Meltem Göksel

Synthesis of asymmetric zinc(II) phthalocyanines with two different functional groups & spectroscopic properties and photodynamic activity for photodynamic therapy

Zinc(II) phthalocyanine containing [2-(tert-butoxycarbonyl)amino]ethoxy and iodine groups (A and B), as well as their deprotected mono-amino and tri-iodine zinc(II) phthalocyanine (2) were obtained. This structure surrounds by substituents with functional groups. From this perspective it can be used a starting material for many reactions and applications, such as sonogashira coupling, carbodiimide coupling. An example of a first diversification reaction of this compound was obtained with conjugation of a biotin. Asymmetrically biotin conjugated and heavy atom bearing zinc(II) phthalocyanine (3) were synthesized characterized for the first time and photophysical, photochemical and photobiological properties of these phthalocyanines were compared in this study.

Silicon(IV) phthalocyanine-biotin conjugates: Synthesis, photophysicochemical properties and in vitro biological activity for photodynamic therapy

Silicon (IV) phthalocyanines bearing one or two biotin groups on the axially positions were synthesized, and these novel phthalocyanines were characterized by elemental analysis and standard spectroscopic techniques such as FT-IR, 1H NMR, UV-vis and MALDI-TOF. The synthesized compounds are the first examples of axially biotin substituted silicon (IV) phthalocyanines. These phthalocyanines were designed as targeting photosensitizers for the treatment of cancer by photodynamic therapy (PDT) technique. The phthalocyanine ring was selected for its photosensitizer ability and the biotin group was selected as a targeting agent for increasing accumulation of these photosensitizers in tumor cells. The photophysical (fluorescence quantum yields and lifetimes) and photochemical (singlet oxygen generation) properties of the target silicon(IV) phthalocyanines were investigated in DMSO. The photosensitizing efficiency of the studied phthalocyanines was tested against human cervical cancer (HeLa) cells at different photosensitizer concentrations. Both axially mono- and bis-biotin substituted silicon(IV) phthalocyanines present high photocytotoxicity against HeLa cancer cells with the cell survival degree ranging from 13% to 50%. The photosensitivity and the intensity of damage were found to be directly related to the concentration of the used photosensitizers. According to the obtained results, both silicon(IV) phthalocyanine derivatives could be promising as photosensitizers for treatment of cancer by PDT technique.

The water soluble axially disubstituted silicon phthalocyanines: photophysicochemical properties and in vitro studies

Two novel silicon(IV) phthalocyanines bearing 1,3-bis[3(dimethylamino)phenoxy]propan-2-ol or 1,3-bis[3(diethylamino)phenoxy]propan-2-ol groups at their axial positions were synthesized. These phthalocyanines were converted into their water soluble derivatives by the quaternization reaction with methyl iodide. The quaternized phthalocyanines show excellent solubility aqueous solutions without any aggregation which makes them potential photosensitizers for use in photodynamic therapy (PDT). For this reason, the photophysical and photochemical properties such as fluorescence quantum yields, lifetimes, singlet oxygen generation and photodegradation of both non-ionic (3 and 5) and quaternized cationic silicon(IV) phthalocyanines were investigated. Furthermore, the cytotoxicity of PDT was determined by colorimetric proliferation assay against to hepatocellular carcinoma (HuH-7) cancer cells. In this study, the cells were incubated with a novel water soluble silicon(IV) phthalocyanine derivatives and thereafter the cells were illuminated using broad-band incoherent light source.Graphical abstract

Axially substituted silicon(IV) phthalocyanine and its quaternized derivative as photosensitizers towards tumor cells and bacterial pathogens

Axially di-(alpha,alpha-diphenyl-4-pyridylmethoxy) silicon(IV) phthalocyanine (3) and its quaternized derivative (3Q) were synthesized and tested as photosensitizers against tumor and bacterial cells. These new phthalocyanines were characterized by elemental analysis, and different spectroscopic methods such as FT-IR, UV-Vis, MALDI-TOF and 1H NMR. The photophysical properties such as absorption and fluorescence, and the photochemical properties such as singlet oxygen generation of both phthalocyanines were investigated in solutions. The obtained values were compared to the values obtained with unsubstituted silicon(IV) phthalocyanine dichloride (SiPcCl2). The addition of two di-(alpha,alpha-diphenyl-4-pyridylmethanol) groups as axial ligands showed an improvement of the photophysical and photochemical properties and an increasement of the singlet oxygen quantum yield (ΦΔ) from 0.15 to 0.33 was determined. The photodynamic efficacy of synthesized photosensitizers (3 and 3Q) were evaluated with promising photocytotoxicity (17% cell survival for 3 and 28% for 3Q) against the cervical cancer cell line (HeLa). The photodynamic inactivation of pathogenic bacterial strains Streptococcus mutans, Staphylococcus aureus, and Pseudomonas aeruginosa suggested a high susceptibility with quaternized derivative (3Q). The both Gram-positive bacterial strains were fully photoinactivated with 11μM 3Q and mild light dose 50J.cm-2. In case of P. aeruginosa the effect was negligible for concentrations up to 22μM 3Q and light dose 100J.cm-2. The results suggested that the novel axially substituted silicon(IV) phthalocyanines have promising characteristic as photosensitizer towards tumor cells. The quaternized derivative 3Q has high potential for photoinactivation of pathogenic bacterial species.

Novel carbazole containing zinc phthalocyanine photosensitizers: Synthesis, characterization, photophysicochemical properties and in vitro study

Tetra and octa substituted novel zinc(II) phthalocyanines (3a and 5a) bearing carbazole groups were synthesized by cyclotetramerization of respective phthalonitrile derivatives (3 and 5). The zinc(II) phthalocyanines (3a and 5a) were converted into the water-soluble quaternized derivatives (3b and 5b) by utilizing dimethylsulphate as quaternizing agent. The synthesized novel compounds were confirmed thruogh FT-IR, UV-vis and MALDI-TOF mass spectroscopic data and elemental analysis as well. The photophysical (fluorescence quantum yields and lifetimes) and photochemical (singlet oxygen generation) properties of new phthalocyanines were determined in dimethylsulfoxide (DMSO). The photophysical and photochemical results were compared according to the number of the carbazole groups on the phthalocyanine core. Additionaly, in vitro photocytotoxicity of the targeted compounds were examined against to hepato cellular carcinoma (HuH-7) cancer cell line for determination of their photosensitizing ability.

Photophysicochemical, calf thymus DNA binding and in vitro photocytotoxicity properties of tetra-morpholinoethoxy-substituted phthalocyanines and their water-soluble quaternized derivatives

In this study, morpholinoethoxy-substituted metal-free (3), zinc(II) (4) and indium(III) (5) phthalocyanines were synthesized. These phthalocyanines were converted to their water-soluble quaternized derivatives (3Q–5Q) using excess methyl iodide as a quaternization agent. All these phthalocyanines (Pcs) were characterized by elemental analysis and different spectroscopic methods such as FT-IR, 1H NMR, UV–Vis and mass spectrometry. The photophysical and photochemical properties such as fluorescence and generation of singlet oxygen were investigated for determination of these phthalocyanines as photosensitizers in photodynamic therapy (PDT) applications. The binding properties of quaternized phthalocyanines (3Q–5Q) to calf thymus DNA (CT-DNA) were investigated by UV–Vis and fluorescence spectrophotometric methods. The quenching effect of all quaternized phthalocyanines on the fluorescence intensity of SYBR Green–DNA complex was determined. The mixtures of 3Q, 4Q or 5Q and DNA solutions were used to determine the change in Tm of double helix DNA with thermal denaturation profile. In addition, thermodynamic parameters considering their aggregation in buffer solution, which shows the spontaneity of the reactions between DNA and quaternized Pcs were investigated. On the other hand, in vitro phototoxicity and cytotoxicity behavior of the quaternized water-soluble phthalocyanine photosensitizers (3Q–5Q) were tested against the cervical cancer cell line named HeLa for evaluation of their suitability for treatment of cancer by PDT method.Graphical abstractPeripherally tetra-substituted neutral and quaternized metal-free and metallophthalocyanines (MPcs) (Zn, In) bearing morpholinoethoxy groups were prepared. The binding of quaternized compounds (3Q–5Q) to CT-DNA were examined using UV–Vis, fluorescence spectra, thermal denaturation profiles and KSV values. Besides, thermodynamic studies indicated that binding of 3Q–5Q to DNA was spontaneous. On the other hand, in vitro phototoxicity and cytotoxicity behavior of the quaternized water-soluble phthalocyanine photosensitizers (3Q–5Q) were tested against the cervical cancer cell line named HeLa for evaluation of their suitability for treatment of cancer by PDT method.

Peptide-substituted phthalocyanine photosensitizers: design, synthesis, photophysicochemical and photobiological studies

A series of phthalocyanine-peptide-quencher conjugates (6-9) were synthesized as photosensitizers for photodynamic therapy in cancer treatment. The photophysical, photochemical and photobiological properties of these activatable molecular beacons were also investigated in this study. For this purpose, the fluorescence, singlet oxygen and photodegradation quantum yields and fluorescence lifetime values of the compounds were determined in DMSO solutions. The phototoxicity and cytotoxicity of the systems were studied against the cervical cancer cell line named HeLa for an evaluation of their suitability for photodynamic therapy. The results showed that a maximum of 80% of HeLa cells were killed following light irradiation with photodynamic efficiency. All of the results showed that the novel activatable molecular beacons could be suitable candidates for cancer treatment via PDT technique.

A novel of PEG-conjugated phthalocyanine and evaluation of its photocytotoxicity and antibacterial properties for photodynamic therapy

A poly(ethylene glycol) (PEG)-conjugated silicon(IV) phthalocyanine axially substituted with (PEG1000) chains (SiPc-PEG) was synthesized, and this novel phthalocyanine was characterized by 1H-NMR, FT-IR and UV-Vis spectrophotometric methods. Elemental analysis data were beneficial for the evaluation of the chemical structure of the new compound. The total number of (O–CH2–CH2 units was calculated as 44 and the structure of the new PEG-conjugated silicon phthalocyanine was determined by the use of integral areas in 1H-NMR spectrum and the ratio of SiPc:PEG1000 was found as 1:2. The photophysical and photochemical properties were determined in both DMSO and aqueous solutions. In addition, the photocytotoxicity of the novel PEG-conjugated silicon(IV) phthalocyanine wasalso examined by testing against human cervical-carcinoma (HeLa) and hepato-carcinoma cells (HuH-7). The IC50 value for the SiPc-PEG compound was determined as 0.28 μM for HeLa cells and 0.4μM for HuH-7 cells. These results imply that HeLa cell...