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).     

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.     

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.     

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).     

Photophysical properties and photodynamic activity in vivo of some tetrapyrroles

Some of the photophysical properties (stationary absorbance and fluorescence, fluorescence decay times and singlet oxygen quantum yields) of pheophorbide a, metal-free, ClAl-, Cu- and Mg-t-butyl-substituted phthalocyanines, metal-free, ClAl- and Cu-t-butyl-substituted naphthalocyanines and of a number of tetraphenylporphyrins (5,10,15,20-tetraphenylporphyrin, 5,10,15,20-tetra(m-hydroxyphenyl)porphyrin, 5,10,15,20-tetra(p-hydroxyphenyl)porphyrin) have been studied in comparison with hematoporphyrin IX in order to select potent photosensitizers for the photodynamic treatment of cancer. The photodynamic activity of these compounds was investigated using Lewis lung carcinoma in mice. As a consequence of the photophysical parameters (relatively short singlet state lifetimes, and high singlet oxygen quantum yields) the photodynamic activities of pheophorbide a, t-butyl-substituted ClAl-phthalocyanine and ClAl-naphthalocyanine were selected for study in greater detail. Under the conditions employed in the present study, pheophorbide a was found to be the most effective sensitizer, as judged from its strong absorption at the excitation wavelength as compared with the hematoporphyrin derivative and greater singlet oxygen quantum yield relative to the phthalocyanines and naphthalocyanines. The photodynamic activity was observed to be strongly dependent on the photophysical parameters of the compounds. The primary mechanism underlying the photodynamic activity of these sensitizers probably consists of energy transfer from the lowest triplet state of the dyes to molecular oxygen, resulting in the formation of singlet oxygen (type II of photosensitization).     

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.     

Temperature effect on the luminescence of synthetized Yt base in PVA film

The mean phosphorescence lifetimes, fluorescence yields and phosphorescence-to-fluorescence quantum yields ratios of Y_t base in PVA films were measured in the temperature range of 100–250°K. The quantum yield of triplet state formation was found to be temperature independent at a wide range of lower temperatures. The radiative and nonradiative rate constants for triplet state were measured.     

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.     

Molecularly Engineered Phthalocyanines as Hole‐Transporting Materials in Perovskite Solar Cells Reaching Power Conversion Efficiency of 17.5%

Easily accessible tetra‐5‐hexylthiophene‐, tetra‐5‐hexyl‐2,2′‐bisthiophene‐substituted zinc phthalocyanines (ZnPcs) and tetra‐tert ‐butyl ZnPc are employed as hole‐transporting materials in mixed‐ion perovskite [HC(NH₂)₂]_0.85(CH₃NH₃)_0.15Pb(I_0.85Br_0.15)₃ solar cells, reaching the highest power conversion efficiency (PCE) so far for phthalocyanines. Results confirm that the photovoltaic performance is strongly influenced by both, the individual optoelectronic properties of ZnPcs and the aggregation of these tetrapyrrolic semiconductors in the solid thin film. The optimized devices exhibit PCE of 15.5% when using tetra‐5‐hexyl‐2,2′‐bisthiophene substituted ZnPcs, 13.3% for tetra‐tert ‐butyl ZnPc, and a record 17.5% for tetra‐5‐hexylthiophene‐based analogue under standard global 100 mW cm^?2 AM 1.5G illumination. These results boost up the potential of solution‐processed ZnPc derivatives as stable and economic hole‐transport materials for large‐scale applications, opening new frontiers toward a realistic, efficient, and inexpensive energy production.     

金属酞菁光敏剂的三阶非线性光学性能研究

从光动力治疗癌症的疗效着眼研究酞菁配合物的三阶非线性光学性能。用时间分辨简并四波混频方法测量苯硫基钛菁锌(C56H32S4Zn),苯硫基铝酞菁(C56H32AlN8O4)以及烷氧基铝酞菁(C56H32AlN8O4)的三阶非线性光极化率;测量四波混频响应的衰减过程;研究时间响应的超快过程和慢过程及其动力学机制,它们分别对应于单态和三线态的寿命。在荧光显微成像系统中观察三种酞菁光敏剂对人肝癌细胞杀伤的形态变化,并用MTT方法检测细胞存活率。对三种酞菁配合物的三线态量子产率和寿命进行测定,结果与它们对人肝癌细胞的光动力杀伤作用相关联。     

Syntheses and properties of trimethylaminophenoxy-substituted Zn((II))-phthalocyanines

The syntheses, photophysical properties and in vitro biological behavior of a series of nine Zn((II))-phthalocyanines (ZnPcs) bearing one to eight positively-charged trimethylaminophenoxy groups are reported. All ZnPcs are highly soluble in polar organic solvents, and show fluorescence and singlet oxygen quantum yields in the ranges 0.11-0.21 and 0.16-0.47, respectively. The cytotoxicity of the ZnPcs depends on both the number of charges and their site of substitution (α vs. β) on the Pc isoindole units; the most promising for PDT application are the α-substituted di-cationic ZnPcs 6a and 17a.     

Synthesis and photodynamic activity of novel asymmetrically substituted fluorinated phthalocyanines

A series of asymmetrically substituted dodecafluorinated phthalocyanines has been synthesized via the Kobayashi ring expansion reaction of the corresponding dodecafluorinated boron subphthalocyanine with differently substituted 1,3-diiminoisoindolines. The mild reaction conditions employed during this ring expansion reaction gave rise exclusively to 3:1 asymmetrically substituted dodecafluorinated phthalocyanines. Metal insertion into the metal-free phthalocyanines was accomplished by heating at 40 degrees C in N,N-dimethylformamide in the presence of zinc bromide. The resulting zinc dodecafluorophthalocyanines were formulated as Cremophor EL oil-water emulsions and evaluated as photosensitizers in vitro against EMT-6 mouse mammary tumor cells. As compared to the previously studied zinc hexadecafluorophthalocyanine, these new asymmetrical zinc dodecafluorophthalocyanines exhibited improved photodynamic activity.     

Temperature-dependent triplet and fluorescence quantum yields of the photosystem II reaction center described in a thermodynamic model.

A key step in the photosynthetic reactions in photosystem II of green plants is the transfer of an electron from the singlet-excited chlorophyll molecule called P680 to a nearby pheophytin molecule. The free energy difference of this primary charge separation reaction is determined in isolated photosystem II reaction center complexes as a function of temperature by measuring the absolute quantum yield of P680 triplet formation and the time-integrated fluorescence emission yield. The total triplet yield is found to be 0.83 +/- 0.05 at 4 K, and it decreases upon raising the temperature to 0.30 at 200 K. It is suggested that the observed triplet states predominantly arise from P680 but to a minor extent also from antenna chlorophyll present in the photosystem II reaction center. No carotenoid triplet states could be detected, demonstrating that the contamination of the preparation with CP47 complexes is less than 1/100 reaction centers. The fluorescence yield is 0.07 +/- 0.02 at 10 K, and it decreases upon raising the temperature to reach a value of 0.05-0.06 at 60-70 K, increases upon raising the temperature to 0.07 at approximately 165 K and decreases again upon further raising the temperature. The complex dependence of fluorescence quantum yield on temperature is explained by assuming the presence of one or more pigments in the photosystem II reaction center that are energetically degenerate with the primary electron donor P680 and below 60-70 K trap part of the excitation energy, and by temperature-dependent excited state decay above 165 K. A four-compartment model is presented that describes the observed triplet and fluorescence quantum yields at all temperatures and includes pigments that are degenerate with P680, temperature-dependent excited state decay and activated upward energy transfer rates. The eigenvalues of the model are in accordance with the lifetimes observed in fluorescence and absorption difference measurements by several workers. The model suggests that the free energy difference between singlet-excited P680 and the radical pair state P680+l- is temperature independent, and that a distribution of free energy differences represented by at least three values of about 20, 40, and 80 meV, is needed to get an appropriate fit of the data.     

2,5-Dimethylphenacyl carbamate: a photoremovable protecting group for amines and amino acids.

2,5-Dimethylphenacyl (DMP) carbamates (1a-c) released the corresponding free amines or amino acids in high chemical yields, albeit with quantum yields Phi of only 0.04-0.09, upon irradiation in either aprotic or protic solvents. The photoreaction proceeded principally from the triplet excited state via the E-photoenol. The lifetimes of the triplet enol and the E- and Z-enols in the ground state were determined by laser flash photolysis. The primary photoinitiated transformation liberated a carbamic acid derivative, which subsequently decarboxylated to the amino group-containing compound. Exhaustive irradiation of a DMP-protected aniline (1a) in acetonitrile did not provide aniline in quantitative chemical yields, because it was involved in reductive cleavage of the starting material as an electron donor, thereby decreasing the overall deprotection yield (86%). Phenylalanine methyl ester, liberated from 1c, was, however, obtained in excellent chemical yield (97%). It was also found that the carbamates, while thermally stable, released amines with higher quantum yields in acidic methanol solutions. The DMP chromophore is proposed as an excellent photoremovable protecting group for amino acids and, under specific conditions, for amines in organic synthesis and biochemistry.     

Photodynamic potentialities of some phenothiazine derivatives

Summary The quantum yields of fluorescence and phosphorescence and the triplet lifetimes were determined for 29 phenothiazine derivatives; the _p values are varying from 0.2 to 1. The irradiation of phenothiazine derivatives in aerated solutions yields from the triplet state to the formation of singlet oxygen and more especially of superoxide ions and cation-radicals characteristic of the dye. Relative values of the formation rate were determined for these two mechanisms. Production of cation-radicals was correlated with phototoxicity in vivo. Chlorination enhances the two phenomena and acetylation reduces to nothing. A maximum value was estimated for the quantum yield of photoionization.     

Verteporfin, photofrin II, and merocyanine 540 as PDT photosensitizers against melanoma cells

The efficiency of photodynamic effect (PDE) for Photofrin II (PfII), Verteporfin, and Merocyanine 540 (MC540) was compared against neoplastic cells. Triplet state lifetimes and singlet molecular oxygen quantum yields were correlated with biological effect. PfII triplet lifetime was two times longer than that of Verteporfin, however, its singlet molecular oxygen quantum yield was two times lower in comparison with Verteporfin. High singlet molecular oxygen quantum yield of Verteporfin resulted in high biological efficacy. To achieve 50% mortality of cells four times lower light dose and five times lower concentration of Verteporfin were applied in comparison with PfII. The same level of cell damage was reached using 10 times higher light dose and two times higher concentration of MC540 in comparison with PfII. Our results confirm that singlet molecular oxygen based mechanism, prevalent for Verteporfin and PfII, was highly effective against melanoma cells. Verteporfin can be used at small doses with high cellular damage efficiency.     

Effect of heteroatom-doped carbon quantum dots on the red emission of metal-conjugated phthalocyanines through hybridization

Quantum dots (QDs) are significant fluorescent materials for energy transfer studies with phthalocyanines (Pcs) and phthalocyanine (Pc)-like biomolecules (such as chlorophylls). Carbon-based QDs, especially, have been used in numerous studies concerning energy transfer with chlorophylls, but the numbers of studies concerning energy transfer between phthalocyanines and carbon-based QDs are limited. In this study, peripherally, hydroxythioethyl terminal group substituted metal-free phthalocyanine (H₂Pc) and zinc phthalocyanine (ZnPc) were noncovalently (electrostatic and/or π–π interaction) attached to carbon QDs containing boron and nitrogen to form QD-Pc nanoconjugates. The QD-Pc conjugates were characterized using different spectroscopic techniques (Fourier transform infrared spectroscopy and transmission electron microscopy). The absorption and fluorescence properties of QD-Pc structures in solution were studied. It was found that the quantum yields of the QDs slightly decreased from 30% to 25% upon doping the QDs with heteroatoms B and N. Förster resonance energy transfer efficiency was calculated as 33% for BCN-QD/ZnPc. For the other conjugates, almost no energy transfer from QDs to Pc cores was observed. It was shown that the energy transfer between QDs to Pc cores was completely different from the energy transfer between QDs and photosynthetic pigments, and therefore we concluded that heteroatom doping in the QD structure and the existence of zinc metal in the phthalocyanine structure is obligatory for an efficient energy transfer.     

Structure-photodynamic activity relationships of substituted zinc trisulfophthalocyanines

To identify optimal features of metalated sulfophthalocyanine dyes for their use as photosensitizers in the photodynamic therapy of cancer, we synthesized a series of alkynyl-substituted trisulfonated phthalocyanines and compared their amphiphilic properties to a number of parameters related to their photodynamic potency. Varying the length of the substituted alkynyl side-chain modulates the hydrophobic/hydrophilic properties of the dyes providing a linear relationship between their n-octanol/water partition coefficients and retention times on reversed-phase HPLC. Aggregate formation of the dyes in aqueous solution increased with increasing hydrophobicity while monomer formation was favored by the addition of serum proteins or organic solvent. Trisulfonated zinc phthalocyanines bearing hexynyl and nonynyl substituents exhibited high cellular uptake with strong localization at the mitochondrial membranes, which coincided with effective photocytotoxicity toward EMT-6 murine mammary tumor cells. Further increase in the length of the alkynyl chains (dodecynyl, hexadecynyl) did not improve their phototoxicity, likely resulting from extensive aggregation of the dyes in aqueous medium and reduced cell uptake. Aggregation was evident from shifts in the electronic spectra and reduced capacity to generate singlet oxygen. When monomerized through the addition of Cremophor EL all sulfonated zinc phthalocyanines gave similar singlet oxygen yields. Accordingly, differences in the tendency of the dyes to aggregate do not appear to be a determining factor in their photodynamic potency. Our results confirm that the latter in particular relates to their amphiphilic properties, which facilitate cell uptake and intracellular localization at photosensitive sites such as the mitochondria. Combined, these factors play a significant role in the overall photodynamic potency of the dyes.     

Binding and photochemistry of enantiomeric 2-(3-benzoylphenyl)propionic acid (ketoprofen) in the human serum albumin environment.

Global analysis of circular dichroism multiwavelength data and time resolved fluorescence was applied to investigate the interaction of R(-)- and S(+)-ketoprofen (KP) with human serum albumin (HSA) in buffer solution at neutral pH. The most stable drug:protein adducts of 1 : 1 and 2 : 1 stoichiometry were characterized as regards the stability constants and the absolute circular dichroism spectra. The spectra of the diastereomeric 1 : 1 conjugates are negative with minima at ca. 350 nm for R(-)-KP and 330 nm for S(+)-KP, those of the 2 : 1 complexes are both negative with minimum at 340 nm and quite similar in shape to each other, thereby showing that the protein loses chiral recognition capability upon multiple binding. HSA intrinsic time resolved fluorescence data obtained exciting at 295 nm point to Trp 214 being located in the secondary binding site for both KP enantiomers. The photodegradation of the S(+)- and R(-)-KP:HSA complexes was studied by steady state photolysis using lambda(irr) > 320 nm. No decrease of the photodegradation quantum yields was observed in 1 : 1 complexes. An induction time for the photodegradation course in 2 : 1 complexes was observed. Transient absorption spectroscopy at lambda(exc) = 355 nm showed that triplet KP species were formed with stereo-differentiated lifetimes and high quantum yields (0.7-0.9). Secondary transients were consistent with the occurrence of photodecarboxylation and/or photoreduction within the protein matrix.     

Evaluation of human erythrocytes as model cells in photodynamic therapy

The role of erythrocytes as targets in photodynamic therapy is a controversially discussed topic in the literature. Therefore five different, but well known photosensitisers (three zinc phthalocyanines, tetrabenzoporphine and pheophorbide a delivered in liposomes were used for photodynamic treatment of human erythrocytes. The phototoxic effect on these cells showed pronounced differences. It was in the range: zinc phthalocyanine = pheophorbide a > tetrabenzoporphine > zinc octa-n-alkyl phthalocyanines. Data from the zinc octa-n-alkyl phthalocyanines were compared with photodynamic effects within cutaneous cell lines, treated under the same experimental conditions. The results show that erythrocytes are unlikely to make good models for predicting the efficiency of the photosensitiser in general, and the same applies to cells other than erythrocytes and in vivo. Possible reasons could be differences in dye accumulation. However, erythrocytes may well serve as model cells to explore the cellular and molecular mechanisms of photodynamic treatment.