A Mononuclear Uranium(IV) Single‐Molecule Magnet with an Azobenzene Radical Ligand

A tetravalent uranium compound with a radical azobenzene ligand, namely, [{(SiMe₂NPh)₃‐tacn}U^IV(η²‐N₂Ph₂^.)] ( 2 ), was obtained by one‐electron reduction of azobenzene by the trivalent uranium compound [U^III{(SiMe₂NPh)₃‐tacn}] ( 1 ). Compound 2 was characterized by single‐crystal X‐ray diffraction and ¹H NMR, IR, and UV/Vis/NIR spectroscopy. The magnetic properties of 2 and precursor 1 were studied by static magnetization and ac susceptibility measurements, which for the former revealed single‐molecule magnet behaviour for the first time in a mononuclear U^IV compound, whereas trivalent uranium compound 1 does not exhibit slow relaxation of the magnetization at low temperatures. A first approximation to the magnetic behaviour of these compounds was attempted by combining an effective electrostatic model with a phenomenological approach using the full single‐ion Hamiltonian.     

Life and health insurance behaviour of individuals having undergone a predictive genetic testing programme for hereditary non-polyposis colorectal cancer

Objective and Methods: We describe the insurance behaviour of subjects (n=271) who had previously taken a predictive genetic test for hereditary non-polyposis colorectal cancer (HNPCC); 31% of them were mutation positive, indicating a high risk of cancer. One year after testing, subjects were sent a questionnaire including questions about their present life and health insurance before participation in the study, and their actual and planned purchase of the insurance policies during the testing programme which compromised a pre-test counseling session, a period for reflection, the testing, and a test disclosure session. Results: Thirty percent reported that they already had a life insurance and 14% a health insurance before participating in the study. The mutation-positive subjects possessed a health insurance significantly more often than the mutation-negative individuals (21 vs. 11%, p=0.02) and similar trend was observed for life insurance (36 vs. 28%, p=0.12). Life and health insurance policies purchased just before testing was reported by 3 and 2% of the subjects, respectively. Life and health insurance policies purchased after testing were reported by 3 and <1% respectively, and planned purchase by 3 and 2%, respectively. No statistically significant differences were found between the groups defined by mutation status in reports of life or health insurance behaviour during or after the programme. Conclusion: According to self-reported data, the mutation-positive subjects did not differ from the others in the purchase of life or health insurance policies. However, the mutation-positive individuals reported that they possessed health insurance policies before entering the study more often than their counterparts.     

Characterization of cyanide-trapped methylated metabonates formed during reactive drug metabolite screening in vitro

Reactive metabolites are estimated to be one of the main reasons behind unexpected drug-induced toxicity, by binding covalently to cell proteins or DNA. Due to their high reactivity and short lifespan, reactive metabolites are analyzed after chemical trapping with nucleophilic agents such as glutathione or cyanide. Recently, unexplained and uncharacterized methylated reaction products were reported in a human liver microsome based reactive metabolite trapping assay utilizing potassium cyanide as a trapping agent. Here, a similar assay was utilized to produce mono- or dimethylated and further cyanide-trapped reaction products from propranolol, amlodipine and ciprofloxacin, followed by ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC/TOF-MS) and ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) experiments for their more detailed structural elucidation. Formation of all observed cyanide-trapped products was clearly NADPH-dependent and thus metabolism-mediated. The suggested reaction pathways included N-methylation leading to iminium formation in primary and/or secondary amines preceded by cytochrome P450 (CYP)-mediated reactions. As the methylation reaction was suggested to be involved in formation of the actual reactive iminium ion, the observed cyanide-trapped products were experimental artifacts rather than trapped reactive metabolites. The results stress that to avoid overestimating the formation of reactive metabolites in vitro, this methylation phenomenon should be taken into account when interpreting the results of cyanide-utilizing reactive metabolite trapping assays. This in turn emphasizes the importance of identification of the observed cyano conjugates during such studies. Yet, metabolite identification has a high importance to avoid overestimation of in vitro metabolic clearance in the cases where this kind of metabonate formation has a high impact in the disappearance rate of the compound.     

Syntheses, characterization, biological activity and fluorescence properties of bis-(salicylaldehyde)-1,3-propylenediimine Schiff base ligand and its lanthanide complexes

Eight new lanthanide metal complexes [LnL(NO(3))(2)]NO(3) {Ln(III) = Nd, Dy, Sm, Pr, Gd, Tb, La and Er, L = bis-(salicyladehyde)-1,3-propylenediimine Schiff base ligand} were prepared. These complexes were characterized by elemental analysis, thermogravimetric analysis (TGA), molar conductivity measurements and spectral studies ((1)H NMR, FT-IR, UV-vis, and luminescence). The Schiff base ligand coordinates to Ln(III) ion in a tetra-dentate manner through the phenolic oxygen and azomethine nitrogen atoms. The coordination number of eight is achieved by involving two bi-dentate nitrate groups in the coordination sphere. Sm, Tb and Dy complexes exhibit the characteristic luminescence emissions of the central metal ions attributed to efficient energy transfer from the ligand to the metal center. Most of the complexes exhibit antibacterial activity against a number of pathogenic bacteria.     

Predicting binding energies of CDK6 inhibitors in the hit-to-lead process

The main challenge for the ??hit-to-lead?? stage in the drug discovery process relies on the accuracy of existing docking methods. In fact, accuracy of docking methods depends not only on the scoring function used to rank the poses but also on the ability of the docking method to reproduce the experimental binding mode. At this purpose, the performance of different approximations to properly dock and score compounds with known activity in a narrow range of IC₅₀ values was analyzed. A set of five ATP-competitive CDK6 inhibitors and three receptor conformations for CDK6 were considered for analysis, and three methodologies were used and analyzed in order to include different degrees of receptor flexibility. Thus, a completely rigid receptor is considered when using Glide, while the so-called Induced Fit Docking Protocol accounts for receptor sidechain rearrangements. Finally, force field calculations were also performed in order to consider a completely flexible receptor.     

Revealing indigenous Indonesian traditional medicine: anti-infective agents

Indonesia is rich in medicinal plants which the population has used traditionally from generation to generation for curing diseases. Our interest in the treatment of infectious diseases has lead to the investigation of traditional Indonesian treatments. In this review, we present a comprehensive review of ethnopharmacologically directed screening in Indonesian medicinal plants to search for new anti-viral, antimalarial, anti-bacterial and anti-fungal agents. Some potent drug leads have been isolated from Indonesian medicinal plants. Further research is still required for the lead development as well as the search for new bioactive compounds from the enormous medicinal plant resources.     

Determination of talc in geological samples by infrared spectrometry

Talc is determined by infrared spectrometry in talc ore and mineral mixtures containing clinochlore chlorite, dolomite and magnesite as major minerals. When the Si-O-Si vibration at 668 cm^?1 is used, the calibration graph is linear up to about 0.5 mg of talc. Band overlap from chlorite is corrected by using the ratio of absorbances at 668 and 3620 cm^?1. Talc (?15%) in talc/carbonate/chlorite mixtures and ore was determined with relatively good precision and accuracy (recovery 91.2–97.4%). The sample sizes were 0.5–1 mg for 40–60% talc and 0.5–1.5 mg for 7.5–15% talc. The recoveries were worse (84.0–94.6%) for < 15% talc. The precision for unknown samples of talc ore varied from 1.5 to 4.0% (n=4).     

Flow transients induced on a 2D airfoil by pulse-modulated actuation

The transitory response of the flow over a stalled, 2D airfoil to a momentary synthetic jet actuation that is realized by low-duty cycle amplitude modulation of the actuator’s resonant waveform is investigated experimentally using hot-wire anemometry and flow visualization. The pulse-like actuation results in the shedding of large vortical structures and a momentary flow attachment.     

Comparison of agarose and cross-linked protein gels as magnetic resonance imaging phantoms

Measurements of the magnetic field dependence of spin-lattice relaxation rates and the response of the water-proton signal intensity to off-resonance radio frequency fields show that the commonly used agarose phantom provides a less faithful representation for the magnetic response of tissue than does a cross-linked protein system. The origin of these differences lies in the structure and intramolecular dynamics of the macromolecular system used to make the gel. These distinctions will also cause differences in the magnetic response of the water spin system when paramagnetic relaxation agents or contrast agents are incorporated. Use of a thermally cross-linked bovine serum albumin phantom is suggested.