Multicomponent Porphyrin-Based Tetragonal Prismatic Metallacages and their Photophysical Properties

Abstract

Multicomponent coordination-driven self-assembly has proved to be a convenient approach to prepare advanced supramolecular coordination complexes (SCCs), especially for those with three-dimensional structures. Herein, we report the preparation of three tetragonal prismatic cages via the self-assembly of Pt(PEt₃)₂(OTf)₂, three different linear dipyridyl ligands and porphyrin-based sodium benzoate ligands. Due to the efficient charge separation in the coordination process of Pt(PEt₃)₂(OTf)₂ with pyridine and carboxylic acid and the directionality of metal-coordination bonds, these cages were prepared in high isolated yields (more than 90%). The absorption and emission properties as well as the singlet oxygen quantum yields of these cages were also studied, showing their potential applications as contrast agents for bio-imaging and photosensitizers for photodynamic therapy.

1. Introduction

Three-dimensional cage molecules have received much attention during the last two decades not only due to their appealing structures but also because they can provide cavities for molecular encapsulation, sensing and catalysis.^[1] Additional functionalities such as luminescence,^[2] electrochemical^[3] and liquid crystalline^[4] properties can also be incorporated into these cages through the introduction of ligands with the desired properties. Covalent cage molecules normally call for tedious and time-consuming synthesis and purification, while the preparation of cages via non-covalent self-assembly offers an alternative approach to reduce the synthetic steps and provides diverse supramolecular coordination complexes (SCCs) with interesting functionalities.^[5] Particularly in this filed, metal-coordination-driven self-assembly^[6] plays an important role to prepare cage molecules because its high directionality gives an efficient pathway to control the orientation and geometry for the structures, making it easy to predict the formation of the final constructs. For example, Fujita’s group has prepared a series of M_nL_2n polyhedral via the self-assembly of tetra-coordinated palladium salts and bent dipyridyl units.^[7] Nitschke and coworkers reported the formation of tetrahedral cages via multicomponent self-assembly of metal ions (Fe(II), Zn(II), etc), 2-formylpyridine derivatives and diamine or triamine moieties.^[8] Stang et. al. showed that emissive tetragonal prismatic cages could be prepared efficiently via the self-assembly of tetraphenylethene derivatives, Pt(PEt₃)₂(OTf)₂ and dipyridyl or dicarboxylic acid units.^[9]

Porphyrins and their derivatives are an important class of molecules, which have been widely used in natural systems such as photosynthesis^[10] and hemoglobin,^[11] as well as in artificial systems such as photodynamic therapy,^[12] molecular electronics^[13] and biomimetic catalysis.^[14] They can also serve as building blocks for advanced SCCs^[15] based on their highly symmetric structures and coordinated properties towards metal ions. In 2014, Stang and coworkers reported the preparation of tetragonal prismatic cages based on tetrapyridyl porphyrin as the faces,^[16] indicating that the solubilities of these cages were increased compared with free porphyrins. Herein, we further explore the multicomponent self-assembly and prepare three tetragonal prismatic metallacages based on sodium benzoatedecorated porphyrin units. The absorption and emission of these cages in six common organic solvents were studied in detail. All the cages feature a strong absorption band centered at ca. 420 nm, corresponding to their Soret bands. Four Q bands were also observed ranging from 500 to 700 nm. Different from the tetrapyridyl porphyrin-based cages, these cages show two strong emission bands with similar intensities centered at ca. 650 nm and 720 nm, indicating that they can emit in the NIR region, which are of vital importance for bioimaging applications. More importantly, these cages exhibit good singlet oxygen quantum yields (Φ_Δ), showing their potential use as photosensitizers for photodynamic therapy towards cancer treatment.

2. Results and Discussion

2.1. Cage Preparation and Characterization

The cages were prepared in high isolated yields using a procedure reported in literature with minor modifications.^[9b] Sodium benzoate-decorated porphyrin 1, Pt(PEt₃)₂(OTf)₂ 2 and dipyridyl ligands 3 were mixed in 1:4:2 molar ratio and heated in acetone/water (v/v, 4:1) at 50°C for 12 h. After cooling, the solvent was removed and the residue was redissolved in acetone. The mixture was filtered to remove the formed byproducts and then ether or ethyl acetate (5 equiv. compared to acetone) was added to the clear acetone solution to give precipitates, which were further collected by centrifugation. The precipitation process was repeated for three times to afford cages 4a–4c (Scheme 1) in reasonably good yields and purities. It is worth mentioning that due to the use of sodium benzoate-decorated porphyrin which can be dissolved well in water, the solubility of the reactance is increased compared with using tetrapyridyl porphyrin as the faces, which will benefit the coordination process to give high yields for the cages.

Scheme 1.

Cartoon representations of the self-assembly of metallacages 4a, 4b and 4c.

The structure of cages 4a–4c was first examined by multinuclear NMR (³¹P{¹H} NMR and ¹H NMR), electrospray ionization time-of-flight mass (ESI-TOF-MS). It can be seen from the ³¹P{¹H} NMR spectra (Figure 1) that all the cages exhibit upfield chemical shift changes compared with Pt(PEt₃)₂(OTf)₂ 2 and split into two doublets of equal intensity with concomitant ¹⁹⁵Pt satellites because of the different coordination environments of Pt(II) with pyridyl and carboxylic units. Peaks were found at 5.90 and 0.13 ppm for 4a, 5.25 and 0.30 ppm for 4b, 5.68 and 0.40 ppm for 4c, respectively. Proton NMR spectra gave more insights into the coordination interactions and revealed the purities of these metallacages. The pyridyl (α-pyridyl and β-pyridyl) protons shifted downfield, which is a characteristic feature for the formation of Pt(II)-pyridine coordination bonds.^[9a,b] For metallacage 4a, α-pyridyl protons H₁ shifted from 8.75 ppm to 9.32 ppm and β-pyridyl protons H₂ shifted from 7.78 ppm to 8.46 ppm (Figure 1, spectra a and b). Similar trends were also observed for metallacages 4b and 4c. Protons H₃, H₄ and H₅ of metallacage 4b shifted from 8.61 ppm, 7.60 ppm and 7.54 ppm to 9.07 ppm, 8.08 ppm and 7.96 ppm, respectively (Figure 1, spectra c and d). Protons H₆ and H₇ of metallacage 4c shifted from 8.69 ppm and 7.55 ppm to 9.24 ppm and 8.06 ppm, respectively (Figure 2, spectra e and f). Benzyl protons H_a and H_b shifted upfield and pyrrolyl protons H_c split into two set of peaks, as compared to tetracarboxyphenylporphyrin. The methylene and methyl protons split into two set of signals. Overall, all the chemical shifts changes agree well with previous reported results,^[9b] indicating the formation of discrete, highly symmetric tetragonal prismatic metallacages.

Figure 1.

Partial ³¹P{¹H} NMR spectra (121.4 MHz, CD₃COCD₃, 295 K) of2 (a), 4a (b), 4b (c) and 4c (d).

Figure 2.

Partial ¹H NMR spectra (400 MHz, CD₃COCD₃, 295 K) of 3a (a), 4a (b), 3b (c), 4b (d), 3c (e) and 4c (f). The residual ether or ethyl acetate peaks are marked with asterisks.

ESI-TOF-MS characterization is a widely used method to determine the stoichiometry of the metallacages. In the ESI-TOF-MS spectra of metallacages 4a–4c (Figure 3), three intense peaks with charge states from 3+ to 5+ were assigned, which confirms the formation of tetragonal prismatic metallacages. Isotopically well resolved peaks at m/Z=2130.3379, 1587.6704 and 1585.6301 were found for 4a, 4b and 4c, corresponding to [4a – 3OTf]³⁺, [4b – 4OTf]⁴⁺ and [4c – 4OTf]⁴⁺, respectively. These peaks are in good agreement with their calculated theoretical distributions, which supports the composition of metallacages 4a–4c.

Figure 3.

ESI-TOF-MS spectra of metallacages 4a (a), 4b (b) and 4c(c).

2.2. Photophysical Studies

The absorption and emission spectra of metallacages 4a–4c were collected in six commonly used solvents, including DMSO, DMF, acetonitrile, acetone, methanol and dichloromethane due to their good solubility in these solvents. The absorption spectra of these cages are similar in different solvents, showing a strong Soret peak centered at ca. 420 nm and four Q bands centered at ca. 650 nm (Q1), 590 nm (Q2), 550 nm (Q3) and 515 nm (Q4), respectively (Figure 4, spectra a, c and e), which are similar with the absorption for porphyrin derivatives.^[16] The Soret absorption is attributed to the S₀ to S₂ transition while the Q bands are the transitions from S₀ to S₁ state.

Figure 4.

The UV/Vis absorption (a, c, e) and emission (b, d, f) spectra of metallacages 4a (a, b), 4b (c, d) and 4c (e, f) in different solvents (λ_ex = 365 nm, c = 10.0 μM).

Two intense emission bands centered at ca. 650 nm [Q₍₀, ₀₎] and 720 nm [Q₍₀,₁₎] with similar intensities were found from the emission spectra of metallacages 4a–4c, no variation in polar (DMSO, DMF, acetonitrile and methanol) or less polar solvents (acetone and dichloromethane), corresponding to the emission from the S₁ singlet state. It is worth noting that the formation of metallacage structure increases the emission intensity at ca. 720 nm compared with that located at ca. 650 nm, indicating that the formation of metal-coordination bonds strongly influences the emission properties of the metallacages. This brings the emission bands of these cages into the NIR region, making them serve as potential contrast agents for bio-imaging.

It is well known that porphyrin derivatives would generate singlet oxygen (¹O₂) upon light irradiation, which makes them widely used as photosensitizers for photodynamic therapy.^[12] The singlet oxygen quantum yields (Φ_Δ) of metallacages 4a–4c were measured using 1,3-diphenylisobenzofuran (DPBF) as ¹O₂ scavenger and 5,10,15,20-tetraphenylporphyrin (TPP) as reference (Φ_Δ=0.64).^[17] Time dependent absorbance spectroscopy of DPBF was collected in the presence of different metallacages upon light irradiation (Figure 5). Continuous decrease of the absorption band centered at 420 nm was observed for all the metallacages, suggesting that ¹O₂ which induces the decomposition of DPBF was gradually generated upon light irradiation. The Φ_Δ values of metallacages 4a, 4b and 4c were calculated to be 0.73, 0.62 and 0.73 in DMSO, respectively. The Φ_Δ values of metallacages 4a and 4c are even higher than that of TPP because the Pt(II) would promote intersystem crossing,^[18] benefiting better ¹O₂ generation efficiency for metallacages. Considering the potential anticancer activity of Pt(PEt₃)₂(OTf)₂,^[19] these metallacages could be potentially used as cancer theranostic agents including bio-imaging, chemotherapy and photodynamic therapy.

Figure 5.

Time dependent UV/Vis absorption of the mixture of DPBF with 4a (a), 4b (b), 4c (c) and TPP (d) in DMSO upon light irradiation (λ_ex = 365 nm). The concentration was 20 μM for DPBF and 2 μM for metallacages 4a–4c and TPP.

3. Summary

In summary, based on the self-assembly of a benzoate porphyrin derivative, Pt(PEt₃)₂(OTf)₂ and dipyridyl ligands, three tetragonal prismatic metallacages were efficiently prepared. These metallacages were well characterized by ³¹P{¹H} NMR, ¹H NMR as well as ESI-TOF-MS and the photophysical studies reveal that they exhibit emission in the NIR region and good singlet oxygen quantum yields. This study not only offers a general method for the preparation of porphyrin-based tetragonal prismatic cages by the variation of dipyridyl units but also provides a type of potential candidates towards cancer photochemotherapy.

4. Experimental Section

All reagents were purchased from commercially available suppliers and used without further purification. Compound 3c was prepared according to a procedure reported in literature.^[20] NMR spectra were recorded on a Varian Unity 300 MHz or Bruker 400 MHz spectrometer. ¹H NMR chemical shifts are reported relative to residual solvent signals, and ³¹P{¹H} NMR chemical shifts are referenced to an external unlocked sample of 85% H₃PO₄ (δ = 0.0). Mass spectra were carried out on Bruker AutoFlex TOF/TOF mass spectrometer. The UV-vis experiments were conducted on a DH-2000-BAL scan spectrophotometer. The fluorescent experiments were conducted on an FLS920 fluorescence spectrophotometer.

General Procedure for Metallacages

Compound 1 (2.20 mg, 2.50 μmol), 2 (7.30 mg, 10.0 μmol) and 3 (0.78 mg for 3a, 0.91 mg for 3b, 0.90 mg for 3c, 5.00 μmol) were mixed in a 1 : 4 : 2 molar ratio and dissolved in acetone/water (5.0 mL, 4:1, v/v). The whole reaction mixture was heated at 50 °C for 12 h and then cooled down. The solvent was removed by nitrogen flow. The residue was redissolved in acetone (1.0 mL), filtered and then ether (for 4a and 4b) or ethyl acetate (for 4c) (5.0 mL) was added to the clear acetone solution to give precipitates which were collected by centrifugation. The precipitation process was repeated for three times to obtain metallacages 4a–4c as red powders.

Cage 4a (8.13 mg, 95%). ¹H NMR (400 MHz, CD₃COCD₃, 295 K): 9.32 (d, J= 6.4 Hz, 16H), 8.46 (d, J=6.4 Hz, 16H), 8.14 (d, J=7.8 Hz, 16H), 8.01 (d, J=7.8 Hz, 16H), 7.87 (d, J=8.0 Hz, 8H), 7.34 (d, J=8.0 Hz, 8H), 2.07–2.40 (m, 96H), 1.40–1.61 (m, 144H). ³¹P{¹H} NMR (121.4 MHz, CD₃COCD₃, 295 K) δ (ppm): 5.25 ppm (d,²J_P-P=21.3 Hz, ¹⁹⁵Pt satellites, ¹J_Pt-P=3302 Hz), 0.30 ppm (d, ²J_P-P=21.3 Hz, ¹J_Pt-P = 3302 Hz).

Cage 4b (7.85 mg, 90%). ¹H NMR (400 MHz, CD₃COCD₃, 295 K ): 9.11 (s, 8H), 9.07 (d, J=6.4 Hz, 16H), 8.16 (d, J=8.2 Hz, 16H), 8.08 (d, J=6.4 Hz, 16H), 8.05 (d, J=8.2 Hz, 16H), 7.96 (s, 8H), 2.08–2.38 (m, 96H), 1.38–1.51 (m, 144 H). ³¹P NMR (121.4 MHz, CD₃COCD₃, 295 K) δ (ppm) : 6.18 ppm (d, ²J_P-P=20.7 Hz, ¹⁹⁵Pt satellites, ¹J_Pt-P=3355 Hz, 1.22 ppm (d, ²J_P-P=20.7 Hz, ¹⁹⁵Pt satellites, ¹J_Pt-P=3355 Hz).

Cage 4c (7.98 mg, 92%). ¹H NMR (400 MHz, CD³COCD₃, 295 K): 9.24 (d, J=6.2 Hz, 16H), 9.12 (s, 8H), 8.18 (d, J=8.1 Hz, 16H), 8.10 (d, J=8.1 Hz, 16 H), 8.06 (d, J=6.2 Hz, 16 H), 7.93 (s, 8H), 1.95–2.41 (m, 96H), 1.30–1.57 (m, 144 H). ³¹P NMR (121.4 MHz, CD₃COCD₃, 295 K) δ (ppm): 5.68 (d, ²J_P-P=21.2 Hz, ¹⁹⁵Pt satellites, ¹J_Pt-P=3354 Hz), 0.40 (d, ²J_P-P=21.2 Hz, ¹⁹⁵Pt satellites, ¹J_Pt-P=3354 Hz).