Tertiary Nitrogen Atom Research Articles

PROTIC POLYMERIC IONIC LIQUID OF A BLOCK OLIGOMERIC STRUCTURE WITH IONIC BONDS IN THE MAIN CHAIN

A method for the synthesis of protic polymeric ionic liquid (PIL) of a block oligomeric structure with ionic bonds in the main chain, which turns into a liquid state at temperatures below 50 °C, was developed. Ionic bonding was used to form a polymer chain. It was formed as a result of neutralization reaction between oligomers of telechelic structure with terminal acidic and basic groups. A new linear oligomer containing basic tertiary nitrogen atoms at the ends of the oligoether chain (PEO-2NEt2) was obtained by reaction of α,ω-diglycidyl ether of polyethylene glycol MW 1000 with N,N-diethylamine. A linear oligomer with terminal sulfonic acid groups (PEO-2SO3H), which is a product of the interaction of polyethylene glycol (MW 1000) with the cyclic anhydride of 2-sulfobenzoic acid, was used as an acidic linear oligomer. The synthesis of PIL [PEO-2H-2NEt2]2+ [PEO-2SO3]2- was carried out by neutralization of basic oligomer PEO-2NEt2 with the acidic oligomer PEO-2SO3H in their molar ratio of 1:1. The structure of the obtained compound was characterized by the methods of FTIR and 1H NMR spectroscopy. According to the DSC data, the synthesized PIL contains an amorphous phase with a glass transition temperature of -49.7 °С and a crystalline phase with a melting temperature of 34.5 °С. The decomposition onset temperature corresponding to 5% weight loss is 271 °C according to the TGA. The ionic conductivity of PIL studied by dielectric relaxation spectroscopy under anhydrous conditions in the range from 40 °C to 100 °C increases with increase in temperature and reaches 2.7·10-4 S/cm. The resulting compound is promising as a proton-conducting medium for various electrochemical devices.

Fatty acid amides of plant origin in elastomeric compositions

One of the strategic directions of chemical technology eco-modernization is the use of renewable natural raw materials to create ingredients for elastomeric composites. The use of fatty acids amides of sunflower oil, such as monoethanolamide and diethanolamide of sunflower oil fatty acids, and oleic acid amide, has been proposed for the rubber industry; their main characteristics have been determined. The effectiveness of the action of fatty acid amides in sulfur vulcanization system has been studied in unfilled and filled elastomeric composites of a model type based on butadiene--methylstyrene rubber with the presence of the investigated substances at a dosage of 1.5 phr per 100.0 phr of the rubber base. Using the rheometry method, it has been shown that the investigated fatty acid amides significantly activate and deepen the degree of sulfur vulcanization, and their activity in the composition of accelerated sulfur vulcanization activators depends on the structure. Fatty acid diethanolamide with a tertiary nitrogen atom exhibited the maximum activity. A positive effect of fatty acid amides on the gain coefficient, complex dynamic modulus, and mechanical loss tangent of rubber has been established.

Design of new zwitterionic microparticles with intrinsic antibacterial activity

AbstractThe crosslinked porous microparticles based on glycidyl methacrylate, N‐vinylimidazole, and triethylene glycol dimethacrylate (molar ratio between monomers 40:30:30) obtained in the presence of three porogenic agents (toluene, n‐butyl acetate, and toluene:n‐butyl acetate mixture, 1:1, v/v) are used as precursors in the polymer analogous reactions with some betainizing agents (sodium monochloroacetate, acrylic acid, methacrylic acid and 1,3–propane sultone) in order to introduce the carboxybetaine/sulfobetaine groups to the tertiary nitrogen atom from the imidazole ring. ATR–FTIR spectroscopy is used to highlight the presence of carboxybetaine/sulfobetaine groups on the structure of the microparticles, but also to calculate the degree of betainization (55.91%–90.2%) The zwitterionic microparticles are characterized by scanning electron and atomic force microscopies, equilibrium swelling ratio as a function of pH values, swelling kinetics, ion exchange capacities and particle size distribution. Also, the parameters of porous structure (pore diameter, pore volume, porosity, and specific surface area) are determined by mercury porosimetry. The antibacterial properties of Gram‐positive (Enterococcus faecalis and Staphylococcus aureus) and Gram‐negative (Escherichia coli and Klebsiella pneumoniae) bacteria are evaluated. It is found that the zwitterionic structures containing a shorter length alkyl chain between ionic groups exhibit excellent antibacterial activity of about 80%–92%.

Sorption Extraction of Gallium from Alumina-Alkaline Solutions

AbstractThe possibility of sorption concentration of gallium from alumina-alkaline solutions resulting by leaching of recycled soda with sludge water during alumina production—which are middlings of alumina production—has been studied. During bauxite processing, soda is accumulated in recycled alkali solutions, extracted by evaporation and used in sintering. The sludge water is formed during storage of wastes pumped in the form of slurry to the settling tank and can be used in production as wash water. Sorption processes with application of ion exchange resins with high capacity and selectivity, presented in the world market in a large assortment, seem to be a promising direction of gallium concentration from alumina-alkaline solutions. On the basis of the analysis carried out, anion exchangers AN-31 and D-403 OH form were selected for sorption concentration of gallium from alumina-alkaline solutions. A comparative analysis of the sorption properties showed that the D-403 anion exchange resin exhibited better selectivity and a higher dynamic exchange capacity for gallium. The high capacity for gallium absorption with the D-403 anion exchanger resulted from its greater basicity, since the oxyhydryl groups at the β-, γ- and δ-positions in the resin matrix exert a greater negative inductive effect on the tertiary nitrogen atom, which has a lone electron pair, compared to the oxyhydryl and hydroxy groups in the β- and γ-positions relative to the secondary nitrogen atom of the anion exchange resin AN- 31. Due to the unshared electron pair of the nitrogen atom, an additional covalent effect arose, causing stronger chemical bonding between the gallium ions and the D-403 anion exchange matrix. Studies were carried out to determine the optimal conditions for the desorption of gallium with a 2 N sodium hydroxide solution. The gallium content in the alkaline eluates was suitable for electrolytic production of metallic gallium.

Complexes of N-Chloroquinuclidinium with Chloride: Strong Halogen Bonding via Chlorine Atoms

Crystallization of N-chlorosaccharin with quinuclidine (QN) produced QN-Cl+ cations showing a covalent bond between chlorine and a tertiary nitrogen atom. Strong (supramolecular) halogen bonds between the QN-Cl+ and Cl- anions...

Intramolecular Enhancement of a Zirconium-Based Metal-Organic Framework for Coordination-Induced Electrochemiluminescence Bleomycin Analysis.

It is significantly vital to develop a convenient assay method in clinical treatment due to an atypically low abundance (∼5 μM) of bleomycin (BLM) used in clinics. Herein, an electrochemiluminescence (ECL) biosensor using a zirconium-based metal-organic frameworks (Zr-MOFs) as an intramolecular coordination-induced electrochemiluminescence (CIECL) emitter was proposed for sensitive detection of BLM. Zr-MOFs were synthesized using Zr(IV) as metal ions and 4,4',4″-nitrilotribenzoic acid (H3NTB) as ligands for the first time. The H3NTB ligand not only acts as coordination units bonding with Zr(IV) but functions as a coreactant to enhance ECL efficiency rooted in its tertiary nitrogen atoms. Specifically, a long guanine-rich (G-rich) single-stranded DNA (ssDNA) was released by the target-BLM-controlled DNA machine that could perform π-π stacking with another G-quadruplex, ssDNA-rhodamine B (S-RB), by shearing DNA's fixed sites 5'-GC-3' and the auxiliary role of exonuclease III (Exo III). Finally, due to the quenching effect of rhodamine B, a negative correlation trend was obtained between ECL intensity and BLM concentration in the range from 5.0 nM to 50 μM and the limit of detection was 0.50 nM. We believe that it is a promising approach to guide the preparation of CIECL-based functional materials and establishment of analytical methods.

Extraction of Rh(III) from hydrochloric acid by protonated NTAamide(C6) and analogous compounds and understanding of extraction equilibria by using UV spectroscopy and DFT calculations.

Extraction of Rh from hydrochloric acid is conducted using NTAamide(C6) (N,N,N´,N´,N´´,N´´-hexahexyl-nitrilotriacetamide) and other related compounds. We use the ion-pair extraction of anionic species of Rh-chloride and protonated extractant. Rh ions exist as Rh(Cl)n(H2O)6-n (n ≤ 5) and the tertiary nitrogen atom in an extractant are protonated to produce a quaternary amine in acidic condition. The D(Rh) values are changeable because the Rh-Cl-H2O complex forms from + 3 to - 2 valency. Rh-chloride ion with a peak of spectrum at 504nm can be extracted effectively, where RhCl4(H2O)- and RhCl5(H2O)2- exist from Density functional theory calculation and UV spectrum. The maximum distribution ratio (D) of Rh(III) is 16, and 85mM Rh can be extracted from 1M HCl dissolving 96mM, due to less third phase formation. Approximate 80% of Rh can be stripped by the water-soluble reagents having the activities of neutralization and solvation. The figure for the Graphical Index saved in the JPEG, PNG or TIFF format at 300 dpi should be pasted with the size adjusted to the frame below (5 cm long and 8 cm wide).

Divergent Asymmetric Total Synthesis of (-)-Voacafricines A and B.

A divergent asymmetric total synthesis of voacafricines A and B, hexacyclic monoterpene indole alkaloids, has been accomplished featuring the following key steps: a) a catalyst-controlled asymmetric Pictet-Spengler reaction of 6-methoxytryptamine with a chiral α-ketoester affording a 1,1-disubstituted tetrahydro-β-carboline in excellent yield and diastereoselectivity; b) oxidative cleavage of a 3,5-disubstituted cyclopentene furnishing a dialdehyde intermediate, which was effectively differentiated through spontaneous cyclization with the neighboring hydroxy and secondary amine functions; c) intramolecular nucleophilic addition of a tertiary amino nitrogen atom to the in situ generated oxonium species generating stereoselectively an unprecedented 8-alkyl octahydro-2H-5,8-methanofuro[2,3-b]azepin-8-ium motif bearing five contiguous stereocenters. The synthesis confirmed the absolute configuration of these two natural products.

Divergent Asymmetric Total Synthesis of (−)‐Voacafricines A and B

AbstractA divergent asymmetric total synthesis of voacafricines A and B, hexacyclic monoterpene indole alkaloids, has been accomplished featuring the following key steps: a) a catalyst‐controlled asymmetric Pictet–Spengler reaction of 6‐methoxytryptamine with a chiral α‐ketoester affording a 1,1‐disubstituted tetrahydro‐β‐carboline in excellent yield and diastereoselectivity; b) oxidative cleavage of a 3,5‐disubstituted cyclopentene furnishing a dialdehyde intermediate, which was effectively differentiated through spontaneous cyclization with the neighboring hydroxy and secondary amine functions; c) intramolecular nucleophilic addition of a tertiary amino nitrogen atom to the in situ generated oxonium species generating stereoselectively an unprecedented 8‐alkyl octahydro‐2H‐5,8‐methanofuro[2,3‐b]azepin‐8‐ium motif bearing five contiguous stereocenters. The synthesis confirmed the absolute configuration of these two natural products.

Piperazine ring toxicity in three novel anti-breast cancer drugs: an in silico and in vitro metabolic bioactivation approach using olaparib as a case study.

The metabolic activation of small-molecule drugs into electrophilic reactive metabolites is widely recognized as an indicator of idiosyncratic adverse drug reactions (IADRs). Three novel anti-breast cancer drugs containing piperazine rings, ribociclib (Kisqali®, RCB), abemaciclib (Verzenio®, ABC), and olaparib (Lynparza®, OLP), were selected to study the effect of different chemical environment on the piperazine ring activation using in silico and in vitro metabolic experiments. ABC and RCB were previously studied and we noticed the piperazine ring in ABC could be strongly bioactivated generating more reactive intermediates than piperazine ring in RCB. OLP was further used as a case study to show the power of in silico software to predict the piperazine ring activation that was approved using in vitro experiments. Initially, predictions of susceptible sites in the metabolism and reactivity pathways were performed using the StarDrop P450 model and XenoSite reactivity tool, respectively. Later, in vitro OLP metabolites were characterized based on rat liver microsomes (RLMs) using KCN (trapping agent) using LC-MS/MS. The main goal of the current study was to answer the question of whether the presence of a piperazine ring in the chemical structure should be always considered a structural alert. Piperazine ring in RBC and ABC was bioactivated through a metabolic sequence that involves the hydroxylation of α-carbon to the tertiary nitrogen atoms of the piperazine ring. In the case of OLP, no cyano adduct was formed due to the presence of two carbonyl groups attached to the two nitrogen atoms of the piperazine ring (neutral amide groups). From the results, piperazine ring in certain cases should not be considered as a structural alert as in the case of OLP due to the presence of two electron withdrawing group that stops the proposed toxicity. Also blocking the bioactive center (α-carbon) using steric hindrances such as methyl group, also the isosteric replacement of α-carbon hydrogen with fluoro atom can aid in reducing the toxic side effects of ABC and RCB. These experiments were done in vitro through incubation with RLMs in the presence of KCN. Also, the results are supported by data generated from in silico software. In the future, drug discovery studies using this concept could be undertaken, allowing for the development of new drugs with reasonable safety profiles. Overall, in vitro RLMs incubations and in silico experiments were able to predict successfully that the piperazine ring should not always be considered a structural alert.

SYNTHESIS AND BIOLOGICAL ACTIVITY OF 3d-­METAL COMPLEXES WITH BIS(PHOSPHONOMETHYL)AMINOSUNRIC ACID

New complexes of 3d-metals (Co2+, Ni2+, Zn2+) with bis(phosphonomethyl)aminosuccinic acid (H6BPMAS) have been synthesized. The complexes were studied in aqueous solutions at ratios M2+:H6BPMAS = 1:1 in a wide pH range (1÷10). Regardless of the nature of the metal, the formation of complexes of the general composition [M(HnBPMAS)(OH)m] (n= 4÷0, m=1÷0) is shown. The stability constants of the formed differently protonated complexes are calculated and diagrams of their distribution are plotted. It is shown that the process of complexation takes place most completely in the region of pH>4. For all bis(phosphonomethyl)aminosuccinates of 3d metals, the dominance of the complex with one form of the ligand occurs in approximately the same pH ranges. A close order of change in the values of lgKst. complexes testifies to the same type of structure of their internal coordination sphere.
 Solid complexes of the composition Na4[MBPMAS]⋅4H2O were synthesized. Their composition, structure, and thermal characteristics were determined by the set of me­thods such as diffuse reflectance spectroscopy, IR spectroscopy, DTA and non-quantitative mass spectrometry. It is proved that the complexes have the structure of a distorted octahedron, in which the 3-d metal ions are bound to the oxygen atoms of the carboxyl and phosphonic groups and the tertiary nitrogen atom of the ligand. At the same time, two 5-membered (aminomethylenephosphonic and glycine) and one 6-membered (β-alanine) metallocycles are formed in bis(phosphonomethyl)aminosuccinates.
 The biological activity of H6BPMAS and its complexes with Ni(II) and Co(II) against non-pathogenic bacterial species of microorganisms Pseudomonas fluorescens and Pseudomonas aureofaciens was studied. The study of the activity of substances was carried out in a liquid sterile Hiss medium. The maxi­mum stimulating effect on the growth of bacterial cultures for the studied compounds was recorded at a concentration of 1 µM in 24 hours after the start of cultivation of mic­ro­organisms. The highest growth of microorganisms was recorded for metal complexes (50% Na4[CoBPMAS]·4H2O and 35% Na4[NiBPMAS]·4H2O). The maximum stimulating effect on the growth of bacterial cultures is shown by the Co(II) complex, which is able to initiate the synthesis of one of the most important growth hormones - heteroauxin.

Structure-property relationship of thermoplastic polyurethane cationomers carrying quaternary ammonium groups

This study reports the synthesis and characterization of thermoplastic polyurethane cationomers and its dispersion in water. The cationomeric polyurethanes were synthesized by reacting polyol, isocyanate, NMDEA and dihydrazide followed by ionization of the tertiary nitrogen atoms of NMDEA moieties with alkyl bromides. Variations were done with respect to chain length of cationizing agent, isocyanate type and chain extender and all the compositions were compression molded into sheets. The ionization of the tertiary nitrogen atom in the PU backbone was confirmed by NMR and GPC results showed that the compositions with increasing alkyl chain length showed increasing molecular weight. The cationomers showed a Tg corresponding to the soft segments around −60°C and hard segment in the 5–15°C range. PU cationomers exhibited enhanced tensile strength and elongation but lower storage modulus compared to the unionized samples. Water contact angle measurements indicated that the contact angle increased with increase in the length of the pendant alkyl groups and the composition carrying sebacic dihydrazide as chain extender in the place of adipic dihydrazide exhibited the highest contact angle (112°). The polymers had antifouling properties since there was no growth of microorganisms over the films and solution of polymer in DMSO (2 mg/ml) exhibited antimicrobial properties against E. coli and S. aureus with a growth inhibition of 10 to 29% and 9 to28% respectively. Among all the cationomers, the one carrying C8 alkyl chain as pendant group with the right balance of hydrophilicity-hydrophobicity could be dispersed in water yielding cationomeric waterborne PU dispersion. This dispersion was very stable and suitable for coating hydrophobic surfaces like polypropylene.

Dinuclear vs. Mononuclear Copper(II) Coordination Species of Tylosin and Tilmicosin in Non-Aqueous Solutions.

The veterinary 16-membered macrolide antibiotics tylosin (HTyl, 1a) and tilmicosin (HTilm, 1b) react with copper(II) ions in acetone at metal-to-ligand molar ratio of 1:2 to form blue (2) or green (3) metal(II) coordination species, containing nitrate or chloride anions, respectively. The complexation processes and the properties of 2–3 were studied by an assortment of physicochemical techniques (UV-Vis, EPR, NMR, FTIR, elemental analysis). The experimental data revealed that the main portion of copper(II) ions are bound as neutral EPR-silent dinuclear complexes of composition [Cu2(µ-NO3)2L2] (2a–b) and [Cu2(µ-Cl)2Cl2(HL)2] (3a–b), containing impurities of EPR-active mono-species [Cu(NO3)L] (2a’–b’) and [CuCl2(HL)] (3a’–b’). The possible structural variants of the dinuclear- and mono-complexes were modeled by the DFT method, and the computed spectroscopic parameters of the optimized constructs were compared to those measured experimentally. Using such a combined approach, the main coordination unit of the macrolides, involved in the complex formation, was defined to be their mycaminosyl substituent, which acts as a terminal ligand in a bidentate mode through the tertiary nitrogen atom and the oxygen from a deprotonated (2) or non-dissociated (3) hydroxyl group, respectively.

Borneol Ester Derivatives as Entry Inhibitors of a Wide Spectrum of SARS-CoV-2 Viruses.

In the present work we studied the antiviral activity of the home library of monoterpenoid derivatives using the pseudoviral systems of our development, which have glycoproteins of the SARS-CoV-2 virus strains Wuhan and Delta on their surface. We found that borneol derivatives with a tertiary nitrogen atom can exhibit activity at the early stages of viral replication. In order to search for potential binding sites of ligands with glycoprotein, we carried out additional biological tests to study the inhibition of the re-receptor-binding domain of protein S. For the compounds that showed activity on the pseudoviral system, a study using three strains of the infectious SARS-CoV-2 virus was carried out. As a result, two leader compounds were found that showed activity on the Wuhan, Delta, and Omicron strains. Based on the biological results, we searched for the potential binding site of the leader compounds using molecular dynamics and molecular docking methods. We suggested that the compounds can bind in conserved regions of the central helices and/or heptad repeats of glycoprotein S of SARS-CoV-2 viruses.

Synthesis, characterisation and coordination properties of 5-methyl-3-formylpyrazole 4 N-benzylthiosemicarbazone (HMPzNB) Cobalt(III), nickel(II) and copper(II) complexes with a NNS donor system

The title ligand, 5-methyl-3-formylpyrazole 4 N-benzylthiosemicarbazone (abbreviated as HMPzNB) has been synthesised and physicochemically characterised by elemental analysis, IR, PMR and mass spectrum. The ligational behaviour of the pyrazole-derived thiosemicarbazone, HMPzNB, has been examined by isolation and characterisation of its complexes with Co III , Ni II and Cu II with different counterions. Elemental analyses, magnetic and spectral features indicate [Co(MPzNB) 2 ]X (X = Cl - , Br - , NO - 3 , ClO - 4 or BF - 4 ) as the diamagnetic octahedral species with the ligand in the deprotonated thiol form, while [Ni(HMPzNB) 2 ]X 2 (X = Cl - , Br-, NO - 3 or ClO - 4 ) is proposed as octahedral complex with the ligand in the neutral thione form. However, in the neutral condition (pH ∼6) nickel(II) salt affords octahedral bis-nickel(II) complex, Ni(MPzNB) 2 , while copper(II) salt gives [Cu(MPzNB)]X (X = Cl - , Br - , NO - 3 or ClO - 4 ), with the deprotonated ligand. 5-Methyl-3-formylpyrazole 4N-benzylthiosemicarbazone possesses in its structure, the tertiary nitrogen atom ( 2 N) of the pyrazole ring, the azomethine nitrogen and the sulphur atom as potential binding sites; thus the title ligand is expected to behave as a potential NNS tridentate during complex formation with a metal ion.

P5C as an Interface of Proline Interconvertible Amino Acids and Its Role in Regulation of Cell Survival and Apoptosis.

Studies of cancer metabolism have focused on the production of energy and the interconversion of carbons between cell cycles. More recently, amino acid metabolism, especially non-essential amino acids (NEAAs), has been investigated, underlining their regulatory role. One of the important mediators in energy production and interconversion of carbons in the cell is Δ1-pyrroline-5-carboxylate (P5C)—the physiological intracellular intermediate of the interconversion of proline, ornithine, and glutamate. As a central component of these conversions, it links the tricarboxylic acid cycle (TCA), urea cycle (UC), and proline cycle (PC). P5C has a cyclic structure containing a tertiary nitrogen atom (N) and is in tautomeric equilibrium with the open-chain form of L-glutamate-γ-semialdehyde (GSAL). P5C is produced by P5C synthase (P5CS) from glutamate, and ornithine via ornithine δ-amino acid transferase (δOAT). It can also be converted to glutamate by P5C dehydrogenase (P5CDH). P5C is both a direct precursor of proline and a product of its degradation. The conversion of P5C to proline is catalyzed by P5C reductase (PYCR), while proline to P5C by proline dehydrogenase/oxidase (PRODH/POX). P5C-proline-P5C interconversion forms a functional redox couple. Their transformations are accompanied by the transfer of a reducing-oxidizing potential, that affect the NADP+/NADPH ratio and a wide variety of processes, e.g., the synthesis of phosphoribosyl pyrophosphate (PRPP), and purine ribonucleotides, which are crucial for DNA synthesis. This review focuses on the metabolism of P5C in the cell as an interconversion mediator of proline, glutamate, and ornithine and its role in the regulation of survival and death with particular emphasis on the metabolic context.

Synthesis and Aggregation of Novel Sugar-based Gemini Surfactants in Aqueous Solution

Abstract Novel sugar-based gemini surfactants with a 1,3-propan-2-ol spacer (1, 3-(N- alkyl-2-D-glucosaminyl acetyl) propan-2-ol, Glu(n)-3(OH)-Glu(n), n = 12, 14) were synthesized with D-(+)-glucono-1,5-lactone as starting material in two steps, whose structures were confirmed using proton nuclear magnetic resonance spectroscopy (1H NMR) and carbon nuclear magnetic resonance carbon spectroscopy (13C NMR). The micellization of Glu(n)-3(OH)-Glu(n) (n = 12, 14) in aqueous solution at 25.0°C was investigated by using surface tension measurement. The results show that the critical micelle concentration (CMC) of Glu(12)-3(OH)-Glu(12) is around 10–5 mol × L–1, and is one order of magnitude smaller than that of Glu(14)-3(OH)-Glu(14), indicating that the surface activity of Glu(12)-3(OH)-Glu(12) is superior to that of Glu(14)-3(OH)-Glu(14). Moreover, the aggregation behavior of Glu(12)-3(OH)-Glu(12) in aqueous solution at different pH values was investigated by surface tension, dynamic light scattering (DLS), and cryogenic transmission electron microscopic (Cryo-TEM) measurements. The results indicate that the CMC slightly increases with the decrease of the solution pH. The microstructure of Glu(12)-3(OH)-Glu(12) aggregates transitions from micelle to vesicle with the solution pH from acidic to neutral and alkaline. The microstructural transformation of Glu(12)-3(OH)-Glu(12) with the solution pH is mainly determined by the protonation of the two tertiary amine nitrogen atoms in its hydrophilic headgroups.

Nickel(II) complexes of two potentially heptadentate(N7) Tripodal Schiff-base ligands; X-ray crystal structure and theoretical studies

In absolute methanol, one equivalent of tripodal tetraamines bis(3-aminopropyl)(2-aminoethyl)amine, ppe or (3-aminopropyl)-bis(2-aminoethyl)amine, pee condenses with three equivalents of 2-pyridinecarboxaldehyde. Upon the addition of Ni(II) salt to the solutions of produced Schiff base ligands, two new Schiff-base complexes, [Ni(py3ppe)](ClO4)2, (1), and [Ni(py3pee)](ClO4)2, (2), were prepared. Both complexes 1 and 2 were characterized by X-ray crystal structure analysis, CHN elemental analysis and FT-IR spectroscopy. The data show that both complexes have a distorted trigonal antiprism geometry for Ni(II) ion, in which the tertiary nitrogen atom has been not coordinated to the central metal ion. A DFT theoretical study at bp86/def2-tzvp level of theory on a series of this type of Ni(II) complexes shows that, interestingly, the values of metal–ligand interaction energies are very similar and are about 510 ± 2 kcal mol−1.

STUDY OF THE STABILITY OF THE SUBSTANCE 3-[2-(4-PHENYL-1-PIPERAZINO)-2-OXOETHYL]QUINAZOLINE-4(3Н)-ONE UNDER STRESSFUL CONDITIONS

The aim of the research was to study the stability of a new pharmaceutical substance 3-[2-(4-phenyl-1-piperazino)-2-oxoethyl]quinazoline-4(3Н)-one under stress conditions.Materials and methods. The study was conducted in accordance with the recommendations of the ICH guidelines. The object of the study was a previously unknown derivative of quinazoline-4(3H)-one: 3-[2-(4-phenyl-1-piperazino)-2-oxoethyl] quinazoline-4(3Н)-one synthesized in Volgograd state medical university. The following laboratory equipment was used: HPLC chromatograph, HPLC-MS, centrifuge, electronic scales, pH meter, thermostat, laboratory filters. The computational experiment was conducted on a computer with an Intel Xeon E3-1230 processor using the programs ORCA 4.1. and GROMACS 2019.Results. The influence of the most unfavorable environmental factors, such as high temperature, light, oxidants, hydrolysis in acidic and alkaline environments, affect the stability of the test substance. The results of the computer-based stability prediction were confirmed by HPLC and HPLC-MS, and the degradation products of the substance under stressful conditions were determined. The conducted studies showed that the test substance is stable to UV radiation at the wavelength of 365 nm, at the elevated temperature (80°C), to the action of oxidants. But it is unstable to hydrolysis: in an alkaline medium of sodium hydroxide 1M, a break in the amide group occurs with the formation of 2-(4-oxoquinazoline-3-yl)acetic acid and 1-phenylpiperazine. And in an acidic environment, hydrochloric acid 1M is also destroyed, but it is significantly reduced, presumably due to the protonation and stabilization of tertiary nitrogen atoms in the molecule.Conclusion. The conducted research makes it possible to conclude that the test substance 3-[2-(4-phenyl-1-of piperazino)-2-oxoethyl]quinazoline-4(3Н)-one is stable to aggressive environmental factors, with the exception of hydrolysis in an alkaline environment that will be further considered in the preparation of regulatory documents for this pharmaceutical substance.

Structural and thermal analysis of some imipramine complexes

imipramine interacts with transition metals to give different molar ratios (M:L), (1:1) with Mn(II), Zn(II), Cd(II) and Hg(II) and (1:2) with Cr(III), Fe(III), Co(II), Ni(II) and Cu(II) .All were characterized by elemental analysis, IR, electronic spectra and magnetic susceptibility. IR spectra indicated that imipramine behaves as a bidentate ligand through its heterocyclic nitrogen atom and the tertiary nitrogen atom of the side chain. The geometry around the metal atoms is octahedral in all complexes except for Zn has tetrahedral structure. It was indicated by TGA and DTA analysis that the thermal decomposition of most complexes ended with the formation of metal oxides and carbon residue as a final product. For this reaction, the kinetic parameters and the orders were estimated. The decomposition course and steps were also analyzed. Consequently, decomposition mechanisms were suggested.