CN104761578B - Based on rhodium tetraphenylporphyrin azepine fluorine boron two pyrroles's near infrared absorption phosphor material and its preparation method and purposes - Google Patents

Abstract

A class of near-infrared compounds based on rhodium-porphyrin-azafluoroborodipyrrole, which have the following structures: Compared with the prior art, the present invention has the remarkable advantage that rhodium porphyrin-azafluoroboron dipyrrole {Rh(ttp)-aza-BODIPY} compound is synthesized for the first time through the axial connection of Rh-C bonds. These compounds combine the optical properties of the transition metal rhodium and aza‑BODIPY. ^On the one hand, due to the unique d electron configuration of the central metal Rh ^Ш , this compound has a very efficient intersystem crossing coefficient, resulting in long-lived phosphorescent emission and singlet oxygen. On the other hand, aza‑BODIPY has a very strong absorption in the near-infrared region, which can successfully redshift the absorption wavelength of the compound to the near-infrared region, which is more conducive to a wide range of applications. The invention discloses its preparation method.

Description

Near-infrared absorbing phosphorescent materials based on rhodium tetraphenylporphyrin-azafluoroboron dipyrrole and Its preparation and use

technical field

The invention relates to a near-infrared absorbing phosphorescent material, in particular to a rhodium tetraphenylporphyrin-azafluoroboron dipyrrole {Rh(ttp)-aza-BODIPY} near-infrared absorbing phosphorescent material and its preparation method and application.

Background technique

Near-infrared absorbing fluorescent dyes have become a research hotspot in recent years due to their unique properties, and have been widely used in various fields. In the near-infrared region, biological tissue absorption and scattering are minimal, [cf.: (a) Aubin, J.E. Autofluorescence of viable cultured mammalian cells. J. Histochem. Cytochem., 1979, 27, 36–43.12. (b) Weisleder, R.A clearer vision for in vivo imaging. Nat. biothchnol., 2001, 19, 316-317.] Therefore, it can greatly improve the tissue penetration ability of photons and avoid the influence of autofluorescence interference, reducing the light damage to organisms. [See: (a) Wu, X.M., etal. In vivo and in situ tracking cancer chemotherapy by highly photostable NIRfluorescent theranostic prodrug. J. Am. Chem. Soc., 2014, 136, 3579-3588. (b) Wu, X.M. ; Chang S.; Sun X.R., et al. Constructing NIR silica-cyanine hybrid nanocomposite for bioimaging in vivo: a breakthrough in photo-stability and bright fluorescence with large Stokes shift. Chem. Sci., 2013, 4, 1221–1228.] Phosphorescence Compounds are considered to be a class of materials with great potential, and have been widely used in fields such as OLEDs and solar cells. [See: (a) Li, L.L.; Diau, E.W-G. Porphyrin-sensitized solar cells. Chem. Soc. Rev., 2013, 42, 291-304.] Compared with traditional fluorescent materials, phosphorescent compounds have long luminescence lifetime and Advantages of large Stokes shifts. Another important advantage is that phosphorescent materials show unique advantages in OLED applications. For example, fluorescent materials can only form singlet excitons through singlet-singleton energy transfer, while phosphorescent materials can not only form singlet excitons through singlet - Singlet energy transfer, and at the same time, excitons can be formed through triplet-triplet energy transfer, so the theoretical maximum internal quantum yield of phosphorescent materials can reach 100%, which can overcome the limitation of 25% internal quantum yield of fluorescent materials . [See: (a) Tao, Y.T.; Yang, C.H.; Qin, J.G. Organic host materials for phosphorescent organic light-emitting diodes. Chem. Soc. Rev., 2011, 40, 2943-2970. (b) Baldo, M.A.; O'Brien, B.F.; You, Y., et al.Highly efficient phosphorescent emission from organicelectroluminescent devices.Nature,1998,395,151-154.] Therefore, based on the advantages of near-infrared absorption and phosphorescent emission, near-infrared absorbing phosphorescent materials will be used in the future It has broad application prospects in military, energy, biology and environment.

Transition metal complexes are a class of phosphorescent materials with excellent properties. Their notable advantage is long luminescence lifetime. Such materials have weak or no absorption in the near-infrared region, which severely limits the application of such compounds. At present, the most commonly used near-infrared dyes are organic fluorescent small molecules. Generally, the purpose of red-shifting the absorption wavelength is achieved by organic compound structure modification. However, its luminescence lifetime is generally very short, and its lifetime can be extended by introducing heavy atoms. The stability will gradually decrease with the red shift of the absorption wavelength. For example, the stability of Cy5 and Cy7 in the current commercial near-infrared dyes is poor, which greatly limits their wide application. [See: (a) Benson, RC; Kues, HAAbsorption and fluorescence properties of cyanine dyes. Chem. Eng. Data, 1977, 22, 379-383. (b) Zhang XF; Xiao, Y.; Qi, J., et al .Long-wavelength, photostable, two-photon excitable BODIPY fluororephores readily modifiable formolecular probes. J. Org. Chem., 2013, 78, 9153-9160.] As a class of natural photosensitizer, porphyrin widely exists in nature, and plays an important role. It is a kind of ligand with extremely strong coordination ability. Most of the elements in the periodic table, including metals and nonmetals, can coordinate with porphyrin to form compounds with various properties, but its significant disadvantage is that it is nearly Infrared absorption is relatively weak. One of the methods to redshift the porphyrin absorption wavelength to the near-infrared region is by fusing aromatic rings on the porphyrin ring. Using this method, Pd and Pt porphyrin NIR-absorbing phosphorescent compounds have been designed and synthesized, but this This method can only obtain one class of compounds. [See: (a) Niedermair, F.; Borisov, SM; Zenkl, G., et al. Tunable phosphorescent NIR oxygen indicators based on mixed benzo-and naphthoporphyrin complexes. Inorg. Chem., 2010, 49, 9333-9342. (b) Sommer, JR; Shelton, AH; Parthasarathy, A., et al. Photophysical properties of near-infrared phosphorescentπ-extended platinum porphyrins. Chem. Mater., 2011, 23, 5296-5304. ; Cheprakov, AV; Sakadzìc, S., et al.Densritic phosphorescentprobes for oxygen imaging in biological systems.ACS Appl.Mater.Interfaces, 2009,1,1292-1304.] A class of typical near-infrared dyes is a new type of fluorescent compound developed in the past ten years, and is more and more favored by scientists. Such compounds have strong molar absorptivity in the near-infrared region, but their luminescence lifetime is short. [See: (a) Loudet, A.; Burgess, K. BODIPYdyes and their derivatives: syntheses and spectroscopic properties. Chem. Rev. 2007, 107, 4891–4932. (b) Kiloran, J., Allen, L., Gallagher , JF, Gallagher, WM; O'Shea, DFSynthesis of BF ₂ chelates oftetraarylazadipyrromethenes and evidence for their photodynamic therapeutic behavior.Chem.Commun.,2002,17,1862-1863.(c)Pierre,AB,et al.Two-photoabsorption -related properties of functionalized BODIPY dyes in the infrared range up to telecommunications wavelengths.Adv.Mater.2009,21,1151-1154.] In addition, aza-BODIPY also has relatively negative reduction potential energy, such as its S ₁ excited state The energy is lower than ordinary BODIPY, which makes it an ideal intramolecular energy acceptor. [See: (a) Guo, S.; Ma, LH; Zhao, J., et al. BODIPY triads triplet photosensitizers enhanced with intramolecular resonance energy transfer (RET): broadband visible light absorption and application in photooxidation. Chem. Sci., 2014, 5, 489–500. (b) Bandi, V.; El-Khouly, ME; Nesterov, VN, et al. Self-assembled via metal-ligand coordination azaBODIPY-zinc phthalocyanine and azabodipy-zinc naphthalocyanine conjugates: synthesis, structure, and photoinduced electron transfer.J.Phys.Chem.C,2013,117,5638-5649.] Therefore, aza-BODIPY is an ideal fluorescent molecule that enhances the absorption of rhodium porphyrin in the near-infrared region.

Contents of the invention

In the present invention, we cleverly linked rhodium porphyrin and aza-BODIPY directly via metal-carbon bonds for the first time. In this connection mode, transition metal d orbitals and aza-BODIPY directly participate in the bonding of frontier molecular orbitals, and due to the participation of heavy metal d orbitals, the intersystem crossing coefficient is significantly increased, thereby effectively improving the luminescence lifetime. At the same time, aza-BODIPY can also successfully redshift the absorption of transition metal complexes to the near-infrared region. Using this method, we have designed and synthesized a series of rhodium tetraphenylporphyrin-azafluoroboron dipyrrole {Rh(ttp)-aza-BODIPY} near-infrared absorbing phosphorescent materials. This is a very simple and flexible method, and a series of near-infrared absorbing phosphorescent materials can be obtained by changing transition metal complexes or changing their connection with near-infrared dyes, which provides us with a novel and convenient synthesis method.

The content of the present invention is to design and provide a kind of rhodium porphyrin-azafluoroboron dipyrrole {Rh(ttp)-aza-BODIPY} near-infrared absorbing phosphorescent material and its preparation method and property research.

The technical scheme that the present invention relates to is as follows:

A class of near-infrared compounds based on rhodium porphyrin-azafluoroboron dipyrrole, which have the following structures:

The preparation method of above-mentioned compound is as follows:

A method for preparing the above-mentioned near-infrared compound based on rhodium porphyrin-azafluoroboron dipyrrole, it comprises the following steps:

Add rhodium tetraphenylporphyrin chloride (Rh(ttp)Cl) (1eq), halogenated azafluoroboron dipyrrole (halogenated aza-BODIPY) (1.1eq), K ₂ CO ₃ (20eq ) and benzene solvent, the reaction mixture was refrigerated and _{degassed three} times, and reacted at 150°C under the protection of nitrogen. Near-infrared absorbing phosphorescent compound of porphyrin-azafluoroboron dipyrrole.

The structure of the photosensitizer was characterized and confirmed by 1H-NMR, UV-Vis, Fluorescence spectral, MALDI-TOF MASS.

Beneficial effects of the present invention

Compared with the prior art, the present invention has the remarkable advantage that the rhodium porphyrin-azafluoroboron dipyrrole {Rh(ttp)-aza-BODIPY} compound is synthesized for the first time through the Rh-C bond axial connection mode. These compounds have both the optical properties of transition metal rhodium and aza-BODIPY. ^On the one hand, due to the unique d electron configuration of the central metal Rh ^Ш , this compound has a very efficient intersystem crossing coefficient, resulting in long-lived phosphorescent emission and singlet oxygen. On the other hand, aza-BODIPY has a very strong absorption in the near-infrared region, which can successfully redshift the compound to the near-infrared region, which is more conducive to a wide range of applications. These research results provide us with a more convenient and flexible method for synthesizing near-infrared absorbing phosphorescent materials. Due to the advantages of near-infrared absorption, long-life phosphorescence, and the ability to generate singlet oxygen that kills cancer cells at the same time, this type of compound has phosphorescence imaging and photodynamic therapy properties, so it can be used for real-time diagnosis and treatment of cancer. Second, due to the heavy atom effect, an effective intersystem crossing coefficient is produced, which can be used as a triplet photosensitizer for photocatalytic reactions. 3. It can be used in photoelectric materials. Compared with traditional fluorescent materials, phosphorescent compounds have a long phosphorescence decay lifetime. Another important feature is that they can capture singlet and triplet excitons at the same time, reaching 100% utilization efficiency of the theoretical value of internal quantum efficiency, which can be used in OLEDs.

Description of drawings

Fig. 1 is the ultraviolet absorption spectrum of photosensitizer A among the present invention;

Fig. 2 is the ultraviolet absorption spectrum of photosensitizer B among the present invention;

Fig. 3 is the ultraviolet absorption spectrum of photosensitizer C among the present invention;

Fig. 4 is the emission spectrum of photosensitizer A in the present invention;

Fig. 5 is the emission spectrum of photosensitizer B among the present invention;

Fig. 6 is the emission spectrum of photosensitizer C in the present invention;

Fig. 7 is photosensitizer A in the present invention, B and C stability;

Fig. 8 is photosensitizer A in the present invention, B and methylene blue singlet oxygen production efficiency contrast;

Fig. 9 is photosensitizer C and methylene blue singlet oxygen production efficiency contrast among the present invention;

Fig. 10 is the MTT assay test result of photosensitizer C in the present invention.

detailed description

The instruments used for detection are: Bruker ARX500 nuclear magnetic resonance instrument (TMS is internal standard, deuterated C ₆ D ₆ is solvent), Shimadzu UV-4500 ultraviolet-visible spectrophotometer (scanning range 300-900nm, slit width 2.0nm ), Hitachi F-4600 US BrukerDaltonicsautoflexII mass spectrometry workstation.

The synthesis of embodiment 1. compound A:

Add rhodium tetraphenylporphyrin chloride Rh(ttp)Cl (15.8mg, 0.019mmol), bromoazafluoroboron dipyrrole aza-BODIPY-a (13.7mg, 0.021mmol), K ₂ CO ₃ (53.9mg, 0.39mmol) and 1.0mL of benzene, the reaction mixture was refrigerated and degassed three times, and reacted at 150°C for 28 hours under the protection of nitrogen. After the reaction was completed, the solvent was spin-dried under reduced pressure, and then separated by silica gel column chromatography using CH ₂ Cl ₂ /hexane (1:1) developing solvent to obtain 17.1 mg of compound A. Yield: 61%. R _f =0.61 (CH ₂ Cl ₂ /hexane=1:1). ¹ H NMR (400MHz, CDCl ₃ ): δ0.44(d, J=8.5Hz, 2H), 2.69(s, 12H), 5.45(d, J=8.4Hz ,2H),5.98(s,1H),6.75(s,1H),7.30-7.36(m,6H),7.45(d,J=8.0Hz,2H),7.51-7.52(m,9H),7.56- 7.63(m,3H),7.80(d,J=3.3Hz,2H),8.04(d,J=7.7Hz,4H),8.09(d,J=7.8Hz,4H),8.87(s,8H). ; HRMS (FABMS): Calcd for [C ₈₀ H ₅₆ BBrF ₂ RhN ₇ ] ⁺ ([M] ⁺ ): m/z 1347.2903. Found: m/z.1347.2906. Its ultraviolet absorption spectrum is shown in Figure 1, its emission spectrum is shown in Figure 4, its stability is shown in Figure 7, and its comparison with methylene blue singlet oxygen generation efficiency is shown in Figure 8.

Embodiment 2. Synthesis of compound B:

Add rhodium tetraphenylporphyrin chloride Rh(ttp)Cl (15.8mg, 0.019mmol), bromoazafluoroboron dipyrrole aza-BODIPY-b (13.7mg, 0.021mmol), K ₂ CO ₃ (53.9mg, 0.39mmol) and 1.0mL of benzene, the reaction mixture was refrigerated and degassed three times, and reacted at 150°C for 30 hours under the protection of nitrogen. After the reaction was completed, the solvent was spin-dried under reduced pressure, and then separated by silica gel column chromatography using CH ₂ Cl ₂ /hexane (1:1) developing solvent to obtain 11.4 mg of compound B. Yield: 66%. R _f =0.57 (CH ₂ Cl ₂ /hexane=1:1). ¹ H NMR (400MHz, CDCl ₃ ): δ0.52(d, J=8.6Hz, 2H), 2.71(s, 12H), 5.57(d, J=9.0Hz ,2H),6.22(s,1H),6.71(s,1H),7.25-7.30(m,3H),7.48(d,J=7.8Hz,2H),7.51-7.58(m,9H),7.60- 7.67(m, 6H), 7.82(d, J=7.2Hz, 2H), 8.06(d, J=7.6Hz, 8H), 8.83(s, 8H).HRMS(FABMS): Calcd for [C ₈₀ H ₅₆ BBrF ₂ RhN ₇ ] ⁺ ([M] ⁺ ):m/z1347.2903.Found:m/z.1347.2908.

Its ultraviolet absorption spectrum is shown in Figure 2, its emission spectrum is shown in Figure 5, its stability is shown in Figure 7, and its comparison with methylene blue singlet oxygen generation efficiency is shown in Figure 8.

Embodiment 3. Synthesis of compound C:

Add rhodium tetraphenylporphyrin chloride Rh(ttp)Cl (15.8mg, 0.019mmol), bromoazafluoroboron dipyrrole aza-BODIPY-c (13.7mg, 0.021mmol), K ₂ CO ₃ (53.9mg, 0.39mmol) and 1.0mL of benzene, the reaction mixture was refrigerated and degassed three times, and reacted at 150°C for 32 hours under the protection of nitrogen. After the reaction was completed, the solvent was spin-dried under reduced pressure, and then separated by silica gel column chromatography using CH ₂ Cl ₂ /hexane (1:1) developing solvent to obtain 6.74 mg of compound B. Yield: 39%. ¹ HNMR (400 MHz, CDCl ₃ ): δ0.40(d, J＝8.4Hz, 1H), 0.44(s, 1H), 2.67(s, 12H), 5.00(t, J ₁ ＝4.0Hz, J ₂ ＝7.8Hz, 1H), 5.51 (s, 1H), 6.33 (d, J = 7.4Hz, 1H), 6.69 (s, 1H), 6.88 (t, J ₁ = 7.8Hz, J ₂ = 7.8Hz, 1H), 7.17 (d, J ＝7.8Hz,1H),7.37-7.39(m,8H),7.47-7.50(m,2H),7.53-7.55(m,5H),7.71(s,1H),7.81-7.82(m,4H), 7.84 (d, J = 8.0Hz, 4H), 7.99 (d, J = 7.4Hz, 4H), 8.08 (s, 8H). HRMS (FABMS): Calcd for [C ₈₀ H ₅₆ BBrF ₂ RhN ₇ ] ⁺ ( [M] ⁺ ):m/z1347.2903.Found:m/z.1347.2906.

Its ultraviolet absorption spectrum is shown in Figure 3, its emission spectrum is shown in Figure 6, its stability is shown in Figure 7, and its comparison with methylene blue singlet oxygen generation efficiency is shown in Figure 9.

Example 4. Application

We used ultraviolet spectroscopy to test the stability of the target compound and the efficiency of singlet oxygen with methylene blue as a reference and a monochromatic laser with a wavelength of 671nm as a light source. The experimental results show that the synthesized target compound has good stability and high singlet oxygen generation efficiency, and can be successfully applied to photodynamic therapy. We carried out the MTT assay test of photosensitizer C in HeLa cells under the condition of light and without light to detect its cytotoxicity. The experimental results show that under the condition of no light source, with the increase of the photosensitizer concentration, the activity of the cells basically does not change and maintains at about 100%. The results show that the cells do not die in the dark in the presence of the photosensitizer. In contrast, under the irradiation of a 671 nm laser light source, the cell viability decreased sharply with the increase of the photosensitizer concentration, indicating that photosensitizer C has strong phototoxicity. Therefore, the target compound has no dark toxicity, has strong phototoxicity, and can be successfully used to prepare a drug for photodynamically treating cancer cells. Its MTTassay test results are shown in Figure 10.

Claims (3)

1. a class of near-infrared compounds based on rhodium porphyrin-azafluoro boron dipyrrole, characterized in that they have the following structure: 2. a kind of method preparing the near-infrared compound based on rhodium porphyrin-azafluoro boron dipyrrole described in claim 1 is characterized in that it comprises the following steps: Add rhodium tetraphenylporphyrin chloride, halogenated aza-fluoro boron dipyrrole (halogenated aza-BODIPY), K ₂ CO ₃ and benzene solvent in the reactor, the ratio of the amount of their substances is: rhodium tetraphenyl Porphyrin chloride: haloazafluoroborate dipyrrole: K ₂ CO ₃ =1:1.1:20, the reaction mixture was refrigerated and degassed three times, and reacted at 150°C under nitrogen protection. After the reaction was completed, the solvent was spin-dried under reduced pressure , using a developing solvent of CH ₂ Cl ₂ /hexane with a volume ratio of 1:1 for silica gel column chromatography to obtain a rhodium porphyrin-azafluoroboron dipyrrole compound. 3. the application of the near-infrared compound based on rhodium porphyrin-azafluoroboripyrrole described in claim 1 in the preparation of the medicine for photodynamic therapy of cancer cells.