Beate Röder

Singlet oxygen quantum yields of different photosensitizers in polar solvents and micellar solutions

The singlet oxygen luminescence method and the photochemical methods using 1,3-diphenylisobenzofuran (DPBF) or bilirubin ditaurate (BDT) as chemical quenchers were employed to determine the single oxygen quantum yields (ΦΔ) of different phthalocyanines and tris(2,2″-bipyridyl)ruthenium(II) dichloride in dimethylformamide (DMF) or aqueous micellar solution of 0.1 M CTAC (cetyltrimethylammonium chloride). Additionally, a perylenetetracarboxylic acid diimide derivative was examined in DMF. In a series of tetrasulfonated phthalocyanines (PTS) the following order was found: ZnPTS > GaPTS > AlPTS ≈ H2PTS > CoPTS. In general, the singlet oxygen quantum yields are higher in DMF than in 0.1 M CTAC/H2O. The results obtained with the photochemical systems are comparable with those obtained by the photophysical method. The photochemical DPBF method results in absolute values of ΦΔ. However, in micellar solution, chain reactions occur when DPBF is used as chemical quencher in the photo-oxidative process. This problem ...

Novel photosensitizer-protein nanoparticles for photodynamic therapy: photophysical characterization and in vitro investigations.

In this work two types of pheophorbide-HSA (Pheo-HSA) nanoparticles, PHSA40 and PHSA100, were prepared and their photophysical and photosensitizing properties were investigated. Due to intramolecular interactions the singlet oxygen quantum yield of PHSA40 and PHSA100 is very low (less than 0.1). Intracellular uptake and phototoxicity of pheophorbide a as well as of the Pheo-HSA nanoparticles were studied in Jurkat cells. The HSA nanoparticles do not influence the amount of dye accumulation in cells. After 24h incubation, PHSA40 and PHSA100 showed a higher phototoxicity than Pheo. The reason for this behavior is an efficient nanoparticle decomposition in the cellular lysosomes. The process of drug release during incubation of cells with Pheo-HSA nanoparticles was illustrated by fluorescence lifetime imaging (FLIM) and confocal laser scanning microscopy (CLSM). The final phototoxicity of Pheo-HSA is at the same scale as induced by free Pheo. The drug release ability of HSA nanoparticles shows the possibility to use such formulations as drug carriers in PDT treatment. Therefore, this work constructs a standard for further investigation and optimization of photosensitizer-HSA drug carrier system.

New insights to primary photodynamic effects--Singlet oxygen kinetics in living cells.

The kinetics of chemical singlet oxygen quencher consumption inside living cells during low dose illumination was revealed via time resolved singlet oxygen luminescence detection. Deviations of the measured data from the common theoretical model for (1)O(2) kinetics forced the authors to consider a one-dimensional diffusion model for description of the kinetics of singlet oxygen generated by membrane localized photosensitizers. Our observations reconcile seemingly contradictory reports presenting different values for the efficiency of singlet oxygen interaction with cells.

Photodynamic inactivation of multi-resistant bacteria (PIB) - a new approach to treat superficial infections in the 21st century.

The increasing resistance of bacteria against antibiotics is one of the most important clinical challenges of the 21st century. Within the gram‐positive bacteria the methicillin‐resistant Staphylococcus aureus and Enterococcus faecium represent the major obstacle to successful therapy. Apart from the development of new antibiotics it requires additional differently constituted approaches, like photodynamic inactivation in order to have further effective treatment options against bacteria available. Certain dyes, termed photosensitizers, are able to store the absorbed energy in long‐lived electronic states upon light activation with appropriate wavelengths and thus make these states available for chemical activation of the immediate surroundings. The interaction with molecular oxygen, which leads to different, very reactive and thus cytotoxic oxygen species, is highlighted. In this review the application of the photodynamic inactivation of bacteria will be discussed regarding the possible indications in dermatology, like localized skin and wound infections or the reduction of nosocomial colonization with multi‐resistant bacteria on the skin. The crucial advantage of the local application of photosensitizers followed by irradiation of the area of interest is the fact that independent of the resistance pattern of a bacterium a direct inactivation takes place similarly as with an antiseptic. In this review the physical‐chemical and biological basics of photo‐dynamic inactivation of bacteria (PIB) will be discussed as well as the possible dermatological indications.

Preparation and photophysical properties of halogenated silicon(IV) phthalocyanines substituted axially with poly(ethylene glycol) chains

Abstract A series of silicon(IV) phthalocyanines with two axial poly(ethylene glycol) chains SiPcX 8 [(OCH 2 CH 2 ) n OCH 3 ] 2 (X=H, Cl, Br; n ≈16) have been prepared of which the photosensitizing properties are enhanced as the periphery of the macrocycle is substituted with heavier halogens.

On the Influence of Higher Excited States on the ISC Quantum Yield of Octa‐aL‐alkyloxy‐substituted Zn‐Phthalocyanine Molecules Studied by Nonlinear Absorption

Abstract— Octa‐aL‐alkyloxy‐substituted Zn‐phthalocyanines are an interesting class of far red‐absorbing photosensitizers. The chemical structure, the calculated steric conformation, the observed linear optical properties and an anomalous luminescence from a higher than S, excited state are reported. To study the optical properties of higher excited states and their occupation dynamics up to delay times of 15 ns we have carried out measurements of transient absorption spectra after 14 ps pulsed, resonant B‐band and Q‐band excitation. From these measurements the excited state singlet‐singlet and triplet‐triplet spectra as well as the intersystem crossing (ISC) quantum yields are obtained. The main result is an excitation wavelength‐dependent ISC quantum yield that can be explained by an additional ISC channel between higher excited singlet and triplet states. The large rate of this channel is justified by the resonance between higher triplet states, observed in the triplet‐triplet spectrum and the B, absorption band. Using kinetic model calculations, a lifetime of the higher excited singlet state of some picoseconds is predicted and the influence of a two‐step absorption process on the population density of this higher excited singlet state is discussed.

On the Correlation Between Hydrophobicity, Liposome Binding and Cellular Uptake of Porphyrin Sensitizers

Abstract A crucial factor in choosing a porphyrin or analogous photosensitizer for photodynamic therapy (PDT) is its ability to incorporate into the cells. For hydrophobic compounds that partition passively into the cytoplasmic membrane, a partition coefficient between an organic solvent and water, P, is one factor that could be used to predict the molecules ability to diffuse into biomembranes. We synthesized several porphyrins, modified with two, three or four meso-substituents and studied their spectroscopic and photophysical properties. The octanol–water partitioning coefficients, log P, were calculated as a parameter for hydrophobicity. We found these porphyrins to be very hydrophobic, with log P values in the range of 8.9–11.8. These were correlated with the binding constants of these porphyrins into liposomes, Kb, as well as to their uptake by cells. The correlation between the estimated log P and Kb is nearly linear but negative, indicating, apparently, that there is lesser binding to liposomes with increased hydrophobicity. On the other hand, all of the studied porphyrins are taken up by cells, but there is no clear correlation between cellular uptake and the log P or Kb. Lipinskis pharmacological “rule of 5” predicts poor permeation of drugs into cells when log P is greater than five. This may be relevant for diffusional binding to liposomes, where aqueous aggregation can interfere strongly with cellular uptake. In such extreme conditions, neither liposome binding nor other rules seem to predict porphyrin behavior in vitro.

Globular dendrimers involving a C60 core and a tetraphenyl porphyrin function

The nanoenvironment provided by the neighboring dendra characteristically influences the redox potentials and the photophysical properties of the tetraphenylporphyrin–zinc (Zn-TPP; denoted as P in Figure) chromophore within the dendrimers 1, which are based on C60 as a structure-determining core. Such functional dendrimers represent a new prototype of model systems for heme proteins (1).

Photophysical studies of the pheophorbide a dimer

This work reports on a monomer-dimer equilibrium state of pheophorbide a in solution. A methodology for controlling the equilibrium constant by use of temperature and solvent variation is described. The absorption spectrum of the dimer is calculated, using different prepared equilibria of monomer and dimer in solution. We propose that these aggregates provide a good model for understanding the dimerization process in tetrapyrroles.

Correlation of photophysical parameters with macrocycle distortion in porphyrins with graded degree of saddle distortion

Different porphyrin conformations are believed to play a role in controlling the cofactor properties in natural tetrapyrrole-protein complexes. In order to study the correlation between macrocycle nonplanarity and physicochemical properties in detail, a series of six porphyrins with graded degree of macrocycle distortion was investigated. These conformationally designed porphyrins are based on the successive introduction of beta-ethyl groups into the tetraphenylporphyrin parent macrocycle and the degree of nonplanarity is dependent on the number and localization of the beta-ethyl meso-phenyl interactions. The electronic properties of the complete series of porphyrins were investigated in solution. It was found that the singlet and triplet properties depend not only on the out-of-plane distortion parameter but also on the type of central metal. Moreover, it was found that macrocycle distortion affects the singlet state properties significantly stronger than the triplet properties. In addition, the efficiency of energy transfer to molecular oxygen was investigated. It was shown that the singlet oxygen quantum yield depends strongly on the triplet state lifetime of the porphyrins, resulting in differences between the decrease of intersystem crossing and singlet oxygen quantum yield. The observed gradual change of electronic parameters of base free tetraphenylporphyrins with increasing deformation of the macrocycle indicates the validity of using conformationally designed porphyrins to fine-tune photophysical properties.