Near-infrared aggregation-induced emission material with cyanine structure as well as preparation method and application of near-infrared aggregation-induced emission material
By introducing a triphenylamine rotor unit into the molecular structure of cyanine dye IR780, TPADIR material was designed, which solved the problems of easy photobleaching and low light conversion efficiency of cyanine dye, and achieved a highly efficient photothermal and photodynamic synergistic effect, providing a new generation of photosensitizers for non-invasive treatment of bacterial infections.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-12-31
- Publication Date
- 2026-04-03
AI Technical Summary
Existing cyanine dyes are prone to photobleaching at long wavelengths, have low light conversion efficiency, and their biocompatibility and triplet-related reactive oxygen species generation capacity decrease when photostability is improved.
By introducing a triphenylamine rotor unit into the molecular structure of cyanine dye IR780, monosubstituted derivative TPAIR and disubstituted derivative TPADIR were designed and synthesized. These derivatives dissipate excited-state energy by promoting molecular motion, thereby enhancing photostability and photothermal conversion efficiency.
TPADIR exhibits excellent antibacterial activity against Staphylococcus aureus and MRSA under 808 nm laser irradiation, with a bactericidal rate exceeding 90%, and is almost non-toxic under light-free conditions, demonstrating good photoselectivity and biosafety.
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Figure CN121779299A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the fields of biomedical engineering and organic synthesis technology, and particularly relates to a near-infrared aggregation-induced emission material with a cyanin structure, its preparation method and application. Background Technology
[0002] Bacterial infections have long posed a significant global health challenge and were a leading cause of death before the early 20th century, with diseases such as pneumonia and tuberculosis being the most prevalent. The discovery of antibiotics marked one of the most groundbreaking medical advances in the fight against bacterial infections over the past century. However, the long-term and repeated use of antibiotics has led to the emergence of drug-resistant bacteria, creating an urgent need for new and effective strategies to combat bacterial infectious diseases. Phototherapy, including photodynamic therapy and photothermal therapy, provides a non-invasive treatment approach by converting light energy into reactive oxygen species or high heat energy to eradicate bacteria. The synergistic combination of photodynamic therapy and photothermal therapy is considered a highly effective method for achieving superior therapeutic outcomes.
[0003] To achieve such treatments, photosensitizers possessing both photothermal and photodynamic therapy capabilities are highly favored. The development of these photosensitizing molecules should prioritize designs that operate at long wavelengths (>700 nm) and have high molar extinction coefficients for efficient phototherapy. In recent years, cyanine dyes have attracted attention as promising near-infrared probes due to their excellent absorption in the near-infrared region, deep tissue penetration, ease of synthesis, and low biotoxicity. Many cyanine dyes simultaneously exhibit photothermal effects and the ability to generate reactive oxygen species at a single wavelength (808 nm), enabling synergistic photodynamic and photothermal therapy for treating bacterial infections. However, due to their inherent photochemical properties, cyanine dyes are prone to photobleaching, resulting in low light conversion efficiency. Improving photostability typically involves introducing triplet quenchers or redox substituents to inhibit photochemical degradation. However, these modifications often come at the cost of reduced biocompatibility and reduced reactive oxygen species generation associated with triplet states.
[0004] Therefore, there is an urgent need to provide a new near-infrared aggregation-induced emission material with a cyanine structure and its preparation method, which can enhance its photostability and improve its light conversion efficiency while protecting the structure of the cyanine dye. Summary of the Invention
[0005] To address the aforementioned technical problems, this invention proposes a near-infrared aggregation-induced emission material with a cyanine structure, its preparation method, and its applications. This invention utilizes the principle of promoting molecular motion to dissipate excited-state energy, designing a novel cyanine structure that improves the stability of the cyanine dye structure, enhances its photostability, and increases its light conversion efficiency.
[0006] To achieve the above objectives, the present invention provides the following technical solution:
[0007] A near-infrared aggregation-induced emission material with a cyanine structure, based on IR780 dye, introduces triphenylamine rotor units into its molecular structure to enhance molecular motion and improve photostability and photothermal conversion efficiency.
[0008] This invention selects IR780 as a representative cyanine dye, and modifies its molecular design by introducing triphenylamine rotor units to enhance molecular motion, thereby designing and synthesizing two derivatives: monosubstituted (TPAIR) and disubstituted (TPADIR).
[0009] Furthermore, according to the experimental data of this invention, compared with unmodified IR780, TPAIR and TPADIR prepared by this invention exhibit significantly improved photostability and photothermal conversion efficiency in the monomeric state. In the aggregated state, TPADIR exhibits the highest PCE; and TPADIR can still generate reactive oxygen species in the aggregated state, exhibiting strong antibacterial activity.
[0010] Optionally, the structural formula of the IR780 dye is:
[0011] .
[0012] Optionally, the triphenylamine rotor unit is 4-(diphenylamino)phenol or 4,4'-(phenylazine)diphenol. Other triphenylamine phenols exhibit lower reactivity with IR780.
[0013] Optionally, the near-infrared aggregation-induced emission material with a cyanin structure is a monosubstituted derivative TPAIR or a disubstituted derivative TPADIR, with the specific chemical structural formula as follows:
[0014] or .
[0015] A method for preparing a near-infrared aggregation-induced emission material with a cyanin structure includes the following steps:
[0016] Under nitrogen protection, the triphenylamine rotor unit and triethylamine (TEA) are dissolved in an organic solvent;
[0017] Add IR780 dye (i.e. IR780 iodide) and heat and stir to react;
[0018] After removing the organic solvent, the near-infrared aggregation-induced emission material with the cyanin structure was purified by silica gel column chromatography. Dichloromethane / methanol / ethyl acetate was used as the eluent.
[0019] Optionally, the mass ratio of the triphenylamine rotor unit to triethylamine is 6:1-2.
[0020] Optionally, the organic solvent is DMF.
[0021] Optionally, the heating and stirring reaction conditions are: heating to 85°C and stirring for 4 hours.
[0022] Optionally, the eluent used in the silica gel column chromatography is a mixture of dichloromethane, methanol, and ethyl acetate, with a volume ratio of 10:1:1.
[0023] The above-mentioned near-infrared aggregation-induced emission materials with cyanin structure are used in the preparation of photosensitizers for combined photothermal / photodynamic therapy of bacterial infections.
[0024] Compared with the prior art, the present invention has the following advantages and technical effects:
[0025] This invention successfully constructed a class of novel photosensitive materials (TPAIR and TPADIR) with near-infrared aggregation-induced emission properties by introducing a single triphenylamine rotor unit into the molecular structure of the cyanine dye IR780. This design cleverly utilizes the intramolecular rotational freedom of triphenylamine to promote the efficient non-radiative dissipation of excited-state energy, thereby significantly improving the photostability and photothermal conversion efficiency of the materials. Particularly noteworthy is that the disubstituted derivative TPADIR, in its aggregated state, not only maintains excellent near-infrared absorption and fluorescence emission capabilities but also efficiently generates reactive oxygen species, exhibiting a powerful synergistic effect of photothermal and photodynamic processes.
[0026] Experimental results show that TPADIR exhibits excellent antibacterial activity against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) under 808 nm laser irradiation, with a bactericidal rate exceeding 90%. Furthermore, it demonstrates almost no toxicity under light-free conditions, exhibiting good photoselectivity and biosafety. Simultaneously, its preparation method is simple, the raw materials are readily available, and the yield is moderate, possessing good reproducibility and scalability potential.
[0027] In summary, this invention overcomes the bottlenecks of traditional cyanine dyes, such as easy photobleaching and low light conversion efficiency. While ensuring high biocompatibility, it achieves synergistic enhancement of photostability, photothermal properties, and photodynamic activity, providing a promising new generation of near-infrared photosensitizer platform for precise and non-invasive treatment of drug-resistant bacterial infections. Attached Figure Description
[0028] The accompanying drawings, which form part of this invention, are used to provide a further understanding of the invention. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an undue limitation of the invention. In the drawings:
[0029] Figure 1 This is a schematic diagram of the reaction for preparing near-infrared aggregation-induced emission materials with an anthocyanin structure according to the present invention;
[0030] Figure 2 The UV-Vis absorption spectra (a) and fluorescence emission spectra (b) of the TPADIR compound synthesized in Example 2, the TPAIR compound synthesized in Example 1, and the original IR780 dye in Comparative Example 1 in the near-infrared region are shown.
[0031] Figure 3 Table a shows the absorption spectrum changes of TPADIR, TPAIR, and IR780 under continuous irradiation with 808 nm laser (0.8 W / cm²) (30-second intervals); table b shows the temperature change trends of TPADIR (20 μM aqueous solution), TPAIR (20 μM aqueous solution), and IR780 (20 μM aqueous solution) during three heating-cooling cycles (0.8 W / cm²); table c compares the photothermal conversion efficiencies of TPADIR, TPAIR, and IR780 in DMSO and aqueous solutions.
[0032] Figure 4 The images show the photodynamic effects of the materials in Embodiments 1, 2, and Comparative Example 1 of this invention.
[0033] Figure 5 This is a diagram illustrating the antibacterial effect of the material in Example 2 of the present invention. Detailed Implementation
[0034] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.
[0035] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Every smaller range between any stated value or intermediate value within a stated range, and any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.
[0036] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.
[0037] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be apparent to those skilled in the art. This specification and embodiments are merely exemplary.
[0038] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.
[0039] Unless otherwise specified, "room temperature" in this invention refers to 20-30℃.
[0040] All raw materials used in this invention were purchased from the market.
[0041] The technical solution of the present invention will be further illustrated by the following embodiments.
[0042] Example 1 Synthesis of TPAIR compound
[0043] A method for preparing a near-infrared aggregation-induced emission material with a cyanin structure includes the following steps:
[0044] Under a nitrogen atmosphere and at room temperature, 60 mg of 4-(diphenylamino)phenol and 10 mg of triethylamine (TEA) were dissolved in 5 mL of anhydrous DMF. Then, 5 mL of IR780 iodide dissolved in anhydrous DMF (the mass ratio of anhydrous DMF to IR780 iodide was 1180:53) was added, and the mixture was heated to 85 °C and stirred for 4 hours. After removing the DMF, the product was purified by silica gel column chromatography using dichloromethane / methanol / ethyl acetate (volume ratio = 10:1:1) as the eluent. The final product was a green solid, TPAIR, in 41.6% yield.
[0045] 1H NMR (500 MHz, CDCl3) δ 7.93 (d, J = 15 Hz, 2H), 7.39 (d, J = 15 Hz,2H), 7.30 (d, J = 10 Hz, 2H), 7.23 (t, J = 15 Hz, 2H), 7.19 (m, 8H), 7.0 (d,J = 10 Hz, 2H), 6.96 (t, J = 20 Hz, 6H), 6.16 (d, J = 15 Hz, 2H), 4.15 (t, J= 15 Hz, 4H), 2.77 (t, J = 10 Hz, 4H), 2.06 (t, J = 10 Hz, 2H), 1.93 (m, 4H), 1.44 (s, 12H), 1.08 (t, J = 15 Hz, 6H).
[0046] 13 C NMR (125 MHz, CDCl3) δ=171.76, 163.81, 156.01, 147.77, 142.44,142.33, 141.86, 141.81, 140.95, 129.19, 128.77, 127.63, 125.00, 122.98,122.79, 122.37, 122.07, 115.44, 110.84, 100.51, 100.39, 48.96, 46.28, 29.73,27.99, 24.65, 21.11, 20.88, 11.74. HRMS, m / z: ([M]+), calculated value: 764.4580, measured value: 764.4587.
[0047] Example 2 Synthesis of TPADIR compounds
[0048] A method for preparing a near-infrared aggregation-induced emission material with a cyanin structure includes the following steps:
[0049] Under a nitrogen atmosphere and at room temperature, 60 mg of 4,4'-(phenylazine)diphenol and 20 mg of triethylamine (TEA) were dissolved in 5 mL of anhydrous DMF. Then, 5 mL of IR780 iodide dissolved in anhydrous DMF (mass ratio of anhydrous DMF to IR780 iodide 59:5) was added, and the mixture was heated to 85 °C and stirred for 4 hours. After removing the DMF, the product was purified by silica gel column chromatography using dichloromethane / methanol / ethyl acetate (volume ratio = 10:1:1) as eluent. The final product was a green solid, TPADIR, in 38% yield.
[0050] 1 H NMR (500 MHz, CDCl3) δ 7.91 (d, J = 10 Hz, 4H), 7.38 (s, 4H), 7.32(s, 4H), 7.23 (s, 4H), 7.16 (d, J = 5 Hz, 2H), 7.12 (d, J = 5 Hz, 4H), 1.43 (s, 24H), 1.05 (s, 12H).
[0051] 13 C NMR (125 MHz, CDCl3) δ 171.84, 163.98, 155.54, 147.87, 142.37,141.76, 140.93, 129.31, 128.79, 125.66, 125.11, 123.29, 122.65, 122.22,115.50, 110.78, 100.39, 77.32, 77.07, 76.81, 48.98, 46.17, 31.51, 30.14,29.70, 28.04, 24.47, 21.17, 20.87, 11.69. HRMS, m / z: ([M]+), calculated value: 641.8972, measured value: 641.9007.
[0052] Comparative Example 1
[0053] Original IR780 dye.
[0054] Effect verification
[0055] Example 1: TPADIR exhibits near-infrared absorption and emission, as determined by ultraviolet absorption and fluorescence emission spectroscopy. Figure 2 As shown.
[0056] Figure 2The UV-Vis absorption and fluorescence emission spectra of the synthesized TPADIR and TPAIR compounds and the original IR780 dye in Comparative Example 1 in the near-infrared region are shown. The results show that TPADIR has a strong and sharp absorption peak at approximately 780 nm, indicating that it retains the excellent near-infrared absorption characteristics of cyanine dyes, which is beneficial for deep tissue penetration; simultaneously, it exhibits significant fluorescence emission near 820 nm, confirming its near-infrared luminescence properties.
[0057] Example 2: Comparison of the photothermal properties of TPAIR and TPADIR in DMSO and aqueous solution demonstrates that modification with TPA units can improve the photothermal properties and photostability of TPADIR monomers and aggregates, such as... Figure 3 As shown.
[0058] Figure 3 Table a shows the absorption spectrum changes of TPADIR, TPAIR, and IR780 under continuous irradiation with an 808 nm laser (0.8 W / cm²) (30-second intervals); table b shows the temperature change trends of TPADIR (20 μM aqueous solution), TPAIR (20 μM aqueous solution), and IR780 (20 μM aqueous solution) during three heating-cooling cycles (0.8 W / cm²); table c compares the photothermal conversion efficiencies of TPADIR, TPAIR, and IR780 in DMSO and aqueous solutions. Figure 3 As can be seen from this, compared to the commercial dye IR780, from Figure 3 As can be observed in section a, TPADIR and TPAIR exhibit good photostability. Compared to the commercial dye IR780, from... Figure 3 As can be observed in section c, TPADIR and TPAIR exhibit good photothermal conversion coefficients. Compared to the commercial dye IR780, from... Figure 3 As can be observed in b, TPADIR and TPAIR have good photothermal stability.
[0059] Example 3: Comparing the changes in ROS generation capacity of TPAIR, TPADIR, and IR780 in DMSO solution with increasing aqueous solution volume demonstrates that TPADIR has good photodynamic effects. Figure 4 As shown.
[0060] Figure 4The figure shows the photodynamic effects of the materials in Examples 1 and 2 of this invention, as well as the comparative examples. It illustrates the changing trends in the reactive oxygen species (ROS) generation capacity of TPAIR, TPADIR, and IR780 in DMSO solution as the water volume ratio increases (i.e., the polar environment is enhanced, and the degree of molecular aggregation increases). The results show that as the water content increases, the ROS yield of TPADIR is significantly higher than that of TPAIR and the original IR780, especially maintaining a strong ability to generate ROS even at high water ratios, indicating its excellent photodynamic performance in the aggregated state. This demonstrates that TPADIR, by introducing a bis(triphenylamine) rotor unit, effectively enhances molecular motion and excited-state energy dissipation, suppresses non-radiative decay pathways, and thus maintains efficient ROS generation in the aggregated environment, exhibiting remarkable photodynamic therapeutic potential.
[0061] Example 4: Bacteria (Staphylococcus aureus and MRSA) cultured in liquid LB medium were washed three times with PBS. The absorbance of the collected bacterial suspension at 600 nm was adjusted to OD600 = 1.0. The suspension was then diluted with PBS to 1 × 10⁻⁶ of its original concentration. 6 One part was incubated with TPADIR molecules for 30 minutes. After incubation, the bacterial culture was subjected to 808 nm laser (power density 0.8 W cm⁻¹) treatment. -2 Irradiate for 10 minutes. After irradiation, further dilute the solution with PBS to 1×10⁻⁶ of the original concentration. 4 One-fifth of the solution (50 μL) was spread onto a solid LB agar plate. The plate was incubated at 37°C for 18 hours, and the colonies were counted and photographed using a digital camera.
[0062] The formula for calculating bacterial survival rate is: (B / A × 100%);
[0063] Where A represents the average colony count without treatment, and B represents the average colony count after treatment with TPADIR molecules.
[0064] The dark treatment group was conducted under the same experimental conditions, but without laser irradiation. Results showed that TPADIR exhibited good antibacterial properties, such as... Figure 5 As shown.
[0065] Figure 5This figure shows the antibacterial effect of the material in Example 2 of the present invention. It illustrates the antibacterial effect of TPADIR against Staphylococcus aureus and MRSA under 808 nm laser irradiation. The results show that under light irradiation, the survival rates of both bacteria were significantly reduced, with the survival rate of Staphylococcus aureus decreasing to approximately 2% and the survival rate of MRSA decreasing to approximately 5%, indicating that TPADIR possesses highly efficient photodynamic bactericidal ability. This confirms that TPADIR can achieve potent and selective killing of drug-resistant bacteria under near-infrared light irradiation, demonstrating good potential for clinical application.
[0066] The above are merely preferred embodiments of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the scope of the technology disclosed in the present invention should be included within the scope of protection of the present invention.
Claims
1. A near-infrared aggregation-induced emission material with a cyanin structure, characterized in that, Based on the IR780 dye, a triphenylamine rotor unit was introduced into its molecular structure.
2. The near-infrared aggregation-induced emission material with a cyanin structure according to claim 1, characterized in that, The structural formula of the IR780 dye is: 。 3. The near-infrared aggregation-induced emission material with a cyanin structure according to claim 1, characterized in that, The triphenylamine rotor unit is 4-(diphenylamino)phenol or 4,4'-(phenylazine)diphenol.
4. A near-infrared aggregation-induced emission material with a cyanin structure according to claim 3, characterized in that, The chemical structural formula is as follows: or .
5. A method for preparing a near-infrared aggregation-induced emission material with a cyanin structure as described in any one of claims 1-4, characterized in that, Includes the following steps: Under nitrogen protection, the triphenylamine rotor unit and triethylamine were dissolved in an organic solvent; Add IR780 dye and heat and stir to react; After removing the organic solvent, the near-infrared aggregation-induced emission material with the cyanin structure was prepared by silica gel column chromatography.
6. The method for preparing the near-infrared aggregation-induced emission material with a cyanin structure according to claim 5, characterized in that, The mass ratio of the triphenylamine rotor unit to triethylamine is 6:1-2.
7. The method for preparing the near-infrared aggregation-induced emission material with a cyanin structure according to claim 5, characterized in that, The organic solvent is DMF.
8. The method for preparing the near-infrared aggregation-induced emission material with a cyanin structure according to claim 5, characterized in that, The conditions for the heating and stirring reaction are: heating to 85°C and stirring for 4 hours.
9. The method for preparing the near-infrared aggregation-induced emission material with a cyanin structure according to claim 5, characterized in that, The eluent used in the silica gel column chromatography is a mixture of dichloromethane, methanol, and ethyl acetate in a volume ratio of 10:1:
1.
10. The application of the near-infrared aggregation-induced emission material with a cyanin structure as described in any one of claims 1-4 in the preparation of a photosensitizer for combined photothermal / photodynamic therapy of bacterial infections.