Eugeny A. Ermilov

Brightness through Local Constraint-LNA-Enhanced FIT Hybridization Probes for In Vivo Ribonucleotide Particle Tracking

Imaging the dynamics of RNA in living cells is usually performed by means of transgenic approaches that require modification of RNA targets and cells. Fluorogenic hybridization probes would also allow the analysis of wild-type organisms. We developed nuclease-resistant DNA forced intercalation (FIT) probes that combine the high enhancement of fluorescence upon hybridization with the high brightness required to allow tracking of individual ribonucleotide particles (RNPs). In our design, a single thiazole orange (TO) intercalator dye is linked as a nucleobase surrogate and an adjacent locked nucleic acid (LNA) unit serves to introduce a local constraint. This closes fluorescence decay channels and thereby increases the brightness of the probe-target duplexes. As few as two probes were sufficient to enable the tracking of oskar mRNPs in wild-type living Drosophila melanogaster oocytes.

Omega-3 fatty acids: Benefits for cardio-cerebro-vascular diseases

BACKGROUND AND PURPOSE Intracranial artery stenosis (ICAS) is a narrowing of an intracranial artery, which is a common etiology for ischemic stroke. In this commentary, we review key aspects of the discrimination between non-stroke controls and ischemic stroke patients on the background of phospholipid ω3-fatty acid (DHA, EPA) composition. The discussion is embedded in the presentation of general effects of long-chain ω3 polyunsaturated fatty acids (PUFAs) in cardio-cerebro-vascular diseases (CCVDs) and Alzheimer dementia (AD). SUMMARY OF COMMENTARY ICAS is a common stroke subtype and has emerged as a major factor in recurrent stroke and vascular mortality. DHA and EPA are important fatty acids to distinguish between NCAS (no cerebral arteriosclerotic stenosis) and ICAS in stroke. The risk of ICAS is inversely correlated with the DHA content in phospholipids. Furthermore, a mechanistic explanation has been proposed for the beneficial effects of PUFAs in CCVDs and AD. CONCLUSIONS Whereas the beneficial effects of EPA/DHA for cardiovascular diseases and stroke seem to be beyond question, preventive effects in patients with very mild cognitive dysfunction and beginning Alzheimers disease undoubtedly need confirmation by larger clinical trials. A collaborative international basic science approach is warranted considering cautiously designed studies in order to avoid ethical problems.

Formation and energy transfer property of a subphthalocyanine–porphyrin complex held by host–guest interactions

A stable 2 : 1 host-guest complex is formed between a beta-cyclodextrin-conjugated subphthalocyanine and a tetrasulfonated porphyrin in water. The complex exhibits an energy transfer property from the excited subphthalocyanine to the porphyrin core with an excitation energy transfer quantum yield of 0.38.

Annulated Dinuclear Metal-Free and Zn(II) Phthalocyanines : Photophysical Studies and Quantum Mechanical Calculations

The results of steady-state and time-resolved absorption and fluorescence experiments as well as quantum mechanical density functional theory (DFT) calculations of metal-free and Zn(II) mononuclear and dinuclear (sharing a common benzene ring) phthalocyanines are presented. A detailed comparison between measured and calculated absorption spectra of all compounds is done, showing a good agreement between theory and experiment. The NH tautomerization for phthalocyanines with an extended pi-electron system was shown for the first time at room temperature. The photophysical properties of all possible NH tautomers of metal-free dinuclear Pc have been fully characterized. In the first tautomer, Pc(parallel), both pairs of hydrogen atoms are parallel to the connection line of two Pc units. The maximum of the lowest-energy Q absorption band, lambda abs, in Pc(parallel) is located at 832 nm, whereas the spectral position of the fluorescence maximum lies at lambdafl=837 nm. The second NH tautomer, Pc(perpendicular) (lambdaabs=853 nm, lambdafl=860 nm), presents the two pairs of hydrogen atoms perpendicularly orientated to the covalent axis, and the third one, Pc(mix) (lambdaabs=864 nm, lambdafl=872 nm), contributing in a minor extend to the absorption and fluorescence spectra of the metal-free dinuclear phthalocyanine, has one perpendicular and one parallel pair of hydrogen atoms. Obviously, only one configuration exists in the case of the Zn(II)-containing dinuclear phthalocyanine (lambdaabs=845 nm, lambdafl=852 nm).

Synthesis and characterization of quantum dots designed for biomedical use

Semiconductor quantum dots (QDs) have become promising nanoparticles for a wide variety of biomedical applications. However, the major drawback of QDs is their potential toxicity. Here, we determined possible cytotoxic effects of a set of QDs by systematic photophysical evaluation in vitro as well as in vivo. QDs were synthesized by the hydrothermal aqueous route with sizes in the range of 2.0-3.5 nm. Cytotoxic effects of QDs were studied in the human pancreatic carcinoid cell line BON. Cadmium telluride QDs with or without zinc sulfide shell and coated with 3-mercaptopropionic acid (MPA) were highly cytotoxic even at nanomolar concentrations. Capping with l-glutathione (GSH) or thioglycolic acid (TGA) reduced the cytotoxicity of cadmium telluride QDs and cadmium selenide QDs. Determination of the toxicity of QDs revealed IC50 values in the micromolar range. In vivo studies showed good tolerability of CdSe QDs with ZnS shell and GSH capping. We could demonstrate that QDs with ZnS shell and GSH capping exhibit low toxicity and good tolerability in cell models and living organisms. These QDs appear to be promising candidates for biomedical applications such as drug delivery for enhanced chemotherapy or targeted delivery of light sensitive substances for photodynamic therapy.

Tetra-triethyleneoxysulfonyl substituted zinc phthalocyanine for photodynamic cancer therapy

Photodynamic therapy (PDT) has emerged as an effective and minimally invasive treatment option for several diseases, including some forms of cancer. However, several drawbacks of the approved photosensitizers (PS), such as insufficient light absorption at therapeutically relevant wavelengths hampered the clinical effectiveness of PDT. Phthalocyanines (Pc) are interesting PS-candidates with a strong light absorption in the favourable red spectral region and a high quantum yield of cancer cell destroying singlet oxygen generation. Here, we evaluated the suitability of tetra-triethyleneoxysulfonyl substituted zinc phthalocyanine (ZnPc) as novel PS for PDT. ZnPc-induced phototoxicity, induction of apoptosis as well as cell cycle arresting effects was studied in the human gastrointestinal cancer cell lines of different origin. Photoactivation of ZnPc-pretreated (1-10 μM) cancer cells was achieved by illumination with a broad band white light source (400-700 nm) at a power density of 10 J/cm(2). Photoactivation of ZnPc-loaded cells revealed strong phototoxic effects, leading to a dose-dependent decrease of cancer cell proliferation of up to almost 100%, the induction of apoptosis and a G1-phase arrest of the cell cycle, which was associated with decrease in cyclin D1 expression. By contrast, ZnPc-treatment without illumination did not induce any cytotoxicity, apoptosis, cell cycle arrest or decreased cell growth. Antiangiogenic effects of ZnPc-PDT were investigated in vivo by performing CAM assays, which revealed a marked degradation of blood vessels and the capillary plexus of the chorioallantoic membrane of fertilized chicken eggs. Based on our data we think that ZnPc may be a promising novel photosensitizer for innovative PDT.

Switching the photoinduced processes in host–guest complexes of β-cyclodextrin-substituted silicon(IV) phthalocyanines and a tetrasulfonated porphyrin

Porphyrins and phthalocyanines are two attractive classes of functional dyes for the construction of artificial light harvesting and charge separation molecular systems. The assembly of these components by supramolecular approach is of particular interest as this provides a facile route to build multi-chromophoric arrays with various architectures and tuneable photophysical properties. We report herein a series of host-guest complexes formed between a tetrasulfonated porphyrin and several silicon(IV) phthalocyanines substituted axially with two permethylated β-cyclodextrin units via different spacers. As shown by electronic absorption and fluorescence spectroscopic methods, the two components bind spontaneously in a 1:1 manner in water with large binding constants in the range of 1.1 × 10(7) to 3.5 × 10(8) M(-1). The photophysical properties of the resulting supramolecular complexes have also been studied in detail using steady-state and time-resolved optical spectroscopic methods. It has been found that two major photoinduced processes, namely fluorescence resonance energy transfer and charge transfer are involved which are controlled by the spacer between the β-cyclodextrin units and the silicon centre of phthalocyanine. Despite the fact that charge transfer is a thermodynamically favourable process for all the complexes, only the ones with a tetraethylene glycol or oxo linker exhibit an efficient charge transfer from the excited phthalocyanine to the porphyrin entity. The lifetimes of the corresponding charge-separated states have been determined to be 200 and 70 ps by picosecond pump-probe experiments.

Spectroscopic study of NH-tautomerism in novel cycloketo-tetraphenylporphyrins

The NH-tautomerism is a fundamental property of all metal-free porphyrins. In the present study it was investigated for three novel nonsymmetrical cycloketo-tetraphenylporphyrins in isotropic solutions. The combination of steady-state absorption and fluorescence techniques with decay-associated fluorescence spectroscopy was demonstrated to be a powerful tool to bring into light the photophysical properties of individual NH-tautomers even at room temperature. For all investigated free-base porphyrins, the equilibrium concentration of one tautomer, named T1, which has a lower frequency of the S(0,0)-->S(1,0) transition, was found to be higher than the concentration of the other tautomer, named T2, even at room temperature. Lowering the temperature enriches the population of tautomer T1 and it becomes dominant in absorption and fluorescence. The fluorescence decay time of tautomer T1 was found to be approximately three times shorter compared to that of tautomer T2, whereas both tautomers have similar fluorescence quantum yields. In contrast only one conformation exists for zinc cycloketo-porphyrin, which was used as reference compound.

Observation of polymer degradation processes in photovoltaic modules via luminescence detection

The estimation of PV-modules lifetime facilitates the further development and helps to lower risks for producers and investors. One base for this extensive testing work is the knowledge of the degradation kinetics of encapsulating polymer materials. Besides ethylen-vinylacetate copolymer (EVA), which is the prevalent material for encapsulation, new materials like Poly-Vinyl-Butyral (PVB), and thermoplastic Poly-Urethan (TPU) become available and need the assessment of their properties and the durability impact. In this context is it very important to identify the extent of degradation caused by different parameters in order to identify the determining factor of polymer degradation as well as potential interactions between different degradation processes. To simulate long time degeneration processes accelerated aging under damp-heat and high-UV conditions was performed on different EVA, TPU, and PVB samples. In this paper we report first results on measuring fluorescence spectra from different encapsulation materials after accelerated ageing in dependence on time and aging procedure. Our investigations clearly demonstrate that it is possible to follow damp-heat and UV induced aging processes of different polymers used in PV-modules as encapsulation materials by luminescence detection.

A light-harvesting porphyrin-boron dipyrromethene conjugate

Click chemistry has been successfully applied to prepare a conjugate of zinc(II) porphyrin with four boron dipyrromethene moieties. Upon excitation at the latter, an efficient excitation energy transfer to the porphyrin core occurs with an energy transfer quantum yield of 0.98, making this conjugate a promising light-harvesting system.