A simple and effective method was proposed for the synthesis of new phosphinic peptides in free form, structural isosteres of the dipeptide components of beta-amyloid (Aβ42), potential inhibitors of zinc-metalloproteinases.

The synthesis of a phosphinic structural analogue of the tetrapeptide Met-Glu-γ-His-Phe by adding the dipeptide component His-Phe to the adamantyl ester of the phosphinic pseudo-Met-[P]-Glu-peptide in the form of cyclic glutamate anhydride is proposed. The conditions for the interaction of phosphinic pseudo-Met-[P]-Glu-anhydride with His-Phe in free form to form phosphinic Met-[P]-Glu-γ-His-Phe tetrapeptide have been found. A chromatographic mass-spectrometry study, including MS2, and NMR of the phosphinic tetrapeptide on 1H, 13C, 31P nuclei was carried out using the methods of two-dimensional 1H–1H COSY, 1H–13C HSQC and 1H–13C HMBC NMR spectroscopy.

The reaction between dialkyl methylenebiscarbamates and phosphonous carboxylic acids affords N-protected phosphinic pseudopeptides incorporating glycine isostere. The compounds obtained are promising building blocks for subsequent peptide modification.

The amidoalkylation of a phosphonous acid containing a structural isostere of diethyl glutamiate, using ethyl carbamate and 3-(methylthio)propionaldehyde, was proposed for the synthesis of NC(O)OEt-protected phosphinic pseudo-Met-Glu-peptide. Subsequent adamantyl protection of the phosphorylic function and hydrolysis of carboxylic groups made it possible to obtain phosphinic Met-[P]-Glu peptide in the form of cyclic glutamate anhydride. It was found that the latter reacts with the third amino acid component histidine to form the phosphinic Met-[P]-Glu-γ-His tripeptide.

The variability of radon-220 (thoron) distribution in the surface atmosphere is investigated by mathematical modeling of thoron turbulent transport, based on the data of continuous field natural observations at Borok Geophysical Observatory (Central Russia). The thoron flux from the surface was set according to the observations. Variations of turbulent diffusion coefficient altitude profiles were calculated by the observations of wind velocity pulsations at two altitudes made synchronously on the same location. The altitude profiles of thoron volumetric activity typical for the atmospheric surface layer are estimated. It is shown that the thoron volumetric activities at any altitudes vary concurrently, but the largest thoron volumetric activity, as well as its gradient, occurs below 0.5 m at nighttime.

An unusual greater reactivity of phosphonous propionic acids was found in comparison with phosphonous propionic esters in carbamate version of Kabachnik-Fields reaction. Compounds of tricoordinated phosphorus generated in situ during the amidoalkylation of hydrophosphorylic compounds in acetyl chloride/acetic anhydride mixture were found by 31P NMR analysis. A hypothesis is proposed about the generation of spirophosphoranes in situ to explain the mechanism for the formation of the phosphorus-carbon bond in the reaction under study.

Mathematical model of dynamics of altitude distribution of natural radon isotopes in the surface atmosphere above land, parameterized by results of synchronous surface aerophysical and radonometric observations, is considered. The results of numerical solution of model equations parameterized by the observable in Borok Geophysical Observatory data are presented. The daily variations of volumetric activity of radon isotopes caused by the daily variation of the turbulent regime of the undisturbed surface atmosphere, characteristic of land of medium latitudes, are obtained.

BACKGROUND:Treatment of neurodegenerative diseases, such as Parkinson's disease, Huntington's chorea, Alzheimer's disease, is one of the priority directions in modern medicine. Thus, search and production of new physiologically active substances for the treatment of neurodegenerative disorders is one of the most important tasks for organic chemistry. The approach based on the replacement of a peptide bond in a peptide molecule with a structural isostere, non-hydrolyzable methylene phosphoryl fragment makes it possible to increase the metabolic stability of peptide molecules to the destructive action of peptidases. METHODS:This work is devoted to the approbation of a new synthetic approach to the production of physiologically active substances in a series of peptide-type compounds with activity by replacing the peptide bond with isosteric methylene-phosphoryl fragment with the preservation of the original amino acid sequence. RESULTS:A phosphine analog of the known physiologically active tripeptide proline-glycine-proline was obtained, cytotoxicity and neuroprotective properties of the initial tripeptide and its phosphine analog were studied. CONCLUSION:Preliminary biological tests have shown that the obtained phosphine analog of the proline-glycine-proline tripeptide is involved in modulating the formation of sediments in the cellular system of proteinopathy, which may indicate their potential antiaggregatory properties.

Racemic phosphinic tripeptide 1 pyrrolidin-2-yl-{3-[(2-hydroxycarbonyl)-pyrrolidin-1-yl]-3-oxo-propyl}-phosphinic acid has been synthesized, its high resistance toward leucine aminopeptidase, carboxypeptidase Y, and the enzyme system of rat brain membranes has been shown. In vitro experiments with using Semax synthetic peptide have shown that the effect of tripeptide 1 on the hydrolysis rate of Semax in the case of leucine aminopeptidase and carboxypeptidase Y is minimal. In experiments using the enzyme system of rat brain membranes, the decrease of the rate of Semax hydrolysis has been more evident.

В данной работе представлены результаты исследования биоактивных наночастиц силиката магния. Сами наночастицы получали методом химического осаждения в водной среде. Размер и форму образцов исследовали на ПЭМ-микроскопе. Установлено, что поверхность образцов представлена крупными агрегатами. В свою очередь, агрегаты состоят из сферических наночастиц силиката магния с размерами от 10 до 20 нм. На следующем этапе, с помощью нейросетевой обработки экспериментальных данных проводили оптимизацию синтеза наночастиц. Анализ полученной тернарной поверхности показал, что для получения образцов с наименьшим размером агрегатов (700 нм) параметрами синтеза являются: температура – 50 °С, скорость перемешивания – 600 об/мин, концентрация прекурсора – 0,5 моль/л. Определив оптимальные параметры синтеза силиката магния, проводили компьютерное квантово-химическое моделирование. В результате расчетов обнаружено, что энергия конфигурации составила E = –709,302 ккал/моль, величина химической жесткости η = 0,191 эВ, а мягкости – S = 2,62 эВ–1. На основе полученных данных можно заключить, что MgSiO3 обладает высокой стабильностью и характеризуется, как относительно мягкая молекула. На заключительном этапе работы образцы исследовали на ИК-спектрометре. Анализ ИК-спектра показал наличие характерных полос поглощения, которые соответствуют колебаниям связей в молекуле MgSiO3.

Phosphinic isosteres of leucylglycine and isoleucylglycine were obtained by amidoalkylation of (3-benzyloxy-3-oxopropyl)phosphonous acid bearing the structural isostere fragment of glycine benzyl ester in acetyl chloride. A three-component amide version of the Kabachnik–Fields reaction involving methyl (benzyl) carbamates and 2(3)-methylbutanals was studied. The reaction proceeded under the conditions of acylation of the starting (3-benzyloxy-3-oxopropyl)phosphonous acid and in situ generation of a bisacetyl derivative of the three-coordinated phosphorus, the formation of which was detected using NMR 31Р.

The amidoalkylation reactions of a phosphonous acid containing a structural isostere of leucine in acetyl chloride and(or) acetic anhydride were studied under conditions of acid catalysis. A two-component method for the synthesis of a phosphinic analogue of alanylleucine using ethylidenebis(benzylcarbamate) was proposed.

The SRS-05 radon-recording seismic station is widely used to monitor the volumetric activity of radon, primarily to detect its increase as an earthquake precursor. The low sensitivity of the sensor does not allow real-time recording of background volumetric activity of radon isotopes 222 Rn (radon) and 220 Rn (thoron). However, accurate measurement of background volumetric activity of radon isotopes is of great interest, especially in studies of ionization processes and the electric state of the near-surface atmosphere. This paper proposes a method for determining the mean background volumetric activity of radon isotopes based on α-spectra from a radon-recording seismic station over a long period (several days). The determined background volumetric activity of 222 Rn and 220 Rn in soil and near-surface atmosphere at the Borok Geophysical Observatory are presented.

The variability of radon distribution in the surface atmosphere is investigated by numerical modeling of radon turbulent transport, based on the data of continuous field natural observations. The boundary conditions, including the radon flux from the surface and radon volumetric activity variation near the surface, were set according to the observations. Variations of turbulent diffusion coefficient altitude profiles were calculated by the observations of wind velocity pulsations at two altitudes made synchronously on the same location. The altitude profiles of radon volumetric activity typical for the atmospheric surface layer over the land of middle latitudes are obtained. It is shown that the radon volumetric activities at any altitudes vary concurrently, but the near-surface radon volumetric activity are greater than one at 10 m. The relative difference between them varies from 10 % (near local midnight) to 120 % (near local midday). The most considerable increase of the radon volumetric activity gradient occurs below 2 m.

An acid-catalyzed three-component reaction between hypophosphorous acid, aldehydes and alkyl carbamates under mild conditions afforded bis(α-aminoalkyl)phosphinic acids. The proposed facile single-stage protocol is prospective for expansion of a range of phosphinic analogues of HIV protease inhibitors.

Radon-222 is inert radioactive gas with a half-life period of 3.8 days, it is a decay product of radium-226. Being escaped from minerals and underground waters into pore space of rocks and soil, it is transported to the surface by diffusion and advection and gone to the atmosphere. When modeling processes of atmosphere radon transport one sets value of radon flux from the surface, depending on contents of radium-226 in rocks and conditions of radon transport in soil, especially on soil porosity and humidity. The impact of radon turbulent transport in the atmospheric boundary layer (ABL) on radon flux density from the surface is estimated in this paper. It is shown that both for stationary state and for typical diurnal variations of the radon volumetric activity (VA) in the ABL, the correction to the radon flux density caused by its turbulent transport in the ABL is negligible (less than 1%) and doesn’t exceed measurement errors. Thus, when calculating radon VA in the ABL it is really possible to set an average value of the radon flux density on the surface as a boundary condition.

The phosphine block N-Cbz-Pro-ψ[P(O)(OAd)CH2]-GlyOH has been synthesized for subsequent peptide assembly. A procedure has been proposed for the preparation of phosphorus prolylglycine isostere by three-center two-component amide version of the Kabachnik–Fields reaction. A combination of amide and carbonyl fragments in the molecule of 4-N-Cbz-aminobutyraldehyde makes it possible to accomplish cyclization with generation in situ of a cyclic pyrrolidine Schiff base, followed by Arbuzov phosphorylation of the latter with diacetyl 2-(ethoxycarbonyl)ethyl phosphonite generated in situ.