Incorporation of β-Alanine in Cu(II) ATCUN Peptide Complexes Increases ROS Levels,DNA Cleavage and Antiproliferative Activity**

Redox-active Cu(II) complexes are able to form reactive oxygen species (ROS) in the presence of oxygen and reducing agents. Recently, Faller et al. reported that ROS generation by Cu(II) ATCUN complexes is not as high as assumed for decades. High complex stability results in silencing of the Cu(II)/Cu(I) redox cycle and therefore leads to low ROS generation. In this work, we demonstrate that an exchange of the α-amino acid Gly with the β-amino acid β-Ala at position 2 (Gly2→β-Ala2) of the ATCUN motif reinstates ROS production (^•OH and H₂O₂). Potentiometry, cyclic voltammetry, EPR spectroscopy and DFT simulations were utilized to explain the increased ROS generation of these β-Ala2-containing ATCUN complexes. We also observed enhanced oxidative cleavage activity towards plasmid DNA for β-Ala2 compared to the Gly2 complexes. Modifications with positively charged Lys residues increased the DNA affinity through electrostatic interactions as determined by UV/VIS, fluorescence, and CD spectroscopy, and consequently led to a further increase in nuclease activity. A similar trend was observed regarding the cytotoxic activity of the complexes against several human cancer cell lines where β-Ala2 peptide complexes had lower IC₅₀ values compared to Gly2. The higher cytotoxicity could be attributed to an increased cellular uptake as determined by ICP-MS measurements.     

Application of colloidal palladium nanoparticles for labeling in electron microscopy

The application of palladium nanoparticles as electron-dense markers for labeling in both transmission and scanning electron microscopy requires their conjugation to a specific protein. The conjugation protocol described here includes the dihydrolipoic acid (DHLA) capping of Pd nanoparticles (8 nm equivalent diameter) and their subsequent covalent attachment to functional protein molecules such as streptavidin, protein A, or avidin. The single-step reaction was mediated using the cross-linking agent ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC). The final Pd conjugates were fully functional, as demonstrated by labeling of ultrathin resin sections of either bovine serum albumin or secretory granules of the salivary gland isolated from the partially fed female Ixodes ricinus tick. The results of bovine serum labeling were quantified, statistically evaluated, and compared with results obtained using commercially available gold particle conjugates (10 nm diameter). The highest values of labeling density were achieved using both streptavidin-Pd (106 ± 7 particles/μm2) and protein A-Au conjugates (130 ± 18 particles/μm2) compared to a commercial streptavidin-Au (66 ± 16 particles/μm2) and protein A-Pd conjugates (70 ± 11 particles/μm2). The concentrations of both DHLA and EDC, pH during conjugation, and finally thorough washing away of unbound proteins crucially influenced conjugation.     

Das Verhalten von Natriumsulfantimonat (Schlippes Salz) zu einigen Metallsalzl?sungen. (Vort?ufige Mitteilung.)

Ohne Zusammenfassung     

Differences in auditory performance between monaural and dichotic conditions. I: masking thresholds in frozen noise.

Thresholds of a 5-ms, 1-kHz signal were determined in the presence of a frozen-noise masker. The noise had a flat power spectrum between 20 Hz and 5 kHz and was presented with a duration of 300 ms. The following interaural conditions were tested with four listeners: Noise and signal monaural at the same ear (monaural condition, NmSm), noise and signal identical at both ears (diotic condition, NoSo), noise identical at both ears and signal monaural (dichotic condition, NoSm) and uncorrelated noise at the two ears and signal monaural (NuSm). The signal was presented at a fixed temporal position with respect to the frozen noise in all measurements and thresholds were determined for different starting phases of the carrier frequency of the signal. Variation of the carrier phase strongly influenced the detection in the diotic condition and the masked thresholds varied by more than 10 dB. The pattern of thresholds for the monaural condition was less variable and the thresholds were generally higher than for the diotic condition. The monaural-diotic difference for specific starting phases amounted to as much as 8 dB. Comparison measurements using running noise maskers revealed no such difference. This relation between monaural and diotic thresholds was further investigated with eight additional subjects. Again, monaural and diotic thresholds in running noise were identical, while in frozen noise, diotic thresholds were consistently lower than monaural thresholds, even when the ear with the lower NmSm threshold was compared. For the starting phase showing the largest monaural-diotic difference, the thresholds for NoSm lay between the monaural and the diotic values. At other starting phases, the NoSm threshold was clearly lower than both the NmSm and the NoSo threshold. One possible explanation of the observed monaural-diotic differences relates to contralateral efferent interaction between the right and the left hearing pathway. A prediction based on this explanation was verified in a final experiment, where frozen-noise performance for NmSm was improved by simultaneously presenting an uncorrelated running noise to the opposite ear.     

Die differentiellen Anregungsfunktionen dern+2-Zustände von Helium

Energy and angular dependences for the electron impact excitation of the Helium 2³ S, 2¹ S, 2³ P, and 2¹ P states have been measured using monochromatic (0.05 eV) electrons in the energy range from 19 to 23 eV and for scattering angles ranging from 0 to 110°. The structures near the 2³ S-threshold have been analyzed in terms of resonant and non resonant i.e. direct scattering phase shifts. The first peak in this excitation function at 19.95 eV is mostly due to the rapid change with collision energy of the directs-wave phase of the inelastic scattering, which in turn is a consequence of the existence of the 2² S-resonance at 19.3 eV. The energy position and behaviour with collision energy of the first peak at 20.7 eV in the 2¹ S-channel is in agreement with the predictions for the existence of a virtual resonance state ofBurke et al. A term sceme of the He^? resonances with assignments of configurations is presented.     

Precipitates originating from tungsten crucible parts in AlN bulk crystals grown by the PVT method

In order to evaluate the possible involvement of crucible materials in the growth of AlN bulk crystals grown by physical vapor transport, we applied growth conditions with a high vertical thermal gradient and hence high supersaturation of aluminum vapor. Under these conditions, precipitates formed causing diffuse grayish substructures at the initial growth interface and in the crystal body, decorating dislocations. Electron microscopy studies revealed that the precipitates are elongated, single‐phase particles with sizes of 50–500 nm of commensurate structure, oriented along the <110> direction. Chemical analysis of the precipitates showed tungsten as well as carbon and oxygen. The lattice parameters of the precipitates are in close agreement to hexagonal tungsten hemicarbide (W₂C). The possible transport from the tungsten parts and its conversion into tungsten hemicarbide precipitates is discussed. We thus conclude that the W₂C precipitates may contribute to the decoration of dislocations, even in growth with moderate thermal gradients.     

Thermolytic ring closure reactions of 4‐azido‐3‐phenylsulfanyl‐and 4‐azido‐3‐phenylsulfonyl‐2‐quinolones to 12H‐quinolino‐[3,4‐b][1,4]benzothiazin‐6(5H)‐ones

4‐Hydroxy‐3‐phenylsulfanyl‐2‐quinolones 2 and 4‐hydroxy‐3‐sulfonyl‐2‐quinolones 7 , which are readily accessible from 4‐hydroxy‐2‐quinolones 1 and diphenyldisulfide or thiophenol, can be converted to 4‐azido‐3‐phenylsulfanyl‐2‐quinolones 10 or 4‐azido‐3‐phenylsulfonyl‐2‐quinolones 12 via 4‐chloro‐3‐phenylsul‐fanyl‐2‐quinolones 5 or 4‐chloro‐3‐phenylsulfonyl‐2‐quinolones 9 , respectively. Thermolysis of the azides 10 and 12 results in a cyclization reaction to give quinolino[3,4‐b][1,4]benzothiazinone 11 and quino‐lino[3,4‐b][1,4]benzothiazinone dioxides 13 , respectively. The conditions for thermolysis have been studied by differential scanning calorimetry (DSC).