Birgit Wagner

The mechanism of singlet to triplet transitions of pentacene guests in p-terphenyl and benzoic acid crystals

Abstract In this paper we examine the effect of the different site configurations on the S 1 ⇝T 1 intersystem crossin (ISC) of pentacene in p -terphenyl (ptp) and benzoic acid (bza) crystals by measuring site-selectively the fluorescence quantum yield of pentacene as function of temperature in the range 4.2–140 K. The local structures of the four sites (O 1 , O 2 , O 3 , O 4 ) for pentacene in ptp are simulated using the Buckingham (exp-6) potential. The present study provides a rationalization for the temperature dependent ISC rates of pentacene at O 1 and O 2 in ptp and pentacene in bza as well as for the enhanced, temperature independent ISC rates of pentancene at O 3 and O 4 in ptp.

Pseudolocal phonons in p-terphenyl : pentacene single crystals

The structural nature of the phonon sidebands in the fluorescence and excitation spectra of pentacene guests in p‐terphenyl crystals at 4.2 K are investigated using site‐selective spectroscopy. The distinct features in the phonon sideband structure were observed to depend significantly on the guest site configuration of pentacene occupying four inequivalent sites in the triclinic p‐terphenyl lattice. The sharp peaks dominating the phonon sideband structure are assumed to arise from the pseudolocal phonons. The eigenvalues and eigenvectors of the pseudolocal phonons are calculated carrying out a modified normal mode analysis on the distinct pentacene site configurations including the contribution of all intermolecular atom‐pair interactions.

Vibronically induced intersystem crossing in pentacene in p-terphenyl and benzoic acid crystals

Abstract The temperature behaviour of pentacene fluorescence of p-terphenyl: pentacene and benzoic acid: pentacene is investigated by site-selectively measuring the fluorescence quantum yield Φ F of pentacene in the four sites (O 1 , O 2 , O 3 , O 4 ) in p-terphenyl (ptp) and in the single site (O 0 ) in benzoic acid (bza) varying the temperature from 4.2 to 140 K. A theoretical analysis of the experimental data yields that the temperature dependences of Φ ptp F (O 1 ), Φ ptp F (O 2 ) and Φ bza F (O 0 ) arise from a vibronically induced intersystem crossing due to an out-of-plane vibrational mode of pentacene.

Taxol Inclusion Complexes with a Cyclodextrin Dimer: Possibilities to Detoxify Chemotherapeutics and to Target Drugs Specifically to Tumors?

The natural drug, paclitaxel (taxol), is highly effectiveas a tumor chemotherapeuticwith a low probability of inducing chemoresistance,but shows severe toxic side effectsat the therapeutic dose. How can this toxicitybe overcome? Here we report the synthesisof cyclodextrin dimers connected at thesecondary face by amide-bonded aliphatic spacers.The spacer length of one of the dimers referred to asdiβCD(2N-A4C5A4) or dimer 7cmatches the distance between the twobenzoic acid residues of paclitaxel. We investigated the physical inclusion of taxol into this dimer using the TNS-label competition method. Affinity constants with the dimer in comparison to free β-cyclodextrin are found to be of the order of 107 l/mole.When included into the cyclodextrin dimer, the drug shows a considerable time delay of incorporation into human tumor cell cultures (OAT SCLC cells) or a total exclusion from the cells. This is the prerequisite to avoid intoxication of other organs of a patient. Possibilities are discussed to detoxify chemotherapeutics and to target their inclusioncomplexes specifically to tumors using specific biological signals.

Carrier systems in PDT II: accumulation strategies of biotin-avidin coupled photosensitizers developed on cultured tumor cells

Two possibilities to accumulate photosensitizing drugs at the surface of cultured tumor cells were exploited: biotinylation of the cell surface followed by avidin and dibiotin, and reaction with a biotinylated antibody followed by avidin and biotinylated sulfophthalocyanin. Both reactions were performed successfully. The latter leads to enhanced phototoxicity of the accumulated drug.

How many molecules of a photosensitizer are necessary to photosensitize a tumor cell

Diglycosylated porphyrinoids were shown to stack at the outer cell membrane of tumor cells in vitro. Similar phototoxicities are acquired as with the non-glycosylated drugs at amounts of only 1% of that normally taken up of the non-glycosylated drugs. This means that a strict positioning of sensitizers at sensitive compartments may reduce the amount of sensitizer necessary to sensitize a tumor cell to about 106 molecules per cell. Similar numbers were seen only in erythrocytes and with immunoconjugates in ovarian cancer. This low amount facilitates photosensitizer transport against intratumoral pressure gradients.

Intermolecular and Intramolecular Radiationless Processes in p-Terphenyl and Benzoic-Acid Single Crystals Doped with Tetra-Cene or Pentacene

Abstract Singlet excitation energy transfer processes and inter-system crossing in the mixed crystalline systems, p-terphenyl: :tetracene, p-terphenyl:pentacene and benzoic acid:pentacene were investigated in the temperature range 2 - 300 K using stationary fluorescence spectroscopy.

Cyclodextrin Dimers Used To Prevent Side Effects of Photochemotherapy and General Tumor Chemotherapy

Recent developments of polyphasic tumor detection and tumor therapy including applications of dimeric cyclodextrin inclusion complexes of high affinity for Photodynamic Tumor Therapy (PTT) porphyrinoids are discussed in the light of future applications of similar methodology to general tumor chemotherapy. These approaches hopefully will end the martyrium of patients undergoing tumor chemotherapy today.

Subcellular storage compartments of bacteriopheophorbide sensitizers

Fluorescence colocalization with the Golgi specific stain, NBD-ceramide, and the mitochondrial localizing stain, Rhodamine 123, confirmed the earlier assumption that the Golgi apparatus is one of the prominent storage compartments for bacteriopheophorbide esters in OAT 75 SCLC cells and several amelanotic melanoma cell lines (A375, Melur SP18, SkAMel 25). Furthermore, a diffuse staining of mitochondria, of non-structured cytoplasm, and an additional storage in melanine vesicles of the amelanotic melanoma cells suggests further storage compartments with quantitatively different contributions to the phototoxicity of bacteriochlorophyll-derived photosensitizers. Independent observations of early phototoxic effects on microfilamentous networks, enzymatic activities (succinate dehydrogenase, lactate dehydrogenase), and redistribution phenomena following primary uptake of the sensitizers let us assume that only a part of the 108 molecules taken up by a cell contribute directly to phototoxicity. Thus it may be asked if a proper subcellular positioning of only a few sensitizer molecules may have similar phototoxic effects as the huge amounts stored at apparently ineffective sites.

Photosensitization of tumor cells: are comparable conditions an impossible dream?

Photodynamic therapy (PDT)-induced kinetics of apoptosis were studied in V79 cells using several differently localized photosensitizing dyes, mostly tetraphenylporphine derivatives. Apoptotic fractions were quantified by flow cytometry after staining the samples by the terminal deoxynucleotidyl transferase (TdT)-assay. Methylene blue derivative (MBD), a new dye for PDT, and 5-aminolevulinic acid (ALA)-induced protoporphyrin IX that are both localized in mitochondria, induced apoptosis rapidly within hours after PDT. With MBD it was shown that rapid apoptosis was induced only with dye concentration above a certain threshold. With a lower dye concentration apoptosis was delayed more than one day and was induced due to inhibition of oxidative phosphorylation. After PDT with two membrane localized dyes, tetra(3- hydroxyphenyl)porphyrin (3THPP) and Photofrin, maximal induction of apoptosis took about 12 h. With two lysosomal localized sulfonated meso-tetraphenylporphines (TPPS2a and TPPS4) no apoptosis was induced until more than 12 h after PDT. The results are discussed in relation to evidence in the literature on the nature of possible pathways involved.