S. N. Adamovich

Tris(2-hydroxyethyl)ammonium salts: 2,8,9-Trihydroprotatranes

New method of synthesis of tris(2-hydroxyethyl)ammonium salts, 2,8,9-trihydroprotatranes X-[HN(CH2CH2OH)3]+, based on the reaction of tris(2-hydroxyethyl)amine (triethanolamine) with ammonium salts NH4X (X = F, Cl, Br, I, NO3, ClO4) was developed. 1H, 13C, 15N NMR and IR spectra of these protatranes were investigated, as well as those of their analogs with X = RCH2COO (R = H; 2-MeC6H4O; 2-Me-4ClC6H3O; 2-MeC6H4S; 4-ClC6H4S; 4-ClC6H4SO2; 3-IndS; 3-(PhCH2-IndS) prepared from the corresponding acids RCH2COOH and triethanolamine. The parameters of IR and NMR spectra of the studied protatranes were governed by the nature of substituent X, which also determined the character of the intra and intermolecular hydrogen bonds NH⋯O and OH⋯O in the protatrane framework.

Pharmacologically active salts and ionic liquids based on 2-hydroxyethylamines, arylchalcogenylacetic acids, and essential metals

The review summarizes the data on the synthesis, physicochemical properties, structure, and pharmacological activity elucidation of salts and ionic liquids synthesized based on 2-hydroxyethylamines, aryl chalcogenylacetic acids, and essential metals. The practical application prospects of these novel compounds in medicine and biotechnology are discussed.

Reaction of pharmacological active tris-(2-hydroxyethyl)ammonium 4-chlorophenylsulfanylacetate with ZnCl2 or NiCl2: first conversion of a protic ionic liquid into metallated ionic liquid

The reaction of pharmacological active protic ionic liquid tris-(2-hydroxyethyl)ammonium 4-chlorophenylsulfanylacetate H+N(CH2CH2OH)3 ∙ (-OOCCH2SC6H4Cl-4) (1) with zinc or nickel chloride in a ratio of 2:1 affords stable at room temperature powder-like adducts [H+N(CH2CH2OH)3]2 ∙ [M(OOCCH2SC6H4Cl-4)2Cl2]2-, M = Zn (2), Ni (3). By recrystallization from aqueous alcohol compound 2 unexpectedly gives Zn(OOCCH2SC6H4Cl-4)2 ∙ 2H2O (4). Unlike 2, compound 3 gives crystals [N(CH2CH2OH)3]2Ni2+ · [-OOCCH2SC6H4Cl-4]2 (5), which have a structure of metallated ionic liquid. The structure of 5 has been proved by X-ray diffraction analysis. It is the first example of the conversion of a protic ionic liquid into potentially biological active metallated ionic liquid (1 → 3 → 5).

NMR spectra of metallated alkanolammonium ionic liquids

According to the 1Н, 13С, and 15N NMR spectral data, metallated alkanolammonium ionic liquids exist as equilibrium of mono-, bi-, and tricyclic structures under the biomimetic conditions (Н2О, 25 °C). The equilibrium shift depends on the metal nature and affects the change of all parameters in the NMR spectra.

Synthesis and crystal structure of 1,4,10,13-tetraoxa-7,16-diazoniumcyclo-octadecane bis(4-chloro-2-methyl-phenoxyacetate)

The title compound was prepared by the reaction of 1,4,10,13-tetraoxa-7,16-diazacyclo-octadecane with 4-chloro-2-methyl-phenoxyacetic acid in a ratio of 1:2. The structure has been proved by the data of elemental analysis, IR spectroscopy, NMR (1H, 13C) technique and by X-ray diffraction analysis. Intermolecular hydrogen bonds between the azonium protons and oxygen atoms of the carboxylate groups were found. Immunoactive properties of the title compound have been screened. The compound has the ability to suppress spontaneous and Con A-stimulated cell proliferation in vitro and therefore can be considered as immunodepressant.

Synthesis and structure of complexes of p-chlorophenylsulfanylacetic acid triethanolammonium salts with metal chlorides

According to the data of the 15N NMR, IR spectroscopy, and quantum-chemical calculations the products of interaction of chlorides of biogenic metals MCl2 (M = Zn, Ni, Ca) with triethanolammonium salts of acetic and p-chlorophenylsulfanylacetic acids are complexes formed by metal di(p-chlorophenylsulfanylacetates) with protonated triethanolamine via the coordination bonds M…OH.

Indole-3-ylsulfonyl acetate tris-(2-hydroxyethyl)-ammonium is an effective antioxidant and cell membranes stabilizer

390 The problem of leading Russian medications of the next generation for patients suffering from autoim mune diseases and secondary immunodeficiency (including that caused by viral/retroviral infection) and patients immunocompromised after X ray and chemotherapy, oncological diseases, injuries, severe burns, long term chronic illnesses, etc. is of current interest. Previously, we showed that [1–5] indole 3 ylsulfo nyl acetate tris (2 hydroxyethyl) ammonium 3 Ind S CH2COO NH(CH2CH2OH)3 or indacetamine (INA) has high immune and erythropoiesis stimulat ing activities. In an in vitro culture, the substance dose dependently inhibits spontaneous and mitogen stimulated splenocyte proliferation by suppressing stimulated production of proinflammatory cytokines (IL 1β, TNFα). In intact animals in vivo, INA signif icantly stimulates primary and secondary humoral immune responses and macrophage phagocytic activ ity, suppresses delayed hyperresponsiveness, and has significant effects on marrow hematopoietic progeni tors of erythropoiesis. The erythropoiesis modulating properties are expressed in hematocrit and hemato globulin normalization, elimination of reticulocytosis from peripheral blood, and effective impact on early steps of marrow erythroid progenitor’s differentiation. INA has a noticeable influence on the functional properties of hematopoietic stem cells, stimulates the growth of granuloid, and inhibits the growth of eryth roid colonies. We studied the antiaggregant, membrane protec tive, and antioxidant effects of INA on erythrocytes and platelets in vivo in order to explore the spectrum of its biological action. Many critical body states (stress; hypertension; allergic, wound, and toxic infection shock; and car diovascular diseases) have a disintegrative effect on erythrocytes. In this case, the reduction in erythrocyte membrane charge together with its electrophoretic mobility occurs, which leads to cell aggregation. For studying the INA effect on erythrocytes, it was added to physiological saline washing incubated erythrocytes during 15 min at 37°С. About the same amount of physiological saline was added to control samples. The cataphoretic mobility of erythrocytes was increased by 9–20% during incubation with INA at concentrations of 10–4 to 10–2 M. INA at concentrations of 10–10 to 10–2 M increased the erythrocyte membrane resistance to extreme chemical and mechanical factors (HCl, saponins, bacterial endotoxin, ultrasound, and γ radiation). At concentrations of 10–8 to 10–4 M, the protective effect under γ irradiation was 19–49%; against saponins, 18–39%. During investigation of erythrocytes postra diational hemolysis, INA showed a high protective effect at exposure doses of γ irradiation by 60Co from 50 to 500 krad. After preliminary incubation of a 5% rabbit erythrocyte suspension with INA at 10–4 to 10–2 M during 30 min before 500 krad irradiation, erythrocyte hemolysis was about 0.7–18% (if the erythrocyte hemolysis in the control group was taken to be 100%). The INA protective effect against endotoxin induced hemolysis was studied during incubation of rabbit erythrocyte suspension with INA at concentra tions of 10– 6 to 10–4 M during 15 min at 37°С with subsequent adding of 1 mg/ml endotoxin. After eryth rocyte membrane damage, hematoglobulin is released from the cell. Therefore, the level of cell destruction was estimated by the amount of released free hemato globulin. At concentrations of 10–6 to 10–5 M, INA decreased the free hematoglobulin release from cells for 60 min by 36–49%; at a concentration of 10–4 M INA decreased its release for 180 min by 39–60%. The INA effect on erythrocyte aggregation induced by a mixture of γ globulin and fibrinogen, as well as by alcian blue, has been analyzed. INA at concentrations of 10–4 to 10–3 M inhibited alcian dependent aggrega tion by 25–78%; at concentrations of 10–3 to 10–2 M INA inhibited erythrocyte aggregation under the influence of γ globulin–fibrinogen mixture by 19 ⎯ 60%. Considering a significant role of platelets in hemo stasis and disseminated intravascular clotting, the INA Indole 3 ylsulfonyl Acetate Tris (2 Hydroxyethyl) Ammonium Is an Effective Antioxidant and Cell Membranes Stabilizer

Synthesis and pharmacological activity of tris-(2-hydroxyethyl)ammonium 4-chlorophenylsulfonylacetate (sulfacetamine)

Methods for the synthesis of 4-chlorophenylsulfonylacetic acid and its tris-(2-hydroxyethyl)ammonium salt (sulfacetamine) were developed. Results of in vitro and in vivo experiments showed that sulfacetamine possessed high antithrombotic, membrane-stabilizing, antioxidant, hypocholesterolemic, and adaptogenic activity with low toxicity to animals.

New quaternary ammonium salts and metal complexes of organylheteroacetic acids with diaza-18-crown-6 ether

Quaternary ammonium salts 2(RCH2COO)−·(2H·DACE)+ were synthesized in up to 98% yield by the reaction of biologically active organylheteroacetic acids (OHA) RCH2COOH with diaza-18-crown-6 ether (DACE).

Complex compounds of biogenic metals, aroxyacetic acids, and triethanolamine

A series of previously unknown promising biologically active compounds, complexes of biogenic metal salts, aroxyacetic acid salts, and triethanolamine, were prepared. The structure and acid-base properties of these compounds were studied by NMR and IR spectroscopy and by potentiometric titration.