Synthesis, photophysical and photochemical studies of new water-soluble indium(III) phthalocyanines.

The preparation of water-soluble indium(III)phthalocyanine complexes is described for the first time in this study. Peripherally and non-peripherally 3-hydroxypyridine tetrasubstituted indium(III) phthalocyanines (5a, 6a) and their quaternarized derivatives (5b, 6b) have been synthesized and characterized by elemental analysis, IR, 1H NMR spectroscopy, electronic spectroscopy and mass spectra. The quaternarized compounds (5b, 6b) show excellent solubility in water, which makes them potential photosensitizers for use in photodynamic therapy (PDT) applications. Photochemical and photophysical measurements were conducted on 3-pyridyloxy appended indium(III) phthalocyanines in dimethylsulfoxide (DMSO) for non-ionic (5a, 6a) and in both DMSO and water for quaternarized (5b, 6b) derivatives. General trends are described for quantum yields of photodegradation, fluorescence lifetimes, fluorescence quantum yields, triplet lifetimes and triplet quantum yields as well as singlet oxygen quantum yields of these compounds. The singlet oxygen quantum yields (Phi(Delta)), which give an indication of the potential of the complexes as photosensitizers in applications where singlet oxygen is required (Type II mechanism) are very high (Phi(Delta) > 0.55). Thus, these complexes may be useful as Type II photosensitizers.     

Water-soluble cationic gallium(III) and indium(III) phthalocyanines for photodynamic therapy

The new tetra-non-peripheral and peripheral 2-mercaptopyridine substituted gallium(III) and indium(III) phthalocyanine complexes (np-GaPc, p-GaPc, np-InPc and p-InPc) and their quaternized derivatives (Qnp-GaPc, Qp-GaPc, Qnp-InPc and Qp-InPc) have been synthesized and characterized. The quaternized complexes show excellent solubility in water, which makes them potential photosensitizer for use in photodynamic therapy (PDT) of cancer. Photophysical and photochemical properties of these phthalocyanines were investigated. General trends are described for quantum yields of photodegradation, fluorescence and fluorescence lifetimes as well as singlet oxygen quantum yields of these compounds. In this study, the effects of the position of the substituents, the nature of the metal ion and quaternization of the substituents on the photophysical and photochemical parameters of the gallium(III) and indium(III) phthalocyanines are also reported. This study also presented the ionic gallium(III) and indium(III) phthalocyanines strongly bind to bovine serum albumin (BSA).     

Synthesis, photophysical and photochemical properties of novel soluble tetra[4-(thiophen-3yl)-phenoxy]phthalocyaninato zinc(II) and Ti(IV)O complexes

The synthesis, photophysical and photochemical properties of zinc and oxo-titanium phthalocyanine derivatives 4-(tetra[4-(thiophen-3yl)-phenoxy]phthalocyaninato)zinc(II), (2); and 4-(tetra[4-(thiophen-3yl)-phenoxy]phthalocyaninato)oxo-titanium(IV), (3), are described for the first time. These peripherally substituted complexes (2 and 3) have been synthesized and characterized by elemental analysis, IR, ¹H NMR and electronic spectroscopy. The compounds (2 and 3) have good solubility in organic solvents such as CHCl₃, DCM, DMSO, DMF, THF and toluene and are not aggregated within a wide concentration range. General trends are described for singlet oxygen, photodegradation, fluorescence quantum yields, triplet quantum yields and triplet life times of these complexes in DMSO, DMF and THF. Compound 2 has higher fluorescence quantum yields, triplet quantum yields and triplet life times than 3, however, the former has lower singlet oxygen quantum yields and photodegradation quantum yields than the latter.     

Spectral, photophysical and photochemical properties of tetra- and octaglycosylated zinc phthalocyanines

Photophysical and photochemical properties of a series of tetra- and octaglycosylated zinc phthalocyanines (ZnPcs) substituted with glucose and galactose moieties have been reported. Spectral properties of these phthalocyanines are compared in DMSO. Absorption spectra of the non-peripherally tetra-substituted ZnPcs 2 showed a significant red shift in their Q-band maxima as compared to the peripherally substituted analog 1. All the complexes gave high triplet quantum yields ranging from 0.68 to 0.88, whereas triplet lifetimes were in the range of 100-430 μs in argon-saturated solutions. The octagalactosylated ZnPc 3b showed the highest triplet quantum yield and singlet oxygen quantum yield of 0.88 and 0.69, respectively. The fluorescence quantum yields and lifetimes of all the compounds under investigation were within the range of zinc phthalocyanine complexes.     

Synthesis and photophysical properties of 1,1′-binaphthol substituted phthalocyanines

We report on the synthesis, characterization and photophysical properties of a new symmetrically tetra substituted {at non-peripheral positions with tetra(1,1′-bi-binaphtoxy)} phthalocyanines containing H₂, Mg(II), Al(III)Cl, Si(IV)Cl₂ in the central cavity. The synthesized compounds were characterized by the elemental analyses, UV-Vis, FT-IR and ¹H NMR spectroscopies. The fluorescence quantum yields, triplet quantum yields and lifetimes of the newly synthesized H₂, Mg, Al, and Si phthalocyanines were explored. Triplet quantum yields ranged from 0.24 to 0.54. The triplet lifetime for the silicon phthalocyanine derivative was the highest ever reported for a phthalocyanine (∼3.5 ms).     

DNA-binding,enzyme inhibition,and photochemical properties of chalcone-containing metallophthalocyanine compounds

In this study, two novel phthalocyanine complexes were synthesized using their corresponding metal salts and 4-(4-(3-(2,4,5-trimethoxyphenyl)acryloyl)phenoxy)phthalo-nitrile as chalcone ligand (4), which was prepared from the reaction of 4-nitrophthalonitrile with 4-hydroxyphenyl-3-(2,4,5-trimethoxyphenyl)prop-2-en-1-one (3). These metallophthalocyanines showed good solubility in organic solvents such as CDCl₃, DCM, THF, DMF, and DMSO. The novel phthalocyanine compounds 4a (Pc-Zn) and 4b (Pc-Co) were characterized using their UV–vis, FT-IR, ¹H NMR, ¹³C NMR, and MALDI-TOF mass spectra and elemental analysis. Then the DNA-binding and xanthine oxidase and carbonic anhydrase-I inhibition properties of compounds 4a and 4b were investigated. Photochemical properties (such as singlet oxygen generation and photodegradation) of this novel chalcone phthalocyanine (4a) were determined in dimethyl sulfoxide (DMSO).     

Impact of iron-complex (Fe(III)-NTA) on photoinduced degradation of 4-chlorophenol in aqueous solution.

In this research work, the photochemical impact of Fe(III)-nitrilotriacetic acid complex (FeNTA) on the fate of an organic pollutant (4-chlorophenol (4-CP)) was investigated in natural waters. The quantum yields of the photodecomposition of the FeNTA complex and of Fe(II) formation, by an intra-molecular photoredox process (the first stage of the reaction) are high. This photoredox reaction represents the first step of the process leading to 4-CP disappearance. Whereas oxygen does not affect FeNTA photodegradation, 4-CP depletion requires the presence of oxygen. The radical species HO and CO3*- responsible of the degradation were identified by ESR spectroscopy under irradiation. Two different wavelength-dependent mechanisms of 4-chlorophenol degradation are proposed. It clearly appears that under solar irradiation, iron organic complexes like FeNTA can play a significant role on the fate of the organic compounds present in natural waters.     

A comparative study of water soluble 5,10,15,20-tetrakis(2,6-dichloro-3-sulfophenyl)porphyrin and its metal complexes as efficient sensitizers for photodegradation of phenols.

5,10,15,20-Tetrakis(2,6-dichloro-3-chlorosulfophenyl)porphyrin and its tin and zinc complexes were synthesized with high yields and fully characterized. The corresponding water-soluble 5,10,15,20-tetrakis(2,6-dichloro-3-sulfophenyl)porphyrins were obtained by hydrolysis with water. An extensive photophysical study of the new water soluble porphyrinic compounds was carried out including absorption and fluorescence spectra, fluorescence quantum yields, triplet absorption spectra, triplet lifetimes, triplet and singlet oxygen quantum yields. These sensitizers were successfully used in the photodegradation of 4-chlorophenol and 2,6-dimethylphenol. A comparison is made of their efficiencies, and some mechanistic considerations are highlighted.     

磷光过渡金属配合物用于生物成像及癌症治疗的研究进展

顺铂及其衍生物在抗肿瘤方面取得了很大成功,但是传统的铂类抗癌药物的毒副作用和耐药性限制了这类化合物在临床上的进 一步开发。近年来,非铂类化合物,如具有 d6 电子结构的磷光过渡金属钌 ( II )、铱 ( III ) 和铼 ( I ) 配合物,由于其丰富的光物理和 光化学性质、氧化还原性质、多样的几何构型和水溶性好等优势吸引了越来越多的关注。综述上述 3 种金属配合物在生物成像及抗肿 瘤方面的研究进展。     

A series of iridium complexes equipped with inert shields: Highly efficient bluish green emitters with reduced self-quenching effect in solid state

In this paper, we synthesize a series of cyclometalated ligands and their corresponding Ir(III) complexes using pentane-2,4-dione as the auxiliary ligand. We discuss the photophysical properties of these Ir(III) complexes in detail, including their UV-Vis absorption spectra, photoluminescence spectra in solid and liquid states, luminescence decay lifetimes, and luminescence quantum yields. The correlation between self-quenching effect and molecular structure is also investigated. It is found that these Ir(III) complexes are solid-emitting ones due to their reduced self-quenching in solid state. Theoretical calculation and experimental data reveal that the following two reasons should be responsible for the reduced self-quenching in solid state: (1) pentane-2,4-dione, phenyl, and triphenylamine moieties serve as inert shields for the excited state Ir(III) complexes; (2) the radiative decay process in these Ir(III) complexes is accelerated by the introduction of electron-donors, and thus partly immune from self-quenching caused by intermolecular action.     

Cytotoxic effect, differentiation, inhibition of growth and theoretical calculations of an N,N-donor ligands and its platinum(II), palladium(II) and copper(II) complexes

The new pyrazole ligand 5-(2-hydroxyphenyl)-3-methyl-1-(2-pyridylo)-1H-pyrazole-4-carboxylic acid methyl ester (2) and the corresponding Pt(II), Pd(II) and Cu(II) complexes 3-5 have been synthesized as potential anticancer compounds, and characterized using IR, and (1)H NMR as well as mass spectrometry. The 3-D structures of the Cu(II) complexes were determined by quantum mechanic calculation DFT methodology (density functional theory). The cytotoxicity assay of the ligand and complexes has been performed on leukemia cell lines. In general, the complexes showed lower cytotoxicity than cisplatin, and the Pt(II) and Cu(II) complexes were found to be more efficient in the induction of leukemia cell death than the Pd(II) complex. Our investigations indicate that the antiproliferating activity of the Pt(II) and Cu(II) complexes was partly due to the modulation of cellular differentiation.     

Photophysical, photochemical and electrochemical properties of a series of aromatic electron acceptors based on N-heterocycles

The electronic absorption and luminescence spectra, photoreactivity, and the electrochemical properties of a series of aromatic electron acceptors based on the 4,4′-bipyridinium, 1,2-bis(4-pyridinium)ethylene, and 2,7-diazapyrenium cations have been investigated. All these species exhibit distinctive absorption spectra and some of them show fluorescence and phosphorescence bands. The compounds based on the 1,2-bis(4-pyridinium)ethylene unit provide the interesting possibility of studying the E-Z photoisomerization of the vinylic double bond. The photophysical and photochemical properties have been also interpreted on the basis of quantum chemical calculations. All the examined compounds exhibit reduction processes at mild negative potentials that reveal their electron accepting character. We found that the photophysical, photochemical and electrochemical properties of such compounds are not only determined by the structure of the N-heterocyclic central moiety, but are also remarkably affected by the peripheral substituents linked to the quaternarized nitrogen atoms.     

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.     

Preparation and in vitro photodynamic activities of novel axially substituted silicon (IV) phthalocyanines and their bovine serum albumin conjugates

Two novel axially substituted phthalocyanines, namely bis(4-(4-acetylpiperazine)phenoxy)phthalocyaninatosilicon (IV) (1) and its N-methylated derivative 2, have been synthesized. The dicationic phthalocyanine 2 is non-aggregated in water and exhibits good photophysical properties. The non-covalent BSA conjugates of these compounds have also been prepared. Compound 2 and the conjugate 2-BSA show extremely high photodynamic activities toward B16 melanoma cancer cell lines. The corresponding 50% growth-inhibitory (IC50) ratios are 33 and 38 nM, respectively.     

Synthesis and spectral properties of Zr(IV) and Hf(IV) phthalocyanines with β-diketonates as axial ligands

The series of new zirconium(IV) and hafnium(IV) phthalocyanines with various β-dicarbonyl ligands were prepared via direct interaction between di(chloro)zirconium(IV) or hafnium(IV) phthalocyanines and free β-diketones and also with 4-benzoyl-3-methyl-1-phenyl-2-pyrazolin-5-one. The structure of the obtained bis(β-dicarbonilato) zirconium(IV) and hafnium(IV) phthalocyanines was studied by two dimension ¹H NMR spectroscopy (COSY, NOESY, ROESY). Absorption and fluorescence spectroscopic studies have been investigated in various solvents. Analyzed compounds of concentration range below 10^?5 mol/dm³ do not aggregate in the organic solvents. Fluorescence quantum yields (Φ_F) and natural life times (τ) of zirconium phthalocyanine complexes have been calculated in toluene, DMSO and THF.     

On the structure of the N,N′-dimethylpropyleneurea and dimethylsulfoxide solvated gallium(III) and indium(III) ions and bromide complexes in solution and solid state, and the complex formation of the gallium(III) and indium(III) bromide systems in N,N′-dimethylpropyleneurea

The structures of the N,N′-dimethylpropyleneurea (DMPU) solvated gallium(III) and indium(III) ions have been determined in DMPU solution by means of EXAFS. The gallium(III) ion is five-coordinate with a mean Ga-O bond distance of 1.924(5) Å, while the larger indium(III) ion is octahedrally coordinated with a mean In-O bond distance of 2.146(3) Å. The complex formation equilibria in DMPU for the gallium(III) and indium(III) bromide systems have been studied calorimetrically at 298 K. Three relatively strong complexes are formed in the indium(III) bromide system in DMPU, whereas no stability constants could be established in the gallium(III) bromide system as the heats of complex formation were very close to zero. Gallium(III) bromide is present as DMPU solvated GaBr₃ complexes in solution with three equatorial Ga-Br bonds at 2.328(3) Å, and two Ga-O bonds at 1.92(3) Å in the apical positions of a distorted trigonal bipyramid. The DMPU solvated indium(III) bromide has the same configuration with a mean In-Br bond distance of 2.510(3) Å, and two In-O bonds at 2.201(6) Å. Indium(III) binds three bromides and three Me₂SO molecules through the oxygen atoms in octahedral fac-configuration with mean In-Br and In-O bond distances of 2.630(3) and 2.211(15) Å, respectively.     

Modification of the heme·heme oxygenase system with iron and cobalt tetrasulfonated phthalocyanines

Modification of heme·heme oxygenase by iron(III) and cobalt(II) tetrasulfonated phthalocyanines has been performed. New compounds have been isolated and their properties have been investigated by difference spectroscopy, electrophoresis, molecular weight estimation, electron paramagnetic resonance (EPR) and carboxymethylation at histidyl groups. Spectrophotometric titration data indicate the ratio of the reagents in this process to be 1:1. The visible absorption spectra show the main peak at 650 nm for the iron compound and 682 nm for the cobalt one. Electrophoresis and molecular weight estimation show both complexes to be monomers. Cobalt(II) tetrasulfonated phthalocyanine, under aerobic conditions with heme oxygenase protein, undergoes autooxidation to the cobalt(III) complex, as has been proved by EPR and spectroscopic data. Iron and cobalt phthalocyanine modified heme·heme oxygenase with excess dithionite is reduced at the phthalocyanine ligand. In the presence of oxygen, the reduction product transforms into oxygenated Fe(III)Lheme oxygenase or Co(III)heme oxygenase, respectively. Reduction of the iron(III) model complex with ascorbic acid under anaerobic conditions leads to degradation of the phthalocyanine moiety, while Co(III)heme oxygenase with ascorbic acid is reduced to Co(II)Lheme oxygenase. As has been shown by carboxymethylation of the heme oxygenase protein at the histidine residues, the predominant binding site of both phthalocyanine complexes is the heme-binding histidyl residue. There is evidence that there is a second binding site with lower affinity towards Co(II)L on the heme oxygenase protein. Iron and cobalt tetrasulfonated phthalocyanines are not able to displace heme from the heme·heme oxygenase complex. In this reaction the iron complex undergoes degradation and the cobalt one gives a hybrid compound with heme·heme oxygenaseHeme oxygenase protein complexes with iron and cobalt tetrasulfonated phthalocyanines do not exhibit activity in their oxidative degradation.     

Synthesis and photodynamic activity of zinc(II) phthalocyanine derivatives bearing methoxy and trifluoromethylbenzyloxy substituents in homogeneous and biological media

Two zinc(II) phthalocyanines bearing either four methoxy (ZnPc 3) or trifluoromethylbenzyloxy (ZnPc 4) substituents have been synthesized by a two-step procedure starting from 4-nitrophthalonitrile. Absorption and fluorescence spectroscopic studies were analyzed in different media. These compounds are essentially non-aggregated in the organic solvent. Fluorescence quantum yields (phi(F)) of 0.26 for ZnPc 3 and 0.25 for ZnPc 4 were calculated in tetrahydrofuran (THF). The photodynamic activity of these compounds was compared in both THF containing photooxidizable substrates and in vitro on Hep-2 human larynx-carcinoma cell line. The production of singlet molecular oxygen, O(2)((1)Delta(g)), was determined using 9,10-dimethylanthracene yielding values of approximately 0.56 for both sensitizers. Under these conditions, the addition of beta-carotene (Car) suppresses the O(2)((1)Delta(g))-mediated photooxidation. In biological medium, no dark cytotoxicity was found for cells incubated with 0.1 microM of phthalocyanines 3 and 4 for 24 h. However, under similar conditions 0.5 microM of ZnPc 4 was toxic (70% cell survival). The uptake into Hep-2 cells was evaluated using 0.1muM of sensitizer, reaching values of approximately 0.05 nmol/10(6) cells after 3h of incubation at 37 degrees C. The cell survival after irradiation of the cultures with visible light was dependent upon both light exposure level and intracellular sensitizer concentration. A higher photocytotoxic effect was found for ZnPc 3 with respect to 4 (32%/70% cell survival after 15 min of irradiation). Also, these studies were performed treating the cells with 0.5 microM of ZnPc 3. In this case, an increase in the uptake (approximately 0.28 nmol/10(6) cells) was observed, which is accompanied by a higher photocytotoxic activity (20% cell survival). These results show that even though both sensitizer present similar photophysical properties in homogeneous medium, the photodynamic behavior in cellular media can significantly be changed.     

Synthesis, spectral properties and supramolecular dimerisation of heteroleptic triple-decker phthalocyaninato complexes with one outer crown-substituted ligand

Four complexes - [(15C5)₄Pc]M(Pc)M(Pc), (Pc²⁻ - phthalocyaninato-dianion, [(15C5)₄Pc]²⁻ - 2,3,9,10,16,17,24,25-tetrakis(15-crown-5)phthalocyaninato-dianion, M = Sm, Dy, Tm, Y) were obtained via the reaction of M(Pc)₂, H₂[(15C5)₄Pc] and M(acac)₃. The influence of the stability of starting M(Pc)₂ on the yields of target compounds was investigated. Increasing the stability of M(Pc)₂ leads to higher yields of [(15C5)₄Pc]M(Pc)M(Pc) and lower yields of scrambling products. All complexes were characterized by ¹H NMR, UV-Vis and FT-IR spectroscopy as well as MALDI TOF mass-spectrometry. The analysis of ¹H NMR spectra was performed in terms of lanthanide-induced shifts. Cation-induced dimerisation was studied by means of spectrophotometric titration. Supramolecular dimers {2[(15C5)₄Pc]M(Pc)M(Pc) · 4K⁺} are the largest discrete cofacial supramolecular assemblies built of phthalocyanine building blocks reported up-to-date. The observed increase of the intermolecular excitonic interaction between building blocks with the increase of REE(III) size is tentatively explained in terms of metal-size dependent deformation of phthalocyanine ligands in sandwich complexes.     

Comparative photophysical investigation of oxygen and sulfur as covalent linkers on octaalkylamino substituted zinc(II) phthalocyanines.

This work describes a systematic comparison of oxygen and sulfur as covalent linkers on octasubstituted zinc(II) phthalocyaninates. Most photophysical parameters that make phthalocyanines technologically relevant, e.g. molar absorption coefficients, fluorescence, triplet and singlet oxygen quantum yields, are essentially unaffected by the substitution. The energy content of the first triplet state was observed to be close to the first singlet state of molecular oxygen for both spacers, as follows from photoacoustic determinations. Nonetheless, a bathochromic shift of 30 nm in the absorption and emission maxima, and of 60 nm in the triplet-triplet absorption spectra were observed when alkyloxyl and alkylsulfanyl moieties were alternatively present. Fluorescence quantum yields proved to be much more sensitive towards aggregation than the absorption spectra. Therefore, a novel fluorescence data analysis provided aggregation parameters and photophysical properties of the monomeric species. It was observed that the tendency towards dimerization is slightly higher with sulfur linkers. These results set a foundation for the rational design of conveniently substituted phthalocyaninates with different connectors between the macrocycle and the side chains.