Light-driven molecular machine and its application in transmembrane delivery of trivalent metal drugs

Abstract

The application discloses a light-driven molecular machine and application thereof in transmembrane delivery of trivalent metal drugs. The molecular machine has a light-driven molecular motor based on a tetra-substituted crowded olefin, and the light-driven molecular motor is composed of a core unit, a polyethylene glycol chain and a trivalent metal ion coordination group. The application utilizes the directional rotating motion of the molecular motor under light irradiation, embeds the molecular motor into a phospholipid bilayer membrane, and realizes the light-controllable transmembrane transportation of trivalent metal ions through a 'binding-release' mechanism. The molecular machine can selectively complex trivalent metal ions (such as Bi 3+ , Ga 3+ , Ce 3+ , etc.), and accelerate the transmembrane transportation of the ions under light driving, so as to destroy the ion balance between the inside and outside of bacteria. Experiments prove that the system has significant light-controlled antibacterial activity on Staphylococcus aureus. The application has the advantages of controllable structure, precise time and space, easy derivatization and the like, and has a good application prospect in the fields of antibacterial treatment and biological medicines.

Description

Technical Field

[0001] This invention belongs to the fields of chemical biology and pharmaceutical technology, specifically relating to a light-driven molecular machine and its application in transmembrane delivery of trivalent metal drugs. Background Technology

[0002] Trivalent metal drugs have a long history of application in clinical medicine. Trivalent bismuth preparations, such as bismuth potassium citrate and bismuth salicylate, have been widely used to treat gastric ulcers and Helicobacter pylori infection; trivalent gallium compounds, such as gallium citrate and gallium nitrate, have shown potential in tumor diagnosis and treatment. In recent years, the antibacterial activity of trivalent metal ions has been increasingly recognized. They exert their antibacterial effects through multiple mechanisms, including generating reactive oxygen species, interfering with bacterial metabolism, and damaging DNA, providing new insights into combating bacterial resistance.

[0003] However, the clinical application of trivalent metal drugs faces a key bottleneck—low intracellular drug accumulation. This stems from the lack of natural transmembrane transport proteins in organisms that specifically recognize and transport trivalent metal ions. The phospholipid bilayer of the cell membrane has naturally low permeability to polar molecules and charged ions. Trivalent metal ions have high charge density and strong hydration, making passive diffusion across the hydrophobic regions of the membrane difficult. This necessitates high concentrations of trivalent metal drugs to achieve therapeutic effects, but high concentrations often carry the risk of cytotoxicity, limiting their application.

[0004] To overcome this obstacle, researchers have developed artificial molecular machines for transmembrane transport of metal ions. These molecules can insert into the phospholipid bilayer, achieving selective transmembrane ion transport by forming ion channels or acting as mobile carriers. Research on artificial molecular machines for monovalent ions such as potassium and sodium, and divalent ions such as calcium and magnesium, is relatively mature, laying the foundation for understanding the ion transmembrane mechanism. To date, research on artificial molecular machines for trivalent metal ions is almost nonexistent. This is a scientific challenge that has not yet been fully explored because molecular machines capable of effectively "binding" trivalent ions, traversing the hydrophobic region of the membrane, and then "releasing" them within the membrane place stringent requirements on the complexing ability and selectivity of the ligands—overly strong coordination makes intracellular release difficult, while underly weak coordination fails to effectively load ions to cross the membrane barrier. This unique challenge makes simply applying the design principles of molecular machines for monovalent and divalent ions ineffective; therefore, there is an urgent need to develop novel artificial molecular machines specifically for trivalent metal ions.

[0005] To address the aforementioned technological gaps and scientific challenges, this invention reports for the first time a class of artificial transmembrane delivery systems specifically designed for trivalent metal ions, providing a novel strategy for the precise delivery of trivalent metal drugs. Summary of the Invention

[0006] This invention aims to address the problems of low intracellular accumulation and limited efficacy of trivalent metal drugs due to the lack of natural transmembrane transport proteins in existing technologies, as well as the technological gap in selective transmembrane delivery of trivalent metal ions using existing light-driven molecular machines. It provides a light-driven molecular machine and its application in transmembrane delivery of trivalent metal drugs. Based on a light-driven unidirectional rotating molecular motor, this invention constructs a "bind-release" trivalent metal ion transport system that can be embedded in a phospholipid bilayer. Under light-driven illumination, it accelerates the transmembrane transport of trivalent metal ions, disrupting the intracellular and extracellular ion balance of bacteria, and achieving light-controlled antibacterial activity against Staphylococcus aureus. This invention not only provides new insights into the rational design of trivalent metal drugs but also opens up a new pathway to enhance drug efficacy by actively promoting the entry of trivalent metal drugs into cells, showing significant application prospects in the field of antibacterial therapy.

[0007] To achieve the above objectives, the technical solution adopted by the present invention is as follows: In a first aspect, the present invention provides a light-driven molecular machine having light-driven molecular motors (LDMMs) based on tetrasubstituted crowded olefins, with the following general structural formula:

[0008] Where n=3 or 9, representing polyethylene glycol (PEG) chains of different lengths; R is a trivalent metal ion coordinating group selected from cycloheptatrienolone, catechol, hydroxyl groups and their derivatives. The molecular motor has the following structural features: 1. Photo-driven core unit: a photo-driven unidirectional rotating molecular motor framework based on tetrasubstituted crowded olefins, which can undergo directional conformational changes under alternating light irradiation; 2. Metal ion coordination unit: a trivalent metal ion coordination group located on both sides of the molecular backbone, selected from one of cycloheptatrienolone, catechol, hydroxyl group and its derivatives; 3. Connection method: Polyethylene glycol (PEG) is used to connect the coordinating groups and the core unit through nucleophilic substitution, condensation reaction and click chemistry reaction.

[0009] Furthermore, the flexible connecting arm is a polyethylene glycol chain with different degrees of polymerization, and the polyethylene glycol chain is PEG9; Furthermore, the trivalent metal ion coordinating group R is independently selected from one or more of cycloheptatrienolone, catechol, hydroxyl groups and their derivatives, preferably cycloheptatrienolone.

[0010] Furthermore, the molecular structure of the light-driven molecular motor is any one of the following LDMM1-LDMM4: .

[0011] Furthermore, the molecular motor forms a complex with trivalent metal ions, wherein the trivalent metal ions are selected from Ga. 3 + Ce 3+ Bi 3+ One or more of them.

[0012] Secondly, this invention provides a method for preparing the aforementioned light-driven molecular machine. The preparation of the light-driven molecular motor based on a tetrasubstituted crowded olefin involves connecting a trivalent metal ion coordinating group R to polyethylene glycol (PEG) via a condensation reaction, a nucleophilic substitution reaction, and a click chemistry reaction. Specifically, it includes the following steps: (1) Preparation of the core unit of azide-modified light-driven molecular motor based on tetrasubstituted crowded olefins; (2) The trivalent metal ion coordination group R is linked to the PEG molecule through condensation reaction or nucleophilic substitution reaction to prepare an alkynyl PEG chain modified coordination group intermediate; (3) The intermediate in step (2) is coupled with the core unit in step (1) via a Cu-catalyzed Click reaction, and after purification, a photo-driven molecular motor is obtained. This invention provides a chemical synthesis method for LDMM1-LDMM4. The synthetic route is as follows, including the following steps: .

[0013] Synthesis of the core unit: The synthesis was performed following published literature (Angew. Chem. Int. Ed. 2022, 61, e202204605) and Chinese patent (CN 114478504 A). Naphthalene was used as a substrate, and a Friedel-Crafts reaction was conducted under the catalysis of Lewis acid AlCl3 to generate a cyclic ketone product. This was subsequently converted to a thione via Lawson's reagent. This synthesized the rotor part of the molecular machine. Using 9-thioxanthone as a substrate, a thione molecule was generated through sequential bromination and Lawson reactions. This thione molecule was further condensed with hydrazine to generate the stator part of the molecular machine—a hydrazone derivative. The naphthalene derivative containing the thione group and the dibromo-substituted hydrazone underwent a Barton-Kellogg reaction under the oxidation of MnO2 to generate a cyclic thioethane derivative. This molecule was reduced by P(III) to the core structure of a tetrasubstituted olefin. Subsequently, a Sonogashira coupling reaction under Pd catalysis yielded the product molecule. TBAF was used to rapidly deprotect the silane protecting group, generating a product molecule containing a hydroxyl group. Finally, DPPA was used as the azide-reducing agent to synthesize the core structure of the molecular machine containing an azide group in a mild and safe manner.

[0014] Synthesis of metal-bonded and linking units: Cycloheptatrienolone was reacted with formaldehyde under alkaline and high-temperature conditions to obtain methylene hydroxylated juniper alcohol derivative 1. Subsequently, it underwent a halogen nucleophilic substitution reaction with 1-bromo-3,6,9,12-tetraoxapentadecan-14-yne at high temperature to obtain product 2.

[0015] Using alkynyl decaglycol as a raw material, it undergoes an Appel reaction with CBr4 to obtain product 3, and finally undergoes the same substitution reaction with juniper alcohol derivative 1 under alkaline conditions to obtain product 4.

[0016] Using 3,4-dihydroxybenzoic acid as a raw material, a condensation reaction was carried out with alkynyl decaethylene glycol under high temperature and catalysis of p-toluenesulfonic acid to obtain product 5.

[0017] Finally, compounds 2, 4, 5, and alkynyl decaglycol were reacted with the core unit via Cu-catalyzed Click reactions to yield LDMM1-LDMM4. The molecular structure of the molecular motor was characterized and verified by 1H NMR spectroscopy, 1C NMR spectroscopy, or high-resolution mass spectrometry.

[0018] The above compounds possess membrane anchoring properties and the ability to "bind-release" metal ions.

[0019] The molecular motor described in this invention possesses an amphiphilic structure and can spontaneously insert into the bacterial phospholipid bilayer membrane. Utilizing the fluorescence resonance energy transfer (FRET) phenomenon between the molecular machine and Nile Red (NR), this study first measured the excitation and emission spectra of both in different solvent systems (90% H₂O + 10% DMSO and a bacterial membrane simulation environment). The degree of spectral overlap indicates that the molecular motor has good affinity for Gram-positive bacterial membranes. Preferably, it can effectively anchor to Staphylococcus aureus membranes.

[0020] The core of the molecular motor described in this invention for achieving transmembrane transport of trivalent metal ions lies in its working mechanism of "extracellular binding-photodriven transport-intracellular release". To verify the feasibility of this mechanism, four LDMMs and different trivalent metal ions (Ce) were systematically evaluated. 3+ Bi 3+ Ga 3+ The binding properties of glutathione (GSH) and its release behavior in a simulated intracellular environment were investigated. Furthermore, to simulate the competitive binding of active thiol substances to metal ions in the intracellular environment, different concentrations of glutathione (GSH) or acetylcysteine ​​(NAC) were added to the juniper alcohol-metal ion complex system.

[0021] The coordination characteristics of LDMM with trivalent metal ions were determined by ultraviolet-visible absorption spectroscopy using the continuous variation method and the molar ratio method.

[0022] The spectral changes (unit: nm) of the binding and release capabilities of LDMM with three trivalent metal ions are shown in the table below:

[0023] Thirdly, the present invention provides the application of the above-mentioned light-driven molecular machine in the preparation of antibacterial drugs, which has the effects of transmembrane transport of trivalent metal ions and antibacterial effect.

[0024] Furthermore, the antibacterial drug is used to inhibit methicillin-resistant Staphylococcus aureus (MRSA). Methicillin- resistance Staphylococcus aureus The growth of MRSA.

[0025] Furthermore, the light-driven molecular motor based on tetrasubstituted crowded olefins achieves antibacterial activity through the following mechanism: (a) Molecular motors are embedded in the phospholipid bilayer of the bacterial cell membrane; (b) Under external light stimulation, the molecular motor rotates in one direction; (c) The complexed trivalent metal ions are transported across the membrane into the bacterial cell via a “bind-release” mechanism; (d) Disruption of the intracellular and extracellular ion balance of bacteria, leading to bacterial death.

[0026] This invention provides a specific application of the aforementioned light-driven molecular motors: Using MRSA as a model strain, this invention quantitatively analyzes the effects of different molecular motors (LDMM1-LDMM4) on Bi using ICP-MS. 3+ Ce 3+ Ga 3+ Transmembrane transport efficiency of three metal ions. The selected metal ion sources were colloidal bismuth citrate, cerium trichloride, and gallium nitrate.

[0027] The results showed that LDMM2 and Bi 3+ The combination of these molecules all exhibited the highest intracellular accumulation enhancement effect in the strains. After activation with ultraviolet light (365 nm, 10 mW / cm²) for 5 minutes, the light-illuminated group was 1.5 times that of the dark-field control group. Free bismuth is difficult to enter cells. Other molecular motor-metal ion combinations also showed varying degrees of transport enhancement effects, but the LDMM2-Bi combination was the most significant, indicating that this molecular motor has selective transmembrane transport capabilities for trivalent bismuth ions.

[0028] Based on the results of intracellular accumulation measurement, this invention further employs colony counting to evaluate the photo-controlled synergistic antibacterial effect of the LDMM2 and CBS combination on the strain. Under UV light activation, treatment with the LDMM2 and CBS complex reduced the Staphylococcus aureus colony count by 1.7 Log under light. 10CBS refers to colloidal bismuth subcitrate.

[0029] This invention is the first to report a light-driven molecular motor that can be used for transmembrane transport of trivalent metal ions, filling a technological gap in this field. Among them, LDMM2 exhibits the best ability to transport trivalent metal ions and synergistic antibacterial activity.

[0030] Fourthly, the present invention provides a light-controlled antibacterial method, comprising the following steps: After co-incubating the above-mentioned light-driven molecular motor based on tetrasubstituted crowded olefins, trivalent metal ions, and bacteria, ultraviolet light with a wavelength of 365 nm is applied to drive the molecular motor to rotate, thereby realizing the transmembrane transport of trivalent metal ions and killing bacteria.

[0031] Compared with existing technologies, this invention has the following advantages: it achieves ion transmembrane transport through a "binding-release" mechanism rather than a complete "molecular drilling" mechanism, maintaining selectivity for trivalent metal ions. The synthesized LDMM2, i.e., juniperol, with its coordinating group, exhibits moderate binding affinity for trivalent metal ions. Combined with a competitive release mechanism using intracellular active thiol groups, it forms a complete "extracellular binding-photodriven transport-intracellular release" cycle, demonstrating a significant photocontrolled synergistic antibacterial effect against Staphylococcus aureus. This invention provides a novel strategy for the precise delivery of trivalent metal drugs, possessing significant theoretical implications and promising clinical translational prospects in the field of antibacterial therapy. Attached Figure Description

[0032] Figure 1 The following are FRET fluorescence intensity diagrams of LDMM2 and Nile Red provided by this invention; wherein, (a) is a fluorescence image of bacteria under a confocal microscope; (b) is the fluorescence intensity distribution corresponding to (a); and (c) is a quantitative comparison of fluorescence intensity in different groups.

[0033] Figure 2 The LDMM2 provided by this invention is for Bi 3+The UV-Vis spectra of ion binding and release are shown in Figure 1. (a) is the UV-Vis spectrum of CBS added to LDMM2 solution; (b) is the binding ratio curve of [Bi] and LDMM2, with the horizontal axis representing the molar ratio of [Bi] to [LDMM-PEG10-Hino] and the vertical axis representing the absorbance at the maximum absorption peak (410 nm), where [LDMM-PEG10-Hino] represents LDMM2; (c) is the UV-Vis spectrum of GSH added to LDMM2-Bi solution; and (d) is the binding ratio curve of GSH and LDMM-PEG10-Hino-Bi, with the horizontal axis representing the molar ratio of [GSH] to [LDMM-PEG10-Hino-Bi] and the vertical axis representing the absorbance at the maximum absorption peak (410 nm), where [LDMM-PEG10-Hino-Bi] represents the LDMM2-Bi complex.

[0034] Figure 3 This invention provides a method for determining the transport of Bi in Staphylococcus aureus using ICP-MS with LDMM1-LDMM4. 3+ The cumulative results are shown in the graph.

[0035] Figure 4 This invention provides a method for determining the transport of Bi in Staphylococcus aureus using ICP-MS. 3+ Ga 3+ Ce 3+ The cumulative results of ions are shown in the figure; where Dark represents the dark treatment group, UV represents the ultraviolet activation group, and MM2 represents LDMM2.

[0036] Figure 5 This is a diagram illustrating the synergistic antibacterial effect of LDMM2 and CBS provided by the present invention.

[0037] Figure 6 This is a schematic diagram of the mechanism of LDMM2 provided by the present invention.

[0038] It should be noted that in the attached figure, * indicates statistically significant difference, * indicates P<0.05, ** indicates P<0.01, and *** indicates P<0.001; T represents the standard deviation (SD) of three independent experiments (n=3). Detailed Implementation

[0039] The present invention will be further described in detail below with reference to embodiments, but the embodiments of the present invention are not limited thereto. Unless otherwise specified, the experimental methods in the following embodiments are conventional methods. Unless otherwise specified, the experimental materials used in the following embodiments are commercially available.

[0040] Example 1: Synthesis of a light-driven molecular machine The synthetic route for the light-driven molecular motor LDMM1 is as follows:

[0041] Synthesis of Compound 1 Hinokitiol (5.00 g, 30.4 mmol) and potassium hydroxide (2.05 g, 36.5 mmol) were dissolved in 50 mL of formaldehyde in methanol (formaldehyde mass fraction 37%), and the mixture was heated to 60 °C and stirred for 6 hours. The reaction progress was monitored by thin-layer chromatography. After the reaction, the reaction solution was cooled to room temperature, the pH was adjusted to 2-3 with 1M dilute hydrochloric acid, and 100 mL of dichloromethane was added for extraction. The organic phase was separated and retained. The aqueous phase was extracted three times with dichloromethane (50 mL × 3). The organic phases were combined, washed once with saturated sodium chloride solution, and dried over anhydrous sodium sulfate. The desiccant was removed by filtration, and the solvent was removed by vacuum distillation in a 40 °C water bath to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: methanol: dichloromethane = 1:10), the target component was collected, and the solvent was removed by vacuum distillation to obtain pure product 1 (hydroxymethylated juniperol) as a red solid with a yield of 70% (4.12 g).

[0042] The structure of compound 1 is characterized as follows: 1 HNMR (600 MHz, CDCl3) δ 7.62 (d, J = 10.3 Hz, 1H),7.20 (s, 1H), 6.88 (d, J = 10.3 Hz, 1H), 4.68 (s, 2H), 2.75 (hept, J = 6.8 Hz, 1H), 1.12 (d, J = 7.2 Hz, 6H). 13 CNMR (151 MHz, CDCl3) δ 172.9, 165.2, 158.5,139.6, 136.6, 126.2, 119.4, 63.2, 38.4, 23.2. Synthesis of Compound 2 Compound 1 (hydroxymethylated juniperol, 0.50 g, 2.57 mmol) and 1-bromo-3,6,9,12-tetraoxapentadecano-14-yne (0.84 g, 2.83 mmol) were dissolved separately in 15 mL of N,N-dimethylformamide. Anhydrous potassium carbonate (0.71 g, 5.15 mmol) was added, and the mixture was heated to 50 °C with stirring for 16 hours. The reaction progress was monitored by thin-layer chromatography. After the reaction was completed, the reaction solution was cooled to room temperature and quenched with saturated ammonium chloride aqueous solution. The mixture was extracted with 30 mL of dichloromethane, and the organic phase was separated. The aqueous phase was extracted three times with dichloromethane (30 mL × 3). The organic phases were combined, washed once with saturated sodium chloride solution, and dried over anhydrous sodium sulfate. The desiccant was removed by filtration, and the solvent was removed by vacuum distillation in a 50 °C water bath to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: methanol: dichloromethane = 1:10), the target component was collected, and the solvent was removed by vacuum distillation to obtain pure product 2 (alkynyl PEG4 chain modified juniper alcohol derivative) as a red oily substance with a yield of 61% (0.64 g).

[0043] The structure of compound 2 is characterized as follows: 1 HNMR (600 MHz, CDCl3) δ 7.41 (d, J = 9.4 Hz, 1H), 6.86 (s, 1H), 6.82 (d, J = 9.4 Hz, 1H), 4.62 (s, 2H), 4.23 (t, J = 5.2 Hz, 2H), 4.17 (d, J = 2.4 Hz, 2H), 3.95 (t, J = 5.1 Hz, 2H), 3.77 – 3.72 (m, 2H), 3.70 –3.60 (m, 10H), 2.84 (hept, J = 6.9 Hz, 1H), 2.41 (t, J = 2.4 Hz, 1H), 1.24 (d, J = 6.9 Hz, 6H). 13 CNMR (126 MHz, CDCl3) δ 179.9, 163.0, 154.4, 145.1, 136.0,125.0, 116.8, 79.7, 74.6, 71.1, 70.7 – 70.6 (m),70.5, 69.4, 69.2, 68.9, 67.2,58.5, 38.9, 23.6. Synthesis of the light-driven molecular motor LDMM1 Compound 2 (a cynomol derivative modified with an alkynyl PEG4 chain, 0.30 g, 0.73 mmol) and the core structure (an azide-modified light-driven molecular motor backbone, 0.19 g, 0.33 mmol) were dissolved in 15 mL of tetrahydrofuran. Copper sulfate aqueous solution (16.67 mg, 0.07 mmol) and sodium ascorbate aqueous solution (26.45 mg, 0.13 mmol) were added sequentially. The reaction mixture was stirred at room temperature for 16 hours. After the reaction was complete, 30 mL of dichloromethane was added for extraction, and the organic phase was separated. The aqueous phase was extracted three times with dichloromethane (30 mL × 3). The combined organic phases were washed once with saturated sodium chloride solution and dried over anhydrous sodium sulfate. The desiccant was removed by filtration, and the solvent was removed by vacuum distillation of the filtrate in a 50 °C water bath to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: methanol: dichloromethane = 1:10), the target component was collected, and the solvent was removed by vacuum distillation to obtain the pure product LDMM1 as a dark green solid with a yield of 74% (0.34 g).

[0044] The structure of compound LDMM1 is characterized as follows: 1 HNMR (600 MHz, CD3OD) δ 8.10 (s, 1H), 7.81 – 7.76 (m, 2H), 7.75 –7.70 (m, 3H), 7.67 (s, 1H), 7.51 (t, J = 7.9 Hz, 2H), 7.47 (d, J = 8.3 Hz, 1H), 7.21 (d, J = 9.6 Hz, 1H), 7.18 (t, J = 7.4 Hz, 1H), 7.03 (t, J = 6.9 Hz, 4H), 6.99 (d, J = 9.9 Hz, 1H), 6.79 – 6.75 (m, 1H), 6.73 (d, J = 7.5 Hz, 1H), 6.60(d, J = 1.7 Hz, 1H), 4.65 (t, J = 6.6 Hz, 2H), 4.62 (s, 2H), 4.61 (d, J= 2.5Hz, 4H), 4.56 – 4.48 (m, 2H), 4.42 – 4.29 (m, 2H), 4.24 – 4.16 (m, 5H), 3.87(q, J = 4.6 Hz, 4H), 3.71 (dd, J = 15.3, 5.8 Hz, 1H), 3.67 – 3.63 (m, 6H), 3.60 – 3.58 (m, 2H), 3.57 – 3.53 (m, 6H), 3.51 (dt, J = 5.7, 3.1 Hz, 6H), 3.49 –3.45 (m, 4H), 3.09 – 3.04 (m, 2H), 2.93 – 2.84 (m, 2H), 2.72 (t, J = 6.5 Hz, 2H), 2.64 (d, J = 15.6 Hz, 1H), 1.24 (dd, J = 6.9, 3.1 Hz, 12H), 0.72 (d, J =6.9 Hz, 3H). 13 CNMR (151 MHz, CD3OD_SPE) δ 179.8, 163.6, 155.7, 148.8, 147.9,147.3, 145.9, 145.6, 141.3, 138.9, 137.0, 136.8, 135.7, 135.5, 134.6, 132.5,131.9, 131.8, 130.8, 130.5, 130.0, 129.2, 128.8, 128.6, 128.1, 126.7, 126.4,126.1, 125.6, 125.5, 125.4, 125.0, 122.9, 122.8, 118.1, 87.3, 86.5, 83.6,83.1, 71.6, 71.5 – 71.2 (m), 70.5, 70.5, 70.1, 70.0 (d, J = 2.2 Hz), 65.0,64.8, 63.3, 50.1, 49.9, 40.6, 39.8, 39.2, 23.9, 22.2, 21.9, 19.7. The synthetic route for the light-driven molecular motor LDMM2 is as follows:

[0045] Synthesis of Compound 3 The compound monoethynyldecaglycol (0.50 g, 1.01 mmol) was dissolved in 15 mL of dichloromethane and cooled to 0 °C in an ice bath. Triphenylphosphine (0.40 g, 1.51 mmol) and carbon tetrabromide (0.50 g, 1.51 mmol) were added sequentially, and the mixture was slowly restored to room temperature and stirred for 16 hours. The reaction progress was monitored by thin-layer chromatography. After the reaction was completed, 30 mL of water was added to quench the reaction, and the mixture was extracted three times with ethyl acetate (30 mL × 3). The organic phases were combined, washed once with saturated sodium chloride solution, and dried over anhydrous sodium sulfate. The desiccant was removed by filtration, and the solvent was removed by vacuum distillation in a 50 °C water bath to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: methanol:dichloromethane = 1:10), and the target fraction was collected. The solvent was removed by vacuum distillation to obtain pure product 3 (bromomonyynyldecaglycol) as a pale yellow oil with a yield of 78% (0.44 g).

[0046] The structure of compound 3 is characterized as follows: 1 HNMR (400 MHz, CDCl3) δ 4.15 (d, J = 2.4 Hz, 2H), 3.76 (t, J = 6.3 Hz, 2H), 3.69 – 3.57 (m, 36H), 3.42 (t, J = 6.3 Hz, 2H), 2.41(t, J = 2.4 Hz, 1H); 13 CNMR (101 MHz, CDCl3) δ 79.7, 74.6, 71.2, 70.6, 70.6 –70.5 (m), 70.4, 69.1, 58.4, 30.4. Synthesis of Compound 4 Compound 3 (bromomonynedecaglycol, 0.40 g, 0.71 mmol) and compound 1 (hydroxymethylated juniperol, 0.15 g, 0.79 mmol) were dissolved in 15 mL of N,N-dimethylformamide, and anhydrous potassium carbonate (0.22 g, 1.59 mmol) was added. The mixture was heated to 50 °C and stirred for 16 hours. The reaction progress was monitored by thin-layer chromatography. After the reaction was completed, the reaction solution was cooled to room temperature and quenched with saturated ammonium chloride aqueous solution. The solution was extracted with 30 mL of dichloromethane, and the organic phase was separated. The aqueous phase was extracted three times with dichloromethane (30 mL × 3). The organic phases were combined, washed once with saturated sodium chloride solution, and dried over anhydrous sodium sulfate. The desiccant was removed by filtration, and the solvent was removed by vacuum distillation in a 50 °C water bath to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: methanol: dichloromethane = 1:10), the target component was collected, and the solvent was removed by vacuum distillation to obtain pure product 4 (PEG10 chain-linked juniper alcohol derivative) as a red oily substance with a yield of 43% (0.23 g).

[0047] The structure of compound 4 is characterized as follows: 1 HNMR (600 MHz, CDCl3) δ 7.41 (d, J = 9.3 Hz, 1H), 6.82 (s, 1H), 6.78 (d, J = 9.3 Hz, 1H), 4.58 (s, 2H), 4.18 (t, J = 5.0 Hz, 2H), 4.13 (d, J = 2.4 Hz, 2H), 3.90 (t, J = 5.0 Hz, 2H), 3.71 – 3.67 (m, 2H), 3.60 –3.64 (m, 2H), 3.62 – 3.55 (m, 32H), 2.80 (h, J = 6.8 Hz, 1H), 2.40 (t, J = 2.4Hz, 1H), 1.19 (d, J = 6.9 Hz, 6H); 13 CNMR (151 MHz, CDCl3) δ 179.5, 162.7,154.0, 145.2, 135.4, 124.8, 116.6, 79.6, 74.6, 70.9, 70.6 – 70.4 (m), 70.3,69.2, 69.0, 68.7, 66.2, 58.3, 38.7, 23.4. Synthesis of the light-driven molecular motor LDMM2 Compound 4 (a PEG10-linked juniper alcohol derivative, 0.15 g, 0.22 mmol) and the core structure (an azide-modified light-driven molecular motor backbone, 0.06 g, 0.10 mmol) were dissolved in 15 mL of tetrahydrofuran. Copper sulfate aqueous solution (5.1 mg, 0.02 mmol) and sodium ascorbate aqueous solution (8.1 mg, 0.04 mmol) were added sequentially. The reaction was stirred at room temperature for 16 hours, and the reaction progress was monitored by thin-layer chromatography. After the reaction was complete, 30 mL of dichloromethane was added for extraction, and the organic phase was separated. The aqueous phase was extracted three times with dichloromethane (30 mL × 3). The combined organic phases were washed once with saturated sodium chloride solution and dried over anhydrous sodium sulfate. The desiccant was removed by filtration, and the solvent was removed by vacuum distillation in a 50 °C water bath to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: methanol: dichloromethane = 1:10), the target component was collected, and the solvent was removed by vacuum distillation to obtain the pure product LDMM2 as a dark green solid with a yield of 83% (0.16 g).

[0048] The structure of compound LDMM2 is characterized as follows: 1 HNMR (600 MHz, DMSO) δ 8.21 (s, 1H), 7.89 –7.84 (m, 3H), 7.80 (d, J = 8.1 Hz, 1H), 7.63 (d, J = 7.9 Hz, 2H), 7.57 (d, J =9.4 Hz, 2H), 7.54 (d, J = 8.3 Hz, 1H), 7.26 – 7.20 (m, 1H), 7.04 (dd, J = 8.1, 1.8 Hz, 1H), 6.96 (d, J = 9.4 Hz, 2H), 6.90 (s, 2H), 6.80 (t, J = 7.6 Hz, 1H), 6.68 (d, J = 8.6 Hz, 1H), 6.57 (d, J = 1.8 Hz, 1H), 5.31 (t, J = 5.5 Hz, 2H), 4.62 (t, J = 6.7 Hz, 2H), 4.55 (s, 2H), 4.45 (d, J= 2.7 Hz, 2H), 4.42 (d, J =6.7 Hz, 4H), 4.38 – 4.29 (m, 2H), 4.20 – 4.12 (m, 2H), 3.80 – 3.71 (m, 4H), 3.64 – 3.58 (m, 4H), 3.56 – 3.48 (m, 6H), 3.49 – 3.43 (m, 60H), 3.06 (t, J =6.7 Hz, 2H), 2.87 (hept, J = 6.8 Hz, 2H), 2.74 (t, J = 6.8 Hz, 2H), 2.62 (d, J =15.8 Hz, 1H), 1.20 (d, J = 6.9 Hz, 12H), 0.65 (d, J = 6.9 Hz, 3H). 13 CNMR (151MHz, DMSO) δ 177.4, 161.6, 152.3, 147.1, 146.8, 146.4, 144.0, 143.7, 139.7,137.2, 134.8, 133.6, 132.7, 132.4, 130.7, 130.6, 130.3, 129.7, 129.3, 128.8,128.2, 128.1, 128.0, 127.9, 127.8, 126.2, 124.9, 124.5, 124.3, 124.1, 124.0,123.9, 121.3, 121.0, 115.8, 87.6, 86.7, 82.0, 81.4, 70.1, 69.9 – 69.7 (m), 68.9, 68.9, 68.7, 68.5, 63.6, 63.4, 61.1, 48.1, 47.8, 37.7, 37.5, 23.3, 21.0,20.6, 19.2. The synthetic route for the light-driven molecular motor LDMM3 is as follows:

[0049] Synthesis of Compound 5 3,4-Dihydroxybenzoic acid (0.50 g, 3.25 mmol) and the compound monoalkynyldecaethylene glycol (1.61 g, 3.24 mmol) were dissolved in 25 mL of toluene, and p-toluenesulfonic acid (0.11 g, 0.65 mmol) was added. The mixture was heated to reflux and stirred for 6 hours, with the reaction progress monitored by thin-layer chromatography. After the reaction was completed, the reaction solution was cooled to room temperature, and the solvent was removed by vacuum distillation to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: methanol:dichloromethane = 1:15), and the target fraction was collected. The solvent was removed by vacuum distillation to obtain product 5 (3,4-dihydroxybenzoic acid-PEG10-alkynyl ester), a pale yellow oil with a yield of 76% (1.56 g).

[0050] The structure of compound 5 is characterized as follows: 1 HNMR (400 MHz, CDCl3) δ 7.63 – 7.45 (m, 2H), 6.88 (s, 1H), 4.44 – 4.35 (m, 2H), 4.16 (d, J = 2.4 Hz, 2H), 3.80 – 3.74 (m, 2H), 3.74 – 3.55 (m, 36H), 2.42 (t, J = 2.3 Hz, 1H). 13 CNMR (101 MHz, CDCl3) δ 166.6,150.0, 144.2, 123.3, 121.9, 116.9, 115.0, 79.7, 74.8, 70.9, 70.6 – 70.4(m),69.4, 69.1, 63.9, 58.4. Synthesis of the light-driven molecular motor compound LDMM3 Compound 5 (3,4-dihydroxybenzoic acid-PEG10-alkynyl ester, 0.10 g, 0.16 mmol) and the core structure (azide-modified light-driven molecular motor backbone, 0.04 g, 0.07 mmol) were dissolved in 15 mL of tetrahydrofuran. Copper sulfate aqueous solution (3.59 mg, 0.01 mmol) and sodium ascorbate aqueous solution (5.69 mg, 0.03 mmol) were added sequentially. The reaction was stirred at room temperature for 16 hours. After the reaction was complete, the solvent was removed by vacuum distillation in an 80 °C water bath to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: methanol:dichloromethane = 1:10), and the target fraction was collected. The solvent was removed by vacuum distillation to obtain the pure product LDMM3 as a pale yellow solid, with a yield of 53% (0.07 g).

[0051] Compound LDMM3 exhibits poor solubility in common deuterated reagents, thus preventing the acquisition of a definitive NMR spectrum. High-resolution mass spectrometry (HR-MS) characterization is shown as: HR MS(ESI) (m / z): [M+2H] 2+ calcd for C95H124N6O28S2 ,914.9104 ,found 914.9139. The synthesis route of LDMM4 is as follows:

[0052] Synthesis of the light-driven molecular motor compound LDMM4 Compound 3 (monoyne decaglycol, 0.12 g, 0.24 mmol) and the core structure (azide-modified light-driven molecular motor framework, 0.06 g, 0.11 mmol) were dissolved in 15 mL of tetrahydrofuran. Copper sulfate aqueous solution (5.48 mg, 0.02 mmol) and sodium ascorbate aqueous solution (8.70 mg, 0.04 mmol) were added sequentially. The reaction was stirred at room temperature for 16 hours, and the reaction progress was monitored by thin-layer chromatography. After the reaction was complete, the solvent was removed by vacuum distillation in an 80 °C water bath to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: methanol:dichloromethane = 1:10), and the target fraction was collected. The solvent was removed by vacuum distillation to obtain the pure product LDMM4 (a control molecule without coordinating groups) as a pale yellow solid, with a yield of 82% (0.14 g).

[0053] The structure of compound LDMM4 is characterized as follows: 1 HNMR (600 MHz, CDCl3) δ 7.78 – 7.73 (m, 3H),7.70 (d, J = 7.6 Hz, 1H), 7.48 (dd, J = 14.5, 8.0 Hz, 2H), 7.44 (d, J = 8.2 Hz,1H), 7.40 (s, 1H), 7.23 – 7.17 (m, 2H), 6.99 (dd, J = 8.1, 1.8 Hz, 1H), 6.81(t, J = 7.6 Hz, 1H), 6.75 (d, J = 8.2 Hz, 1H), 6.67 (d, J = 1.7 Hz, 1H), 4.69(s, 2H), 4.60 (t, J= 7.4 Hz, 4H), 4.31 (td, J = 6.8, 3.4 Hz, 2H), 4.19 (t, J =6.5 Hz, 1H), 3.71 – 3.69 (m, 4H), 3.65 – 3.55 (m, 76H), 3.05 (t, J = 7.0 Hz, 2H), 2.69 (t, J = 6.9 Hz, 2H), 2.64 (d, J = 15.5 Hz, 2H), 0.77 (d, J = 6.9 Hz, 3H). 13 CNMR (151 MHz, CDCl3) δ 147.5, 146.3, 145.2, 144.8, 139.8, 137.6, 136.0,135.6, 134.5, 133.1, 131.6, 130.8, 130.6, 129.4, 129.3, 128.7, 127.9, 127.8,127.4, 126.6, 125.9, 124.9, 124.4, 123.9, 123.1, 123.0, 121.1, 121.0, 85.6,84.8, 83.1, 82.4, 72.6, 70.6 – 70.4 (m), 70.1, 69.7, 69.6, 64.6, 64.4, 61.6,48.9, 48.8, 39.7, 37.9, 21.7, 21.5, 19.6. Example 2: Membrane Anchoring Experiment of a Photo-Driven Molecular Machine To verify the localization of the light-driven molecular motor in the bacterial membrane and its energy transfer relationship with the membrane probe Nile Red, FRET analysis was performed using fluorescence spectroscopy.

[0054] Fluorescence spectroscopy was performed using a steady-state fluorescence spectrometer equipped with a temperature-controlled sample cell support. LDMM molecular motors and Nile Red were prepared as stock solutions using dimethyl sulfoxide (DMSO). The buffer system was Tris-HCl buffer (pH 7.4, containing 10% DMSO). Staphylococcus aureus was used as the bacterial membrane system. Excitation and emission spectra of LDMM and Nile Red were measured separately in a 90% H₂O + 10% DMSO mixed solution. The excitation wavelength for LDMM was set to 405 nm, and the emission spectrum was collected in the range of 420–600 nm. The excitation wavelength for Nile Red was set to 550 nm, and the emission spectrum was collected in the range of 570–700 nm. Simultaneously, the absorption spectrum of Nile Red in the range of 450–600 nm was measured. The spectral acquisition conditions were: excitation and emission slit widths of 5 nm, scan rate of 120 nm / min, and isothermal temperature of 25 ± 0.5 ℃.

[0055] Experimental results showed that LDMM exhibited a characteristic emission peak at 488 nm under 405 nm excitation, with an emission spectrum covering the 480-520 nm range. Nile red exhibited a characteristic emission peak at 630 nm under 550 nm excitation, and its absorption spectrum partially overlapped with that of LDMM in the 480-520 nm range, preliminarily meeting the spectral overlap condition required for FRET. LDMM and Nile red were co-dissolved in a 90% H2O + 10% DMSO mixed solution to a final concentration of 5 μM for both. Emission spectra were collected in the 450-700 nm range under 405 nm excitation. Control groups included LDMM solution (5 μM) and Nile red solution (5 μM) alone, measured under the same conditions. The FRET effect was determined by comparing the intensity changes of the characteristic emission peak (630 nm) of Nile red.

[0056] like Figure 1 As shown, the experimental results indicate that under 405 nm excitation, the emission intensity of Nile Red at 630 nm is significantly enhanced in the presence of LDMM compared to the Nile Red alone group, suggesting the existence of energy transfer from LDMM (donor) to Nile Red (acceptor).

[0057] The above results indicate that LDMM can be effectively embedded in the bacterial membrane bilayer, and its emission spectrum has good spectral overlap with the absorption spectrum of the membrane probe Nile Red. The two can undergo FRET in the membrane environment, providing an experimental basis for further research on the localization of molecular motors in bacterial membranes and their photo-driven function.

[0058] Example 3: Simulation Experiment of Binding and Intracellular Release of Trivalent Ions by a Photodriven Molecular Machine The present invention preferably uses LDMM2 and Bi. 3+To verify the molecular motor's ability to bind trivalent metal ions and its release behavior under simulated intracellular conditions, a titration experiment was performed using ultraviolet-visible absorption spectroscopy.

[0059] 1. LDMM2 and Bi 3+ Combination experiment 2 mL of 50 μM LDMM2 Tris-HCl buffer solution (pH 7.4, containing 10% DMSO) was placed in a thermostatic quartz cuvette and the temperature was controlled at 25 ± 0.5 ℃. 1 mM CBS solution (bismuth ion source) was added sequentially using a pipette, 5 μL each time, and mixed by pipetting for 5 seconds. After standing for 30 seconds, the UV-Vis absorption spectra in the 200-800 nm range were recorded. Newly generated absorption peaks in the 250-800 nm range were identified using the difference spectroscopy method (ΔA = Asample - Ablank). The wavelength with the largest change in absorption peak value during the binding experiment was used as the monitoring wavelength. [Bi 3+ Plot the absorbance as a function of [Bi] / [LDMM2] molar ratio on the x-axis and the absorbance change ΔA on the y-axis. 3+ A graph showing the change in [Bi³]. The binding ratio was determined using the tangent method, and the results show that when [Bi³]... + When the ratio of LDMM2 to Bi reaches approximately 0.3, the curve shows an inflection point, indicating that LDMM2 and Bi... 3+ The stoichiometric ratio of the two molecules is approximately 3:1, meaning three LDMM2 molecules are bound to one Bi molecule. 3+ Ions form complexes.

[0060] 2. GSH / NAC competitive release experiment In [Bi 3+ In a complex system with a 1:1 molar ratio of LDMM2 to [LDMM2], 100 mM glutathione solution was added sequentially using a pipette, with 5 μL added each time and mixed by pipetting for 5 seconds. After standing for 30 seconds, the UV-Vis absorption spectra in the 200-800 nm range were recorded. The LDMM2-Bi complex was monitored by differential spectroscopy. 3+ Changes in the characteristic absorption peak of the complex. Another equal volume of the complex system was used, and a competitive release experiment was conducted by successively adding 100 mM acetylcysteine ​​solution using the same method.

[0061] With [GSH] / [LDMM2-Bi 3+ A curve is plotted with the molar ratio on the x-axis and the absorbance change ΔA at the characteristic wavelength on the y-axis. For example... Figure 2 As shown, the experimental results indicate that with the increase of GSH concentration, LDMM2-Bi 3+The characteristic absorption peak of the complex gradually decreased and recovered to the position of the characteristic absorption peak of free LDMM2. When the GSH concentration reached 5 mM, the absorbance recovered to more than 80% of that of free LDMM2, proving that the active thiol substance can competitively bind to and capture trivalent bismuth ions in the complex, thereby achieving effective release of metal ions.

[0062] The above results indicate that LDMM2 has a positive effect on Bi. 3+ It has moderate binding affinity and can effectively capture metal ions in the extracellular environment to form complexes. At the same time, the high concentration of active thiol substances (such as GSH and NAC) in the cell can induce the release of metal ions through competitive binding, which verifies the feasibility of the working cycle of the molecular motor "extracellular binding-photodriven transport-intracellular release".

[0063] Example 4: ICP-MS determination of trivalent bismuth ion transmembrane transport facilitated by a light-driven molecular machine. To verify whether the photoactivated molecular motor LDMM can promote the transmembrane transport of trivalent metal ions and achieve their accumulation in bacteria, this study investigated the mechanism of action of LDMM, a photoresponsive transmembrane molecular motor. Figure 6 As shown, in a high-concentration extracellular environment of bismuth ions, the molecular motor undergoes ligand exchange reactions with bismuth complexes through covalent (or coordination) and non-covalent interactions, thereby binding bismuth ions. Under photo-driven conditions, the tetrasubstituted olefin at the center of the molecular motor undergoes photoisomerization. Simultaneously, polyethylene glycol undergoes irregular thermal motion, causing disturbances in the cell membrane. Finally, the ion carriers bound to bismuth ions migrate to the intracellular region, where, under the influence of ion concentration and active thiol compounds, bismuth ions are released intracellularly, thus enabling the accumulation of bismuth compounds within the cell.

[0064] This invention employs inductively coupled plasma mass spectrometry to accurately quantify intracellular bismuth content.

[0065] Methicillin-resistant Staphylococcus aureus (MRSA) strains were cultured to the logarithmic growth phase, and the bacterial cells were collected by centrifugation and resuspended in fresh culture medium to adjust to the appropriate concentration. The bacterial suspension was aliquoted into centrifuge tubes, and each tube was supplemented with a fixed concentration of CBS (final concentration 50 μM) and different concentrations of LDMM (final concentrations of 0, 2.5, 5.0, 7.5, and 10.0 μM), and incubated at 37 ℃ for 1 hour. After incubation, the bacterial suspensions were divided into two groups: a light group was irradiated with 365 nm ultraviolet light (10 mW·cm²). -2The samples were irradiated for 5 minutes (the dark control group was placed in the dark for the same time). All samples were centrifuged at 4°C (8000 rpm, 5 minutes) to collect bacterial cells, and the supernatant was discarded. The bacterial precipitate was resuspended in pre-cooled PBS buffer and washed, centrifuged, and the supernatant was discarded. This washing was repeated four times to thoroughly remove residual extracellular bismuth ions. Simultaneously, half of the washed bacterial solution was dried and weighed to determine the bacterial weight of each group for normalizing the ICP-MS results. 1 mL of 70% nitric acid was added to the washed bacterial precipitate, and the solution was heated in a metal bath at 95°C for 2 hours until the solution was clear. The digestion solution was diluted with ultrapure water to an appropriate factor, filtered through a 0.22 μM filter membrane, and the bismuth content was determined using an Agilent 8900 ICP-MS. Blank control and standard curve samples were also measured. Intracellular bismuth content was normalized based on bacterial dry weight and expressed as micrograms of bismuth per gram of bacterial cells (μg Bi / g cells).

[0066] like Figure 3 As shown, the results indicate that in the dark, LDMM at various concentrations binds some metal compounds to the cell membrane, leading to a positive correlation between metal and LDMM concentration, but the concentration remains relatively low. However, after UV activation, the intracellular bismuth content in the 10 μM LDMM group increased sharply by approximately 1.5 times compared to the dark control (p<0.0001), and showed a gradual increasing trend with increasing LDMM concentration. These results clearly confirm that photoactivated LDMM can significantly promote the accumulation of bismuth in bacterial cells. Figure 4 The figure shows a summary of the results of LDMM2 on the accumulation of different trivalent metal ions in cells.

[0067] Example 5: Evaluation of the synergistic antibacterial effect of light-driven molecular motor LDMM and bismuth drugs To systematically evaluate the synergistic antibacterial potential of the light-driven molecular motor LDMM and bismuth citrate, this invention employs a checkerboard method and a plate counting method for combined drug sensitivity analysis to determine the optimal dose window for the synergistic effect.

[0068] First, determine the subtoxic concentration range of each treatment factor. Take methicillin-resistant Staphylococcus aureus (MRSA) bacterial suspensions in the logarithmic growth phase and co-incubate them with different concentrations of LDMM (0-20 μM) or bismuth citrate (0-100 μM), or expose them to 365 nm ultraviolet light (10 mW·cm²) for different durations (0-5 minutes). -2After incubation, the bacterial suspension was serially diluted and spread onto solid culture medium, and incubated overnight at 37 °C. The effect of each treatment on bacterial survival was assessed by colony counting. The experiment determined that LDMM concentration ≤10 μM, CBS concentration ≤50 μM, and UV irradiation time of 1 minute were subtoxic doses that did not affect bacterial survival and were used in subsequent synergistic antibacterial experiments. A checkerboard method combined antibacterial experiment was conducted under both light and dark conditions. Methicillin-resistant Staphylococcus aureus (MRSA) bacterial suspension in the logarithmic growth phase was adjusted to a concentration of approximately 10 μM. 6 CFU / mL. Different concentrations of LDMM (final concentrations of 0, 2.5, 5.0, 7.5, and 10.0 μM) and colloidal bismuth subcitrate (final concentrations of 0, 10, 20, 30, 40, and 50 μM) were added to 96-well plates to form a 6×5 concentration matrix. An equal volume of bacterial culture was added to each well, and the plates were incubated at room temperature for 1 hour. After incubation, the light-treated group was exposed to 365 nm ultraviolet light (10 mW·cm²). -2 The irradiation time was 1 minute, and the dark control group was placed in the dark for the same time. Immediately after the light exposure, the bacterial solution in each well was serially diluted, spread on solid culture medium, and incubated overnight at 37 °C. Colony forming units were counted, and the bacterial survival rate of each treatment group was calculated.

[0069] Experimental results showed that, under dark control conditions, none of the combinations of LDMM and bismuth citrate concentrations exhibited significant antibacterial activity, with bacterial survival rates all above 90%. Under 1 minute UV light activation, when the LDMM concentration was 10 μM, even when combined with a low dose of bismuth citrate (10 μM), the antibacterial effect was significantly enhanced compared to the control group (p<0.05), and the bacterial survival rate decreased to approximately 80%. As the concentration of colloidal bismuth citrate increased to 25 μM and 50 μM, the overall colony count showed a decreasing trend; when the bismuth citrate concentration was 50 μM, the bacterial survival rate dropped below 60%. These results indicate that LDMM2 and bismuth citrate can achieve a synergistic photodynamic antibacterial effect in the low-dose range under UV activation conditions.

[0070] like Figure 5 The diagram shows the synergistic antibacterial effect of LDMM2 and CBS provided by this invention. This embodiment clarifies the optimal dose window for the synergistic effect of LDMM and bismuth citrate: 10 μM LDMM2 combined with 50 μM CBS, under 365 nm UV light activation for 1 minute, achieves a significant synergistic antibacterial effect. This result provides key parameters for subsequent mechanism analysis and treatment of animal infection models.

[0071] The above embodiments are only for illustrating the technical concept and features of the present invention, and are intended to enable those skilled in the art to understand the content of the present invention and implement it accordingly. They should not be used to limit the scope of protection of the present invention. All equivalent changes or modifications made in accordance with the spirit and essence of the present invention should be covered within the scope of protection of the present invention.

Claims

1. A light-driven molecular machine, characterized in that, The molecular machine has a light-driven molecular motor based on a tetrasubstituted crowded olefin. The light-driven molecular motor consists of a core unit, a polyethylene glycol chain, and trivalent metal ion coordinating groups, and its structure is shown below: ； The molecular motor forms a complex with a trivalent metal ion selected from one or more of Ga 3+ , Ce 3+ , Bi 3+ .

2. A method for preparing the light-driven molecular machine according to claim 1, characterized in that, The synthetic route for the light-driven molecular motor LDMM1 is as follows: ； The synthetic route for the light-driven molecular motor LDMM2 is as follows: ； The synthetic route for the light-driven molecular motor LDMM3 is as follows: ； The synthetic route for the light-driven molecular motor LDMM4 is as follows: 。 3. The application of the light-driven molecular machine of claim 1 in the preparation of an antibacterial drug, wherein the antibacterial drug is used to inhibit the growth of methicillin-resistant Staphylococcus aureus.

4. Use according to claim 3, characterized in that, The light-driven molecular motor achieves its antibacterial activity through the following mechanism: (a) Molecular motors are embedded in the phospholipid bilayer of the bacterial cell membrane; (b) Under external light stimulation, the molecular motor rotates in one direction; (c) The complexed trivalent metal ions are transported across the membrane into the bacterial cell via a "binding-release" mechanism; (d) Disruption of the intracellular and extracellular ion balance of bacteria, leading to bacterial death.

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