Method for constructing atypical near-infrared light-emitting polymer based on itaconic anhydride and application thereof

Abstract

The application discloses a method for constructing atypical near-infrared light-emitting polymers based on itaconic anhydride and application thereof, and belongs to the technical field of organic light-emitting materials. The method comprises the following steps: first, preparing a thiol-containing intermediate by reacting N-methyldiethanolamine derivatives with double / multi-thiol compounds; and then, performing nucleophilic ring-opening polymerization on the thiol-containing intermediate and itaconic anhydride to obtain a target polymer. The polymer is completely composed of non-conjugated structural units and does not contain a pi-conjugated aromatic ring, and the light emission is derived from cluster-induced light emission promoted by strong ion interaction formed in the polymerization process. By selecting different thiol compounds and regulating the topological structure (linear or hyperbranched) of the polymer, a polymer with an emission wavelength in the 600-800 nm near-infrared region can be prepared. The polymer has the advantages of simple synthesis, good water solubility, high biocompatibility, aggregation-induced light emission, pH / ion response and the like, and has important application value in the fields of near-infrared fluorescence imaging and biosensing.

Description

Technical Field

[0001] This invention belongs to the field of organic light-emitting materials technology, specifically relating to a method and application of constructing atypical near-infrared light-emitting polymers based on itaconic anhydride. Background Technology

[0002] Organic fluorescent materials, especially those exhibiting aggregation-caused emission (AIE) behavior, have been widely used in organic light-emitting diodes (OLEDs), sensors, and novel bioimaging technologies. Among these, organic light-emitting polymers (OLEPs) have attracted considerable attention due to their superior properties, such as designable molecular structures, stable performance, and unique fluorescence signal amplification. However, traditional OLEPs, due to their large π-conjugated aromatic structures, inevitably suffer from poor photostability, hydrophilicity, high biotoxicity, and environmental unfriendliness, significantly limiting their application in the biological field. Furthermore, their high cost and complex, multi-step synthesis process further restrict their large-scale application. Therefore, developing novel, green, hydrophilic, and biocompatible OLEPs using simple methods has significant scientific and economic value.

[0003] It is noteworthy that in recent years, an increasing number of natural polymers (such as rice and cellulose), biomacromolecules (such as peptides and proteins), and synthetic polymers (such as PAN and PAM) have been found to emit intrinsic fluorescence under ultraviolet light and possess AIE properties. The core difference between these nonconventional luminescent polymers (NLPs) and traditional OLEP lies in the fact that they contain only nonconventional chromophores (NCCs), specifically including non-conjugated functional groups rich in n or π electrons, such as amino (NH), hydroxyl (-OH), ester (-COO-), amide (NHCO), thioether (-S-), and cyano (C≡N). In the aggregated state, the electron clouds of these functional groups overlap, forming through-space conjugation (TSC) through intramolecular and intermolecular interpenetration. This triggers energy level splitting and a reduction in the band gap, thereby promoting electron transitions and producing clustering-triggered emission (CTE). Compared to traditional OLEP, NLPs are easier to synthesize and functionally modify; more importantly, their chemical composition is closer to that of biological macromolecules, exhibiting excellent water solubility and biocompatibility. Therefore, NLPs offer a novel approach to solving the application challenges of traditional OLEP in the life sciences and possess broad development potential.

[0004] However, due to the lack of conjugated structures, the emission wavelengths of NLPs reported to date are limited to the visible light region, with very few reports on near-infrared (NIR) luminescent NLPs. In the last decade, to obtain better image quality and higher signal-to-background ratios, fluorescence imaging techniques have primarily focused on the NIR (780-1700 nm) window. Therefore, the lack of NIR luminescent NLPs has become a significant bottleneck limiting their biological applications.

[0005] Since Tucker et al. first reported synthetic NLPs in 2001, most early synthesized NLPs have emitted fluorescence in the blue light region, while NLPs with green, yellow, and red fluorescence emission are still relatively rare. In recent years, with the progress in the study of luminescence mechanisms, researchers have gradually developed new NLP materials with long-wavelength emission and made some progress. Among them, the research groups of Academician Tang Benzhong of Hong Kong University of Science and Technology, who proposed the AIE concept, Researcher Yuan Wangzhang of Shanghai Jiaotong University, who proposed the CTE mechanism, and Professor Wang Huiliang of Beijing Normal University have carried out systematic theoretical and applied research on NLPs with long-wavelength emission and achieved a series of results. At present, researchers mainly use two strategies to synthesize long-wavelength luminescent NTLs: (1) to form clusters with a greater degree of TSC; (2) to enhance the intermolecular interaction, thereby enhancing the cluster rigidity and thus suppressing non-radiative decay. In fact, in strategy (1), TSC is conjugated through the overlap and sharing of electron clouds, which does not depend on the formation of actual covalent bonds. Therefore, non-covalent interactions play a crucial role in both strategies, forming the foundation and key to designing long-wavelength luminescent NTLs. For a long time, researchers have generally constructed NTL systems using two types of non-covalent interactions: hydrogen bonds and van der Waals forces. However, the limited strength of these two weak bonds results in insufficient TSC (transient charge concentration) and conformational rigidity of the luminescent clusters in the polymer system, failing to meet the low bandgap requirement for NIR luminescence, thus limiting the NIR luminescence of NTLs. Therefore, exploring the construction of NLPs with NIR emission based on stronger non-covalent interactions is not only helpful in solving their biological applications but also of great significance in understanding their luminescence mechanism.

[0006] Building upon existing research, this invention introduces non-conjugated zwitterionic ions (I-TEA) into the linear polymer backbone and hyperbranched framework. Utilizing the strong intra- and inter-chain ionic interactions, it constructs near-infrared (NIR) luminescent non-conjugated luminescent polymers (NLPs), developing a novel, green, and biocompatible non-aromatic near-infrared luminescent non-conjugated luminescent polymer (OLEP). This invention will systematically study the design, synthesis, and optical properties of NIR fluorescence emission, high quantum yield NLPs, and delve into their luminescence mechanism, elucidating the structure-activity relationship between polymer structure and luminescence properties, and their potential biological applications. This research not only provides feasible ideas and methods for designing and synthesizing novel NIR luminescent OLEPs with structures more closely resembling biological macromolecules, effectively promoting a redshift in NLP emission wavelengths, but also has significant theoretical guiding significance for solving the key scientific problem of "near-infrared luminescence limitation" in NLPs using strong non-covalent interactions, laying a solid theoretical foundation for the application of NLPs materials in the biological field. Summary of the Invention

[0007] The purpose of this invention is to overcome the technical bottleneck of limited near-infrared emission from existing atypical luminescent polymers and to provide a method for constructing atypical near-infrared luminescent polymers based on itaconic anhydride. This method successfully prepares NLPs with emission wavelengths reaching the near-infrared region by introducing strong ion interactions, exhibiting excellent aggregation-induced emission characteristics, pH stability, and biocompatibility.

[0008] Another object of the present invention is to provide the application of the above-mentioned atypical near-infrared luminescent polymers in fields such as bioimaging and fluorescence sensing.

[0009] To achieve the above objectives, the present invention adopts the following technical solution: In a first aspect, the present invention provides an atypical near-infrared luminescent polymer based on itaconic anhydride. This polymer is prepared by a nucleophilic ring-opening polymerization reaction of a thiol-containing intermediate and itaconic anhydride. Its structure does not contain π-conjugated aromatic rings, and its fluorescence emission wavelength is located in the near-infrared region (above 600 nm), exhibiting aggregation-induced emission properties.

[0010] The thiol-containing intermediate is obtained by reacting the N-methyldiethanolamine derivative monomer DMA, as shown in formula (I), with a compound containing dithiol or polythiol groups. The structural formula of the monomer DMA is as follows: The dithiol-containing compound can be selected from 1,2-ethanedithiol, 1,5-pentanedithiol, bis(2-mercaptoethyl) ether, etc. The resulting thiol-containing intermediate has a linear structure, which is then polymerized with itaconic anhydride to obtain linear near-infrared luminescent polymers (such as ITA-L-P1, ITA-L-P2, ITA-L-P3). The fluorescence emission wavelength of these linear polymers is typically between 594 nm and 603 nm.

[0011] When the dithiol-containing compound is a bis(2-mercaptoethyl) ether, the oxygen atom in its molecule has an electron-donating effect, which can further enhance ion interactions and optimize the near-infrared luminescence properties of the polymer.

[0012] The thiol-containing intermediate can also be obtained by reacting the monomer DMA with a compound containing multiple thiol groups (such as trimethylolpropane tris(3-mercaptopropionate)). The resulting thiol-containing intermediate has a branched structure, which, upon polymerization with itaconic anhydride, yields a hyperbranched near-infrared luminescent polymer (such as ITA-B-P1). The hyperbranched structure exhibits denser molecular packing and stronger intra- and inter-chain interactions, which can more effectively promote TSC and further redshift the emission wavelength. Experiments show that the fluorescence emission wavelength of this hyperbranched polymer can be redshifted to 620 nm, and the long-wavelength edge of the emission spectrum can be extended to 800 nm, completely covering the near-infrared region.

[0013] Secondly, the present invention provides a method for preparing the above-mentioned atypical near-infrared luminescent polymer, comprising the following steps: (1) Synthesis of thiol-containing intermediates: The monomer DMA was reacted with a thiol-containing compound (dithiol or polythiol) in the presence of triethylamine (an acid-binding agent) in N,N-dimethylformamide (DMF) solvent at room temperature for 4-6 hours. After the reaction was completed, the product was precipitated with methanol, centrifuged, washed and dried under vacuum to obtain thiol-containing intermediates with different structures (L-P1, L-P2, L-P3, B-P1).

[0014] The molar ratio of monomer DMA to thiol-containing compound is 1:0.8-1.2 (preferably 1:1); the molar ratio of thiol to triethylamine is 1:3-1:5.

[0015] (2) Nucleophilic ring-opening polymerization: The thiol-containing intermediate obtained in step (1) was dissolved in dry DMF and slowly added dropwise to a DMF solution containing itaconic anhydride under nitrogen protection. The reaction was stirred at 20-30°C for 12-18 hours. After the reaction solution was cooled, it was precipitated with methyl tert-butyl ether (or a mixture of n-hexane and methyl tert-butyl ether), the precipitate was collected by centrifugation, washed and vacuum dried to obtain the target atypical near-infrared luminescent polymer (ITA-L-P1 / 2 / 3, ITA-B-P1). The molar ratio of the thiol-containing intermediate to itaconic anhydride was 1:1-1:3.

[0016] Thirdly, the present invention provides applications of the aforementioned atypical near-infrared luminescent polymer. This polymer can be used for iron ion detection, or phosphate / lactate ion detection, exhibiting specific fluorescence quenching responses to Fe²⁺ and Fe³⁺ ions, and fluorescence enhancement responses to PO³⁻ and Lac⁻ ions.

[0017] Based on its excellent near-infrared luminescence properties, good water solubility, biocompatibility, and pH / ion response characteristics, this polymer can be used to prepare near-infrared fluorescent probes, bioimaging reagents (especially for deep tumor imaging), and ion sensing materials (such as specific detection of Fe²⁺ / Fe³⁺).

[0018] The beneficial effects of this invention are: 1. Innovative Luminescence Mechanism and Superior Near-Infrared Performance: This invention is the first to propose and verify a strategy for constructing NIR-luminescent NLPs using strong intra- and inter-chain ionic interactions within polymer chains. Ionic bonds introduced by itaconic anhydride effectively enhance the rigidity and electron delocalization of the luminescent clusters, successfully extending the emission wavelength of NLPs from the visible light region to the near-infrared region (600-800 nm), breaking through the bottleneck of traditional near-infrared luminescence in NLPs.

[0019] 2. Green structure and high biocompatibility: The polymer is composed entirely of non-conjugated structural units (ester groups, amide groups, tertiary amine salts, etc.) and does not contain any π-conjugated aromatic rings. Its chemical composition is closer to that of biological macromolecules, and it has low cytotoxicity and good biocompatibility, making it a promising candidate for application in the biomedical field.

[0020] 3. Excellent optical properties: The obtained polymer not only has NIR luminescence capability, but also exhibits typical aggregation-induced emission (AIE) characteristics, overcoming the aggregation quenching problem of traditional dyes. At the same time, it is fluorescently stable within the physiologically relevant pH range (3-10) and has specific ion responsiveness (such as fluorescence quenching of Fe³⁺).

[0021] 4. The synthesis method is simple and efficient: It adopts a two-step synthesis method, the raw materials are cheap and readily available, the reaction conditions are mild, the post-processing is simple (precipitation method), no complex column chromatography is required, it is suitable for large-scale preparation, and the cost is low.

[0022] 5. High structural designability: By selecting different thiol compounds (controlling alkyl chain length, introducing heteroatoms) and controlling the polymer topology (linear or hyperbranched), the emission wavelength, quantum efficiency and response performance of the polymer can be precisely controlled to meet the needs of different application scenarios. Attached Figure Description

[0023] Figure 1 The image shows a comparison of the UV absorption, fluorescence excitation, and emission spectra of the monomer DMA, each intermediate, and the final polymer in the examples.

[0024] Figure 2 The images show the three-dimensional fluorescence spectra of each substance in the examples.

[0025] Figure 3 The following are fluorescence emission spectra of the substances in the examples at different excitation wavelengths, demonstrating their excitation dependence.

[0026] Figure 4 The graph shows the fluorescence intensity changes of linear and hyperbranched polymers in solutions with different pH values ​​in the examples.

[0027] Figure 5 The fluorescence spectra of linear and hyperbranched polymers at different concentrations in the examples illustrate their concentration-dependent luminescence behavior.

[0028] Figure 6 The fluorescence spectra of the four polymers in the examples in different proportions of unsuitable solvents (methyl tert-butyl ether) demonstrate their AIE properties.

[0029] Figure 7 The graph shows the relative fluorescence intensity changes of the four polymers in the examples under the presence of different ions, illustrating their ion response characteristics.

[0030] Figure 8 This image shows the penetration imaging of the hyperbranched polymer ITA-B-P1 in the MKN-45 tumor cell sphere (MCTS) model, demonstrating its ability to penetrate and image deep tumors.

[0031] Figure 9 The image shows the ¹H NMR spectrum of the polymer ITA-L-P1.

[0032] Figure 10 The image shows the carbon nuclear magnetic resonance (¹³C NMR) spectrum of the polymer ITA-L-P1.

[0033] Figure 11 The image shows the ¹H NMR spectrum of the polymer ITA-B-P1.

[0034] Figure 12 The image shows the carbon nuclear magnetic resonance (¹³C NMR) spectrum of polymer ITA-B-P1. Detailed Implementation

[0035] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. The following embodiments are used to illustrate the invention but are not intended to limit its scope.

[0036] Example 1 Synthesis of Monomeric DMA In a dry reaction flask, N-methyldiethanolamine (0.1617 g, 1.357 mmol) and 1.5 mL dichloromethane were added and stirred to dissolve. Under ice bath conditions, triethylamine (0.1511 g, 1.493 mmol) was slowly added dropwise as an acid-binding agent, and the mixture was stirred for 30 minutes. Acryloyl chloride (0.614 g, 6.784 mmol) was then added dropwise. After the addition was complete, the ice bath was removed, and the reaction was allowed to proceed at room temperature for 3 hours. The reaction was monitored for completeness by TLC (eluent: petroleum ether / ethyl acetate = 2:1). The reaction solution was quenched with ice water, extracted with dichloromethane, and the organic phase was concentrated to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 4:1 (v / v)), and dried under vacuum at 40 °C for 24 hours to obtain a colorless, transparent liquid product, DMA, in 68% yield.

[0037] ¹H NMR (400 MHz, Chloroform-d) δ 6.41 (dd, J = 17.4, 1.5 Hz, 2H), 6.12 (dd, J = 17.3, 10.5 Hz, 2H), 5.83 (dd, J = 10.4, 1.5 Hz, 2H), 4.30 (s, 4H), 2.85 (s, 4H), 2.43 (s, 3H).

[0038] 13C NMR (151 MHz, cdcl3) δ 166.04, 131.03,128.22, 61.69, 55.46,42.46. Example 2: Synthesis of linear intermediate L-P1 DMA monomer (0.2 g, 0.881 mmol) was dissolved in 2 mL of DMF for later use. DMF (2 mL), triethylamine (0.0891 g, 0.880 mmol), and 1,2-ethylenedithiol (0.0829 g, 0.880 mmol) were added to a dry three-necked flask and stirred until homogeneous. Under N2 protection and at room temperature, the DMA solution was slowly added, and the reaction was continuously stirred for 4 h. After the reaction was complete, the reaction solution was added dropwise to excess methanol to precipitate the product. The precipitate was collected by centrifugation and dried under vacuum at 25 °C for 12 h to obtain a pale yellow viscous product, L-P1, with a yield of 76.7%. GPC analysis showed that the polymer had a number-average molecular weight (Mn) of 14103 and a weight-average molecular weight (Mw) of 19158. The calculated PDI was 1.358, indicating a degree of polymerization of 31, suggesting that the polymer has high polymerization activity.

[0039] 1H NMR (400 MHz, Chloroform-d) δ 2.31 – 2.37 (s, 3H), 2.59 – 2.66(t,4H), 2.67 – 2.72 (t, 4H), 2.72 – 2.75 (s, 4H), 2.78 – 2.83 (t, 4H), 4.15 –4.21 (t, 4H). 13C NMR (101 MHz, CDCl3) δ 171.74, 62.82, 55.88, 42.41, 34.82, 32.58,27.00. Example 3 Synthesis of linear intermediate L-P2 The synthesis method was the same as in Example 2, except that 1,2-ethanedithiol was replaced with an equimolar amount of 1,5-pentanedithiol. A pale yellow viscous product, L-P2, was obtained in 79.23% yield. 1 H NMR and 13 ¹³C NMR spectroscopy and high-temperature gel permeation chromatography (GPC) analysis showed that the polymer had a number-average molecular weight (Mn) of 14958 and a weight-average molecular weight (Mw) of 17613. The calculated PDI was 1.777, and the degree of polymerization of the polymer was estimated to be 30, successfully verifying the molecular structure of L-P2.

[0040] 1H NMR (400 MHz, Chloroform-d) δ 1.40 – 1.53 (m, 3H), 1.53 – 1.70(m,5H), 2.33 – 2.37 (s, 3H), 2.48 – 2.56 (t, 5H), 2.57 – 2.65 (t, 4H), 2.67 –2.74 (t, 4H), 2.74 – 2.82 (t, 5H), 4.16 – 4.22(t, 4H). 13C NMR (151 MHz, cdcl3) δ 171.91, 62.38, 55.90, 42.89, 34.83, 32.00,29.11, 28.01, 26.95. Example 4 Synthesis of linear intermediate L-P3 The synthesis method was the same as in Example 2, except that 1,2-ethanedithiol was replaced with an equimolar amount of bis(2-mercaptoethyl) ether. A pale yellow viscous product, L-P3, was obtained in 65.84% yield. The molecular structure of LP was determined by... 1 H NMR and 13 The results were confirmed by 1200 nm NMR and high-temperature gel permeation chromatography (GPC). GPC tests showed that the polymer had a number-average molecular weight (Mn) of 11930 and a weight-average molecular weight (Mw) of 14443. The calculated PDI was 1.210, and the degree of polymerization of the polymer was estimated to be 23.

[0041] 1H NMR (400 MHz, Chloroform-d) δ 2.32 – 2.38 (s, 3H), 2.59 – 2.67(m,4H), 2.67 – 2.76 (m, 9H), 2.79 – 2.85 (m, 4H), 3.56 – 3.68 (m, 5H), 4.14 –4.24 (m, 4H). 13C NMR (151 MHz, cdcl3) δ 171.80, 70.66, 62.38, 55.89, 42.87, 34.89,31.61, 27.42. Example 5: Synthesis of linear polymer ITA-L-P1 Itaconic anhydride (ITA, 0.2 g, 1.8 mmol) was placed in a dry three-necked flask and purged with N2 for 30 minutes. Intermediate L-P1 (0.1 g, 7.09 μmol) was dissolved in 10 mL of DMF and slowly added dropwise to the flask using a syringe. The reaction mixture was stirred at room temperature under N2 protection for 12–18 hours. After the reaction was complete, the reaction mixture was added dropwise to a hexane / methyl tert-butyl ether (1:1, v / v) mixed solvent to precipitate the polymer. The precipitate was centrifuged, washed 3–5 times with the mixed solvent, and dried under vacuum at 54 °C for 36 hours to obtain the linear polymer ITA-L-P1 in 81.5% yield.

[0042] 1H NMR (400 MHz, DMSO-d6) δ 1.82 – 1.87 (s, 1H), 2.46 – 2.52(m, 4H), 2.56 – 2.64 (t, 3H), 2.67 – 2.70 (m, 5H), 2.70 – 2.75 (t, 4H), 4.07 – 4.27(m, 4H). 13C NMR (101 MHz, DMSO) δ 177.59, 171.79, 162.77, 137.99, 55.45, 49.06, 36.25, 34.95, 31.74, 31.23, 27.30, 26.63. Example 6 Synthesis of linear polymer ITA-L-P2 The synthesis method was the same as in Example 5, except that intermediate L-P2 was used instead of L-P1. A dark reddish-brown viscous liquid, ITA-L-P2, was obtained with a yield of 74.26%.

[0043] 1H NMR (400 MHz, DMSO-d6) δ 1.33 – 1.44 (m, 2H), 1.44 – 1.57 (m, 5H), 1.98 – 2.00 (s, 1H), 2.56 – 2.61 (m, 5H), 2.66 – 2.71 (m, 5H), 2.76 – 2.86 (m,4H), 3.53 – 3.63 (t, 1H), 4.09 – 4.20 (m, 4H), 6.68 (s, 1H). 13C NMR (101 MHz, DMSO) δ 171.72, 162.77, 130.15, 55.03, 36.24,34.81, 33.40, 31.40, 31.23, 29.08, 27.29, 26.58. Example 7 Synthesis of linear polymer ITA-L-P3 The synthesis method was the same as in Example 5, except that intermediate L-P3 was used instead of L-P1. A dark reddish-brown viscous liquid, ITA-L-P3, was obtained in 73.52% yield. ¹H NMR (400 MHz, DMSO-d6) δ 2.29 – 2.34 (s, 3H), 2.54 – 2.60 (t, 2H), 2.62 – 2.66 (t, 1H), 2.68 – 2.73 (m, 2H), 2.84 – 2.89 (s, 2H), 4.09 – 4.13 (m, 4H), 6.66 (s, 1H). 13C NMR (101 MHz, DMSO) δ 179.33, 177.67, 171.78, 162.77, 130.15,70.44, 61.45, 55.34, 36.24, 34.97, 31.23, 31.15, 27.11,11.59. Example 8 Synthesis of hyperbranched intermediate B-P1 DMA monomer (0.2 g, 0.881 mmol) was dissolved in 3 mL of DMF for later use. DMF (3 mL), triethylamine (0.187 g, 1.848 mmol), and trimethylolpropane tris(3-mercaptopropionate) (0.38 g, 0.958 mmol) were added to a dry three-necked flask and stirred until homogeneous. Under N2 protection and at room temperature, the DMA solution was slowly added, and the reaction was continuously stirred for 4 hours. After the reaction was complete, the product was precipitated with methanol, centrifuged, and dried under vacuum at 25 °C for 12 hours to obtain intermediate B-P1 with a yield of 89%. GPC analysis showed that the polymer had a number-average molecular weight (Mn) of 16692 and a weight-average molecular weight (Mw) of 19573. The calculated PDI was 1.173, indicating a degree of polymerization of 15.

[0044] 1H NMR (400 MHz, DMSO-d6) δ 0.76 – 0.93 (t, 3H), 1.38 – 1.46 (m, 2H), 2.20 – 2.26 (s, 6H), 2.52 – 2.65 (m, 29H), 2.65 – 2.76 (m, 27H), 2.83 – 2.92 (s, 6H), 3.95 – 4.02 (m, 8H), 4.04 – 4.11 (m, 8H). 13C NMR (101 MHz, DMSO) δ 171.79, 171.53, 171.39, 63.87, 62.44,55.71, 42.85, 40.94, 38.43, 26.60, 26.53, 22.91, 7.67. Example 9 Synthesis of hyperbranched polymer ITA-B-P1 Itaconic anhydride (ITA, 0.3 g, 2.677 mmol) was placed in a dry three-necked flask and purged with N2 for 30 minutes. Intermediate B-P1 (0.03 g, 1.80 μmol) was dissolved in 10 mL of DMF and slowly added dropwise to the flask over 15 minutes using a syringe. The reaction mixture was stirred at room temperature under N2 protection for 12–18 hours. After the reaction was complete, the reaction mixture was added dropwise to a hexane / methyl tert-butyl ether (1:1, v / v) mixed solvent to precipitate the polymer. The precipitate was centrifuged, washed 3–5 times with the mixed solvent, and dried under vacuum at 54 °C for 36 hours to obtain the hyperbranched polymer ITA-B-P1, with a yield of 89.3%.

[0045] 1H NMR (400 MHz, DMSO-d6) δ 0.78 – 0.90 (m, 10H), 1.38 – 1.51 (m, 8H), 2.06 – 2.10 (s, 4H), 2.57 – 2.65 (m, 25H), 2.84 – 3.01 (m, 14H), 3.25 – 3.46(m, 65H), 3.93 – 4.06 (s, 16H), 4.11 – 4.28(m, 9H), 7.07 – 7.10 (s, 1H). 13C NMR (101 MHz, CDCl3) δ 167.52, 164.59, 158.81, 141.83, 135.38,125.13, 60.13, 41.00, 35.98, 31.42. Performance Testing and Results Analysis The monomers, intermediates, and final polymers prepared in the above examples were subjected to a series of spectroscopic characterizations and performance tests, and the results are as follows: Figures 1-8 As shown.

[0046] 1. Investigation of Ultraviolet Absorption As shown in Figure 1, the UV absorption bands of both the monomer DMA and the thiol intermediate are concentrated in the 200-300 nm range, corresponding to the nn transition of the N-related chromophore. The excitation wavelength is 400-420 nm, and the emission wavelength is 383-473 nm, both confined to the visible light region, with no NIR luminescence behavior. After itaconic anhydride nucleophilic ring-opening polymerization, the linear polymer ITA-L-P1 / 2 / 3 extends its absorption band to longer wavelengths, with the excitation wavelength red-shifted to 553-554 nm, and the emission wavelengths being 594 nm, 595 nm, and 603 nm, respectively, entering the 600-620 nm orange-red near-infrared region. The hyperbranched polymer ITA-B-P1 red-shifts its excitation wavelength to 503 nm, and its emission wavelength further red-shifts in the near-infrared region, with a fluorescence intensity much higher than that of the linear polymer. The results show that itaconic anhydride polymerization is the key to polymer NIR luminescence. It expands the electron delocalization range and reduces the band gap by introducing non-covalent ion interactions; the growth of alkyl chains in the linear chain achieves a slight redshift in emission wavelength, and the electron donor effect of oxygen atoms makes the redshift more significant; the dense molecular packing of hyperbranched structures further reduces the band gap and improves luminescence efficiency.

[0047] 2. Investigation of Optical Properties As shown in Figure 2, the fluorescence of the thiol intermediate is concentrated in the visible light region (Ex=400-420 nm, Em=450-500 nm), with no obvious signal in the near-infrared region. The fluorescence hotspot of the linear polymer ITA-L-P1 / 2 / 3 redshifts to the near-infrared region (Ex=550-560 nm, Em=590-610 nm), and the signal intensity gradually increases with the length of the alkyl chain and the introduction of oxygen atoms, with ITA-L-P3 showing the best signal. The fluorescence hotspot of the hyperbranched polymer ITA-B-P1 redshifts to a deeper region in the near-infrared region, and the signal coverage extends to Ex=450-550 nm, Em=500-650 nm, exhibiting the highest fluorescence intensity among all samples. The results indicate that the target polymer polymerized with itaconic anhydride possesses structural specificity for NIR luminescence; oxygen atom modification of the linear chain enhances the stability of the NIR fluorescence signal; and the hyperbranched structure, by strengthening intermolecular interactions, forms more stable luminescent clusters, improving the excitation universality and signal intensity of NIR luminescence.

[0048] As shown in Figure 3, the emission peak of the monomer DMA broadens significantly with changing excitation wavelength, exhibiting strong excitation dependence, and its emission is always limited to the visible light region. The linear polymers ITA-L-P1 / 2 / 3 have stable emission peaks in the near-infrared region of 594-603 nm within the excitation wavelength range of 553-554 nm, with regular peak shapes and significantly reduced excitation dependence. Among them, ITA-L-P3 has the best emission peak stability. The hyperbranched polymer ITA-B-P1 has an excitation wavelength range of 450-550 nm, and its emission peaks are stable in the near-infrared region under different excitation wavelengths, with basically no excitation dependence. The fluorescence intensity is significantly improved with optimization of the excitation wavelength. When the excitation wavelength is 600 nm, its emission wavelength redshifts to 620 nm, and the long-wavelength edge of the fluorescence emission spectrum extends to 800 nm, successfully covering the near-infrared region. This characteristic not only reflects the energy characteristics of excited-state transitions in polymer chromophores but also highlights the modulating effect of hyperbranched topology on fluorescence emission wavelength, laying an experimental foundation for its application in near-infrared fluorescence imaging, optoelectronic devices, and other fields. The results show that the ionic bonds formed during polymerization mediate the luminescent clusters, enhancing excited-state stability and reducing excitation dependence; the introduction of oxygen atoms in the linear chain strengthens the ionic bonds, further optimizing excited-state stability; and the high conformational rigidity of the hyperbranched structure makes the non-radiative decay of the excited-state luminescent clusters negligible, exhibiting optimal excitation wavelength universality.

[0049] 3. pH responsiveness As shown in Figure 4, to evaluate the pH-responsive fluorescence performance of four atypical luminescent polymers, their fluorescence intensity changes within the pH range of 1-13 were tested. The results showed that all four polymers exhibited typical pH-responsive characteristics: fluorescence intensity peaked in the weakly acidic range (pH 2-4), remained at a high level in the neutral range (pH 6-8), and underwent significant quenching in the strongly alkaline range (pH>11). Among them, the hyperbranched polymer ITA-B-P1, due to its structural advantages, exhibited significantly better fluorescence stability and anti-quenching ability than the linear polymers in the neutral and weakly alkaline ranges. This series of polymers showed stable fluorescence within the physiological / pathological pH range (5.0-7.4), making them fully suitable for biological testing scenarios such as bioimaging and tumor-targeted sensing, with ITA-B-P1 showing the best potential for biological applications.

[0050] 4. Concentration dependence and AIE characteristics As shown in Figure 5, the fluorescence intensity of all polymers increased significantly with increasing solution concentration, while the emission wavelength remained stable without any red or blue shift. Under the same concentration gradient, the fluorescence intensity of the hyperbranched polymer ITA-B-P1 increased much more than that of the linear polymer, achieving significant NIR luminescence even at low concentrations. Among the linear polymers, ITA-L-P3 showed the best increase in fluorescence intensity with concentration. The results indicate that concentration changes only affect luminescence efficiency by regulating the polymer aggregation state, without altering the chromophore electron delocalization characteristics. At low concentrations, the polymer chains are dispersed, with free intramolecular movement, and non-radiative decay is dominant, resulting in low luminescence intensity. At high concentrations, the polymer chains cluster to form stable luminescent clusters, activating ionic and hydrogen bonds, restricting intramolecular movement, increasing radiative decay, and enhancing luminescence. Hyperbranched structures can cluster even at low concentrations, exhibiting a more sensitive concentration response. The introduction of oxygen atoms in the linear chains promotes intermolecular polar interactions, accelerating the clustering process and resulting in superior concentration response characteristics for ITA-L-P3.

[0051] As shown in Figure 6, to investigate the aggregation-induced emission (AIE) characteristics of four atypical near-infrared luminescent polymers, DMSO was used as a good solvent and MTBE as a poor solvent, and the fluorescence emission intensity at different MTBE volume fractions was tested. The results showed that all four polymers exhibited typical AIE behavior: as shown in Figure 1a, the fluorescence intensity of the linear polymer ITA-L-P1 first increased and then decreased with increasing MTBE content; excessively high proportions of poor solvent led to fluorescence quenching due to excessive aggregation; and so on. Figure 1As shown in Figures b and 1c, the fluorescence intensity of ITA-L-P2 and ITA-L-P3 steadily increases with increasing MTBE content, with ITA-L-P3 exhibiting superior clustering stability. As shown in Figure 1d, the hyperbranched polymer ITA-B-P1 exhibits the most prominent AIE effect, with fluorescence intensity continuously increasing with the proportion of undesirable solvents, and showing no significant quenching even at high MTBE contents, demonstrating significantly better aggregation stability than linear polymers. In summary, the luminescence of this series of polymers exhibits a clear aggregation dependence, and the hyperbranched structure can effectively improve AIE performance and aggregation stability, providing a theoretical basis for their application in the field of bioimaging.

[0052] 5. Ion responsiveness To systematically evaluate the ion recognition characteristics and anti-interference capabilities of four atypical near-infrared luminescent polymers with itaconic anhydride groups, the changes in relative fluorescence intensity (I / I0) in the presence of different common ions and small molecules were tested. The results are as follows: Figure 7 As shown, the fluorescence responses of the four polymers exhibit a consistent regularity: Fe² + Fe³ + All systems exhibited significant fluorescence quenching effects, with Fe³⁺ showing the most significant effect. + The quenching degree is generally stronger, indicating that the material has a specific recognition ability for iron ions; PO₃ - Phosphate and lactate significantly enhanced fluorescence intensity, indicating that these anions can further activate cluster luminescence by strengthening intermolecular interactions and increasing cluster rigidity. Other common cations, anions, and small molecules had no significant effect on the fluorescence of the system, with an I / I0 ratio essentially consistent with the blank group, demonstrating excellent anti-interference performance. Furthermore, the hyperbranched polymer ITA-B-P1 exhibited a more pronounced quenching response to iron ions and a stronger enhancement effect on phosphate and lactate ions, demonstrating superior overall anti-interference performance compared to linear polymers, thus verifying the optimizing effect of the branched structure on ion response performance. In summary, this series of atypical near-infrared luminescent polymers exhibits a specific fluorescence quenching response to iron ions, a fluorescence enhancement response to phosphate and lactate ions, and excellent anti-interference ability against other common ions, showing promising application potential in fields such as iron ion detection and biomolecule sensing.

[0053] 6. Bioimaging Applications To evaluate the in vivo tumor penetration potential of ITA-B-P1, MKN-45 cells were used as a model to simulate the complex microenvironment of solid tumors. Figure 8As shown, the penetration of ITA-B-P1 within the MCTS exhibits a significant time-dependent effect: at 3 h, the fluorescence signal is mainly concentrated on the outer layer of the sphere, indicating that the material has initially adsorbed onto the tumor surface and begun to penetrate; after 12 h, the fluorescence signal gradually diffuses into the interior region of the sphere over time, with a significant increase in internal brightness; from 24 h to 36 h, the fluorescence almost completely covers the entire MCTS cross-section, and the central region also shows a uniform fluorescence distribution. This dynamic process fully demonstrates that ITA-B-P1 possesses excellent tumor penetration capabilities, efficiently overcoming the physical barrier of the MCTS and achieving uniform penetration from the outside in. Compared to the challenge of limited penetration depth of traditional quantum dot materials in in vitro spherical models, ITA-B-P1, relying on its excellent physicochemical properties, can serve as a highly efficient fluorescent probe for deep and precise imaging within MKN-45 tumor spheres, providing solid experimental evidence for its application in tumor diagnosis and treatment and bioimaging.

[0054] In summary, this invention uses itaconic anhydride as a building block and nucleophilic ring-opening reaction as the core strategy to design and synthesize linear atypical near-infrared luminescent polymers (ITA-L-P1 / 2 / 3) and hyperbranched polymers (ITA-B-P1). A series of spectroscopic methods were used to characterize their photophysical properties and environmental response behavior, exploring the regulatory mechanism of structure on near-infrared luminescence performance. Spectroscopic characterization confirmed the successful preparation of the target polymers. Compared to the monomer DMA, which only emits light in the visible region, the linear polymers achieved near-infrared luminescence at 594-603 nm, while the hyperbranched polymers exhibited a more significant redshift in emission wavelength and higher fluorescence intensity. With alkyl chain growth and the introduction of oxygen atoms, the emission wavelength showed a significant redshift, and the optimization effect of oxygen atom introduction on the luminescence performance of the linear polymers was superior to that of alkyl chain growth. The excitation dependence of this series of polymers was significantly reduced, fluorescence was stable within the pH range of 3-10, and fluorescence intensity significantly increased with increasing concentration. The hyperbranched polymers showed better environmental adaptability and concentration response, confirming that they possess typical cluster-induced emission characteristics. Structure-property relationship studies have shown that the nucleophilic ring-opening polymerization of itaconic anhydride is key to the near-infrared luminescence of polymers. Increased branching can strengthen ionic bonding and improve the conformational rigidity of luminescent clusters, effectively optimizing near-infrared luminescence performance. This work clarifies the structural regulation rules of non-conjugated near-infrared luminescent polymers, laying an important foundation for their application in structural design, performance optimization, and bioimaging.

Claims

1. An atypical near-infrared luminescent polymer constructed based on itaconic anhydride, characterized in that, The polymer is prepared by nucleophilic ring-opening polymerization of a thiol-containing intermediate and itaconic anhydride. It has a fluorescence emission wavelength in the near-infrared region and exhibits aggregation-induced emission properties.

2. The atypical near-infrared luminescent polymer according to claim 1, characterized in that, The thiol-containing intermediate is obtained by reacting the N-methyldiethanolamine derivative monomer shown in formula (I) with a compound containing a dithiol group; The compound containing a dithiol group is selected from at least one of 1,2-ethanedithiol, 1,5-pentanedithiol, and bis(2-mercaptoethyl) ether.

3. The atypical near-infrared luminescent polymer according to claim 2, characterized in that, The thiol-containing intermediate has a linear structure, and the atypical near-infrared luminescent polymer is a linear polymer with a fluorescence emission wavelength between 594 nm and 603 nm.

4. The atypical near-infrared luminescent polymer according to claim 2, characterized in that, The compound containing a dithiol group is a bis(2-mercaptoethyl) ether.

5. The atypical near-infrared luminescent polymer according to claim 1, characterized in that, The thiol-containing intermediate is obtained by reacting the N-methyldiethanolamine derivative monomer shown in formula (I) with a compound containing multiple thiol groups, wherein the compound containing multiple thiol groups is trimethylolpropane tris(3-mercaptopropionate); the atypical near-infrared luminescent polymer is a hyperbranched polymer.

6. The atypical near-infrared luminescent polymer according to claim 5, characterized in that, The fluorescence emission wavelength of the hyperbranched polymer is red-shifted to 620 nm, and the long-wavelength edge of its emission spectrum extends to 800 nm.

7. A method for preparing an atypical near-infrared luminescent polymer according to any one of claims 1-6, characterized in that, Includes the following steps: (1) Synthesis of thiol-containing intermediate: The N-methyldiethanolamine derivative monomer and the thiol-containing compound were reacted in the presence of triethylamine in N,N-dimethylformamide solvent at room temperature. After precipitation, washing and drying, the thiol-containing intermediate was obtained. (2) Nucleophilic ring-opening polymerization: The thiol-containing intermediate obtained in step (1) is dissolved in N,N-dimethylformamide and added dropwise to an N,N-dimethylformamide solution containing itaconic anhydride under inert gas protection. The reaction is stirred at 20-30°C for 12-18 hours. After the reaction is completed, the polymer is precipitated, washed and dried to obtain the atypical near-infrared luminescent polymer.

8. The preparation method according to claim 7, characterized in that, In step (1), the molar ratio of the monomer DMA to the mercapto-containing compound is 1:0.8-1.2; the molar ratio of the mercapto group to triethylamine in the mercapto-containing compound is 1:3-1:5; in step (2), the molar ratio of the mercapto-containing intermediate to itaconic anhydride is 1:1-1:

3.

9. The application of the atypical near-infrared luminescent polymer according to any one of claims 1-6 in the detection of iron ions or phosphate / lactate ions, characterized in that, The polymer exhibits a specific fluorescence quenching response to Fe²⁺ and Fe³⁺ ions, and a specific fluorescence enhancement response to PO³⁻ and Lac⁻ ions.

10. The use of any one of the atypical near-infrared luminescent polymers according to claims 1-6 in the preparation of bioimaging reagents or fluorescent sensing materials.

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