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Potential photosensitizer candidates for PDT including 7-oxy-3-thiomethylphenyl coumarino-phthalocyanines
Inorganica Chimica Acta 498 (2019) 119137
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Research paper
Potential photosensitizer candidates for PDT including 7-oxy-3thiomethylphenyl coumarino-phthalocyanines
T
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Baybars Köksoya,b, , Mahmut Durmuşb, Mustafa Buluta a b
Marmara University, Department of Chemistry, Kadıköy, 34722 İstanbul, Turkey Gebze Technical University, Department of Chemistry, Gebze, 41400 Kocaeli, Turkey
A R T I C LE I N FO
A B S T R A C T
Keywords: Phthalocyanine Coumarin Singlet oxygen
In this work, the novel phthalonitrile derivatives and their peripheral/nonperipheral phthalocyanine analogues including 7-oxy-3-(p-thiomethylphenyl) coumarin were synthesized and purified. All these novel compounds were characterized by common characterization methods such as FT-IR, UV–vis, MALDI-TOF, 1H-NMR and elemental analysis. Furthermore, the photochemical and photophysical properties of newly synthesized zinc(II) and indium(III) phthalocyanines were investigated in N,N-dimethylformamide (DMF) solutions. The substituent effect toward the phthalocyanine center and the metal effect on the photophysicochemical properties were also investigated.
1. Introduction Coumarins (1-benzopyran-2-one) are a group of naturally occurring heterocyclic compounds that include a lactone ring [1]. Consequently, various coumarins such as osthole, umbelliferone, scoparone have been isolated from some plants [2]. Some synthetic coumarins exhibit good photophysical, photochemical and biological activity properties and have an extensive usability as photosensitizers in photodynamic therapy, laser dyes [3] anti-HIV [4], antitumor [5], antibacterial [6], antioxidant [7], and anti-microbial [8] applications. Phthalocyanines are a group of aromatic macrocyclic compounds with 18-π electronic structure. These compounds show structural similarities with porphyrins, represent notable properties such as high thermal-chemical stability, and high efficiency in electron transfer [9]. These green/blue-colored macrocyclic compounds are used in some applications due to their stability, assorted coordination properties and advanced spectroscopic characteristics [10]. Also they are used in some technological applications such as chemical sensors [11], liquid crystals [12], catalysts [13], non-linear optics [14], and as photosensitizers in photodynamic therapy (PDT) [15,16]. One of the main problems of phthalocyanines is their low solubility in common organic solvents or water. The solubility of these compounds in organic solvents can be increased by attaching long chain alkyl or alkoxy groups on the phthalocyanine skeleton [17–21] and also the solubility in aqueous solutions can be improved by substitution of some groups such as sulfonates, carboxylates, phosphonates or quaternized amino groups [22].
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Although water-soluble phthalocyanine photosensitizers are preferred for PDT, phthalocyanines which are soluble in DMF or DMSO (these solvents can be easily mixed with water) are widely used for that purpose as their photocatalytic activity decreases in neat water due to their aggregation behaviour. In recent years, photodynamic therapy (PDT) has been an important method of cancer treatment using three effective components; photosensitizer, light, and oxygen. The mechanism of PDT is based on the interaction between the excited photosensitizer and nearby molecules, and this interaction establishes the formation of singlet oxygen (1O2). It can damage the biological substrates and eventually lead to cell death [23]. Over the last few years, the hybridization or coupling of different coumarin derivatives with varied tetrapyrrolic macrocycle such as phthalocyanine, porphyrine and corrole molecules [24] has been performed and the chemical and physical properties of the resulting conjugates have been investigated. These macrocycles have showed remarkable properties such as good solubility, effective energy transfer, some biological activities, and well singlet oxygen generation ability due to the presence of coumarin molecules. Also another advantage of these hybrid macrocycles for PDT applications can be their “imaging” which depends on the excellent fluorescence properties of coumarins. For these reasons, we designed and synthesized novel phthalonitriles and their metallo-phthalocyanine (zinc and indium) derivatives by attaching a 7-hydroxy-3-(p-thiomethylphenyl) coumarin group and also studied their photophysicochemical properties in DMF as a potential
Corresponding author at: Gebze Technical University, Department of Chemistry, Gebze, 41400 Kocaeli, Turkey. E-mail addresses: [email protected], [email protected] (B. Köksoy).
https://doi.org/10.1016/j.ica.2019.119137 Received 14 July 2019; Received in revised form 6 September 2019; Accepted 6 September 2019 Available online 07 September 2019 0020-1693/ © 2019 Elsevier B.V. All rights reserved.
Inorganica Chimica Acta 498 (2019) 119137
B. Köksoy, et al.
candidate for PDT application.
m/z: calcd. 410.44, found 411.60 [M + H]+.
2. Synthesis
2.3. General synthesis of zinc(II) phthalocyanines (2a and 3a)
2.1. 7-Hydroxy-3(p-thiomethylphenyl) coumarin (1)
The phthalonitrile compounds (2 or 3) (0.1 g, 0.243 mmol) and Zn (CH3COO)2·2H2O (0.0133 g, 0.06075 mmol) were dissolved in a Schlenk tube in 2 mL of N,N-Dimethylaminoethanol (DMAE). The reaction mixture was stirred and heated at 160 °C for 16 h under an argon atmosphere. After cooling to room temperature, the green mixture was poured into 50 mL of hot water. Then, the precipitate was centrifuged and washed several times with hot water, acetic acid, methanol, ethanol, ethylacetate, diethylether and purified by column chromatography on silica gel using THF as an eluent and final product was dried in vacuum.
A mixture of 2,4-dihydroxybenzaldehyde (1.51 g, 10.9 mmol), p(thiomethylphenyl) acetic acid (2 g, 10.9 mmol), anhydrous NaOAc (1.36 g, 16.35 mmol) and 15 mL acetic anhydride was heated at 160 °C while stirring under nitrogen atmosphere for 10 h. After removal of acetic acid by distillation, the resulting solid was dissolved in 100 mL THF:methanol (3:1) mixture and then LiOH (1 g, 42 mmol) in 5 mL water was added to the suspension. About 3 h later, the reaction mixture was poured into 100 mL ice-water and treated with 10% HCl, the precipitate was collected by filtration. The dried product was purified by recrystallization from methanol. Yield 2.3 g (74.2%). Mp 230–232 °C. Anal. Calcd for C16H12O3S: C, 67.59; H, 4.25%; Found: C, 67.57; H, 4.22%. 1H-NMR (500 MHz, CDCl3): δH, ppm 8.13 (s, 1H, lactone-H), 7.66 (d, 2H, J = 8.09 Hz, Ar-H), 7.57 (d, 1H, J = 8.33 Hz, Ar-H), 7.31 (d, 2H, J = 8.11 Hz, Ar-H), 6.79 (d, 1H, J = 8.33 Hz, Ar-H), 6.72 (s, 1H, Ar-H), 3.41 (bs, 1H, ArOH), 2.50 (s, 3H, -SCH3). FT-IR (ATR): υmax, cm−1: 3209 (–OH), 3055–3034 (Ar-CH), 2926 (AliphaticCH), 1685 (lactone-C=O), 1605–1566 (Ar-C=C) and 809 (Ar-SCH3). UV–vis (THF): λmax = 352 nm. Florescence (THF): λem = 444 nm. MS (MALDI-TOF) m/z: calcd. 284.33, found 285.31 [M+H]+, 307.58 [M +Na]+.
2.3.1. 1(4), 8(11), 15(18), 22(25)-Tetrakis [7-oxy-3(pthiomethylphenyl)coumarino] phthalocyaninato zinc(II) (2a) Yield 28 mg (26.9%). Mp: > 300 °C. Anal. calcd. for C96H56N8O12S4Zn: C, 67.54; H, 3.30; N, 6.56%; found: C, 67.49; H, 3.26; N, 6.52%. 1H-NMR (500 MHz, DMSO‑d6): δH, ppm 8.41–7.15 (m, 44H, Ar-H), 2.52 (s, 12H, -SCH3). FT-IR (ATR): υmax, cm−1: 3073–3029 (Ar-CH), 2990–2911 (Aliphatic-CH), 1724 (lactone-C=O), 1607–1477 (Ar-C=C), 1275 (Ar-O-Ar) and 817 (Ar-SCH3). UV–vis (DMF): λmax, (log ε), 350 (5.08), 621 (4.32), 689 (5.06) nm. MS (MALDI-TOF) m/z: calcd. 1707.17, found 1707.18 [M]+. 2.3.2. 2(3), 9(10), 16(17), 23(24)-Tetrakis [7-oxy-3(pthiomethylphenyl)coumarino] phthalocyaninato zinc(II) (3a) Yield: 34 mg (32.7%). Mp: > 300 °C. Anal. calcd. for C96H56N8O12S4Zn: C, 67.54; H, 3.30; N, 6.56%; Found: C, 67.52; H, 3.25; N, 6.53%. 1H-NMR (500 MHz, DMSO‑d6): δH, ppm 8.39–7.16 (m, 44H, Ar-H), 2.52 (s, 12H, -SCH3). FT-IR (ATR): υmax, cm−1: 3067–3030 (Ar-CH), 2951–2864 (Aliphatic-CH), 1720 (lactone-C=O), 1602–1468 (Ar-C=C), 1260 (Ar-O-Ar) and 820 (Ar-SCH3). UV–vis (THF): λmax, (log ε), 354 (4.98), 610 (4.31), 677 (5.05) nm. MS (MALDI-TOF) m/z: calcd. 1707.17, found 1708.99 [M+H]+.
2.2. General synthesis of phthalonitrile derivatives (2 and 3) 7-Hydroxy-3(p-thiomethylphenyl) coumarin (1) (1.42 g, 5 mmol) and 3-nitrophthalonitrile or 4-nitrophthalonitrile (0.86 g, 5 mmol) were dissolved in 50 mL of dry dimethylformamide (DMF) under an argon atmosphere and anhydrous K2CO3 (1.04 g, 7.5 mmol) was added and this mixture was stirred for 48 h at 50–60 °C. After cooling to room temperature, the reaction mixture was treated with diluted HCl. The solid product was filtered, washed with water and dried. The crude product was purified by silica gel column chromatography using CHCl3 as an eluent.
2.4. General synthesis of indium(III)acetate phthalocyanines (2b and 3b) The phthalonitrile compounds (2 or 3) (0.1 g, 0.243 mmol) and In (CH3COO)3 (0.0177 g, 0.0607 mmol) were dissolved in a Schlenk tube in 2 mL of DMAE. The reaction mixtures were stirred and heated at 160 °C for 12 h under an argon atmosphere. After cooling to room temperature, the green mixture was poured into 50 mL hot water. Then, the precipitate was centrifuged and washed several times with hot water, methanol, ethanol, ethylacetate, diethylether and purified by column chromatography on silica gel using THF as an eluent and final product was dried in vacuum.
2.2.1. 7-(2,3-Dicyanophenoxy)-3(p-thiomethylphenyl) coumarin (2) Yield 1.87 g (91.1%). Mp 268–269 °C. Anal. calcd. for C24H14N2O3S: C, 70.23; H, 3.44; N, 6.83%; Found: C, 70.19; H, 3.41; N, 6.89%. 1HNMR (500 MHz, CDCl3): δH, ppm 8.29 (s, 1H, lactone-H), 7.94 (dd, 1H, J = 7.78 and 1.07 Hz, Ar-H), 7.87 (dd, 1H, J = 8.59 and 8.64 Hz, Ar-H), 7.86 (dd, 1H, J = 7.77 and 1.07 Hz, Ar-H), 7.67 (d, 2H, J = 8.65 Hz, ArH), 7.50 (dd, 1H, J = 8.56 and 1.14 Hz, Ar-H), 7.35 (d, 1H, J = 2.35 Hz, Ar-H), 7.33 (d, 2H, J = 8.69 Hz, Ar-H), 7.23 (dd, 1H, J = 8.55 and 2.42 Hz, Ar-H), 2.49 (s, 3H, -SCH3). FT-IR (ATR): υmax, cm−1: 3094–3038 (Ar-CH), 2923 (Aliphatic-CH), 2227 (Ar-CN), 1720 (lactone-C=O), 1614–1573 (Ar-C=C), 1278 (Ar-C-O) and 808 (ArSCH3). UV–vis (THF): λmax = 348 nm. Florescence (THF): λem = 461 nm. MS (MALDI-TOF) m/z: calcd. 410.44, found 411.58 [M +H]+, 429.16 [M+H+H2O]+.
2.4.1. 1(4), 8(11), 15(18), 22(25)-Tetrakis [7-oxy-3(pthiomethylphenyl)coumarino] phthalocyaninato indium(III)acetate (2b) Yield 37 mg (33.5%). Mp: > 300 °C. Anal. calcd. for C98H59N8O14S4In: C, 64.83; H, 3.27; N, 6.17%; found: C, 64.80; H, 3.24; N, 6.12%. 1H-NMR (500 MHz, DMSO‑d6): δH, ppm 8.54–7.17 (m, 44H, Ar-H), 2.44 (s, 12H, -SCH3), 2.35 (s, 3H, acetate-CH3). FT-IR (ATR): υmax, cm−1: 3075–3029 (Ar-CH), 2989–2919 (Aliphatic-CH), 1727 (lactone-C=O), 1609–1480 (Ar-C=C), 1275 (Ar-O-Ar) and 820 (ArSCH3). UV–vis (DMF): λmax, (log ε), 352 (5.01), 635 (4.34), 706 (5.03) nm. MS (MALDI-TOF) m/z: calcd. 1815.65, found 1910.56 [M–OAc–DHB]+, 1933.52 [M–OAc–DHB+Na]+.
2.2.2. 7-(3,4-Dicyanophenoxy)-3(p-thiomethylphenyl) coumarin (3) Yield 1.76 g (85.7%). Mp 205–206 °C. Anal. calcd. for C24H14N2O3S: C, 70.23; H, 3.44; N, 6.83% found: C, 70.20; H, 3.38; N, 6.91%. 1HNMR (500 MHz, CDCl3): δH, ppm 8.29 (s, 1H, lactone-H), 8.15 (d, 1H, J = 8.74 Hz, Ar-H), 7.93 (d, 1H, J = 2.52 Hz, Ar-H), 7.85 (d, 1H, J = 8.60 Hz, Ar-H), 7.67 (d, 2H, J = 8.67 Hz, Ar-H), 7.56 (dd, 1H, J = 8.71 and 2.58 Hz, Ar-H), 7.32 (d, 2H, J = 8.70 Hz, Ar-H), 7.31 (d, 1H, J = 2.38 Hz, Ar-H), 7.18 (dd, 1H, J = 8.61 and 2.34 Hz, Ar-H), 2.50 (s, 3H, -SCH3). FT-IR (ATR): υmax, cm−1: 3062–3034 (Ar-CH), 2923 (Aliphatic-CH), 2230 (Ar–CN), 1720 (lactone-C=O), 1615–1589 (ArC=C), 1254 (Ar-C-O) and 820 (Ar-SCH3). UV–vis (THF): λmax = 350 nm. Florescence (THF): λem = 472 nm. MS (MALDI-TOF)
2.4.2. 2(3), 9(10), 16(17), 23(24)-Tetrakis [7-oxy-3(pthiomethylphenyl)coumarino] phthalocyaninato indium(III)acetate (3b) Yield 41 mg (37.1%). Mp: > 300 °C. Anal. calcd. for C98H59N8O14S4In: C, 64.83; H, 3.27; N, 6.17%; found: C, 64.79; H, 3.23; N, 6.15%, 1H-NMR (500 MHz, DMSO‑d6): δH, ppm 8.38–7.20 (m, 44H, 2
Inorganica Chimica Acta 498 (2019) 119137
B. Köksoy, et al.
Scheme 1. Synthetic pathway of the phthalonitriles (2 and 3) and phthalocyanines (2a-b and 3a-b) including 7-oxy-3-(p-thiomethylphenyl)coumarin groups. i) 3-nitro-1,2-dicyanobenzene, K2CO3, DMF, 50–60 °C ii) 4-nitro-1,2-dicyanobenzene, K2CO3, DMF, 50–60 °C, iii) Zn(OAc)2·2H2O, DMAE, 160 °C, iv) In(OAc)3, DMAE, 160 °C.
The 1H-NMR spectra of 1–3 showed resonance bands at 8.13–6.72 ppm (for 1), 7.94–7.23 ppm (for 2) and 8.15–7.18 ppm (for 3). The lactone proton (at 4-position of the coumarin skeleton) was assigned to a singlet in lower field than other aromatic protons at 8.13 ppm for 1 and 8.29 ppm for both phthalonitrile compounds (2 and 3). The thiomethyl protons on the phenyl group of coumarin moiety were observed at 2.50 ppm for 1, 2.49 ppm for 3 and 2.50 ppm for 2 as singlet peaks. The MALDI-TOF mass spectra of compounds 1–3 showed m/z peaks at 285.31 for [M+H]+ and at 307.58 for [M+Na]+ for compound 1, at 411.58 m/z for [M+H]+ and at 429.16 m/z for [M+H +H2O]+ for compound 2 and at 411.60 m/z for [M+H]+ for compound 3. The peaks appearing at 2227 cm−1 for 2 and 2230 cm−1 for 3 disappeared in the FT-IR spectra of the metallophthalocyanines 2a-b and 3a-b as expected. This is an important clue concerning the formation of the phthalocyanine macrocycle from the corresponding phthalonitriles. The typical ester carbonyl (lactone ring) vibration was observed in the range of 1727–1720 cm−1 for all metallophthalocyanines (2a-b and 3a3b). The aromatic C-H and aliphatic C-H stretching peaks for all synthesized phthalocyanines appeared between 3073 and 3029 cm−1 and 2990–2864 cm−1, respectively. Another typical band (Ar-O-Ar) was observed at 1275 cm−1 for non-peripherally (2a-b) and 1260–1261 cm−1 for peripherally (3a-b) substituted phthalocyanines. The ground-state electronic spectra of phthalocyanines have two clear bands, one of which is observed in the range of 650–750 nm and another one appearing at nearly 300 nm. In this work, each metallophthalocyanine derivative exhibited a sharp-single Q band at 689 nm for 2a, at 706 nm for 2b, at 677 nm 3a and at 687 nm for 3b in their ground-state electronic spectra. B bands of these phthalocyanines were observed within the range of 350–356 nm (Fig. 1). The 1H-NMR spectra of zinc(II) (2a and 3a) and indium(III) acetate (2b and 3b) phthalocyanines bearing coumarin groups showed characteristic aromatic (phthalocyanine-H and coumarin-lactone-H) and aliphatic (–SCH3) protons for each phthalocyanine. The Ar-H peaks were assigned between 8.54 and 7.15 ppm for all synthesized phthalocyanines. The aliphatic protons of the –SCH3 group were observed at 2.44 ppm for indium (III)acetate (2b-3b) and 2.52 ppm for zinc(II) (2a3a) phthalocyanines. Additionally, the singlet peaks were observed only for the indium complexes at 2.35 ppm for 2b and at 2.88 ppm for 3b were assigned to their acetate groups.
Ar-H), 2.44 (s, 12H, -SCH3), 2.88 (s, 3H, acetate-CH3). FT-IR (ATR): υmax, cm−1: 3068–3030 (Ar-CH), 2990–2918 (Aliphatic-CH), 1725 (lactone-C=O), 1603–1471 (Ar-C=C), 1261 (Ar-O-Ar) and 818 (ArSCH3). UV–vis (DMF): λmax, (log ε) 356 (5.16), 617 (4.36), 687 (5.05) nm. MS (MALDI-TOF) m/z: calcd. 1815.65, found 1815.37 [M]+, 1910.47 [M−OAc+DHB]+.
3. Results and discussion 3.1. Synthesis and characterization Scheme 1 points out the synthesis methodology for the novel 7hydroxy-3(p-thiomethylphenyl) coumarin (1) which was prepared in a Perkin condensation of 2,4-dihydroxybenzaldehyde with p-(thiomethylphenyl)acetic acid. The target phthalonitrile precursors 7-(2,3dicyanophenoxy)-3(p-thiomethylphenyl) coumarin (2) and 7-(3,4-dicyanophenoxy)-3(p-thiomethylphenyl) coumarin (3) were obtained from the SNAr reaction between 3-/4-nitrophthalonitrile with 7-hydroxy-3(p-thiomethylphenyl) coumarin (1). The metallo-phthalocyanines (2a, 2b, 3a and 3b) were synthesized with anhydrous zinc(II) and indium(III) metal salts using the phthalonitrile precursors (2 or 3) in dry DMAE (Scheme 1). Various spectroscopic characterization techniques such as UV/Vis, IR, 1H-NMR spectroscopy and MALDI-TOF mass spectrometry were used for the characterization of the newly synthesized compounds. The results obtained from these techniques are compatible with the proposed structures for all the newly prepared compounds. The FT-IR spectrum of 7-hydroxy-3(p-thiomethylphenyl) coumarin (1) exhibits characteristic peaks at 1720 cm−1 (for lactone -C=O), 1600 cm−1 (for -C=C), 3209 cm−1 (for aromatic-OH). The obtained peaks between 3070 and 3050 cm−1 for aromatic C-H and 1591–1465 cm−1 for aromatic C=C also confirmed the structure of the coumarin (1). The vibration bands were observed at 3094–3034 cm−1 (aromatic C-H), 2923 cm−1 (aliphatic C-H), 2230 and 2227 cm−1 (CN), 1720 cm−1 (lactone C=O), 1615–1573 cm−1 (aromatic C=C) and 1278–1254 cm−1 (Ar-O-Ar) for phthalonitrile compounds 2 and 3. Compared to the FT-IR spectrum of 1, a disappearance of the OH stretching band was observed, as was the appearance of an intense vibration (C≡N) at 2227 cm−1 for 2 and 2230 cm−1 for 3 that are the proof of formation the corresponding phthalonitriles. 3
Inorganica Chimica Acta 498 (2019) 119137
B. Köksoy, et al.
Fig. 3. Ground-state electronic absorption spectra of phthalocyanine 3a in DMF at different concentration (2 × 10−6–12 × 10−6 M). (Inset: Concentration versus absorbance).
Fig. 1. Ground-state electronic absorption spectra of synthesized zinc(II) and indium(III) phthalocyanines in DMF.
3.3. Fluorescence studies In recent years, fluorescence and fluorescent molecules have been important for PDT. In particular, fluorescent molecules may play a key role for the in vivo studies of 3rd generation photosensitizers to monitor how these molecules move in the body and whether they accumulate in the cancer cell. Therefore, the fluorescence behaviour of the photosensitizers is important. The fluorescence properties were investigated to understand which molecule may be suitable for imaging and to determine to fluorescence quantum yield and lifetime. Fig. 4 shows fluorescence emission, absorption and excitation spectra of compound 2a in DMF as an example for the studied zinc(II) phthalocyanines. Fluorescence emission data for all studied phthalocyanines are given in Table 1. Both zinc(II) phthalocyanines (2a and 3a) showed nearly the same fluorescence behaviour in DMF. The excitation spectra were similar to the absorption spectra, and both were mirror images of the fluorescence spectra for these phthalocyanines (2a and 3a) in DMF (Fig. 4 as an example for 2a). It is obvious that the similarity of the Qband absorption and the Q band maxima of the excitation spectra for these phthalocyanines suggest that the nuclear configurations of the ground and excited states are almost the same and are not affected by excitation. There was no emission peak in the fluorescence spectra of the indium(III) phthalocyanines (2b and 3b) bearing 7-oxy-3-(p-thiomethyl) phenyl coumarin group because of the heavy atom effect of the indium metal in the phthalocyanine cavity.
Fig. 2. MALDI-TOF spectrum of phthalocyanine 2a.
The MALDI-TOF spectra of 2a, 3a and 2b, 3b were recorded using 2,5-dihydroxybenzoic acid matrix. While compounds 2a (Fig. 2) and 3a showed only the molecular ion peak [M]+ and [M+H]+ in their spectra, the phthalocyanines 2b and 3b showed [M+−OAc+DHB] peaks. The molecular ion peaks (m/z) were detected at 1707.18 Da for 2a, at 1708.99 Da for 3a, at 1910.56 Da for 2b, and at 1815.37 and 1910.47 Da for 3b.
700 0.6
600
Aggregation is one of the most encountered disadvantages of phthalocyanines and it affects both photophysical, photochemical and electrochemical properties which depend on some conditions such as concentration, temperature, substituents and solvents [25]. In this study, the aggregation properties of zinc(II) and indium(III) acetate phthalocyanines including 7-oxy-3-(p-thiomethyl) phenyl coumarin (2a-b and 3a-3b) were examined at 12-2 × 10−6 concentration range in DMF (Fig. 3 as an example for 3a). The Beer-Lambert law was fitted for the studied phthalocyanines (2a-b, 3a-b) in the 12 × 10−6 to 2 × 10−6 M concentration range. There was no indication for an aggregation of these coumarin-substituted zinc and indium metallophthalocyanines in DMF.
Emission
Intensity(a.u)
500
0.5
Exicitation
400
0.4
Absorption 0.3
300 200
0.2
100
0.1
0 500
Absorption
3.2. Aggregation studies
0 550
600 650 700 Wavelength(nm)
750
800
Fig. 4. Electronic absorption, fluorescence emission and excitation spectra of the phthalocyanine 2a in DMF. (Excitation wavelength = 650 nm). 4
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Table 1 Photophysicochemical data for 7-oxy-3-(p-thiomethylphenyl)coumarin substituted zinc(II) and In(III) acetate phthalocyanines in DMF. Compound
Q band λmax, (logε)
Emission wavelength λem
ΦF
τF(ns)
Φd(×10−5)
ΦΔ
2a 2b 3a 3b StdZnPc [25] StdInOAcPc [31]
689 706 677 687 670 683
701 – 685 – 676 693
0.12 – 0.09 – 0.17 0.019
2.48 – 2.02 – 1.03 1.66
30.95 30.27 22.61 18.66 2.33 54.07
0.81 0.87 0.78 0.85 0.56 0.75
(5.06) (5.03) (5.05) (5.05) (5.37) (4.90)
The fluorescence quantum yields (ΦF) of compounds 2a and 3a are listed in Table 1. The ΦF values of the indium(III) phthalocyanines (2b and 3b) were not evaluated because these phthalocyanines did not produce any emission in their fluorescence studies. Both zinc(II) phthalocyanines including the 7-oxy-3-(p-thiomethyl) phenyl coumarin group showed lower ΦF values than an unsubstituted zinc(II) phthalocyanine (StdZnPc) (ΦF = 0.17 [26]) which was used as a standard for the fluorescence quantum yield calculations. The zinc(II) phthalocyanine derivative 2a showed a higher fluorescence quantum yield than its counterpart 3a in DMF. The fluorescence lifetimes (τF) were determined by the time-correlated photon counting (TCSPC) method in DMF and the τF values are given in Table 1. Only zinc(II) phthalocyanines (2a and 3a) have measurable fluorescence lifetimes due to non-fluorescent behaviour of the indium(III) phthalocyanines (2b and 3b) again. The TCSPC fluorescence decay curve of phthalocyanine 2a in DMF is given in Fig. 5 as an example. The τF values of the coumarin-substituted zinc(II) phthalocyanine complexes (2a and 3a) amount to 2.48 and 2.02 ns, respectively. The obtained τF values for these phthalocyanines are higher compared to the standard zinc(II) phthalocyanine (1.03 ns [26]) in DMF. Both fluorescence quantum yield and lifetime of the novel zinc(II) phthalocyanines (2a and 3a) were found similar to other coumarin substituted zinc(II) phthalocyanines’ values given in the literature [27,28] and are higher than those of fluorophenylcoumarin-substituted phthalocyanine counterpart given in the literature [29].
Fig. 6. The absorption spectral changes during the determination of singlet oxygen quantum yields. This determination was for compound 3a in DMF at a concentration of 1 × 10−5 M. (Inset: Plot of DPBF absorbance versus time).
and 3b were studied and calculated in DMF by a chemical method using 1,3-diphenylisobenzofuran (DPBF) as a quencher. The decrease of the absorbance of DPBF at 414 nm was observed using a UV–Vis spectrophotometer. No change was not observed in the Q band shapes and intensities of phthalocyanines 2a-b and 3a-b suggesting that these phthalocyanines do not decompose during the singlet oxygen measurements (Fig. 6). The ΦΔ values of the phthalocyanine compounds 2ab and 3a-3b were found higher than those of standard zinc(II) (StdZnPc) and indium(III) acetate (StdInOAcPc) phthalocyanines in DMF (Table 1), suggesting that the substitution of the coumarin groups on the phthalocyanine ring increased the singlet oxygen generation of the target photosensitizers. So, in this work, the studied indium(III) acetate phthalocyanines (2b and 3b) showed higher singlet oxygen quantum yields than their zinc(II) phthalocyanine (2a and 3a) counterparts. This means that the indium(III) acetate phthalocyanines 2b and 3b including 7-oxy-3-(p-thiomethyl) phenyl coumarin moieties generate more singlet oxygen than the zinc(II) phthalocyanine derivatives 2a and 3a. The higher singlet oxygen production capability of the indium(III) phthalocyanines is due to the heavy atom effect of indium. The heavy atom encourages an intersystem crossing between the excited singlet state and triplet state of the photosensitizers. Also, the nonperipherally substituted indium(III) phthalocyanine (3b) (ΦΔ = 0.85) (Table 1), which may be result of the absorption of light at longer wavelength. The obtained singlet oxygen quantum yields of the novel phthalocyanines (2a-b and 3a-b) were found to be higher than those of 3phenyl coumarin-substituted phthalocyanines according to the results reported in the literature [27,28,30].
3.4. Singlet oxygen studies The Singlet oxygen quantum yields (ΦΔ) for compounds 2a, 2b, 3a
3.5. Photodegradation studies Fig. 5. Time correlated single photon counting (TCSPC) fluorescence decay curve of phthalocyanine 2a in DMF.
Photostability is another property important for PDT and other photocatalytic applications. Under strong light irradiation, 5
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general analysis methods and elemental analysis as well. The photophysicochemical properties of the phthalocyanines were investigated in DMF. The effect of the position of the substituents on the phthalocyanine macrocycle (non-peripheral or peripheral) and the effect of the metal ion in the phthalocyanine center (zinc or indium) on these properties were also determined. All phthalocyanines formed monomeric species in DMF. Although 7-oxy-3-(p-thiomethyl) phenyl coumarin-substituted zinc(II) phthalocyanines (2a and 3a) showed a similar fluorescence behaviour in DMF, the indium(III) derivatives (2b and 3b) did not show any fluorescence emission due to heavy atom effect of the indium central metal in the phthalocyanine cavity. The results showed that all novel phthalocyanines (2a-b and 3a-3b) generated singlet oxygen. Especially the non-peripherally substituted indium(III) acetate derivative (2b) showed the highest singlet oxygen quantum yield (ΦΔ = 0.87) due to higher intersystem crossing behaviour of the large indium atom in the phthalocyanine cavity. All studied phthalocyanines (2a-b and 3a-3b) showed moderate stability which is suitable for photodynamic activity. Finally, the studied coumarinophthalocyanines showed good photophysical and photochemical properties, particularly singlet oxygen generation, making them good candidates for PDT applications.
Fig. 7. The absorption spectral changes of phthalocyanine 2a in DMF under light irradiation showing the disappearance of the Q-band at ten minutes intervals. (Inset: Plot of absorbance versus time).
Acknowledgment
photosensitizers suitable for PDT must be stable. Generally, phthalocyanines show good resistance against light irradiation. In this study, the photodegradation of the phthalocyanines was monitored by ground state electronic spectroscopy. The decrease of the Q band absorption peak without any decomposition of its shape proves that the photodegradation is not associated with a phototransformation into different forms of the phthalocyanines absorbing in the visible region (Fig. 7). The photodegradation quantum yields (Φd) of the phthalocyanine compounds (2a-b and 3a-b) are supplied in Table 1. The values for the standard zinc(II) and indium(III) acetate phthalocyanines are also given in this table for determination of the effect of the substitution on the photodegradation behaviour. Table 1 shows that the zinc(II) phthalocyanines including coumarin groups (2a and 3a) are less stable to degradation compared to standard ZnPc in DMF. Similarly, the Φd values of these substituted zinc(II) phthalocyanines (Φd = 30.95 × 10−5 for 2a and Φd = 22.61 × 10−5 for 3a) were found higher than those of the unsubstituted ZnPc (Φd = 2.33 × 10−5). So, the attachment of 7-oxy-3(p-thiomethylphenyl) coumarin groups to ZnPc seems to decrease the stability of the complexes in DMF. In contrast, the peripherally and nonperipherally substituted indium(III) acetate complexes (2b and 3b) are more stable than the standard indium(III) acetate phthalocyanine because the Φd values of these substituted indium(III) acetate phthalocyanines (Φd = 30.27 × 10−5 for 2b and Φd = 18.66 × 10−5 for 3b) were found to be lower than those of the standard InOAcPc (Φd = 54.05 × 10−5). The photostability of the indium(III) acetate phthalocyanines (2b and 3b) is lower than that of the zinc(II) phthalocyanine counterparts (2a and 3a) due to the out of cavity behaviour of the larger indium(III) atom. The substitution of the 7-oxy-3-(p-thiomethylphenyl) coumarin groups on the peripheral positions of the phthalocyanine macrocycle produced more stable phthalocyanine derivatives compared to the substitution of this group to the non-peripheral positions. All synthesized zinc(II) and indium(III) acetate phthalocyanines bearing coumarin groups (2a-b and 3a-b) showed similar stabilities with Φd values in the same order of magnitude (about 10−4 − 10−5) as those of corresponding phthalocyanines containing different coumarin substituents [27,29].
We are thankful to the Research Foundation of Marmara University, Commission of Scientific Research Project (BAPKO) FEN-A100713–0327. Appendix A. Supplementary data Supplementary data to this article can be found online at https:// doi.org/10.1016/j.ica.2019.119137. References [1] R.A. Irgashev, A.A. Karmatsky, P.A. Slepukhin, G.L. Rusinov, V.N. Charushin, Tetrahedron Lett. 54 (2013) 5734–5738. [2] A.M. Hamdy, N. Eleya, H.H. Mohammed, Z. Khaddour, T. Patonay, A. Villinger, P. Langer, Tetrahedron Lett. 54 (2013) 3568–3571. [3] H.M.H. Belal, M.K. Gasser, M.K. Rasha, M. Bulut, Spectrochim. Acta A: Mol. Biomol. Spect. 158 (2016) 34–42. [4] T.O. Olomola, S. Mosebi, R. Klein, T.T. Johnstone, J. Coates, R. Hewer, P.T. Kaye, Bioorg. Chem. 57 (2014) 1–4. [5] M. Basanagouda, V.B. Jambagi, N.N. Barigidad, S.S. Laxmeshwar, V.D. Narayanachar, Eur. J. Med. Chem. 74 (2014) 225–233. [6] Y. Tada, Y. Shikishima, Y. Takaishi, H. Shibata, T. Higuti, G. Honda, M. Ito, Y. Takeda, O.K. Kodzhimatov, O. Ashurmetov, Y. Ohmoto, Phytochemistry 59 (2002) 649–654. [7] J.B. Veselinovic, A.M. Veselinovic, Z.J. Vitnik, V.D. Vitnik, G.M. Nikolic, Chem. Biol. Int. 214 (2014) 49–56. [8] H.A. El-Wahaba, M.A. El-Fattahb, N.A. El-Khalikc, H.S. Nassara, M.M. Abdelalla, Prog. Org. Coat. 77 (2014) 1506–1511. [9] N.B. McKeown, Phthalocyanine Materials: Synthesis, Cambridge University Press, Cambridge, Structure and Function, 1998. [10] A. Lever, E. Milaeva, The Phthalocyanines, Properties and Applications Vol. 2 (1992) 162–227. [11] G. Guillaud, J. Simon, J.P. Germain, Coord. Chem. Rev. 180 (1998) 1433–1484. [12] T. Basova, A. Hassan, M. Durmuş, A.G. Gürek, V. Ahsen, Coord. Chem. Rev. 310 (2016) 131–153. [13] C. Huang, R. Liu, W. Yang, C. Zhang, H. Zhu, Inorg. Chim. Acta 467 (2017) 307–315. [14] G.D.L. Torre, P. Vazquez, F.A. Lopez, T. Torres, J. Mater. Chem. 8 (1998) 1671–1683. [15] T. Stuchinskaya, M. Moreno, M.J. Cook, D.R. Edwards, D.A. Russell, Photochem. Photobiol. Sci. 10 (2011) 822–831. [16] R.F. Donnelly, P.A. McCarron, M.M. Tunney, Microbiol. Res. 163 (2008) 1–12. [17] C.C. Leznoff, A.B.P. Lever, Phthalocyanines Properties and Applications, VCH, Weinheim, 1989. [18] Ö. Bekaroglu, Appl. Organomet. Chem. 10 (1996) 605–622. [19] M.J. Cook, A.J. Dunn, S.D. Howe, A.J. Thomson, K.J. Harrison, J. Chem. Soc. Perkin Trans. 1 (1988) 2453–2458. [20] P.M. Burnham, M.J. Cook, L.A. Gerrard, M.J. Heeney, D.L. Hughes, Chem. Commun. 16 (2003) 2064–2065. [21] H. Ali, J.E. Van Lier, Chem. Rev. 99 (1999) 2379–2450. [22] F. Dumoulin, M. Durmuş, V. Ahsen, T. Nyokong, Coord. Chem. Rev. 254 (2010)
4. Conclusion In this study, novel zinc(II) and indium(III) acetate phthalocyanines bearing four 7-oxy-3-(p-thiomethyl) phenyl coumarin groups were synthesized. These novel compounds were fully characterized by 6
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[27] E.N. Kaya, M. Durmuş, M. Bulut, J. Porphyr. Phthalocyanines 19 (2015) 1114–1122. [28] A. Tastemel, B.Y. Karaca, M. Durmuş, M. Bulut, J. Lumin. 168 (2015) 163–171. [29] T. Erdogan, M. Bulut, M. Çamur, J. Photochem. Photobiol. A 300 (2015) 6–14. [30] M. Piskin, M. Durmuş, M. Bulut, J. Photochem. Photobiol. A 223 (2011) 37–49. [31] E. Gürel, M. Pişkin, S. Altun, Z. Odabaş, M. Durmuş, Dalton Trans. 44 (2015) 6202–6211.
2792–2847. [23] P. Zhang, W. Steelant, M. Kumar, M. Scholfield, J. Am. Chem. Soc. 129 (2007) 4526–4527. [24] A.F.R. Cerqueira, V.A.S. Almodovar, M.G.P.M.S. Neves, A.C. Tome, Molecules 22 (2017) 1–26. [25] H. Enkelkamp, R.J.M. Nolte, J. Porp. Phthal. 4 (2000) 454. [26] Y. Zorlu, F. Dumoulin, M. Durmuş, V. Ahsen, Tetrahedron 66 (2010) 3248–3258.
7
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Inorganica Chimica Acta journal homepage: www.elsevier.com/locate/ica
Research paper
Potential photosensitizer candidates for PDT including 7-oxy-3thiomethylphenyl coumarino-phthalocyanines
T
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Baybars Köksoya,b, , Mahmut Durmuşb, Mustafa Buluta a b
Marmara University, Department of Chemistry, Kadıköy, 34722 İstanbul, Turkey Gebze Technical University, Department of Chemistry, Gebze, 41400 Kocaeli, Turkey
A R T I C LE I N FO
A B S T R A C T
Keywords: Phthalocyanine Coumarin Singlet oxygen
In this work, the novel phthalonitrile derivatives and their peripheral/nonperipheral phthalocyanine analogues including 7-oxy-3-(p-thiomethylphenyl) coumarin were synthesized and purified. All these novel compounds were characterized by common characterization methods such as FT-IR, UV–vis, MALDI-TOF, 1H-NMR and elemental analysis. Furthermore, the photochemical and photophysical properties of newly synthesized zinc(II) and indium(III) phthalocyanines were investigated in N,N-dimethylformamide (DMF) solutions. The substituent effect toward the phthalocyanine center and the metal effect on the photophysicochemical properties were also investigated.
1. Introduction Coumarins (1-benzopyran-2-one) are a group of naturally occurring heterocyclic compounds that include a lactone ring [1]. Consequently, various coumarins such as osthole, umbelliferone, scoparone have been isolated from some plants [2]. Some synthetic coumarins exhibit good photophysical, photochemical and biological activity properties and have an extensive usability as photosensitizers in photodynamic therapy, laser dyes [3] anti-HIV [4], antitumor [5], antibacterial [6], antioxidant [7], and anti-microbial [8] applications. Phthalocyanines are a group of aromatic macrocyclic compounds with 18-π electronic structure. These compounds show structural similarities with porphyrins, represent notable properties such as high thermal-chemical stability, and high efficiency in electron transfer [9]. These green/blue-colored macrocyclic compounds are used in some applications due to their stability, assorted coordination properties and advanced spectroscopic characteristics [10]. Also they are used in some technological applications such as chemical sensors [11], liquid crystals [12], catalysts [13], non-linear optics [14], and as photosensitizers in photodynamic therapy (PDT) [15,16]. One of the main problems of phthalocyanines is their low solubility in common organic solvents or water. The solubility of these compounds in organic solvents can be increased by attaching long chain alkyl or alkoxy groups on the phthalocyanine skeleton [17–21] and also the solubility in aqueous solutions can be improved by substitution of some groups such as sulfonates, carboxylates, phosphonates or quaternized amino groups [22].
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Although water-soluble phthalocyanine photosensitizers are preferred for PDT, phthalocyanines which are soluble in DMF or DMSO (these solvents can be easily mixed with water) are widely used for that purpose as their photocatalytic activity decreases in neat water due to their aggregation behaviour. In recent years, photodynamic therapy (PDT) has been an important method of cancer treatment using three effective components; photosensitizer, light, and oxygen. The mechanism of PDT is based on the interaction between the excited photosensitizer and nearby molecules, and this interaction establishes the formation of singlet oxygen (1O2). It can damage the biological substrates and eventually lead to cell death [23]. Over the last few years, the hybridization or coupling of different coumarin derivatives with varied tetrapyrrolic macrocycle such as phthalocyanine, porphyrine and corrole molecules [24] has been performed and the chemical and physical properties of the resulting conjugates have been investigated. These macrocycles have showed remarkable properties such as good solubility, effective energy transfer, some biological activities, and well singlet oxygen generation ability due to the presence of coumarin molecules. Also another advantage of these hybrid macrocycles for PDT applications can be their “imaging” which depends on the excellent fluorescence properties of coumarins. For these reasons, we designed and synthesized novel phthalonitriles and their metallo-phthalocyanine (zinc and indium) derivatives by attaching a 7-hydroxy-3-(p-thiomethylphenyl) coumarin group and also studied their photophysicochemical properties in DMF as a potential
Corresponding author at: Gebze Technical University, Department of Chemistry, Gebze, 41400 Kocaeli, Turkey. E-mail addresses: [email protected], [email protected] (B. Köksoy).
https://doi.org/10.1016/j.ica.2019.119137 Received 14 July 2019; Received in revised form 6 September 2019; Accepted 6 September 2019 Available online 07 September 2019 0020-1693/ © 2019 Elsevier B.V. All rights reserved.
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candidate for PDT application.
m/z: calcd. 410.44, found 411.60 [M + H]+.
2. Synthesis
2.3. General synthesis of zinc(II) phthalocyanines (2a and 3a)
2.1. 7-Hydroxy-3(p-thiomethylphenyl) coumarin (1)
The phthalonitrile compounds (2 or 3) (0.1 g, 0.243 mmol) and Zn (CH3COO)2·2H2O (0.0133 g, 0.06075 mmol) were dissolved in a Schlenk tube in 2 mL of N,N-Dimethylaminoethanol (DMAE). The reaction mixture was stirred and heated at 160 °C for 16 h under an argon atmosphere. After cooling to room temperature, the green mixture was poured into 50 mL of hot water. Then, the precipitate was centrifuged and washed several times with hot water, acetic acid, methanol, ethanol, ethylacetate, diethylether and purified by column chromatography on silica gel using THF as an eluent and final product was dried in vacuum.
A mixture of 2,4-dihydroxybenzaldehyde (1.51 g, 10.9 mmol), p(thiomethylphenyl) acetic acid (2 g, 10.9 mmol), anhydrous NaOAc (1.36 g, 16.35 mmol) and 15 mL acetic anhydride was heated at 160 °C while stirring under nitrogen atmosphere for 10 h. After removal of acetic acid by distillation, the resulting solid was dissolved in 100 mL THF:methanol (3:1) mixture and then LiOH (1 g, 42 mmol) in 5 mL water was added to the suspension. About 3 h later, the reaction mixture was poured into 100 mL ice-water and treated with 10% HCl, the precipitate was collected by filtration. The dried product was purified by recrystallization from methanol. Yield 2.3 g (74.2%). Mp 230–232 °C. Anal. Calcd for C16H12O3S: C, 67.59; H, 4.25%; Found: C, 67.57; H, 4.22%. 1H-NMR (500 MHz, CDCl3): δH, ppm 8.13 (s, 1H, lactone-H), 7.66 (d, 2H, J = 8.09 Hz, Ar-H), 7.57 (d, 1H, J = 8.33 Hz, Ar-H), 7.31 (d, 2H, J = 8.11 Hz, Ar-H), 6.79 (d, 1H, J = 8.33 Hz, Ar-H), 6.72 (s, 1H, Ar-H), 3.41 (bs, 1H, ArOH), 2.50 (s, 3H, -SCH3). FT-IR (ATR): υmax, cm−1: 3209 (–OH), 3055–3034 (Ar-CH), 2926 (AliphaticCH), 1685 (lactone-C=O), 1605–1566 (Ar-C=C) and 809 (Ar-SCH3). UV–vis (THF): λmax = 352 nm. Florescence (THF): λem = 444 nm. MS (MALDI-TOF) m/z: calcd. 284.33, found 285.31 [M+H]+, 307.58 [M +Na]+.
2.3.1. 1(4), 8(11), 15(18), 22(25)-Tetrakis [7-oxy-3(pthiomethylphenyl)coumarino] phthalocyaninato zinc(II) (2a) Yield 28 mg (26.9%). Mp: > 300 °C. Anal. calcd. for C96H56N8O12S4Zn: C, 67.54; H, 3.30; N, 6.56%; found: C, 67.49; H, 3.26; N, 6.52%. 1H-NMR (500 MHz, DMSO‑d6): δH, ppm 8.41–7.15 (m, 44H, Ar-H), 2.52 (s, 12H, -SCH3). FT-IR (ATR): υmax, cm−1: 3073–3029 (Ar-CH), 2990–2911 (Aliphatic-CH), 1724 (lactone-C=O), 1607–1477 (Ar-C=C), 1275 (Ar-O-Ar) and 817 (Ar-SCH3). UV–vis (DMF): λmax, (log ε), 350 (5.08), 621 (4.32), 689 (5.06) nm. MS (MALDI-TOF) m/z: calcd. 1707.17, found 1707.18 [M]+. 2.3.2. 2(3), 9(10), 16(17), 23(24)-Tetrakis [7-oxy-3(pthiomethylphenyl)coumarino] phthalocyaninato zinc(II) (3a) Yield: 34 mg (32.7%). Mp: > 300 °C. Anal. calcd. for C96H56N8O12S4Zn: C, 67.54; H, 3.30; N, 6.56%; Found: C, 67.52; H, 3.25; N, 6.53%. 1H-NMR (500 MHz, DMSO‑d6): δH, ppm 8.39–7.16 (m, 44H, Ar-H), 2.52 (s, 12H, -SCH3). FT-IR (ATR): υmax, cm−1: 3067–3030 (Ar-CH), 2951–2864 (Aliphatic-CH), 1720 (lactone-C=O), 1602–1468 (Ar-C=C), 1260 (Ar-O-Ar) and 820 (Ar-SCH3). UV–vis (THF): λmax, (log ε), 354 (4.98), 610 (4.31), 677 (5.05) nm. MS (MALDI-TOF) m/z: calcd. 1707.17, found 1708.99 [M+H]+.
2.2. General synthesis of phthalonitrile derivatives (2 and 3) 7-Hydroxy-3(p-thiomethylphenyl) coumarin (1) (1.42 g, 5 mmol) and 3-nitrophthalonitrile or 4-nitrophthalonitrile (0.86 g, 5 mmol) were dissolved in 50 mL of dry dimethylformamide (DMF) under an argon atmosphere and anhydrous K2CO3 (1.04 g, 7.5 mmol) was added and this mixture was stirred for 48 h at 50–60 °C. After cooling to room temperature, the reaction mixture was treated with diluted HCl. The solid product was filtered, washed with water and dried. The crude product was purified by silica gel column chromatography using CHCl3 as an eluent.
2.4. General synthesis of indium(III)acetate phthalocyanines (2b and 3b) The phthalonitrile compounds (2 or 3) (0.1 g, 0.243 mmol) and In (CH3COO)3 (0.0177 g, 0.0607 mmol) were dissolved in a Schlenk tube in 2 mL of DMAE. The reaction mixtures were stirred and heated at 160 °C for 12 h under an argon atmosphere. After cooling to room temperature, the green mixture was poured into 50 mL hot water. Then, the precipitate was centrifuged and washed several times with hot water, methanol, ethanol, ethylacetate, diethylether and purified by column chromatography on silica gel using THF as an eluent and final product was dried in vacuum.
2.2.1. 7-(2,3-Dicyanophenoxy)-3(p-thiomethylphenyl) coumarin (2) Yield 1.87 g (91.1%). Mp 268–269 °C. Anal. calcd. for C24H14N2O3S: C, 70.23; H, 3.44; N, 6.83%; Found: C, 70.19; H, 3.41; N, 6.89%. 1HNMR (500 MHz, CDCl3): δH, ppm 8.29 (s, 1H, lactone-H), 7.94 (dd, 1H, J = 7.78 and 1.07 Hz, Ar-H), 7.87 (dd, 1H, J = 8.59 and 8.64 Hz, Ar-H), 7.86 (dd, 1H, J = 7.77 and 1.07 Hz, Ar-H), 7.67 (d, 2H, J = 8.65 Hz, ArH), 7.50 (dd, 1H, J = 8.56 and 1.14 Hz, Ar-H), 7.35 (d, 1H, J = 2.35 Hz, Ar-H), 7.33 (d, 2H, J = 8.69 Hz, Ar-H), 7.23 (dd, 1H, J = 8.55 and 2.42 Hz, Ar-H), 2.49 (s, 3H, -SCH3). FT-IR (ATR): υmax, cm−1: 3094–3038 (Ar-CH), 2923 (Aliphatic-CH), 2227 (Ar-CN), 1720 (lactone-C=O), 1614–1573 (Ar-C=C), 1278 (Ar-C-O) and 808 (ArSCH3). UV–vis (THF): λmax = 348 nm. Florescence (THF): λem = 461 nm. MS (MALDI-TOF) m/z: calcd. 410.44, found 411.58 [M +H]+, 429.16 [M+H+H2O]+.
2.4.1. 1(4), 8(11), 15(18), 22(25)-Tetrakis [7-oxy-3(pthiomethylphenyl)coumarino] phthalocyaninato indium(III)acetate (2b) Yield 37 mg (33.5%). Mp: > 300 °C. Anal. calcd. for C98H59N8O14S4In: C, 64.83; H, 3.27; N, 6.17%; found: C, 64.80; H, 3.24; N, 6.12%. 1H-NMR (500 MHz, DMSO‑d6): δH, ppm 8.54–7.17 (m, 44H, Ar-H), 2.44 (s, 12H, -SCH3), 2.35 (s, 3H, acetate-CH3). FT-IR (ATR): υmax, cm−1: 3075–3029 (Ar-CH), 2989–2919 (Aliphatic-CH), 1727 (lactone-C=O), 1609–1480 (Ar-C=C), 1275 (Ar-O-Ar) and 820 (ArSCH3). UV–vis (DMF): λmax, (log ε), 352 (5.01), 635 (4.34), 706 (5.03) nm. MS (MALDI-TOF) m/z: calcd. 1815.65, found 1910.56 [M–OAc–DHB]+, 1933.52 [M–OAc–DHB+Na]+.
2.2.2. 7-(3,4-Dicyanophenoxy)-3(p-thiomethylphenyl) coumarin (3) Yield 1.76 g (85.7%). Mp 205–206 °C. Anal. calcd. for C24H14N2O3S: C, 70.23; H, 3.44; N, 6.83% found: C, 70.20; H, 3.38; N, 6.91%. 1HNMR (500 MHz, CDCl3): δH, ppm 8.29 (s, 1H, lactone-H), 8.15 (d, 1H, J = 8.74 Hz, Ar-H), 7.93 (d, 1H, J = 2.52 Hz, Ar-H), 7.85 (d, 1H, J = 8.60 Hz, Ar-H), 7.67 (d, 2H, J = 8.67 Hz, Ar-H), 7.56 (dd, 1H, J = 8.71 and 2.58 Hz, Ar-H), 7.32 (d, 2H, J = 8.70 Hz, Ar-H), 7.31 (d, 1H, J = 2.38 Hz, Ar-H), 7.18 (dd, 1H, J = 8.61 and 2.34 Hz, Ar-H), 2.50 (s, 3H, -SCH3). FT-IR (ATR): υmax, cm−1: 3062–3034 (Ar-CH), 2923 (Aliphatic-CH), 2230 (Ar–CN), 1720 (lactone-C=O), 1615–1589 (ArC=C), 1254 (Ar-C-O) and 820 (Ar-SCH3). UV–vis (THF): λmax = 350 nm. Florescence (THF): λem = 472 nm. MS (MALDI-TOF)
2.4.2. 2(3), 9(10), 16(17), 23(24)-Tetrakis [7-oxy-3(pthiomethylphenyl)coumarino] phthalocyaninato indium(III)acetate (3b) Yield 41 mg (37.1%). Mp: > 300 °C. Anal. calcd. for C98H59N8O14S4In: C, 64.83; H, 3.27; N, 6.17%; found: C, 64.79; H, 3.23; N, 6.15%, 1H-NMR (500 MHz, DMSO‑d6): δH, ppm 8.38–7.20 (m, 44H, 2
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Scheme 1. Synthetic pathway of the phthalonitriles (2 and 3) and phthalocyanines (2a-b and 3a-b) including 7-oxy-3-(p-thiomethylphenyl)coumarin groups. i) 3-nitro-1,2-dicyanobenzene, K2CO3, DMF, 50–60 °C ii) 4-nitro-1,2-dicyanobenzene, K2CO3, DMF, 50–60 °C, iii) Zn(OAc)2·2H2O, DMAE, 160 °C, iv) In(OAc)3, DMAE, 160 °C.
The 1H-NMR spectra of 1–3 showed resonance bands at 8.13–6.72 ppm (for 1), 7.94–7.23 ppm (for 2) and 8.15–7.18 ppm (for 3). The lactone proton (at 4-position of the coumarin skeleton) was assigned to a singlet in lower field than other aromatic protons at 8.13 ppm for 1 and 8.29 ppm for both phthalonitrile compounds (2 and 3). The thiomethyl protons on the phenyl group of coumarin moiety were observed at 2.50 ppm for 1, 2.49 ppm for 3 and 2.50 ppm for 2 as singlet peaks. The MALDI-TOF mass spectra of compounds 1–3 showed m/z peaks at 285.31 for [M+H]+ and at 307.58 for [M+Na]+ for compound 1, at 411.58 m/z for [M+H]+ and at 429.16 m/z for [M+H +H2O]+ for compound 2 and at 411.60 m/z for [M+H]+ for compound 3. The peaks appearing at 2227 cm−1 for 2 and 2230 cm−1 for 3 disappeared in the FT-IR spectra of the metallophthalocyanines 2a-b and 3a-b as expected. This is an important clue concerning the formation of the phthalocyanine macrocycle from the corresponding phthalonitriles. The typical ester carbonyl (lactone ring) vibration was observed in the range of 1727–1720 cm−1 for all metallophthalocyanines (2a-b and 3a3b). The aromatic C-H and aliphatic C-H stretching peaks for all synthesized phthalocyanines appeared between 3073 and 3029 cm−1 and 2990–2864 cm−1, respectively. Another typical band (Ar-O-Ar) was observed at 1275 cm−1 for non-peripherally (2a-b) and 1260–1261 cm−1 for peripherally (3a-b) substituted phthalocyanines. The ground-state electronic spectra of phthalocyanines have two clear bands, one of which is observed in the range of 650–750 nm and another one appearing at nearly 300 nm. In this work, each metallophthalocyanine derivative exhibited a sharp-single Q band at 689 nm for 2a, at 706 nm for 2b, at 677 nm 3a and at 687 nm for 3b in their ground-state electronic spectra. B bands of these phthalocyanines were observed within the range of 350–356 nm (Fig. 1). The 1H-NMR spectra of zinc(II) (2a and 3a) and indium(III) acetate (2b and 3b) phthalocyanines bearing coumarin groups showed characteristic aromatic (phthalocyanine-H and coumarin-lactone-H) and aliphatic (–SCH3) protons for each phthalocyanine. The Ar-H peaks were assigned between 8.54 and 7.15 ppm for all synthesized phthalocyanines. The aliphatic protons of the –SCH3 group were observed at 2.44 ppm for indium (III)acetate (2b-3b) and 2.52 ppm for zinc(II) (2a3a) phthalocyanines. Additionally, the singlet peaks were observed only for the indium complexes at 2.35 ppm for 2b and at 2.88 ppm for 3b were assigned to their acetate groups.
Ar-H), 2.44 (s, 12H, -SCH3), 2.88 (s, 3H, acetate-CH3). FT-IR (ATR): υmax, cm−1: 3068–3030 (Ar-CH), 2990–2918 (Aliphatic-CH), 1725 (lactone-C=O), 1603–1471 (Ar-C=C), 1261 (Ar-O-Ar) and 818 (ArSCH3). UV–vis (DMF): λmax, (log ε) 356 (5.16), 617 (4.36), 687 (5.05) nm. MS (MALDI-TOF) m/z: calcd. 1815.65, found 1815.37 [M]+, 1910.47 [M−OAc+DHB]+.
3. Results and discussion 3.1. Synthesis and characterization Scheme 1 points out the synthesis methodology for the novel 7hydroxy-3(p-thiomethylphenyl) coumarin (1) which was prepared in a Perkin condensation of 2,4-dihydroxybenzaldehyde with p-(thiomethylphenyl)acetic acid. The target phthalonitrile precursors 7-(2,3dicyanophenoxy)-3(p-thiomethylphenyl) coumarin (2) and 7-(3,4-dicyanophenoxy)-3(p-thiomethylphenyl) coumarin (3) were obtained from the SNAr reaction between 3-/4-nitrophthalonitrile with 7-hydroxy-3(p-thiomethylphenyl) coumarin (1). The metallo-phthalocyanines (2a, 2b, 3a and 3b) were synthesized with anhydrous zinc(II) and indium(III) metal salts using the phthalonitrile precursors (2 or 3) in dry DMAE (Scheme 1). Various spectroscopic characterization techniques such as UV/Vis, IR, 1H-NMR spectroscopy and MALDI-TOF mass spectrometry were used for the characterization of the newly synthesized compounds. The results obtained from these techniques are compatible with the proposed structures for all the newly prepared compounds. The FT-IR spectrum of 7-hydroxy-3(p-thiomethylphenyl) coumarin (1) exhibits characteristic peaks at 1720 cm−1 (for lactone -C=O), 1600 cm−1 (for -C=C), 3209 cm−1 (for aromatic-OH). The obtained peaks between 3070 and 3050 cm−1 for aromatic C-H and 1591–1465 cm−1 for aromatic C=C also confirmed the structure of the coumarin (1). The vibration bands were observed at 3094–3034 cm−1 (aromatic C-H), 2923 cm−1 (aliphatic C-H), 2230 and 2227 cm−1 (CN), 1720 cm−1 (lactone C=O), 1615–1573 cm−1 (aromatic C=C) and 1278–1254 cm−1 (Ar-O-Ar) for phthalonitrile compounds 2 and 3. Compared to the FT-IR spectrum of 1, a disappearance of the OH stretching band was observed, as was the appearance of an intense vibration (C≡N) at 2227 cm−1 for 2 and 2230 cm−1 for 3 that are the proof of formation the corresponding phthalonitriles. 3
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Fig. 3. Ground-state electronic absorption spectra of phthalocyanine 3a in DMF at different concentration (2 × 10−6–12 × 10−6 M). (Inset: Concentration versus absorbance).
Fig. 1. Ground-state electronic absorption spectra of synthesized zinc(II) and indium(III) phthalocyanines in DMF.
3.3. Fluorescence studies In recent years, fluorescence and fluorescent molecules have been important for PDT. In particular, fluorescent molecules may play a key role for the in vivo studies of 3rd generation photosensitizers to monitor how these molecules move in the body and whether they accumulate in the cancer cell. Therefore, the fluorescence behaviour of the photosensitizers is important. The fluorescence properties were investigated to understand which molecule may be suitable for imaging and to determine to fluorescence quantum yield and lifetime. Fig. 4 shows fluorescence emission, absorption and excitation spectra of compound 2a in DMF as an example for the studied zinc(II) phthalocyanines. Fluorescence emission data for all studied phthalocyanines are given in Table 1. Both zinc(II) phthalocyanines (2a and 3a) showed nearly the same fluorescence behaviour in DMF. The excitation spectra were similar to the absorption spectra, and both were mirror images of the fluorescence spectra for these phthalocyanines (2a and 3a) in DMF (Fig. 4 as an example for 2a). It is obvious that the similarity of the Qband absorption and the Q band maxima of the excitation spectra for these phthalocyanines suggest that the nuclear configurations of the ground and excited states are almost the same and are not affected by excitation. There was no emission peak in the fluorescence spectra of the indium(III) phthalocyanines (2b and 3b) bearing 7-oxy-3-(p-thiomethyl) phenyl coumarin group because of the heavy atom effect of the indium metal in the phthalocyanine cavity.
Fig. 2. MALDI-TOF spectrum of phthalocyanine 2a.
The MALDI-TOF spectra of 2a, 3a and 2b, 3b were recorded using 2,5-dihydroxybenzoic acid matrix. While compounds 2a (Fig. 2) and 3a showed only the molecular ion peak [M]+ and [M+H]+ in their spectra, the phthalocyanines 2b and 3b showed [M+−OAc+DHB] peaks. The molecular ion peaks (m/z) were detected at 1707.18 Da for 2a, at 1708.99 Da for 3a, at 1910.56 Da for 2b, and at 1815.37 and 1910.47 Da for 3b.
700 0.6
600
Aggregation is one of the most encountered disadvantages of phthalocyanines and it affects both photophysical, photochemical and electrochemical properties which depend on some conditions such as concentration, temperature, substituents and solvents [25]. In this study, the aggregation properties of zinc(II) and indium(III) acetate phthalocyanines including 7-oxy-3-(p-thiomethyl) phenyl coumarin (2a-b and 3a-3b) were examined at 12-2 × 10−6 concentration range in DMF (Fig. 3 as an example for 3a). The Beer-Lambert law was fitted for the studied phthalocyanines (2a-b, 3a-b) in the 12 × 10−6 to 2 × 10−6 M concentration range. There was no indication for an aggregation of these coumarin-substituted zinc and indium metallophthalocyanines in DMF.
Emission
Intensity(a.u)
500
0.5
Exicitation
400
0.4
Absorption 0.3
300 200
0.2
100
0.1
0 500
Absorption
3.2. Aggregation studies
0 550
600 650 700 Wavelength(nm)
750
800
Fig. 4. Electronic absorption, fluorescence emission and excitation spectra of the phthalocyanine 2a in DMF. (Excitation wavelength = 650 nm). 4
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Table 1 Photophysicochemical data for 7-oxy-3-(p-thiomethylphenyl)coumarin substituted zinc(II) and In(III) acetate phthalocyanines in DMF. Compound
Q band λmax, (logε)
Emission wavelength λem
ΦF
τF(ns)
Φd(×10−5)
ΦΔ
2a 2b 3a 3b StdZnPc [25] StdInOAcPc [31]
689 706 677 687 670 683
701 – 685 – 676 693
0.12 – 0.09 – 0.17 0.019
2.48 – 2.02 – 1.03 1.66
30.95 30.27 22.61 18.66 2.33 54.07
0.81 0.87 0.78 0.85 0.56 0.75
(5.06) (5.03) (5.05) (5.05) (5.37) (4.90)
The fluorescence quantum yields (ΦF) of compounds 2a and 3a are listed in Table 1. The ΦF values of the indium(III) phthalocyanines (2b and 3b) were not evaluated because these phthalocyanines did not produce any emission in their fluorescence studies. Both zinc(II) phthalocyanines including the 7-oxy-3-(p-thiomethyl) phenyl coumarin group showed lower ΦF values than an unsubstituted zinc(II) phthalocyanine (StdZnPc) (ΦF = 0.17 [26]) which was used as a standard for the fluorescence quantum yield calculations. The zinc(II) phthalocyanine derivative 2a showed a higher fluorescence quantum yield than its counterpart 3a in DMF. The fluorescence lifetimes (τF) were determined by the time-correlated photon counting (TCSPC) method in DMF and the τF values are given in Table 1. Only zinc(II) phthalocyanines (2a and 3a) have measurable fluorescence lifetimes due to non-fluorescent behaviour of the indium(III) phthalocyanines (2b and 3b) again. The TCSPC fluorescence decay curve of phthalocyanine 2a in DMF is given in Fig. 5 as an example. The τF values of the coumarin-substituted zinc(II) phthalocyanine complexes (2a and 3a) amount to 2.48 and 2.02 ns, respectively. The obtained τF values for these phthalocyanines are higher compared to the standard zinc(II) phthalocyanine (1.03 ns [26]) in DMF. Both fluorescence quantum yield and lifetime of the novel zinc(II) phthalocyanines (2a and 3a) were found similar to other coumarin substituted zinc(II) phthalocyanines’ values given in the literature [27,28] and are higher than those of fluorophenylcoumarin-substituted phthalocyanine counterpart given in the literature [29].
Fig. 6. The absorption spectral changes during the determination of singlet oxygen quantum yields. This determination was for compound 3a in DMF at a concentration of 1 × 10−5 M. (Inset: Plot of DPBF absorbance versus time).
and 3b were studied and calculated in DMF by a chemical method using 1,3-diphenylisobenzofuran (DPBF) as a quencher. The decrease of the absorbance of DPBF at 414 nm was observed using a UV–Vis spectrophotometer. No change was not observed in the Q band shapes and intensities of phthalocyanines 2a-b and 3a-b suggesting that these phthalocyanines do not decompose during the singlet oxygen measurements (Fig. 6). The ΦΔ values of the phthalocyanine compounds 2ab and 3a-3b were found higher than those of standard zinc(II) (StdZnPc) and indium(III) acetate (StdInOAcPc) phthalocyanines in DMF (Table 1), suggesting that the substitution of the coumarin groups on the phthalocyanine ring increased the singlet oxygen generation of the target photosensitizers. So, in this work, the studied indium(III) acetate phthalocyanines (2b and 3b) showed higher singlet oxygen quantum yields than their zinc(II) phthalocyanine (2a and 3a) counterparts. This means that the indium(III) acetate phthalocyanines 2b and 3b including 7-oxy-3-(p-thiomethyl) phenyl coumarin moieties generate more singlet oxygen than the zinc(II) phthalocyanine derivatives 2a and 3a. The higher singlet oxygen production capability of the indium(III) phthalocyanines is due to the heavy atom effect of indium. The heavy atom encourages an intersystem crossing between the excited singlet state and triplet state of the photosensitizers. Also, the nonperipherally substituted indium(III) phthalocyanine (3b) (ΦΔ = 0.85) (Table 1), which may be result of the absorption of light at longer wavelength. The obtained singlet oxygen quantum yields of the novel phthalocyanines (2a-b and 3a-b) were found to be higher than those of 3phenyl coumarin-substituted phthalocyanines according to the results reported in the literature [27,28,30].
3.4. Singlet oxygen studies The Singlet oxygen quantum yields (ΦΔ) for compounds 2a, 2b, 3a
3.5. Photodegradation studies Fig. 5. Time correlated single photon counting (TCSPC) fluorescence decay curve of phthalocyanine 2a in DMF.
Photostability is another property important for PDT and other photocatalytic applications. Under strong light irradiation, 5
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general analysis methods and elemental analysis as well. The photophysicochemical properties of the phthalocyanines were investigated in DMF. The effect of the position of the substituents on the phthalocyanine macrocycle (non-peripheral or peripheral) and the effect of the metal ion in the phthalocyanine center (zinc or indium) on these properties were also determined. All phthalocyanines formed monomeric species in DMF. Although 7-oxy-3-(p-thiomethyl) phenyl coumarin-substituted zinc(II) phthalocyanines (2a and 3a) showed a similar fluorescence behaviour in DMF, the indium(III) derivatives (2b and 3b) did not show any fluorescence emission due to heavy atom effect of the indium central metal in the phthalocyanine cavity. The results showed that all novel phthalocyanines (2a-b and 3a-3b) generated singlet oxygen. Especially the non-peripherally substituted indium(III) acetate derivative (2b) showed the highest singlet oxygen quantum yield (ΦΔ = 0.87) due to higher intersystem crossing behaviour of the large indium atom in the phthalocyanine cavity. All studied phthalocyanines (2a-b and 3a-3b) showed moderate stability which is suitable for photodynamic activity. Finally, the studied coumarinophthalocyanines showed good photophysical and photochemical properties, particularly singlet oxygen generation, making them good candidates for PDT applications.
Fig. 7. The absorption spectral changes of phthalocyanine 2a in DMF under light irradiation showing the disappearance of the Q-band at ten minutes intervals. (Inset: Plot of absorbance versus time).
Acknowledgment
photosensitizers suitable for PDT must be stable. Generally, phthalocyanines show good resistance against light irradiation. In this study, the photodegradation of the phthalocyanines was monitored by ground state electronic spectroscopy. The decrease of the Q band absorption peak without any decomposition of its shape proves that the photodegradation is not associated with a phototransformation into different forms of the phthalocyanines absorbing in the visible region (Fig. 7). The photodegradation quantum yields (Φd) of the phthalocyanine compounds (2a-b and 3a-b) are supplied in Table 1. The values for the standard zinc(II) and indium(III) acetate phthalocyanines are also given in this table for determination of the effect of the substitution on the photodegradation behaviour. Table 1 shows that the zinc(II) phthalocyanines including coumarin groups (2a and 3a) are less stable to degradation compared to standard ZnPc in DMF. Similarly, the Φd values of these substituted zinc(II) phthalocyanines (Φd = 30.95 × 10−5 for 2a and Φd = 22.61 × 10−5 for 3a) were found higher than those of the unsubstituted ZnPc (Φd = 2.33 × 10−5). So, the attachment of 7-oxy-3(p-thiomethylphenyl) coumarin groups to ZnPc seems to decrease the stability of the complexes in DMF. In contrast, the peripherally and nonperipherally substituted indium(III) acetate complexes (2b and 3b) are more stable than the standard indium(III) acetate phthalocyanine because the Φd values of these substituted indium(III) acetate phthalocyanines (Φd = 30.27 × 10−5 for 2b and Φd = 18.66 × 10−5 for 3b) were found to be lower than those of the standard InOAcPc (Φd = 54.05 × 10−5). The photostability of the indium(III) acetate phthalocyanines (2b and 3b) is lower than that of the zinc(II) phthalocyanine counterparts (2a and 3a) due to the out of cavity behaviour of the larger indium(III) atom. The substitution of the 7-oxy-3-(p-thiomethylphenyl) coumarin groups on the peripheral positions of the phthalocyanine macrocycle produced more stable phthalocyanine derivatives compared to the substitution of this group to the non-peripheral positions. All synthesized zinc(II) and indium(III) acetate phthalocyanines bearing coumarin groups (2a-b and 3a-b) showed similar stabilities with Φd values in the same order of magnitude (about 10−4 − 10−5) as those of corresponding phthalocyanines containing different coumarin substituents [27,29].
We are thankful to the Research Foundation of Marmara University, Commission of Scientific Research Project (BAPKO) FEN-A100713–0327. Appendix A. Supplementary data Supplementary data to this article can be found online at https:// doi.org/10.1016/j.ica.2019.119137. References [1] R.A. Irgashev, A.A. Karmatsky, P.A. Slepukhin, G.L. Rusinov, V.N. Charushin, Tetrahedron Lett. 54 (2013) 5734–5738. [2] A.M. Hamdy, N. Eleya, H.H. Mohammed, Z. Khaddour, T. Patonay, A. Villinger, P. Langer, Tetrahedron Lett. 54 (2013) 3568–3571. [3] H.M.H. Belal, M.K. Gasser, M.K. Rasha, M. Bulut, Spectrochim. Acta A: Mol. Biomol. Spect. 158 (2016) 34–42. [4] T.O. Olomola, S. Mosebi, R. Klein, T.T. Johnstone, J. Coates, R. Hewer, P.T. Kaye, Bioorg. Chem. 57 (2014) 1–4. [5] M. Basanagouda, V.B. Jambagi, N.N. Barigidad, S.S. Laxmeshwar, V.D. Narayanachar, Eur. J. Med. Chem. 74 (2014) 225–233. [6] Y. Tada, Y. Shikishima, Y. Takaishi, H. Shibata, T. Higuti, G. Honda, M. Ito, Y. Takeda, O.K. Kodzhimatov, O. Ashurmetov, Y. Ohmoto, Phytochemistry 59 (2002) 649–654. [7] J.B. Veselinovic, A.M. Veselinovic, Z.J. Vitnik, V.D. Vitnik, G.M. Nikolic, Chem. Biol. Int. 214 (2014) 49–56. [8] H.A. El-Wahaba, M.A. El-Fattahb, N.A. El-Khalikc, H.S. Nassara, M.M. Abdelalla, Prog. Org. Coat. 77 (2014) 1506–1511. [9] N.B. McKeown, Phthalocyanine Materials: Synthesis, Cambridge University Press, Cambridge, Structure and Function, 1998. [10] A. Lever, E. Milaeva, The Phthalocyanines, Properties and Applications Vol. 2 (1992) 162–227. [11] G. Guillaud, J. Simon, J.P. Germain, Coord. Chem. Rev. 180 (1998) 1433–1484. [12] T. Basova, A. Hassan, M. Durmuş, A.G. Gürek, V. Ahsen, Coord. Chem. Rev. 310 (2016) 131–153. [13] C. Huang, R. Liu, W. Yang, C. Zhang, H. Zhu, Inorg. Chim. Acta 467 (2017) 307–315. [14] G.D.L. Torre, P. Vazquez, F.A. Lopez, T. Torres, J. Mater. Chem. 8 (1998) 1671–1683. [15] T. Stuchinskaya, M. Moreno, M.J. Cook, D.R. Edwards, D.A. Russell, Photochem. Photobiol. Sci. 10 (2011) 822–831. [16] R.F. Donnelly, P.A. McCarron, M.M. Tunney, Microbiol. Res. 163 (2008) 1–12. [17] C.C. Leznoff, A.B.P. Lever, Phthalocyanines Properties and Applications, VCH, Weinheim, 1989. [18] Ö. Bekaroglu, Appl. Organomet. Chem. 10 (1996) 605–622. [19] M.J. Cook, A.J. Dunn, S.D. Howe, A.J. Thomson, K.J. Harrison, J. Chem. Soc. Perkin Trans. 1 (1988) 2453–2458. [20] P.M. Burnham, M.J. Cook, L.A. Gerrard, M.J. Heeney, D.L. Hughes, Chem. Commun. 16 (2003) 2064–2065. [21] H. Ali, J.E. Van Lier, Chem. Rev. 99 (1999) 2379–2450. [22] F. Dumoulin, M. Durmuş, V. Ahsen, T. Nyokong, Coord. Chem. Rev. 254 (2010)
4. Conclusion In this study, novel zinc(II) and indium(III) acetate phthalocyanines bearing four 7-oxy-3-(p-thiomethyl) phenyl coumarin groups were synthesized. These novel compounds were fully characterized by 6
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