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A metal iridium complex that responds synergistically to tumor microenvironment ph/hypoxia and its application

A technology of metal iridium and complexes, which is applied in the field of phosphorescent metal iridium complexes, can solve the problems of reducing the effect and improving actual production, and achieves the effect of improving sensitivity and high signal-to-noise ratio

Active Publication Date: 2021-05-28
NANJING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the current photochemical probes that can respond to acidification and hypoxia at the same time are often realized by the sharing of multiple indicator dyes, and the sharing of multiple dyes often results in overlaps in the commonly used wavelength window (350-1000nm) , Potential side effects in biological applications, reduced effects, increased actual production and use costs, etc.

Method used

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  • A metal iridium complex that responds synergistically to tumor microenvironment ph/hypoxia and its application
  • A metal iridium complex that responds synergistically to tumor microenvironment ph/hypoxia and its application
  • A metal iridium complex that responds synergistically to tumor microenvironment ph/hypoxia and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] The preparation of embodiment 1 probe Ir-NIR-pH-1

[0035] Synthesis of Compound 1-(benzo[b]thiophen-2-yl)-isoquinoline(Hiqbt)

[0036]

[0037]Under argon protection, 1-bromoisoquinoline (1g, 4.8mmol) and benzo[b]thiophen-2-ylboronic acid (856mg, 4.8mmol) were dissolved in tetrahydrofuran (24mL), and potassium carbonate solution ( 1M, 24mL) and tetrakistriphenylphosphine palladium (227mg, 0.24mmol, 5% n / n), react overnight at 60°C, and monitor the progress of the reaction with TCL. After the reaction was finished, cool to room temperature, reclaim the organic phase, extract the aqueous phase twice with dichloromethane and combine the organic phases, dry over anhydrous sodium sulfate, evaporate the solvent under reduced pressure, and separate by column chromatography to obtain a light yellow Hiqbt solid (85.6 %).

[0038] Synthesis of Compound 4-Ethynylphenol

[0039]

[0040] Trimethylsilylacetylene (1.9 mL, 13.44 mmol) was added dropwise to 4-iodophenol (2.04...

Embodiment 2

[0053] The synthesis of embodiment 2 probe Ir-NIR-1

[0054]

[0055] Take the synthesized iridium complex chlorine bridge dimer Ir 2 (iqbt) 4 Cl 2 (154mg, 0.1mmol), L2 (56mg, 0.2mmol) and a mixed solvent of dichloromethane and methanol (12mL, 2:1, volume ratio) were placed in a three-necked flask, and heated to reflux for 6h under an argon atmosphere. After the reaction, the reaction mixture was cooled to room temperature, and 1 mmol of ammonium hexafluorophosphate was added. The suspension was stirred for 15 min and filtered to remove insoluble inorganic salts. The solvent was evaporated under reduced pressure, and column chromatography gave dark red Ir-NIR-pH-1 solid (62%). 1 H NMR (400MHz, CD 3 CN-d 3 )δ9.07(d, J=8.4Hz, 3H), 8.57(dd, J=8.3, 1.4Hz, 1H), 8.43(s, 1H), 8.33(dd, J=5.0, 1.4Hz, 1H), 8.27(dd, J=5.1, 1.4Hz, 1H), 7.96–7.87(m, 6H), 7.87–7.79(m, 3H), 7.78–7.64(m, 3H), 7.49(d, J=6.9Hz, 3H), 7.36(dd, J=10.5, 6.6Hz, 2H), 7.22–7.10(m, 4H), 6.70(t, J=7.6Hz, 2H),...

Embodiment 3

[0056] Example 3 Determination of the absorption spectrum and phosphorescence spectrum of the probe Ir-NIR-pH-1.

[0057] Accurately weigh the probe Ir-NIR-pH-1 and the probe Ir-NIR-1, transfer them into 5mL volumetric flasks, dilute to volume with DMSO, and prepare a concentration of 1.0×10 -3 mol / L solution, pipette 25 μL of the solution into a 5mL volumetric flask, and use DMSO and PBS buffer solution with a pH of 7.4 to make a concentration of 1.0×10 -5 mol / L solution, so that the volume fraction of DMSO in the buffer solution is 10%, and its ultraviolet spectrum is measured. The phosphorescence spectrum was measured using the maximum absorption wavelength of the ultraviolet spectrum as the excitation wavelength of the phosphorescence spectrum. Accurately weigh the compound to be tested and prepare a concentration of 1.0×10 -5 The mol / L containing DMSO volume fraction is 10% PBS buffer solution, and its spectral properties under acidic and alkaline conditions are determi...

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Abstract

The present invention designs a class of phosphorescent ion-type iridium complexes capable of fluorescence imaging under hypoxic conditions, which has the following structure: or the present invention utilizes the probes of the phosphorescent ion-type iridium complexes, in vitro single layer cells and three-dimensional tumor multiple A synergistic response to acidification and hypoxia was achieved in the spheroid, and the probe could obtain a larger signal change than the traditional single-factor response probe. This probe provides a new idea for the design of phosphorescent probes for early diagnosis, and will have potential application value in early diagnosis and observational treatment of cancer.

Description

technical field [0001] The invention belongs to the field of metal complexes, and in particular relates to a phosphorescent metal iridium complex responsive to tumor microenvironment pH / hypoxia and its application. Background technique [0002] Early diagnosis of tumors is of great significance in improving the effect of tumor treatment and the survival rate of cancer patients, which can not only improve the quality of life of patients, but also reduce the pain, mental and economic burden of patients. At present, the early diagnosis of cancer is mainly through tumor marker detection, gene detection, ultrasound imaging (US), magnetic resonance imaging (MRI), thermal tomography (TTM), positron emission tomography (PET- CT) etc. to achieve. Compared with these traditional medical methods, the fluorescence imaging method can detect a series of related biological processes of the tumor in real time and in situ while realizing the non-destructive detection of the tumor location i...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07F15/00C09K11/06G01N21/64
CPCC07F15/0033C09K11/06C09K2211/185G01N21/6486
Inventor 何卫江郭子建韩重齐芬
Owner NANJING UNIV