We report the generation of gas-phase riboguanosine radicals that were tagged at ribose with a fixed-charge 6-(trimethylammonium)hexane-1-aminocarbonyl group. The radical generation relied on ...electron transfer from fluoranthene anion to noncovalent dibenzocrown-ether dication complexes which formed nucleoside cation radicals upon one-electron reduction and crown-ether ligand loss. The cation radicals were characterized by collision-induced dissociation (CID), photodissociation (UVPD), and UV–vis action spectroscopy. Identification of charge-tagged guanosine radicals was challenging because of spontaneous dissociations by loss of a hydrogen atom and guanine that occurred upon storing the ions in the ion trap without further excitation. The loss of H proceeded from an exchangeable position on N-7 in guanine that was established by deuterium labeling and was the lowest energy dissociation of the guanosine radicals according to transition-state energy calculations. Rate constant measurements revealed an inverse isotope effect on the loss of either hydrogen or deuterium with rate constants k H = 0.25–0.26 s–1 and k D = 0.39–0.54 s–1. We used time-dependent density functional theory calculations, including thermal vibronic effects, to predict the absorption spectra of several protomeric radical isomers. The calculated spectra of low-energy N-7-H guanine-radical tautomers closely matched the action spectra. Transition-state-theory calculations of the rate constants for the loss of H-7 and guanine agreed with the experimental rate constants for a narrow range of ion effective temperatures. Our calculations suggest that the observed inverse isotope effect does not arise from the isotope-dependent differences in the transition-state energies. Instead, it may be caused by the dynamics of post-transition-state complexes preceding the product separation.
The simple preparation of the natural sphingoid bases possessing cytotoxic activity – the marine drugs Clavaminol A and Xestoaminol C and all their unnatural stereoisomers – in high enantiomeric ...purity (ca. 95 % of major enantiomer) was described. The individual enantiomers were obtained by the utilization of asymmetric Henry reaction. The diastereomers of target compounds were separated by column chromatography after transformation into corresponding 2‐phenyloxazoline derivatives. The individual stereoisomers of Clavaminol A and Xestoaminol C were evaluated for antiproliferative activity in cancer cell lines (A‐549; Jurkat; SH‐SY5Y, MG‐63). From the obtained IC50 values is obvious, that the stereoisomers of Xestoaminol C are more potent inhibitors of cell proliferation than the stereoisomers of Clavaminol A. Further, it was found, that stereoisomers with syn‐configuration exhibited larger antiproliferative effects in comparison with the stereoisomers having anti‐configuration, in both sphingoid bases. Nevertheless, the values of IC50 found for individual enantiomers in each of the enantiomeric pairs are rather comparable implying a possibility of using racemic mixtures for induction of cytotoxicity.
Clavaminol A and Xestoaminol C, the sphingoid bases isolated from some marine sponges, possess interesting cytotoxicity. However, their preparation in enantiomerically pure forms takes many efforts. Here, we synthetized all stereoisomers of these compounds by application of enantioselective catalysis and we revealed, that more easily available racemic forms exhibit similar cytotoxicity as enantiomerically pure forms.
The synthesis of tritium-labelled glycine transporter 1 inhibitor Org24598 is reported. Because of the instability of the Org24598 skeleton under hydrogenation conditions, a synthetic approach using ...an in-house prepared tritium-labelled alkylating agent (
HMeI, SA = 26.2 Ci/mmol) was employed. Alternative methods of labelling are discussed.
Fertility transition is taking place in all post‐communist countries. Not many studies have been conducted at the subnational level to prove the universal nature of this transition or, on the ...contrary, the diversity of regional trajectories. This study attempts to reveal whether the same explanatory schemes can be applied to fertility transformation mechanisms on a regional as well as a national level. Using a principal component analysis and a cluster analysis, significant spatial differences were found. A rather unique finding is that while there is some convergence in terms of intensity, fertility tempo is a major factor for diversity. This study tries to explain regional differences and, their changes over time. Some economic factors are identified as being important for explaining spatial differences in the fertility quantum and – alongside some cultural factors – in the fertility tempo as well.
Noncanonical nucleobases and nucleosides represent newly discovered species of relevance for DNA ionization. We report a targeted synthesis of gas-phase 9-methylene(1
)adenine cation radical (
) as a ...low-energy isomer of ionized 9-methyladenine. Ion
showed unique collision-induced dissociation and UV-vis photodissociation action spectra that distinguished it from other cation radical isomers. Ab initio energy calculations with coupled cluster theory extrapolated to the complete basis set limit, CCSD(T)/CBS, identified cation radical
as the global energy minimum of the adenine-related C
H
N
isomers. The action spectrum of
was assigned on the basis of vibronic absorption spectra that were calculated with time-dependent density functional theory for multiple vibrational configurations of thermal ions. The major dissociation of
proceeded by hydrogen loss that was elucidated by deuterium labeling at the exchangeable N-1 and NH
positions and C-8 position and by kinetic analysis. The dissociation involved a reversible rearrangement to intermediate dihydropteridine structures, yielding a protonated aminopteridine as the product, which was identified by multistep UV-vis action spectroscopy. We also report a computational study of related noncanonical isomers of 2'-deoxyadenosine cation radical having the radical defect at C-1' that were found to be thermodynamically more stable than the canonical isomer in both the gas phase and aqueous solution. The noncanonical isomers were calculated to have extremely low ion-electron recombination energies of 4.42-5.10 eV that would make them dead-end hole traps if produced by DNA ionization.
This paper describes the preparation of enantioselective catalysts based on derivatives of imidazolidine‐4‐thione and their subsequent anchoring by means of a sulfur atom on a polymeric carrier. ...First, we verified the catalytic activity and enantioselectivity in the Henry reaction of the homogeneous variants of the catalysts, i.e., the copper(II) complexes of 2‐(pyridine‐2‐yl)imidazolidine‐4‐thiones and 4‐benzylsufanyl‐2‐(pyridine‐2‐yl)imidazolines themselves. It was found that these catalysts exhibit high enantioselectivity (up to 98% ee). Subsequently, the imidazolidine‐4‐thione catalysts were immobilized by anchoring to polymeric carriers based on a copolymer of styrene and 4‐vinylbenzyl chloride. These heterogeneous catalysts were analogously tested with regard to their catalytic activity and enantioselectivity in the Henry reaction, and moreover, the possibility of their separation and reuse was studied. It was found that all the prepared immobilized catalysts are highly enantioselective (up to 97% ee). Their recycling ability was tested in Henry reaction of 2‐methoxybenzaldehyde with nitromethane. It was found that they can be recycled more than ten times without any decrease of their enantioselectivity. Therefore, they present a better means of catalysis than the original copper(II) complexes of imidazolidine‐4‐ones from both economic as well as ecological points of view. Thus, such immobilized catalysts exhibit high application potential for the asymmetric Henry reaction.
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The preparation of a new series of 2-(pyridine-2-yl)imidazolidine-4-thione derivatives is described. Their corresponding copper(II) complexes were found to be highly enantioselective ...catalysts for asymmetric Henry reactions (up to 98% ee). Immobilization of these complexes by anchoring onto Merrifield™ resin with respect to their use as recyclable catalysts was subsequently performed. The heterogeneous catalysts prepared in this way were tested in the asymmetric Henry reactions and showed high catalytic activity; they can be easily recycled, although their enantioselectivities were only moderate (∼50% ee).
Four bacterial isolates, which produced polyunsaturated fatty acids (PUFA), were isolated from water samples of radioactive springs collected from Jáchymov spa. Jáchymov (Sankt Joachimsthal) is a ...city in northwestern Bohemia, where Marie and Pierre Curie isolated radium in 1898 from the mineral uraninite. To date, four springs (Agricola, Behounek, C1, and Curie) have been used for spa purposes, that is for the treatment of nervous and rheumatic disorders by constantly produced radioactive gas radon (222Rn) dissolved in the water. The radioactivity reaches 24 kBq/L. Using 16S rRNA gene sequence analysis, all four isolates were identified as members of the genus Kocuria, with two isolates designated 208 and 401 affiliated with Kocuria kristinae, while isolates 101 and 301 most likely with K. rhizophila. The content of fatty acids in polar lipids was determined by gas chromatography–mass spectrometry (GC–MS) and two PUFA, that is arachidonic and eicosapentaenoic, were identified. The position of double bonds was confirmed by GC–MS of 3‐pyridylcarbinol (formerly picolinyl) esters. We assume that all four isolates of Kocuria produce PUFA to increase the stability of cell membranes, which may be impaired by the reaction of the reactive oxygen species. These can arise, for example, because of α radiation during 222Rn decay.
Dynamic economic expansion of metropolitan regions in post-communist central Europe induces dynamic traffic growth, which calls for new transport network solutions and improvements to existing ...transport infrastructure within the regions. This is also the case of Bratislava as the capital city of post-communist Slovakia, which has recently been facing new economic and urban development challenges. A booming labour market, intensive suburbanisation processes, traffic expansion and urban (re-)development bring new conflicts and demand for grand-scale transport projects. An ongoing upgrade of the motorway system in the region of Bratislava will result in the construction of a substantial part of an orbital motorway surrounding the southern and eastern parts of the city. The potential effects of the motorway network-upgrade projects on the city urbanism are probably immense. This paper attempts to evaluate the possible changes in accessibility within the road network after completion of motorway upgrading project D4/R7 in the metropolitan area of Bratislava. The interaction potential of both population and jobs was applied here to assess possible impacts of road network enhancement on accessibility of places of residence and of work.
The main objective of this study is interested primarily in the inter-individual diversity in fertility according to the parity distribution of women reproduction in Czech Republic and Slovakia. The ...authors identify a sharp decline in the concentration of reproduction during the 20th century at very low levels. It was primarily the result of a very low childlessness with combination of significant domination of the two-child family model. This trend has reversed for the most recent cohorts. It appears that this development mainly triggered by pluralization of reproductive behavior. The youngest cohort tends to increase childlessness as well as increase the proportion of women with only one child. The growing concentration of reproduction suggests that future society in Czech Republic and Slovakia should not simply focus on "average" women (or mother) but should take into an account a wide spectrum of orientations and life strategies.
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![Synthesis of [ 3 H]Org24598...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0362-4803/small "Synthesis of [ 3 H]Org24598 using in-house prepared [ 3 H]MeI")
