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CN-121991135-A - Metal iridium complex modified by pyrazole functional group, and preparation method and application thereof

CN121991135ACN 121991135 ACN121991135 ACN 121991135ACN-121991135-A

Abstract

The application belongs to the technical field of antibacterial medicines, and particularly relates to a metal iridium complex modified by pyrazole functional groups, and a preparation method and application thereof. The structural formula of the metal iridium complex modified by the pyrazole functional group is shown as a formula I. According to the application, pyrazole groups are introduced into the ligand of the cyclometallated iridium complex, so that the capability of penetrating and destroying bacterial cell membranes is obviously enhanced, and the antibacterial activity is improved. Experiments prove that the iridium complex provided by the application can induce cell content leakage and membrane depolarization to play a bactericidal role by destroying membrane integrity, can obviously inhibit the formation of staphylococcus aureus pigment and biomembrane, is not easy to induce bacteria to generate drug resistance, and has a good application prospect in clinical anti-infection treatment. Formula I.

Inventors

  • LIAO XIANGWEN
  • QIAN XUE
  • TU XI
  • WANG JINTAO

Assignees

  • 江西科技师范大学

Dates

Publication Date
20260508
Application Date
20260311

Claims (10)

  1. 1. The metal iridium complex with pyrazole functional group modification is characterized in that the structural formula of the metal iridium complex with pyrazole functional group modification is shown as formula I: Formula I.
  2. 2. The method for preparing a metallic iridium complex modified with pyrazole functional groups according to claim 1, comprising the steps of: under the condition of inert protective gas, mixing a compound shown in a structure of a formula I-a and a compound shown in a structure of a formula I-b with ammonium acetate, and then carrying out condensation reaction in a reaction solvent to obtain a compound shown in an intermediate formula I-c; Mixing a compound shown in the intermediate formula I-c with a compound shown in the structure of the formula I-d, reacting under the condition of inert protective gas, adding potassium hexafluorophosphate after the reaction is finished, centrifuging or filtering, and purifying to obtain the metal iridium complex modified by the pyrazole functional group; The structural formulas of the compound shown in the structure of the formula I-a, the compound shown in the structure of the formula I-b, the compound shown in the intermediate formula I-c and the compound shown in the structure of the formula I-d are as follows: 。
  3. 3. The preparation method according to claim 2, wherein the molar ratio of the compound represented by the structure of formula I-a, the compound represented by the structure of formula I-b and ammonium acetate is 1:1:30.
  4. 4. A method of preparing according to claim 3, wherein the reaction solvent is acetic acid solution.
  5. 5. The method according to claim 2, wherein the inert shielding gas is at least one of helium, argon, and nitrogen.
  6. 6. The preparation method according to claim 2, wherein the ratio of the compound represented by the intermediate formula I-c to the compound represented by the structure of the formula I-d is 0.1 mmol/0.2 mmol.
  7. 7. The method of claim 2, wherein the condensation reaction is carried out at a temperature of 120 ℃ to 150 ℃ for a time of 2h to 5 h.
  8. 8. The use of a metallic iridium complex modified with pyrazole functional groups according to claim 1 for the preparation of a medicament for inhibiting staphylococcus aureus.
  9. 9. The use of the iridium complex modified with pyrazole functional groups according to claim 1 for preparing a medicament for inhibiting golden yellow pigment produced by staphylococcus aureus.
  10. 10. Use of a metallic iridium complex modified with pyrazole functional groups according to claim 1 for the preparation of a medicament for inhibiting or eradicating staphylococcus aureus biofilm.

Description

Metal iridium complex modified by pyrazole functional group, and preparation method and application thereof Technical Field The application belongs to the technical field of antibacterial medicines, and particularly relates to a metal iridium complex modified by pyrazole functional groups, and a preparation method and application thereof. Background Staphylococcus aureus (Staphylococcus aureus) is one of the most common pathogens clinically, causing a range of mild skin infections to severe systemic diseases (such as pneumonia, sepsis and endocarditis). With the long-term and non-standard use of traditional antibiotics, the problem of bacterial drug resistance is increasingly serious. The pathogenicity of staphylococcus aureus is closely related to various virulence factors secreted by staphylococcus aureus. Wherein, alpha-hemolysin can penetrate host cell membrane to form holes to cause cell lysis, while golden yellow pigment is used as an important antioxidant to help bacteria resist oxidative damage of host immune system. In addition, the bacteria have extremely strong capacity of forming a biological film, and the existence of the biological film improves the resistance of the bacteria to environmental pressure and antibiotics by hundreds of times, so that infection is repeated and is difficult to eradicate. Traditional antibacterial drug development tends to have single bactericidal effect, and bacteria are easy to induce to generate drug resistance through gene mutation. In recent years, metal complexes have shown great potential in the antibacterial field due to their unique steric structure and multi-target mechanism of action. In particular to a cyclometallated iridium complex which has excellent photophysical property and structural adjustability. However, iridium complexes in the prior art often have the problems of poor hydrophilic-hydrophobic balance, weak ability to penetrate bacterial cell membranes, and the like. Therefore, development of a novel multifunctional antibacterial agent capable of inhibiting toxin secretion and biofilm formation while sterilizing has become a problem to be solved in the field of antibacterial drug research. Disclosure of Invention The invention aims to solve the defects in the prior art, and provides a metal iridium complex modified by pyrazole functional groups, and a preparation method and application thereof, wherein the technical scheme is as follows: In a first aspect, the invention provides a metal iridium complex modified by a pyrazole functional group, wherein the structural formula of the metal iridium complex modified by the pyrazole functional group is shown as formula I: Formula I. The iridium (III) complex with pyrazole structure modification provided by the invention has excellent antibacterial activity on staphylococcus aureus, is unique in action mechanism, is not easy to induce drug resistance, is high in vivo safety, and can be used for treating bacterial infection. The structural design core of the complex is that a pyrazole group is taken as a nitrogenous five-membered heterocycle, has unique hydrogen bond donor and acceptor sites, and can generate rich interaction with biological macromolecules. By precisely introducing pyrazole functional groups into iridium complex ligands, not only can the electron distribution of metal centers be regulated, but also the pyrazole ring can generate specific affinity with phospholipid components on the surface of bacterial cell membranes. The structural modification can obviously reduce the energy barrier of the complex penetrating through the membrane barrier, induce membrane depolarization and cause physical damage, thereby inhibiting golden yellow pigment secretion and biofilm formation while rapidly sterilizing, and the bacteria are extremely difficult to generate drug resistance due to the mechanism of physically damaging the membrane. In a second aspect, the invention provides a preparation method of the iridium metal complex modified by pyrazole functional groups, which comprises the following steps: Under the condition of inert protective gas, carrying out condensation reaction on a compound shown in a structure of a formula I-a and a compound shown in a structure of a formula I-b in a reaction solvent to obtain an intermediate compound shown in a formula I-c; Mixing a compound shown in the intermediate formula I-c with a compound shown in the structure of the formula I-d, reacting under the condition of inert protective gas, adding potassium hexafluorophosphate after the reaction is finished, centrifuging or filtering, and purifying to obtain the metal iridium complex modified by the pyrazole functional group; The structural formulas of the compound shown in the structure of the formula I-a, the compound shown in the structure of the formula I-b, the compound shown in the intermediate formula I-c and the compound shown in the structure of the formula I-d are as follows: 。 as a further preferred embo