Halogenated Flavonoid Derivatives Display Antiangiogenic Activity

Antiangiogenic agents attenuate tumours’ growth and metastases and are therefore beneficial as an adjuvant or standalone cancer regimen. Drugs with dual antiproliferative and antiangiogenic activities can achieve anticancer efficacy and overcome acquired resistance. In this study, synthetic flavones (5a,b) with reported anticancer activity, and derivatives (4b and 6a), exhibited significant inhibition of endothelial cell tube formation (40–55%, 12 h) at 1 µM, which is comparable to sunitinib (50% inhibition at 1 µM, 48 h). Flavones (4b, 5a,b and 6a) also showed 25–37% reduction in HUVECs migration at 10 µM. In a Western blotting assay, 5a and 5b subdued VEGFR2 phosphorylation by 37% and 57%, respectively, suggesting that VEGFR2 may be their main antiangiogenic target. 5b displayed the best docking fit with VEGFR2 in an in silico study, followed by 5a, emphasizing the importance of the 7-hydroxyl group accompanied by a 4−C=S for activity. Conversely, derivatives with a 4-carbonyl moiety fitted poorly into the target’s binding pocket, suggesting that their antiangiogenic activity depends on a different target. This study provides valuable insight into the Structure Activity Relationships (SAR) and modes of action of halogenated flavones with VEGFR2 and highlights their therapeutic potential as antiangiogenic/anticancer lead compounds.     

Synthesis,structure, and magnetic properties of the single-molecule magnet [Ni(21)(cit)(12)(OH)(10)(H(2)O)(10)](16-)

The preparation of two new compounds containing the cluster [Ni(21)(cit)(12)(OH)(10)(H(2)O)(10)](16-) is presented, together with a detailed magnetic investigation of one of the compounds. We found that this cluster shows an unexpected stability and that it exists as different stereoisomers. Compound 1 contains the achiral cluster with a Delta-Lambda configuration, and compound 2 contains a pair of enantiomeric clusters with the configurations Delta-Delta and Lambda-Lambda, respectively. Magnetic measurements of 1 in the millikelvin range were necessary to determine the spin ground state of S = 3, and they also revealed a magnetic anisotropy within the ground state. A frequency-dependent out-of-phase signal was found in alternating current susceptibility measurements at very low temperatures, which indicates a slow relaxation of the magnetization. Thus, individual molecules are acting as single magnetic units, which is a rare phenomenon for nickel clusters. The energy barrier exhibited by compound 1 has been calculated to be 2.9 K.     

Revisiting the form of dead time corrections for neutron coincidence counting

A standard nondestructive assay technique for determining the mass of plutonium in an item is passive neutron coincidence counting. In passive neutron coincidence counting, the dead time or rate loss corrections for the singles and doubles neutron counting rates are routinely made using empirical relationships that are based on the design and performance of the individual counter used to make the measurements. The empirical methods were developed ahead of any supporting theory for dead time losses and have worked well to date for the majority of safeguards measurement scenarios. Modern applications using highly efficient systems with short neutron lifetimes together with the challenges posed by highly multiplying items mean dead time corrections of higher fidelity are needed. While many attempts have been made to develop dead time corrections that are based on the physical principles of the measurements being performed, these corrections have often been found to be difficult to implement in a real system. For instance, Matthes and Haas developed an approach in 1985 which did not gain favor largely because the form of the doubles correction apparently required numerical integration which was difficult to implement with the computer technology of that time. A recent review into the approach that was developed by Matthes and Haas has determined that a straightforward analytical expression can be derived for the doubles correction that is similar to the singles rate correction that was developed in their original work. An analysis of the expressions is presented here to show how they relate to the traditional empirical methods. Further, we illustrate their implications and limitations. For instance the empirical methods do not address within burst losses i.e. rate related losses due to the correlated neutron bursts from fission, whereas the Matthes and Hass expression for singles counting does exhibit such an effect.     

Rotational spectra of S- and S-containing isotopologues of laser ablation generated tin monosulfide

Using a newly constructed source, tin monosulfide is produced by the reaction between carbonyl sulfide and the products resulting from the ablation of tin metal by the pulsed output of a frequency-doubled Nd:YAG laser (λ = 532 nm). Entrained in argon carrier gas, SnS is introduced into the cavity of a Balle-Flygare Fourier transform microwave spectrometer that has a frequency range encompassing the two lowest rotational transitions (J = 1 − 0 and 2 − 1) for this molecule. Except for ¹¹⁵Sn³⁴S, spectra are obtained in natural abundance for all ³⁴S-containing isotopologues with naturally occurring tin isotopes. Additionally, spectra were obtained for the rare isotopologues, ¹¹⁵Sn³²S and ¹²⁰Sn³³S. Resolution of the hyperfine structure in the latter species allows a more precise determination of its ³³S nuclear quadrupole coupling constant. Spectra for all species containing ³⁴S are analyzed in terms of mass-independent Dunham parameters and are combined with all available isotopologues to determine Born-Oppenheimer breakdown terms for both tin and sulfur.     

Reactivity and Synthetic Utility of 1,3,2λ5-Dioxaphospholanes

Abstract

The kinetics of Lewis acid-mediated decomposition and definitions of the synthetic applicability of 1,3,2λ⁵-dioxaphospholanes for (i) the syntheses of highly-hindered epoxides, and (ii) the stereospecific functionalizations of stereocenters in 1,2-diol arrays are described.