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CN-122011042-A - Photosensitizer with high singlet oxygen quantum yield and preparation method and application thereof

CN122011042ACN 122011042 ACN122011042 ACN 122011042ACN-122011042-A

Abstract

The invention provides a photosensitizer with high singlet oxygen quantum yield, a preparation method and application thereof, and belongs to the technical field of coordination chemistry and biomedicine. The photosensitizer with high singlet oxygen quantum yield specifically introduces two carbazole groups into the phenanthroline ligand of the ruthenium complex for modification. The structure modification strategy obviously enhances the light absorption capacity of the complex in the visible light region, and improves the singlet oxygen quantum yield of the complex in a breakthrough manner. In vitro cell experiments show that the composition has excellent phototoxicity to various tumor cell strains, and has low toxicity under dark conditions, and good photodynamic therapy selectivity. In vivo tumor-bearing mouse model experiments prove that the tumor growth can be effectively inhibited under the illumination condition, and no obvious systemic toxicity is observed. The photosensitizer has the remarkable advantage of extremely high singlet oxygen quantum yield, and has great application potential and development value in the field of tumor photodynamic therapy.

Inventors

  • CHEN LIANGYU
  • LU JIE
  • RU JIAXI
  • SHEN ZHIFA

Assignees

  • 慈溪市人民医院医疗健康集团(慈溪市人民医院)

Dates

Publication Date
20260512
Application Date
20260130

Claims (10)

  1. 1. A high singlet oxygen quantum yield photosensitizer characterized by the structure of formula I: The compound of the formula I, X in the formula I is PF 6 - , halogen ion, BF 4 - 、ClO 4 - or CF 3 SO 3 - .
  2. 2. The high singlet oxygen quantum yield photosensitizer according to claim 1 wherein the halogen ions comprise chloride ions.
  3. 3. The high singlet oxygen quantum yield photosensitizer according to claim 1 or 2 wherein the singlet oxygen quantum yield of the high singlet oxygen quantum yield photosensitizer is greater than 150%.
  4. 4. The high singlet oxygen quantum yield photosensitizer according to claim 1 having a structure represented by formula a: Formula A.
  5. 5. The method for preparing the photosensitizer with high singlet oxygen quantum yield according to any one of claims 1 to 4, which is characterized by comprising the following steps: carrying out coordination reaction on a ruthenium (II) complex precursor and a phen-Car ligand in an organic solvent under the protection of inert atmosphere to obtain a coordination product, wherein the ruthenium (II) complex precursor is cis-bis (2, 2' -bipyridine) ruthenium (II) dichloride hydrate; Anion exchange is carried out on the coordination product to obtain the photosensitizer with high singlet oxygen quantum yield; The phen-Car ligand has a structure shown in a formula II: Formula II.
  6. 6. The method according to claim 5, wherein the temperature of the coordination reaction is 45-80 ℃ and the time is 6-24 hours.
  7. 7. The method according to claim 5, wherein the organic solvent is a mixed solvent of halogenated alkane and alcohol.
  8. 8. The use of a high singlet oxygen quantum yield photosensitizer according to any one of claims 1 to 4 in the manufacture of a photodynamic therapy drug.
  9. 9. The use according to claim 8, wherein the photodynamic therapy drug is for the treatment of tumours.
  10. 10. An anti-tumor pharmaceutical composition, comprising an active ingredient and a pharmaceutically acceptable carrier or adjuvant, wherein the active ingredient comprises the high singlet oxygen quantum yield photosensitizer of any one of claims 1-4.

Description

Photosensitizer with high singlet oxygen quantum yield and preparation method and application thereof Technical Field The invention relates to the technical field of coordination chemistry and biomedicine, in particular to a photosensitizer with high singlet oxygen quantum yield, a preparation method and application thereof. Background Photodynamic therapy (Photodynamic Therapy, PDT) is a therapeutic technique that uses the interaction of light, a photosensitizer and oxygen to produce cytotoxic reactive oxygen species (e.g., singlet oxygen, 1O2) to selectively kill diseased cells. The core of the clinical curative effect depends on key performance parameters of the photosensitizer, namely, the photosensitizer has strong absorption in a light region with better biological tissue permeability (commonly referred to as a near infrared window of 600-850 nm) or at least a visible light region with stronger penetrability, and has high singlet oxygen quantum yield (phi delta) so as to realize high-efficiency treatment under limited illumination dose. Currently, metallic ruthenium (II) polypyridine complexes (e.g., classical systems based on2, 2' -bipyridine or 1, 10-phenanthroline) are of great interest as emerging photosensitizer candidates. However, they face two interrelated fundamental challenges in clinical transformation: first, light absorption contradicts tissue penetration. Most conventional ruthenium complexes have their maximum absorption wavelength (λmax) concentrated in the ultraviolet to blue-green region (e.g., 450-500 nm). Although blue light centered at 470nm has application value in superficial treatment, the wavelength is more remarkable in scattering and absorption in biological tissues and has limited penetration depth, which severely restricts the effective treatment of deep or large-volume tumors. Although researchers have focused on achieving red shift of the absorption spectrum by expanding the ligand pi conjugated system, problems such as complicated molecular structure, reduced stability, or altered excited state properties are often associated. Second, a more critical challenge is the inefficiency of excited state energy utilization. Even if the photosensitizer is excited in the visible region, the efficiency of PDT is directly determined by whether the generated excited state energy can be efficiently converted into killing singlet oxygen. The excited state of classical Ru (II) polypyridine complexes is usually dominated by the metal-ligand charge transfer state, which is not ideal for intersystem crossing to long-lived triplet states, and for triplet energy transfer to oxygen molecules, resulting in a generally low singlet oxygen quantum yield (typically < 20%). This means that most of the absorbed light energy is dissipated as heat or in a non-radiative form, resulting in wasted light energy and forcing the need to increase the light dose or the drug dose in clinical treatment, potentially increasing phototoxicity and therapeutic side effects of normal tissue. In summary, the state of the art is that ruthenium-based photosensitizers either have limited absorption intensity in the visible region and low quantum yields, or it is difficult to achieve a certain red shift of the absorption wavelength and a breakthrough improvement in quantum yield while maintaining good photostability and biocompatibility. Development of a novel photosensitizer with ultra-high singlet oxygen quantum yield at clinically relevant illumination wavelengths (even in the visible region of relatively limited penetration depth) is a valuable and urgent development direction to improve PDT efficiency and reduce therapeutic condition requirements. Disclosure of Invention In view of the above, the present invention aims to provide a photosensitizer with high singlet oxygen quantum yield, and a preparation method and application thereof. The photosensitizer with high singlet oxygen quantum yield can realize breakthrough promotion of the singlet oxygen quantum yield, so that potential limitation of the photosensitizer in tissue penetration depth is made up by extremely high photodynamic conversion efficiency, and finally the novel anti-tumor photosensitizer with high efficiency and low dosage requirement is obtained. In order to achieve the above object, the present invention provides the following technical solutions: The invention provides a photosensitizer with high singlet oxygen quantum yield, which has a structure shown in a formula I: The compound of the formula I, X in the formula I is PF 6-, halogen ion, BF 4-、ClO4- or CF 3SO3-. Preferably, the halogen ion comprises chloride (Cl -). Preferably, the high singlet oxygen quantum yield photosensitizer has a singlet oxygen quantum yield greater than 150%. Preferably, it has a structure represented by formula a: Formula A. The invention also provides a preparation method of the photosensitizer with high singlet oxygen quantum yield, which comprises the following ste