NIR-II small molecule compound with photo-thermal antibacterial effect as well as preparation method and application of NIR-II small molecule compound

Abstract

The invention relates to the technical field of biological medicine, in particular to an NIR-II small-molecule compound with a photo-thermal antibacterial effect and a preparation method and application thereof.According to the D-A-pi-D type NIR-II small-molecule compound, furan or thiophene is introduced to a benzothiopyranium parent nucleus to serve as a pi bridge, a triphenylamine group serves as an electron donor, and the NIR-II small-molecule compound with the photo-thermal antibacterial effect is obtained through synthesis of the D-A-pi-D type NIR-II small-molecule compound with the photo-thermal antibacterial effect. The small molecule fluorescence imaging capability and the molar extinction coefficient of the D-A-pi-D type compound can be effectively improved, so that relatively high photothermal conversion efficiency is achieved. Especially, after the compound I6 is irradiated by 808nm laser, the photothermal conversion rate is the maximum and reaches 61.3%. In photo-thermal antibacterial treatment, deep penetration and local precise heating characteristics of NIR-II photo-thermal can be utilized to quickly destroy drug-resistant bacteria and biological membrane structures thereof, so that effective sterilization is realized. Therefore, the NIR-II small molecule compound prepared by the invention can be applied to the field of antibacterial medicines.

Description

Technical Field

[0001] This invention relates to the field of biomedicine, and in particular to a NIR-II small molecule compound with photothermal antibacterial activity, its preparation method, and its application. Background Technology

[0002] Drug-resistant bacterial infections have posed a serious threat to public health and safety worldwide. The multidrug resistance mechanisms of bacteria to traditional antibiotics have led to frequent infections characterized by high infectivity, high mortality, and high recurrence rates, severely threatening patients' lives and quality of life. As a common clinical disease, the incidence of drug-resistant bacteria continues to rise, significantly prolonging treatment cycles, increasing treatment difficulty, and leading to a marked increase in mortality.

[0003] Traditional antibiotics have revealed numerous drawbacks in combating drug-resistant bacterial infections: First, bacteria rapidly acquire multidrug resistance through gene mutation and horizontal gene transfer, rendering traditional antibiotics ineffective; second, bacterial biofilm structures form physical barriers, hindering drug penetration and making it difficult to achieve effective therapeutic drug concentrations at the lesion site; furthermore, the complex microenvironment at the lesion site and the uncertainty of the host immune response pose significant challenges to precise drug delivery, often leading to unstable treatment outcomes or recurrent infections. Therefore, the development of novel treatment strategies targeting drug-resistant bacterial infections is urgently needed.

[0004] In recent years, photothermal therapy has demonstrated unique advantages as a novel physical antibacterial method. Photothermal therapy uses a specific wavelength light source to convert light energy into heat energy, locally and rapidly raising the temperature of the lesion area, thereby directly destroying bacterial cell structure and its biofilm. In particular, photothermal therapy utilizing the near-infrared II window, due to its greater tissue penetration depth and weaker tissue scattering and autofluorescence, can provide more precise and efficient treatment for deep infections while minimizing damage to surrounding healthy tissue.

[0005] In the selection of photothermal agents, small-molecule organic photothermal agents have attracted widespread attention due to their excellent biocompatibility, degradability, well-defined molecular structure, and ease of modification. Among them, molecules with aggregation-induced emission properties show significantly enhanced photothermal conversion efficiency in the nanoscale state, demonstrating great potential. However, existing small-molecule photothermal agents still face challenges in photothermal conversion efficiency, photostable stability, and targeting when used for antibacterial treatment of deep tissues such as the lungs. Therefore, the development of novel and highly efficient NIR-II small-molecule photothermal agents is of great significance for promoting the clinical application of photothermal therapy in the treatment of drug-resistant bacterial infections. Summary of the Invention

[0006] The purpose of this invention is to address the shortcomings of existing technologies by proposing a NIR-II small molecule compound with photothermal antibacterial activity, its preparation method, and its application. This compound can achieve a rapid increase in temperature in the infected area under 808nm laser irradiation, effectively destroying drug-resistant bacteria and their biofilm structure, thereby achieving highly efficient killing of drug-resistant bacteria.

[0007] To achieve the above objectives, the present invention adopts the following technical solution:

[0008] A small molecule compound of the NIR-II class with photothermal antibacterial activity has the following general formula I structure:

[0009]

[0010] in,

[0011] R2 represents oxygen and sulfur;

[0012] Each R1 and R3 is independently selected from benzene rings, substituted benzene rings, and heteroaromatic rings.

[0013] Preferably, R2 is selected from O and S; R1 and R3 are selected from -4-Ph(4-OMe), -4-Ph(4-NMe2), and 4-Ph-4-N(Ph)2.

[0014] Preferably, the NIR-II small molecule compounds are selected from:

[0015]

[0016]

[0017] Its structural formula is shown in Table 1:

[0018] Table 1. Compound codes and corresponding structures for some compounds of general formula I.

[0019]

[0020]

[0021] I1: (E)-4-(2-[5-[4-(dimethylamino)phenyl]thiophene-2-yl]vinyl)-2-(4-methoxyphenyl)sulfonium perchlorate

[0022] I2: (E)-4-(2-{5-[4-(diphenylamino)phenyl]thiophene-2-yl}vinyl)-2-(4-methoxyphenyl)sulfonium perchlorate

[0023] I3: (E)-2-[4-(diphenylamino)phenyl]-4-(2-{5-[4-(diphenylamino)phenyl]thiophene-2-yl}vinyl)sulfonium perchlorate

[0024] I4: (E)-4-(2-{5-[4-(dimethylamino)phenyl]furan-2-yl}vinyl)-2-(4-methoxyphenyl)sulfonium perchlorate

[0025] I5: (E)-4-(2-{5-[4-(diphenylamino)phenyl]furan-2-yl}vinyl)-2-(4-methoxyphenyl)sulfonium perchlorate

[0026] I6: (E)-2-[4-(diphenylamino)phenyl]-4-(2-{5-[4-(diphenylamino)phenyl]furan-2-yl}vinyl)sulfonium perchlorate

[0027] This invention also provides a method for preparing NIR-II small molecule compounds with photothermal antibacterial activity, comprising the following steps:

[0028]

[0029] (1) Using compound 1 as raw material, under ice bath conditions, tetrahydrofuran was used as solvent to react with methyl magnesium chloride (CH3MgCl) until the reaction was complete. Then, under ice bath conditions, 10% HClO4 aqueous solution was added dropwise until the reaction was complete to obtain intermediate compound 2.

[0030] (2) Then compound 2 and the corresponding aldehyde compound were added to the reaction flask, protected with nitrogen, and then sodium acetate and acetic anhydride solution were added. The mixture was refluxed at 120°C to obtain the target product I.

[0031] R1, R2, and R3 are defined as in general formula I.

[0032] By adopting the above technical solutions, all compounds of general formula I of the present invention can be prepared by the above or similar preparation methods, and the appropriate starting materials can be selected according to the different substituents and their positions. Those skilled in the art should recognize that the above route helps in understanding the present invention, but does not limit the scope of the invention; unless otherwise specified, variables are defined as mentioned in general formula I.

[0033] The NIR-II small molecule compounds described in this invention exhibit fluorescence emission properties in the near-infrared II region (NIR-II, 1000-1700 nm), with a maximum fluorescence emission wavelength exceeding 1000 nm. This fluorescence emission characteristic provides a significant advantage in in vivo deep tissue imaging, effectively reducing interference from biological tissue autofluorescence and scattered light, thereby obtaining fluorescence images with higher signal-to-noise ratio, higher spatial resolution, and deeper penetration depth.

[0034] The NIR-II small molecule compounds described in this invention can efficiently convert light energy into heat energy through non-radiative transition pathways under irradiation with a specific wavelength light source, thereby achieving photothermal conversion and generating a significant photothermal effect, which enables rapid and controllable temperature rise in a localized area.

[0035] Preferably, the NIR-II small molecule compound has a photothermal antibacterial therapeutic effect. When irradiated with near-infrared light, the compound absorbs light energy and rapidly generates heat, resulting in a local temperature increase. This causes bacterial protein denaturation and cell membrane structure destruction, thereby effectively killing a variety of bacteria, including drug-resistant bacteria, and achieving photothermal antibacterial therapy for drug-resistant bacterial infections.

[0036] Compared with the prior art, the present invention has the following beneficial effects:

[0037] The novel small-molecule NIR-II photothermal agent provided by this invention has a fluorescence emission wavelength exceeding 1000 nm and a high photothermal conversion efficiency. Under laser irradiation, it can rapidly generate enough heat to kill bacteria, effectively eliminating drug-resistant bacteria and destroying their biofilms. Utilizing the deeper tissue penetration capability of NIR-II light, precise photothermal therapy for deep tissues can be achieved. Attached Figure Description

[0038] Figure 1 Normalized UV spectra of the compounds of the present invention in water / DMSO solutions of different proportions (0%, 99%);

[0039] Figure 2 The fluorescence spectra of the compound of the present invention (10 μM) in water / DMSO solutions of different proportions (0%, 99%) are shown.

[0040] Figure 3 This is a photothermal test result of the compound (30 μM) of this invention in DMSO solution;

[0041] Figure 4 This is a diagram showing the photothermal antibacterial effect of the compound (80 μM) of this invention. Detailed Implementation

[0042] The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings, so that those skilled in the art can better understand the advantages and features of the present invention, thereby making a clearer definition of the scope of protection of the present invention. The embodiments described in this invention are only some embodiments of the present invention, not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0043] Note: Unless otherwise specified in the examples, the techniques or conditions described in the literature in this field, or the product instructions, shall be followed. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased through legitimate channels.

[0044] Unless otherwise specified, the experimental methods used in the following examples are conventional methods. Unless otherwise specified, the experimental materials used in the following examples are commercially available products.

[0045] Example 1: (E)-4-(2-[5-[4-(dimethylamino)phenyl]thiophen-2-yl]vinyl)-2-(4-methoxyphenyl)sulfonium(I1)

[0046] Compound 2-(4-methoxyphenyl)-4H-thiaran-4-one (268.3 mg, 1 mmol) was added to a double-necked flask. Under nitrogen protection, anhydrous THF was added under ice bath conditions until the compound was completely dissolved. Then, CH3MgCl (3 mol / L, 1 mL) was slowly added, and the mixture was stirred for 4 h until the reaction was complete. Next, 10% HClO4 aqueous solution (10 mL) was added dropwise under ice bath conditions until the reaction was complete. The mixture was extracted with dichloromethane (30 mL), and the organic layer was dried over anhydrous Na2SO4, filtered, and evaporated to dryness to obtain compound 2a.

[0047] Subsequently, compound 2a and 5-(4-(dimethylamino)phenyl)thiophene-2-carboxaldehyde (231.3 mg, 1 mmol) were added to a reaction flask. Under nitrogen protection, 20 mg of sodium acetate and 5 mL of acetic anhydride solution were added. The mixture was refluxed at 120 °C for 2 h. After monitoring the reaction until it was complete, the crude product was subjected to column chromatography to obtain the target product, a reddish-brown solid powder I1 (312 mg, yield 53.8%).

[0048] 1H NMR(500MHz,DMSO-d6)δ7.97–7.94(m,2H),7.82(d,J=8.8Hz,2H),7.69–7.62(m,3H),7.53(d,J =4.0Hz,1H),7.23(s,1H),7.14(d,J=8.8Hz,2H),6.89–6.77(m,6H),3.96(s,3H),3.00(s,6H).

[0049] HRMS: m / z, calculated for C 30 H 26 NOS2 + [M] + 480.14503, found 480.14456.

[0050] Example 2: (E)-4-(2-{5-[4-(diphenylamino)phenyl]thiophen-2-yl}vinyl)-2-(4-methoxyphenyl)sulfonium perchlorate (I2)

[0051] The synthesis steps and molar amounts of compound I2 were the same as those of I1, except that 5-(4-(dimethylamino)phenyl)thiophen-2-carboxaldehyde was replaced with 5-(4-(diphenylamino)phenyl)thiophen-2-carboxaldehyde, yielding blue-black solid powder I2 (492 mg, yield 69.9%).

[0052] 1 H NMR(400MHz,DMSO-d6)δ8.34–7.94(m,6H),7.80–7.58(m,3H),7.39–7.35(m ,5H),7.29–7.21(m,3H),7.19–7.11(m,7H),7.01–6.97(m,3H),3.95(s,3H).

[0053] 13 C NMR(126MHz,DMSO-d6 with a little CDCl3)δ147.37,147.32,146.68,146.62,146.60,131.01,130.65,130.59,129.64,129.46,126.47,125.23,125.18,124.42,124.37,57.14.

[0054] HRMS: m / z, calculated for C 40 H 30 NOS2 + [M] +604.17633, found 604.17578.

[0055] Example 3: (E)-2-[4-(diphenylamino)phenyl]-4-(2-{5-[4-(diphenylamino)phenyl]thiophen-2-yl}vinyl)sulfonium perchlorate (I3)

[0056] The synthesis steps and molar amounts of compound I3 were the same as those of I1. Compound 2-(4-methoxyphenyl)-4H-thiaran-4-one was replaced with 2-(4-(diphenylamino)phenyl)-4H-thiaran-4-one, and 5-(4-(dimethylamino)phenyl)thiophen-2-carboxaldehyde was replaced with 5-(4-(diphenylamino)phenyl)thiophen-2-carboxaldehyde, to obtain blue-black solid powder I3 (525 mg, yield 62.4%).

[0057] 1 H NMR (500MHz, Pyridine-d5) δ7.68–7.59(m,8H),7.50–7.24(m,13H),7.19–6.90(m,16H).

[0058] 13 C NMR(126MHz,Pyridine-d5)δ147.76,147.47,147.27,138.38,131.83,131.33,129.91,129.81,128.00,12 7.52,127.40,126.99,126.73,125.76,125.34,125.11,124.60,124.13,123.80,122.68,121.77,116.43.

[0059] HRMS: m / z, calculated for C 51 H 37 N2S2 + [M] + 741.23927, found 741.23865.

[0060] Example 4: (E)-4-(2-{5-[4-(dimethylamino)phenyl]furan-2-yl}vinyl)-2-(4-methoxyphenyl)sulfonium perchlorate (I4)

[0061] The synthesis steps and molar amounts of compound I4 were the same as those of I1, except that 5-(4-(dimethylamino)phenyl)thiophene-2-carboxaldehyde was replaced with 5-(4-(dimethylamino)phenyl)furan-2-carboxaldehyde, yielding reddish-brown solid powder I4 (341 mg, yield 60.5%).

[0062] 1 H NMR (400MHz, DMSO-d6) δ8.90(d,J=8.1Hz,1H),8.63(s,1H),8.58(d,J=14.3Hz,1H),8.20(dd,J=7.9,1.6Hz,1H),8.13–8.0 6(m,2H),8.07–7.80(m,6H),7.53(d,J=4.3Hz,1H),7.22(d,J=8.8Hz,2H),6.90(d,J=8.8Hz,2H),3.92(s,3H),3.14(s,6H).

[0063] 13 C NMR(126MHz,DMSO-d6)δ163.50,163.46,163.42,163.38,153.48,132.93,130.75 ,129.84,128.57,128.45,128.34,115.66,114.57,114.54,112.98,56.30,40.33.

[0064] HRMS: m / z, calculated for C 30 H 26 NO2S + [M] + 464.16788, found 464.16772.

[0065] Example 5: (E)-4-(2-{5-[4-(diphenylamino)phenyl]furan-2-yl}vinyl)-2-(4-methoxyphenyl)sulfonium perchlorate (I5)

[0066] The synthesis steps and molar amounts of compound I5 were the same as those of I1, except that 5-(4-(dimethylamino)phenyl)thiophene-2-carboxaldehyde was replaced with 5-(4-(diphenylamino)phenyl)furan-2-carboxaldehyde, yielding blue-black solid powder I5 (457 mg, yield 66.4%).

[0067] 1 H NMR (400MHz, DMSO-d6) δ8.48–8.06(m,12H),7.43(t,J=7.9Hz,5H),7.33–7.17(m,7H),7.01(s,3H),3.95(s,3H).

[0068] 13C NMR (126MHz, DMSO-d6) δ146.35,130.46,128.15,127.97,126.24,125.50,120.59,116.06,56.53.

[0069] HRMS: m / z, calculated for C 40 H 30 NO2S + [M] + 588.19918, found 588.19800.

[0070] Example 6: (E)-2-[4-(diphenylamino)phenyl]-4-(2-{5-[4-(diphenylamino)phenyl]furan-2-yl}vinyl)sulfonium perchlorate (I6)

[0071] The synthesis steps and molar amounts of compound I6 were the same as those of I1. Compound 2-(4-methoxyphenyl)-4H-thiaran-4-one was replaced with 2-(4-(diphenylamino)phenyl)-4H-thiaran-4-one, and 5-(4-(dimethylamino)phenyl)thiophene-2-carboxaldehyde was replaced with 5-(4-(diphenylamino)phenyl)furan-2-carboxaldehyde, to obtain blue-black solid powder I6 (533 mg, yield 64.6%).

[0072] 1 H NMR(500MHz,DMSO-d6)δ8.93–8.78(m,2H),8.53(s,1H),8.31(s,1H),8.12–7.90(m,6H ),7.50(t,J=7.8Hz,5H),7.43(t,J=7.9Hz,4H),7.39–7.13(m,14H),7.02–6.94(m,4H).

[0073] 13 C NMR (126MHz, DMSO-d6) δ146.46,145.29,139.28,130.70,130.42,127.15,126.84,126.12,126.07,125.31,120.85,119.02.

[0074] HRMS: m / z, calculated for C 51 H 37 N2OS + [M] + 725.26211, found 725.26190.

[0075] Example 7: Ultraviolet spectral detection of the compounds of the present invention

[0076] In this embodiment, a 10 μM DMSO / deionized aqueous solution of the compounds (I1-I6) of this invention was prepared, and ultraviolet absorption spectra in the wavelength range of 400-900 nm were collected using a UV spectrophotometer. Figure 1 DMSO stock solutions (5 mM) for compounds I1, I2, I3, I4, I5, and I6 were prepared. Different volumes of DMSO, deionized water, and dichloroethane were added to cuvettes, and then the stock solutions of each compound were added to prepare 10 μM test solutions for UV absorption spectroscopy detection. The scanning wavelength range was set to 400-900 nm. The results are as follows: Figure 1 As shown: Figure 1 A represents the UV absorption spectrum of compound I1 in H2O and DMSO. Figure 1 B represents the UV absorption spectra of compound I2 in H2O and DMSO. Figure 1 C represents the UV absorption spectrum of compound I3 in H2O and DMSO. Figure 1 D represents the UV absorption spectrum of compound I4 in H2O and DMSO. Figure 1 E represents the ultraviolet absorption spectrum of compound I5 in H2O and DMSO. Figure 1 F represents the ultraviolet absorption spectra of compound I6 in H2O and DMSO.

[0077] Test results show that all target compounds exhibit maximum absorption peaks in the 600–900 nm range in 1% DMSO aqueous solution, indicating that these compounds can effectively absorb photon energy from the visible to near-infrared II region and have potential application prospects as optical functional materials.

[0078] Example 8: Fluorescence Spectroscopic Detection of the Compounds of the Present Invention

[0079] In this embodiment, the compounds (I1-I6) of the present invention were further formulated into a 10 μM DMSO / deionized aqueous solution, and their fluorescence emission performance in the near-infrared II (NIR-II) region was tested. Figure 2 Prepare DMSO stock solutions (5 mM) for compounds I1, I2, I3, I4, I5, and I6. Add the stock solutions to a cuvette containing DMSO and deionized water, and disperse thoroughly before use for fluorescence spectroscopy detection. Set the excitation wavelength to 808 nm (0.8 W cm⁻¹). -2 The scanning range was 950-1500 nm. All tests were performed at room temperature (26°C). Results are as follows: Figure 2 As shown: Figure 2 A represents the fluorescence spectrum of compound I1 in H2O and DMSO. Figure 2B represents the NIR-II fluorescence spectra of compound I2 in H2O and DMSO. Figure 2 C represents the NIR-II fluorescence spectrum of compound I3 in H2O and DMSO. Figure 2 D represents the NIR-II fluorescence spectrum of compound I4 in H2O and DMSO. Figure 2 E represents the NIR-II fluorescence spectrum of compound I5 in H2O and DMSO. Figure 2 F represents the NIR-II fluorescence spectrum of compound I6 in H2O and DMSO.

[0080] Test results show that the compound of the present invention exhibits excellent luminescence properties with a wavelength exceeding 1000 nm, and is expected to be used in the field of near-infrared II bioimaging.

[0081] Example 9: Photothermal test of the compound of the present invention

[0082] This embodiment further evaluates the photothermal properties of the compound of the present invention in a 1% DMSO aqueous solution (30 μM). Figure 3 A DMSO solution containing compounds I1, I2, I3, I4, I5, and I6 (30 μM) was subjected to an 808 nm laser (0.8 W cm⁻¹). -2 Continuous irradiation was performed, and the temperature change was measured every 10 seconds using a TES-1320 digital thermometer, while maintaining a constant distance between the light source and the sample. After irradiation, the solution was cooled to room temperature, and the temperature change was again measured every 10 seconds. The photothermal curve was obtained, and the photothermal conversion efficiency was calculated. The results are as follows: Figure 3 As shown: Figure 3 A represents the photothermal curve of compound I1 in DMSO. Figure 3 B is the photothermal conversion coefficient of compound I1 in DMSO. Figure 3 C represents the photothermal curve of compound I2 in DMSO. Figure 3 D is the photothermal conversion coefficient of compound I2 in DMSO. Figure 3 E represents the photothermal curve of compound I3 in DMSO. Figure 3 F is the photothermal conversion coefficient of compound I3 in DMSO. Figure 3 G represents the photothermal curve of compound I4 in DMSO. Figure 3 H is the photothermal conversion coefficient of compound I4 in DMSO. Figure 3 I represents the photothermal curve of compound I5 in DMSO. Figure 3 J is the photothermal conversion coefficient of compound I5 in DMSO. Figure 3 K represents the photothermal curve of compound I6 in DMSO. Figure 3 L is the photothermal conversion coefficient of compound I6 in DMSO.

[0083] In 808nm near-infrared laser (0.8W cm⁻¹) -2 Under irradiation, all compounds exhibited a significant photothermal effect. For example... Figure 3 As shown, under the same irradiation conditions, compounds I1, I2, I3, I4, I5, and I6 increased the solution temperature by 21.3℃, 31.2℃, 33.5℃, 26.5℃, 33.5℃, and 39.3℃, respectively. Among them, compound I6 showed the most significant temperature increase. Further calculations revealed the photothermal conversion efficiencies of each compound to be 35.4%, 49.5%, 57.2%, 47.1%, 55.1%, and 61.3%, respectively. These results indicate that the compounds of this invention, particularly compound I6, possess excellent photothermal conversion performance and show promising application prospects in the field of photothermal therapy.

[0084] Example 10: Detection of the photothermal antibacterial effect of compound I6 of the present invention

[0085] This embodiment further evaluates the performance of compound I6 of the present invention in 808 nm near-infrared laser (0.8 W cm⁻¹). -2 The photothermal antibacterial effect under irradiation. For example... Figure 4 Methicillin-resistant Staphylococcus aureus (MRSA) or normal human immortalized keratinocytes (HaCaT cells) were incubated for 15 minutes with a culture medium solution containing compounds I1, I2, I3, I4, I5, and I6 (80 μM). Subsequently, 808 nm laser (0.8 W cm⁻¹) was used. -2 Irradiate continuously for 10 minutes, and finally use OD detection. 600 Bacterial viability was calculated using the MTT assay to determine cell viability. Results are as follows: Figure 4 As shown: Figure 4 A represents the survival rate of methicillin-resistant Staphylococcus aureus (MRSA) bacteria after incubation with compound I6 under light or non-light conditions. Figure 4 B represents the survival rate of HaCaT cells under light or no light conditions after incubation with compound I6.

[0086] Under the same irradiation conditions, compound I6 showed the best bactericidal effect, with a bacterial survival rate of less than 10%, while the bacterial survival rate was higher than 80% under non-irradiation conditions. Furthermore, compound I6 showed a survival rate of over 80% in normal HaCaT cells under both light and non-light conditions, demonstrating that this type of photothermal agent can achieve targeted photothermal antibacterial effects against bacteria.

[0087] In summary, through rational molecular design, employing heteroatom substitution and extended conjugation strategies to enhance intramolecular electron push-pull effects, a DA-π-D type molecular structure was constructed, using benzothiopyranonium as a strong electron-withdrawing group, furan or thiophene as a π-bridge, and a triphenylamine group as an electron donor. This series of molecules exhibits strong absorption in the NIR-II region and demonstrates excellent photothermal conversion performance and aggregation-induced emission characteristics. Under 808 nm laser irradiation, these compounds can achieve a rapid and uniform increase in temperature in the infected area, effectively disrupting drug-resistant bacteria and their biofilm structure, thereby achieving highly efficient treatment of drug-resistant bacterial infections.

[0088] The descriptions and practices disclosed in this invention are readily apparent and understandable to those skilled in the art, and various modifications and refinements can be made without departing from the principles of this invention. Therefore, any modifications or improvements made without departing from the spirit of this invention should also be considered within the scope of protection of this invention.

Claims

1. A small molecule compound of the NIR-II class with photothermal antibacterial activity, characterized in that, It has the following general formula I structure: in, R2 represents oxygen and sulfur; Each R1 and R3 is independently selected from benzene rings, substituted benzene rings, and heteroaromatic rings.

2. The NIR-II small molecule compound with photothermal antibacterial activity according to claim 1, characterized in that, R2 is O or S; R1 and R3 are selected from -4-Ph(4-OMe), -4-Ph(4-NMe2), and 4-Ph-4-N(Ph)2.

3. The NIR-II small molecule compound with photothermal antibacterial activity according to claim 1, characterized in that, The NIR-II small molecule compounds are selected from:

4. A method for preparing a NIR-II small molecule compound with photothermal antibacterial activity according to any one of claims 1-3, characterized in that, Includes the following steps: (1) Using compound 1 as raw material, under ice bath conditions, tetrahydrofuran was used as solvent to react with methyl magnesium chloride (CH3MgCl) until the reaction was complete. Then, under ice bath conditions, 10% HClO4 aqueous solution was added dropwise until the reaction was complete to obtain intermediate compound 2. (2) Then compound 2 and the corresponding aldehyde compound were added to the reaction flask, protected with nitrogen, and then sodium acetate and acetic anhydride solution were added. The mixture was refluxed at 120°C to obtain the target product I. R1, R2, and R3 are defined as in general formula I.

5. A small molecule compound of NIR-II as described in any one of claims 1-3 has fluorescence emission properties in the near-infrared II region, and its maximum fluorescence emission wavelength exceeds 1000 nm.

6. A small molecule compound of NIR-II as described in any one of claims 1-3, which can undergo photothermal conversion after light irradiation to produce a photothermal effect.

7. The use of the NIR-II small molecule compound as described in any one of claims 1-3 in the preparation of antibacterial drugs.

8. The application according to claim 7, characterized in that, The NIR-II small molecule compounds described above have photothermal antibacterial therapeutic effects, generating heat by absorbing energy from a light source, thereby effectively killing drug-resistant bacteria.

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