scholarly journals Redox Conversions of 5-Methyl-6-nitro-7-oxo-4,7-dihydro-1,2,4triazolo[1,5-a]pyrimidinide L-Arginine Monohydrate as a Promising Antiviral Drug

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 5087
Author(s):  
Alexandra Ivoilova ◽  
Ludmila V. Mikhalchenko ◽  
Anton Tsmokalyuk ◽  
Marina Leonova ◽  
Andrey Lalov ◽  
...  
Keyword(s):  
Esr Spectroscopy ◽  
Nitroxyl Radical ◽  
Ion Pairs ◽  
Antiviral Drug ◽  
Electrode Reaction ◽  
Buffer Solution ◽  
Simultaneous Formation ◽  
Two Stages ◽  
Kinetics Of ◽  
Second Peak

This article presents the results of a study of electrochemical transformations in aqueous and aprotic media of 5-methyl-6-nitro-7-oxo-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidinide l-arginine monohydrate (1a, Triazid) obtained by electrochemical methods and ESR spectroscopy. The effect of pH on the current and the reduction potential of 1a in an aqueous Britton–Robinson buffer solution was studied. It was found that 1a is irreversibly reduced in aqueous acidic media on a glassy carbon electrode in one stage with the participation of six electrons and the formation of 5-methyl-6-amino-7-oxo-1,2,4-triazolo[1,5-a]pyrimidin. The electroreduction of 1a in DMF on a background of tetrabutylammonium salts proceeds in two stages, controlled by the kinetics of second-order reactions. In the first stage, the reduction of 1a is accompanied by protonation by the initial compound of the basic intermediate products formed in the electrode reaction (self-protonation mechanism). The second quasi-reversible stage of the electroreduction 1a corresponds to the formation of a dianion radical upon the reduction of the heterocyclic anion 5-methyl-6-nitro-7-oxo-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidin, which is formed upon the potentials of the first peak. The ESR spectrum of the radical dianion was recorded upon electroreduction of Triazid in the presence of Bu4NOH. The effect of the formation of ion pairs on the reversibility of the second peak of the 1a transformation is shown. A change in the rate and regioselectivity of the protonation of the dianion radical in the presence of Na+ and Li+ ions is assumed. The results of studying the electroreduction of 1a by ESR spectroscopy with a TEMPO trap make it possible to assume the simultaneous formation of both a nitroxyl radical and a radical with the spin density localized on the nitrogen at the 4 position of the six-membered ring.

Discreteness-of-charge effects in electrode kinetics. II. The electroreduction of hexamminocobalt(III) cation in the presence of specifically adsorbed nitrate anions

1983 ◽  
Vol 61 (12) ◽  
pp. 2821-2826 ◽  
Author(s):  
W. Ronald Fawcett ◽  
Kveta Markušová
Keyword(s):  
Ion Pairs ◽  
Electrode Reaction ◽  
Ion Concentration ◽  
Charge Effects ◽  
Interfacial Kinetics ◽  
Rate Of Reaction ◽  
Layer Effect ◽  
Kinetics Of ◽  
Nitrate Anions ◽  
Cation Nature

The kinetics of electroreduction of the hexamminocobalt(III) cation have been studied at a Hg electrode in aqueous solutions of NaNO3 + NaF and KNO3 + KF with an ionic strength of 0.2 M. The rate of reaction was observed to increase with increasing nitrate ion concentration but was independent of the cation nature. Analysis of the double layer effect for this system indicates that ion pairs formed between the reacting cation and anions of the base electrolyte also participate in the electrode reaction, and that attractive interactions between the reactant and adsorbed anions have a significant influence on the interfacial kinetics.

Copolymerization of Isobutene and Isoprene at “High” Temperature with Syncatalyst Systems Based on Aluminum Organic Compounds

1976 ◽  
Vol 49 (4) ◽  
pp. 937-959 ◽  
Author(s):  
S. Cesca ◽  
M. Bruzzone ◽  
A. Priola ◽  
G. Ferraris ◽  
P. Giusti
Keyword(s):  
Energy Savings ◽  
Ion Pairs ◽  
Great Part ◽  
Methyl Chloride ◽  
Reactivity Ratio ◽  
Experimental Conditions ◽  
Noticeable Increase ◽  
Catalyst Systems ◽  
Kinetics Of ◽  
Kinetics Of Vulcanization

Abstract New catalyst systems based on alkylaluminum derivatives and halogen or interhalogen compounds were found highly efficient in the synthesis of high-molecular-weight IIR at temperatures above − 50°C. The reaction mechanism was studied in detail for the system Et2AlCl + Cl2. The reactions occurring between chlorine, isobutene, Et2AlCl, and the solvent (CH3Cl) were elucidated and studied under various experimental conditions (e.g. presence or absence of light, simultaneous presence of the copolymerization system components, temperature, type of halogen, use of model compound of isobutene). It was concluded that halogenium ions, i.e. Cl+, Br+, or I+, are the initiating species. Kinetic and conductometric investigations showed that scarcely dissociated ion pairs, e.g. Cl+[Et2AlCl2]−, were formed in the absence of monomer; but in the presence of isobutene, a noticeable increase of the electrical conductivity and rapid polymerization occurred. The maximum polymerization rate was first order with respect to the concentrations of monomer, Cl2, and Et2AlCl. In the homopolymerization of isobutene, transfer to monomer and termination reactions were negligible. The MW of IIR was found to be mainly dependent on the concentrations of the catalyst components, on isoprene concentration, and on temperature. The reactivity ratio of isobutene with isoprene was found to be r1=2.5±0.5 at −35°C, while the activation energies relative to MW were −5.8 ± 0.4, kcal/mol for polyisobutene, and −5.7 ± 0.7 and − 4.3 ± 0.5 kcal/mol for IIR containing, respectively, 1.3 and 1.9 mol% of isoprene. The evaluation of some physicochemical and technological properties of typical IIR produced with the system Et2AlCl + Cl2, indicated that isoprene is randomly distributed along the chains and that the MWD is monomodal, while the glass transition temperature, tensile properties, mechanical-dynamic spectra, and kinetics of vulcanization are very similar to those of commercial IIR. Very preliminary data, referring to several classes of new catalyst systems yielding IIR having good properties, were also obtained. The syncatalyst systems here described can work in a homogeneous phase consisting of an aliphatic hydrocarbon besides methyl chloride, still giving IIR with high MW. Therefore, a completely homogeneous process can be envisioned for the synthesis of IIR at −50°C thus avoiding a great part of the fouling problems of the slurry process. The economic advantage of using “high” temperatures of polymerization is briefly discussed in terms of energy savings.

Study of the permeability of fluorinated high-pressure polyethylene for temporary fuel storage

2021 ◽  
pp. 65-69
Author(s):  
Юрий Николаевич Рыбаков ◽  
Александр Васильевич Дедов ◽  
Роман Игоревич Кюннап ◽  
Сергей Владимирович Ларионов
Keyword(s):  
Molecular Weight ◽  
High Pressure ◽  
Diesel Fuel ◽  
Permeability Coefficient ◽  
Layer Structure ◽  
Storage Period ◽  
High Pressure Polyethylene ◽  
Fuel Storage ◽  
Two Stages ◽  
Kinetics Of

Исследована проницаемость фторированного полиэтилена высокого давления (ПВД), предназначенного для изготовления ремонтных и технологических вкладышей резервуаров складов временного хранения топлива. Использование таких вкладышей позволяет снизить технологические потери углеводородов и увеличить надежность хранилищ из полимерных материалов. В качестве объекта исследования использовали пленки ПВД 10204-003 толщиной 100 мкм. Проницаемость пленок определяли при контакте с бензином марок Нормаль-80, Премиум-95, авиационным керосином ТС-1 и дизельным топливом. Рассмотрен механизм формирования структуры поверхностного фторированного слоя. Исследована кинетика изменения коэффициента проницаемости исходного и модифицированного полиэтилена в течение возможного срока хранения топлив. По результатам исследования установлено: 1) в полиэтилене перенос топлива протекает в две стадии, что определяется раздельной диффузией низкомолекулярных и высокомолекулярных фракций углеводородов; 2) фторирование полиэтилена приводит к уменьшению коэффициента проницаемости (что имеет практическое значение для сохранения качества топлива), но не влияет на перенос фракции углеводородов минимальной молекулярной массы. The permeability of fluorinated high-pressure polyethylene (HDPE), intended for the manufacture of repair and technological liners of tanks for temporary fuel storage has been investigated. As the object of research, 10204-003 HDPE films with 100 μm thickness were used. The permeability of the films was determined by contact with gasoline of the Normal-80 and Premium-95 brands, aviation kerosene TS-1, and diesel fuel. The formation mechanism of the surface fluorinated layer structure was considered. The kinetics of changes in the permeability coefficient of the original and modified polyethylene during the possible fuel storage period has been studied. It has been established that the transfer of fuel in polyethylene proceeds in two stages, which is determined by the separate diffusion of low-molecular and high-molecular hydrocarbon fractions. Fluoridation of polyethylene decreases the permeability coefficient, but does not affect the transfer of hydrocarbon fraction with the minimum molecular weight.

Biochemical and Biophysical characterization of the main protease, 3-chymotrypsin-like protease (3CLpro), from the novel coronavirus disease 19 (COVID-19)

2020 ◽  
Author(s):  
Juliana C. Ferreira ◽  
Wael M. Rabeh
Keyword(s):  
Antiviral Drug ◽  
Analytical Techniques ◽  
The Novel ◽  
Buffer Solution ◽  
Biophysical Characterization ◽  
Main Protease ◽  
Wide Ph Range ◽  
The Stability ◽  
Ph Range ◽  
Novel Coronavirus

Abstract Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is responsible for the novel coronavirus disease 2019 (COVID-19). An appealing antiviral drug target is the coronavirus 3C-like protease (3CLpro) that is responsible for the processing of the viral polyproteins and liberation of functional proteins essential for the maturation and infectivity of the virus. In this study, multiple thermal analytical techniques have been implemented to acquire the thermodynamic parameters of 3CLpro at different buffer conditions. 3CLpro exhibited relatively high thermodynamic stabilities over a wide pH range; however, the protease was found to be less stable in the presence of salts. Divalent metal cations reduced the thermodynamic stability of 3CLpro more than monovalent cations; however, altering the ionic strength of the buffer solution did not alter the stability of 3CLpro. Furthermore, the most stable thermal kinetic stability of 3CLpro was recorded at pH 7.5, with the highest enthalpy of activation calculated from the slope of Eyring plot. The biochemical and biophysical properties of 3CLpro explored here will improve the solubility and stability of 3CLpro for optimum conditions for the setup of an enzymatic assay for the screening of inhibitors to be used as lead candidates in the drug discovery and antiviral design for therapeutics against COVID-19.

scholarly journals Differential Biodegradation Kinetics of Collagen Membranes for Bone Regeneration

Polymers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1290
Author(s):  
Manuel Toledano ◽  
Samara Asady ◽  
Manuel Toledano-Osorio ◽  
Franklin García-Godoy ◽  
María-Angeles Serrera-Figallo ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Hydrolytic Degradation ◽  
Phosphate Buffer Solution ◽  
Buffer Solution ◽  
Barrier Membranes ◽  
Time Points ◽  
Equine Pericardium ◽  
Collagen Membranes ◽  
Kinetics Of ◽  
Digital Caliper

Native collagen-based membranes are used to guide bone regeneration; but due to their rapid biodegradation, this treatment is often unpredictable. The purpose of this study was to investigate the biodegradability of natural collagen membranes. Three non-cross-linked resorbable collagen barrier membranes were tested: Derma Fina (porcine dermis), Evolution Standard (equine pericardium) and Duo-Teck (equine lyophilized collagen felt). 10 × 10 mm2 pieces of membranes were submitted to three different degradation procedures: (1) hydrolytic degradation in phosphate buffer solution, (2) enzyme resistance, using a 0.25% porcine trypsin solution, and (3) bacterial (Clostridium histolyticum) collagenase resistance test. Weight measurements were performed with an analytic microbalance. Thickness was measured with a digital caliper. Membranes were analyzed at different time-points, up to 21 d of immersion. A stereomicroscope was used to obtain membranes’ images. ANOVA and Student Newman Keuls were used for mean comparisons (p < 0.05), except when analyzing differences between time-points within the same membrane and solution where pair-wise comparisons were applied (p < 0.001). Derma Fina attained the highest resistance to all degradation challenges. Duo-Teck was the most susceptible membrane to degradation, complete degradation occurred as soon as 8 h. The bacterial collagenase solution performed as the most aggressive test as all membranes presented 100% degradation before 21 d.

scholarly journals Assessment of in Vitro Comparative Dissolution Kinetics of Moxonidine Products as a Factor Potentially Determining Effectiveness of Antihypertensive Treatment

2019 ◽  
Vol 14 (6) ◽  
pp. 951-957
Author(s):  
G. V. Ramenskaya ◽  
I. E. Shokhin ◽  
N. I. Gaponova ◽  
V. R. Abdrakhmanov
Keyword(s):  
Generic Drugs ◽  
Dissolution Kinetics ◽  
Acetate Buffer Solution ◽  
Medicinal Products ◽  
Buffer Solution ◽  
Reference Drug ◽  
Similarity Factor ◽  
Kinetics Of ◽  
Comparative Dissolution

Aim. Investigation of comparative dissolution kinetics of generic medicinal products containing moxonidine versus reference drug. Material and methods. Objects of the research were film-coated tablets containing moxonidine (INN) in a dose 0.4 mg: a reference drug Physiotens® and 4 generic drugs. In vitro dissolution test of moxonidine from the study drugs was performed using comparative dissolution kinetics test (CDKT). The CDKT was performed in the media with the following pH: 1.2 (1:9 mixture of 0.1 M hydrochloric acid and water), 4.5 (acetate buffer solution, prepared as per State Pharmacopoeia, XIII), and 6.8 (phosphate buffer solution, prepared as per State Pharmacopoeia, XIII). The sampling for dissolved moxonidine was performed 5, 10, 15, 20, and 30 min after the test was started. An high performance liquid chromatography method with ultraviolet detection at 220 nm was used to assay. Results. Within 15 min more that 85% of moxonidine dissolved from the reference drug and all study drugs at pH 1.2; dissolution profiles were similar without calculation of similarity factor f2. Similarly, at pH 4.5 dissolution profiles of study drugs #2 and #3 were similar to that of the reference drug, and the similarity factor f2 was not calculated. However, in case of study drugs #1 and #4 significant differences were observed at a single time point (15 min), which suggests that their dissolution profiles are non-similar to that of the reference drug. Similarity factors f2 were calculated 17.52 and 35.30, respectively (less than 50). At pH 6.8 similarity factors f2 for all study generic drugs were also less than 50 (23.8, 49.8, 38.6, and 35.9), so their dissolution curves were non-similar to that of reference drug. Conclusion. In our study we observed difference in release in vitro of medicinal products containing moxonidines: none of the study drugs was fully similar to the reference drug in all media. The differences observed at pH 6.8 were noteworthy, where the samples had or faster kinetics (study drugs #2 and #3), or slower dissolution kinetics (test drugs #1 and #4). Observed differences in moxonidine release rate may impact absorption of active pharmaceutical ingredient into the blood following drug administration.

INTRACELLULAR CA++ MOBILIZATION IN GRAY PLATELET SYNDROME. ELECTRONMICROSCOPIC STUDIES ON AEQUORIN LOADED PLATELETS

1987 ◽  
Author(s):  
K Mori ◽  
S Suzuki ◽  
K Sugai ◽  
Y Akutsu ◽  
M Ishikawa ◽  
...  
Keyword(s):  
Morphological Changes ◽  
Peripheral Blood Smear ◽  
Buffer Solution ◽  
A 23187 ◽  
Tubular System ◽  
Intracellular Ca ◽  
Trace Line ◽  
Platelet Aggregates ◽  
Gray Platelet Syndrome ◽  
Second Peak

Light microscopic examinations on platelets in Gray Platelet Syndrome(GPS) showed peculiar gray colored platelets due to deficiency in ^-granules on the peripheral blood smear by May-Grunwald-Giemsa stain. Besides α-granule deficiency, however, several morphological abnormalities, especially abnormal features of dense tubular system(DTS) etc., were recognized in the transmission electronmicroscopic examinations. In the platelet function tests, release abnormalities rather than storage-pool deficiency were noted. We were strongly interested in the relationships between these morphological and functional abnormalities, because DTS in the platelets have been thought to be main storage sites of intracellular Ca ion.We examined the intracellular Ca++ mobilization using aequo-rin loaded platelets by means of Lumi-aggregometer(Salzman's method) under the stimulation of A-23187 and thrombin, and also morphological changes of platelets during the process of platelet aggregation by light |ipd transmission electronmicroscope.Intracellular Ca concentration increased dose-dependently after addition of A-23187 in both normal and GPS platelets. Namely, besides the first peak of emission which located at the same site as normal control, the slowly appearing second peak were recognized on the trace line by the addition of A-23187 and also abnormal by thrombin in GPS platelets. Transmission electronmi-crographs showed insufficient contraction of platelet-aggregates and malformation or wide appearance of pseudopods by the addition of A-23187 and thrombin. Most of the contractile gels, which were usually seen in the center of the platelets, were slightly enlarged and eccentric in the position. Delayed intracellular Ca mobilization were also noted even in the buffer solution containing EGTA.From above mentioned results, intracellular Ca++ mobilization were abnormal and these low and delayed mobilization were thou -ght to be related with prominent abnormal morphology, especially abnormalities of DTS in the GPS platelets.

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