New water-soluble cationic indium (III) phthalocyanine bearing thioquinoline moiety;Synthesis,photophysical and photochemical studies with high singlet oxygen yield

Abstract

The synthesis and characterization of (4) - tetra[2-thioquinoline]phthalocyaninato indium (III) (2) and quaternized (4)- tetra[2-thioquinoline]phthalocyaninato indium (III) (3), are described. Photochemical and photophysical properties of 2 and 3 in DMSO; and of 3 in water are also presented. A comparison between the photophysical and photochemical parameters of 2 and 3 showed that 2 is a better photosensitizer than 3. The quantum yield values of fluorescence (Φ_F), and singlet oxygen formation (Φ_Δ) for 2 are 0.012 and 0.74, respectively. These values are higher than those for 3, which exhibited the values 0.006 and 0.66, respectively. The values for 3 in aqueous solution are 0.002 and 0.17 (0.42 plus Triton X-100) respectively due to aggregation behavior in the solution, and these values suggest that indium phthalocyanine 2 and its water-soluble derivative 3 can find use as photosensitizer in the photodynamic therapy (PDT) of cancer.

Keywords

Indium (III) phthalocyanine photochemistry singlet oxygen photophysics

1 Introduction

Phthalocyanines (Pc) are among the most remarkable molecules of recent times in many fields of technical application such as semiconductors, electrochemical sensors, electrochromic materials, dye sensitized solar cells (DSSC), nonlinear optics, and photocatalytic degradation of environment pollutants and photodynamic therapy of cancer (PDT) [1 –5]. Their high conjugation, molar absorption coefficient, chemical and physical stability make these molecules even more special for the applications.

PDT is based on the administration of a non-toxic photosensitizer to the cancer cells followed by activation by light of suitable wavelength. The light excitation of a photosensitizer which induces a localized oxidative damage within the cells by formation of highly reactive oxygen species, the most important of which is singlet oxygen [6]. Photosensitized oxidations involving singlet oxygen are implicated in a variety of areas such as photodegradation of dyes, DNA damage, and are responsible for tumor necrosis in PDT. The photosensitizers are usually aromatic molecules such as porphyrin, phthalocyanines, boron dipyrromethene that can form long-lived triplet excited states and have high singlet oxygen quantum yields [7, 8]. An important consideration when designing molecules for PDT is the presence of a heavy central metal ion, substituent, and the number of charges that the molecule possesses [9].

There is a need for phthalocyanine complexes with improved photophysicochemical properties. Modifications in the Pc macrocycle can be made by incorporation of targeted substituents, metal atom ions and nano particles etc. Hence this study focuses on the influence of thioquinoline groups as substituent which is linked to Pc with sulfur bridge and heavy indium as central atom on the photophysical and photochemical properties of new complexes (2 and 3). It has been shown in previous studies that the phthalocyanine molecules with this property have shown better photochemical properties [10 –14]. However, studies on water-soluble indium phthalocyanine (InPc) derivatives are scarce in the literature [15]. In particular, for photodynamic therapy applications, the medicine is injected into the patient’s blood stream, and since the blood itself is a hydrophilic system, water solubility becomes crucial for a potential photosensitizers in PDT. Due to their ability to their photo activation properties makes phthalocyanines potential anticancer agents [16].

The quinolines and their derivatives are significant compounds which exhibit diverse biological activities due to their ring systems [17 –19]. A large variety of quinolines are reported to exhibit substantial anti-cancer activity [20 –24] through a variety of mechanisms.

It has been given in the literature that some quinolines derivatives give good photochemical results for photodynamic therapy applications [6 , 26].

This work investigates the photosensitizing tendencies of a In^3 + tetra thioqinoline substituted phthalocyanine and its quaternized derivative (Scheme 1). The effect of the substituent and solvent on the photophysical and photochemical properties of the new complexes will also be discussed. The solvents studied are: dimethylsulfoxide (for 2 and 3) and water (for 3). The combination of quaternizable thioqinoline group and heavy indium atom in the designed phthalocyanine compounds improve solubility of 3 in water and enhance intersystem crossing, hence large singlet oxygen quantum yield in DMSO and aqueous media [15].

Scheme 1

Synthetic route of (4)- tetra[2-thioquinoline]phthalocyaninato indium (III) (2) and its quaternized derivative (3), (i) Anhydrous InCl₃, n-pentanol, 7 h, argon atm, (ii) DMS, dry DMF, 12 h, argon atm.

2 Experimental

2.1 Equipments

UV/Vis spectra were recorded on a Cary 500 UV-Vis/NIR spectrophotometer. Fluorescence excitation and emission spectra were recorded on a Varian Eclipse spectrofluoremeter using 1 cm pathlength cuvettes at room temperature. IR spectra (KBr pellets) were recorded on a Bio-Rad FTS 175 C FTIR spectrometer. ¹H NMR spectra were recorded in DMSO-d₆ solutions on a Varian 500 MHz spectrometer. Positive ion and linear mode MALDI-MS spectra of complexes were obtained in Dithranol (DIT) for non-ionic complex (2) and dihydroxybenzoic acid for ionic complex (3) as MALDI matrix using nitrogen laser accumulating 50 laser shots using Bruker Microflex LT MALDI-TOF mass spectrometer. Photo-irradiations were performed using a General Electric quartz line lamp (300 W). A 600 nm glass cut off filter (Schott) and a water filter were used to filter off ultraviolet and infrared radiations respectively. An interference filter (Intor, 670 nm or 700 nm with a band width of 40 nm) was additionally placed on the light path before the sample. Light intensities were measured with a POWER MAX5100 (Molelectron detector incorporated) power meter.

2.2 Materials

Zinc(II) phthalocyanine (ZnPc), chlorophyll a, 1,3-diphenylisobenzofuran (DPBF), zinc tetrasulfophthalocyanine (ZnPcS₄), Thioquinoline, dimethylsulphoxide (DMSO) and dimethylformamide (DMF), methanol, n-hexane, chloroform (CHCl₃), dichloromethane (DCM), tetrahydrofuran (THF), acetone, ethanol, Indium (III) chloride, K₂CO₃, dimethylsulphate (DMS) and Triton X-100 were purchased from Aldrich. 9,10-Antracenediyl-bis(methylene)dimalonic acid (ADMA) was purchased from Fluka. 4-[2-thioquinoine]-phthalonitrile (1) has been reported before [27].

3 Photophysical parameters

3.1 Fluorescence quantum yields and lifetimes

Fluorescence quantum yields (Φ_F) were determined in DMSO by the comparative method using by equation 1 [28, 29].

$Φ F = Φ F (Std) \frac{F . AStd . n^{2}}{FStd . A . n_{Std}^{2}}$ (1)

where F and F_Std are the areas under the fluorescence emission curves of the samples (2,3) and the standard, respectively. A and A_Std are the respective absorbances of the samples and standard at the excitation wavelengths, respectively. n² and $n_{Std}^{2}$ are the refractive indices of solvents used for the samples and standard, respectively. Unsubstituted ZnPc (Φ_F = 0.20) [30] was employed as the standard in DMSO. The absorbance of the solutions at the excitation wavelength ranged between 0.04 and 0.05.

4 Photochemical parameters

4.1 Singlet oxygen quantum yields

Singlet oxygen quantum yield (Φ_Δ) determinations are carried out using the experimental set-up described in literature in DMSO and water [31 –33]. Typically, a 3 mL portion of the respective standard ZnPc and sample [33] solutions (C = 1×10^–5 M) containing the singlet oxygen quencher was irradiated in the Q band region with the photoirradiation set-up described in the references [31 –33]. Φ_Δ values were determined in air using the relative method with ZnPc as standard in DMSO. 1,3-Diphenylisobenzofuran (DPBF) and 9,10-Antracenediyl-bis(methylene)dimalonic acid (ADMA) was used as chemical quencher for singlet oxygen. Equation 2 was employed for the determination of Φ_Δ values:

$Φ_{Δ} = Φ_{Δ}^{Std} \frac{R . I_{abs}^{Std}}{R^{Std} . I_{abs}}$ (2)

where $Φ_{Δ}^{Std}$ is the singlet oxygen quantum yields for the standards ZnPc $(Φ_{Δ}^{Std} = 0.67 in DMSO)$ and ZnPcS $(Φ_{Δ}^{Std} = 0.56 in water)$ [34]. R and R_Std are the DPBF and ADMA photobleaching rates in the presence of the respective samples and standards, respectively. I_abs and $I_{abs}^{Std}$ are the rates of light absorption by the samples and standard, respectively. To avoid chain reactions induced by quencher (DPBF and ADMA) in the presence of singlet oxygen, the concentration of quencher (DPBF and ADMA) was lowered to ∼3×10^–5 M [35]. Solutions of sensitizer (C = 1×10^–5 M) containing quencher (DPBF and ADMA) were prepared in the dark and irradiated in the Q band region. DPBF and ADMA degradation at 417 and 380 nm were monitored respectively. The light intensity 6.21×10¹⁵ photons s^–1 cm^–2 was used for Φ_Δ determinations.

4.2 Photodegradation quantum yields

Photodegradation quantum yield (Φ_d) determinations are carried out using the experimental set-up described in the literature [31 –33]. Photodegradation quantum yields were determined using equation 3 in DMSO.

$Φ_{d} = \frac{(C_{0} - C_{t}) . V . N_{A}}{I_{abs} . S . t}$ (3)

where C₀ and C_t are the samples concentrations before and after irradiation, respectively. V is the reaction volume, N_A the Avogadro’s constant, S the irradiated cell area and t the irradiation time, I_abs is the overlap integral of the radiation source light intensity and the absorption of the samples. A light intensity of 2.17×10¹⁶ photons s^–1 cm^–2 was employed for Φ_d determinations.

5 Synthesis

5.1 4-[2-Mercaptoquinoline]-phthalonitrile (1)

Were prepared, purified and characterized according to literature procedure [6].

5.2 (4)- tetra[2-thioquinoline]phthalocyaninato indium (III) (2)

A mixture of anhydrous indium (III) chloride (0.77 g, 3.48 mmol), phthalonitrile (1) (1.00 g, 3.48 mmol) and n-pentanol (3 mL) was stirred at 160C for 7 h under argon atmosphere. After cooling, the solution was dropped in n-hexane. The green solid product was precipitated and collected by filtration and washed successively with methanol, ethanol and n-hexane. The crude product was purified with column chromatography (silica gel) using DCM-THF (3:0.5) solvent system. Yield: 0.7 g (61%). UV/Vis (DMSO): λ_max nm (log ɛ) 339 (3.89), 629 (3.36), 698.50 (4.00). IR [(KBr) ν_max/cm^–1]: 3055(Ar–CH), 1587(C = C), 1494, 1446, 1331, 1224, 1121(C-S-C), 941, 778, 706. ¹H-NMR (DMSO-d₆): δ, ppm 9.35–7.91 (36 H, m, Pc–H and quinoline-H). Calc. for C₆₈H₃₆ClN₁₂S₄In: MALDI–TOF–MS m/z: Calc. 1299; Found [M–Cl+DIT+3H]⁺ 1487, [M–Cl]⁺ 1262.3.

5.3 Quarternarized (4)- tetra[2-thioquinoline]phthalocyaninato indium (III) (3)

This complex was prepared according to the method previously reported by Smith et al. [6]. Compound 3 (50 mg, 0.032 mmol) was heated to 120C in freshly distilled DMF (3 ml) and excess dimethyl sulphate (0.1 ml) was added dropwise. The mixture was stirred at 120C for 12 h. After this time, the mixture was cooled to room temperature and the product was precipitated with hot acetone and collected by filtration. The green solid product was washed successively with hot ethyl acetate, ethanol, chloroform, dichloromethane, THF, n-hexane and diethylether. The resulting hygroscopic product was dried over phosphorous pentoxide. Yield: 0.06 g (63%). UV/Vis (DMSO):λ_max nm (log ɛ) 363 (3.89), 699.50 (4.45). IR [(KBr) ν_max/cm^–1]: 3061 (Ar-CH), 2962 (CH), 1594 (C = C), 1488, 1382, 1308 (S = O), 1130 (C-S-C), 1092 (S = O), 742, 637 (S–O). ¹H-NMR (DMSO): δ, ppm 9.21–7.58 (36 H, m, Pc–H and quinoline-H), 4.24 (12 H, s, CH₃). Calc. for C₇₂H₄₈ClN₁₂O₈S₆In MALDI–TOF–MS m/z: Calc. 1551.2; Found; 1574.3 [M + Na]⁺, 1517.4 [M–Cl+H]⁺, 1447.9 [M–2CH₃–SO₄ + Na]⁺, 1390 [M–Cl–2CH₃–SO₄]⁺.

6 Results and discussion

6.1 Synthesis and characterization

The preparation of phthalocyanine derivatives from the aromatic nitriles occurs under different reaction conditions. The synthesis of indium phthalocyanine complex (2) was achieved by treatment of phthalonitrile 1 with anhydrous InCl₃ in dry n-pentanol (Scheme 1). Column chromatography with silica gel was employed to obtain the pure products from the reaction mixtures.

Quaternization of indium phthalocyanine compound (3) was achieved by reaction with excess dimethylsulphate (DMS) as quaternization agent in dry DMF at 120C. Yield of the product was 82% for 3. After reaction with DMS, the quaternized indium complex (3) is highly soluble in water.

Generally, phthalocyanines are insoluble in most organic solvents and water; however introduction of some substituents on the ring increases the solubility. Complexes 2 and 3 exhibited excellent solubility in many common organic solvents such as DMF and DMSO. Quaternized complex (3) is very soluble in water as well. The new compounds were characterized by UV-vis, FT-IR and ¹H-NMR spectroscopies as well as MALDI-TOF mass spectra.

When conversion into indium phthalocyanine derivation (2), the characteristic CN stretch at 2229 cm^–1 of the phthalonitrile 1 disappeared in the FTIR spectrum, indicative of metallo-phthalocyanine formation. The characteristic vibrations corresponding to ether groups (C–S–C) were observed at 1121 cm^–1 (for 2) and 1130 cm^–1 (for 3). Aromatic CH stretching at 3061–3055 cm^–1 were observed for both complexes. Aliphatic CH stretching at ca. 2962 cm^–1, S = O stretching at 1308 cm^–1 and 1092 cm^–1, S–O stretching at 637 cm^–1 for 3 are indicative of quaternization formation.

The complexes were also characterized by ¹H NMR with all the substituents and ring protons observed in their respective regions. Compound 2 showed the phthalocyanine ring protons and thioqinoline group protons as multiplets between 9.35 and 7.91 ppm for a total of 36 protons as expected. Although the presence of phthalocyanine aggregation at the concentrations used for the NMR measurements may lead to broadening of the aromatic signals [15], the observed spectra of complexes (2 and 3) were relatively well resolved.

The ¹H NMR spectra of the quaternized phthalocyanine complex (3) showed less resolved patterns compared to non-quaternized derivative. This complex (3) showed the phthalocyanine ring protons and thioquinoline group protons as unresolved multiplets between 9.21 and 7.58 ppm integrating for a total of 36 protons. The methyl protons which integrated for 12 protons were observed 4.24 ppm for quaternized complex (3) as a singlet.

The mass spectra of these phthalocyanine derivatives (2 and 3) confirmed the proposed structures by the observation of molecular ion peaks at m/z = 1487 as [M–Cl+DIT+3H]⁺ and 1262.3 [M–Cl]⁺ for 2. The molecular ion peaks of quaternized complex 3 showed parent ions at m/z = 1574.3 as [M + Na]⁺, 1517.4 [M–Cl+H]⁺, 1447.9 [M–2CH₃–SO₄ + Na]⁺, 1390 [M–Cl–2CH₃–SO₄]^+, respectively. MALDI–TOF–MS spectra of quaternized phthalocyanine complex 3 show the base peak cleavage of anion and methyl groups, as it is often observed for this type of compounds [6] (Fig. 1 as an example for 2).

Fig.1

The mass spectra of the compound 2.

Figure 2 shows the UV-Vis absorption spectra of 2 and 3 in DMSO; the well defined Q band maxima at 700 nm (2) and 702 nm (3) (Table 1) are usual for monomeric phthalocyanine complexes [16]. The Soret bands of these complexes exist at 341 nm (2) and 366 nm (3) (Fig. 2), and are broad due to incomplete merging of the B₁ and B₂ bands. The Q and B (Soret) bands both arise from π–π* transitions and can be explained in terms of linear combination of transitions from a_1u (Q) and a_2u/b_2u (B) HOMO orbitals to the doubly degenerate e_g (LUMO) orbitals [36]. In water, the absorption spectrum of 3 shows cofacial aggregation, as evidenced by the presence of two non-vibrational peaks in the Q band region, Fig. 3, Table 1. The lower energy (red-shifted) band at about 700 nm is due to the monomeric species, while the higher energy (blue-shifted) band at about 640 nm is due to the aggregated species. Addition of 0.25 mL of Triton X-100 to an aqueous solution of 3 brought about considerable increase in intensity of the low energy side of the Q band (Fig. 3), suggesting that addition of Triton X-100 breaks up the aggregates. However, some aggregated portions of 3 still remained in solution even after addition of Triton X-100, as shown in Fig. 3. Aggregated MPcs exhibit limited applicability in photocatalysis because the aggregates convert electronic excitation energy into vibrational energy, due to the closeness of the individual molecules; thereby reducing the excited state lifetimes of the complexes. In this work, photophysical and photochemical studies on 3 in aqueous solution were also carried out in the presence of Triton X-100 to hinder aggregation, as seen in Fig. 3. The Q band position of 3 in water (700 nm, in the presence of Triton X-100) is almost the same as that in DMSO (Fig. 2), suggesting that solvent effect on the spectral position of this complex is insignificant [15].

Fig.2

UV-Vis absorption spectra of complex 2 and 3 in DMSO.

Fig.3

UV-Vis absorption spectra 3 in water and in water containing Triton X-100.

Table 1

Spectral parameters of 2 and 3 in DMSO and water

Complex	Solvent	Q band λ_max, (nm)	Excitation λ_Ex, (nm)	Emission λ_Em, (nm)	Stokes shift Δ _S _tokes, (nm)
2	DMSO	699	700	712	13
3	DMSO	700	700	720	20
	Water	654,703	704	721	18
	Water+TX–100	700	708	711	11
ClInPc	DMSO	686	689	700	14

Figure 4 displays the absorption, fluorescence excitation and fluorescence emission spectra of 2 in DMSO and 3 in water. Fluorescence emission peaks were observed at: 712 nm for 2 and 720 nm for 3; 721 nm in water, respectively (Table 1 and Fig. 4). Stokes’ shifts were calculated from the absorption bands that populate the fluorescent state, i.e. λ_Q (Exc). A constant Stokes’ shift of 11–20 nm is calculated, as expected given the similarity of these molecules. The absorption spectrum was not exactly similar to excitation spectrum due to aggregation behavior in complex 3. The excitation spectrum was a mirror image of the fluorescent spectra for 2. For complexes 3 in DMSO and in water, there was a clear narrowing of the excitation spectra compared to absorption spectra due to aggregation evident in the latter. The fluorescence spectra were mirror images of the excitation spectra for complex 2 in DMSO. The proximity of the wavelength of each component of the Q band absorption to the Q band maxima of the excitation spectra for all complexes suggest that the nuclear configurations of the ground and excited states are similar and not affected by excitation in DMSO [38].

Fig.4

Absorption, excitation and emission spectra of the compounds 2 (a) in DMSO and 3 (b) in water.

6.2 Photophysical and chemical parameters

6.2.1 Fluorescence quantum yields

The fluorescence quantum yields (Φ_F) of 2 (in DMSO) and 3 (in DMSO and water) are given in Table 2. All complexes have lower fluorescence quantum yield than unsubstituted indium and zinc phthalocyanines. The Φ_F values of indium (III) Pc complexes are lower than other MPc complexes due to indium being a very heavy metal. But, these Φ_F values are also similar and typical with photophysical values of other studied indium Pc complexes in the solvents [12 , 39]. The lower values for 3 (Φ_F = 0.0063 in DMSO and 0.0020 in water) are ascribed to the aggregation behavior in the solvents especially in water. It was observed that when the amount of TX-100 was added to the aqueous solution, the fluorescence yield of 3 was increased (Φ_F = 0.016 in water plus TX-100). Triton X-100 as surfactant breaks up the aggregates. Same properties also were observed for 2 in DMSO. Complex 2 has unimportant aggregation tendency in DMSO (Fig. 5). The band at around 640 nm in DMSO for 2 can be attributed to aggregation [6]. Also addition of Triton X-100 to solutions 2 in DMSO resulted in the decrease in the high energy band due to the aggregates and the increase in the low energy band due to the monomer (Figs. 5 and 6).

Fig.5

UV-Vis absorption spectra 2 in DMSO and in DMSO containing Triton X-100

Fig.6

UV-Vis absorption spectra 2 in DMSO at different concentration (A: 2×10^–5, B: 4×10^–5, C: 2×10^–5, D: 2×10^–5, E: 10×10^–5)

Table 2

Photophysical and photochemical properties of the complexes (2 and 3) in DMSO and water

Complex	Solvent	Φ _F	Φ_d (10^–4)	Φ _Δ
2	DMSO	0.012	1.56	0.74
	DMSO TX-100	0.019	2.12	0.80
3	DMSO	0.0063	3.21	0.66
	Water	0.0020	148	0.17
	Water TX-100	0.016	4.26	0.42
ClInPc	DMSO	0.018	9.9	0.61

6.2.2 Singlet oxygen and photodegradation quantum yields

The singlet oxygen generates as a result of the energy transfer from the triplet state of photosensitizers to ground state molecular oxygen during the photocatalytic reactions. Efficiency of this transfer is very important to generate large amounts of moment singlet oxygen. The singlet oxygen quantum yields (Φ_Δ) of photosensitizers show the capability of the samples to act as photosensitizers in PDT applications. Quantum yields of singlet oxygen were determined in air using the relative method with ZnPc (in DMSO) and ZnTSPc (in water) as references; DPBF and ADMA respectively as chemical quenchers for singlet oxygen, using Equation (2).

The Φ_Δ values for 2 (Φ_Δ = 0.74) and 3 (Φ_Δ = 0.66) in DMSO are almost identical within experimental error (10%). Comparing the Φ_Δ values for 3 in DMSO (0.66) and water (0.17), the smaller value in water is ascribed to aggregation tendency of 3 in aqueous media and the quenching of singlet oxygen by water compared to that in DMSO (Fig. 7, Table 2).

Fig.7

A typical spectrum for the determination of singlet oxygen quantum yield. This figure was for complex 2 in DMSO.

When added TX-100 to the solutions, we observed that the singlet oxygen quantum yield increased for both complexes 2 (from 0.74 to 0.80 in DMSO) and 3 (from 0.17 to 0.42 in water). The breakdown of the aggregation improved the photophysical and photochemical properties of the phthalocyanine compound as it increased the monomeric property of the compound. The Φ_Δ values of thioquinoline substituted indium (III) Pc complexes (2 and 3) are higher than unsubstituted In(III)Pc derivative [37] in DMSO.

All complexes give remarkable singlet oxygen quantum yields ranging from 0.66 to 0. 80 which are higher than the literature of In(III) phthalocyanines [15 , 41] in DMSO. In particular, similar singlet oxygen quantum yields were also obtained with respect to similar phthalocyanine complexes in the literature [42].Water soluble derivative also showed similar singlet oxygen quantum yield with literature [43, 44].

Photodegradation of phthalocyanine photosensitizers is important parameter for photocatalytic studies such as PDT due to singlet oxygen attack under light irradiation. During this process photosensitizers should stay stable in the body under applied light intensity to generate high singlet oxygen and demonstrate photodynamic activity. Photodegradation quantum yield values (Φ_Pd) give important information about stability of Pcsin the solutions under applied light. The efficiency of degradation of an absorbing species as a result of photon absorption. The complexes have a decrease in the Q band in spectra following photodegradation. The photodegradation quantum yields of InPc complexes are in order of 10^–4 which is moderate stability under applied irradiation in DMSO [45]. The spectral changes observed for both complexes during irradiation are as shown in Fig. 8 (using complex 3 as an example in DMSO) and Table 2. Photodegradation quantum yield (Φ_d) value of compound 3 in water (Φ_d: 1. 23×10^–3) is less stable compare to in DMSO (Φ_d: 1.56×10^–4) and compound 2 in DMSO (Φ_d: 3.21×10^–4). Complex 3 is stable in DMSO than in water. The photodegradation quantum yields were lower for complexes 2 and 3 when compared to respective unsubstituted ClInPc complex in DMSO.

Fig.8

The photodegradation of compound 3 in DMSO showing the disappearance of the Q band at 5 min intervals.

7 Conclusions

In conclusion, this work has described the synthesis, spectral, photophysical and photochemical properties of two new highly soluble thioquinoline substituted indium (III) phthalocyanine photosensitizer candidates in DMSO and Water (for 3). The effect of quaternization on these properties is also presented. We have shown that quaternization improves water solubility and also enhances the photophysical and photochemical value of the ClInPc derivative. Although, the photophysical and photochemical properties relevant for photosensitization gave more attractive values in DMSO (0.66–0.80) and water plus TX-100 (0.42), the values in water are good enough for PDT applications. This work will certainly enrich the limited literature on the potentials of cationic indium phthalocyanines as photosensitizers in photodynamic therapy applications. Especially, the complex 3 is even more appropriate due to water solubility.

Footnotes

Acknowledgments

This work was supported by Yildiz Technical University (Project Number: 2016-01-02-DOP05).

References

Bonnett

, 1st ed. Gordon and Breach Science: Amsteldijk, The Netherlands, 90-5699-248-1 (2000), 199–222.

Snow

A.W

, Barger

W.R.

, Beverley

, 1st ed.; Beverley

, Lever

A.P.

, Leznoff

C.C.

, WILEY VCH publishers: New York, America 9780471188636(198), 341–392.

Idowu

, Loewenstein

, Hastall

, Nyokong

, Schlettwein

, J of Porphyr and Phthalocyanines 14 (2000), 142–149.

Sezer

, Şener

M.K

, Koca

, Erdoğmuş

and Avcıata

, Synthetic Metals 160 (2010), 2155–2166.

Fernándeza

, Esteves

V.I.

, Cunh

Â.

, Schneider

R.J.

, Tomé

J.P.C.

, J Porphyr Phthalocyanines 20 (2016), 150–166.

Yaşa

, Erdoğmuş

, Uğur

A.L.

, Şener

M.K.

, Avcıata

and Nyokong

, J Porphyr Phthalocyanines 16 (2012), 845–854.

Mantareva

, Kussovski

V.I.

, Angelov

, Wöhrle

R.E.

, Popova

, Dimirov

, Photochem Photobiol Sci 10 (2011), 91–102.

Garland

M.J.

, Cassidy

C.M.

, Woolfson

, Donnelly

R.F.

, Future Med Chem 1 (2009), 667–691.

Olawale

A.Z.

, Osifeko

, Nyokong

, Inorganica Chim Acta 476 (2018), 68–76.

10.

Güzel

, Atmaca

G.Y.

, Erdoğmuş

and Koçak

M.B.

, J Coord Chem 70 (2017), 2659–2670.

11.

Günsel

, Güzel

, Bilgiçli

A.T.

, Atmaca

G.Y.

, Erdoğmuş

and Yarasir

N.M.

, J Lumin 192 (2017), 888–892.

12.

Keskin

, Okuyucu

, Altındal

, Erdoğmuş

, New J Chim 40 (2016), 5537–5545.

13.

Can

O.S.

, Kaya

E.N.

, Durmuş

, and Bulut

, J Photochem Photobiol A Chem Chemistry 317 (2016), 56–67.

14.

Günsel

Bilgiçli

A.T.

, Kırbaç

, Güney

and Kandaz

, J Photochem Photobiol A Chem Chemistry 310 (2015), 155–164.

15.

Durmuş

, Erdogmus

, Ogunsipe

and Nyokong

, Dyes Pigm 82 (2009), 244–250.

16.

Bağda

, Bağda

, Durmuş

and Photochem

, Photobiol B Biol 175 (2017), 9–19.

17.

Larsen

R.D.

, Corley

E.G.

, King

A.O.

, Carroll

J.D.

, Davis

, Verhoeven

T.R.

, Reider

P.J.

, J Org Chem 61 (1996), 3398–3405.

18.

Roma

, Di Braccio

, Grossi

, Mattioli

and Ghia

, Eur J Med Chem 35 (2000), 1021–1035.

19.

Chen

Y.L.

, Fang

K.C.

, Sheu

J.Y

, Hsu

S.L.

and Tzeng

C.C.

, J Med Chem 44 (2001), 2374–2377.

20.

Dubé

, et al, Bioorg Med Chem Lett 8 (1998), 1255–1260.

21.

Alqasoumi

S.I.

, Al-Taweel

A.M.

, Alafeefy

A.M.

, Noaman

, Ghorab

M.M.

, Eur J Med Chem 45 (2010), 738–744.

22.

Behforouz

, et al, Bioorg Med Chem 15 (2007), 495–510.

23.

Kemnitzer

, et al, Bioorg Med Chem Lett 18 (2008), 6259–6264.

24.

Ferlin

M.G.

, Gatto

, Chiarelotto

, Palumbo

, Bioorg Med Chem 9 (2009), 1843–1848.

25.

Bıyıklıoğlu

, Durmuş

and Kantekin

, J Photochem Photobiol A Chem 211 (2010), 32–41.

26.

Erdogmus

, Nyokong

, J Mol Struct 977 (2010), 26–38.

27.

Arici

, Bozoglu

, Erdogmus

, Ugur

A.L.

, Koca

, Electrochim Acta 113 (2013), 668–678.

28.

Fery-Forgues

, Lavabre

, J Chem Edu 76 (1999), 1260–1269.

29.

Maree

M.D.

, Nyokong

, Suhling

, Phillips

, J Porphyrin Phthalocyanines 6 (2002), 373–376.

30.

Nyokong

, Effects of substituents on the photochemical and photophysical properties of main group metal phthalocyanines, Coord Chem Rev 251 (2007), 1707–1722.

31.

Brannon

J.H.

, Madge

, J Am Chem Soc 102 (1980), 62–65.

32.

Ogunsipe

, Nyokong

, J Photochem Photobiol A Chem 173 (2005), 211–220.

33.

Seotsanyana-Mokhosi

, Kuznetsova

, Nyokong

, Photochem Photobiol A Chem 140 (2001), 215–222.

34.

Kuznetsova

, Gretsova

, Kalmkova

, Makarova

, Dashkevich

, Negrimovskii

, Kaliya

, Luk’yanets, E Russ J Gen Chem 70 (2000), 133–140.

35.

Spiller

, Kliesch

, Wöhrle

, Hackbarth

, Roder

, Schnurpfeil

, J Porphyrin Phthalocyanines 45 (1998), 145–158.

36.

Arici

, Bozoglu

, Erdogmus

, Ugur

A.L.

, Koca

, Electrochim Acta 113 (2013), 668–678.

37.

Durmus

, Nyokong

, Tetrahedron 63 (2007), 1385–1394.

38.

Erdogmus

, Ugur

A.L.

, Memisoglu

, Erden

İ.

, J Lumin 134 (2013), 483–490.

39.

Durmus

, Nyokong

, Polyhedron 26 (2007), 3323–3335.

40.

Ertunç

, Sevim

A.M.

, Durmuş

and Bayır

Z.A.

, Polyhedron 102 (2015), 649–656.

41.

Güzel

, Şaki

, Akın

, Nebioğlu

, Şişman

, Erdoğmuş

and Koçak

M.B.

, Synthetic Metals 245 (2018), 127–134.

42.

Soyer Can

, Kaya

E.N.

, Durmuş

and Bulut

, J Photochem Photobiol A Chem 317 (2016), 56–67.

43.

Durmuş

, and Ahsen

, Journal of Inorganic Biochemistry 104 (2010), 297–309.

44.

Çamur

, Ahsen

and Durmuş

, Journal of Photochemistry and Photobiology A: Chemistry 219 (2011), 217–227.

45.

Maree

S.E.

, Nyokong

, J Porphyr Phthalocyanine 5 (2001), 782–792.