Near-infrared dye based on N-heterocyclic substituted bis-perylene functional group as well as preparation method and application of near-infrared dye

Abstract

The invention discloses a bis-perylene dye with near-infrared absorption and luminescence properties. The structural formula of the near-infrared bis-perylene fluorescent dye is shown in the specification, wherein R represents substituted or unsubstituted alkyl or aryl; x and Y are selected from N-heterocyclic groups and halogen, at least one substituent group is a ternary, quaternary, five-membered or six-membered N-heterocyclic group, and the N-heterocyclic group is connected to a bis-perylene skeleton through a C-N bond. After one or two N-heterocyclic groups are introduced into a bay region of bis-perylene diimide, compared with a simple perylene diimide derivative, the absorption wavelength, the fluorescence emission wavelength and the chemiluminescence wavelength of the obtained compound all show near-infrared characteristics, and meanwhile, due to introduction of the N-heterocyclic groups, the fluorescence emission wavelength and the chemiluminescence wavelength of the obtained compound all show near-infrared characteristics. The molar extinction coefficient of the compound in a near-infrared region is greatly increased, and compared with a commercial photosensitizer indocyanine green (ICG), the series of compounds have better light stability and more efficient singlet oxygen generation capacity. # imgabs0 #

Description

Technical Field

[0001] The invention belongs to the technical field of organic compounds, and in particular relates to the preparation and application of a bisperylene diimide near-infrared dye with an N-heterocyclic group. Background Art

[0002] Cancer has always been one of the biggest threats to human health. Traditional methods of treating cancer are mainly chemotherapy and radiotherapy, but because these two methods inevitably have disadvantages such as large drug side effects, drug resistance, and no selectivity, scientific researchers have been exploring new non-invasive and efficient therapies. Photodynamic therapy (PDT) that uses photosensitizers (PS) to produce reactive oxygen species (ROS) is a non-invasive and highly effective treatment method. PDT shows great potential in cancer treatment. PDT includes three elements: photosensitizer (PS), oxygen, and light. Under the irradiation of red light or near-infrared light, the photosensitizer produces free radicals or singlet oxygen (ROS) through type I or type II pathways. 1 Most reported or commercially available PSs are mainly based on various types of polypyrrole macrocycles, including clinically used ICG, which have limitations, such as low photostability.

[0003] Perylene diimide derivatives (PDIs) are planar conjugated fused-ring macromolecules with excellent photophysical properties. Due to their high fluorescence quantum yield, unique electrochemical properties, and good stability, they are widely used in fluorescent probes, photoacoustic imaging, photodynamic therapy, and photovoltaic materials. PDIs have strong absorption capacity in the visible light region at 525 nm, and also have advantages such as high photostability and thermal stability and easy modification. PDIs obtained by conventionally expanding the conjugated structure and introducing different groups in the bay region show a gradual red-shifted absorption from the visible light region to the near-infrared region. Akkaya and colleagues first reported the application of bay-substituted PDIs in PDT, revealing the potential application value of photosensitizers based on PBIs dyes (The Journal of Physical Chemistry A, 2008, 112(37):8617-8632.). The present invention discloses a novel near-infrared bis-perylene diimide derivative.

[0004] Prior art discloses a class of near-infrared dyes based on perylene diimide, an N-heterocyclic group, and a phenoxy group (CN111909150 A). These dyes directly connect the perylene diimide, the N-heterocyclic group, and the phenoxy group as the core molecular structure. However, the UV-visible absorption spectrum of the synthesized product is limited to 350 to 750 nm, not exceeding 750 nm, limiting its application in optoelectronics and medicine. Therefore, improvements to these compounds are needed. Summary of the Invention

[0005] In response to the deficiencies in the prior art, the present invention prepares a near-infrared absorbing organic dye based on a bisperylene diimide and an N-heterocyclic group. The dye is prepared using a tetrahalogenated bisperylene diimide and an N-heterocyclic compound as raw materials via a nucleophilic substitution reaction. The preparation method is simple and the conditions are mild. Compared with simple perylene diimide dyes, the prepared organic dye exhibits a significant red shift in UV absorption spectrum, fluorescence emission spectrum, and chemiluminescence spectrum, reaching the near-infrared region. This provides a stable near-infrared bisperylene fluorescent dye with longer absorption and emission wavelengths. Based on this dye, a more efficient photosensitizer for generating singlet oxygen is provided.

[0006] The structural formula of the near-infrared bis-perylene fluorescent dye provided by the present invention is as shown in Formula 1:

[0007]

[0008] In Formula 1, R represents a substituted or unsubstituted alkyl or aryl group;

[0009] X and Y are selected from N-heterocyclic groups and halogens, and at least one substituent is an N-heterocyclic group, and the N-heterocyclic group is connected to the bisperylene skeleton through a CN bond.

[0010] Specifically, in Formula 1, R is selected from a C4-C18 linear alkyl group or an ether-substituted linear alkyl group, or a phenyl group or an alkyl-substituted phenyl group, preferably 2,6-diisopropylphenyl group.

[0011] Specifically, the N-heterocyclic group is a three-membered, four-membered, five-membered or six-membered aliphatic nitrogen-containing heterocyclic group, 1-aziridine, 1-azetidinyl, N-tetrahydropyrrolyl, N-hexahydropyridinyl, N-morpholinyl, N-thiomorpholinyl, N-piperazinyl, N-(N'-methyl)piperazinyl, N-(N'-ethyl)piperazinyl, N-(N'-propyl)piperazinyl, N-(N'-butyl)piperazinyl, N-(N'-cyclopropyl)piperazinyl, N-(N'-acetyl)piperazinyl; the halogen is bromine or chlorine.

[0012] Specifically, in Formula 1, the substitution of X and Y is as follows 1) or 2):

[0013] 1) One substituent is the N-heterocyclic group, and the other three substituents are all halogens;

[0014] 2) Two substituents are the N-heterocyclic groups, and the other two substituents are halogens.

[0015] Preferred compounds are:

[0016] One substituent is N-morpholinyl, and three substituents are chlorine;

[0017] One substituent is 1-azetidinyl, and three substituents are chlorine;

[0018] One substituent is N-(N'-methyl)piperazinyl, and three substituents are chlorine;

[0019] One substituent is N-(N'-cyclopropyl)piperazinyl, and three substituents are chlorine;

[0020] Two substituents are morpholinyl, and two substituents are chlorine;

[0021] Two substituents are N-hexahydropyridyl, and two substituents are chlorine;

[0022] Two substituents are N-(N'-methyl)piperazinyl, and two substituents are chlorine;

[0023] Two substituents are N-(N'-cyclopropyl)piperazinyl, and two substituents are chlorine; the structures of the preferred compounds are shown in Formula A-1 to Formula B-4:

[0024]

[0025]

[0026] The N-heterocyclic-substituted bisperylene functional group near-infrared dyes described herein react with a tetrahalogenated bisperylene derivative using an N-heterocyclic compound as a reaction reagent, solvent, and acid-binding agent. The N-heterocyclic compound is selected from aziridine, azetidine, tetrahydropyrrole, hexahydropyridine, morpholine, thiomorpholine, piperazine, N-methylpiperazine, N-ethylpiperazine, N-propylpiperazine, N-butylpiperazine, N-cyclopropylpiperazine, and N-acetylpiperazine. These N-heterocyclic compounds are liquid at room temperature and can be used as solvents. The reaction temperature is -10-60°C, preferably 0-5°C for monosubstitution reactions and 40-50°C for disubstitution reactions. The reaction time is 5-60 minutes, preferably 5-10 minutes for monosubstitution reactions and 25-30 minutes for disubstitution reactions.

[0027] An important application of perylene-functional dyes is as chemiluminescent dyes in diaryl oxalate-hydrogen peroxide systems. Perylene-functional dyes that produce orange, red, and near-infrared chemiluminescence have been commercialized, but chemiluminescent dyes with a maximum emission wavelength exceeding 800 nm are rare. The N-heterocyclic-substituted bisperylene-functional near-infrared dye synthesized in the present invention can achieve near-infrared chemiluminescence with a maximum emission wavelength exceeding 800 nm in the diaryl oxalate-hydrogen peroxide system, making it suitable for covert tracing applications. Furthermore, the N-heterocyclic-substituted bisperylene-functional near-infrared dye synthesized in the present invention exhibits excellent near-infrared absorption and photoluminescence properties, making it suitable for use in fluorescent anti-counterfeiting materials.

[0028] Near-infrared photosensitizers are increasingly used in photodynamic therapy. When these photosensitizers enter tumor tissue, they can generate free radicals or singlet oxygen under irradiation with red or near-infrared light, thereby destroying the tumor tissue and achieving the therapeutic goal. The N-heterocycle-substituted bisperylene functional group near-infrared dye synthesized in this invention has good photostability and a high singlet oxygen quantum yield, showing potential application value in the field of photodynamic therapy. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 The ultraviolet absorption spectra of formula A-1 to formula A-4 are

[0030] Figure 2 The fluorescence emission spectra of Formula A-1 to Formula A-4 are

[0031] Figure 3 The chemiluminescence spectra of formula A-1 to formula A-4 are

[0032] Figure 4 The ultraviolet absorption spectra of formula B-1 to formula B-4 are

[0033] Figure 5 The fluorescence emission spectra of Formula B-1 to Formula B-4 are

[0034] Figure 6 The chemiluminescence spectra of formula B-1 to formula B-4 are

[0035] Figure 7 Normalized photostability comparison chart of ICG and Formulas A-1 to A-4

[0036] Figure 8 Normalized photostability comparison chart of ICG and Formula B-1 to Formula B-4 DETAILED DESCRIPTION

[0037] The following describes specific embodiments of the present invention to further illustrate the near-infrared dye based on N-heterocyclic-substituted bisperylene functional groups of the present invention, but is not limited to the enumerated embodiments.

[0038] Unless otherwise specified, the experimental methods used in the following examples are conventional methods.

[0039] Unless otherwise specified, the materials and reagents used in the following examples can be obtained from commercial sources.

[0040] Example 1

[0041] Preparation of intermediate 1b, the reaction equation is as follows:

[0042]

[0043] Synthesis of intermediate 1b: 1a (2.0 g, 2.36 mmol), cuprous iodide (2.7 g, 14.18 mmol), L-proline (1.9 g, 16.52 mmol), potassium carbonate (3.3 g, 23.6 mmol), and 40.0 mL of DMSO were added to a 100 mL reaction tube. The mixture was reacted at 75°C for 12 h, and then post-treated with dilute hydrochloric acid. Subsequently, 50 mL of ethyl acetate and 200 mL of saturated brine were added for extraction. The organic phase was washed with saturated brine (200 mL x 3), collected, and dried over anhydrous sodium sulfate. Finally, the organic solvent was removed by rotary evaporation to obtain a purple-black crude product. The crude product was separated by silica gel column chromatography (PE / DCM = 1:1, v / v) to obtain 1b as a purple-black solid (536.6 mg, 15%). 1 H NMR(400MHz,Chloroform-d)δ10.10(s,2H),9.34(s,2H),9.09(s,2H),7.60–7.41(m,8H),7.34(dd ,J=7.7,1.4Hz,2H),7.28–7.25(m,2H),3.55(hept,J=6.4Hz,2H),2.99(hept,J=6.8Hz,2H),2.55( hept,J=6.8Hz,2H),2.26(hept,J=6.7Hz,2H),1.63(d,J=6.8Hz,6H),1.45(d,J=6.7Hz,6H),1.28( dd,J=6.8,2.4Hz,12H),1.11(d,J=6.8Hz,6H),1.02(dd,J=6.9,5.1Hz,12H),0.83(d,J=6.8Hz,6H). 13 C NMR (101MHz, CDCl3-d) δ163.52,162.96,162.92,162.70,146.54,146.40,145.34,144.9 7,136.69,136.52,136.37,136.01,134.47,133.10,131.42,130.54,130.40,130.08,129 .86,127.32,126.42,126.29,125.54,124.72,124.51,124.32,124.14,123.74,121.79, 121.46,118.88,30.14,29.30,24.80,24.63,24.39,24.18,24.12,23.87.HRMS(ESI):m / z calcd for C 96 H 75 Cl4N4O8[M+H]+ 1551.4338, found 1551.4310. Maximum UV absorption wavelength (λ max ) is 655 nm, and the maximum fluorescence emission wavelength (λ max FL ) is 675nm.

[0044] The combination of NMR characterization data and the molecular weight given by mass spectrometry shows that the structure of the obtained compound is correct.

[0045] Example 2

[0046] The preparation of the compound of formula A-1, the reaction equation is as follows:

[0047]

[0048] Synthesis of Formula A-1: 1b (400.0 mg, 0.26 mmol) and cesium carbonate (767.9 mg, 2.36 mmol) were added to a 10 mL reaction tube. The tube was evacuated and purged with nitrogen three times. Then, 2.0 mL of morpholine was added and the reaction was carried out in an oxygen-free environment. The reaction was allowed to proceed at 0°C for 10 min. Subsequently, 25 mL of dichloromethane and 50 mL of deionized water were added for extraction. The aqueous phase was washed with dichloromethane (25 mL x 3). The organic phases were combined and dried over anhydrous sodium sulfate. Finally, the organic solvent was removed by rotary evaporation to obtain a wine-red crude product. The crude product was separated by silica gel column chromatography (PE / DCM / EA = 15:1:1, v / v) to obtain a wine-red solid of Formula A-1 (257.2 mg, 62%). 1H NMR(400MHz,CDCl3)δ10.10(s,1H),10.02(s,1H),9.30(s,1H),9.23(s,1H),9.07(s,1H),9.06(s,1H),7.59–7.40(m,8H),7.33(dt,J=7.7,1.7Hz,2H),7.27–7.22(m,2H),4.57(ddd,J=12.3,8.8,3.1Hz,1H),4.45(d,J=13.8Hz,1H),4.28(dt,J=11.6,3.6Hz,1H),3.99(ddd,J=11.5,8.8,2.8Hz,1H),3.83(dt,J=11.4,3.6Hz,1H),3.56(dt,J=20.1,6.8Hz,2H),3.50–3.43(m,1H),3.37(ddd,J=12.6,9.0,3.2Hz,1H),2.99(p,J=6.7Hz,2H),2.61–2.49(m,2H),2.50–2.42(m,1H),2.36(q,J=6.8Hz,1H),2.28(q,J=6.9Hz,1H),1.62(dd,J=12.0,6.7Hz,6H),1.44(dd,J=6.8,3.5Hz,6H),1.33–1.23(m,12H),1.14–1.05(m,9H),1.04–0.97(m,9H),0.86(d,J=6.8Hz,3H),0.79(d,J=6.8Hz,3H). 13C NMR (101MHz, CDCl3) δ164.10,163.65,163.38,163.10,163.07,162.87,151.76,146.68 ,146.61,146.37,145.43,145.30,144.96,144.83,136.34,136.19,136.04,135.74,135 .40,134.82,134.07,133.86,133.80,131.06,130.75,130.70,130.65,130.56,130.47,130.43,129.95,129.90,129.80,129.73,129.06,128.47,127.83,127.69,127.32,127 .17,127.07,126.13,125.84,125.43,125.32,124.43,124.35,124.27,124.22,124.11,124.04,124.04,124.03,123.91,123.46,123.27,122.16,121.98,121.93,121.24,121 .01,119.98,119.59,116.82,112.64,67.08,66.14,52.85,48.08,30.09,29.99,29.21 ,24.79,24.68,24.46,24.33,24.15,24.08,24.08,23.94,23.81,23.77.HRMS(ESI):m / z calcd forC 100 H 83 Cl3N5O9[M+H] + 1603.5285, found 1603.5204. Maximum UV absorption wavelength (λ max ) is 797 nm, and the maximum fluorescence emission wavelength (λ max FL ) is 828 nm, and the maximum chemiluminescence wavelength (λ max CL ) is 848nm.

[0049] The combination of NMR characterization data and the molecular weight given by mass spectrometry shows that the structure of the obtained compound is correct.

[0050] Example 3

[0051] The preparation of the compound of formula A-2, the reaction equation is as follows:

[0052]

[0053] Synthesis of Formula A-2: 1b (400.0 mg, 0.26 mmol) and cesium carbonate (767.9 mg, 2.36 mmol) were added to a 10 mL reaction tube. The tube was evacuated and purged with nitrogen three times. 2.0 mL of azetidine was then added and the reaction was carried out in an oxygen-free environment. The reaction was allowed to proceed at 0°C for 10 min. Subsequently, 25 mL of dichloromethane and 50 mL of deionized water were added for extraction. The aqueous phase was washed with dichloromethane (25 mL x 3). The organic phases were combined and dried over anhydrous sodium sulfate. Finally, the organic solvent was removed by rotary evaporation to obtain a wine-red crude product. The crude product was separated by silica gel column chromatography (PE / DCM / EA = 15:1:1, v / v) to obtain a wine-red solid of Formula A-2, 238.5 mg, 59%. 1 H NMR (400MHz, CDCl3) δ10.12(s,1H),10.09(s,1H),9.30(s,1H),9.11(s,1 H),9.08(s,1H),8.86(s,1H),7.59–7.40(m,8H),7.33(d,J=7.7Hz,2H),7. 27–7.21(m,2H),5.08–5.03(m,1H),4.71(q,J=8.6Hz,1H),4.00(td,J=9. 8,4.9Hz,1H),3.58(dp,J=16.0,6.8Hz,2H),3.00(p,J=6.8Hz,2H),2.87(d ,J=8.4Hz,1H),2.63(q,J=9.1Hz,1H),2.54(tt,J=7.5,3.7Hz,2H),2.44( dt,J=9.5,4.9Hz,1H),2.37(q,J=6.8Hz,1H),2.33–2.23(m,1H),1.66–1.5 7(m,6H),1.45(d,J=6.7Hz,6H),1.32–1.23(m,12H),1.09(dd,J=11.9,6. 9Hz,9H),1.05–0.97(m,9H),0.87(d,J=6.8Hz,3H),0.79(d,J=6.8Hz,3H). 13C NMR (101MHz, CDCl3) δ164.27,163.95,163.76,163.69,163.24,163.17,162.89,149 .60,146.82,146.65,146.40,145.44,145.35,144.91,144.81,136.18,136.10,135. 83,135.82,135.08,134.62,133.80,133.67,133.30,130.99,130.81,130.51,130.36,130.04,129.89,129.77,129.71,129.65,129.23,128.01,127.41,127.18,126.95 ,126.60,126.25,126.00,125.66,125.44,124.95,124.61,124.44,124.35,124.17,124.09,124.03,123.98,123.90,123.17,122.53,122.14,121.82,121.33,120.93, 120.71,116.32,108.06,56.65,53.26,30.09,29.99,29.23,29.17,24.77,24.68,24 .51,24.35,24.32,24.18,24.09,24.05,23.95,23.80,23.74,16.73.HRMS(ESI):m / z calcd for C 99 H 81 Cl3N5O8[M+H] + 1573.5179, found 1573.5223.λ max is 799nm, λ max FL is 849nm, λ max CL It is 847nm.

[0054] The combination of NMR characterization data and the molecular weight given by mass spectrometry shows that the structure of the obtained compound is correct.

[0055] Example 4

[0056] The preparation of the compound of formula A-3, the reaction equation is as follows:

[0057]

[0058] Synthesis of Formula A-3: 1b (400.0 mg, 0.26 mmol) and cesium carbonate (767.9 mg, 2.36 mmol) were added to a 10 mL reaction tube. The tube was evacuated and purged with nitrogen three times. 2.0 mL of N-methylpiperazine was then added and the reaction was carried out in an oxygen-free environment. The reaction was allowed to proceed at 0°C for 10 min. Subsequently, 25 mL of dichloromethane and 50 mL of deionized water were added for extraction. The aqueous phase was washed with dichloromethane (25 mL x 3). The organic phases were combined and dried over anhydrous sodium sulfate. Finally, the organic solvent was removed by rotary evaporation to obtain a wine-red crude product. The crude product was separated by silica gel column chromatography (PE / DCM / EA = 15:1:1, v / v) to obtain 268.2 mg of Formula A-3 as a wine-red solid (64%). 1 H NMR(400MHz, CDCl3)δ10.08(s,1H),10.03(s,1H),9.31(s,1H),9.20(s,1H),9.07(s,1H),9.04(s,1H),7.59–7.40(m,8H),7.33(d, J=7.6Hz,2H),7.24(dd,J=7.4,1.7Hz,2H),4.55(s,2H),3.54(dp,J=13.6,6.8Hz,3H),3.36–3.23(m,2H),3.04–2.93(m,3H),2.79(d ,J=5.9Hz,3H),2.53(ddt,J=13.7,9.6,6.8Hz,3H),2.30(dp,J=30.8,6.8Hz,3H),1.61(dd,J=10.8,6.7Hz,6H),1.44(d,J=6.8Hz,6 H),1.28(dt,J=13.6,6.7Hz,12H),1.10(dd,J=6.9,4.5Hz,9H),1.01(q,J=7.0Hz,9H),0.86(d,J=6.8Hz,3H),0.79(d,J=6.8Hz,3H). 13C NMR (101MHz, CDCl3) δ164.03,163.64,163.36,163.09,162.85,151.74,146.63,14 6.58,146.36,145.41,145.28,145.00,144.83,136.35,136.18,136.04,135.73,1 35.41,134.83,134.01,133.85,133.80,131.06,130.71,130.67,130.62,130.45,129.94,129.88,129.78,129.72,129.28,128.36,127.78,127.37,127.22,127.13 ,126.12,125.85,125.42,125.34,124.42,124.39,124.33,124.32,124.26,124.20,124.10,124.02,123.90,123.47,123.27,122.30,121.97,121.90,121.00,119. 99,119.58,116.87,54.89,54.29,52.02,47.25,45.53,30.08,29.98,29.20,24.7 8,24.67,24.46,24.31,24.18,24.08,24.03,23.94,23.81,23.76.HRMS(ESI):m / z calcd forC 101 H 86 Cl3N6O8[M+H] + 1616.5601, found 1616.5620.λ max is 798nm, λ max FL is 819nm, λ max CL It is 844nm.

[0059] The combination of NMR characterization data and the molecular weight given by mass spectrometry shows that the structure of the obtained compound is correct.

[0060] Example 5

[0061] The preparation of the compound of formula A-4, the reaction equation is as follows:

[0062]

[0063] Synthesis of Formula A-4: 1b (400.0 mg, 0.26 mmol) and cesium carbonate (767.9 mg, 2.36 mmol) were added to a 10 mL reaction tube. The tube was evacuated and purged with nitrogen three times. 2.0 mL of N-cyclopropylpiperazine was then added and the reaction was carried out in an oxygen-free environment. The reaction was allowed to proceed at 0°C for 10 min. Subsequently, 25 mL of dichloromethane and 50 mL of deionized water were added for extraction. The aqueous phase was washed with dichloromethane (25 mL x 3). The organic phases were combined and dried over anhydrous sodium sulfate. Finally, the organic solvent was removed by rotary evaporation to obtain a wine-red crude product. The crude product was separated by silica gel column chromatography (PE / DCM / EA = 15:1:1, v / v) to yield 256.1 mg of Formula A-4 as a wine-red solid (61%). 1 H NMR (400MHz, CDCl3) δ10.10(s,1H),10.03(s,1H),9.31(s,1H),9.25(s,1H),9.08(s,1H),9.03(s,1H),7.59–7.40(m,8H),7.33(dd,J=7.7,1 .6Hz,2H),7.24(dd,J=7.4,1.8Hz,2H),4.54(s,2H),3.56(dt,J=17.4,6.7Hz,2H),3.28(s,2H),3.00(ddq,J=11.0,6.8,4.1,3.3Hz,2H),2.8 0(s,2H),2.54(dp,J=10.6,6.8Hz,3H),2.32(dt,J=31.7,6.8Hz,2H),2.25–2.13(m,1H),1.70(s,1H),1.62(dd,J=9.8,6.8Hz,6H),1.45(dd, J=6.8,2.5Hz,6H),1.36–1.22(m,12H),1.10(t,J=6.3Hz,9H),1.07–0.96(m,9H),0.87(d,J=6.8Hz,3H),0.80(d,J=6.8Hz,3H),0.54(s,4H). 13C NMR (101MHz, CDCl3) δ164.13,163.67,163.40,163.13,163.12,162.86,151.98,1 46.70,146.61,146.37,145.42,145.29,144.97,144.81,136.31,136.15,135.97, 135.75,135.31,134.20,133.78,131.04,130.77,130.72,130.48,130.42,129.97,129.86,129.77,129.71,128.53,127.91,127.23,127.10,127.13,126.10,125. 80,125.43,125.23,124.40,124.30,124.25,124.19,124.10,124.01,123.99,123.89,123.37,123.25,122.18,121.99,121.95,120.98,119.93,119.62,116.70,1 12.45,53.48,52.97,47.81,38.13,30.08,29.98,29.19,24.78,24.68,24.47,24 .35,24.31,24.15,24.09,24.04,23.94,23.81,23.75,5.97,5.96.HRMS(ESI):m / z calcd for C 103 H 88 Cl3N6O8[M+H] + 1642.5758, found 1642.5733.λ max is 801nm, λ max FL is 851nm, λ max CL It is 848nm.

[0064] The combination of NMR characterization data and the molecular weight given by mass spectrometry shows that the structure of the obtained compound is correct.

[0065] Example 6

[0066] The preparation of the compound of formula B-1, the reaction equation is as follows:

[0067]

[0068] Synthesis of Formula B-1: 1b (400.0 mg, 0.26 mmol) and cesium carbonate (767.9 mg, 2.36 mmol) were added to a 10 mL reaction tube. The tube was evacuated and purged with nitrogen three times. Then, 2.0 mL of morpholine was added and the reaction was carried out in an oxygen-free environment. The reaction was carried out at 50°C for 30 min. Subsequently, 25 mL of dichloromethane and 50 mL of deionized water were added for extraction. The aqueous phase was washed with dichloromethane (25 mL x 3). The organic phases were combined and dried over anhydrous sodium sulfate. The organic solvent was removed by rotary evaporation to obtain a grass-green crude product. The crude product was separated by silica gel column chromatography (PE / DCM = 2:1, v / v) to obtain a grass-green solid of Formula B-1, 286.3 mg, 67%. 1 H NMR(400MHz, CDCl3)δ10.00(s,2H),9.18(s,2H),9.03(s,2H),7.57–7.40(m,8 H),7.33(dd,J=7.7,1.4Hz,2H),7.25(dd,J=7.5,1.7Hz,2H),4.51(ddd,J=13. 4,8.1,3.0Hz,2H),4.39–4.31(m,2H),4.27(dt,J=7.8,3.5Hz,2H),4.02(ddd, J=11.1,8.2,2.7Hz,2H),3.83(dt,J=11.7,3.9Hz,2H),3.60–3.52(m,2H),3.51 –3.46(m,2H),3.31(ddd,J=12.1,8.4,3.3Hz,2H),3.00(p,J=6.7Hz,2H),2.54 (dd,J=13.8,6.9Hz,2H),2.47(d,J=3.9Hz,2H),2.36(h,J=6.8Hz,2H),1.64–1 .59(m,6H),1.44(d,J=6.8Hz,6H),1.29(d,J=6.8Hz,6H),1.25(d,J=6.8Hz,6H ),1.08(dd,J=10.0,6.8Hz,12H),0.99(d,J=6.8Hz,6H),0.84(d,J=6.8Hz,6H). 13C NMR (101MHz, CDCl3) δ164.21,163.47,163.15,151.31,146.75,146.33,145.36,144.85,136. 03,134.67,133.37,130.93,130.73,129.63,128.96,128.31,128.12,127.80,127.04,126.67 ,124.26,124.11,124.07,123.93,123.78,122.36,121.77,121.27,119.76,117.77,113.74, 67.03,66.15,52.70,48.03,29.98,29.15,24.75,24.54,24.29,24.04,23.77.HRMS(ESI):m / z calcd for C 104 H 91 Cl2N6O 10 [M+H] + 1654.6202,found1654.6174.λ max is 816nm, λ max FL is 842nm, λ max CL It is 849nm.

[0069] The combination of NMR characterization data and the molecular weight given by mass spectrometry shows that the structure of the obtained compound is correct.

[0070] Example 7

[0071] The preparation of the compound of formula B-2, the reaction equation is as follows:

[0072]

[0073] Synthesis of Formula B-2: 1b (400.0 mg, 0.26 mmol) and cesium carbonate (767.9 mg, 2.36 mmol) were added to a 10 mL reaction tube. The tube was evacuated and purged with nitrogen three times. 2.0 mL of hexahydropyridine was then added and the reaction was carried out in an oxygen-free environment. The reaction was carried out at 50°C for 30 min. Subsequently, 25 mL of dichloromethane and 50 mL of deionized water were added for extraction. The aqueous phase was washed with dichloromethane (25 mL x 3). The organic phases were combined and dried over anhydrous sodium sulfate. The organic solvent was removed by rotary evaporation to obtain a grass-green crude product. The crude product was separated by silica gel column chromatography (PE / DCM = 2:1, v / v) to obtain a grass-green solid of Formula B-2, 258.3 mg, 61%. 1H NMR (400MHz, CDCl3) δ9.98(s,2H),9.21(s,2H),8.99(s,2H),7.59–7.38(m,8H),7.32(dd,J=7.7,1.4Hz,2H),7.23(dd,J=7.3 ,1.8Hz,2H),4.56(d,J=14.2Hz,2H),4.37(t,J=12.0Hz,2H),3.56(h,J=7.0Hz,2H),3.13(t,J=11.4Hz,2H),3.00(p,J=6.8Hz, 2H),2.62–2.48(m,4H),2.38(p,J=6.8Hz,2H),2.09(s,2H),1.84(d,J=23.9Hz,6H),1.60(d,J=6.8Hz,8H),1.54(s,2H),1.43 (d,J=6.8Hz,6H),1.26(dd,J=17.9,6.8Hz,12H),1.08(dd,J=12.4,6.8Hz,12H),0.99(d,J=6.8Hz,6H),0.85(d,J=6.8Hz,6H). 13 CNMR(101MHz,CDCl3)δ164.51,164.38,163.73,163.31,151.96,146.88,146.37,145.42,144.84,1 35.97,135.55,133.27,131.13,130.93,129.95,129.53,129.31,128.91,128.34,127.41,127.14,1 26.69,124.19,124.03,123.72,123.61,122.59,121.39,120.42,119.50,117.53,112.45,53.48,4 9.28,41.10,29.97,29.13,26.38,26.30,24.80,24.56,24.32,24.10,24.02,23.77.HRMS(ESI):m / z calcd for C 106 H 95 Cl2N6O8[M+H] + 1650.6617,found1650.6622.λ max It is 839nm.

[0074] The combination of NMR characterization data and the molecular weight given by mass spectrometry shows that the structure of the obtained compound is correct.

[0075] Example 8

[0076] The preparation of the compound of formula B-3, the reaction equation is as follows:

[0077]

[0078] Synthesis of Formula B-3: 1b (400.0 mg, 0.26 mmol) and cesium carbonate (767.9 mg, 2.36 mmol) were added to a 10 mL reaction tube. The tube was evacuated and purged with nitrogen three times. 2.0 mL of N-methylpiperazine was then added and the reaction was carried out in an oxygen-free environment. The reaction was carried out at 50°C for 30 min. Subsequently, 25 mL of dichloromethane and 50 mL of deionized water were added for extraction. The aqueous phase was washed with dichloromethane (25 mL x 3). The organic phases were combined and dried over anhydrous sodium sulfate. The organic solvent was removed by rotary evaporation to obtain a grass-green crude product. The crude product was separated by silica gel column chromatography (PE / DCM = 2:1, v / v) to obtain Formula B-3 as a grass-green solid, 313.5 mg, 72% yield. 1 H NMR (400MHz, CDCl3) δ10.00(s,2H),9.18(s,2H),9.00(s,2H),7.49(ddd,J=32.9,16.8,8.1Hz,8H),7.32(d,J= 7.5Hz,2H),7.25(d,J=7.4Hz,2H),4.60–4.42(m,4H),3.54(p,J=6.8Hz,2H),3.25(s,4H),2.99(h,J=6.7Hz,3H ),2.74(s,6H),2.52(p,J=6.9Hz,8H),2.37(p,J=6.8Hz,3H),1.60(d,J=6.8Hz,6H),1.43(d,J=6.8Hz,6H),1.2 9(d,J=7.0Hz,6H),1.24(d,J=6.7Hz,6H),1.08(t,J=6.2Hz,12H),0.98(d,J=6.8Hz,6H),0.84(d,J=6.9Hz,6H). 13C NMR (101MHz, CDCl3) δ164.26,163.52,163.21,151.42,146.76,146.35,145.39,144.90,136.02,134.9 3,133.36,130.97,130.78,130.64,129.60,128.86,128.70,128.16,127.70,127.10,127.04,126.70,1 24.22,124.09,124.03,123.86,123.76,123.71,122.41,121.75,121.07,119.69,117.70,55.09,54.5 5,52.22,47.59,45.91,29.97,29.15,24.75,24.55,24.30,24.07,24.03,23.78,23.75.HRMS(ESI):m / z calcd forC 106 H 97 Cl2N8O8[M+H] + 1680.6835, found 1680.6884.λ max is 819nm, λ max FL is 841nm, λ max CL It is 846nm.

[0079] The combination of NMR characterization data and the molecular weight given by mass spectrometry shows that the structure of the obtained compound is correct.

[0080] Example 9

[0081] The preparation of the compound of formula B-4, the reaction equation is as follows:

[0082]

[0083] Synthesis of Formula B-4: 1b (400.0 mg, 0.26 mmol) and cesium carbonate (767.9 mg, 2.36 mmol) were added to a 10 mL reaction tube. The tube was evacuated and purged with nitrogen three times. 2.0 mL of N-cyclopropylpiperazine was then added and the reaction was carried out in an oxygen-free environment. The reaction was carried out at 50°C for 30 min. Subsequently, 25 mL of dichloromethane and 50 mL of deionized water were added for extraction. The aqueous phase was washed with dichloromethane (25 mL x 3). The organic phases were combined and dried over anhydrous sodium sulfate. The organic solvent was removed by rotary evaporation to obtain a grass-green crude product. The crude product was separated by silica gel column chromatography (PE / DCM = 2:1, v / v) to obtain 309.5 mg of Formula B-4 as a grass-green solid (69%). 11H NMR (400 MHz, CDCl3) δ 10.00 (s, 2H), 9.21 (s, 2H), 8.99 (s, 2H), 7.58–7.39 (m, 8H), 7.32 (dd, J = 7.7, 1.5 Hz, 2H), 7.25 (dd, J = 7.4, 1.8 Hz, 2H), 4.45 (s, 4H), 3.56 (h, J = 6.8 Hz, 2H), 3.24 (s, 4H), 3.00 (h, J = 6.7 Hz, 2H), 2.80 (s, 4H), 2.52 (h, J = 6.7 Hz, 4H), 2.38 (hept, J = 6.9 Hz, 2H), 2.27 (s, 2H), 1.72 (s, 2H), 1.61 (d, J = 6.8 Hz, 6H), 1.44 (d, J = 6.8 Hz, 6H), 1.30 (d, J = 6.8 Hz, 6H), 1.25 (d, J = 6.7 Hz, 6H), 1.08 (t, J = 7.4 Hz, 12H), 0.99 (d, J = 6.8 Hz, 6H), 0.85 (d, J = 6.8 Hz, 6H), 0.52 (s, 8H). 13 13C NMR (101 MHz, CDCl3) δ 164.39, 164.32, 163.56, 163.24, 151.58, 146.84, 146.37, 145.40, 144.87, 136.02, 135.12, 133.31, 131.05, 130.85, 130.54, 129.61, 129.57, 128.84, 128.72, 128.24, 127.65, 127.14, 127.09, 126.69, 124.24, 124.09, 124.04, 123.84, 123.77, 123.72, 122.49, 121.67, 120.92, 119.69, 117.67, 113.18, 53.48, 53.00, 52.48, 47.85, 38.34, 29.99, 29.16, 29.12, 24.79, 24.59, 24.34, 24.10, 24.05, 23.80, 23.76, 6.17, 5.99. HRMS (ESI): m / z calcd for C 110 H 101 Cl2N8O8 [M + H] + 1732.7148, found 1732.7131. λ max is 821 nm, λ max FL is 849 nm, λ max CL is 850 nm.

[0084] The combination of NMR characterization data and the molecular weight given by mass spectrometry shows that the structure of the obtained compound is correct.

[0085] Prepare a UV-2501PC ultraviolet spectrometer and scan the wavelength range from 300 nm to 900 nm.

[0086] UV-vis absorption spectrum test conditions: All products were dissolved in dichloromethane solution, and the concentration of the prepared solution was 2×10 -5 mol / L, a two-way quartz cuvette was selected as the sample cell, and the scanning range was set to 300nm-900nm.

[0087] Table 1 Maximum UV absorption wavelength of each compound

[0088] sample Formula A-1 Formula A-2 Formula A-3 Formula A-4 Peak absorption wavelength (nm) 797 799 798 801 sample Formula B-1 Formula B-2 Formula B-3 Formula B-4 Peak absorption wavelength (nm) 842 --- 841 821

[0089] The maximum ultraviolet absorption wavelengths of the compounds represented by formulas A-1 to B-4 are shown in Table 1. It can be seen that the bisperylene diimide compounds of the present invention, which are connected to an N-heterocyclic group, have an N-heterocyclic group in the bisperylene diimide structure, which shifts the maximum ultraviolet absorption wavelength to a near-infrared band exceeding 750 nm. A Shimadzu RF-5301PC fluorescence spectrometer was prepared, with a scanning wavelength range of 300 nm to 900 nm. After completing the above-mentioned ultraviolet test, the test solution was used in parallel to test its fluorescence spectrum. A four-way quartz cuvette was selected as the sample cell. The excitation wavelength was the maximum absorption wavelength of the corresponding sample. The starting wavelength was set according to the maximum absorption wavelength value of each sample, and the end wavelength was set to 900 nm.

[0090] Table 2 Maximum fluorescence emission wavelength of each compound

[0091] sample Formula A-1 Formula A-2 Formula A-3 Formula A-4 Peak emission wavelength (nm) 828 849 819 851 sample Formula B-1 Formula B-2 Formula B-3 Formula B-4 Peak emission wavelength (nm) 816 --- 846 849

[0092] The maximum fluorescence emission wavelengths of the compounds represented by Formulas A-1 to B-4 are shown in Table 2. It can be seen that the bisperylene diimide compounds of the present invention, which are connected to an N-heterocyclic group, have a maximum fluorescence emission wavelength shifted to the near-infrared band exceeding 750nm when an N-heterocyclic group is present on the bisperylene diimide structure. A Shimadzu RF-5301PC fluorescence spectrometer was used, with a scanning wavelength range of 300nm-900nm. Chemiluminescence spectrum test conditions: A four-way quartz cuvette was used as the sample cell, 2mg of the compound was weighed, 1mL of diaryl oxalate solution was added, and 1mL of hydrogen peroxide solution was immediately added after sufficient dissolution. The compound was then tested using a fluorescence spectrometer in a test range of 300nm-900nm.

[0093] Table 3 Maximum chemiluminescence wavelength of each compound

[0094] sample Formula A-1 Formula A-2 Formula A-3 Formula A-4 Peak emission wavelength (nm) 848 847 844 848 sample Formula B-1 Formula B-2 Formula B-3 Formula B-4 Peak emission wavelength (nm) 849 --- 846 850

[0095] The maximum chemiluminescence wavelengths of the compounds represented by Formulas A-1 to B-4 are shown in Table 3. It can be seen that the bisperylene diimide compounds of the present invention, incorporating an N-heterocyclic group, exhibit a maximum chemiluminescence wavelength shifted to the near-infrared range exceeding 750 nm when an N-heterocyclic group is present in the bisperylene diimide structure. A UV-2501PC ultraviolet spectrometer and an 808 nm LED light source were prepared.

[0096] The conditions for the photostability test are as follows: the commercial photosensitizer ICG and the compounds of formula 1-1 to formula 1-5 are dissolved in DMF solution respectively, and 2×10 -5 mol / L solution. The solution was irradiated with an 808nm LED light source for 12 minutes at an irradiance of 0.5W / cm 2 After every two minutes of irradiation, a UV test is performed to indirectly characterize the photostability of the compound by the change in the UV absorption curve.

[0097] Table 4 Photostability properties of each compound

[0098] sample ICG Formula A-1 Formula A-2 Formula A-3 Formula A-4 A(％) 12 78 81 73 78 sample Formula B-1 Formula B-2 Formula B-3 Formula B-4 A(％) 84 66 79 67

[0099] Note: A (%) is the ratio of the sample absorbance after 12 minutes of irradiation to the initial absorbance. The photostability of the compounds represented by Formula A-1 to Formula B-4 and the comparative compound ICG are shown in Table 4. It can be seen that the bisperylene diimide compound with an N-heterocyclic group connected thereto of the present invention has more stable photostability than the commercial photosensitizer ICG when an N-heterocyclic group exists on the bisperylene diimide structure.

[0100] Prepare a UV-2501PC ultraviolet spectrometer and an 808 nm LED light source.

[0101] Test conditions: ICG and the compounds of formula A-1 to formula B-4 were dissolved in DMSO solution to prepare 3×10 - 6 mol / L solution, take 1mL of sample solution in a two-way quartz cuvette, then add an appropriate amount of DPBF DMSO solution so that the absorbance of the solution at 410nm is about 0.8. Then irradiate the solution with an 808nm LED light source under light-proof conditions with an irradiance of 1W / cm 2 After irradiation for a certain period of time, a UV test is performed to detect changes in the absorbance of the solution. The entire process is carried out under light-proof conditions.

[0102] Table 5 Singlet oxygen quantum yield of each compound

[0103] sample ICG Formula A-1 Formula A-2 Formula A-3 Formula A-4 Φ(%) 7.7 7.5 20.7 15.4 14.1 sample Formula B-1 Formula B-2 Formula B-3 Formula B-4 Φ(%) 50.2 37.9 31.0 32.8

[0104] The photostability properties of the compounds represented by Formula A-1 to Formula B-4 and the comparative compound ICG are shown in Table 4. It can be seen that the bisperylene diimide compound of the present invention having an N-heterocyclic group connected thereto has a more efficient singlet oxygen quantum yield than the commercial photosensitizer ICG when an N-heterocyclic group exists on the bisperylene diimide structure.

Claims

1. A near-infrared dye based on an N-heterocyclic substituted bisperylene functional group and its preparation method and application, characterized in that In Formula 1, R represents a substituted or unsubstituted alkyl or aryl group; X and Y are selected from N-heterocyclic groups and halogens, and at least one substituent is an N-heterocyclic group, and the N-heterocyclic group is connected to the bisperylene skeleton through a CN bond. 。 2. The near-infrared dye based on N-heterocyclic substituted bisperylene functional groups and its preparation method and use according to claim 1, characterized in that: In formula 1, R is selected from a C4-C18 straight-chain alkyl group or an ether-substituted straight-chain alkyl group, or a phenyl group or an alkyl-substituted phenyl group.

3. The compound according to any one of claims 1 to 2, characterized in that: The N-heterocyclic group is a three-membered, four-membered, five-membered or six-membered aliphatic nitrogen-containing heterocyclic group selected from 1-aziridine, 1-azetidinyl, N-tetrahydropyrrolyl, N-hexahydropyridinyl, N-morpholinyl, N-thiomorpholinyl, N-piperazinyl, N-(N'-methyl)piperazinyl, N-(N'-ethyl)piperazinyl, N-(N'-propyl)piperazinyl, N-(N'-butyl)piperazinyl, N-(N'-cyclopropyl)piperazinyl, N-(N'-acetyl)piperazinyl; the halogen is bromine or chlorine.

4. The compound according to any one of claims 1 to 3, characterized in that: In formula 1, the substitutions of X and Y are as follows 1) or 2): 1) One substituent is the N-heterocyclic group, and the other three substituents are all halogens; 2) Two substituents are the N-heterocyclic groups, and the other two substituents are halogens.

5. The method for preparing the compound according to any one of claims 1 to 2, characterized in that The method uses an N-heterocyclic compound as a reaction reagent, a solvent and an acid-binding agent to react with a tetrahalogenated bisperylene derivative.

6. The method according to claim 5, characterized in that The N-heterocyclic compound used is selected from aziridine, azetidine, tetrahydropyrrole, hexahydropyridine, morpholine, thiomorpholine, piperazine, N-methylpiperazine, N-ethylpiperazine, N-propylpiperazine, N-butylpiperazine, N-cyclopropylpiperazine, and N-acetylpiperazine.

7. The method according to claim 5, characterized in that The reaction temperature of the reaction is -10-60° C., and the reaction time is 5-60 minutes.

8. Use of the compound according to any one of claims 1 to 4 in the near infrared field, characterized in that As a near-infrared absorbing and emitting dye, it is used in the field of near-infrared chemiluminescence of diaryl oxalate-hydrogen peroxide.

9. Use of the compound according to any one of claims 1 to 4 as a near-infrared photosensitizer for generating singlet oxygen in photodynamic therapy.

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