Small molecule organic dye and preparation method and application thereof

Abstract

The present invention provides a small molecule organic dye and a preparation method and application thereof. The small molecule organic dye adopts 1,3-indanedione and its dicyanomethylene derivatives as the D-A type molecule of the A part to produce a significant ICT effect for extraordinary phototherapy applications. Generally, these D-π-A type molecules are designed to connect the D-block to the C2 position of the A group derived from 1,3-indanedione to extend the coupling. In addition to 1,3-indanedione, indanone can also serve as a good A group. In particular, indanone is derived into dicyanomethylene indene, making it an interesting new A structure for near-infrared active molecules, a D-π-A configured molecule, in which dicyanomethylene indene is the A group, and a new molecular skeleton composed of dicyanomethylene indene (DCMI) is used as a π-conjugated acceptor, which is connected to a triarylamine donor for adjusting absorption. Among them, the maximum absorption rate of the embedded high quinone π bridge is 783 nm, which can be studied for phototherapy applications.

Description

Technical Field

[0001] The invention relates to the field of bionano photosensitizers, and in particular to a small molecule organic dye and a preparation method and application thereof. Background Art

[0002] Triple-negative breast cancer (TNBC) is a fatal female cancer with high rates of metastasis and recurrence. The median overall survival of metastatic triple-negative breast cancer is about one year. Currently, chemotherapy options for TNBC are limited and have systemic toxic effects. Therefore, bio-nano photosensitizers need to be used in the preparation and treatment process, and the preparation of bio-nano photosensitizers requires small molecule organic dyes as raw materials. Summary of the invention

[0003] The purpose of the present invention is to overcome the shortcomings of the prior art and provide a small molecule organic dye and its preparation method and application

[0004] To achieve the above object, the technical solution adopted by the present invention is: a small molecule organic dye, the chemical structure of the small molecule organic dye is shown in formula I,

[0005]

[0006] The above-mentioned small molecule organic dyes adopt 1,3-indanedione and its dicyanomethylene derivatives as the A part. DA-type molecules are developed to produce obvious ICT effects for extraordinary phototherapy applications. Generally, these D-π-A-type molecules are designed to connect the D-block to the C2 position of the A group derived from 1,3-indanedione to extend the -coupling. In addition to 1,3-indanedione, indanone can also serve as a good A group. In particular, the derivatization of indanone to dicyanomethyleneindene makes it an interesting new A structure for near-infrared active molecules. The molecules of D-π-A configuration, in which dicyanomethyleneindene is the A group, and the new molecular skeleton composed of dicyanomethyleneindene (DCMI) as a π-conjugated acceptor, which is connected to a triarylamine donor for adjusting the absorption. Among them, the absorption rate embedded in the high quinone π bridge is maximal at 783nm, which can be studied for phototherapy applications.

[0007] The present invention also provides a method for preparing the above-mentioned small molecule organic dye, which comprises the following steps:

[0008] N, N-bis(4-methylphenyl)-3-(tributyltinyl)benzo[c]thiophene-1-amine or N, N-bis(4-methylphenyl)-3-(tributyltinyl)thiophene-1-amine is reacted with 2-(3-chloro-1H-inden-1-ylidene)malononitrile in toluene reflux under the catalysis of bis(triphenylphosphine)palladium dichloride to obtain a compound represented by formula (II) or formula (I).

[0009] The preparation method of the small molecule organic dye has safe reaction conditions and high yield.

[0010] Preferably, the reflux reaction time is 4 to 18 hours.

[0011] The preparation method of the small molecule organic dye has safe reaction conditions and high yield.

[0012] Preferably, the preparation process of 2-(3-chloro-1H-inden-1-ylidene)malononitrile is as shown in formula (III):

[0013]

[0014] Preferably, the preparation process of N,N-bis(4-methylphenyl)-3-(tributyltinyl)thiophene-1-amine is as shown in formula (IV):

[0015]

[0016] Preferably, the preparation process of N,N-bis(4-methylphenyl)-3-(tributylstannyl)benzo[c]thiophene-1-amine is as shown in formula (V):

[0017]

[0018] TIPS stands for triisopropylsilane, and its structure is as follows

[0019] The present invention also provides the use of the above-mentioned small molecule organic dye in the preparation of nano photosensitizers modified with outer membrane vesicles of engineered bacteria.

[0020] The beneficial effects of the present invention are as follows: the present invention provides a small molecule organic dye and a preparation method and application thereof. The small molecule organic dye of the present invention adopts 1,3-indanedione and its dicyanomethylene derivatives as the A part of the DA-type molecule to produce a significant ICT effect for extraordinary phototherapy applications. Generally, these D-π-A-type molecules are designed to connect the D-block to the C2 position of the A group derived from 1,3-indanedione to extend the -coupling. In addition to 1,3-indanedione, indanone can also serve as a good A group. In particular, indanone is derived into dicyanomethyleneindene, making it an interesting new A structure for near-infrared active molecules, a molecule of D-π-A configuration, in which dicyanomethyleneindene is the A group, and a new molecular skeleton composed of dicyanomethyleneindene (DCMI) is used as a π-conjugated acceptor, which is connected to a triarylamine donor for adjusting absorption. Among them, the maximum absorption rate of the embedded high quinone π bridge is 783nm, which can be studied for phototherapy applications. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 11 is the chemical structure of the small molecule organic dye according to the embodiment of the present invention.

[0022] Figure 2 1 is the chemical structure of the small molecule organic dye according to the embodiment of the present invention.

[0023] Figure 3 The chemical structure of the small molecule organic dye in the comparative example of the present invention.

[0024] Figure 4 This is a diagram of the small molecule organic dye and its fluorescence characterization results according to an embodiment of the present invention.

[0025] Among them, DIcyanomethyleneindene is dicyanomethyleneindene, phenylene is phenyl, Thiophene is thiophene, Benzothiophene is phenylthiophene, Absorbtion is absorbance, F uorescence intensity is fluorescence intensity, and wavelength is wavelength.

[0026] Figure 5 This is a flow chart of the chemical reaction preparation of small molecule organic dyes according to an embodiment of the present invention. The numbers with % below the reaction arrows in the figure represent the yield of the reaction step.

[0027] Figure 6 The NMR spectrum of the small molecule organic dye compound of the embodiment of the present invention is shown in Figure 1, wherein a is the chemical structure of the small molecule organic dye, a is 1H NMR spectrum, and b is 13CNMR.

[0028] Figure 7 The NMR spectrum of the small molecule organic dye compound of the embodiment of the present invention is shown in Figure 1, wherein a is the chemical structure of the small molecule organic dye, a is 1H NMR spectrum, and b is 13CNMR.

[0029] Figure 8 The NMR spectrum of the small molecule organic dye compound of the comparative example of the present invention is shown in Figure 1, wherein a is the chemical structure of the small molecule organic dye, a is 1H NMR spectrum, and b is 13CNMR. DETAILED DESCRIPTION

[0030] In order to better illustrate the purpose, technical solutions and advantages of the present invention, the present invention will be further described below in conjunction with specific embodiments.

[0031] Example 1

[0032] As a small molecule organic dye (BThDCMI) in an embodiment of the present invention, the chemical structure of the small molecule organic dye is shown in Formula I,

[0033]

[0034] The preparation method of the small molecule organic dye of this embodiment comprises the following steps:

[0035] N, N-bis(4-methylphenyl)-3-(tributyltinyl)benzo[c]thiophene-1-amine and 2-(3-chloro-1H-inden-1-ylidene)malononitrile are reacted in toluene under reflux for 5 hours under the catalysis of bis(triphenylphosphine)palladium dichloride to obtain the compound represented by formula (I). The specific preparation process is as follows Figure 5 The yield was 65%.

[0036] The chemical structure of 2-(3-chloro-1H-inden-1-ylidene)malononitrile is shown in Formula VI.

[0037]

[0038] The NMR characterization results of the small molecule organic dye compound represented by formula Ⅰ are as follows Figure 6 shown.

[0039] Example 2

[0040] As a small molecule organic dye (ThDCMI) in an embodiment of the present invention, the chemical structure of the small molecule organic dye is shown in Formula II,

[0041]

[0042] The preparation method of the small molecule organic dye of this embodiment comprises the following steps:

[0043] N, N-bis(4-methylphenyl)-3-(tributyltinyl)thiophene-1-amine and 2-(3-chloro-1H-inden-1-ylidene)malononitrile are reacted in toluene under reflux for 12 hours under the catalysis of bis(triphenylphosphine)palladium dichloride to obtain the compound shown in formula (II). The specific preparation process is as follows Figure 5 The yield was 88%.

[0044] The NMR characterization results of the small molecule organic dye compound shown in Formula II are as follows Figure 7 shown.

[0045] Comparative Example 1

[0046] As a small molecule organic dye (PhDCMI) of the comparative example of the present invention, the chemical structure of the small molecule organic dye is shown in Formula VI,

[0047]

[0048] The preparation method of the small molecule organic dye of this embodiment comprises the following steps:

[0049] The compound represented by formula (VIII) and 2-(3-chloro-1H-inden-1-ylidene)malononitrile are reacted in tetrahydrofuran aqueous solution at -78°C in the presence of tetrakis(triphenylphosphine)palladium catalyst and potassium carbonate to obtain the compound represented by formula (VI). The specific preparation process is as follows Figure 5 shown.

[0050]

[0051] The NMR characterization results of the small molecule organic dye compound shown in Formula VI are as follows Figure 8 shown.

[0052] Experimental methods

[0053] The small molecule organic dyes of the examples and comparative examples were characterized by fluorescence, and the experimental results are as follows: Figure 1 As shown, Figure 4 Preparation and characterization of OBDlp. Figure 4 (a) Schematic diagram of the preparation of PhDCMI, ThDCMI and BThDCMI. Figure 4 (b) Absorption of PhDCMI. Figure 4 (c) Absorption of ThDCMI. Figure 4 (d) Absorption of BThDCMI.

[0054] Depend on Figure 4 It can be seen that the new molecular skeleton composed of dicyanomethyleneindene (DCMI) acts as a π-conjugated acceptor, which is connected to a triarylamine donor for adjusting absorption. Among them, the maximum absorption rate of the embedded high quinone π bridge is 783nm, which can be studied for phototherapy applications and has a near-infrared response, wherein the small molecule dye of Example 1 has a longer wavelength and is closer to the near-infrared. Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention rather than to limit the scope of protection of the present invention. Although the present invention is described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solution of the present invention can be modified or equivalently replaced without departing from the essence and scope of the technical solution of the present invention.

Claims

1. A small molecule organic dye, characterized in that: The chemical structure of the small molecule organic dye is shown in Formula I or Formula II.

2. The method for preparing a small molecule organic dye according to claim 1, characterized in that: The preparation method of the small molecule organic dye comprises the following steps: N, N-bis(4-methylphenyl)-3-(tributyltinyl)benzo[c]thiophene-1-amine or N, N-bis(4-methylphenyl)-3-(tributyltinyl)thiophene-1-amine is reacted with 2-(3-chloro-1H-inden-1-ylidene)malononitrile in toluene reflux under the catalysis of bis(triphenylphosphine)palladium dichloride to obtain a compound represented by formula (II) or formula (I).

3. The method for preparing a small molecule organic dye according to claim 2, characterized in that: The reflux reaction time is 4 to 18 hours.

4. The method for preparing a small molecule organic dye according to claim 2, characterized in that: The preparation process of 2-(3-chloro-1H-inden-1-ylidene)malononitrile is shown in formula (III):

5. The method for preparing a small molecule organic dye according to claim 2, characterized in that: The preparation process of N, N-bis(4-methylphenyl)-3-(tributyltinyl)thiophene-1-amine is shown in formula (IV):

6. The method for preparing a small molecule organic dye according to claim 2, characterized in that: The preparation process of N, N-bis(4-methylphenyl)-3-(tributylstannyl)benzo[c]thiophene-1-amine is shown in formula (V):

7. Use of the small molecule organic dye as claimed in claim 1 in the preparation of nano photosensitizers modified with outer membrane vesicles of engineered bacteria.

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