO-d6) δ 9.68 (s, 2H), 9.61 (s, 2H), 9.20 (t, J=7.5 Hz,
4H), 8.62 (d, J=8.2 Hz, 2H), 8.44 (d, J=7.5 Hz, 2H), 8.37 (td, J=8.0,1.3 Hz, 4H), 8.24
(d, J=8.4 Hz, 2H), 7.94 (t, J=6.5 Hz, 4H), 7.83 (t, J=7.6Hz, 2H), 7.75 (t, J=7.4Hz,
1H),7.60–7.51(m,4H)。
Ir-11:1H NMR(400MHz,DMSO-d6)δ9.68(s,2H),9.59(s,2H),9.30(s,1H),9.23(t,J
=8.1Hz, 4H), 8.59 (d, J=8.8Hz, 1H), 8.37 (ddd, J=20.0,8.0,4.1Hz, 7H), 8.05 (d, J=
8.7Hz, 1H), 7.97 (dd, J=13.4,5.7Hz, 4H), 7.77 (d, J=8.3Hz, 1H), 7.66-7.51 (m, 7H), 7.39
(t, J=7.3Hz, 1H), 4.58 (t, J=6.8Hz, 2H), 2.07 (s, 3H), 1.42-1.17 (m, 8H), 0.82 (t, J=
7.1Hz,3H)。
The absorption spectrum of complex of iridium Ir-1, Ir-2 and Ir-3 are tested:
The spectrum test concentration that the present invention uses for Ir-1 and Ir-3 is 10 μM, Ir-2 is 30 μM, and test solvent is acetonitrile
Solution, when surveying emission spectrum.
The absorption of complex is as shown in Figure 1.Complex is in ultra-violet (UV) band 250-380nm and visible blue area 400-500nm
Stronger absorption is shown, especially the complex can be subtracted significantly by excited by visible light when doing cell imaging experiment
Damage of the excitation light source to cell is lacked.
Complex of iridium Ir-4, Ir-2, Ir-8 (Ir-5, Ir-2, Ir-9/Ir-6, Ir-2, Ir-10/Ir-7, Ir-2, Ir-
11) absorption spectrum test result is substantially the same as complex of iridium Ir-1, Ir-2 and Ir-3.
The singlet oxygen yield of complex of iridium Ir-1, Ir-2, Ir-3 and Ir-1:Ir-2=(1:1/1:2/1:3/1:4)
Experiment:
The test concentrations that the experiment of singlet oxygen yield that the present invention uses uses for Ir-1 and Ir-3 are 10 μM, Ir-2 30
μM, test solvent is acetonitrile solution, and using white light, xenon lamp power is 12mW, with 1,3- diphenyl isobenzofuran
(DPBF) it is singlet oxygen depleting agents, the singlet oxygen yield of complex is determined by reference method.
The singlet oxygen quantum yield of complex is as shown in Figure 2.The absorption of DPBF does not increase substantially with light application time in figure
It grows and changes, it was confirmed that complex Ir-1, Ir-2 and Ir-3 produce singlet oxygen under illumination.By comparing we have found that phosphorescence
The singlet oxygen yield highest of ion pair complex of iridium Ir-3, illustrates that ion pair complex of iridium can be used for optical dynamic therapy, passes through
Energy transmission between zwitterion complex improves singlet oxygen yield.
The singlet oxygen yield of Ir-1:Ir-2=(1:1/1:2/1:3/1:4) as shown in figure 3, by with Ir-1, Ir-2 ratio
Compared with being allowed to singlet under illumination there are energy transmission between the zwitterion of phosphorescence ion pair complex of iridium Ir-3 of the invention
Yield is improved, and illustrates the energy transmission between zwitterion complex, improves singlet oxygen yield.
Complex of iridium Ir-4, Ir-2, Ir-8 and Ir-4:Ir-2=(1:1/1:2/1:3/1:4) [(Ir-5, Ir-2, Ir-
9 and Ir-5:Ir2=(1:1/1:2/1:3/1:4)/Ir-6, Ir-2, Ir-10 and Ir-6:Ir2=(1:1/1:2/1:3/1:
4)/Ir-7, Ir-2, Ir-11) and Ir-7:Ir2=(1:1/1:2/1:3/1:4)] singlet oxygen yield experimental result it is basic
Ibid.
Phosphorescence ion pair complex of iridium Ir-3 generates the test experience of singlet oxygen in the cell:
We generate Ir-3 using a kind of fluorescence probe (DCFH-DA) for detecting reactive oxygen species in the cell
Active oxygen is detected.It is transformed into cell and in the cell under the action of hydrolase because DCFH-DA can be entered
DCFH, when generating active oxygen into the cell, DCFH, which is oxidized, generates the very high green light DCF of quantum efficiency, to realize to cell
The Turn-On response of interior active oxygen detection.It is incubated for HepG2 cell with Ir-3, DCFH-DA solution is added into cell culture fluid,
Continue to be incubated for.12mW cm is used later-2White light distinguish irradiating cell, then with laser scanning co-focusing microscope to intracellular DCF
The fluorescence bands of sending carry out intracellular Fluorescence imaging.Then DCF is collected in the optical signal of 505-560nm wave band.Such as Fig. 4 institute
Show, after illumination after a period of time, the optical signal of intracellular 505-560nm wave band is remarkably reinforced, it was demonstrated that living in cell
The generation of property oxygen.Therefore, it was demonstrated that Ir-3 in the cell generates the ability of active oxygen.
Phosphorescence ion pair complex of iridium Ir-8, Ir-9, Ir-10, Ir-11 generate the test experience of singlet oxygen in the cell
As a result substantially same Ir-3.
The Flow cytometry experiments of phosphorescence ion pair complex of iridium Ir-3 optical dynamic therapy effect:
In order to study effect of the phosphorescence ion pair complex of iridium in PDT application, we make by model of HepG2 cell line
For the research object of ion pair photodynamics anticancer therapy application.We pass through Annexin V-FITC/propidium
The double fluorescent staining experiments of iodide (PI), to monitor apoptosis, and then study phosphorescence ion pair complex of iridium and adjust
Under photodynamic therapy induction cell death.Turn up because the cell of early apoptosis will appear intercellular membrane, so by its
On inner membrance serine protease exposure in the solution, Annexin V-FITC can specificity in conjunction with serine protease and
Lead to fluorescence enhancement, to realize the detection to viable apoptotic cell, PI can be realized in conjunction with the DNA in cell to cell
The specific stain of core, but it can not pass through the complete cell membrane of normal cell, and cell membrane integrity and permeability can be
It dies down when cell is in apoptosis advanced stage or necrosis, therefore PI may be implemented to carry out the nucleus in apoptosis advanced stage or non-viable non-apoptotic cell
Dyeing.Thus, in flow cytometry experiment, different fluorescent staining situation AnnexinV-FITC-/PI-, Annexin V-
FITC+/PI-With Annexin V-FITC+/PI+Respectively correspond living cells under normal condition, thin in apoptosis early stage
Born of the same parents and in apoptosis advanced stage or downright bad cell are as shown in figure 5, contain Ir-3 material in the case where not applying illumination
Cell, which is compared, is not added the cell of material, and the ratio of apoptosis or non-viable non-apoptotic cell only rises to 2.24% by 1.62%, illustrates Ir-3 material
Material lower dark toxicity under dark condition, has good biocompatibility；Under conditions of by identical illumination, contain
The cell of material, which is compared, is not added the cell of material, and the ratio of apoptosis or non-viable non-apoptotic cell has risen to 11.5% by 7%, illustrates material
Phototoxicity with higher.
The Flow cytometry experiments of the optical dynamic therapy effect of phosphorescence ion pair complex of iridium Ir-8, Ir-9, Ir-10, Ir-11
As a result substantially same Ir-3.
Phosphorescence ion pair complex of iridium of the invention has lower dark toxicity and higher phototoxicity, is to be applied to well
The photosensitizer of optical dynamic therapy.
Of the invention is not limited to the above embodiment the specific technical solution, all technologies formed using equivalent replacement
Scheme be the present invention claims protection scope.
Claims (4)
1. a kind of complex of iridium with phosphorescence ion-pair structure, it is characterised in that the ion pair complex of iridium has the following structure
Formula:
R1、R2Can be one kind of having structure:
2. the complex of iridium preparation method according to claim 1 with phosphorescence ion-pair structure, it is characterised in that the party
The synthetic route of method is as follows:
Specifically: step 1 as above exists aldehyde compound and 2- acetylpyridine, sodium hydroxide and ammonium hydroxide shown in figure reaction I
25 DEG C of reactions obtain terpyridyl derivative in 12 hours in ethanol solution；
Step 2, as above shown in figure reaction II, the terpyridyl derivative and three hydrated iridium trichlorides that reaction I is obtained are in second two
In alcohol diethyl ether solution lower 160 DEG C of nitrogen protection it is closed be protected from light 15 minutes, after being cooled to room temperature, filter, with water, cold ethyl alcohol and
Ether washs respectively, obtains terpyridyl complex of iridium；
Step 3 as above shown in figure reaction III, will react the terpyridyl complex of iridium that ii is obtained and spread out with another terpyridyl
Biology in ethylene glycol ethyl ethers ethereal solution under nitrogen protection 180 DEG C it is closed be protected from light 20 minutes, hexafluoro is added after being cooled to room temperature
The reaction was continued 5 minutes for aqueous potassium phosphate solution, filters washing and obtains cationic terpyridyl complex of iridium symmetrically or non-symmetrically；
Step 4, as above shown in figure reaction IV, under nitrogen protection, C^N ligand and three hydrated iridium trichlorides ethylene glycol ethyl ether/
Water volume ratio is to obtain iridium dichloro bridge within confined reaction 24 hours for 110 DEG C in the mixed liquor of 3:1；
Step 5, as above shown in figure reaction V, by the obtained dichloro bridge of reaction iv and tetrabutyl cyanamide in methylene chloride/methanol
Volume ratio is to react 4 hours for lower 25 DEG C of nitrogen protection in 2:1 mixed liquor, and chromatographic column separating-purifying obtains anion complex of iridium；
Step 6, will react the anion complex of iridium that v is obtained and the cationic terpyridyl complex of iridium that step iii is obtained exists
It is reacted 4 hours for 25 DEG C in acetone soln, adds water and stirs suction filtration, precipitating is purified to obtain final ion pair complex of iridium.
3. the application of phosphorescence ion pair complex of iridium according to claim 1, it is characterised in that the ion pair iridium cooperation
Object can be applied to the photosensitizer of the diagnosing and treating purpose of non-disease, generate singlet oxygen under white light illumination.
4. the application of phosphorescence ion pair complex of iridium according to claim 1, it is characterised in that the ion pair iridium cooperation
Object can be applied to the raising singlet of the diagnosing and treating purpose of non-disease by the energy transmission between zwitterion complex
Oxygen yield.
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