Photochromic merocyanine compounds containing aldehyde groups, and methods of making and using the same
By synthesizing photochromic cyanine compounds containing aldehyde groups, the thermodynamic instability and insufficient water solubility of open-ring cyanine structures were solved, achieving stable existence and good dispersibility of the compounds at room temperature, and expanding their applications in biocompatible photochromic probes and drug delivery.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- ANHUI NORMAL UNIV
- Filing Date
- 2026-02-06
- Publication Date
- 2026-05-29
Smart Images
Figure CN122102998A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a photochromic anthocyanin compound containing an aldehyde group, its preparation method, and its application. Background Technology
[0002] Spiropyran is an important class of organic photochromic compounds. Its molecules can undergo reversible conversion between two isomers: closed-ring spiropyran (SP) and open-ring cyanine (MC). The photoisomerization mechanism is shown in Figure 1.
[0003] When spiropyran is in its closed-ring state, the molecule is electrically neutral with no net charge and virtually no ion-binding ability. Under ultraviolet light irradiation, the CO bond in spiropyran breaks, forming a zwitterionic structure and producing N2O. + and O - Two active sites can complex with metal ions of opposite charge. The coordination of the metal ion stabilizes the MC state, preventing it from thermally relaxing back to the SP state, thereby producing a detectable change in color or fluorescence signal.
[0004] Most spiropyrans synthesized in existing technologies are closed-ring spiropyrans (SP). The open-ring cyanine (MC) structure of traditional spiropyrans is thermodynamically unstable and readily reverts to the colorless SP structure at room temperature through spontaneous ring closure. Synthetic reports of introducing aldehyde groups into the open-ring cyanine are extremely rare, mainly due to the inherent chemical instability of aldehydes. They readily undergo Cannizzaro disproportionation in strong bases and alcoholic solvents and are easily oxidized to carboxylic acids in air, resulting in numerous byproducts and low yields. Furthermore, the similarity in structure and polarity between the starting materials and products makes product separation and purification difficult. In addition, while most aldehyde-containing open-ring cyanine derivatives exhibit good photoresponsiveness in organic solvents, their water solubility and stability in complex aqueous systems still require improvement. Summary of the Invention
[0005] To address the aforementioned technical problems, this invention provides a photochromic cyanine compound containing an aldehyde group, its preparation method, and its applications.
[0006] The technical solution adopted in this invention is as follows:
[0007] This invention provides a photochromic cyanine compound containing an aldehyde group, the structural formula of which is: Where R is H or an alkoxy group with four or fewer carbon atoms; n = 1 or 2.
[0008] Furthermore, R is preferably methoxylated.
[0009] The present invention also provides a method for preparing the cyanine compound containing an aldehyde group as a photochromic part. The preparation method includes the following steps: dissolving 2-hydroxy-5-methylisophthalaldehyde in an organic solvent, adding an organic solvent containing an indolonyl sulfonate compound dropwise under an inert atmosphere, refluxing the reaction, and purifying the reaction solution by post-treatment to obtain the cyanine compound containing an aldehyde group as a photochromic part.
[0010] The structural formula of the indolonyl sulfonate compound is: .
[0011] The molar ratio of 2-hydroxy-5-methylisophthalaldehyde to indolonyl sulfonate compounds is 1:1 to 1.2.
[0012] The organic solvent is anhydrous ethanol; the concentration of 2-hydroxy-5-methylisophthalaldehyde in the organic solvent is 1~1.5M.
[0013] The reflux reaction time is 30-40 hours.
[0014] The inert atmosphere is nitrogen.
[0015] When R is an alkoxy group with four or fewer carbon atoms, the reaction solution is purified by recrystallization, and the concentrated reaction solution is then poured into ethanol for recrystallization.
[0016] When R is H, the reaction solution is purified by column chromatography. The reaction solution is concentrated and then purified by column chromatography using dichloromethane and methanol as eluents. The volume ratio of dichloromethane to methanol is gradually changed from 20:1 to 7:1.
[0017] The present invention also provides the application of the aforementioned photochromic anthocyanin compounds containing aldehyde groups in metal ion recognition.
[0018] Compared with the prior art, the present invention has the following beneficial effects:
[0019] In the preparation method of photochromic cyanine compounds containing aldehyde groups provided by this invention, 2-hydroxy-5-methylisophthalaldehyde is used as a dialdehyde electrophilic reagent, which condenses with the active methylene group of an indolonium salt compound to form a conjugated double bond, constructing a larger planar π-conjugated system. The planar configuration of the open-ring cyanine is locked through the conjugated electron delocalization effect, effectively suppressing its spontaneous ring-closing tendency and achieving long-term stability of the MC structure at room temperature. The stabilized cyanine compounds show significantly reduced sensitivity to solvent polarity, temperature, and pH, and can maintain the open-ring state without relying on harsh conditions such as low temperature and strongly polar solvents, providing a wider adaptability window for applications in complex environments.
[0020] The method for preparing cyanine compounds containing aldehyde groups for photochromic fractions provided by this invention reduces the generation of reaction byproducts by using an inert atmosphere and controlling the order of reactant addition, thus synthesizing cyanine compounds containing aldehyde groups that are both lipophilic and water-soluble. A nitrogen atmosphere effectively suppresses oxidation side reactions, while adding an organic solvent containing indole-1,5-alkyl sulfonate compounds dropwise to an organic solution of 2-hydroxy-5-methyl-isophthalaldehyde allows for precise control of local reactant concentrations. When the organic solvent containing indole-1,5-alkyl sulfonate compounds is added dropwise, the excess dialdehyde substrate ensures that each indole salt molecule undergoes a 1:1 selective condensation with only one aldehyde group, preventing the indole salt from cross-linking with two aldehyde groups to form multi-substituted byproducts.
[0021] The photochromic cyanine compounds containing aldehyde groups provided by this invention utilize alkyl sulfonate groups of the indolonium salt parent compound to provide strong hydrophilic sites, resulting in high water solubility. The conjugated hydrophobic regions of the benzene ring, alkyl group, and open-ring cyanine portion introduced by 2-hydroxy-5-methyl-isophthalaldehyde enhance the dispersibility of these compounds in organic solvents, thus exhibiting good amphiphilicity and achieving natural oil-water compatibility. This characteristic makes them promising candidates for use as biocompatible photochromic probes, directly applicable to intracellular pH / polarity detection and liposome-encapsulated light-controlled drug delivery, enabling them to cross biological membrane barriers without additional modification.
[0022] The photochromic cyanine compound containing an aldehyde group provided by this invention retains one active aldehyde group in its structural formula. This allows it to be further coupled with amino, hydrazine, or other groups through Schiff base reactions, click chemistry, etc., to rapidly introduce targeted ligands, such as RGD peptides, folic acid, fluorescent probes such as rhodamine, Cy5, or chemotherapeutic drugs. This achieves an integrated function of photochromism-targeted imaging-treatment, expanding its application in precision diagnosis and treatment of tumors. Attached Figure Description
[0023] Figure 1 This is a schematic diagram illustrating the reversible conversion between the closed-ring spiropyran (SP) and the open-ring anthocyanin (MC) isomers.
[0024] Figure 2 A schematic diagram of the structure of anthocyanin compounds containing aldehyde groups, provided by the present invention;
[0025] Figure 3 This is a synthetic route diagram of MC1, a photochromic compound containing an aldehyde group, from Example 1;
[0026] Figure 4 This is a synthetic route diagram for MC2, a photochromic compound containing an aldehyde group, from Example 2;
[0027] Figure 5 The 1H NMR spectrum of MC1, a photochromic compound containing an aldehyde group, from Example 1;
[0028] Figure 6 The mass spectrum of MC1, a photochromic compound containing an aldehyde group, from Example 1;
[0029] Figure 7 The 1H NMR spectrum of MC2, a photochromic compound containing an aldehyde group, from Example 2;
[0030] Figure 8 The carbon NMR spectrum of MC2, a photochromic compound containing an aldehyde group, from Example 2;
[0031] Figure 9 The mass spectrum of MC2, a photochromic compound containing an aldehyde group, from Example 2;
[0032] Figure 10 The diagram shows the changes (A) and the schematic diagram (B) of the cyanine compound MC1 containing an aldehyde group in Example 1 before and after the addition of zinc ions.
[0033] Figure 11 The graph shows the changes in the cyanine compound MC1 containing an aldehyde group in Example 1 before and after the addition of zinc ions and before and after ultraviolet irradiation.
[0034] Figure 12 The diagram shows the changes (A) and the schematic diagram (B) of the cyanine compound MC2 containing an aldehyde group in Example 2 before and after the addition of zinc ions.
[0035] Figure 13 The graph shows the changes in the cyanine compound MC2 containing an aldehyde group in Example 2 before and after the addition of zinc ions and before and after ultraviolet irradiation. Detailed Implementation
[0036] The present invention will now be described in detail with reference to the embodiments.
[0037] The 3-(5-methoxy-2,3,3-trimethyl-3H-indol-1-onthium-1-yl)propane-1-sulfonate and 4-(2,3,3-trimethyl-3H-indol-1-onthium-1-yl)butane-1-sulfonate used in the examples were prepared in accordance with the literature. Synthesized using a similar method, the synthetic route is as follows: Figure 3 , 4 As shown.
[0038] Example 1
[0039] A photochromic anthocyanin compound MC1 containing an aldehyde group has the following structural formula: Its synthetic route is as follows Figure 3 As shown.
[0040] The preparation method of the cyanine compound MC1 containing an aldehyde group and photochromic fraction is as follows:
[0041] 0.4087 g (2.49 mmol) of 2-hydroxy-5-methylisophthalaldehyde was dissolved in 20 mL of anhydrous ethanol. Under a nitrogen atmosphere, 10 mL of an ethanol solution of 3-(5-methoxy-2,3,3-trimethyl-3H-indol-1-onth-1-yl)propane-1-sulfonate with a concentration of 0.249 mmol / mL was added dropwise. The mixture was refluxed and stirred for 37 h. The reaction solution was concentrated and recrystallized from ethanol to obtain 0.375 g of red solid, which is MC1, a photochromic cyanine compound containing an aldehyde group, with a yield of 32.91%.
[0042] That 1 H NMR (400 MHz, DMSO-d6) δ 11.68 (s, 1H), 10.12 (s, 1H), 8.57 (d,J = 2.2 Hz, 1H), 8.43 (d, J = 16.4 Hz, 1H), 7.99 (d, J = 8.9 Hz, 1H), 7.93(d, J = 16.5 Hz, 1H), 7.83 (d, J = 2.1 Hz, 1H), 7.53 (d, J = 2.5 Hz, 1H), 7.19 (dd, J = 8.9, 2.5 Hz, 1H), 4.84 (t, J = 7.9 Hz, 2H), 3.90 (s, 3H), 2.65(t, J = 6.3 Hz, 2H), 2.40 (s, 3H), 2.20 (d, J = 6.4 Hz, 2H), 1.78 (s, 6H), as Figure 5 As shown.
[0043] Its mass spectrometry is as follows Figure 6 As shown.
[0044] Example 2
[0045] A photochromic anthocyanin compound MC2 containing an aldehyde group has the following structural formula: Its synthetic route is as follows Figure 4 As shown.
[0046] The preparation method of the cyanine compound MC2 containing an aldehyde group, which is a photochromic component, is as follows:
[0047] 0.1986 g (1.2 mmol) of 2-hydroxy-5-methylisophthalaldehyde was dissolved in 10 mL of anhydrous ethanol. Under a nitrogen atmosphere, 5 mL of an ethanol solution of 4-(2,3,3-trimethyl-3H-indol-1-onthium-1-yl)butane-1-sulfonate with a concentration of 0.24 mmol / mL was added dropwise. The mixture was refluxed and stirred for 40 h. After concentration, the reaction solution was purified by column chromatography using a mixed solution of dichloromethane and methanol as the eluent. The volume ratio of dichloromethane to methanol was gradually changed from 20:1 to 7:1 to obtain 4028 g of product, with a yield of 75.52%.
[0048] That 1 H NMR (500 MHz, DMSO-d6) δ 9.92 (s, 1H), 7.36 (d, J = 2.3 Hz, 1H), 7.31 (d, J = 2.2 Hz, 1H), 7.12 (d, J = 7.1 Hz, 2H), 7.07 (d, J = 10.4 Hz,1H), 6.78 (t, J = 7.4 Hz, 1H), 6.61 (d, J = 7.7 Hz, 1H), 5.94 (s, 1H), 3.15(d, J = 7.5 Hz, 2H), 2.39 – 2.36 (m, 2H), 2.25 (s, 3H), 1.63 (dd, J = 19.8,7.9 Hz, 2H), 1.58 – 1.54 (m, 2H), 1.25 (s, 3H), 1.13 (s, 3H). (e.g.) Figure 7 As shown.
[0049] That 13 C NMR (101 MHz, DMSO-d6) δ 188.12, 155.16, 147.25, 136.70, 134.38, 129.99, 129.01, 128.37, 127.16, 122.05, 121.96, 121.28, 120.39, 119.16, 106.91, 105.88, 52.41, 51.59, 43.71, 28.20, 26.25, 23.17, 20.52, 20.29. (e.g.) Figure 8 As shown.
[0050] Its mass spectrometry is as follows Figure 9 As shown.
[0051] Test Example 1
[0052] The synthesized compound MC1 was mixed with ZnBr2 in equal amounts, and water was used as a solvent to prepare a ZnBr2 concentration of 5 × 10⁻⁶. -5 A solution of M is prepared, and simultaneously, aqueous solutions of compound MC1 with the same molar concentration are prepared. The comparison between the two is as follows: Figure 10 As shown in Figure A. From Figure 10 A clear color difference is visible between the two solutions. The aqueous solution of compound MC1 is purple, as shown in the image. Figure 10 The left image in Figure A shows the mixture of MC1 and ZnBr2, which is pink. Figure 10 The right image in Figure A is shown in the diagram.
[0053] The UV spectra of compound MC1 aqueous solution, mixed solution of MC1 and ZnBr2, compound MC1 aqueous solution after irradiation with 405nm UV light for 20s, and mixed solution of MC1 and ZnBr2 after irradiation with 405nm UV light for 15s were measured respectively. Figure 11 As shown in the figure, after ultraviolet irradiation, MC1 transforms from a colored open-ring anthocyanin structure to a colorless closed-ring spiropyran structure, and the absorption peak in the 560-580 nm range is significantly weakened. This can be seen from the figure. 2+ The presence of [something] does not affect the photochromic process of MC1.
[0054] Test Example 2
[0055] The synthesized compound MC2 and ZnBr2 were mixed in equal amounts with water as a solvent to prepare a solution of 5 × 10⁻⁶. -5 A solution of M is prepared, and simultaneously, aqueous solutions of compound MC2 with the same mass concentration are prepared. The comparison between the two is as follows: Figure 12 As shown in Figure A. From Figure 12 A clear color difference is visible between the two solutions. The aqueous solution of compound MC2 is purple, as shown in the image. Figure 12 The left image in Figure A shows the mixture of MC2 and ZnBr2, which is pink. Figure 12 The right image in Figure A is shown in the diagram.
[0056] The UV spectra of compound MC2 aqueous solution, mixed solution of MC2 and ZnBr2, the UV spectra of compound MC2 aqueous solution after irradiation with 405nm UV light for 20s, and the UV spectra of the mixed solution of MC2 and ZnBr2 after irradiation with 405nm UV light for 15s were measured respectively. Figure 13 As shown in the figure, after ultraviolet irradiation, MC2 transforms from a colored open-ring cyanine structure to a colorless closed-ring spiropyran structure, and the strong absorption peak in the 560-580 nm range is significantly weakened. This can be seen from the figure. 2+ The presence of [something] does not affect the photochromic process of MC2.
[0057] The above detailed description of a photochromic cyanine compound containing an aldehyde group, its preparation method, and its application, with reference to the embodiments, is illustrative rather than limiting. Several embodiments may be listed within the defined scope. Therefore, variations and modifications without departing from the overall concept of the present invention should be within the protection scope of the present invention.
Claims
1. A photochromic anthocyanin compound containing an aldehyde group, characterized in that, The structural formula of the cyanine compound containing an aldehyde group and photochromic fraction is: Where R is H or an alkoxy group with four or fewer carbon atoms; n = 1 or 2.
2. The photochromic anthocyanin compound containing an aldehyde group according to claim 1, characterized in that, R stands for methoxy group.
3. The method for preparing photochromic anthocyanin compounds containing aldehyde groups as described in claim 1 or 2, characterized in that, The preparation method includes the following steps: dissolving 2-hydroxy-5-methylisophthalaldehyde in an organic solvent, adding an organic solvent containing indolonyl sulfonate compounds dropwise under an inert atmosphere, refluxing the reaction, and purifying the reaction solution by post-treatment to obtain photochromic anthocyanin compounds containing aldehyde groups.
4. The preparation method according to claim 3, characterized in that, The structural formula of the indolonyl sulfonate compound is: .
5. The preparation method according to claim 3, characterized in that, The molar ratio of 2-hydroxy-5-methylisophthalaldehyde to indolonyl sulfonate compounds is 1:1 to 1.
2.
6. The preparation method according to any one of claims 3-5, characterized in that, The organic solvent is anhydrous ethanol; the concentration of 2-hydroxy-5-methylisophthalaldehyde in the organic solvent is 1~1.5M.
7. The preparation method according to any one of claims 3-5, characterized in that, The reflux reaction time is 30-40 hours.
8. The preparation method according to any one of claims 3-5, characterized in that, When R is an alkoxy group with four or fewer carbon atoms, the reaction solution is purified by recrystallization, and the concentrated reaction solution is then poured into ethanol for recrystallization.
9. The preparation method according to any one of claims 3-5, characterized in that, When R is H, the reaction solution is purified by column chromatography. After the reaction solution is concentrated, it is purified by column chromatography using a mixed solution of dichloromethane and methanol as the eluent. The volume ratio of dichloromethane to methanol is gradually changed from 20:1 to 7:
1.
10. The application of the aldehyde-containing photochromic cyanine compounds as described in claim 1 in metal ion recognition.