Non-natural nucleosides based on 1,2,4-triazolo[5,1-c][1,2,4]triazin-4(6H)- ones

Two regioselective methods for the synthesis of nucleosides in the series of 3-phenyl- and 3- ethoxycarbonyl-1,2,4-triazolo[5,1-c][1,2,4]triazin-4-ones were developed. The first route involves a Vorbrüggen glycosylation reaction. The second one is based on condensation of 1,2,4- triazolo[5,1-c][1,2, 4]triazin-4-one sodium salts with protected 1-bromo-sugar derivatives

Synthesis of acyclic nucleoside analogues by one-step Vorbrüggen glyco-sylation of 1,2,4-triazolo[1,5-a]pyrimidine-7-ones

New analogues of acyclovir have been prepared by reacting 1,2,4 -triazolo[1,5-a]pyrimidin-7-ones 1а-i and (2-acetoxyethoxy)methyl acetate 2 in the presence of trimethylsilyl trifluoromethanesulfonate as a catalyst. The interaction between the compounds 1а-е and 2 has led to a mixture of N3 and N4 isomers. In contrast, the reaction of compounds 1g-i and 2 proceeded selectively to form N3 isomers. In the case of compounds 1a-c the predominant product is the one with the acyclic moiety in azine ring (N4 isomer). Interaction between 1d-f and 2 has led to mixtures comprising mainly N3 isomer. It has been found that the ratio of glycosylation products 1 and 2 are thermodynamically controlled. The structure of the obtained compounds has been proved by 1Н, 13С, two-dimensional 1Н-13С NMR spectroscopy and X-ray analysis

Spin-spin coupling constants 13C-15N and 1H-15N in the investigation of azido-tetrazole tautomerism in a series of 2-azidopyrimidines

A new method was developed for the investigation of an azido-tetrazole equilibrium based on using a complex analysis of 13C-15N and 1H-15N spin-spin coupling constants. The use of this approach became possible due to the selective inclusion of 15N isotopes into the structures of 2-azidopyrimidines and their cyclic analogs tetrazolo[1,5-a]pyrimidines. © 2013 Springer Science+Business Media New York

Long-range 1H-15N J couplings providing a method for direct studies of the structure and azide-tetrazole equilibrium in a series of azido-1,2,4-triazines and azidopyrimidines

The selectively 15N labeled azido-1,2,4-triazine 2*A and azidopyrimidine 4*A were synthesized by treating hydrazinoazines with 15N-labeled nitrous acid. The synthesized compounds were studied by 1H, 13C, and 15N NMR spectroscopy in DMSO, TFA, and DMSO/TFA solutions, where the azide-tetrazole equilibrium could lead to the formation of two tetrazoles (T, T′) and one azide (A) isomer for each compound. The incorporation of the 15N label led to the appearance of long-range 1H-15N coupling constants (JHN), which can be measured easily by using amplitude-modulated 1D 1H spin-echo experiments with selective inversion of the 15N nuclei. The observed JHN patterns enable the unambiguous determination of the mode of fusion between the azole and azine rings in the two groups of tetrazole isomers (2*T′, 4*T′ and 2*T, 4*T), even for minor isoforms with a low concentration in solution. However, the azide isomers (2*A and 4*A) are characterized by the absence of detectable J HN coupling. The analysis of the JHN couplings in 15N-labeled compounds provides a simple and efficient method for direct NMR studies of the azide-tetrazole equilibrium in solution. © 2013 American Chemical Society

Incorporation o f stable isotopes 2H, 13C and 15N in the structure of azolo[5,1-c][l,2,4]triazines and azolo[1,5-a]pyrimidine as a tool for studying the chemical and biological transformations of nitrogenous heterocycles

It is shown that selective incorporation of stable isotopes allows one to expand standard capabilities of NMR spectroscopy and is an effective approach to the study of the structure and reactivity of organic compounds. Azidotetrazole equilibrium, Dimroth rearrangement, and adamantylation of azoloazines were examined using compounds labeled by stable isotopes.This work was financially supported by the Ministry o f Education and Science o f the Russian Federation (state contract in 2458)

An inhomogeneous toy-model of the quantum gravity with explicitly evolvable observables

An inhomogeneous (1+1)-dimensional model of the quantum gravity is considered. It is found, that this model corresponds to a string propagating against some curved background space. The quantization scheme including the Wheeler-DeWitt equation and the "particle on a sphere" type of the gauge condition is suggested. In the quantization scheme considered, the "problem of time" is solved by building of the quasi-Heisenberg operators acting in a space of solutions of the Wheeler-DeWitt equation and the normalization of the wave function corresponds to the Klein-Gordon type. To analyze the physical consequences of the scheme, a (1+1)-dimensional background space is considered for which a classical solution is found and quantized. The obtained estimations show the way to solution of the cosmological constant problem, which consists in compensation of the zero-point oscillations of the matter fields by the quantum oscillations of the scale factor. Along with such a compensation, a slow global evolution of a background corresponding to an universe expansion exists.Comment: 18 page

The doctor as a creative person: the essential quality

In article the creative aspect of a profession of the doctor, need of existence of creativity and creative abilities at workers in medicine sulfur is considered.В статье рассматривается необходимость наличия креативности и творческих способностей у работников в сфере медицины

Regulated expression of human beta-defensin-2 leads to altered phenotype and growth patterns of cultured human embryonal kidney cells

Aim: To create cell line with regulated expression of human beta-defensin-2 (hBD-2) and evaluate the influence of expressed peptide on its phenotypic and growth patterns. Materials and Methods: Using cloning techniques, on the base of human embryonic kidney cells of HEK293T line, stable T-rex HEK-hBD2-m cell subline expressing mature biologically active hBD-2 molecule upon the presence of tetracycline in culture medium was generated. The morphological patterns, growth characteristics and colony forming activity of these cells were studied using routine techniques. Results: T-rex HEK-HBD2-m cell subline was shown to express both mRNA and hBD-2m protein upon the presence of 1 µg/ml tetracycline in culture medium as it was demonstrated by RT-PCR and immunocytochemical approach. Upon prolonged expression of hBD-2, the cells acquired special features: they lost ability to grow in monolayer in vitro and to form colonies in soft agar, characteristic to parental HEK293T cells, but possess higher growth rate and longer survival in FBS-free medium than wild type cells. Conclusion: Expression of hBD-2 in T-rex HEK-HBD2-m cell subline results in specific biological consequences that favor cell survival.Цель: создать линию клеток с регулируемой экспрессией бета-дефенсина-2 человека (hBD-2) и проанализировать влияние экспрессии этого пептида на особенности фенотипа и рост клеток. Материалы и методы: клеточная сублиния T-rex HEK hBD2-m, экспрессирующая биологически активную зрелую форму hBD-2 при индукции клеток тетрациклином, получена путем клонирования на основе эмбриональных клеток почки человека линии HEK293T. Морфологические особенности, характеристики роста и показатели колониеобразования в полужидкой среде исследовали стандартными методами. Результаты: с помощью методов РТ-ПЦР и иммуноцитохимии показано, что сублиния клеток T-rex HEK-HBD2- экспрессирует hBD2 в присутствии 1 µг/мл тетрациклина в среде инкубации. Продолжительная экспрессия hBD-2 приводила к тому, что клетки утрачивали способность образовывать монослой при культивировании in vitro и образовывать колонии в полужидкой среде, но характеризовались более высокой скоростью роста и способностью к более продолжительному выживанию в бессывороточной среде, чем исходная линия клеток HEK293T. Выводы: экспрессия hBD-2 в сублинии клеток T-rex HEK-HBD2- cell обусловливает специфические биологические эфеекты, способствующие выживанию клеток

General Relativity as Classical Limit of Evolutionary Quantum Gravity

We analyze the dynamics of the gravitational field when the covariance is restricted to a synchronous gauge. In the spirit of the Noether theorem, we determine the conservation law associated to the Lagrangian invariance and we outline that a non-vanishing behavior of the Hamiltonian comes out. We then interpret such resulting non-zero ``energy'' of the gravitational field in terms of a dust fluid. This new matter contribution is co-moving to the slicing and it accounts for the ``materialization'' of a synchronous reference from the corresponding gauge condition. Further, we analyze the quantum dynamics of a generic inhomogeneous Universe as described by this evolutionary scheme, asymptotically to the singularity. We show how the phenomenology of such a model overlaps the corresponding Wheeler-DeWitt picture. Finally, we study the possibility of a Schr\"odinger dynamics of the gravitational field as a consequence of the correspondence inferred between the ensemble dynamics of stochastic systems and the WKB limit of their quantum evolution. We demonstrate that the time dependence of the ensemble distribution is associated with the first order correction in $\hbar$ to the WKB expansion of the energy spectrum.Comment: 23 pages, to appear on Class. Quant. Gra