Antioxidant Activity of Eugenol And Its Acetyl And Nitroderivatives: A DFT Approach of DPPH Test.

This work evaluates the antioxidant potential of acetyl and nitro derivatives of eugenol through computational techniques. Structural analysis and Hydrogen Atomic Transfer (HAT) antioxidant mechanism were investigated by density functional theory (DFT). Each molecular structure was optimized by the hybrid functional M06-2X with a basis set 6-31+G(d,p), and the HAT mechanism with HO, HOO, CH3O, DPPH radicals was evaluated. In agreement with experimental data from previous studies, two steps of hydrogen transfer were tested. Thermodynamic data showed the need for two stages of hydrogen transfer, followed by the formation of quinones to make the reaction with DPPH spontaneous. Theoretical kinetic data showed that the preferred antioxidant site depends on the instability of the attacking radical and confirmed the antioxidant profile of eugenol (E1) and 5-allyl-3-nitrobenzene-1,2-diol (E5) in the DPPH test. This study shows that the 4-allyl-2-methoxy-(4-nitrophenol) (E4) structure also has an anti-radical activity that is not seen in the experimental due to chemoselectivity of DPPH.

The solubilities of benzoic acid and its nitro-derivatives, 3-nitro and 3,5-dinitrobenzoic acids

The solubilities of benzoic acid and its nitrated derivatives (3-nitrobenzoic acid and 3,5-dinitrobenzoic acid) in seven pure solvents—water, methanol, ethanol, acetonitrile, dichloromethane, toluene, and ethyl acetate—were determined experimentally over a temperature range from 273.15 K to 323.15 K under 101.3 kPa. The solubility of the above substances in these solvents increased with temperature. The solubility values of benzoic acid in these seven solvents follow the following order: ethanol > ethanol > acetonitrile > ethyl acetate > dichloromethane > toluene > water, while the solubility values of its nitrification derivatives in these seven solvents follow the following order: methanol > ethanol > ethyl acetate > acetonitrile > dichloromethane > toluene > water. The solubility of benzoic acid, 3-nitrobenzoic acid, and 3,5-dinitrobenzoic acid were significantly different in the same solvent. The solubilities obtained are very helpful in improving the recrystallization and yields of 3-nitrobenzoic acid and 3,5-dinitrobenzoic acid.

PROPELLANS – PERSPECTIVE FRAME COMPOUNDS FOR THE CREATION OF HIGH-ENERGY SUBSTANCES

Важной задачей современной органической химии является открытие новых, ранее не известных науке веществ, которые могли бы расширить область наших знаний и пополнить номенклатуру высокоэнергетических или биологически активных продуктов. 3,7,10-Триоксо-2,4,6,8,9,11-гексааза[3.3.3|пропеллан и его нитропроизводные являются новейшими продуктами класса гетероциклов, их азотсодержащая полициклическая структура предполагает наличие интересных и полезных свойств, что обусловливает проявленный интерес к данной работе. Химия 3,7,10-триоксо-2,4,6,8,9,11-гексааза[3.3.3|пропеллана малоизучена и представлена лишь двумя алкилпроизводными и теоретическими расчетами энергетических характеристик нитропроизводных. В статье преставлены результаты исследования нитрования 3,7,10-триоксо-2,4,6,8,9,11-гексааза[3.3.3]пропеллана (THAP) концентрированнойазотной кислотой. Установлено, что в процессе нитрования наблюдается протекание двух конкурирующих реакций – лактам-лактимной перегруппировки и нитрования. Было показано, что продукты реакции сильно зависят от температуры реакционной массы. Установлено, что температуре -40 ºС протекает образование лактимной формы ТНАР, тогда как при постепенном увеличении температуры сначала образуется мононитропроизводное пропеллана, а при температуре 40 ºС идёт селективное образование 3,7,10-триоксо-2,6-динитро-2,4,6,8,9,11-гексааза[3.3.3]пропеллана с выходом 30%. An important task of modern organic chemistry is the discovery of new substances previously unknown to science, which could expand the area of our knowledge and replenish the range of high-energy or biologically active products. 3,7,10-Trioxo-2,4,6,8,9,11-hexaaza[3.3.3]propellane and its nitro derivatives are the newest products of the class of heterocycles; interest in this work. The chemistry of 3,7,10-trioxo-2,4,6,8,9,11-hexaaza[3.3.3]propellane is poorly understood and is represented by only two alkyl derivatives and theoretical calculations of the energy characteristics of nitro derivatives. The article presents the results of a study of the nitration of 3,7,10-trioxo-2,4,6,8,9,11-hexaaza[3.3.3]propellane (THAP) with concentrated nitric acid. It was found that in the process of nitration, there are two competing reactions - lactam-lactam rearrangement and nitration. It was shown that the reaction products strongly depend on the temperature of the reaction mixture. It was found that at a temperature of -40 ºС the formation of the lactimic form of THAP proceeds, whereas with a gradual increase in temperature, a mononitro derivative of propellane is first formed, and at a temperature of 40 ºС, the selective formation of 3,7,10-trioxo-2,6-dinitro-2,4,6,8,9,11-hexaaza[3.3.3]propellane in 30% yield.

PROPELLANS – PERSPECTIVE FRAME COMPOUNDS FOR THE CREATION OF HIGH-ENERGY SUBSTANCES

Гетероциклические соединения вызывают большой интерес у исследователей как потенциальные соединения в создании биологически активный веществ или веществ с высокой энергией. 3,7,10-Триоксо-2,4,6,8,9,11-гексааза[3.3.3]пропеллан (ТНАР) состоит из трех конденсированных колец, соединенных одинарной связью C1-C5 является новым, малоизученным веществом, синтезированным во втором десятилетии XXI века. Теоретические расчеты энергий нитропроизводных пропелланов с пятью или шестью атомами азота показали перспективность использования в качестве высокоэнергетических веществ. Целью работы было проведение квантово-химических расчетов теплоты образования и сгорания, а также длины пропеллановой связи нитро- и ацетилпроизводных 3,7,10-триоксо-2,4,6,8,9,11-гексааза[3.3.3]пропеллана и его восстановленного аналога 2,4,6,8,9,11-гексааза[3.3.3]пропеллана (НАР) с различным количеством заместителей. В результате исследовательской работы была выявлена следующая закономерность: последовательное введение нитрогрупп в изучаемую структуру увеличивает теплоты образования получаемых производных, тогда как для ацетильных групп тенденция противоположная. Оказалось, что гексанитропроизводное ТНАР по термодинамической стабильности сравнимо с гексанитробензолом, а восстановленный пропеллан НАР с шестью нитрогруппами сравним с CL-20. Поведение длины пропеллановой связи C1-C5 при последовательном замещении соединения ТНАР нитро- и ацетильными группами. Накопление ацетильных групп вызывает монотонное укорочение этой связи, вплоть до обычной длины C(sp3)-C(sp3). В случае нитрогрупп тенденция более сложная: сначала укорочение, а затем значительное удлинение, до 1.67 Å для шести нитрогрупп в 3,7,10-триоксо-2,4,6,8,9,11-гексанитро-2,4,6,8,9,11-гексааза[3.3.3]пропеллане. Гексаазапропеллан (НАР), несмотря на нежесткую структуру, имеет 22 стабильных конформера, тогда как у ТНАР их 2, и более короткие связи, что вероятно в дальнейшем позволит синтезировать его гексанитро производное. Heterocyclic compounds are of great interest to researchers as potential compounds in the creation of biologically active substances or substances with high energy. 3,7,10-Trioxo-2,4,6,8,9,11-hexaaza[3.3.3]propellane (THAP) consists of three condensed rings connected by a single C1-C5 bond, is a new, poorly studied substance synthesized in the second decade of the 21st century. Theoretical calculations of the energies of nitro-derivatives of propellanes with five or six nitrogen atoms have shown that they are promising for use as high-energy substances. The aim of the work was to carry out quantum-chemical calculations of the heats of formation and combustion, as well as the length of the propellane bond of nitro- and acetyl derivatives of 3,7,10-trioxo-2,4,6,8,9,11-hexaaza[3.3.3]propellane, as well as its reduced analogue 2,4,6,8,9,11-hexaaza[3.3.3]propellane (HAP) with a different number of substitutes. As a result of the research work, the following regularity was revealed: the successive introduction of nitro groups into the structure under study increases the heats of formation of the resulting derivatives, while the trend is opposite for acetyl groups. It turned out that the hexanitro derivative of THAP is comparable in thermodynamic stability to hexanitrobenzene, and the reduced propellane (HAP) with six nitro groups is comparable to CL-20. Behavior of the C1-C5 propellane bond length upon successive substitution of THAP compound with nitro- and acetyl groups. The accumulation of acetyl groups causes a monotonic shortening of this bond, up to the usual length of C(sp3)-C(sp3). In the case of nitro groups, the trend is more complex: first, shortening and then significant lengthening, up to 1.67 Å for six nitro groups in 3,7,10-trioxo-2,4,6,8,9,11-hexanitro-2,4,6, 8,9,11-hexaaza[3.3.3]propellane. Hexaazapropellane (HAP), despite its non-rigid structure, has 22 stable conformers, whereas THAP has two, and shorter bonds, which is likely to make it possible to synthesize its hexanitro derivative in the future.

Synthesis and antiprotozoal activity of pyridine thioaryl ethers

By reaction of pyridine nitro derivatives containing a mobile halogen atom with thiols of the benzene series, twelve thioaryl ethers of nitropyridine were obtained. However, 2-chloro-3-nitropyridine and 2-chloro-5-nitropyridine were used as reactive pyridine compounds. The reaction was carried out in dimethylformamide (DMFA) or dimethyl sulfoxide (DMSO) in the presence of bases: sodium ethylate, potash, sodium hydride. Generally, the yields exceeded 90%. The sulfur containing derivatives of aromatic series were 2-mercaptobenzoic acid (compound 1 of Table 1), methyl ester of 2-mercaptobenzoic acid (compounds 2 and 3 of Table 1), compound 3 being obtained by reduction of nitro group of compound 2. Also the amides of 2-mercaptobenzoic acid were used: 3-dimethylaminopropylamide of 2-mercaptobenzoic acid (compound 4 of Table 1), and also the reduction product of compound 4 to 3-aminopyridine derivative (compound 5 of Table 1) and morfolide of 2-mercaptobenzoic acid (compound 6 of Table 1). To make the water-soluble a sodium salt of 2-mercaptobenzoic acid was obtained (compound 7 of Table 1). A number of compounds with the pyridine ring nitrogroup reduced to amine (compounds 8, 10 of Table 1), as well as a number of derivatives containing both free (compounds 9, 10 of Table 1) and acylated amino group (compound 11 of Table 1) were also obtained. We also prepared compound 12 representing a product of interaction of 2-chloro-3-nitropyridine with 2-mercapto-3-acetylpyridine. We should note that the best nitrogroup reductant for the synthesis of compounds 3, 5, 7, and 10 is powdered iron in alcohol medium containing both inorganic and organic acids (hydrochloric or acetic acid). The application of other reducing agents (sodium sulfide and ammonium sulfide) led to strong resinification of the reaction mixture. The compounds were recrystallized from organic solvents (ethyl acetate, benzene, ethanol) for purification. Significant antiprotozoic activity was found in 7 of 12 compounds (58%), with 3-nitro-2-chloropyridine being the most active (7.8 and 3.9 ?g/ml). To enhance the activity, the synthesis of compounds with an amino group in the benzene ring as well as the introduction of both donor and acceptor substituents into the benzene ring is recommended.

Computational evidence for nitro derivatives of quinoline and quinoline N-oxide as low-cost alternative for the treatment of SARS-CoV-2 infection

A new and more aggressive strain of coronavirus, known as SARS-CoV-2, which is highly contagious, has rapidly spread across the planet within a short period of time. Due to its high transmission rate and the significant time–space between infection and manifestation of symptoms, the WHO recently declared this a pandemic. Because of the exponentially growing number of new cases of both infections and deaths, development of new therapeutic options to help fight this pandemic is urgently needed. The target molecules of this study were the nitro derivatives of quinoline and quinoline N-oxide. Computational design at the DFT level, docking studies, and molecular dynamics methods as a well-reasoned strategy will aid in elucidating the fundamental physicochemical properties and molecular functions of a diversity of compounds, directly accelerating the process of discovering new drugs. In this study, we discovered isomers based on the nitro derivatives of quinoline and quinoline N-oxide, which are biologically active compounds and may be low-cost alternatives for the treatment of infections induced by SARS-CoV-2.

Protolytic Equilibria in Organized Solutions: Ionization and Tautomerism of Fluorescein Dyes and Related Indicators in Cetyltrimethylammonium Chloride Micellar Solutions at High Ionic Strength of the Bulk Phase

Ionic equilibrium of 22 hydroxyxanthenes, including halogen and nitro derivatives of fluorescein, and their thio- and aza analogues, were studied spectrophotometrically in micellar solutions of cetyltrimethylammonium chloride at ionic strength of the bulk phase 4.0 M KCl. This micellar pseudophase is characterized by the electrostatic surface potential of +(15–16) mV and the ETN value of 0.623. In the case of dyes bearing the COOH group, colorless lactone is the predominant tautomer of the molecular form H2R. A new classification of fluoresceins is developed. The dyes were divided into four groups based on the nature of tautomerism of the anions. In the case of the fluorescein type, the monoanions HR− exist predominantly as “carboxylate” tautomers, with ionized carboxylic and non–ionized hydroxylic group. For the dyes of the eosin type, the situation is opposite, while for the intervening type of compounds, the concentrations of the two tautomers are comparable. Dyes capable of forming lactone anions HR− were classified as the fourth type. For some of them, even the dianion R2− exists as a lactone. The relationship between the stepwise ionization constants, Ka1/Ka2, varies from 1.3 to 1.07 × 105 and is determined by the state of tautomeric equilibrium of molecules and ions.