Stability of 47Sc-complexes with acyclic polyamino-polycarboxylate ligands

The aim of this study was to evaluate acyclic ligands which can be applied for labeling proteins such as monoclonal antibodies and their fragments with scandium radionuclides. Recently, scandium isotopes (⁴⁷Sc, ⁴⁴Sc) are more available and their properties are convenient for radiotherapy or PET imaging. They can be used together as “matched pair” in theranostic approach. Because proteins denaturize at temperature above 42 °C, ligands which efficiently form complexes at room temperature, are necessary for labelling such biomolecules. For complexation of scandium radionuclides open chain ligands DTPA, HBED, BAPTA, EGTA, TTHA and deferoxamine have been chosen. We found that the ligands studied (except HBED) form strong complexes within 10 min and that the radiolabelling yield varies between 96 and 99 %. The complexes were stable in isotonic NaCl, but stability of ⁴⁶Sc-TTHA, ⁴⁶Sc-BAPTA and ⁴⁶Sc-HBED in PBS buffer was low, due to formation by Sc³⁺stronger complexes with phosphates than with the studied ligands. From the radiolabelling studies with n.c.a. ⁴⁷Sc we can conclude that the most stable complexes are formed by the 8-dentate DTPA and EGTA ligands.     

Superelectrophilic activation of N-aryl amides of 3-arylpropynoic acids: synthesis of quinolin-2(1H)-one derivatives

The superelectrophilic activation of N-aryl amides of 3-arylpropynoic acids by Bronsted superacids (CF₃SO₃H, HSO₃F) or strong Lewis acids AlX₃ (X=Cl, Br) results in the formation of 4-aryl quinolin-2(1H)-ones in quantitative yields. The vinyl triflates or vinyl chlorides may be formed as additional reaction products. The investigated amides in reactions with benzene give 4,4-diaryl 3,4-dihydroquinolin-2-(1H)-ones under the superelectrophilic activation. 4-Aryl quinolin-2(1H)-ones in POCl₃ are converted into 4-aryl 2-chloroquinolines. 4-Fluorophenyl-4-phenyl 3,4-dihydroquinolin-2-(1H)-one give N-formylation products in a yield of 79% under the Vilsmeier–Haack reaction conditions.     

Investigating the Disordered and Membrane-Active Peptide A-Cage-C Using Conformational Ensembles

The driving forces and conformational pathways leading to amphitropic protein-membrane binding and in some cases also to protein misfolding and aggregation is the subject of intensive research. In this study, a chimeric polypeptide, A-Cage-C, derived from α-Lactalbumin is investigated with the aim of elucidating conformational changes promoting interaction with bilayers. From previous studies, it is known that A-Cage-C causes membrane leakages associated with the sporadic formation of amorphous aggregates on solid-supported bilayers. Here we express and purify double-labelled A-Cage-C and prepare partially deuterated bicelles as a membrane mimicking system. We investigate A-Cage-C in the presence and absence of these bicelles at non-binding (pH 7.0) and binding (pH 4.5) conditions. Using in silico analyses, NMR, conformational clustering, and Molecular Dynamics, we provide tentative insights into the conformations of bound and unbound A-Cage-C. The conformation of each state is dynamic and samples a large amount of overlapping conformational space. We identify one of the clusters as likely representing the binding conformation and conclude tentatively that the unfolding around the central W23 segment and its reorientation may be necessary for full intercalation at binding conditions (pH 4.5). We also see evidence for an overall elongation of A-Cage-C in the presence of model bilayers.     

Stereoselective Synthesis of Multisubstituted Cyclohexanes by Reaction of Conjugated Enynones with Malononitrile in the Presence of LDA

Reaction of linear conjugated enynones, 1,5-diarylpent-2-en-4-yn-1-ones, with malononitrile in the presence of lithium diisopropylamide LDA, as a base, in THF at room temperature for 3–7 h resulted in the formation of the product of dimerization, multisubstituted polyfunctional cyclohexanes, 4-aryl-2,6-bis(arylethynyl)-3-(aryloxomethyl)-4-hydroxycyclohexane-1,1-dicarbonitriles, in yields up to 60%. Varying the reaction conditions by decreasing time and temperature and changing the ratio of starting compounds (enynone and malononitrile) allowed isolating some intermediate compounds, which confirmed a plausible reaction mechanism. The relative stability of possible stereoisomers of such cyclohexanes was estimated by quantum chemical calculations (DFT method). The obtained cyclohexanes were found to possess photoluminescent properties.     

Mechanisms of modulation gap detection

It has been postulated that the central auditory system contains an array of modulation filters, each responsive to a different range of modulation frequencies present at the outputs of the (peripheral) auditory filters. In the present experiments, we tested what we call the "dip hypothesis," that a gap in modulation is detected using the "dip" in the output of the modulation filter tuned to the modulator frequency. In experiment 1, the task was to detect a gap in the sinusoidal amplitude modulation imposed on a 4-kHz carrier. The modulator preceding the gap ended with a positive-going zero-crossing. There were three conditions, differing in the phase at which the modulator started at the end of the gap; zero-phase, at a positive-going zero-crossing; pi-phase, at a negative-going zero-crossing; and "preserved" phase, at the phase the modulator would have had if it had continued without interruption. Modulation frequencies were 5, 10, 20, and 40 Hz. Psychometric functions for detection of the gap were measured using a two-alternative forced-choice task. For the zero-phase and preserved-phase conditions, the detectability index, d', increased monotonically with increasing gap duration. For the pi-phase condition, performance was good (d' > 1) for small gap durations, and initially worsened with increasing gap duration, before improving again for longer gap durations. This is the pattern of results expected from the dip hypothesis, provided that the modulation filters have Q values of 2 or more. However, it is also possible that a rhythm cue was used to improve performance in the pi-phase condition for short gap durations; the introduction of the gap markedly disrupted the regular rhythm produced by the modulator peaks. In experiment 2, the rhythm cue was disrupted by varying the modulator period randomly around its nominal value, except for the modulator periods immediately before and after the gap. This markedly impaired performance, and resulted in psychometric functions that were very similar for the zero-phase and pi-phase conditions. This pattern of results is inconsistent with the dip hypothesis. For both experiments, modulation gap "thresholds" (d' approximately 1) were roughly constant when expressed as a proportion of the modulator period. Possible mechanisms of modulation gap detection are discussed and evaluated.     

Behaviour of copper(II) and nickel(II) dialkyldithiocarbamates on polar and non-polar stationary phases

Summary Fifteen Dialkyldithiocarbamate complexes each of copper(II) and Ni(II) have been prepared and the retention times of these complexes have been measured on the non-polar OV-101 phase and the polar NGA and OV-225 phases. The relationship has been studied between the retention characteristics of the complexes and their structure. The lenght of the alkyl substituent, regarded as a steric hindrance, turned out to affect the retention of the complexes on the non-polar phases.

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Verhalten von Kupfer(II)- und Nickel(II)-dialkyldithiocarbamaten auf polaren und unpolaren stationären Phasen

Zusammenfassung Je 15 Dialkyldithiocarbamatkomplexe von Kupfer(II) und Nickel(II) wurden dargestellt und ihre Retentionszeiten auf der unpolaren Phase OV-101 sowie den polaren Phasen NGA und OV-225 gemessen. Die Beziehung zwischen der Retentionscharakteristik der Komplexe und ihrer Struktur wurde untersucht. Es zeigte sich, daß die Länge des Alkylsubstituenten (als sterische Hinderung) die Retention auf der unpolaren Phase beeinträchtigt.