Structure-property relationship of anilino-squaraines in organic solar cells.

Soluble molecular semiconductors are a promising alternative to semiconducting polymers in the field of organic photovoltaics. Here, three custom-made symmetric 1,3-bis(N,N-alkylated-2,6-dihydroxy-anilino)squaraines containing systematic variations in their molecular structures are compared regarding their applicability as donor materials in bulk-heterojunction solar cells. The terminal substitution pattern of the squaraines is varied from cyclic over linear to branched including a stereogenic center. Single crystal structures are determined, and, in the case of chiral squaraine, unusual formation of stereoisomer co-crystals is revealed. The thin film absorbance spectra show characteristic signatures of H- and J-bands or hint at the formation of tautomers. The general feasibility of these model compounds for photovoltaic applications is studied by light-induced electron spin resonance spectroscopy. The impact of the different molecular substitution patterns on aggregation behavior and, consequently, their optoelectronic solid state properties including charge carrier mobility and finally the solar cell performance are investigated.

Distribution profiles of nitroxide spin probes in human skin--a combined study using spatially resolved electron spin resonance spectroscopy and mass spectrometry.

Electron spin resonance spectroscopy and mass spectrometry are two analytical methods that are very rarely used in combination. In this paper, we will show that the methods complement one another in the example of the distribution of stable nitroxide radicals in human skin, including the spatial resolution of these distribution processes. There are many ESR investigations dealing with this subject, but unfortunately, they are all limited to the detection of paramagnetic species. The combination with MS allows the successful examination of the distribution profile of the main biotransformation product of the nitroxide radicals, the respective "ESR-silent" hydroxylamines. In order to maintain the biological state of the sample material as far as possible, atmospheric pressure matrix-assisted laser desorption/ionization with ion trap detection has been used for the mass spectrometric investigations. The results validate the former findings of the strong reduction of stable free radicals by biological material; moreover, the diamagnetic species formed during these processes have been identified.

Current concepts for quality assured long-distance transport of temperature-sensitive red blood cell concentrates.

BACKGROUND AND OBJECTIVES: The German Armed Forces Blood Service in Koblenz supplies red blood cell concentrates (RBCs) to military and civilian institutions at home and to field hospitals during peacekeeping operations abroad. During long-distance transport, blood products can be exposed to extreme environmental conditions or inappropriate handling, which may compromise product quality. MATERIALS AND METHODS: Different active and passive cooling systems, cooling elements, packaging material and data loggers were examined in a climate chamber. A number of techniques for measuring temperature were investigated in order to preserve the blood products' quality during transport, including some field tests with multiparametric data recording. RESULTS: Any kind of active cooling systems, conventional cooling elements and customary packaging material, as well as temperature-sensitive labels, minimum-maximum thermometers and intra-product measurement were found to be unsuitable for military requirement. The best results were obtained when the passively cooling RCB 25 transport box (Dometic) was used together with latent heat/cold storage elements (deltaT) and Junior data loggers (Escort). CONCLUSION: The elaborated protocol allows temperatures to be maintained between 2 and 6 degrees C as required by European guidelines for at least 36 h each and between 1 and 10 degrees C as required by German guidelines for at least 48 or 64 h at ambient temperatures between -10 and 40 degrees C. Preliminary results indicate that care must be taken concerning additional factors such as air pressure variation or vibration.

Impact of the incorporation of Au nanoparticles into polymer/fullerene solar cells.

The addition of small amounts of dodecylamine-capped Au nanoparticles into the active layer of organic bulk heterojunction solar cells consisting of poly(3-octylthiophene) (P3OT) and C(60) was recently suggested to have a positive impact on device performance due to improved electron transport. This issue was systematically further investigated in the present work. Different strategies to incorporate colloidally prepared Au nanoparticles with a narrow size distribution into organic solar cells with the more common donor/acceptor system consisting of poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl C(61)-butyric acid methyl ester (PCBM) were pursued. Au nanoparticles were prepared with either P3HT or dodecylamine as ligands. Additionally, efforts were undertaken to incorporate nearly ligand-free Au nanoparticles into the system. Therefore, a procedure was successfully developed to remove the dodecylamine ligand shell by a postpreparative ligand exchange with pyridine, a much smaller molecule that can later partly be removed from solid films by annealing. However, for all types of nanoparticles studied here, the performance of the P3HT/PCBM solar cells was found to decrease with the Au particles as an additive to the active layer, meaning that adding Au nanoparticles is not a suitable strategy in the case of the P3HT/PCBM system. Possible reasons are discussed on the basis of detailed investigations of the structure, photophysics and charge transport in the system.

Colloidal synthesis of pt nanoparticles: on the formation and stability of nanowires.

Catalytic properties of Pt nanoparticles can significantly depend on the crystallite shape, which renders shape control an important aim in the chemical synthesis. Starting from a colloidal synthesis of quasispherical Pt nanocrystals capped with dodecylamine ligands, systematic variations of different synthesis parameters were performed in the present work in order to obtain Pt nanowires. Mechanistic investigations revealed that nanowires can form by aggregation of quasispherical particles. The process of wire formation was found to be influenced by parameters such as the concentration of the stabilizing ligands on the particle surface. Furthermore, the thermal stability of the obtained nanoparticles was examined. The nanowires were found to be stable up to approximately 140-160 degrees C. In this temperature range a structural transition to a more spherical crystallite shape occurred, which can be understood by thermodynamic considerations.

Fluorescein isothiocyanate labelled bovine serum albumin (FITC-BSA) as a model protein drug: opportunities and drawbacks.

In the therapy of various diseases, parenterally administered protein drugs are of steadily rising importance. In order to reduce the application frequency, these proteins can be incorporated into drug delivery systems, e.g. biodegradable microparticles from poly(lactic-co-glycolic acid) (PLGA). To evaluate the characteristics of these vehicles, fluorescent labelled proteins like fluorescein isothiocyanate labelled bovine serum albumin (FITC-BSA) may be used as model drugs to allow the visualisation of the protein localisation within the microparticle and the detection of microparticles in cell cultures or tissues. However, the quantification of protein by fluorescence spectroscopy failed. In this study we focused on the mechanism of fluorescence dequenching in a multi-FITC-labelled protein and its impact on a reliable protein determination.

Influence of the primary emulsification procedure on the characteristics of small protein-loaded PLGA microparticles for antigen delivery.

Microparticles prepared from poly(lactic-co-glycolic acid) (PLGA) using a W1/O/W2 double emulsion solvent evaporation method are suitable vehicles for the delivery of proteins to antigen presenting cells, e.g. dendritic cells. In this study, the influence of different techniques for the preparation of the primary W1/O emulsion was investigated with respect to the protein localization within the microparticles, morphological characteristics of these particles, protein burst release and the native state of the released protein. Bovine serum albumin bearing fluorescein isothiocyanate (FITC-BSA) was used as model protein. A static micromixer was applied for the preparation of the W1/O/W2 double emulsion. Employing a rotor-stator homogenizer (Ultra-Turrax) for primary emulsification, microcapsules with a high burst release were produced, because nearly all FITC-BSA was attached to the outside of the particle wall. Using a high pressure homogenizer or an ultrasonic procedure resulted in the formation of microspheres with homogeneous protein distribution and a reduced burst release.

Sufficient penetration of peracetic acid into drilled human femoral heads.

Chemical sterilisation methods for musculoskeletal transplants have the problem of penetration into all tissue strata. The present study examined if a peracetic acid/ethanol solution penetrated to a sufficient extent into specifically prepared femoral heads. To this effect, 10 femoral heads have been provided with drillings (diameter 2 mm, depth 10 mm) at a distance of 15 mm (series B) and placed in a diffusion chamber with sterilisation solution. From an additional central drilling at the femoral neck junction, the sample drawing was made after 30 min each over a period of 4 h for the iodometric determination of peracetic acid (PAA) concentration. Ten femoral heads, which did contain only the central drilling, served as controls (series A). In 9 of the examined femoral heads of series A the defined minimum concentration of PAA of 0.2% (inactivation of bacteria, spores, fungi) has been clearly exceeded over the complete period of measurement. About 0.8% PAA (inactivation of viruses) was achieved within 4 h only with six femoral heads. Nine out of the 10 examined femoral heads in series B show a clearly improved penetration behaviour which was expressed in smaller standard deviations, a faster increase in concentration, as well as in higher starting and final concentrations (approx. 0.9%) of PAA. Previous drying in air leads to a faster penetration into the centre of the bone. Standardised drilling of de-cartilaged femoral heads creates favourable conditions for the penetration of the PAA sterilisation solution into the whole tissue and guarantees a sufficient inactivation of microorganisms.

The effect of nanocrystal surface structure on the luminescence properties: photoemission study of HF-etched InP nanocrystals.

InP nanocrystals with narrow size distribution and mean particle diameter tunable from approximately 2 up to approximately 7 nm were synthesized via the dehalosilylation reaction between InCl3 and tris(trimethylsilyl)phosphine. Specific capping of the nanocrystal surface with a shell of organic ligands protects the nanocrystals from oxidation and provides solubility of the particles in various organic solvents. InP nanocrystals with enhanced photoluminescence (PL) efficiency were obtained from the initial nanocrystals by photoassisted etching of the nanocrystal surface with HF. The resulting PL quantum efficiency of InP nanocrystals dispersed in n-butanol is about three orders of magnitude higher when compared to the nonetched InP samples and approaches approximately 40% at room temperature. High-resolution photoelectron spectroscopy with the use of synchrotron radiation was applied to reveal the changes of the nanocrystal surface responsible for the dramatic improvement of the PL efficiency. The analysis of high-resolution P 2p core-level spectra confirmed significant changes of the nanocrystal surface structure induced by the postpreparative treatments and allowed us to propose the description of the etching mechanism. In the nonetched InP nanocrystals, some surface P atoms generate energy states located inside the band gap which provide nonradiative recombination pathways. Photoassisted treatment of InP nanocrystals with HF results in selective removal of these phosphorous atoms from the nanocrystal surface. The reconstructed surface of the etched InP nanocrystals is terminated mainly with In atoms and is efficiently passivated with tri-n-octylphosphine oxide ligands.

Three-dimensional reconstruction and volumetry of intracranial haemorrhage and its mass effect.

Intracerebral haemorrhage still causes considerable disability and mortality. The studies on conservative and operative management are inconclusive, probably due to inexact volumetry of the haemorrhage. We investigated whether three-dimensional (3-D), voxel-based volumetry of the haemorrhage and its mass effect is feasible with routine computed tomography (CT) scans. The volumes of the haemorrhage, ventricles, midline shift, the intracranial volume and ventricular compression in CT scans of 12 patients with basal ganglia haemorrhage were determined with the 3-D slicer software. Indices of haemorrhage and intracranial or ventricular volume were calculated and correlated with the clinical data. The intended measures could be determined with an acceptable intra-individual variability. The 3-D volumetric data tended to correlate better with the clinical course than the conventionally assessed distance of midline shift and volume of haemorrhage. 3-D volumetry of intracranial haemorrhage and its mass effect is feasible with routine CT examination. Prospective studies should assess its value for clinical studies on intracranial space-occupying diseases.

Photoelectron spectroscopic investigations of chemical bonding in organically stabilized PbS nanocrystals.

The surface structure of organically capped PbS nanocrystals using synchrotron radiation excited core-level photoelectron spectroscopy has been studied. The nanocrystallites prepared by methods of colloidal chemistry have average diameters of 3.1, 3.9, 4.6, and 7.6 nm with narrow size distributions and are stabilized either with oleic acid only or with a combination of trioctylphosphine and oleic acid as ligands. High resolution photoelectron spectroscopy measurements allowed the surface structure to be studied and in particular how the organic ligands bind to the surface of the PbS nanocrystals to be elucidated. The results indicate that the trioctylphosphine ligands passivate only the surface S sites while oleic acid ligands appear to bind mainly to Pb sites.

Simple invasive fixation device for fractionated stereotactic LINAC based radiotherapy.

BACKGROUND: The aim of this study was to develop a relocatable fixation device for linear accelerator (LINAC) based fractionated stereotactic radiotherapy. METHOD: The device consists of a CT- and MRI-compatible stereotactic frame, monocortical titan bone screws, four frame-posts with a lock for the fixation pins and a modified head clamp with additional arms that allows the exact and rigid placement of the frame in the desired final position prior to the final placement of the bone screws. By simply disconnecting the lock from the posts, the frame can be dismounted after treatment planning and after each treatment session. The accuracy of reposition was assessed prospectively, using phantom studies and also by comparison of isocenter movements during fractionated radiotherapy in 10 patients with an intracranial lesion. FINDINGS: No adverse events were seen after the surgical procedure and the screws were well tolerated throughout the course of treatment. The mean isocenter shifts observed during phantom reposition studies were x=0.05 mm, y=-0.32 mm, z=0.18 mm and the mean isocenter shifts during fractionated treatment were x=0.67 mm, y=0.65 mm, z=0.44 mm. INTERPRETATION: This new fixation device provides excellent accuracy of reposition during stereotactic radiotherapy. It appears superior to non-invasive, mask fixation techniques. Safety margins as small as 1-1.5 mm may therefore be sufficient for this method of stereotactic radiotherapy.

Influence of drug treatment on the microacidity in rat and human skin--an in vitro electron spin resonance imaging study.

PURPOSE: The possibilities of the noninvasive examination of microacidity (5) in different depths of the skin in vitro was explored, and the impact of drug treatment on the pH inside the skin was studied. METHODS: Spectral-spatial electron spin resonance imaging (ss-ESRI) and pH-sensitive nitroxides were used to obtain a pH map of rat and human skin in vitro. RESULTS: The dermal application of therapeutically used acids, such as salicylic acid and azelaic acid, caused a plain change of microacidity (pH) inside the skin. Species-linked differences between rat and human skin samples with respect to penetration and microacidity were found. CONCLUSIONS: ESRI has been shown to be a new and completely noninvasive method to monitor microacidity in different skin layers and on the skin surface. This nondestructive method allows serial measurements on skin samples to be performed without any preparatory steps.

Correlation between genotype and phenotype of the human arylamine N-acetyltransferase type 1 (NAT1).

Arylamine N-acetyltransferase 1 (NAT1) conjugates several aromatic amines and their N-hydroxylated metabolites by N- or O-acetylation. NAT1 genotype and phenotype is known to be variable in human populations. In this study, we set out to measure the functional relevance of the frequent NAT1 gene variants for the activity in human red blood cells. Healthy German volunteers (N = 314) were genotyped for NAT1 alleles *3, *4, *10, *11, *14, and *15 using polymerase chain reactions and restriction fragment length pattern analysis, and NAT1 enzyme kinetic parameters were measured in a subset of 105 individuals using p-aminobenzoic acid as specific substrate. There was no functional difference between NAT1 alleles *4 and *10. In particular, there was no trend of increasing activity from NAT1*4/*4 to *4/*10 and *10/*10. Carriers of the NAT1 *11 and *14 alleles had a statistically significant lower enzyme activity compared with carriers of the *3, *4, or *10 alleles. Compared with the wild-type genotype NAT1*4/*4, activity of the NAT1*11/*11, NAT1*11/*10, and NAT1*11/*4 genotypes was reduced by 20.7%, 35.7%, and 31.5%, respectively. Activity of the NAT1*10/*14 and NAT1*4/*14 genotypes was reduced by 49.8% and 55.6%, respectively. The difference in NAT1 activity between the *4/*11 and *4/*14 genotypes was also significant (P < 0.01). The carrier of the NAT1*15/*15 genotype had no detectable enzyme activity. In conclusion, functional consequences of NAT1 mutations were tested in a large population. Activity in carriers of NAT1 alleles *3, *4, and *10 did not differ, alleles NAT1*11 and *14 appeared to be low activity alleles, and allele NAT1*15 had no activity.

Nitroxide metabolism in the human keratinocyte cell line HaCaT.

Metabolism of different nitroxides with piperidine structure used as spin labels in electron spin resonance (ESR) studies in vitro and in vivo was investigated in human keratinocytes of the cell line HaCaT by GC and GC-MS technique combined with S-band ESR. Besides the well known reduction of the nitroxyl radicals to the ESR silent hydroxylamines as primary products our results indicate the formation of the corresponding secondary amines. These reductions are inhibited by the thiol blocking agent N-ethylmaleimide and by the strong inhibitors of the thioredoxin reductase (TR) 2-chloro-2,4-nitrobenzene and 2,6-dichloroindophenol. The competitive inhibitor TR inhibitor azelaic acid and the cytochrome P-450 inhibitor metyrapone lack any effects. The rates of reduction to the hydroxylamines and secondary amines were dependent on the lipid solubility of the nitroxides. Therefore, it can be assumed that the nitroxides must enter the cells for their bioreduction. The mostly discussed intracellular nitroxide reducing substances ascorbic acid and glutathione were unable to form the secondary amines. In conclusion, our results suggest that the secondary amine represents one of the major metabolites of nitroxides besides the hydroxylamine inside keratinocytes formed via the flavoenzyme thioredoxin reductase most probably. Further metabolic conversions were detected with 4-oxo-2,2,6,6-tetramethylpiperidine-1-oxyl and the benzoate of 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl as substrates.

Differential pulse polarography and electron spin resonance spectroscopy of nitroxyl free radicals used as ESR-spin probes.

Differential pulse polarography (DPP) and electron spin resonance (ESR) were used to study the influence of substituents and of the pH of the medium on DPP peak potentials (electrochemical reduction) resp. kreduction (chemical reduction) of nitroxyl free radicals. The DPP peak potentials can be used to select the appropriate nitroxide spin label for relevant biochemical and biophysical applications.

Tetracycline-HCl-loaded poly(DL-lactide-co-glycolide) microspheres prepared by a spray drying technique: influence of gamma-irradiation on radical formation and polymer degradation.

Tetracycline-HCl (TCH)-loaded microspheres were prepared from poly(lactide-co-glycolide) (PLGA) by spray drying. The drug was incorporated in the polymer matrix either in solid state or as w/o emulsion. The spin probe 4-hydroxy-2,2,6, 6-tetramethyl-piperidine-1-oxyl (TEMPOL) and the spin trap tert-butyl-phenyl-nitrone (PBN) were co-encapsulated into the TCH-loaded and placebo particles. We investigated the effects of gamma-irradiation on the formation of free radicals in polymer and drug and the mechanism of chain scission after sterilization. Gamma-Irradiation was performed at 26.9 and 54.9 kGy using a 60Co source. The microspheres were characterized especially with respect to the formation of radicals and in vitro polymer degradation. Electron paramagnetic resonance (EPR) spectroscopy, gel permeation chromatography (GPC), differential scanning calorimetry (DSC), high-performance liquid chromatography (HPLC), gas chromatography-mass spectroscopy (GC-MS), and scanning electron microscopy (SEM) were used for characterization of the microspheres. Using EPR spectroscopy, we successfully detected gamma-irradiation induced free radicals within the TCH-loaded microspheres, while unloaded PLGA did not contain radicals under the same conditions. The relatively low glass transition temperature of the poly(dl-lactide-co-glycolide) (37-39 degrees C) seems to favor subsequent reactions of free radicals due to the high mobility of the polymeric chains. Because of the high melting point of TCH (214 degrees C), the radicals can only be stabilized in drug loaded microspheres. In order to determine the mechanism of polymer degradation after exposure to gamma-rays, the spin trap PBN and the spin probe TEMPOL were encapsulated in the microspheres. gamma-Irradiation of microspheres containing PBN resulted in the formation of a lipophilic spin adduct, indicating that a polymeric radical was generated by random chain scission. Polymer degradation by an unzipping mechanism would have produced hydrophilic spin adducts of PBN and monomeric radicals of lactic or glycolic acid. These degradation products were not detected by EPR. This result is confirmed by the observation that possible diamagnetic reaction products of low molecular weight, consisting of TEMPOL and lactide or glycolide monomers, could not be detected by GC-MS. While an irradiation dose-dependent decrease in molecular weight of PLGA could be verified in agreement with the literature, TCH content of the microspheres was not affected by the exposure to gamma-rays. It can be concluded that EPR spectroscopy in combination with GPC, DSC, and HPLC allows a detailed characterization of the impact of gamma-sterilization on biodegradable parenteral drug delivery systems.

Metabolism of the stable nitroxyl radical 4-oxo-2,2,6, 6-tetramethylpiperidine-N-oxyl (TEMPONE).

The formation of new metabolites of the stable nitroxyl radical 4-oxo-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPONE) inside the isolated perfused rat liver was examined. The paramagnetic 4-hydroxy derivative (TEMPOL) and the diamagnetic 1,4-dihydroxy derivative were found to be the major metabolites besides the well-known corresponding hydroxylamine of TEMPONE. No reoxidation of the hydroxyl group in the 4-position was observed. The conversion of nitroxides to the sterically hindered secondary amines remains speculative. A redox cycle of nitroxide and hydroxylamine including the secondary amines is discussed. For the first time the biotransformation of the stable nitroxyl radical TEMPONE detected by means of GC and GC-MS has been examined and new metabolites have been described, i.e. the newly discussed metabolites have to be considered for the interpretation of electron paramagnetic resonance (EPR), magnetic resonance imaging (MRI) and dynamic nuclear polarization (DNP) measurements on using the spin probe TEMPONE.

Concordance between enzyme activity and genotype of glutathione S-transferase theta (GSTT1).

Blood samples from 140 healthy German volunteers were used to further characterize the genetic polymorphism of the human theta class glutathione S-transferase 1 (GSTT1). For measurements of GSTT1 activity, hemolysates were incubated in vitro with different concentrations of dichloromethane. The resulting enzymatically mediated production of formaldehyde was determined colorimetrically by the Nash reaction. GSTT1 genotyping was performed by polymerase chain reaction (PCR) methods using genomic DNA from total white blood cells. The prevalence of homozygous deletion of the GSTT1 gene was 19.3% (95% confidence limits: 12.2-27.7%). There was a high agreement between genotyping and phenotyping data. The individuals with the null genotype had a rate of formaldehyde production below the limit of quantification. In addition, in the group of GSTT1-positive individuals, we could differentiate highly active people (35.7%) from individuals with an intermediate enzyme activity (45.0%). It can be concluded that the PCR method is suitable to quickly genotype large populations, whereas the phenotyping assay at present offers the advantage of differentiating heterozygously from homozygously active subjects. Our results confirm the ethnic differences in the prevalence of the homozygous deleted genotype which were previously observed and seem to exist even between closely related ethnic groups such as German and Swedish populations.

[Solid phase microextraction (SPME) of sample preparation during of a complex biological matrix in biotransformation studies]. / Untersuchungen zum Einsatz der Festphasenmikroextraktion SPME bei der Probenvorbereitung aus einer komplexen biologischen Matrix im Rahmen von Biotransformationsstudien.

Within the scope of the investigation of drug metabolism in keratinocytes solid phase microextraction (SPME) was investigated as a suitable method for sample preparation. The application of SPME is based on the fact, that a amount of analyte is absorbed by the polymer fiber at equilibrium, and the fiber is localized on a tip of a GC-syringe. The stable nitroxyl radical TEMPO (2,2,6,6-tetramthylpiperidine-1-oxyl) and its apolar metabolite 2,2,6,6-tetramethylpiperidine were analyzed by SPME and subsequent GC using thymol as internal standard. By means of the headspace-technique and an apolar fiber the recovery rate of TEMPO and the metabolite was nearly 100% and the precision was high. However, the results of the direct SPME were unsatisfactory. In comparison with conventional liquid/liquid extraction and solid phase extraction SPE the SPME proved the best results with regard to recovery rate and precision. Furthermore, the main advantages of SPME are the renunciation of organic solvents, the saving of time, the possibility to reuse the fiber about 100-150 times and the option for a complete automatisation of the extraction procedure.