FRET Measurement of Polymer Response under Shear.

Polymer solutions under shear flow are often observed in manufacturing processes. Classically, polymer behavior is represented by Kuhn's bead-spring model, in which only the elongation of polymer chains is assumed. In recent years, the compression of polymer chains under shear flow has been reported. In this study, we investigated the behavior of polymer chains dissolved in various concentrations under shear flow. We measured the time variation of the fluorescence intensity emitted from a FRET (fluorescence resonance energy transfer) polymer, which enabled us to study the change in the distance between both ends of a polymer chain. The polymer chains appeared to stretch and compress depending on the concentration of the polymer solution. The results showed that the deformation of polymer chains was different from the classical theory. The FRET measurement is a promising diagnostic method for understanding the dynamics of polymer chains.

Synthesis, photophysical properties, and photodynamic activity of positional isomers of TFPP-glucose conjugates.

The synthesis and characterization of a 'complete set' of positional isomers of tetrakis(perfluorophenyl)porphyrins (TFPP)-glucose conjugates (1OH, 2OH, 3OH, 4OH, and 6OH) are reported herein. The cellular uptake and photocytotoxicity of these conjugates were examined in order to investigate the influence of location of the TFPP moiety on the d-glucose molecule on the biological activity of the conjugates. An In vitro biological evaluation revealed that the certain of these isomers have a greater effect on cellular uptake and cytotoxicity than others. The TFPP-glucose conjugates 1OH, 3OH, and 4OH were found to exert exceptional photocytotoxicity in several types of cancer cells compared to 2OH and 6OH substituted isomers.

RAFT Synthesis and Characterization of Poly(Butyl-co-2-(N,N-Dimethylamino)Ethyl Acrylates)-block-Poly(Polyethylene Glycol Monomethyl Ether Acrylate) as a Photosensitizer Carrier for Photodynamic Therapy.

Polymer micelles are promising drug delivery systems for highly hydrophobic photosensitizers in photodynamic therapy (PDT) applications. We previously developed pH-responsive polymer micelles consisting of poly(styrene-co-2-(N,N-dimethylamino)ethyl acrylate)-block-poly(polyethylene glycol monomethyl ether acrylate) (P(St-co-DMAEA)-b-PPEGA) for zinc phthalocyanine (ZnPc) delivery. In this study, poly(butyl-co-2-(N,N-dimethylamino)ethyl acrylates)-block-poly(polyethylene glycol monomethyl ether acrylate) (P(BA-co-DMAEA)-b-PPEGA) was synthesized via reversible addition and fragmentation chain transfer (RAFT) polymerization to explore the role of neutral hydrophobic units in photosensitizer delivery. The composition of DMAEA units in P(BA-co-DMAEA) was adjusted to 0.46, which is comparable to that of P(St-co-DMAEA)-b-PPEGA. The size distribution of the P(BA-co-DMAEA)-b-PPEGA micelles changed when the pH decreased from 7.4 to 5.0, indicating their pH-responsive ability. The photosensitizers, 5,10,15,20-tetrakis(pentafluorophenyl)chlorin (TFPC), 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin (TFPP), protoporphyrin IX (PPIX), and ZnPc were examined as payloads for the P(BA-co-DMAEA)-b-PPEGA micelles. The encapsulation efficiency depended on the nature of the photosensitizer. TFPC-loaded P(BA-co-DMAEA)-b-PPEGA micelles exhibited higher photocytotoxicity than free TFPC in the MNNG-induced mutant of the rat murine RGM-1 gastric epithelial cell line (RGK-1), indicating their superiority for photosensitizer delivery. ZnPc-loaded P(BA-co-DMAEA)-b-PPEGA micelles also exhibited superior photocytotoxicity compared to free ZnPc. However, their photocytotoxicity was lower than that of P(St-co-DMAEA)-b-PPEGA. Therefore, neutral hydrophobic units, as well as pH-responsive units, must be designed for the encapsulation of photosensitizers.

Sugar and heavy atom effects of glycoconjugated chlorin palladium complex on photocytotoxicity.

Palladium(II) complexes of glycoconjugated porphyrin and pyrrolidine-fused chlorin were prepared to examine sugar and heavy atom effects on in vitro photocytotoxicity. Cellular uptake into HeLa cells was enhanced by introducing sugar units regardless of other features, such as the central ion (free base or palladium(II) ion) and the ring structure (porphyrin or chlorin). The palladium(II) complex of glycoconjugated pyrrolidine-fused chlorin (PdPC2) exerted an excellent degree of photocytotoxicity not only on HeLa cells, but also on metastatic B16-BL6 cells, weakly metastatic B16F1 cells, and metastatic 4T1 cells. However, free-base glycoconjugated pyrrolidine-fused chlorin (PC2) also exerted similar or much higher photocytotoxicity rather than PdPC2. Therefore, the palladium(II) ion did not improve the in vitro photocytotoxicity of PC2. The enhanced singlet oxygen generation of palladium(II) complexes (i.e., the heavy atom effect) was confirmed at least in O(2)-saturated D(2)O. In addition, the formation of hydrogen peroxide and hydroxyl radical were also detected in O(2)-saturated phosphate buffered saline. However, the reactive oxygen species (ROS) generation efficiency, which is the product of the (relative) quantum yield of each ROS and the light absorbing ability, did not fit the trends of photocytotoxicity seen for the photosensitizers. In our glycoconjugated photosensitizers tested, the best indicator of the photocytotoxicity was found to be the light absorbing ability (namely, the oscillator strength in the wavelength region applied in the photocytotoxicity test). These results indicated that photochemical characteristics of glycoconjugated photosensitizers were notably susceptible to the microenvironment. The biological characteristics, such as the sugar effect, were a much more reliable approach to improving the photocytotoxicity of photosensitizers.

Syntheses, characterization, and antitumor activities of platinum(II) and palladium(II) complexes with sugar-conjugated triazole ligands.

Four platinum(II) and palladium(II) complexes with sugar-conjugated bipyridine-type triazole ligands, [Pt(II)Cl(2)(AcGlc-pyta)] (3), [Pd(II)Cl(2)(AcGlc-pyta)] (4), [Pt(II)Cl(2)(Glc-pyta)] (5), and [Pd(II)Cl(2)(Glc-pyta)] (6), were prepared and characterized by mass spectrometry, elemental analysis, (1)H- and (13)C-NMR, IR as well as UV/VIS spectroscopy, where AcGlc-pyta and Glc-pyta denote 2-[4-(pyridin-2-yl)-1H-1,2,3-triazol-1-yl]ethyl 2,3,4,6-tetra-O-acetyl-ß-D-glucopyranoside (1) and 2-[4-(pyridin-2-yl)-1H-1,2,3-triazol-1-yl]ethyl ß-D-glucopyranoside (2), respectively. The solid-state structure of complex 6 was determined by single-crystal X-ray-diffraction analysis. These complexes exhibited in vitro cytotoxicity against human cervix tumor cells (HeLa) though weaker than that of cisplatin.

Effect of tertiary amino groups in the hydrophobic segment of an amphiphilic block copolymer on zinc phthalocyanine encapsulation and photodynamic activity.

Polymer micelles are promising nanocarriers for hydrophobic photosensitizers of photodynamic therapy (PDT). Poly(styrene-co-(2-(N,N-dimethylamino)ethyl acrylate))-block-poly(polyethylene glycol monomethyl ether acrylate) (P(St-co-DMAEA)-b-PPEGA; 1) was prepared via reversible addition and fragmentation chain transfer (RAFT) polymerization as a carrier for a zinc phthalocyanine (ZnPc) photosensitizer to be used in PDT. The DMAEA-unit composition in the P(St-co-DMAEA) segment was adjusted to 0.40 molar ratio, which caused a sharp increase in water-solubility when the pH decreased from 7.4 to 5.0. The polymer 1 micelle size distribution also shifted to lower when the pH decreased, whereas this change was not observed in PSt-co-PPEGA (2), which was previously reported. The UV-vis spectrum of the ZnPc-loaded micelles of polymer 1 exhibited relatively sharp Q bands, comparable to those measured in DMSO, indicating good compatibility of the condensed core with ZnPc. ZnPc-loaded micelles of polymer 1 exerted excellent photocytotoxicity in the MNNG-induced mutant of the rat murine RGM-1 gastric epithelial cell line (RGK-1). In contrast, the ZnPc-loaded micelles of polymer 2 were completely inactive under the same conditions. Fluorescence from the RGK-1 cells treated with ZnPc-loaded micelles of polymer 1 was observed after 4 h of co-incubation, while no fluorescence was observed in cells treated with ZnPc-loaded micelles of polymer 2. These results indicate that the pH-responsive nature and good compatibility with ZnPc exhibited by the polymer 1 micelles are essential characteristics of ZnPc carriers for efficient photodynamic therapy.

A fluorescent calix[4]arene with naphthalene units at the upper rim exhibits long fluorescence emission lifetime without fluorescence quenching.

We synthesised a new compound with four naphthyl groups in the upper rims of calix[4]arene (1). Compared to the monomer unit, compound 1 has redshifted absorption and fluorescence, together with high fluorescence quantum yield and long fluorescence lifetime, which is extremely rare because long fluorescence lifetime emission tends to reduce the quantum yield. Single-crystal X-ray analysis and quantum calculations in the S1 state revealed π-π through-space interactions between naphthalene rings.

Environment-sensitive emission of anionic hydrogen-bonded urea-derivative-acetate-ion complexes and their aggregation-induced emission enhancement.

Anions often quench fluorescence (FL). However, strong ionic hydrogen bonding between fluorescent dyes and anion molecules has the potential to control the electronic state of FL dyes, creating new functions via non-covalent interactions. Here, we propose an approach, utilising ionic hydrogen bonding between urea groups and anions, to control the electronic states of fluorophores and develop an aggregation-induced emission enhancement (AIEE) system. The AIEE ionic hydrogen-bonded complex (IHBC) formed between 1,8-diphenylnaphthalene (p-2Urea), with aryl urea groups at the para-positions on the peri-phenyl rings, and acetate ions exhibits high environmental sensitivities in solution phases, and the FL quantum yield (QY) in ion-pair assemblies of the IHBC and tetrabutylammonium cations is more than five times higher than that of the IHBC in solution. Our versatile and simple approach for the design of AIEE dye facilitates the future development of environment-sensitive probes and solid-state emitting materials.

Mitochondrial mode of action of a thymidine-based cisplatin analogue breaks resistance in cancer cells.

Cisplatin analogue complexes with platinum(II) and palladium(II) starting from 3',5'-diamino-3',5'-dideoxy-thymidines were synthesized, both with the D-erythro- and D-threo configurations. Complexes of the general formula [MCl(2)L] were obtained and characterized. NMR spectroscopic measurements and single crystal X-ray structure analysis showed that the metal centers are coordinated to the ligands by the amino groups in 3'- and 5'-positions and not through the thymine moiety. All ligands and complexes showed no significant in vitro activities except thymiplatin (cis-dichloro(3',5'-diamino-3',5'-dideoxy-D-threo-thymidine)platinum(II)). Detailed in vitro studies on the apoptosis pathway in lymphoma (BJAB), leukemia (NALM-6), and melanoma cells (Mel-HO) as well as on transfected or resistant cell lines were carried out. Thymiplatin significantly induced an apoptotic response, which was found to be associated with the loss of mitochondrial membrane potential and with caspase activation. The activity was shown to be independent of Fas-associated protein with death domain (FADD), but dependent on Bcl-2 expression. As a consequence, for thymiplatin a mitochondrial mode of action could be assigned. Moreover, the compound showed activity in cells resistant to common drugs, such as daunorubicin and vincristin, and showed synergistic effects with doxorubicin, vincristin, cytarabin, and daunorubicin.

Plasmon-enhanced luminescence from ultrathin hybrid polymer nanoassemblies for microscopic oxygen sensor application.

Plasmon-enhanced luminescence was developed for luminescent oxygen sensor application. Luminescent polymer Langmuir-Blodgett films containing platinum-porphyrin were assembled plane-to-plane with a silver nanoparticle array. The hybrid polymer nanoassemblies allow more than 10-fold luminescence enhancement in air. The luminescence intensity and lifetime measurements as functions of the number of layers revealed that some platinum-porphyrin, which is close to silver nanoparticles, is effectively enhanced. The enhancement enables us to monitor 2D oxygen distribution mapping on the micrometer scale.

Synthesis, photophysical properties and photocytotoxicity of mono-, di-, tri- and tetra-glucosylated fluorophenylporphyrins.

In order to explore the effect of substitution patterns on the photocytotoxicity of glycoconjugated porphyrins, we synthesized and characterized a 'complete set' of tetrakis(perfluorophenyl)porphyrins having beta-d-glucopyranosylthio groups on the phenyl ring. Among five possible derivatives, trans-substituted S-glucosylated porphyrin trans-2(OH) exerted outstanding photocytotoxicity (EC(50) value was < 5 nM) in HeLa cells. The excellent photocytotoxicity of trans-2(OH) was found to be attributable to several factors, namely high optical transition probability in aqueous media, efficient type I photoreactions and enhanced cellular uptake.

Synthesis and photocytotoxicity of S-glucosylated 5,10,15,20-Tetrakis(tetrafluorophenyl)porphyrin metal complexes as efficient (1)O(2)-generating glycoconjugates.

5,10,15,20-Tetrakis(4-(2,3,4,6-tetra-O-acetyl-beta-d-glucopyranosylthio)-2,3,5,6-tetrafluorophenyl)porphyrin 2a and its Zn(II), Pd(II), and Pt(II) complexes 2b, 2c, and 2d were prepared in excellent yields by nucleophilic substitution of the corresponding free-base porphyrin and metalloporphyrins with acetyl 2,3,4,6-tetra-O-acetyl-1-thio-beta-d-glucopyranoside. Deprotection of 2a, 2b, 2c, and 2d by alkaline hydrolysis afforded the corresponding S-glucosylated porphyrin 3a and its metal complexes 3b, 3c, and 3d. The structures and purity of all new photosensitizers were confirmed by elemental analysis and (1)H, (13)C, and (19)F NMR, UV-vis, and steady-state luminescence spectroscopy. The relative efficiency of singlet oxygen ((1)O(2)) production increased in the order of free-base fluoroporphyrins (2a and 3a) < Zn(II) complexes (2b and 3b) < Pd(II) complexes (2c and 3c), which can be explained in terms of the heavy-atom effect, while the (1)O(2)-producing efficiency of Pt(II) complexes (2d and 3d) were exceptionally low. In vitro photocytotoxicity of these eight S-glucosylated photosensitizers was examined in HeLa cells. Although all protected photosensitizers 2a, 2b, 2c, and 2d showed no photocytotoxicity, the photosensitizers 3a, 3b, and 3c exerted potent photocytotoxicity. These results clearly indicated that the sugar moieties of 3a, 3b, and 3c act as not only water-solubility-enhancing functionalities but also cellular-uptake-enhancing elements. Photocytotoxicity testing of 3a, 3b, and 3c in the presence of reactive oxygen species inhibitors suggested that (1)O(2) is the major mediator of cell death. Hence, the Zn(II) and Pd(II) complexes 3b and 3c are promising photosensitizers having cellular uptake-facilitating units (sugar moieties) and enhanced (1)O(2) generation due to the heavy-atom effect.

Antioxidant action of sugar-pendant C60 fullerenes.

The action of C60 fullerene and its derivatives as a radical-scavenging antioxidant has received much attention, but their reactivity toward free radicals and antioxidant capacity have not been well elucidated yet. In the present study, the reactivity of the two types of water-soluble, sugar-pendant C60 fullerenes, C60-1S and C60-2S, toward peroxyl radical and their effect against human plasma lipid peroxidation were measured. The rate constants for the reaction of C60-1S and C60-2S with peroxyl radicals were obtained from their effect on the bleaching of beta-carotene in lipid-SDS micelle system as 4.6 x 10(3) and 8.0 x 10(3) M(-1) s(-1) at 37 degrees C, respectively. They inhibited the free radical-induced lipid peroxidation in human plasma in a concentration-dependent manner. These results suggest that the sugar-pendant fullerenes C60-1S and C60-2S act as a radical-scavenging antioxidant with the activity similar to the phenolic antioxidants.

Extended X-ray absorption fine structure study on reaction of anti-tumor platinum complexes with reduced glutathione.

Reactions of cis-diamminedichloroplatinum(II) (cisplatin) and 1,1-cyclobutanedicarboxylatodiammineplatinum(II) (carboplatin) with reduced glutathione, a tripeptide that is abundant in cells, were studied by means of X-ray absorption spectroscopy. Back-scattering amplitudes F(i)(k) and phase shifts Phi(i)(k) were theoretically derived, and validated by applying them to calculate extended X-ray absorption fine structure (EXAFS) oscillations of cisplatin and K(2)[Pt(SCN)(4)] in the solid state. EXAFS oscillations of reaction mixtures of cisplatin or carboplatin with reduced glutathione were fitted to the standard EXAFS equation using the F(i)(k) and Phi(i)(k) functions to give the coordination numbers of N or O atoms (N(N/O)) and of Cl or S atoms (N(Cl/S)). For both cisplatin and carboplatin, the N(N/O) value decreased and the N(Cl/S) values increased monotonically as the reaction proceeded. However, the reaction rate for carboplatin was significantly slower than that for cisplatin.

Sugar-dependent photodynamic effect of glycoconjugated porphyrins: a study on photocytotoxicity, photophysical properties and binding behavior to bovine serum albumin (BSA).

The photocytotoxicity of four glycoconjugated porphyrins, namely 5,10,15,20-tetrakis[4-(beta-D-glucopyranosyloxy)phenyl]porphyrin (p-1a), 5,10,15,20-tetrakis[4-(beta-D-galactopyranosyloxy)phenyl]porphyrin (p-1b), 5,10,15,20-tetrakis[4-(beta-D-xylopyranosyloxy)phenyl]porphyrin (p-1c) and 5,10,15,20-tetrakis[4-(beta-D-arabinopyranosyloxy)phenyl]porphyrin (p-1d), was evaluated in HeLa cells in the concentration range from 1 to 7 microM using a light dose of 16 J x cm(-2) with a wavelength greater than 500 nm. The photocytotoxicity depends on the sugar moieties, and increases in the order of p-1d

A general route to pendant C-glycosyl 1,2- and 1,3-diamines.

Practical and convenient preparations of C-glycosyl 1,2- and 1,3-alkanediamines are described. Two 1,2-ethylenediamine derivatives were synthesized from acetylated allyl alpha-C-glycosyl compounds via dibromination, azidation, carbohydrate deprotection, and azide reduction. Four 1,3-propanediamine derivatives were prepared from acetylated sugar halides via C-glycosylation with sodiomalononitrile, followed by the reduction of the nitrile moieties and the deacetylation of the carbohydrate moiety. These 1,3-propanediamine derivatives have the beta-anomeric configurations. The methods reported here serve as general routes to access carbohydrate-diamine conjugates with C-glycosyl linkages.

Poly[[{µ(3)-tris-[2-(4-phenyl-1,2,3-triazol-1-yl)eth-yl]amine}silver(I)] hexa-fluorido-phosphate].

The title compound, {[Ag(L)]PF(6))(n) {L is tris-[2-(4-phenyl-1,2,3-triazol-1-yl)eth-yl]amine, C(30)H(30)N(10)}, consists of alternating two-dimensional cationic layers of [Ag(L)](+) and anionic PF(6) (-) layers. Each Ag(I) atom is three coordinated in a T-shaped geometry by three N atoms from three ligands. Each ligand links three Ag(I) atoms, generating a two-dimensional network structure with two different metallacycles, A and B. In A, eight coordination units from four ligands connect four Ag(I) atoms, forming a 48-membered ring. In B, four coordination units from two ligands link two Ag(I) atoms, forming a 24-membered ring. Each B ring is surrounded by four A rings, and each A ring has four A and four B rings as neighbours. This cationic layer thus generates a 4.8(2) topology network, with each Ag(I) centre and ligand acting as a three-connected topological node.

Sugar-dependent aggregation of glycoconjugated chlorins and its effect on photocytotoxicity in HeLa cells.

In order to explore the influence of the sugar moieties of glycoconjugated chlorins on the photocytotoxicity, we studied the photochemical properties of four glycoconjugated chlorins in aqueous media such as cytoplasm and the concentration dependence of photocytotoxicity in HeLa cells. In phosphate-buffered saline, the fluorescence intensities of 5,10,15,20-tetrakis[3-(beta-D-glucopyranosyloxy)phenyl]chlorin (m-1a) and 5,10,15,20-tetrakis[3-(beta-D-galactopyranosyloxy)phenyl]chlorin (m-1b), i.e., chlorins having hexose groups, were about 2-fold greater than those of 5,10,15,20-tetrakis[3-(beta-d-xylopyranosyloxy)phenyl]chlorin (m-1c) and 5,10,15,20-tetrakis[3-(beta-d-arabinopyranosyloxy)phenyl]chlorin (m-1d), i.e., chlorins having pentose groups, owing to a sugar-dependent difference of aggregation behavior. While no cytotoxicity was found in the dark, the highest photocytotoxicity was shown by m-1a (82% inhibition) in HeLa cells. This was higher than those of m-1b, m-1c, m-1d and tetraphenylporphyrin tetrasulfonic acid. The glycoconjugated chlorins except for m-1b appeared to be distributed diffusely throughout the cytoplasm. Among the four photosensitizers, m-1a showed the highest intensity in confocal fluorescence images, in agreement with the in vitro photocytotoxicity results. For m-1c, no photocytotoxicity was found at drug concentrations from 0.2 to 0.04 microM. Hence, sugar-dependent aggregation is not the major reason for the unexpected lack of efficacy of m-1c, which is uptaken efficiently by HeLa cells. For the glycoconjugated chlorins, these results suggest the biological aspects of sugar moiety play much crucial role rather than chemical aspects.

Emergence of physiological rhythmicity in term and preterm neonates in a neonatal intensive care unit.

BACKGROUND: Biological rhythmicity, particularly circadian rhythmicity, is considered to be a key mechanism in the maintenance of physiological function. Very little is known, however, about biological rhythmicity pattern in preterm and term neonates in neonatal intensive care units (NICU). In this study, we investigated whether term and preterm neonates admitted to NICU exhibit biological rhythmicity during the neonatal period. METHODS: Twenty-four-hour continuous recording of four physiological variables (heart rate: HR recorded by electrocardiogram; pulse rate: PR recorded by pulse oxymetry; respiratory rate: RR; and oxygen saturation of pulse oxymetry: SpO2) was conducted on 187 neonates in NICU during 0-21 days of postnatal age (PNA). Rhythmicity was analyzed by spectral analysis (SPSS procedure Spectra). The Fisher test was performed to test the statistical significance of the cycles. The cycle with the largest peak of the periodogram intensities was determined as dominant cycle and confirmed by Fourier analysis. The amplitudes and amplitude indexes for each dominant cycle were calculated. RESULTS: Circadian cycles were observed among 23.8% neonates in HR, 20% in PR, 27.8% in RR and 16% in SpO2 in 0-3 days of PNA. Percentages of circadian cycles were the highest (40%) at < 28 wks of gestational age (GA), decreasing with GA, and the lowest (14.3%) at > or = 37 wks GA within 3 days of PNA in PR and were decreased in the later PNA. An increase of the amplitude with GA was observed in PR, and significant group differences were present in all periods. Amplitudes and amplitude indexes were positively correlated with postconceptional age (PCA) in PR (p < 0.001). Among clinical parameters, oxygen administration showed significant association (p < 0.05) with circadian rhythms of PR in the first 3 days of life. CONCLUSION: Whereas circadian rhythmicity in neonates may result from maternal influence, the increase of amplitude indexes in PR with PCA may be related to physiological maturity. Further studies are needed to elucidate the effect of oxygenation on physiological rhythmicity in neonates.

Syntheses, photophysical properties, and photocytotoxicities of tetrakis(fluorophenyl)porphyrin derivatives bearing 2-hydroxyethylthio groups.

Porphyrin derivatives for photodynamic therapy are frequently modified with hydrophilic groups to improve their water solubility; however, such hydrophilic groups not only improve the solubility but also affect the photodynamic behavior of the compound. The suitable number and pattern of the hydrophilic substituents depend on the nature of the hydrophilic groups. In this article, we explore the optimum architecture for 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin (TFPP) derivatives bearing 2-hydroxyethylthio substituents. All five derivatives, namely mono-, cis-bis-, trans-bis-, tris- and tetrakis-substituted TFPP, were successfully synthesized by the nucleophilic aromatic substitution of TFPP with 2-hydroxyethanethiol, separated, and subsequently identified using ESI-TOF mass spectrometry and (1)H and (19)F NMR spectroscopies. The hydrophilicity of the compounds increased with an increase in the number of 2-hydroxyethylthio groups. The singlet oxygen and hydroxyl radical generation efficiencies were estimated using chemical probes following photoirradiation (λ>500nm). trans-Bissubstituted TFPP exhibited the highest efficiency for both singlet oxygen and hydroxyl radical generation. The photocytotoxicities of the photosensitizers were evaluated in HeLa cells following photoirradiation (λ>500nm, 16Jcm(-2)), and increased with an increase in number of 2-hydroxyethylthio groups. In the case of 2-hydroxyethylthio-substituted TFPPs, the fully substituted TFPP was the most efficient architecture plausibly because of the result of the hydrophilicity of the compound rather than a greater efficiency in the generation of reactive oxygen species.