Organic copper ion complex with high photothermal conversion efficiency and preparation and application thereof
By synthesizing novel organic molecules with copper ion coordination ability and preparing organic copper ion complex Cu2+@BTAA with high photothermal conversion capacity, the problem of limited effect of photothermal-copper ion dual-functional materials in the prior art has been solved, realizing efficient photothermal conversion and dual bactericidal effect of copper ions, thus expanding the potential for biomedical applications.
Patent Information
- Application Number
- CN202511478593.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-10-16
- Publication Date
- 2026-01-27
AI Technical Summary
In existing technologies, the effects of single near-infrared photothermal antibacterial or copper ion antibacterial modes are limited, making it difficult to achieve highly efficient photothermal-copper ion dual-functional materials, which restricts the development and practical application of optical therapy technology.
A novel organic molecule with copper ion coordination ability was synthesized, and an organic copper ion complex Cu2+@BTAA with high photothermal conversion ability was prepared by chemical synthesis method. This achieved redshift in the near-infrared light absorption range and photothermal conversion ability. Combined with the redox properties of copper ions, a dual bactericidal effect was achieved.
It significantly improves the bactericidal efficacy of materials, expands the range of light utilization, and achieves efficient photothermal conversion and dual bactericidal function of copper ions, making it suitable for applications in the biomedical field.
Smart Images
Figure CN121405643A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of biomedical technology, specifically to an organic copper ion complex with high photothermal conversion efficiency and its preparation and application. Background Technology
[0002] Bacterial infections are a common clinical problem, and have become the second leading cause of death worldwide after ischemic heart disease. Antibiotics are the primary treatment for bacterial infections. However, the widespread use of antibiotics has led to the emergence of drug-resistant bacteria, especially multidrug-resistant bacteria, which significantly increase patient mortality. Currently, the development of new antibiotics is far slower than the rate of bacterial evolution. Therefore, there is an urgent need to develop novel antibacterial agents.
[0003] In recent years, near-infrared photothermal therapy (PTT) has attracted widespread attention from researchers due to its significant advantages such as being non-invasive and requiring no surgical incisions. Under near-infrared light (NIR, 780-1700 nm) excitation, photothermal materials utilize their photothermal conversion properties to generate localized high temperatures, which can disrupt bacterial cell membrane structures and cause internal protein denaturation, thereby causing irreversible damage to bacteria and inducing their death. Compared with traditional antibiotic treatment, PTT does not induce antibiotic resistance in bacteria and is therefore considered a highly promising new antibacterial treatment method.
[0004] Metal ion sterilization technology, due to its advantages such as high efficiency, broad spectrum, and long-lasting effect, is an important antibacterial method in the post-antibiotic era. Among many metals, copper is an essential trace mineral element for organisms, and copper ions (Cu) are... 2+ Copper ions play a crucial role in the physiological processes of organisms. Specifically, their redox properties can disrupt the integrity of microbial cell membranes, inactivating key enzymes and degrading DNA, thus achieving a broad-spectrum antibacterial effect. Therefore, copper ions are widely used in antibacterial applications in medical devices and antibacterial coatings.
[0005] Single near-infrared photothermal antibacterial or copper ion antibacterial modes often exhibit limited therapeutic effects. In contrast, materials possessing both near-infrared photothermal and copper ion antibacterial functions can demonstrate more significant therapeutic effects. However, materials achieving this dual function are currently scarce, often requiring the construction of complex material systems using multiple materials, which frequently result in poor performance. This not only limits the development of optical therapy technology but also hinders its practical application. Summary of the Invention
[0006] To address the aforementioned problems, this invention provides an organic copper ion complex with high photothermal conversion efficiency, its preparation, and its application. The organic copper ion complex is simple to prepare, possesses highly efficient photothermal conversion capability excited by near-infrared light, and achieves dual sterilization through photothermal and copper ion stimulation, making it suitable for widespread application.
[0007] In a first aspect, the present invention provides a novel organic molecule with copper ion coordination ability, having the structure shown in the following formula:
[0008]
[0009] R is selected from C 1-12 alkylene, C 3-12 Cycloalkylene, C 5-14 The aryl, C 5-8 subheterocyclic groups, -C 1-12 Alkyl-C 3-8 cycloalkyl-, -C 1-6 Alkoxy-C 1-6 Alkyl, -C 1-12 Alkoxy-C 3-8 cycloalkyl-, -C 1-12 Alkyl-C 5-8 Heterocyclic -, -C 1-12 Alkoxy-C 5-8 Heterocyclic -, -C 1-12 Alkyl-C 5-14 Aryl- or -C 1-12 Alkoxy-C 5-14 Aryl-; the aryl group is selected from phenyl, aniline, naphthyl, pyrrole, imidazolyl, pyridyl, pyrimidinyl, furanyl or thiophene, and the heterocyclic group is selected from tetrahydrofuranyl, piperidinyl, hexahydropyridinyl or piperazine; preferably diethylaniline.
[0010] A second aspect of the present invention provides a method for preparing a novel organic molecule with copper ion coordination ability:
[0011]
[0012] The preparation process includes:
[0013] Step 1: Under nitrogen protection, the nitroso reactant and 2,2'-methylenebisbenzothiazole were mixed in solvent 1. The mixture was heated and stirred for a period of time. After the reaction was completed and cooled to room temperature, the mixture was concentrated by rotary evaporation under reduced pressure, filtered, washed, and dried to obtain the crude product. The crude product was purified by column chromatography to obtain the organic molecule.
[0014] In some embodiments, the molar ratio of the nitroso reactant to 2,2'-methylenebisbenzothiazole is 1:(0.5-2), preferably 1:1.
[0015] In some embodiments, the reaction temperature is 70–90°C and the reaction time is 4–6 hours, preferably 80°C for 5 hours.
[0016] In some embodiments, solvent 1 is selected from at least one of methanol, ethanol, and tetrahydrofuran.
[0017] A third aspect of the present invention provides an organocopper ion complex with high photothermal conversion capability and near-infrared light absorption capability, the material having the structural features shown in the following formula:
[0018]
[0019] In a fourth aspect, the present invention provides a method for preparing an organocopper ion complex with high photothermal conversion capability and near-infrared light absorption capability, the method being as follows:
[0020] Step 2: Mix and stir the organic solution of organic molecules with the aqueous solution of copper salt. After the reaction is completed, the mixture is subjected to vacuum rotary evaporation, washing, and drying to obtain the above-mentioned novel organic complex material.
[0021] In some embodiments, the organic solution is at least one of methanol, ethanol, and tetrahydrofuran, preferably ethanol.
[0022] In some embodiments, the copper salt is at least one of copper chloride, copper nitrate, and copper sulfate, preferably copper chloride.
[0023] In some embodiments, the molar ratio of the organic molecule to the divalent copper ion is 1:(0.1-2), preferably 0.5.
[0024] In some embodiments, the reaction temperature is 20-80°C, preferably at room temperature.
[0025] In some embodiments, the stirring time at room temperature is 3 to 5 hours, preferably 4 hours.
[0026] A fifth aspect of the present invention provides the application of the above-described novel organocopper ion coordination compounds in the preparation of antibacterial materials or devices.
[0027] Beneficial effects
[0028] (1) This invention uses chemical synthesis to synthesize novel organic small molecules containing C=N benzothiazole derivatives, achieving copper loading through coordination. The novel photothermal complex material Cu prepared in step 2... 2+ Compared to the BTAA molecule synthesized in step 1, @BTAA exhibits a significant redshift in light absorption, with its absorption region shifting from the visible light region to the near-infrared region. This property effectively expands the range of light utilization.
[0029] (2) The novel complex material Cu prepared by this invention 2+@BTAA exhibits high photothermal conversion capability under near-infrared irradiation and can also achieve dual bactericidal function by utilizing the properties of copper ions. This dual synergistic effect significantly enhances the bactericidal efficacy of the material and expands its application potential in other biomedical fields. Attached Figure Description
[0030] The accompanying drawings, which form part of this invention, are used to provide a further understanding of the invention. Exemplary embodiments of the invention and their descriptions are used to explain the invention and do not constitute an improper limitation of the invention.
[0031] Figure 1 The BTAA molecular structure prepared in Example 1 of this invention;
[0032] Figure 2 The light absorption and luminescence properties of the BTAA molecules prepared in Example 1 of this invention;
[0033] Figure 3 Cu in Embodiment 2 of the present invention 2+ Light absorption and luminescence properties before and after coordination with BTAA.
[0034] Figure 4 Cu prepared in Example 2 of this invention 2+ Photothermal conversion properties of BTAA complex materials;
[0035] Figure 5 The BTAA and Cu prepared in Examples 1 and 2 of this invention 2+ @BTAA complex materials' bactericidal effect and mechanism against Escherichia coli;
[0036] Figure 6 The BTAA and Cu prepared in Examples 1 and 2 of this invention 2+ @BTAA complex materials' bactericidal effect and mechanism against Staphylococcus aureus. Detailed Implementation
[0037] The present invention will be further illustrated below with reference to specific embodiments. These embodiments are for illustrative purposes only and are not intended to limit the scope of protection claimed by the present invention.
[0038] Example 1
[0039] Preparation of novel small organic molecule BTAA: In a round-bottom flask (100 mL), N,N-diethyl-4-nitrosoaniline (0.178 g, 1 mmol) and 2,2'-methylenebisbenzothiazole (0.282 g, 1 mmol) were dissolved in anhydrous ethanol (20 mL). The mixture was stirred at 80 °C for 5 h under nitrogen protection. After the reaction was completed and cooled to room temperature, the product was concentrated by rotary evaporation under reduced pressure, filtered, washed, and the crude product was purified by column chromatography (ethyl acetate:petroleum ether = 1:3, v:v) to obtain a red powdery BTAA compound. Figure 1 The illustration shows the single-crystal resolved structure of the small molecule BTAA, and its 1H NMR spectrum: 1 H NMR (400MHz, DMSO-D6) δ8.24(d,J=7.7Hz,1H),8.18-8.08(m,2H),7.91(dd,J=6.4,3.0Hz,1H),7.65-7.52(m,1H),7. 47 (dd, J = 6.2, 3.2 Hz, 2H), 6.85 (d, J = 9.2 Hz, 2H), 6.53 (d, J = 9.3 Hz, 2H), 3.28 (q, J = 7.0 Hz, 4H), 1.00 (t, J = 6.9 Hz, 7H).
[0040] The light absorption properties and luminescence properties of the BTAA compound prepared in Example 1 of this invention were tested:
[0041] Figure 2 a represents the ultraviolet-visible-near-infrared absorption spectrum of the BTAA molecular solid prepared in Example 1 of this invention. Figure 2 b represents the normalized UV-Vis-NIR absorption spectra of BTAA in solutions of different polarities; Figure 2 c is the excitation spectrum of BTAA (E m =680nm); Figure 2 d represents the emission spectrum (E) of BTAA solid. x =373nm) and the crystal luminescence under a laser confocal microscope; Figure 2 e represents the emission spectra of BTAA dissolved in different solvents; Figure 2 f represents the fluorescence lifetime of BTAA. As shown in the figure, the light absorption range of small-molecule BTAA is mainly in the visible light range, and its absorption range does not change significantly with the polarity of the solution. BTAA solid powder exhibits fluorescence emission of a certain intensity around 680 nm, but only weak fluorescence is detected when BTAA is dissolved in different solutions. The fluorescence lifetime of BTAA is 1.09 μs.
[0042] Example 2
[0043] A novel organic complex Cu with near-infrared light absorption capability 2+The preparation process of @BTAA includes the following steps:
[0044] (1) First, the interaction between the small molecule BTAA and the metal ion Cu was determined by plotting a Job Plot. 2+ The specific implementation method is as follows: the total molar concentration of the system (5 μM) is kept constant, the component ratio is changed and the light absorption change is tested. The light absorption intensity at 670 nm is selected to draw a Job Plot and the coordination ratio is obtained.
[0045] (2) According to the coordination ratio, the small molecule product BTAA (88.52 mg, 2 mmol) obtained in Example 1 was dissolved in anhydrous ethanol (100 mL) and mixed with an aqueous solution of copper nitrate trihydrate (24.16 mg, 1 mmol). The mixture was stirred at room temperature for 5 h. After the reaction was completed, it was filtered, evaporated under reduced pressure, and dried to obtain a black solid powder of Cu. 2+ @BTAA materials.
[0046] Cu in Embodiment 2 of the present invention 2+ Small molecule BTAA and metal ion Cu in BTAA materials 2+ Coordination ratio and light absorption and luminescence properties testing:
[0047] Figure 3 a represents the Cu content in Embodiment 2 of the present invention. 2+ With the total molar concentration of BTAA remaining constant, the component ratios are changed (the values in the legend are Cu). 2+ The ultraviolet-visible-near-infrared absorption spectrum (molar ratio); Figure 3 b is based on Figure 3 The Job Plot plot drawn by a; Figure 3 c represents BTAA and Cu 2+ @Normalized UV-Vis-NIR absorption spectrum measured by BTAA dissolved in ethanol solution; Figure 3 d is Cu 2+ @BTAA material emission spectrum in solution (E x =390nm). The data shows that Cu 2+ @BTAA's light absorption intensity at 670nm increases with Cu 2+ The proportion initially increases and then decreases, with the maximum intensity converging at Cu. 2+ / [Cu 2+ At position +BTAA] = 0.33, therefore BTAA and Cu 2+ The mixing ratio is 2:1; Cu 2+The light absorption range of @BTAA is significantly red-shifted compared to BTAA, extending into the near-infrared region, indicating that it possesses the basic conditions for near-infrared light applications; the material exhibits only weak luminescence under illumination after dissolving in ethanol, demonstrating its excellent photothermal conversion potential.
[0048] The Cu prepared in Example 2 of this invention 2+ @BTAA material undergoes photothermal performance testing:
[0049] Figure 4 a represents Cu prepared in Example 2 of this invention. 2+ The temperature rise and fall curves of BTAA material dissolved in ethanol under 808nm laser irradiation, and the fitting curve of cooling time versus -ln(θ) (laser power density 1.0W / cm²). 2 ); Figure 4 b is Cu 2+ Infrared image of BTAA material dissolved in ethanol and heated under 808nm laser irradiation during the heating process; Figure 4 c represents different concentrations of Cu 2+ @BTAA material in ethanol solution under 808nm laser (1.0W / cm) 2 Temperature rise under irradiation; Figure 4 d is Cu 2+ @BTAA material (200 μM) under 808 nm laser (1.0 W / cm) 2 ) Cyclic stability test diagram under irradiation. Cu 2+ The BTAA material solution rapidly heated from 28.8℃ to 74.6℃ within 350s under 808nm laser irradiation, with a photothermal conversion efficiency as high as 48.4%. Its temperature rise showed concentration dependence and good cycling stability, demonstrating the good application potential of this material.
[0050] The antibacterial properties of the materials prepared in Examples 1 and 2 of this invention were tested using Escherichia coli and Staphylococcus aureus.
[0051] 100 μL of E. coli solution was added to 900 μL of physiological saline as a blank control group. The treatment procedures for the experimental group were as follows: 900 μL of LTAA (0.2 μmol) and Cu were added respectively. 2+ Cu 2+ @BTAA(0.1μmol)Cu 2+ 100 μL of *E. coli* solution was added to a mixture of 0.2 μmol BTAA and acetone / water (acetone to water volume ratio 1:10) as the experimental group. The bactericidal effect was compared between the experimental group and the control group: First, the mixed solution was placed in an incubator for 2 hours, then removed and divided into three groups. Next, an 808 nm laser (1.0 W / cm²) was used to treat each group.2 After irradiation for 0, 10, and 20 minutes respectively, the bacteria were spread using the plate coating method and placed in a bacterial incubator for incubation. After 24 hours, the bacteria were removed for observation and count.
[0052] Figure 5 a represents the materials prepared in Examples 1 and 2 of this invention, which are cultured together for 2 hours and then subjected to an 808nm laser (1.0W / cm²). 2 The antibacterial effect after irradiation; Figure 5 b represents a mixed culture for 2 hours followed by treatment with an 808nm laser (1.0W / cm²). 2 The number of Escherichia coli colonies after irradiation for different durations; Figure 5 c is the SEM image corresponding to 2 hours of mixed culture followed by 20 minutes of laser irradiation. The results show that after different times of mixed culture and laser irradiation, the small molecule BTAA synthesized in Example 1 did not cause a significant reduction in colony count; Cu 2+ This can reduce the number of colonies, indicating that Cu 2+ It has a certain bactericidal effect; in comparison, Cu 2+ The number of E. coli colonies treated with @BTAA material was significantly reduced, and the reduction was dependent on concentration and laser irradiation time. At a material concentration of 200 μM and irradiation time of 20 min, the sterilization rate of E. coli reached over 99%. SEM images revealed that Cu... 2+ The BTAA material exhibits a bactericidal mechanism, causing varying degrees of damage to the surface of treated E. coli.
[0053] Similar to the experiment targeting *E. coli*, 100 μL of *Staphylococcus aureus* solution was added to 900 μL of physiological saline as a blank control group. The experimental group was treated as follows: 900 μL of BTAA (0.2 μmol) and Cu... 2+ Cu 2+ @BTAA(0.1μmol)Cu 2+ @BTAA (0.2 μmol) in a mixture of acetone and water (acetone to water volume ratio 1:10) was used as the experimental group, with 100 μL of Staphylococcus aureus solution added to each group. The bactericidal effect was compared between the experimental group and the control group: First, the mixed solution was placed in an incubator for 2 hours, then removed and divided into three groups. Next, an 808 nm laser (1.0 W / cm²) was used to treat each group. 2 After irradiation for 0, 10, and 20 minutes respectively, the bacteria were spread using the plate coating method and placed in a bacterial incubator for incubation. After 24 hours, the bacteria were removed for observation and count.
[0054] Figure 6 a represents the materials prepared in Examples 1 and 2 of this invention, which are cultured together for 2 hours and then subjected to an 808nm laser (1.0W / cm²).2 The antibacterial effect after irradiation; Figure 6 b represents a mixed culture for 2 hours followed by treatment with an 808nm laser (1.0W / cm²). 2 The number of Staphylococcus aureus colonies after irradiation for different durations; Figure 6 c shows the SEM image corresponding to 2 hours of mixed culture followed by 20 minutes of laser irradiation. The results show that after different times of mixed culture and laser irradiation, the small molecule BTAA synthesized in Example 1 did not cause a significant reduction in the number of Staphylococcus aureus colonies; while Cu... 2+ This can reduce the number of colonies, indicating that Cu 2+ It has a certain bactericidal effect against Staphylococcus aureus; in comparison, Cu... 2+ The number of Staphylococcus aureus colonies treated with @BTAA material was significantly reduced, and the reduction showed a concentration-dependent effect on laser irradiation time. At a material concentration of 200 μM and irradiation time of 20 min, a sterilization rate of over 99% against Staphylococcus aureus could be achieved. SEM images revealed that Cu... 2+ The BTAA material's bactericidal mechanism results in varying degrees of damage to the surface of Staphylococcus aureus after treatment.
[0055] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.
Claims
1. An organic molecule with copper ion coordination ability, characterized in that, It has the structure shown in the following formula: R is selected from C 1-12 alkylene, C 3-12 Cycloalkylene, C 5-14 The aryl, C 5-8 subheterocyclic groups, -C 1-12 Alkyl-C 3-8 cycloalkyl-, -C 1-6 Alkoxy-C 1-6 Alkyl, -C 1-12 Alkoxy-C 3-8 cycloalkyl-, -C 1-12 Alkyl-C 5-8 Heterocyclic -, -C 1-12 Alkoxy-C 5-8 Heterocyclic -, -C 1-12 Alkyl-C 5-14 Aryl- or -C 1-12 Alkoxy-C 5-14 Aryl-; the aryl group is selected from phenyl, aniline, naphthyl, pyrrole, imidazolyl, pyridyl, pyrimidinyl, furanyl or thiophene, and the heterocyclic group is selected from tetrahydrofuranyl, piperidinyl, hexahydropyridinyl or piperazine.
2. The method for preparing an organic molecule with copper ion coordination ability according to claim 1, characterized in that, include: Under an inert gas atmosphere, the nitroso reactant was reacted with 2,2'-methylenebisbenzothiazole in ethanol at a 1:1 molar ratio at 80°C for 5 h. After the reaction was completed and cooled to room temperature, the product was washed, dried, and concentrated by rotary evaporation under reduced pressure to obtain the crude product. The crude product was then purified by column chromatography to obtain the product described above.
3. An organic molecule with copper ion coordination ability as described in claim 1, and Cu 2+ The resulting organocopper ion coordination compound has the structural characteristics shown in the following formula: 。 4. The method for preparing the organocopper ion coordination compound according to claim 3, characterized in that, include: An ethanol solution containing the organic molecules of claim 1 is mixed with an aqueous solution of copper chloride (organic molecules and Cu). 2+ The mixture (molar ratio 2:1) was stirred at room temperature for 4 hours, and then dried under reduced pressure to obtain the above-mentioned novel organocopper coordination compound.
5. The use of the organic copper ion coordination compound according to claim 4 in the preparation of photothermal antibacterial materials or devices.