Superbright NIR-II fluorescent molecule and application thereof

Abstract

The invention provides a superbright NIR-II fluorescent molecule and application thereof, and belongs to the field of fluorescent molecule design. Shielding electrons of a shielding unit in the superbright NIR-II fluorescent molecule interact with molecules of an electron acceptor aromatic unit and / or an electron donor aromatic unit; the intermolecular and intramolecular interaction of a conjugated skeleton formed by the electron acceptor aromatic unit, the electron donor aromatic unit and the shielding unit is weakened, so that the quantum yield is improved; by limiting the structure of an electron donor aromatic unit and / or a shielding unit in the super-bright NIR-II fluorescent molecule, the super-bright NIR-II fluorescent molecule can be excited to generate super-bright fluorescence under the excitation wavelength of 808nm. The result of the embodiment shows that the quantum yield of the superbright NIR-II fluorescent molecule provided by the invention can reach 61.6%, and the superbright NIR-II fluorescent molecule has high quantum yield, so that the fluorescent brightness of the NIR-II fluorescent molecule is improved.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of fluorescent molecule design, and particularly relates to a super-bright NIR-II fluorescent molecule and application thereof. BACKGROUND

[0002] The emergence of near-infrared region 2 (NIR-II, 1000-1700 nm) phototherapy technology opens up new opportunities for biomedical imaging and treatment. The light in this wavelength range has excellent tissue penetration ability, can effectively penetrate biological tissues and reduce light scattering, thus making deep tissue imaging and treatment possible.

[0003] At the same time, the maximum permissible exposure (MPE) of NIR-II phototherapy technology provides higher safety and effectiveness for clinical application, which makes it attract much attention in the fields of tumor treatment, targeted drug delivery and biological imaging. In order to realize the fluorescence (radiative transition), photothermal (non-radiative transition) and photodynamic properties (reactive oxygen species (ROS) generation) at the same time, the design and function of the phototherapeutic agent need to be finely regulated. The fluorescence property can be used for real-time imaging, while the photothermal property can effectively convert light energy into heat energy to kill tumor cells; at the same time, the photodynamic property relies on the generated ROS to cause oxidative stress of cells, further enhancing the treatment effect. In a related study, a fluorescent molecule with an absorption wavelength greater than 1000 nm can emit fluorescence in the range of 900-1400 nm, which can significantly reduce light scattering and reabsorption, and realize efficient biological imaging. However, the excitation wavelength of this fluorescent molecule is also correspondingly increased to more than 1000 nm, and the excitation cost will also increase accordingly. However, the commonly used equipment at the present stage generally has an excitation wavelength less than 1000 nm, such as 808 nm, but when the fluorescent molecule is excited by an excitation wavelength of 808 nm, the fluorescence brightness is usually low and the imaging quality is poor. SUMMARY

[0004] The present application aims to provide a super-bright NIR-II fluorescent molecule and application thereof. The super-bright NIR-II fluorescent molecule provided by the present application can have a high quantum yield at an excitation wavelength of 808 nm, thereby improving the fluorescence brightness of the NIR-II fluorescent molecule.

[0005] In order to achieve the above-mentioned application purposes, the present application provides the following technical solutions: The present application provides a super-bright NIR-II fluorescent molecule, comprising: an electron acceptor aromatic unit, an electron donor aromatic unit and a shielding unit. The shielding unit is located at at least one end of the super-bright NIR-II fluorescent molecule and is covalently connected to the electron donor aromatic unit; The two free bonds in the electron acceptor aromatic unit are independently covalently connected to the electron donor aromatic unit or halogen; In the aforementioned ultra-bright NIR-II fluorescent molecule, the structural formula of each electron acceptor aromatic unit is independently as follows: One or more of them; In the structural formula of the ultrabright NIR-II fluorescent molecule, Z1, Z2, Z3, and Z4 are independently O, S, Se, N, or Ti; R is independently H or -C. n1 H 2n1+1 Or tert-butyloxycarbonyl; the -C n1 H 2n1+1 In this context, n1 is an integer in the range of 1 to 12; In the aforementioned ultra-bright NIR-II fluorescent molecule, the structural formula of each electron-donating aromatic unit is independently as follows: One or more of them; In the structural formula of the ultra-bright NIR-II fluorescent molecule, P1 and P2 are independently H and -OC. n2 H 2n2+1 -C n2 H 2n2+1 , , -OC n2 H 2n2 B or -C n2 H 2n2 Z; X is independently S, Se, N, O, Ti, or R1; R1 is independently H, -C n1 H 2n1+1 Or alkoxy; m is an integer in the range of 0 to 6; The or -OC n2 H 2n2 The B in B can be Br, I, OTs, OMs, ONs, N3, or OMe independently; The -C n2 H 2n2 Z in Z is Br or N3; The -OC n2 H 2n2+1 -C n2 H 2n2+1 -OC n2 H 2n2 B or -C n2 H 2n2 In Z, n2 is an integer in the range of 1 to 20 independently; The or p in the equation is an integer in the range of 1 to 20. In the ultra-bright NIR-II fluorescent molecule, the structural formula of the shielding unit is independently: , or ; In the structural formula of the ultra-bright NIR-II fluorescent molecule, R2 is independently -(CH2). n3 W, the -(CH2) n3 In W, n3 is an integer in the range of 1 to 20, and -(CH2) n3 The W in W represents H, Br, I, OH, Ots, or N3. , , or The In this context, n is an integer in the range of 4 to 120. or In this context, b is an integer in the range of 1 to 6; Z5 is S, Se, O, or N; X1 is Si, Ge, or C. In the aforementioned ultra-bright NIR-II fluorescent molecule, at least the electron donor aromatic unit includes Or the shielding unit is , , or .

[0006] Preferably, the number of electron acceptor aromatic units in the ultra-bright NIR-II fluorescent molecule does not exceed 3, and the number of electron donor aromatic units does not exceed 3.

[0007] Preferably, the ultra-bright NIR-II fluorescent molecule comprises a shielding unit, an electron donor aromatic unit, and an electron acceptor aromatic unit, and has an S'-DAM structure; Where S' represents the shielding unit, D represents the electron donor aromatic unit, A represents the electron acceptor aromatic unit, and M represents the halogen.

[0008] Preferably, the ultra-bright NIR-II fluorescent molecule comprises two shielding units, one electron acceptor aromatic unit, and two electron donor aromatic units, having a structure of S'1-D1-A-D2-S'2; Wherein, S'1 represents the first shielding unit, S'2 represents the second shielding unit, D1 represents the first electron donor aromatic unit, D2 represents the second electron donor aromatic unit, and A represents the electron acceptor aromatic unit.

[0009] Preferably, the super-bright NIR-II fluorescent molecule comprises two electron acceptor aromatic units, three electron donor aromatic units and two shielding units, having a structure of S'3-D3-A1-D5-A2-D4-S'4; wherein S'3 represents the third shielding unit, S'4 represents the fourth shielding unit, D3 represents the third electron donor aromatic unit, D4 represents the fourth electron donor aromatic unit, D5 represents the fifth electron donor aromatic unit, A1 represents the first electron acceptor aromatic unit, and A2 represents the second electron acceptor aromatic unit.

[0010] Preferably, the electron donor aromatic unit in the super-bright NIR-II fluorescent molecule comprises , and the shielding unit is , , or .

[0011] Preferably, the electron acceptor aromatic unit has a structure of .

[0012] Preferably, in the structure of the super-bright NIR-II fluorescent molecule, Z1 and Z2 are independently O, S, Se or N; P1 and P2 are independently -C n2 H 2n2+1 , -OC n2 H 2n2+1 , -OC n2 H 2n2 B, or , n2 in -OC n2 H 2n2+1 , -C n2 H 2n2+1 or -OC n2 H 2n2 B is independently an integer in the range of 4-16, and B in -OC H n2 H 2n2 B is independently Br, OTs, OMs, N3 or OMe, and p in or is independently an integer in the range of 4-12.

[0013] Preferably, in the structure of the super-bright NIR-II fluorescent molecule, Z1 and Z2 are independently S or Se; P1 and P2 are independently -C n2 H 2n2+1 , -OC n2 H 2n2+1 or -OC n2 H 2n2 B, n2H 2n2+1 , -C n2 H 2n2+1 or -OC n2 H 2n2 n2 in B is independently an integer in the range of 6-12, said -OC n2 H 2n2 B in B is Br, OTs, OMs, N3 or OMe.

[0014] The application also provides application of the super-bright NIR-II fluorescent molecule or the kit in non-disease diagnosis biomedical imaging or labeling of biological macromolecules.

[0015] The super-bright NIR-II fluorescent molecule provided by the application comprises: an electron acceptor aromatic unit, an electron donor aromatic unit and a shielding unit; the shielding unit is located at at least one end of the super-bright NIR-II fluorescent molecule and is covalently connected with the electron donor aromatic unit; two free bonds in the electron acceptor aromatic unit are independently covalently connected with the electron donor aromatic unit or hydrogen; at least the electron donor aromatic unit in the super-bright NIR-II fluorescent molecule comprises or the shielding unit is , , or The shielding unit in the super-bright NIR-II fluorescent molecule provided by the application is located at at least one end of the super-bright NIR-II fluorescent molecule and is covalently connected with the electron donor aromatic unit; two free bonds in the electron acceptor aromatic unit are independently covalently connected with the electron donor aromatic unit or hydrogen; the intermolecular interaction of the conjugated skeleton formed by the electron acceptor aromatic unit, the electron donor aromatic unit and the shielding unit is weakened by the shielding of the shielding unit to the intermolecular and intramolecular interaction of the electron acceptor aromatic unit and / or the electron donor aromatic unit, so that the quantum yield is improved; by limiting the structure of the electron donor aromatic unit and / or the shielding unit in the super-bright NIR-II fluorescent molecule, the super-bright NIR-II fluorescent molecule can be excited to produce super-bright fluorescence under an excitation wavelength of 808 nm. The results of the embodiments show that the quantum yield of the super-bright NIR-II fluorescent molecule provided by the application can reach 61.6%, and the super-bright NIR-II fluorescent molecule has high quantum yield, thereby improving the fluorescence brightness of the NIR-II fluorescent molecule. BRIEF DESCRIPTION OF DRAWINGS

[0016] Figure 1 The hydrogen spectrum of compound 5 in Example 1 of the application; Figure 2 The carbon spectrum of compound 5 in Example 1 of the application; Figure 3 The mass spectrum of compound 5 in Example 1 of the application; Figure 4 hydrogen spectrum of compound 8 in Example 1 of the present invention; Figure 5 carbon spectrum of compound 8 in Example 1 of the present invention; Figure 6 mass spectrum of compound 8 in Example 1 of the present invention; Figure 7 hydrogen spectrum of compound 5 in Example 2 of the present invention; Figure 8 carbon spectrum of compound 5 in Example 2 of the present invention; Figure 9 hydrogen spectrum of compound 8 in Example 2 of the present invention; Figure 10 carbon spectrum of compound 8 in Example 2 of the present invention; Figure 11 mass spectrum of compound 8 in Example 2 of the present invention; Figure 12 hydrogen spectrum of compound 6 in Example 4 of the present invention; Figure 13 carbon spectrum of compound 6 in Example 4 of the present invention; Figure 14 mass spectrum of compound 6 in Example 4 of the present invention; Figure 15 hydrogen spectrum of compound 9 in Example 4 of the present invention; Figure 16 carbon spectrum of compound 9 in Example 4 of the present invention; Figure 17 mass spectrum of compound 9 in Example 4 of the present invention; Figure 18 hydrogen spectrum of compound 5 in Example 5 of the present invention; Figure 19 carbon spectrum of compound 5 in Example 5 of the present invention; Figure 20 mass spectrum of compound 5 in Example 5 of the present invention; Figure 21 hydrogen spectrum of compound 3 in Example 6 of the present invention; Figure 22 carbon spectrum of compound 3 in Example 6 of the present invention; Figure 23 hydrogen spectrum of compound 4 in Example 6 of the present invention; Figure 24 carbon spectrum of compound 4 in Example 6 of the present invention; Figure 25 hydrogen spectrum of compound 6 in Example 7 of the present invention; Figure 26The carbon spectrum of compound 6 in the embodiment 7 of the present application; Figure 27 The hydrogen spectrum of compound 7 in the embodiment 7 of the present application; Figure 28 The carbon spectrum of compound 7 in the embodiment 7 of the present application; Figure 29 The mass spectrum of compound 7 in the embodiment 7 of the present application; Figure 30 The hydrogen spectrum of compound 8 in the embodiment 8 of the present application; Figure 31 The carbon spectrum of compound 8 in the embodiment 8 of the present application; Figure 32 The hydrogen spectrum of compound 9 in the embodiment 8 of the present application; Figure 33 The carbon spectrum of compound 9 in the embodiment 8 of the present application; Figure 34 The absorption spectrum of the super-bright NIR-II fluorescent molecule in the embodiments 1-3 of the present application; Figure 35 The fluorescence spectrum of the super-bright NIR-II fluorescent molecule in the embodiments 1-3 of the present application; Figure 36 The absorption spectrum of the super-bright NIR-II fluorescent molecule in the embodiments 6-8 of the present application; Figure 37 The fluorescence spectrum of the super-bright NIR-II fluorescent molecule in the embodiments 6-8 of the present application; Figure 38 The absorption spectrum of the TPA-C8NPs, OMe-TPA-C8NPs and t-Bu-TPA-C8NPs of the present application; Figure 39 The fluorescence spectrum of the TPA-C8NPs, OMe-TPA-C8NPs and t-Bu-TPA-C8NPs of the present application. DETAILED DESCRIPTION

[0017] The present application provides a super-bright NIR-II fluorescent molecule, comprising: an electron acceptor aromatic unit, an electron donor aromatic unit and a shielding unit. The shielding unit is located at at least one end of the super-bright NIR-II fluorescent molecule and is covalently connected with the electron donor aromatic unit. The two free bonds in the electron acceptor aromatic unit are independently covalently connected with the electron donor aromatic unit or halogen.

[0018] In the present application, the number of electron acceptor aromatic units in the super-bright NIR-II fluorescent molecule is no more than 3, preferably no more than 2; the number of electron donor aromatic units is no more than 3, preferably no more than 2. The present application limits the number of electron acceptor aromatic units and electron donor aromatic units in the super-bright NIR-II fluorescent molecule to the above range, which can ensure that the molecular weight of the super-bright NIR-II fluorescent molecule is not too large.

[0019] In the present application, the structural formula of each electron acceptor aromatic unit in the super-bright NIR-II fluorescent molecule is independently one or more of , preferably .

[0020] In the structural formula of the super-bright NIR-II fluorescent molecule, Z1, Z2, Z3 and Z4 are independently O, S, Se, N or Ti, preferably independently O, S, Se or N, more preferably independently S or Se; R is independently H, -C n1 H 2n1+1 or tert-butoxycarbonyl; the -C n1 H 2n1+1 n1 in the above is an integer in the range of 1 to 12.

[0021] In an embodiment of the present application, the electron acceptor aromatic unit is , wherein in one embodiment of the present application Z1 and Z2 are both S, and in another embodiment of the present application Z1 is S and Z2 is Se. The present application limits the structural formula of the electron acceptor aromatic unit to the above types, which can be beneficial for interaction with the electron donor aromatic unit and the shielding unit, and improve the brightness of the super-bright NIR-II fluorescent molecule.

[0022] In the present application, the structural formula of each electron donor aromatic unit in the super-bright NIR-II fluorescent molecule is independently one or more of .

[0023] In the structural formula of the super-bright NIR-II fluorescent molecule, P1 and P2 are independently H, OC n2 H 2n2+1 , C n2 H 2n2+1 , , , OC n2 H 2n2 B or C n2 H 2n2 Z, preferably independently Cn2 H 2n2+1 OC n2 H 2n2+1 OC n2 H 2n2 B or More preferably, independently for C n2 H 2n2+1 OC n2 H 2n2+1 or OC n2 H 2n2 B; X is independently S, Se, N, O, Ti, or R1, preferably independently O, S, Se, or N; R1 is independently H, C n1 H 2n1+1 or alkoxy; the or -OC n2 H 2n2 The B in B is independently Br, I, OTs, OMs, ONs, N3, or OMe, preferably independently Br, OTs, OMs, N3, or OMe; the -C n2 H 2n2 Z in Z is Br or N3; the -OC n2 H 2n2+1 -C n2 H 2n2+1 -OC n2 H 2n2 B or -C n2 H 2n2 In Z, n2 is independently an integer in the range of 1 to 20, preferably an integer in the range of 4 to 16, and more preferably an integer in the range of 6 to 12; or In this context, p is an integer independently ranging from 1 to 20, preferably an integer independently ranging from 4 to 12; m is an integer independently ranging from 0 to 6.

[0024] In one embodiment of the present invention, the electron donor aromatic unit can be Where Z1 and Z2 can both be S, and P1 and P2 can both be H or -OC. n2 H 2n2+1 or -C n2 H 2n2+1 The -OC n2 H 2n2+1 It can be -OCH3 or -OC8H 17 The -C n2 H 2n2+1 It can be -C8H 17 .

[0025] As another embodiment of the present application, the electron donor aromatic unit can be and wherein Z1 and Z2 can both be S, P1 and P2 can both be H or -C n2 H 2n2+1 ; the -C n2 H 2n2+1 may be -C8H 17 The present application limits the structural formula of the electron donor aromatic unit to the above-mentioned types, which can be beneficial for interaction with the electron acceptor aromatic unit and the shielding unit, and improve the brightness of the super-bright NIR-II fluorescent molecule.

[0026] In the present application, the structural formula of the shielding unit in the super-bright NIR-II fluorescent molecule is independently , or , preferably , or .

[0027] In the structural formula of the super-bright NIR-II fluorescent molecule, R2 is independently - (CH2) n3 W; n3 in the - (CH2) n3 W is an integer in the range of 1-20, preferably an integer in the range of 4-16; W in the - (CH2) n3 W is H, Br, I, OH, Ots, N3, , , or , preferably N3, , or ; n in the - (CH2) is an integer in the range of 4-120, preferably an integer in the range of 10-100; b in the - (CH2) or is independently an integer in the range of 1-6, preferably independently an integer in the range of 2-4; Z5 is independently S, Se, O or N; X1 is independently Si, Ge or C.

[0028] In one embodiment of the present application, the shielding unit is .

[0029] In another embodiment of the present application, the shielding unit is .

[0030] In another embodiment of the present application, the shielding unit is .

[0031] In another embodiment of the present application, the shielding unit is .

[0032] The present application limits the structure of the shielding unit to the above-mentioned type, which can be beneficial for interaction with the electron donor aromatic unit and / or the electron acceptor aromatic unit, and improve the brightness of the super-bright NIR-II fluorescent molecule.

[0033] As an embodiment of the present application, the super-bright NIR-II fluorescent molecule comprises one shielding unit, one electron donor aromatic unit and one electron acceptor aromatic unit, and has the structure of S'-D-A-M; wherein S' represents the shielding unit, D represents the electron donor aromatic unit, A represents the electron acceptor aromatic unit, and M represents halogen.

[0034] As another embodiment of the present application, the super-bright NIR-II fluorescent molecule comprises two shielding units, one electron acceptor aromatic unit and two electron donor aromatic units, and has the structure of S'1-D1-A-D2-S'2; wherein S'1 represents the first shielding unit, S'2 represents the second shielding unit, D1 represents the first electron donor aromatic unit, D2 represents the second electron donor aromatic unit, and A represents the electron acceptor aromatic unit.

[0035] As another embodiment of the present application, the super-bright NIR-II fluorescent molecule comprises two electron acceptor aromatic units, three electron donor aromatic units and two shielding units, and has the structure of S'3-D3-A1-D5-A2-D4-S'4; wherein S'3 represents the third shielding unit, S'4 represents the fourth shielding unit, D3 represents the third electron donor aromatic unit, D4 represents the fourth electron donor aromatic unit, D5 represents the fifth electron donor aromatic unit, A1 represents the first electron acceptor aromatic unit, and A2 represents the second electron acceptor aromatic unit.

[0036] The present application limits the arrangement of the structural units of the super-bright NIR-II fluorescent molecule to the above-mentioned type, which can better improve the brightness of the NIR-II fluorescent molecule.

[0037] In an embodiment of the present application, the super-bright NIR-II fluorescent molecule has a chemical structure as shown in any one of Formula I to Formula VIII: Formula I.

[0038] Formula II.

[0039] Formula III.

[0040] Formula IV.

[0041] Formula V.

[0042] Formula VI.

[0043] Formula VII.

[0044] Formula VIII.

[0045] The shielding unit in the super-bright NIR-II fluorescent molecule provided by the application is located at at least one end of the super-bright NIR-II fluorescent molecule, and is covalently connected with the electron donor aromatic unit, two free bonds in the electron acceptor aromatic unit are independently covalently connected with the electron donor aromatic unit or hydrogen, the intermolecular interaction of the shielding unit with the electron acceptor aromatic unit and / or the electron donor aromatic unit is reduced by shielding the electrons, so that the intermolecular and intramolecular interaction of the conjugated skeleton formed by the electron acceptor aromatic unit, the electron donor aromatic unit and the shielding unit is reduced, and the quantum yield is improved; by limiting the structure of the electron donor aromatic unit and / or the shielding unit in the super-bright NIR-II fluorescent molecule, the super-bright NIR-II fluorescent molecule can be excited to produce super-bright fluorescence under an excitation wavelength of 808 nm.

[0046] The preparation method of the super-bright NIR-II fluorescent molecule is not particularly limited in the application, and the corresponding fluorescent molecule can be obtained by substituting or adding corresponding groups by using the commonly used group addition or substitution method in the art.

[0047] The application also provides application of the super-bright NIR-II fluorescent molecule in non-disease diagnosis biomedical imaging or labeling of biological macromolecules.

[0048] The technical solutions in the application will be described clearly and completely in combination with the embodiments in the application. Obviously, the described embodiments are only some of the embodiments of the application, but not all the embodiments. Based on the embodiments in the application, all other embodiments obtained by those skilled in the art without creative labor fall within the protection scope of the application.

[0049] In the embodiments of the application, all non-preparation raw materials are commercially available products purchased from Shanghai Titan Technology Co., Ltd.

[0050] Embodiment 1 A super-bright NIR-II fluorescent molecule has the chemical structure shown in Formula I.

[0051] The synthesis of the super-bright NIR-II fluorescent molecule (IR-FDBT) of the chemical structure of formula I is as follows: The synthesis of compound 2 is described in the reference "Donor Engineering for NIR-II Molecular Fluorophores with Enhanced Fluorescent Performance" (Yang, Q.; Hu, Z.; Zhu, S.; Ma, R.; Ma, H.; Ma, Z.; Wan, H.; Zhu, T.; Jiang, Z.; Liu, W.; et al. J Am Chem Soc 2018, 140 (5), 1715-1724). Synthesis of compound 5: To a mixture of compound 3 (1 g, 7.14 mmol) and 20 mL of THF, n-BuLi (n-butyllithium, solvent hexane, concentration 1.6 M, 5.36 mL, 8.57 mmol) was added dropwise at -78 °C under nitrogen protection, and the mixture was stirred at this temperature for 2 h. Then, tri-n-butyltin chloride (2.79 g, 8.57 mmol) was added to the mixture, which was then slowly heated to room temperature and stirred for 1 h. The reaction was then extracted with ethyl acetate, and the combined organic phase was dried over anhydrous magnesium sulfate to obtain compound 4. Compound 4 obtained and compound 2 (4.05 g, 7.14 mmol) were added to a 100 ml single-necked flask, Pd(PPh3)4 (200 mg) was added under a nitrogen atmosphere, and finally dry toluene solvent 40 ml was added. After stirring the reaction at 130 °C for 3 h, it was cooled to room temperature, and then the mixture was poured into water and extracted with ethyl acetate twice or three times. The organic phase was taken and dried over anhydrous magnesium sulfate, and the crude product was subjected to column chromatography on PE / DCM 8:1 silica gel to obtain compound 5 as a colorless transparent oil (3.11 g, 69.3%).

[0052] The hydrogen spectrum data of compound 5 is as follows: 1H NMR (500 MHz, Chloroform-d) δ 7.64 (dd, J = 7.4,2.4 Hz, 2 H), 7.57 - 7.49 (m, 3 H), 7.30 - 7.20 (m, 5 H), 3.20 (t, J = 6.9Hz, 4 H), 1.97 - 1.91 (m, 4 H), 1.60 - 1.54 (m, 4 H), 1.12 (ddd, J = 7.5,5.4, 2.3 Hz, 4 H), 1.04 - 0.98 (m, 4 H), 0.65 - 0.54 (m, 4 H); Carbon spectrum data of compound 5: 13 C NMR (126 MHz, Chloroform-d) δ 151.22, 150.53,146.97, 141.05, 140.54, 140.13, 138.25, 133.69, 127.36, 127.05, 126.81,124.94, 122.81, 120.25, 119.93, 119.87, 119.64, 115.18, 55.07, 40.26, 34.01,32.63, 29.06, 27.76, 23.55; Synthesis of compound 8: To a mixture of compound 5 (3.11 g, 4.95 mmol) and 60 mL THF, n-BuLi (solvent is hexane, concentration is 1.6 M, 6.19 mL, 9.90 mmol) was added dropwise under nitrogen protection at -78 °C, and after stirring for 2 h, tri-n-butyltin chloride (3.22 g, 9.90 mmol) was added to the mixture, then the reaction was slowly heated to room temperature and stirred for 1 h, and then the mixture was extracted with ethyl acetate, and the organic phase was taken and dried over anhydrous magnesium sulfate to obtain compound 6; The obtained compound 6 and compound 7 (577 mg, 1.65 mmol) were added to a 100 ml single-necked flask, Pd (PPh3)2Cl2 (200 mg) was added under nitrogen atmosphere, and finally 40 ml of dry toluene solvent was added, and stirred at 130 °C for 3 h, and after the reaction was completed, it was returned to room temperature, then the mixture was poured into water, and extracted twice with ethyl acetate, and the combined organic phase was dried over anhydrous magnesium sulfate, and the crude product was subjected to column chromatography on PE / DCM 1:1 silica gel to obtain compound 8 as a yellow-green solid (1.05 g, 44.0%), which was recorded as IR-FDBT.

[0053] Hydrogen spectrum data of compound 8: 1H NMR (500 MHz, Chloroform-d) δ 7.46 (d, J = 8.6 Hz, 6 H), 7.28 (t, J = 2.2 Hz, 8 H), 7.08 - 7.04 (m, 4 H), 2.10 - 1.78 (m, 8 H), 1.68 - 1.48 (m, 8 H), 1.35 (s, 8 H), 1.18 (s, 24 H); Carbon spectrum data of compound 8: 13 C NMR (126 MHz, Chloroform-d) δ 147.69, 147.64,147.09, 138.54, 138.47, 124.48, 124.01, 119.11, 34.90, 34.55, 34.04, 32.69,31.94 (d, J = 3.2 Hz), 31.46, 30.33, 30.21, 29.73, 29.39, 27.85, 22.72,14.16.

[0054] The hydrogen spectrum of compound 5 in Example 1 is shown in Figure 1 , the carbon spectrum is shown in Figure 2 , and the mass spectrum is shown in Figure 3 ; the hydrogen spectrum of compound 8 (IR-FDBT) in Example 1 is shown in Figure 4 , the carbon spectrum is shown in Figure 5 , and the mass spectrum is shown in Figure 6 . As can be seen from Figures 1-6 , IR-FDBT can be synthesized in Example 1.

[0055] Example 2 A super-bright NIR-II fluorescent molecule has a chemical structure shown in the above Formula II.

[0056] The synthesis formula of the super-bright NIR-II fluorescent molecule (IR-FDA) of the Formula II chemical structure is as follows: The synthesis of compound 2 is referenced from the literature “Donor Engineering for NIR-II Molecular Fluorophores with Enhanced Fluorescent Performance” (Yang, Q.; Hu, Z.; Zhu, S.; Ma, R.; Ma, H.; Ma, Z.; Wan, H.; Zhu, T.; Jiang, Z.; Liu, W.; et al. J Am Chem Soc 2018, 140 (5), 1715-1724). Synthesis of compound 5: To a mixture solution of compound 3 (2 g, 5.49 mmol) in 20 mL THF at -78 °C under nitrogen protection, n-BuLi (solvent: hexane, concentration: 1.6 M, 4.12 mL, 6.59 mmol) was added dropwise to obtain a mixture, and the mixture was stirred at this temperature for 2 h. Then, tri-n-butyltin chloride (2.14 g, 6.59 mmol) was added to the mixture, and the reaction was slowly heated to room temperature and stirred for 1 h. Then, the mixture was extracted twice with ethyl acetate, and the organic phase was dried over anhydrous magnesium sulfate to obtain compound 4; The obtained compound 4 and compound 2 (3 g, 5.28 mmol) were added to a 100 ml single-necked flask, Pd(PPh3)4 (200 mg) was added under a nitrogen atmosphere, and dry toluene solvent 40 ml was finally added. After the reaction was stirred at 130 °C for 3 h, it was cooled to room temperature, and then the mixture was poured into a separatory funnel and extracted twice with ethyl acetate. The combined organic phase was dried over anhydrous magnesium sulfate, and the crude product was subjected to column chromatography on silica gel with PE / DCM 20:1 to obtain compound 5 as a colorless transparent oil (3.32 g, 73.8%).

[0057] Hydrogen spectrum data of compound 5: 1H NMR (500 MHz, Chloroform-d) δ 7.66 (dd, J = 9.1,7.1 Hz, 2 H), 7.41 - 7.33 (m, 2 H), 7.31 - 7.22 (m, 3 H), 6.89 (s, 1 H), 3.19(t, J = 6.9 Hz, 4 H), 2.78 - 2.62 (m, 4 H), 1.92 (t, J = 8.4 Hz, 4 H), 1.75 -1.66 (m, 4 H), 1.61 - 1.55 (m, 4 H), 1.43 - 0.91 (m, 32 H), 0.80 (dt, J =8.8, 6.8 Hz, 6 H); Carbon spectral data of compound 5: 13 C NMR (126 MHz, Chloroform-d) δ 150.58, 140.66,139.48, 136.93, 135.37, 133.95, 131.20, 128.31, 127.36, 127.05, 123.66,122.83, 120.35, 119.92, 119.83, 55.02, 40.29, 33.89, 32.67, 31.92, 29.95,29.79, 29.42, 29.29, 29.13, 28.85, 28.58, 27.83, 23.65, 22.72, 14.17; Synthesis of compound 8: To a mixture of compound 5 (3.32 g, 3.90 mmol) and 60 mL THF at -78 °C under nitrogen protection, n-BuLi (solvent is hexane, concentration is 1.6 M, 4.87 mL, 7.79 mmol) was added dropwise, and the mixture was stirred at this temperature for 2 h. Then tri-n-butyltin chloride (2.53 g, 7.79 mmol) was added to the mixture, and then the reaction was slowly heated to room temperature and reacted for 1 h. The reaction was extracted twice with ethyl acetate and dried over anhydrous magnesium sulfate to obtain compound 6; The obtained compound 6 was added to a 100 ml single necked flask, under nitrogen atmosphere Pd(PPh3)2Cl2(200 mg) was added, finally dry toluene solvent 40 mL was added, stirred at 130 °C for 3 h, after the reaction was completed, it was returned to room temperature, then the mixture was poured into water, and extracted twice with ethyl acetate, the combined organic phase was dried over anhydrous magnesium sulfate, the crude product was subjected to column chromatography on silica gel with PE / DCM 10: 1 to obtain compound 8 as a blue solid (1.47 g, 59.9%), recorded as IR-FDA.

[0058] Hydrogen spectrum data of compound 8: 1 H NMR (500 MHz, Chloroform-d) δ 7.77 - 7.65 (m, 4H), 7.49 - 7.40 (m, 4 H), 7.33 - 7.24 (m, 6 H), 2.75 (dt, J = 72.4, 7.9 Hz, 8H), 1.99 - 1.92 (m, 8 H), 1.75 (dt, J = 16.1, 7.8 Hz, 8 H), 1.65 - 1.48 (m, 8H), 1.38 - 1.27 (m, 8 H), 1.19 - 0.96 (m, 64 H), 0.79 - 0.75 (m, 12 H).

[0059] Carbon spectrum data of compound 8: 13 C NMR (126 MHz, Chloroform-d) δ 153.48, 150.91,150.84, 150.74, 150.63, 142.73, 140.98, 140.87, 140.61, 138.12, 136.90 (d, J= 2.6 Hz), 133.74, 131.16 (d, J = 2.1 Hz), 129.29, 128.37, 127.39, 126.99,123.63, 122.91, 119.94, 116.70, 55.13, 40.28, 33.92, 32.68, 31.89, 31.78,30.11, 29.98, 29.88, 29.64, 29.54, 29.41, 29.31, 29.14, 28.50, 27.85, 22.70,22.64, 14.15.

[0060] The hydrogen spectrum of compound 5 in Example 2 is shown in Figure 7 The carbon spectrum is shown inFigure 8 The hydrogen spectrum of compound 8 (IR-FDA) in Example 2 is shown in FIG. 2A, the carbon spectrum is shown in FIG. 2B, and the mass spectrum is shown in FIG. 2C. Figure 9 The hydrogen spectrum of compound 8 (IR-FDA) in Example 2 is shown in FIG. 2A, the carbon spectrum is shown in FIG. 2B, and the mass spectrum is shown in FIG. 2C. Figure 10 The hydrogen spectrum of compound 8 (IR-FDA) in Example 2 is shown in FIG. 2A, the carbon spectrum is shown in FIG. 2B, and the mass spectrum is shown in FIG. 2C. Figure 11 The hydrogen spectrum of compound 8 (IR-FDA) in Example 2 is shown in FIG. 2A, the carbon spectrum is shown in FIG. 2B, and the mass spectrum is shown in FIG. 2C. Figures 7-11 It can be seen from the above that Example 2 can synthesize IR-FDA.

[0061] Example 3 A super-bright NIR-II fluorescent molecule has a chemical structure shown in the above Formula III.

[0062] The synthesis formula of the super-bright NIR-II fluorescent molecule (IR-FTDA) of the Formula III chemical structure is as follows: The synthesis of compound 2 is described in the reference literature “Donor Engineering for NIR-II Molecular Fluorophores with Enhanced Fluorescent Performance” (Yang, Q.; Hu, Z.; Zhu, S.; Ma, R.; Ma, H.; Ma, Z.; Wan, H.; Zhu, T.; Jiang, Z.; Liu, W.; et al. J Am Chem Soc 2018, 140 (5), 1715-1724.); The synthesis of compound 5 is described in the reference literature “Rational Design of Molecular Fluorophores for Biological Imaging in the NIR-II Window” (Yang Q, Z Ma, H Wang, B Zhou, S Zhu, Y Zhong, J Wang, H Wan, A Antaris, R Ma, X Zhang, J Yang, X Zhang, H Sun, W Liu, Y Liang, H Dai. Adv Mater. 29(12) (2017) 1605497. https: / / doi.org / 10.1002 / adma.201605497); The resulting compound 4 (1 g, 1.74 mmol) was added to a solution of DMF (15 mL) under a nitrogen atmosphere, and 1-bromopyrrolidine-2,5-dione (309.83 mg, 1.74 mmol) was added, and the mixture was stirred at -8°C for 1 hour, and then transferred to room temperature for 4 hours, after which the mixture was poured into water and extracted twice with ethyl acetate, dried over MgS04and evaporated in vacuo, and the crude product was purified by column chromatography on silica gel to obtain compound 5 (903 mg, 79.9%) as a light yellow oil; The synthesis of compound 7 was carried out in accordance with the synthesis of compound 4 in Example 2; Synthesis of compound 8: The resulting compound 7 (1 g, 2.75 mmol) and compound 5 (1.74 g, 2.75 mmol) were added to a 100 mL single-necked flask, Pd(PPh3)4(130 mg) was added under a nitrogen atmosphere, and finally dry toluene solvent 40 mL was added, and stirred at 130°C for 3 h, after which the reaction was returned to room temperature, and then the mixture was poured into water and extracted twice with ethyl acetate, and the combined organic phase was dried over anhydrous magnesium sulfate, and the crude product was purified by column chromatography on silica gel with PE / DCM 10:1 to obtain compound 8 as a colorless transparent oil (1.64 g, 63.9%); Hydrogen spectrum data of compound 8: 1 H NMR (500 MHz, Chloroform-d) δ 7.62 (d, J = 7.7 Hz, 2 H), 7.53 (dd, J = 7.8, 1.7 Hz, 1 H), 7.49 - 7.46 (m, 1 H), 7.30 - 7.21 (m, 4 H), 7.06 (s, 1 H), 6.89 (s, 1 H), 3.18 (t, J = 6.8 Hz, 4 H), 2.75 (dt, J = 117.0, 7.7 Hz, 4 H), 1.93 (t, J = 8.3 Hz, 4 H), 1.75 - 1.64 (m, 4 H), 1.58 - 1.55 (m, 4 H), 1.33 - 0.99 (m, 32 H), 0.83 - 0.78 (m, 6 H); Carbon spectrum data of compound 8: 13C NMR (126 MHz, Chloroform-d) δ 151.23, 150.50, 144.97, 140.95, 140.90, 140.62, 136.90, 135.96, 135.37, 132.95, 132.26, 131.51, 127.32, 127.04, 126.96, 124.74, 123.33, 122.81, 121.06, 120.23, 119.84, 119.65, 55.09, 40.30, 33.97, 32.65, 31.92, 29.87, 29.74, 29.41, 29.28, 29.15, 29.07, 28.87, 28.79, 27.79, 23.56, 22.71, 13.64; Synthesis of compound 11: To a mixture solution of compound 8 (1.64 g, 1.76 mmol) and 30 mL THF, n-BuLi (solvent: hexane, concentration: 1.6 M, 2.19 mL, 3.50 mmol) was added dropwise at -78 °C under a protective gas, and the mixture was stirred at this temperature for 2 h. Then, tri-n-butyltin chloride (1.14 g, 3.50 mmol) was added to the mixture, which was then slowly heated to room temperature and stirred for 1 h. The reaction mixture was extracted twice with ethyl acetate and dried over anhydrous magnesium sulfate to obtain compound 9. Compound 9 obtained and compound 10 (204.9 mg, 0.59 mmol) were added to a 100 mL single-necked flask, Pd(PPh3)2Cl2(100 mg) was added under nitrogen gas protection, and dry toluene solvent 30 mL was finally added. After reaction at 130 °C for 3 h, the mixture was cooled to room temperature, then poured into water, and extracted twice with ethyl acetate. The combined organic phase was dried over anhydrous magnesium sulfate, and the crude product was subjected to column chromatography on silica gel with PE / DCM 5:1 to obtain compound 11 as a blue-green solid (568 mg, 47.2%), which was recorded as IR-FTDA.

[0063] NMR data of compound 11: 1H NMR (500 MHz, Chloroform-d) δ 7.68 - 7.62 (m, 2H), 7.59 - 7.51 (m, 2 H), 7.27 (qd, J = 4.6, 1.8 Hz, 4 H), 7.00 (ddd, J =8.5, 6.2, 2.5 Hz, 1 H), 3.09 (dt, J = 119.0, 7.4 Hz, 4 H), 1.99 - 1.94 (m, 4H), 1.60 - 1.54 (m, 8 H), 1.45 - 1.36 (m, 4 H), 1.31 - 1.22 (m, 32 H), 0.62 -0.55 (m, 3 H); Carbon spectral data of compound 11: 13 C NMR (126 MHz, Chloroform-d) δ 153.41, 151.80,151.46, 150.72, 149.21, 145.47, 143.12, 142.95, 141.02, 140.60, 139.30,138.95, 137.98, 136.87, 135.66, 135.18, 133.01, 132.83, 131.99, 129.96,127.25, 126.96, 124.72, 124.39, 124.09, 123.50, 123.42, 122.86, 120.21,119.81, 119.03, 118.88, 116.62, 115.92, 114.10, 55.14 (d, J = 6.4 Hz), 40.29,35.00, 34.74, 34.46, 33.97, 33.85, 32.67, 31.95, 31.92, 31.89, 31.78, 31.64,31.53, 30.15, 29.84, 29.73, 29.54, 29.39, 29.29, 29.17, 28.42, 28.28, 27.81,26.81, 22.70, 22.64, 17.32, 14.15, 13.63.

[0064] Example 4 A super-bright NIR-II fluorescent molecule has a chemical structure shown in the above Formula IV.

[0065] The synthesis formula of the super-bright NIR-II fluorescent molecule (IR-FDHT) of the Formula IV chemical structure is as follows: wherein the synthesis of compound 2 is referenced in the literature “Donor Engineering for NIR-II Molecular Fluorophores with Enhanced Fluorescent Performance” (Yang, Q.; Hu, Z.; Zhu, S.; Ma, R.; Ma, H.; Ma, Z.; Wan, H.; Zhu, T.; Jiang, Z.; Liu, W.; et al. J Am Chem Soc 2018, 140 (5), 1715-1724.); Synthesis of compound 5: To a mixture of compound 3 (1 g, 5.00 mmol) and 20 mL of THF at -78 °C under nitrogen protection, n-BuLi (solvent: hexane, concentration: 1.6 M, 3.75 mL, 6.00 mmol) was added dropwise, after 2 h of reaction, tri-n-butyltin chloride (1.95 g, 6.00 mmol) was added to the solution, then the reaction was slowly heated to room temperature and stirred for 1 h, then extracted with ethyl acetate twice, dried over anhydrous magnesium sulfate to obtain compound 4; The prepared compound 4 and compound 2 (3 g, 5.28 mmol) were added to a 100 ml single-necked flask, Pd(PPh3)4 (200 mg) was added under nitrogen atmosphere, and finally dry toluene solvent 40 ml was added, stirred at 130 °C for 3 h, after the reaction was completed, the mixture was returned to room temperature, then the mixture was poured into water, extracted with ethyl acetate twice, the combined organic phase was dried over anhydrous magnesium sulfate, and the crude product was subjected to column chromatography on PE / DCM 5:1 silica gel to obtain compound 5 as a colorless transparent oil (1.93 g, 56.1%); Hydrogen spectrum data of compound 5: 1 H NMR (500 MHz, Chloroform-d) δ 7.73 - 7.67 (m, 4H), 7.35 - 7.29 (m, 3 H), 6.27 (s, 1 H), 4.08 (s, 3 H), 3.95 (s, 3 H), 3.27(t, J = 6.8 Hz, 4 H), 1.98 (dt, J = 10.6, 5.3 Hz, 4 H), 1.66 (d, J = 7.3 Hz,4 H), 1.35 (ddd, J = 12.1, 6.8, 3.7 Hz, 4 H), 1.11 - 1.05 (m, 4 H); Carbon NMR data of compound 5: 13 C NMR (126 MHz, Chloroform-d) δ 151.15, 150.73, 150.66, 146.29, 140.73, 140.10, 132.42, 129.43, 127.14, 126.95, 126.02, 125.30, 122.79, 121.45, 119.89, 119.78, 97.17, 60.42, 59.44, 57.68, 54.98, 40.18, 33.96, 32.65, 29.09, 27.77, 26.79, 23.59, 21.07, 17.33, 14.21, 13.61; Synthesis of compound 6: Compound 5 (1.93 g, 2.81 mmol) was weighed, 6-bromo-1-hexanol (2.02 g, 11.22 mmol) was added to a 100 ml single necked flask, followed by NaHS04, under nitrogen atmosphere, finally dry toluene solvent 50 ml was added, after stirring for 3 h at 110 °C, the mixture was poured into water and extracted twice with ethyl acetate, and the organic phase was dried over anhydrous magnesium sulfate and evaporated in vacuum, the crude product was subjected to column chromatography on silica gel with PE / DCM 3: 1 to obtain compound 6 as a colorless transparent oil (2.21 g, 80.1 %).

[0066] Hydrogen NMR data of compound 6: 1 H NMR (500 MHz, Chloroform-d) δ 7.72 (dd, J = 22.7, 7.7 Hz, 4 H), 7.32 (t, J = 6.2 Hz, 3 H), 6.24 (s, 1 H), 4.08 (s, 4 H), 3.76 - 3.73 (m, 2 H), 3.45 (t, J = 6.9 Hz, 2 H), 3.27 (t, J = 6.9 Hz, 4 H), 2.08 - 0.95 (m, 32 H), 0.76 - 0.55 (m, J = 6.4 Hz, 4 H); Carbon NMR data of compound 6: 13C NMR (126 MHz, Chloroform-d) δ 150.74, 150.63, 150.33, 146.31, 140.75, 140.05, 132.47, 129.21, 127.14, 126.96, 126.22, 125.97, 125.14, 122.79, 121.36, 119.89, 119.78, 97.66, 70.36, 68.00, 59.44, 54.99, 40.20, 34.00, 33.88, 32.65, 29.09, 28.98, 27.93, 27.78, 25.63, 25.32, 23.59; Synthesis of compound 9: To a mixture of compound 6 (2.21 g, 2.25 mmol) in 60 mL of THF at -78 °C under nitrogen protection, n-BuLi (solvent in hexane, concentration 1.6 M, 2.81 mL, 4.50 mmol) was added dropwise, and the mixture was stirred at this temperature for 2 h. Then, tri-n-butyltin chloride (1.46 g, 4.50 mmol) was added to the solution, and the reaction was slowly heated to room temperature and stirred for 1 h. The reaction was extracted with ethyl acetate twice, and the organic phase was dried over anhydrous magnesium sulfate to obtain compound 7. Compound 7 prepared and compound 8 (262 mg, 0.75 mmol) were added to a 100 ml single-necked flask, Pd(PPh3)2Cl2(110 mg) was added under nitrogen atmosphere, and finally dry toluene solvent 40 ml was added. It was stirred at 130 °C for 3 h. After the reaction was completed and cooled to room temperature, the mixture was poured into water, and extracted with ethyl acetate twice. The combined organic phase was dried over anhydrous magnesium sulfate, and the crude product was subjected to column chromatography on silica gel with PE / DCM 1:1 to obtain compound 9 as a green solid (0.82 g, 50.8%), which was recorded as IR-FDHT.

[0067] Hydrogen spectrum data of compound 9: 1H NMR (500 MHz, Chloroform-d) δ 7.79 - 7.73 (m, 8H), 7.36 - 7.35 (m, 6 H), 4.16 (s, 8 H), 3.33 - 3.27 (m, 16 H), 2.03 (ddd, J= 12.1, 6.0, 3.4 Hz, 16 H), 1.70 - 1.64 (m, 16 H), 1.37 (s, 8 H), 1.12 (t, J= 7.7 Hz, 16 H), 0.88 (td, J = 6.7, 3.9 Hz, 16 H); Carbon spectral data of compound 9: 13 C NMR (126 MHz, Chloroform-d) δ 152.90, 150.93,150.71, 149.41, 147.69, 147.63, 147.09, 146.54, 140.65, 139.30, 138.54,138.47, 132.92, 131.94, 127.38, 127.05, 126.23, 126.14, 124.48, 124.39,124.00, 123.50, 122.86, 121.50, 120.02, 119.91, 116.58, 114.30, 114.10,72.08, 59.69, 55.10, 40.19, 34.89, 34.54, 33.99, 33.72, 32.64, 32.54, 31.95,31.53, 31.46, 30.21, 29.88, 29.72, 29.09, 27.78, 25.05, 23.62, 22.72, 14.15。

[0068] The hydrogen spectrum of compound 6 in Example 4 is shown in Figure 12 The carbon spectrum is shown in Figure 13 The mass spectrum is shown in Figure 14 The hydrogen spectrum of compound 9 (IR-FDHT) in Example 4 is shown in Figure 15 The carbon spectrum is shown in Figure 16 The mass spectrum is shown in Figure 17 As can be seen from Figures 12-17 Example 4, IR-FDHT can be synthesized.

[0069] Example 5 A super-bright NIR-II fluorescent molecule has the chemical structure shown in the above Formula V. A super-bright NIR-II fluorescent molecule has the chemical structure shown in the above Formula V.

[0070] The synthesis of the super-bright NIR-II fluorescent molecule (IR-FDMT) of the chemical structure of Formula V is as follows: wherein the synthesis of compound 5 is consistent with the synthesis of compound 5 in Example 4; Synthesis of compound 8: To a mixture of compound 5 (1 g, 1.45 mmol) and 20 mL THF at -78 °C, n-BuLi (solvent: hexane, concentration: 1.6 M, 1.82 mL, 2.91 mmol) was added dropwise under nitrogen protection, and the mixture was stirred at this temperature for 2 h. Then, tri-n-butyltin chloride (0.94 g, 2.91 mmol) was added to the mixture, which was then slowly heated to room temperature and stirred for 1 h. Then, the mixture was extracted several times with dichloromethane, and the combined organic phase was dried over anhydrous magnesium sulfate to obtain compound 6. The prepared compound 6 and compound 7 (169.6 mg, 0.48 mmol) were added to a 100 ml single-necked flask, Pd(PPh3)2Cl2 (70 mg) was added under a nitrogen atmosphere, and finally 40 ml of dry toluene solvent was added. The reaction was carried out at 130 °C for 3 h. After the reaction was completed, the mixture was cooled to room temperature, and then the reaction solution was poured into water and extracted several times with dichloromethane. The combined organic phase was dried over anhydrous magnesium sulfate, and the crude product was subjected to column chromatography on silica gel with PE / DCM 2:3 to obtain compound 8 as a green solid (344 mg, 45.5%), which was recorded as IR-FDMT.

[0071] NMR data of compound 8: 1 H NMR (500 MHz, Chloroform-d) δ 7.71 - 7.64 (m, 8H), 7.29 - 7.26 (m, 6 H), 4.11 (s, 6 H), 4.08 (d, J = 5.6 Hz, 6 H), 3.28 (dt,J = 62.6, 6.8 Hz, 8 H), 1.97 - 1.90 (m, 8 H), 1.60 (p, J = 7.0 Hz, 8 H), 0.79(dt, J = 19.4, 6.8 Hz, 16 H), 0.65 (q, J = 10.2 Hz, 8 H); NMR data of compound 8: 13C NMR (126 MHz, Chloroform-d) δ 152.92, 151.31, 151.12, 150.92, 150.05, 146.53, 140.63, 133.14, 133.04, 131.85, 131.76, 127.75, 127.56, 127.24, 126.95, 126.08, 125.72, 125.66, 122.90, 121.58, 119.87, 116.26, 116.21, 114.20, 114.10, 59.69, 59.49, 55.20, 55.14, 40.34, 34.02, 32.66 (d, J = 2.2 Hz), 31.90, 30.09, 29.56, 29.30, 27.80, 27.41, 23.87, 22.68, 14.15, 13.78, 8.73.

[0072] The hydrogen spectrum of compound 5 in Example 5 is shown in Figure 18 The carbon spectrum is shown in Figure 19 The mass spectrum is shown in Figure 20

[0073] Example 6 A super-bright NIR-II fluorescent molecule has a chemical structure shown in the above Formula VI.

[0074] The synthesis formula of the super-bright NIR-II fluorescent molecule (TPA-C8) of the Formula VI is as follows: Wherein, the synthesis of compound 3: dissolve 3.65g (10mmol) 3,6-dioctylthieno[3,2-b]thiophene in 10ml DMF and add 1.78g NBS (10mmol) at one time at 0℃, after constant temperature for 18h, add appropriate amount of water to dissolve all the solids, then extract the product with ethyl acetate for 2 times, wash the combined organic phase with Na2SO3 (aq) for 3 times, dry with MgSO4, evaporate in vacuum, without further purification, to obtain colorless transparent compound 3 (3.8g, 85% yield); The hydrogen spectrum data of compound 3: 1 ​H NMR (500 MHz, CDCl3) δ 7.07 (s, 1H), 2.91 (q, J =7.1 Hz, 2H), 2.84 (dt, J = 15.4, 7.6 Hz, 2H), 1.92 (dhept, J = 17.0, 7.9 Hz,4H), 1.61 (d, J = 7.2 Hz, 2H), 1.60 ~ 1.39 (m, 18H), 1.12 (dt, J = 10.2, 4.9Hz, 6H); Carbon spectrum data of compound 3: 13 C NMR (126 MHz, CDCl3) δ 139.46, 137.88, 137.56,136.30, 135.34, 135.13, 134.64, 134.43, 120.94, 120.28, 109.81, 109.64,32.25, 30.08, 29.94, 29.80, 29.78, 29.75, 29.73, 29.71, 29.68, 29.65, 29.63,29.59, 29.57, 29.26, 29.17, 29.04, 28.99, 28.49, 28.44, 23.04, 14.43。

[0075] Synthesis of compound 4: The resulting 2.2g of compound 3 (5.0 mmol), N,N- diphenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline were added in toluene and water (15ml:5ml) under a protective atmosphere, 200mg Pd(PPh3)4 and potassium dihydrogen phosphate 2.1g (10.0 mmol) were added, heated to 120°C for 18h, after cooling to room temperature, poured into water, extracted twice with ethyl acetate, dried over MgSO4, evaporated in vacuo, the crude product was purified by PE / DCM 6:1 silica gel column chromatography to obtain yellow transparent compound 4 (2.1g, 70%); Hydrogen spectrum data of compound 4: 1H NMR (500 MHz, CDC13) δ 7.31 (s, 2H), 7.23 (dt, J = 22.1, 7.7 Hz, 5H), 7.14 (d, J = 8.0 Hz, 3H), 7.09 (d, J = 8.3 Hz, 2H), 7.02 (t, J = 7.3 Hz, 2H), 6.90 (s, 1H), 2.78 (t, J = 8.0 Hz, 2H), 2.70 (t, J = 7.7 Hz, 2H), 1.75 (p, J = 7.5 Hz, 4H), 1.40 - 1.24 (m, 20H), 0.87 (q, J = 6.5 Hz, 6H); Carbon spectral data for compound 4: 13 C NMR (126 MHz, CDC13) δ 147.95, 147.61, 147.32, 140.61, 138.92, 136.79, 135.37, 130.87, 130.11, 129.42, 129.28, 129.01, 124.81, 124.25, 123.28, 123.05, 122.75, 120.15, 31.99, 29.99, 29.69, 29.53, 29.50, 29.38, 29.35, 29.31, 29.20, 28.89, 28.40, 22.78, 14.23; Synthesis of compound 5: To a mixture of 2.43 g of compound 4 (4 mmol) and 25 mL of THF, n-BuLi (solvent: hexane, concentration: 1.6 M, 3.0 mL, 4.8 mmol) was added dropwise at -78°C under a protective atmosphere. The mixture was stirred at this temperature for 2.0 h, and then tributyltin chloride (1.690 g, 5.2 mmol) was added to the mixture. The mixture was poured into water and extracted twice with ethyl acetate. The combined organic phases were dried over MgSO4and evaporated in vacuo to obtain a crude product. To a mixture of 469 mg of 4,8-dibromo-1H,5H-benzo[1,2-C:4,5-C']bis[[1,2,5]thiadiazole] (1.33 mmol) and 15 mL of toluene, the crude product (4 mmol) was added under a protective atmosphere, followed by the addition of 180 mg of Pd(PPh3)2Cl2. The mixture was stirred at 120°C for 12 h. After cooling to room temperature, the mixture was purified over MgSO4, and then poured into water. The mixture was extracted twice with ethyl acetate, dried over MgSO4, and evaporated in vacuo. The crude product was purified by column chromatography on silica gel (PE / DCM 5:1) to obtain compound 8 as a blue solid (1.22 g, 65%), which was designated as TPA-C8.

[0076] The hydrogen spectrum of compound 3 in Example 6 is shown in Figure 21 The carbon spectrum of compound 3 in Example 6 is shown in Figure 22 The hydrogen spectrum of compound 4 is shown in Figure 23 The carbon spectrum of compound 4 is shown in Figure 24

[0077] Example 7 A super-bright NIR-II fluorescent molecule having a chemical structure shown in Formula VI above.

[0078] The synthesis of the super-bright NIR-II fluorescent molecule (OMe-TPA-C8) of Formula VI is as follows: wherein, the synthesis of compound 6: To a mixture of 4.4 g of compound 3 (10.0 mmol), (4-(bis(4-methoxyphenyl)amino)phenyl)boronic acid 4.2 g (12.0 mmol), and potassium phosphate dibasic 5.1 g (24.0 mmol) in a mixture of toluene and water (15 ml:5 ml), 180 mg of Pd(PPh3)4 was added under a protective atmosphere, and then heated to 120°C for 18 h. After cooling to room temperature, the mixture was poured into water, extracted twice with ethyl acetate, dried over MgSO4, and evaporated in vacuo. The crude product was purified by column chromatography on silica gel (PE / DCM 4:1) to obtain colorless transparent compound 6 (4.0 g, 60%); The hydrogen spectrum data of compound 6: 1 ​H NMR (500 MHz, CDC13) δ 7.28 - 7.23 (m, 2H), 7.10- 7.06 (m, 4H), 6.95 - 6.91 (m, 2H), 6.86 (s, 1H), 6.83 - 6.79 (m, 4H), 3.74(s, 6H), 2.80 - 2.73 (m, 2H), 2.68 (t, J = 7.6 Hz, 2H), 1.78 - 1.70 (m, 4H),1.34 (s, 2H), 1.32 - 1.21 (m, 18H), 0.86 (td, J = 7.0, 3.0 Hz, 6H); Carbon spectral data of compound 6: 13 C NMR (126 MHz, CDC13) δ 156.19, 148.28, 140.71, 140.61, 139.34, 136.56, 135.33, 130.50, 129.94, 127.04, 126.99, 126.93, 119.97, 119.84, 114.84, 55.46, 32.04, 30.01, 29.75, 29.57, 29.54, 29.43, 29.39, 29.37, 29.26, 28.92, 28.42, 22.82, 14.33, 14.28.

[0079] Synthesis of compound 7: To a mixture of 2.67 g of compound 6 (4 mmol) and 25 mL of THF, n-BuLi (solvent: hexane, concentration: 1.6 M, 3.0 mL, 4.8 mmol) was added dropwise at -78 °C under a protective atmosphere. The mixture was stirred at this temperature for 2.0 hours, then tributyltin chloride (1.690 g, 5.2 mmol) was added to the solution, then the mixture was poured into water and extracted twice with ethyl acetate, the combined organic phases were dried over MgS04and evaporated in vacuo to obtain the crude product. To a mixture of 469 mg of 4,8-dibromo-1H,5H-benzo[1,2-C:4,5-C']bis[[1,2,5]thiadiazole] (1.33 mmol) and 15 mL of toluene, the crude product (4 mmol) was added under a protective atmosphere, then 180 mg of Pd(PPh3)2Cl2was added. The mixture was stirred at 120 °C for 12 h, after cooling to room temperature, the mixture was purified over MgS04, after cooling to room temperature, the mixture was poured into water, extracted twice with ethyl acetate, dried over MgS04, evaporated in vacuo, the crude product was column chromatographed on silica gel (PE / DCM 6:1) to obtain compound 7 (1.12 g, 55%) as a blue-green solid, noted as OMe-TPA-C8.

[0080] Hydrogen spectrum data of compound 7: 1 H NMR (500 MHz, CDCl3) δ 7.36 - 7.30 (m, 4H), 7.16- 7.11 (m, 8H), 7.01 - 6.96 (m, 4H), 6.90 - 6.85 (m, 8H), 3.82 (s, 12H), 2.89- 2.82 (m, 4H), 2.71 (t, J = 7.8 Hz, 4H), 1.84 - 1.74 (m, 8H), 1.40 - 1.22(m, 21H), 1.15 (dq, J = 21.7, 6.8 Hz, 9H), 1.07 (s, 12H), 0.82 (dt, J = 19.1,7.0 Hz, 12H). Carbon spectrum data of compound 7: 13C NMR (126 MHz, CDCl3) δ 153.48, 150.74, 150.64, 142.73, 140.88, 140.62, 138.13, 136.90, 133.75, 131.17, 129.30, 128.43, 127.46, 127.09, 123.64, 122.87, 119.99, 119.93, 116.74, 55.08, 45.05, 40.29, 37.13, 33.90, 32.69, 32.52, 31.89, 31.78, 30.16, 30.08, 29.99, 29.89, 29.74, 29.55, 29.41, 29.31, 29.27, 29.18, 29.14, 28.69, 28.51, 27.85, 27.13, 26.56, 23.69, 22.70, 22.65, 14.15, 14.12, 1.05.

[0081] The hydrogen spectrum of compound 6 in Example 7 is shown in Figure 25 The carbon spectrum is shown in Figure 26 The hydrogen spectrum of compound 7 is shown in Figure 27 The carbon spectrum is shown in Figure 28 The mass spectrum is shown in Figure 29

[0082] Example 8 A super-bright NIR-II fluorescent molecule has the chemical structure shown in the above Formula VIII.

[0083] The synthesis formula of the super-bright NIR-II fluorescent molecule (t-Bu-TPA-C8) of the Formula VIII is as follows: Wherein, the synthesis of compound 8: under a protective atmosphere, 6.7 g of compound 3 (15.0 mmol), 4-(tert-butyl)-n-(4-(tert-butyl)phenyl)-n-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl) aniline 8.7 g (18.0 mmol), 5.1 g (24.0 mmol) of potassium dihydrogen phosphate, and a mixed solution of toluene and water (15 ml:5 ml) were added 200 mg of Pd (PPh3)4, heated to 120°C for 18 h, cooled to room temperature, poured into water, extracted twice with ethyl acetate, dried with MgSO4, vacuum evaporated, and the crude product was analyzed by PE / DCM 5:1 silica gel column chromatography to obtain green transparent compound 8 (7.0 g, 65%); The hydrogen spectrum data of compound 8:​1 H NMR (500 MHz, CDCl3) δ 7.30 - 7.21 (m, 6H), 7.05(td, J = 6.9, 1.9 Hz, 6H), 6.85 (s, 1H), 2.78 (t, J = 8.1 Hz, 2H), 2.69 (t, J= 7.8 Hz, 2H), 1.75 (h, J = 7.1 Hz, 4H), 1.40 - 1.23 (m, 38H), 0.86 (dt, J =7.6, 3.9 Hz, 6H); Carbon spectrum data of compound 8: 13 C NMR (126 MHz, CDCl3) δ 147.71, 146.07, 144.97,140.66, 139.29, 136.73, 135.35, 130.68, 130.03, 128.19, 126.25, 124.56,122.19, 120.07, 34.44, 32.08, 31.63, 30.06, 29.78, 29.62, 29.60, 29.48,29.44, 29.41, 29.29, 28.97, 28.46, 22.86, 14.32; Synthesis of compound 9: To a mixture of 2.88 g of compound 8 (4 mmol) and 25 mL of THF at -78°C under a protective atmosphere, n-BuLi (solvent: hexane, concentration: 1.6 M, 3.0 mL, 4.8 mmol) was added dropwise, the mixture was stirred at this temperature for 2.0 hours, then tributyltin chloride (1.690 g, 5.2 mmol) was added to the solution, then the mixture was poured into water and extracted twice with ethyl acetate, the combined organic phases were dried over MgS04and evaporated in vacuo to obtain the crude product, to a mixture of 469 mg of 4,8-dibromo-1H,5H-benzo[1,2-C:4,5-C']bis[[1,2,5]thiadiazole] (1.33 mmol) and 15 mL of toluene under a protective atmosphere, the crude product (4 mmol) was added, then 200 mg of Pd(PPh3)2Cl2was added, the mixture was stirred at 120°C for 12 h, after cooling to room temperature, the mixture was purified over MgS04, after cooling to room temperature, the mixture was poured into water, extracted twice with ethyl acetate, dried over MgS04, evaporated in vacuo, the crude product was column chromatographed on silica gel (PE / DCM 8:1) to obtain compound 9 (1.09 g, 50%) in the form of a blue-green solid, noted t-Bu-TPA-C8.

[0084] Hydrogen spectrum data of compound 9:1 H NMR (500 MHz, CDCl3) δ 7.37 (d, J = 8.2 Hz, 4H),7.30 (d, J = 8.4 Hz, 8H), 7.10 (dd, J = 8.7, 3.7 Hz, 12H), 2.88 (t, J = 7.9Hz, 4H), 2.73 (t, J = 7.8 Hz, 4H), 1.81 (tt, J = 15.3, 7.6 Hz, 9H), 1.36 ~1.09 (m, 76H), 0.95 ~ 0.83 (m, 12H); Carbon spectral data of compound 9: 13 C NMR (126 MHz, CDCl3) δ 153.51, 147.89, 146.17,144.81, 142.78, 140.62, 137.84, 136.86, 130.58, 129.97, 129.07, 127.80,126.22, 124.52, 122.08, 116.74, 34.40, 31.96, 31.83, 31.54, 30.03, 29.79,29.58, 29.39, 29.30, 29.23, 29.17, 28.50, 27.93, 26.92, 22.74, 22.68, 17.58,14.21, 14.17, 13.71.

[0085] The hydrogen spectrum of compound 8 in Example 8 is shown in Figure 30 , and the carbon spectrum is shown in Figure 31 ; the hydrogen spectrum of compound 9 is shown in Figure 32 , and the carbon spectrum is shown in Figure 33 .

[0086] Test Example The luminescent properties of the super-bright NIR-II fluorescent molecules of Examples 1-3 were tested, and the obtained absorption spectrum is shown in Figure 34 , and the fluorescence spectrum is shown in Figure 35 .

[0087] As can be seen from Figure 34 and Figure 35 , the quantum yield of the super-bright NIR-II fluorescent molecules of Examples 1-3 can reach 61.6%.

[0088] The luminescent properties of the super-bright NIR-II fluorescent molecules of Examples 6-8 were tested, and the obtained absorption spectrum is shown in Figure 36 , and the fluorescence spectrum is shown in Figure 37as shown.

[0089] From Figure 36 and Figure 37 It can be seen from Examples 6-8 that the quantum yield of TPA-C8 is 27.4%, and the quantum yield of t-Bu-TPA-C8 is 25.9%.

[0090] The super-bright NIR-II fluorescent molecules of Examples 6-8 are respectively self-assembled with phospholipid-key-polyethylene glycol to obtain TPA-C8 NPs, OMe-TPA-C8 NPs and t-Bu-TPA-C8 NPs. In the present application, the mass ratio of the compound IR-FE-Fc to phospholipid-key-polyethylene glycol (DSPE-PEG) is 1:5; The luminescence performance of TPA-C8 NPs, OMe-TPA-C8 NPs and t-Bu-TPA-C8 NPs is tested, and the obtained absorption spectrum is as shown in Figure 38 , and the fluorescence spectrum is as shown in Figure 39 .

[0091] From Figure 38 and Figure 39 It can be seen that the super-bright NIR-II fluorescent molecules assembled into nanomaterials TPA-C8 NPs and t-Bu-TPA-C8 NPs have a great improvement in fluorescence brightness under the same absorption conditions.

[0092] The shielding unit in the super-bright NIR-II fluorescent molecule is located at at least one end of the super-bright NIR-II fluorescent molecule, and is covalently connected with the electron donor aromatic unit, and the two free bonds in the electron acceptor aromatic unit are independently covalently connected with the electron donor aromatic unit or hydrogen. By shielding the electrons of the shielding unit from the intermolecular interaction of the electron acceptor aromatic unit and / or the electron donor aromatic unit, the intermolecular and intramolecular interaction of the conjugated skeleton is weakened, and the quantum yield is improved. By limiting the structure of the electron donor aromatic unit and / or the shielding unit in the super-bright NIR-II fluorescent molecule, the super-bright NIR-II fluorescent molecule can be excited to produce super-bright fluorescence at an excitation wavelength of 808 nm. The results of the examples show that the quantum yield of the super-bright NIR-II fluorescent molecule provided by the present application can reach 61.6%, and has a high quantum yield, thereby improving the fluorescence brightness of the NIR-II fluorescent molecule.

[0093] The above only describes the preferred embodiments of the present application, and it should be noted that those skilled in the art can make several improvements and refinements without departing from the principles of the present application, and these improvements and refinements should also be considered as the protection scope of the present application.

Claims

1. A superbright NIR-II fluorescent molecule, comprising: Electron acceptor aromatic unit, electron donor aromatic unit, and shielding unit; The shielding unit is located at at least one end of the ultra-bright NIR-II fluorescent molecule and is covalently connected to the electron donor aromatic unit; In the electron acceptor aromatic unit, two free bonds are independently covalently connected to the electron donor aromatic unit or the halogen. In the aforementioned ultra-bright NIR-II fluorescent molecule, the structural formula of each electron acceptor aromatic unit is independently as follows: One or more of them; In the structural formula of the ultrabright NIR-II fluorescent molecule, Z1, Z2, Z3, and Z4 are independently O, S, Se, N, or Ti; R is independently H or -C. n1 H 2n1+1 Or tert-butyloxycarbonyl; the -C n1 H 2n1+1 In this context, n1 is an integer in the range of 1 to 12; In the aforementioned ultra-bright NIR-II fluorescent molecule, the structural formula of each electron-donating aromatic unit is independently as follows: One or more of them; In the structural formula of the ultra-bright NIR-II fluorescent molecule, P1 and P2 are independently H and -OC. n2 H 2n2+1 -C n2 H 2n2+1 , , -OC n2 H 2n2 B or -C n2 H 2n2 Z; X is independently S, Se, N, O, Ti, or R1; R1 is independently H, -C n1 H 2n1+1 Or alkoxy; m is an integer in the range of 0 to 6; The or -OC n2 H 2n2 The B in B can be Br, I, OTs, OMs, ONs, N3, or OMe independently; The -C n2 H 2n2 Z in Z is Br or N3; The -OC n2 H 2n2+1 -C n2 H 2n2+1 -OC n2 H 2n2 B or -C n2 H 2n2 In Z, n2 is an integer in the range of 1 to 20 independently; The or p in the equation is an integer in the range of 1 to 20. In the ultra-bright NIR-II fluorescent molecule, the structural formula of the shielding unit is independently: , or ; In the structural formula of the ultra-bright NIR-II fluorescent molecule, R2 is independently -(CH2). n3 W, the -(CH2) n3 In W, n3 is an integer in the range of 1 to 20, and -(CH2) n3 The W in W represents H, Br, I, OH, Ots, or N3. , , or The In this context, n is an integer in the range of 4 to 120. or In this context, b is an integer in the range of 1 to 6; Z5 is S, Se, O, or N; X1 is Si, Ge, or C. In the aforementioned ultra-bright NIR-II fluorescent molecule, at least the electron donor aromatic unit includes Or the shielding unit is , , or .

2. The ultra-bright NIR-II fluorescent molecule according to claim 1, characterized in that, The number of electron acceptor aromatic units in the ultra-bright NIR-II fluorescent molecule does not exceed 3, and the number of electron donor aromatic units does not exceed 3.

3. The ultra-bright NIR-II fluorescent molecule according to claim 2, characterized in that, The ultra-bright NIR-II fluorescent molecule includes a shielding unit, an electron donor aromatic unit, and an electron acceptor aromatic unit, and has an S'-DAM structure. Where S' represents the shielding unit, D represents the electron donor aromatic unit, A represents the electron acceptor aromatic unit, and M represents the halogen.

4. The ultra-bright NIR-II fluorescent molecule according to claim 2, characterized in that, The ultra-bright NIR-II fluorescent molecule comprises two shielding units, one electron acceptor aromatic unit, and two electron donor aromatic units, and has a structure of S'1-D1-A-D2-S'2; Wherein, S'1 represents the first shielding unit, S'2 represents the second shielding unit, D1 represents the first electron donor aromatic unit, D2 represents the second electron donor aromatic unit, and A represents the electron acceptor aromatic unit.

5. The ultra-bright NIR-II fluorescent molecule according to claim 2, characterized in that, The ultra-bright NIR-II fluorescent molecule comprises two electron acceptor aromatic units, three electron donor aromatic units, and two shielding units, and has a structure of S'3-D3-A1-D5-A2-D4-S'4. Wherein, S'3 represents the third shielding unit, S'4 represents the fourth shielding unit, D3 represents the third electron donor aromatic unit, D4 represents the fourth electron donor aromatic unit, D5 represents the fifth electron donor aromatic unit, A1 represents the first electron acceptor aromatic unit, and A2 represents the second electron acceptor aromatic unit.

6. The ultrabright NIR-II fluorescent molecule according to any one of claims 1 to 5, characterized in that, The electron donor aromatic unit in the ultra-bright NIR-II fluorescent molecule includes The shielding unit is , , or .

7. The ultra-bright NIR-II fluorescent molecule according to claim 6, characterized in that, The structural formula of the electron acceptor aromatic unit is as follows: .

8. The ultrabright NIR-II fluorescent molecule according to claim 7, characterized in that, In the structural formula of the ultrabright NIR-II fluorescent molecule, Z1 and Z2 are independently O, S, Se, or N; P1 and P2 are independently -C. n2 H 2n2+1 -OC n2 H 2n2+1 -OC n2 H 2n2 B or The -OC n2 H 2n2+1 -C n2 H 2n2+1 or -OC n2 H 2n2 In B, n2 is independently an integer in the range of 4 to 16. or -OC n2 H 2n2 The B in B can be Br, OTs, OMs, N3, or OMe independently. or p in the equation is an integer in the range of 4 to 12.

9. The ultra-bright NIR-II fluorescent molecule according to claim 8, characterized in that, In the structural formula of the ultrabright NIR-II fluorescent molecule, Z1 and Z2 are independently S or Se; P1 and P2 are independently -C. n2 H 2n2+1 -OC n2 H 2n2+1 or -OC n2 H 2n2 B, the -OC n2 H 2n2+1 -C n2 H 2n2+1 or -OC n2 H 2n2 In B, n2 is independently an integer in the range of 6 to 12, and -OC n2 H 2n2 In B, B can be Br, OTs, OMs, N3, or OMe.

10. The use of the ultrabright NIR-II fluorescent molecule according to any one of claims 1 to 8 in non-disease diagnostic biomedical imaging or labeling of biomacromolecules.

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