Photoactive ruthenium complex as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of organic synthesis, and particularly provides a photoactive ruthenium complex and a preparation method thereof. The photoactive ruthenium complex provided by the invention not only can be decomposed under illumination to release isoniazide, but also can generate singlet oxygen under illumination excitation, has double antibacterial effects, has an obvious antibacterial effect on mycobacterium smegmatis, and can be used for treating mycobacterium tuberculosis infection.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and specifically relates to a photoactive ruthenium complex and a preparation method and application thereof. Background Art

[0002] Tuberculosis (TB) is a serious disease that mainly affects the lungs. The pathogen of TB is Mycobacterium tuberculosis, and the number of deaths caused by TB each year remains high. The treatment of TB is mainly antibiotic therapy. Commonly used drugs in first-line treatment include isoniazid and rifampicin, but improper use of antibiotics can easily lead to drug resistance. In the isolation and culture of isoniazid-resistant tuberculosis bacteria, about half are prone to the loss or mutation of KatG enzyme, which activates isoniazid to form INH-nicotinamide adenine dicyclobutyric acid (INH-NAD), which can inhibit the InhA enzyme involved in the synthesis of mycophenolic acid, which is an important lipid component of mycobacterial cell wall. The generation of drug-resistant strains requires longer drug treatment and incurs greater treatment costs, and has stronger toxic side effects for patients. Therefore, there is an urgent need to develop new drugs to deal with Mycobacterium tuberculosis infection.

[0003] In the development of new drugs, the use of metal complexes has stood out for its good biological effects. IQG-67 can directly activate isoniazid without an enzyme reaction, and avoids the inactivation of isoniazid in drug-resistant bacteria by replacing the enzyme activation reaction. It has also been reported that octahedral ruthenium (II) polypyridine complexes combined with isoniazid as a means of resisting mycobacteria have good effects in antibacterial experiments. At the same time, the INH-Fe (II) complex has in vitro and in vivo inhibitory activity against InhA enzymes and mycobacteria, including inhibitory activity against drug-resistant strains.

[0004] Photoactive ruthenium complexes are also used as precursors of antibacterial drugs, which can achieve the purpose of light-controlled drug release. Currently, relevant literature has reported ruthenium complexes containing isoniazid, which have shown potential anti-mycobacterial activity. [Ru(bpy)2(INH)2] 2+ It can release INH under blue light irradiation and has anti-Aspergillus fumigatus Mycobacterium effect. [Ru(tyy)(LL)(INH)] 2+ The photoactive ruthenium (II) complex of this type can inhibit the growth of Mycobacterium kansasii under the stimulation of visible light at low concentrations, and the high concentration of the compound also has a certain antibacterial effect in the dark. However, the antibacterial mechanism of these complexes depends only on the release of isoniazid, and continuous drug treatment may still cause drug resistance, and the core problem of isoniazid inactivation in drug-resistant bacteria has not been solved. Summary of the invention

[0005] The purpose of the present invention is to overcome the problem of isoniazid inactivation in drug-resistant bacteria in the prior art.

[0006] To this end, the present invention provides a photoactive ruthenium complex, the structure of which is shown below:

[0007]

[0008] The present invention also provides a method for preparing a photoactive ruthenium complex, comprising the following steps:

[0009] S1. Synthesis of Ru(tpy)Cl3;

[0010] S2, mixing Ru(tpy)Cl3 and 2,2'-biquinoline, adding a reducing agent, reacting under an inert gas atmosphere, and washing the product with HCI to obtain [Ru(tpy)(biq)(Cl)2];

[0011] S3, cis-[Ru(tpy)(biq)(Cl)2] and isoniazid are added to water, reacted under inert gas, filtered, NH4PF6 is added to the filtrate, the precipitate is collected, and washed to obtain a photoactive ruthenium complex (Ru3-INH).

[0012] Specifically, the above step S1 specifically comprises: dissolving RuCl3·3H2O and 2,2:6',2"-terpyridine in methanol, heating the mixture under an inert gas atmosphere to react, and obtaining Ru(tpy)Cl3.

[0013] Specifically, in the above step S2, the mass ratio of Ru(tpy)Cl3 to 2,2'-biquinoline is 172:100.

[0014] Specifically, the reducing agent in the above step S2 includes LiCl and triethylamine.

[0015] Specifically, the inert gas in the above step S2 includes argon.

[0016] Specifically, in the above step S3, the mass ratio of [Ru(tpy)(biq)(Cl)2], isoniazid and NH4PF6 is 132:68:163.

[0017] Specifically, in the above step S3, [Ru(tpy)(biq)(Cl)2] and isoniazid are added to water and reacted under nitrogen at 80°C for 6 hours.

[0018] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0019] The photoactive ruthenium complex provided by the present invention can not only decompose and release isoniazid under light, but also generate singlet oxygen under light excitation, and has a dual antibacterial effect, has a significant antibacterial effect on Mycobacterium smegmatis, and can be used to treat tuberculosis infection.

[0020] The present invention will be further described in detail below with reference to the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 It is a synthetic route diagram of the photoactive ruthenium complex provided by the present invention.

[0022] Figure 2 It is a synthesis route diagram of Ru(tpy)Cl3 provided in an embodiment of the present invention.

[0023] Figure 3 It is a pathway diagram for synthesizing Ru3 from Ru(tpy)Cl3 provided in an embodiment of the present invention.

[0024] Figure 4 It is a pathway diagram for synthesizing Ru3-INH from Ru3 provided in an embodiment of the present invention.

[0025] Figure 5 It is a result diagram of ROS detection using DPBF in Example 2 of the present invention; wherein, a is the fluorescence spectrum of DPBF after green light irradiation of Ru3-INH for different time periods; b is the fluorescence spectrum of DPBF after green light irradiation of Ru1-INH for different time periods; c is the ratio of the fluorescence intensity of DPBF at different time periods to the initial fluorescence intensity after green light irradiation of Ru3-INH and Ru1-INH for different time periods; d is the comparison of the fluorescence intensity of the control group, Ru1-INH, and Ru3-INH after irradiation for 5 minutes.

[0026] Figure 6 It is a graph showing the results of detecting ROS using DCFH in Example 2 of the present invention; wherein, a is the fluorescence spectrum of DCFH after green light irradiation of Ru3-INH and Ru1-INH for different time periods; b is the ratio of the fluorescence intensity of DCFH at different time periods to the initial fluorescence intensity after green light irradiation of Ru3-INH and Ru1-INH for different time periods; c is a comparison of the fluorescence intensities of the control group, Ru1-INH, and Ru3-INH after irradiation for 5 minutes.

[0027] Figure 7 This is the result of fluorescence microscopy detection after mixing Ru3-INH and M. Smegmatis with green light irradiation in Example 2 of the present invention.

[0028] Figure 8 It is a graph of the light-controlled drug release detection results in Example 3 of the present invention; wherein, a is a graph of the ultraviolet spectrum change of Ru3-INH in PBS under green light irradiation at different times (dark room), [Ru3-INH] = 61.5 μM; b is a graph of the ultraviolet spectrum change of Ru1-INH in PBS under green light irradiation at different times (dark room), [Ru1-INH] = 61.5 μM.

[0029] Fig. 9 It is a schematic diagram of the reaction of light-controlled drug releasing isoniazid in Example 3 of the present invention.

[0030] Fig.10 These are the bacterial survival results in Example 4 of the present invention; wherein, a is the bacterial survival rate detection after 40 minutes of green light irradiation after mixing different concentrations of Ru3-INH and E.Coli; b is the bacterial survival rate detection after 40 minutes of green light irradiation after mixing different concentrations of Ru3-INH and B.subtilis.

[0031] Fig.11 The green light (LED 520nm, 16mw / cm2) is obtained by mixing different concentrations of Ru3-INH, different concentrations of Ru1-INH and M. Smegmatis in Example 4 of the present invention. 2 ) Bacterial survival rate test results after 20 minutes of irradiation or in a dark environment.

[0032] Fig.12 It is the green light (LED 520nm, power density 16mw / cm2) after mixing Ru3-INH and M.Smegmatis in Example 4 of the present invention. 2 ) Flat plate test results after 20 minutes of irradiation.

[0033] Fig.13 These are the results of cell activity after culture of Ru3-INH (a), Ru1-INH (b) and MCF10A in Example 5 of the present invention (p≤0.05=*, p≤0.02=**).

[0034] Fig.14 This is the TEM result of ginger vesicles in Example 6 of the present invention.

[0035] Fig.15 This is the ginger vesicle particle size result in Example 6 of the present invention.

[0036] Fig.16 This is the result of the drug release measurement over time of the Ru3-INH-loaded ginger vesicles in Example 6 of the present invention.

[0037] Fig.17 This is a graph showing the ultraviolet spectrum changes of Ru3-INH ginger vesicles in PBS under green light irradiation at different times in Example 6 of the present invention (dark room).

[0038] Fig.18 This is the UV characterization of Ru3-INH before drug loading and the UV characterization of Ru3-INH loaded ginger vesicles in Example 6 of the present invention.

[0039] Fig.193 is a diagram of wound status at different times in Example 7 of the present invention; wherein a is the Ru3-INH+green light group; b is the Ru3-INH+darkness group; c is the PBS+green light group; and d is the PBS+darkness group.

[0040] Fig. 20 This is the wound area detection result in Example 7 of the present invention.

[0041] Fig.21 This is the body weight test result in Example 7 of the present invention. DETAILED DESCRIPTION

[0042] The technical scheme in the present invention will be clearly and completely described below in conjunction with the embodiments. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Although the representative embodiments of the present invention have been described in detail, it will be understood by those skilled in the art that various modifications and changes can be made to the present invention without departing from the scope of the present invention. Therefore, the scope of the present invention should not be limited to the embodiments, but should be limited by the attached claims and their equivalents.

[0043] The present invention provides a photoactive ruthenium complex, the structure of which is shown below:

[0044]

[0045] The present invention also provides a method for preparing a photoactive ruthenium complex, comprising the following steps:

[0046] S1. Synthesis of Ru(tpy)Cl3

[0047] RuCl3·3H2O and 2,2:6',2"-terpyridine were dissolved in methanol and heated to react under an inert gas atmosphere to prepare Ru(tpy)Cl3.

[0048] Specifically, refer to Figure 2 , RuCl3·3H2O and 2,2:6',2"-terpyridine were dissolved in methanol (distilled over Mg). The mixture was heated to reflux under N2, and the reaction solution was cooled to room temperature and then cooled in an ice bath. The brown solid was collected by vacuum filtration, washed with cold methanol until the filtrate was colorless, then washed with ether and air-dried.

[0049] S2, synthesis of Ru3

[0050] Ru(tpy)Cl3 and 2,2'-biquinoline are mixed, a reducing agent is added, and the mixture is reacted under an inert gas atmosphere. The product is washed with HCI to obtain [Ru(tpy)(biq)(Cl)2], i.e., Ru3.

[0051] Specifically, refer to Figure 3 , Ru(tpy)Cl3 and 2,2'-biquinoline were mixed in 75% ethanol, LiCl and triethylamine were added as reducing agents, the mixture was purged with argon, and then heated under argon reflux. The mixture was filtered while hot, the product was collected by evaporation under reduced pressure, and the reaction solution was frozen in a refrigerator. The solid was collected on a frit, partially washed with HCI, and then washed with acetone and anhydrous ether and air-dried.

[0052] The mass ratio of Ru(tpy)Cl3 to 2,2'-biquinoline is preferably 172:100.

[0053] S3, Synthesis of Ru3-INH

[0054] Cis-[Ru(tpy)(biq)(Cl)2] and isoniazid are added to water, reacted under an inert gas, filtered, NH4PF6 is added to the filtrate, the precipitate is collected, and washed to obtain a photoactive ruthenium complex, namely Ru3-INH.

[0055] Specifically, refer to Figure 4 , cis-[Ru(tpy)(biq)(Cl)2] and isoniazid were added to water and reacted under nitrogen at 80°C for 6 hours. The solution was allowed to cool to room temperature and filtered to remove any unreacted starting material. NH4PF6 was then added to form a precipitate. The precipitate was collected by filtration and washed with cold water and ether.

[0056] The photoactive ruthenium complex of the present invention, its preparation method and application effects are studied through specific examples below.

[0057] Embodiment 1:

[0058] Reference Figure 1 The present application provides a photoactive ruthenium complex, which is prepared by the following steps.

[0059] S1. Synthesis of Ru(tpy)Cl3;

[0060] 0.553 g (2.50 mmol) of RuCl3·3H2O and 0.583 g (2.50 mmol) of 2,2:6',2"-terpyridine were dissolved in 50 mL of methanol (distilled over Mg). The mixture was heated to reflux at 70 °C for 3 h under N2, and the reaction solution was cooled to room temperature and then cooled in an ice bath for 0.5 h. The brown solid was collected by vacuum filtration, washed with cold methanol until the filtrate was colorless, then washed with ether 4 times and air-dried.

[0061] S2, synthesis of Ru3

[0062] Ru(tpy)Cl3 (172 mg, 0.39 mmol) and 2,2'-biquinoline (biq, 100 mg, 0.39 mmol) were mixed in 75% ethanol (20 mL), 0.093 g LiCl and 0.086 mL triethylamine were added as reducing agents, the mixture was purged with argon for 7 minutes, and then heated under argon reflux for 4 hours. After that, the mixture was filtered while hot. The product was collected by evaporation under reduced pressure, and the reaction solution was then frozen in a refrigerator for 24 hours. The solid was collected on a frit and partially washed with 2 mL of chilled 3M HCI. The solid was then washed with 3 mL acetone and 15 mL anhydrous ether and air-dried.

[0063] S3, Synthesis of Ru3-INH

[0064] Cis [Ru(tpy)(biq)(Cl)2] (132 mg, 0.2 mmol) and isoniazid (INH) (68 mg, 0.5 mmol) were reacted in 15 ml of water under nitrogen at 80°C for 6 hours. The solution was allowed to cool to room temperature and filtered to remove any unreacted starting material. NH4PF6 (163 mg, 1 mmol) was then added to form a precipitate. The precipitate was collected by filtration and washed with cold water and ether. Ru(bpy)(biq)(INH)2 was dissolved in DMSO.

[0065] Embodiment 2:

[0066] This example studies the light-controlled release of isoniazid and the production of reactive oxygen species of Ru3-INH and Ru1-INH synthesized in Example 1. Ru1-INH was prepared using the method described in the literature, and PBS was used as a control group. The structure of Ru1-INH is shown below:

[0067]

[0068] 1,3-Diphenylisobenzofuran (DPBF) is a highly specific fluorescent probe that reacts to singlet oxygen. It can react with singlet oxygen to form endoperoxides, which then decompose into 1,2-dibenzoylbenzene, a compound that can detect the generation of reactive oxygen species (ROS) in vivo.

[0069] 2',7'-dichlorodihydrofluorescein (DCFH) is a fluorescent probe for measuring reactive oxygen species. When oxidized by ROS to 2',7'-dichlorofluorescein hydrogen probe (2',7'-dichlorofluorescein, DCF), it emits strong fluorescence. DCFH has better lipid solubility and membrane permeability, so it is widely used in the detection of intracellular ROS.

[0070] In this example, the reactive oxygen species (ROS) fluorescent probes DPBF and DCFH were used to detect the activity of ROS under green light irradiation (520 nm, 16 mW / cm 2 )Ru3-INH and Ru1-INH fluorescence results, such as Figure 5-6 The absorbance of Ru3-INH NPs to DPBF gradually increased before and after light irradiation. In contrast, the absorbance of DPBF without Ru3-INH NPs did not change significantly ( Figure 5 By comparing the absorbance of DCFH before and after light irradiation, the DCFH results without Ru3-INH NPs did not change significantly, and only the group using Ru3-INH-NPs showed a significant decrease ( Figure 6 ). These results indicate that Ru3-INH can produce 1 O2.

[0071] 2,7-Dichlorodihydrofluorescein diacetate (DCFH-DA) was used as an indicator again. 50 μM Ru3-INH was mixed with M. smegmatis and then green light (LED 520 nm, power density 16 mw / cm 2 ) was irradiated for 20 min, and then fluorescence microscopy was performed. Ru1-INH and PBS were used as controls. Figure 7 As shown. After entering the bacteria, the non-luminescent DCFH-DA reacts with the ROS produced by Ru3-INH and is converted into highly fluorescent 2',7'-dichlorofluorescein (DCF). Under green LED light, the bacteria incubated with Ru3-INH showed obvious green fluorescence, while the bacteria in the PBS group and Ru1-INH group did not show fluorescence. At the same time, in the absence of green LED light illumination, none of the test groups emitted light. The results further prove that Ru3-INH has the ability to produce ROS in bacteria.

[0072] Embodiment 3:

[0073] In order to investigate the effect of light-controlled drug release of Ru3-INH and Ru1-INH in PBS, the green light (520 nm, V≈2.7 v, 20 mW / cm 2 The UV spectra of Ru3-INH and Ru1-INH in PBS were studied under irradiation. Figure 8-9 After exposing the Ru3-INH solution (61.5uM) to green light for 5 minutes at room temperature, the UV-visible spectrum changed significantly ( Figure 8a), the main absorption band shifted, and the peak intensity at 560nm increased. In less than 2 minutes, the release reaction reached a steady state. The increase in the peak at 560nm with time showed a single exponential relationship, which also indicated that the time required to reach equilibrium was about 2 minutes. In Ru1-INH solution (61.5uM), a similar photorelease reaction was observed under green light irradiation. After 5 minutes of light irradiation, the UV-visible spectrum changed ( Figure 8 b), the main absorption band shifted, and the peak intensity at 460nm increased. The release reaction reached a steady state within 3 minutes. The peak at 560nm increased with time in a single exponential relationship, which also indicated that the time required to reach equilibrium was about 3 minutes.

[0074] Both Ru3-INH and Ru1-INH can release isoniazid under green light excitation. Ru3-INH reaches equilibrium two minutes after irradiation, which is faster than Ru1-INH.

[0075] Embodiment 4:

[0076] This example investigates the bactericidal effect of Ru3-INH.

[0077] Different concentrations of Ru3-INH were mixed with E. coli (Escherichia coli) and B. subtilis (Staphylococcus aureus) and then green light (LED 520nm, 16mw / cm 2 ) irradiated for 40 minutes, and the bacterial survival rate was tested. The results were as follows Fig.10 As shown in Figure 2, for representatives of Gram-negative and Gram-positive bacteria, Escherichia coli and Staphylococcus aureus, high concentrations of Ru3-INH drugs can kill both cells under light excitation, presumably due to the production of a large amount of reactive oxygen species.

[0078] In order to further investigate the bactericidal effect of Ru3-INH and Ru1-INH, different concentrations of Ru3-INH and Ru1-INH were mixed with M. Smegmatis and then illuminated with green light (LED 520nm, 16mw / cm 2 ) After 20 minutes of irradiation, the bacterial survival rate was tested. Fig.11 The results of the Ru3-INH and M.Smegmatis plate experiments are shown in Fig.12 shown.

[0079] For Mycobacterium smegmatis, low concentrations of Ru3-INH and Ru1-INH both have bactericidal effects after green light excitation, but Ru3-INH has a better bactericidal effect, indicating that the superposition of isoniazid and photodynamic therapy has a better antibacterial effect.

[0080] Embodiment 5:

[0081] This example investigates the cytotoxicity of Ru3-INH and Ru1-INH, and the specific steps are as follows:

[0082] 1. Place normal human breast cells MCF-10A into two 96-well plates (5000 cells per well, total volume 100ul) and culture overnight until the cells adhere to the wall.

[0083] 2. Dissolve Ru3-INH and Ru1-INH in different culture media and prepare different concentrations (5-100uM), then replace the original culture medium in the well with 100ul of drug-containing culture medium.

[0084] 3. After replacing all the culture medium with the drug-containing medium, the two 96-well plates were incubated in a dark incubator for 1 hour. Subsequently, one of the 96-well plates was irradiated with excitation light for 20 minutes, while the other plate was kept in the dark. The two 96-well plates were then incubated in a dark incubator for another 24 hours.

[0085] 4. Use the CCK8 method to detect cell survival rate.

[0086] The results are as follows Fig.13 In the dark, both drugs were non-toxic to cells; after light excitation, Ru1-INH still had no cytotoxicity, but Ru3-INH showed a significant cell-killing effect, the reason being the production of reactive oxygen species, which was not conducive to cell survival. This was verified in the fluorescence experiment, where reactive oxygen species were present in both bacteria and cells after green light excitation.

[0087] Embodiment 6:

[0088] Ginger vesicles are an ideal drug carrier with good biocompatibility and high biosafety. Some plant vesicles have therapeutic effects and can be used for cancer or antibacterial treatment. Therefore, ginger vesicles were selected as the carrier of Ru3-INH in this example. Ginger exosomes were extracted according to the reported differential centrifugation method and characterized accordingly: TEM, particle size, and the results are as follows Figure 14-15 shown.

[0089] Ru3-INH was loaded into ginger vesicles by high-speed centrifugation. The drug release results of Ru3-INH loaded ginger vesicles over time were as follows: Fig.16 . For different durations of green light (520nm, V≈2.7v, 20mW / cm 2 ) irradiated the Ru3-INH ginger vesicles in PBS to study the changes in the UV spectrum. The results are as follows Fig.17 UV characterization of Ru3-INH before drug loading and UV characterization of Ru3-INH loaded ginger vesicles as shown in Fig.18 shown.

[0090] The drug-loaded ginger vesicles can be released in vitro, and the UV absorption also changes before and after drug loading, indicating that the drug has been successfully loaded; in the UV photolysis release experiment, it can be seen that the Ru3-INH ginger vesicles can achieve drug release under green light excitation.

[0091] Embodiment 7:

[0092] Wounds of the same size were made on the same part of healthy experimental mice, and then 10 μl of Mycobacterium smegmatis liquid was inoculated. The mice were randomly divided into four groups for treatment. Group a was treated with Ru3-INH and green light (Ru3-INH+light), group b was treated with Ru3-INH and placed in a dark room (Ru3-INH+dark), group c was treated with PBS and green light (PBS+light), and group d was treated with PBS and placed in a dark room (PBS+dark). The experimental period was 8 days, and the wound conditions of each group of mice were observed every day. The results are shown in the figure. Fig.19 The percentage of wound area and body weight change over time are shown in Figure 20-21 The wound healing effect of mice in the Ru3-INH+light group was the fastest, and the weight of mice in all groups decreased in the early stage and gradually increased in the later stage, indicating that the drug had no effect on the survival of mice.

[0093] The above examples are merely illustrative of the present invention and do not constitute a limitation on the protection scope of the present invention. All designs that are the same or similar to the present invention fall within the protection scope of the present invention.

Claims

1. A photoactive ruthenium complex, characterized in that The photoactive ruthenium complex structure is shown below:

2. A method for preparing a photoactive ruthenium complex, characterized in that: The following steps are involved: S1. Synthesis of Ru(tpy)Cl3; S2, mixing Ru(tpy)Cl3 and 2,2'-biquinoline, adding a reducing agent, reacting under an inert gas atmosphere, and washing the product with HCI to obtain [Ru(tpy)(biq)(Cl)2]; S3, cis-[Ru(tpy)(biq)(Cl)2] and isoniazid are added to water, reacted under an inert gas, filtered, NH4PF6 is added to the filtrate, the precipitate is collected, and washed to obtain a photoactive ruthenium complex.

3. The method for preparing the photoactive ruthenium complex according to claim 2, characterized in that: The step S1 specifically comprises: dissolving RuCl3·3H2O and 2,2:6',2"-terpyridine in methanol, heating the mixture under an inert gas atmosphere to react, and obtaining Ru(tpy)Cl3.

4. The method for preparing the photoactive ruthenium complex according to claim 2, characterized in that: The mass ratio of Ru(tpy)Cl3 to 2,2'-biquinoline in step S2 is 172:

100.

5. The method for preparing the photoactive ruthenium complex according to claim 2, characterized in that: The reducing agent in step S2 includes LiCl and triethylamine.

6. The method for preparing the photoactive ruthenium complex according to claim 2, characterized in that: In step S2, the inert gas includes argon.

7. The method for preparing the photoactive ruthenium complex according to claim 2, characterized in that: In the step S3, the mass ratio of [Ru(tpy)(biq)(Cl)2], isoniazid and NH4PF6 is 132:68:

163.

8. The method for preparing the photoactive ruthenium complex according to claim 2, characterized in that: In step S3, [Ru(tpy)(biq)(Cl)2] and isoniazid are added to water and reacted under nitrogen at 80°C for 6 hours.

9. Use of the photoactive ruthenium complex as claimed in claim 1 in the preparation of a medicament for treating tuberculosis.

10. The use according to claim 9, characterized in that: The drug for treating tuberculosis includes a drug for inhibiting the growth of Mycobacterium tuberculosis.

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