Актуальність питання, що розглядається в статті, полягає в доцільності адекватного порівняльного аналізу результатів доклінічного дослідження токсикометричних характеристик потенційних лікарських засобів залежно від їхньої хімічної структури зі спробою визначення фармакофора сполуки – лідера в ряду цих сполук. На етапі порівняльної експериментальної лікарської токсикометрії досліджено у форматі «структура – токсичність» низку вперше цілеспрямовано синтезованих координаційних сполук германію з різними біометалами (магнієм (Mg), манганом (Mn), кобальтом (Co), нікелем (Ni), купрумом (Cu), цинком (Zn), що розглядаються як потенційні лікувально-профілактичні засоби для фармакокорекції кисеньдефіцитних станів організму. Мета дослідження – провести комплексний порівняльний аналіз співвідношення «структура – токсичність» уперше синтезованих біометалевих дигідроксо-μ-біс(глюконато)дигерманатів(IV) 3d-металів. Дослідження виконано на статевозрілих мишах-самцях, які попередньо пройшли необхідні карантинні процедури з наступним дотриманням чинних вимог з біоетики. У токсикометричному експерименті вивчали 6 уперше синтезованих біометалевих дигідроксо-μ-біс(глюконато)дигерманатів(IV) з різними есенціальними мікроелементами (Zn, Mn, Cu, Mg, Co, Ni) за умов одноразового внутрішньоочеревинного (в/о) введення в різних дозах. Усі сполуки, що досліджуються, є водорозчинними. Ступінь токсичності координаційних сполук германію з біометалами визначали за величинами середньосмертельних доз та їхніми довірчими границями. Водночас реєстрували клінічні прояви токсичної дії, а також встановлювали клас небезпеки кожної зі сполук. Експериментально доведено різний ступінь токсичності всіх досліджених сполук. Так, зокрема встановлено, що найтоксичнішою сполукою є мідьвмісна, LD50 якої становить 25,8 (22 ÷ 30) мг/кг і відноситься до III класу небезпеки, тобто, «помірно токсичних», а найменш токсичною виявилася сполука, до складу якої входить Mg, оскільки величина LD50 складає >1580 мг/кг і є «практично нетоксичною» сполукою (V клас). Ранжування координаційних сполук германію з різними біометалами на підставі отриманих токсикометричних даних за ступенем зменшення їхньої гострої токсичності (збільшенням величини LD50) має наступний вигляд: Cu > Ni > Zn > Co > Mn > Mg. У статті розглядаються можливі механізми токсичної дії германійорганічних сполук залежно від мікроелементу, що входить до їхнього складу.

We have previously shown that Bacillus sp. IMV B-7883 exhibits both elastase and fibrinogenolytic activity. One of the approaches to enhance enzymatic activity is the use of coordination compounds capable to affect enzyme’s activity or synthesis. The purpose of this work was to study the effect of mixed-ligand complexes of Ge(IV) – Co(II) (Ni(II), Cu(II)) with 1-hydroxyethane-1,1-diphosphonic acid аnd 2,2′-bipyridine on the activity of elastase and fibrinogenase purified from Bacillus sp. IMV B-7883. Previously synthesized and characterized mixed-ligand complexes and enzymes purified from the supernatant of the bacterial culture liquid were used in the study. Elastase activity was determined colorimetrically with the use of Congo red, fibrinogenase activity was estimated by fibrinogen hydrolysis measured by absorption at 275 nm. It was shown that complexes 1 (C132H164Co4Ge6N24O68P12) and 2 (C132H148Ge6N24Ni4O60P12) inhibited activity of Bacillus sp. IMV B-7883 elastase by 54 and 71% respectively, while complex 3 (C92H128Cu4Ge6N16O63P12) enhanced it by 30%. Stimulating effect of all three complexes on fibrinogenase activity was revealed. Thus, complex 1 and 2 activated the enzyme by more than 50% and complex 1 – by 19%. The data obtained indicate a complex mechanism of the studied complexes influence on enzymatic activity depending on both their composition and structure. Keywords: 1-hydroxyethane-1‚1-diphosphonic acid, 2‚2′-bipyridine, Bacillus sp. IMV B-7883, elastase, fibrinogenase, germanium – 3d-metal, mixed-ligand complexes

In recent years, some researchers have found that although many Gram-negative and Gram-positive bacteria secrete elastase, the bacterial forms of elastase have either a low activity or harmful effects. Therefore, further research is needed in isolating and screening microorganisms that produce a high level of elastase activity. Previously we selected strain Bacillus sp. IMV B-7883, which exhibits fairly high elastase activity. To increase its activity, we chose one of the well-known approaches, in particular, the use of a number of coordination compounds capable to influence elastase activity. In this regard, the purpose of this work was to study the effect of such coordination compounds as hetero-metallic carboxylatogermanates/stannates on the elastase activity of Bacillus sp. IMV B-7883. Methods. The object of the investigation was the strain of Bacillus sp., deposited in the Ukrainian Collection of Microorganisms under the number IMV B-7883, isolated from soil. The culture was grown under conditions of submerged cultivation at 28 °С, with a mixing speed of the nutrient medium of 244 rpm for three to six days (72–144 hours). We used an enzyme purified from the supernatant of the culture liquid by precipitation with 90% ammonium sulfate, with further fractionation on neutral and charged carriers. Elastase activity was determined colorimetrically by the intensity of the color of the solution upon enzymatic hydrolysis of elastin stained with Congo red. As modifiers of enzyme activity, hetero-metallic carboxylatogermanates/stannates were used. Results. Of the 15 studied in this work coordination compounds presented by hetero-metallic carboxylatogermanates/stannates, only 1 [Ba(H2O)6][Ge2(OH)2(C6H8O7)2]·nH2O, n=2 and 3 [Ni (H2O)6][Ge2(OH)2(C6H8O7)2]·nH2O, n=4, depending on the concentration used and incubation time, increase the elastase activity by only 3–5%. All other compounds have an inhibitory effect. Conclusions. Obtained data on the inhibitory effect of hetero-metallic carboxylatogermanates/stannates on the elastase activity of Bacillus sp. IMV B-7883 provide new information which may help in solving the issue of the mechanism of interaction between enzymes and complex chemical molecules.

The intensive development of biotechnology in the last decade is largely determined by the growing requirement needs of both medicine and various industries for products of microbial synthesis, including glycosidases, in particular α-L-rhamnosidases. Their wide use to solve current biological-medical and chemical-technological problems stimulates researchers to search for compounds capable of influencing their catalytic activity. Therefore, the purpose of this work was to isolate and purify α-L-rhamnosidase from a new producer of Penicillium restrictum and to investigate multi-ligand germanium-3d-metal complexes with citric acid, phenanthroline, and bipyridine as effectors of its activity. Methods. The object of the study was α-L-rhamnosidase of P. restrictum. Its purification was carried out by gel filtration and ion exchange chromatography on TSK-gels and Sepharose 6B. The activity of α-L-rhamnosidase was determined using the Davis method with naringin as a substrate. As modifiers of enzyme activity, purposefully synthesized multiligand germanium-3d-metal complexes with citric acid, phenanthroline, and bipyridine ([Ni(bipy)3][Ge(HCit)2]·3H2O (1); [Ni(phen)3][Ge(HCit)2]·2H2O (2); [{Cu(bipy)2}2Ge(m-Cit)2]·12Н2О (3); [{Cu(phen)2}2Ge(m-Cit)2]·13H2O (4); [Zn(bipy)3][Ge(HCit)2]·2H2O (5); [Zn(phen)3][Ge(HCit)2]·3H2O (6)), were used. Results. From the supernatant of culture fluid of P. restrictum, α-L-rhamnosidase was isolated and purified 23.1 times with a yield of 0.09%. The specific activity of the enzyme was 27.8 units/mL. The enzyme was homogeneous according to gel filtration on Sepharose 6B and had a molecular mass of 50 kDa. It was established that the considered coordination compounds are able to regulate the catalytic activity of α-L-rhamnosidase of P. restrictum. All of them manifest themselves either as activators or as inert substances, no inhibition was observed. In addition, the dependence of the degree of enzyme activation by the compounds on their concentration is traced and corresponds to the following series: at a concentration of 0.01% — 1 > 6 ≈ 5 > 3 >2 ≈ 4 and at a concentration of 0.1% — 1 > 4 > 2 > 5 ≈ 6. 3. The catalytic activity is also significantly affected by the time of exposure to the compounds: at a concentration of 0.01% for 1h, the activity of the enzyme at the control level was observed for all compounds, whereas at a concentration of 0.1% for 24 h, the activity increased sharply in the presence of compounds 1 (300%), 6 (153%), and 2 (134%). The action of the others was at the control level. Conclusions. The obtained data on new complex metal compounds with an activating effect on microbial α-L-rhamnosidases. It has been established that compounds whose structural organization ensures the synergism of the action of all components are the most promising enzyme effectors in a series of coordination compounds of biologically active metals and ligands.

There were developed the novel methods for the synthesis of six mixed- metal and mixed-ligand complexes of germanium and rare earth metals (Pr, Nd, Dy, Ho, Tm, Lu) with 1-hydroxyethylidenediphosphonic acid and 2,2´-bipyridine. The compounds have been characterized using various research methods: elemental analysis, mass spectrometry, electrical conductivity, thermogravimetry, IR spectroscopy. It has proved that all complexes are crystal hydrates, belong to heterometallic mixed ligand compounds [Ln(H2O)4(bipy)2]2 [Ge(m-hedp) (m- OH)]6⸱nH2O, Ln=Pr (1); Nd (2); Dy (3); Ho (4); Tm (5); Lu (6); n = 22 (1, 2), 21 (3), 20 (4, 5), 19 (6). Their formation occurs due to the electrostatic interaction of complex cations [Ln(H2O)4(bipy)2]3+ with hexanuclear anions [Ge(m-hedp)(m- OH)]66-. According to the results of measuring the electrical conductivity of dimethylformamide solutions 1–6, it has been established that they belong to triionic electrolytes: λ (in Ohm-1∙сm2∙mol-1) for 1 = 131,3; 2 = 138,8; 3 = 145,8; 4 = 151,1; 5 = 158,3; 6 = 162,7. The cation-anionic type of complexes 1–6 has been confirmed as a result of the analysis of their mass spectrum. The analysis of the mass spectrum showed that the main decomposition direction of the complex is related to the formation of the complex cation fragment [Ln(H2O)4(bipy)2]3+, which corresponds to the most intense peak (m/z = 136, I = 55%). The thermal decomposition of compounds 1–6 includes dehydration, deaquatation, oxidative thermal destruction and the formation of final products as a mixture of Ln2O3 and GeP2O7. On the DTA curves in the interval 70–200 °C the first endothermic effect can be traced, which is accompanied by the removal of a certain number of crystallization and coordination water molecules into the gas phase. Absorption bands of the P-O bond have been detected at ~1053 and ~970 сm-1, that indicates the presence of the fully deprotonated PO32- groups in the composition of complexes. Furthermore, n(OH), ν(Ge–O), d(Ge–OH) bands characteristic for all the previously synthesized compounds with [Ge6(m-OH)6(m-hedp)6]6- anion have been detected in the IR spectra of 1–6. A set of the bands usual for the aromatic molecules n(C–C), das(CH3), ds(CH3), n(Сar=N) has been assigned with 2,2`-bipyridine in the structure of all compounds.

α-L-Rhamnosidase (α-L-rhamnoside-rhamnohydrolase EC 3.2.1.40) showing specificity for terminal α-1,2-, α-1,4- and α-1,6-linked rhamnose residues, which often present in glycoconjugates and synthetic glycosides, can be successfully used in biotechnology for the hydrolysis of rhamnopyranoside residues present in some bioflavonoids, glycoproteins, glycolipids, and other glycoconjugates. Previously, we have shown that a significant part of the coordination compounds of various metals act as effectors of the activity of α-L-rhamnosidases. The aim of this investigation was to study the effect of a number of newly synthesized coordination compounds of Ge(IV) and Ba(II), (Co(II), Ni(II), Cu(II), Zn(II) with gluconic acid on the activity of Penicillium tardum and Eupenicillium erubescens α-L-rhamnosidases. Methods. The objects of the study were Penicillium tardum and Eupenicillium erubescens α-L-rhamnosidases. α-L-Rhamnosidase activity was determined by the Davis method using naringin as a substrate. Coordination compounds Ge(IV) and Ba(II), Co(II), Ni(II), Cu(II) ,and Zn(II) with gluconic acid were used as enzyme activity modifiers. The synthesized complexes correspond to the formulas [М(H2O)6][Ge2(OH)2(C6H8O7)2]·nH2O (М = Ba(1), n=2; Co(2), n=4; Ni(3), n=4; Cu(4), n=4; Zn(5), n=3). Results. The effect of coordination compounds 1-(5) on the activity of α-L-rhamnosidase in two strains of Penicillium tardum and Eupenicillium erubescens was studied depending on the exposure time and concentration of the effector. It was shown that compound (3) at a concentration of 0.01% (1 h incubation) led to a slight (by 5%) increase in the activity of P. tardum α-L-rhamnosidase. Compound 1 at a concentration of 0.1% led to a decrease in the activity of P. tardum α-L-rhamnosidase by 29% during the first hour, and after 24 h of incubation, a decrease in the inhibitory effect to 15% was noted. Compounds 2 and (4) activated the enzyme by 9-39% at 1h exposure. At a concentration of 0.1% and exposure time of 1 h, compound 1 increased the activity of E. erubescens α-L-rhamnosidase by 80%, while at a decrease in concentration to 0.01%, the activity increased only by 29%. In general, it should be noted that in most cases, an increase in the duration of incubation up to 24 h led to a decrease in the level of activation (or inhibition) and a return to the control values of enzyme activity. Conclusions. The variety of effects of metal coordination compounds on the activity of enzymes, depending on the nature of the cation and the origin of the enzyme, has been established. The involvement of Ba(II) had the greatest activating effect on the activity of E. erubescens α-L-rhamnosidase compared to other metals.

The search for effectors capable of influencing the catalytic activity of enzymes is an important area of modern enzymology. The aim of the study was to investigate the ability of 6 coordination compounds with malatogermanate/stannate anions and 1,10-phenanthroline cations of 3d metals to modify α-L-rhamnosidase activity of Penicillium tardum, Penicillium restrictum and Eupenicillium еrubescens strains. α-L-Rhamnosidase activity was determined by the Davis method using naringin as a substrate. It was demonstrated­ that [Ni(phen)3]2[{Sn(HMal)2(Mal)}Cl]•14H2O) in 0.1% concentration had the most pronounced activating effect on α-L-rhamnosidase activity of all strains studied. Noncompetitive inhibition of α-L-rhamnosidase in E. еrubescens by [Cu(phen)3]2[{Sn(HMal)2(Mal)}Cl]•10H2O was shown. The obtained results expand the idea of glycosidases possible activators and inhibitors and indicate the perspective of their use in modern biotechnological processes. Keywords: d-metals, double coordination compounds, Eupenicillium erubescens, germanium(IV), Penicillium restrictum, Penicillium tardum, stannum(IV), α-L-rhamnosidase

In recent years, the particular interest of researchers is focused on such enzymes as α-L-rhamnosidase and α-galactosidase. These enzymes are considered useful for various applications. α-L-rhamnosidases may be applied for debittering of citrus fruit juices, due to the less bitter taste of the derhamnosylated flavonones, for rhamnose production, and for the determination of the anomeric configuration in polysaccharides, glycosides and glycolipids. These enzymes may enhance wine aroma and flavonoid bioavailability, or assist in the synthesis of pharmaceuticals. α-Galactosidase finds application in many areas. It is widely used in the food industry to improve the quality of soy products by hydrolyzing indigestible galactosides such as raffinose and stachyose, in the processing of raw materials in order to increase the yield of sugar from molasses, and for the biotransformation of human blood erythrocytes of group B (III) in universal donor erythrocytes, as well as in enzyme therapy of some congenital disorders of sphingolipid metabolism. Earlier, as a result of screening microorganisms of different taxonomic groups, we has selected active α-L-rhamnosidase and α-galactosidase producers. One way to increase their activity is using various effector compounds capable of modifying the enzyme activity. The study of the influence of various effectors is one of the priority areas of modern research in biochemistry, biocoordination chemistry, and biotechnology. Recent advantages in the area of biocoordination chemistry revealed high activating properties of double heterometallic mixed-ligand coor dination compounds with germanium(IV)/tin(IV) tartaric complex anions and 1,10-phenanthroline/2,2`-bipyridine d-metallic cations. The aim is to estimate the enzyme-effector activity of five similar tartratostannates for the α-L-rhamnosidases of Cryptococcus albidus, Eupenicillium erubescens, and α-galactosidase of Penicillium restrictum. Methods. The activity of α-Galactosidase was determined using p-nitrophenyl-α-D-galactopyranoside («Sigma», USA) as a substrate. The activity of α-L-rhamnosidase was determined using the Davis method. As modifiers of enzyme activity, [Fe(phen)3]2[Sn2(μ-Tart)2(Н2Tart)2]·2H2O (1), [Co(phen)3]2[Sn2(μ-Tart)2(Н2Tart)2]·8H2O (2), [Ni(phen)3]2[Sn2(μ-Tart)2(Н2Tart)2]·2H2O (3), [Cu(phen)3]2[Sn2(μ-Tart)2(Н2Tart)2]·2H2O (4), and [Zn(phen)3]2[Sn2(μ-Tart)2(Н2Tart)2]·6H2O (5) were used. Results. The study of the effect of complexes 1—5, which are supramolecular salts consisting of the same tartrate stannate anion (electrophilic agent) and a 1,10-phenanthroline d-metal cation (nucleophilic agent), on the Cryptococcus albidus, Eupenicillium erubescens α-L-rhamnosidases, and Penicillium restrictum α-galactosidase showed that the compounds tested had a different influence on the enzymes’ activity. The catalytic activity of α-L-rhamnosidase is significantly influenced by all complexes. The effectiveness of compounds 1—5 for P. restrictum α-galactosidase was less pronounced in comparison with C. albidus and E. erubescens α-L-rhamnosidases. It was mostly at the control level. There was observed a certain pattern in the influence of complexes on α-L-rhamnosidases of Cryptococcus albidus and Eupenicillium erubescens. Compounds 2 and 5 turned out to be the most effective and activated enzymes by 500-900%. Conclusions. Compound 2 [Co(phen)3]2[Sn2(μ-Tart)2(Н2Tart)2]·8H2O is promising for further use as an effector of the α-L-rhamnosidase activity.

Objective. To study the antimicrobial activity of double coordination compounds with 1,10-phenanthroline/2,2ʹ-bipyridine complexes of Fe(II)/Co(II)/Ni(II)/Cu(II) as cations and diff erent tartratogermanate(IV) anions, reveal the main factors of their effi ciency and establish relations between their composition, structure features, and biological properties. Methods. The developed synthesis method allowed us to obtain three diff erent tartratogermanate anions, which exist together in the solution and can be selectively recognized by the certain type of 1,10-phenanthroline/2,2ʹ-bipyridine cation. Th e antimicrobial activity of the compound was investigated by a rapid twofold dilution method in a standard liquid nutrient medium (Hottinger digestion) to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). Results. Th e complex nature of studied compounds, synergism of their biologically active structural units, and the presence of diff erent types of intermolecular bonds result in the high antimicrobial activity against a wide range of microorganisms such as gram-positive Planococcus citreus, Microcoсcus luteus, Bacillus cereus, Staphylococcus aureus, Streptococcus lactis, and, in a less degree, gram-negative Escherichia coli and Agrobacterium tumefaciens. Compounds (1)—(8) show a high antimicrobial activity because all of them belong to the type of double coordination compounds and contain similar structural units. Nevertheless, complexes (1) (23.44 μg/mL), (3) (46.9 μg/mL), (4) (23.44 μg/mL), and (8) (46.9 μg/mL) turned out to be the most eff ective, while (6) (>500 μg/mL) and (7) (>500 μg/mL) are less productive. Complexes that have anions [Ge2(OH)(H2Tart)(μ-Tart)2]3- (1), (8) and [Ge2(OH)(HTart)(μ-Tart)2]4- (4) with free hydroxyl and carboxyl groups of the terminal tartaric acid are able to interact with metals in the enzymes of microorganisms and appear to be better antimicrobial drugs because they show lower inhibitory and bactericidal concentrations. Conclusions. Structural features such as the cation-anionic type of compounds, variability of intermolecular interactions, joint of diff erent biologically active units and free chelating groups in tartaric ligands lead to the combination of different action mechanisms and exclude the possibility of strain resistance.

α-L-Rhamnosidase [EC 3.2.1.40], enzyme of the hydrolase family has a wide range of applications: in the food industry, for example, in winemaking to improve the quality and aroma of wines, in the production of citrus juices and drinks to remove bitter components (naringin) that improves the quality and nutritional value of these products; in research as an analytical tool for studying the structure of complex carbohydrate-substituted biopolymers. For the successful use of α-L-rhamnosidases in various biotechnological processes, an important aspect is the development of ways to increase their activity. The main factors affecting the growth and metabolism of microorganisms, including the synthesis of enzymes, are the physicochemical conditions of cultivation, the composition of the nutrient medium, the introduction of substances that raise the yield of the enzyme, which is manifested in an increase in its activity. At present, one of the priority directions of modern research is the study of the effect of various effector compounds that are capable to modify the studied enzymatic activity. In this work, which is a continuation of previous studies, a number of mixed-ligand and mixed-ligand-different-metal coordination germanium compounds of with xylaric acid (H5Xylar), 1,10-phenanthroline (Phen), 2,2-bipyridine (bipy) and ions of 3d-metals (Fe2+, Ni2+, Cu2+, Zn2+) were selected as effectors. Study of the effect of these complexes on the activity of Eupenicillium erubescens, Cryptococcus аlbidus and Penicillium tardum α-L-rhamnosidases were the aim of this work. Methods. The objects of research were α-Lrhamnosidases from Eupenicillium erubescens 248, Cryptococcus albidus 1001, and Penicillium tardum IMV F-100074. The α-L-rhamnosidase activity was determined by the Davis method using naringin as a substrate. We used 12 coordination compounds of germanium as modifiers of enzyme activity, the composition and structure of which were established using a combination of physical and chemical research methods: elemental analysis, thermogravimetry, IR spectroscopy and X-ray structural analysis. Structures of seven compounds are deposited in the Cambridge Crystallographic Database. When studying the effect of various compounds on the activity of enzymes, concentrations of 0.1 and 0.01% were used, exposure times were 0.5 and 24 hours. The test compounds were dissolved in 0.1% dimethyl sulfoxide. UV-spectra of absorption of native and chemical modified preparations of the enzymes were studied by spectrophotometer-fluorimeter DeNovix DS-11 in the range of 220–340 nm, concentration of the enzyme preparation 1.0 mg of protein/mL. Results. Analysis of the totality of the obtained data (exposure time 24 h, concentration 0.1%) regarding the effect of the studied compounds on the activity of E. erubescens, C. albidus and P. tardum α-L-rhamnosidases showed that the influence of the studied modifiers for the activity of α-L-rhamnosidases varies depending on the producer strain. Our data allow us to present the following series of modifiers in accordance with an increase in their effect on the activity of enzymes of different producers: E. еrubescens: 12 < 11 < 5 < 3 < 4=10 < 1 < 3 < 8 < 2 < 6 < 7; C. albidus: 10 < 11 < 12 < 9 < 3 < 1=5 < 8=4 < 2 < 6 < 7; P. tardum: 12=2 < 3 < 4 < 11 < 5 < 8 < 1 < 9 < 6 < 10 < 7. Conclusions. The results obtained allow us to conclude that compound (7)(-tris(bipyridine) nickel(II) μ-dihydroxyxylaratogermanate(IV)) is the most effective activator of α-L-rhamnosidases of all three micromycete strains, compound (6)(tris(phenanthroline)nickel(II) μ-dihydroxyxylaratogermanate(IV)) − on α-L-rhamnosidase from E. erubescens and C. albidus, while compound (10)-(copper(II) μ-dihydroxyxylaratogermanate(IV)-cuprate(II)) − only of P. tardum α-L-rhamnosidase.

Authors have developed optimal conditions and synthetic methods in water-organic solutions for ten heterometallic – mixed-ligand complexes of germanium(IV) and 3d-metals with gallic acid (Н2Gal) and 1,10-phenanthroline (phen), their composition and structure [M(phen)3][Ge(H2O)(HGal)2]∙nH2O (M = Mn (1), Co (2), Ni (3), Zn(5)); [CuCl(phen)2]2[Ge(H2O)(HGal)2]∙2H2O (4). Comparative analysis of their IR-spectra and spectra gallic acid and 1,10-phenanthroline with involvement diffuse reflection spectra allowed to establish coordination sphere of germanium and 3-metals. IR-spectra of complexes 1-5 are similar, therefore coordination of ligands in them is the same. Comparatively to the IR-spectrum of gallic acid, there are absent valence absorption bands of free carboxylic groups while two bands of asymmetric and symmetric oscillation of C-O groups in carboxylate ions CОО- appear in the spectra of complexes. Deformation bands d(Сarom-О-Н) are shifted to the low-frequency region for 50-40 cm-1, which indicates deprotonation and binding to the complexing agent of OH-groups from gallic acid. Appearance of deformation bands d(H2О) at 1625 сm-1 is characteristic for the coordination water in composition of complexes. Presence of coordination and crystalline water as well as unbonded OH-group are confirmed with the band n(Ge-О) at 620 сm-1. Thermal decomposition of mixed-metal complexes starts with an endothermic effect in the temperature range 80-160°С where elimination of certain number of water molecules takes place: two – for 1 and 4, three – for 2 and 5, four – for 3. On the thermogravigrams of all compounds one more endoeffect in the temperature range 160-220°С is presented, where removal of one coordination water molecule happens. It was established, that coordination polyhedron of germanium was formed by five oxygen atoms of deprotonated hydroxyl groups from two molecules of gallic acid and one water molecule in all compounds. Second ligand – 1,10-phenanthroline is coordinated to 3d-metal through heterocyclic nitrogen atoms with formation of cations with different composition [M(phen)3]2+ (M = Mn, Co, Ni, Zn) та [CuCl(phen)2]+.

Tetrachlorozincates [Ge(LH)2][ZnCl4]∙CH3OH were isolated for the first time from isonicotinoylhydrazone 2-hydroxybenzene (2-hydroxynaphyl-1)carbaldehyde (H2L)–GeCl4–ZnCl2–CH3OH systems, in which cations are [Ge(L·H)2]2+ complexes protonated by the pyridine nitrogen atom, with L ligands tridentately coordinated via the azomethine nitrogen atom and oxygen atoms of deprotonated hydroxyazino and hydroxy groups. The complexes were studied using the methods of conductometry, thermogravimetry, IR, and 1H NMR spectroscopy.

This article is dedicated to the investigation of crystalline structure in the complex cation-anionic compounds Cu(Phen)2Cl]2[Ge(HCit)2]⋅6H2O (I), [Cu(Phen)3]2[Ge2(OH)(HTart)(μ-Tart)2]·11H2O (II), [CuCl(Phen)2]4[{Ge2(OH)2(μ-Tart)2}Cl2]·4Н2О (III), [Cu(Phen)3]2[(OH)2Ge2(μ-HXylar)4Ge2(μ-OH)2]·8H2O (IV), [CuCl(Phen)2]4[(OH)2Ge2(μ-HXylar)4Ge2(μ-OH)2]·8H2O (V) using Hirshfeld surface analysis. This method has showed itself as an effective tool for analysis of intermolecular interactions, such as hydrogen bonds or weaker C…H and С…Н…p connections. Three-dimensional picture of close interactions in the crystal was built for each of the compounds I–V, where short connections are red-colored, while others – weaker and shorter – are light areas and small spots. It was established that in the structures of all compounds different types of hydrogen bonds are presented: bifurcate connections, symmetrical О-Н…О, С-Н…С and asymmetrical ones with water molecules. Two-dimensional histograms – 2D-fingerprint plots, allowed to evaluate quantitively connections in the crystals and establish that H…O/O…H and H…H interactions make the biggest contribution to the total surface area. The presence of the big number of crystallization water molecules is determinant for the formation of complex system of hydrogen bonds and strengthening of the structure, that otherwise would be unstable because of the big size of cations and anions. Due to the fact, that all compounds have the same complexing agent Ge(IV), structure of the anion is determined by polydentate ligand. Obtained results are important for the further development of the water role in the processes of crystallization, crystal formation, electrical dissociation and, especially, dissolving of coordination compounds in biological systems.

One of the ways to create new biologically active substances based on enzymes is to obtain highly efficient protein-complex structures. Studies in recent years have shown that the coordination compounds of “essential” germanium with biologically active hydroxycarboxylic and, in particular, with xylaric, acids are characterized by low toxicity and a wide range of pharmacological action. In addition, many of them have proven to be activators of various enzymes. In this regard, the aim of work was to study the effects of mixed ligand and heterometallic coordination compounds of germanium with xylaric acid on the catalytic and some physicochemical properties of Penicillium restrictum IMV F-100139 α-galactosidase and α-L-rhamnosidase. α-Galactosidase activity was determined using p-nitrophenyl-α-D-galactopyranoside as a substrate. The ac tivity of α-L-rhamnosidase was determined using the Davis method. As modifiers of enzyme activity different-ligand and different-metalxylaratogermanates have been used. It was shown that the coordination compound (7) tris(bipyridine)nickel(II) μ-dihydroxyxylaratogermanate(IV) ([Ni(bipy) 3 ] 2 [(OH) 2 Ge 2 (μ-HXylar) 4 Ge 2 (μ-Oh) 2 ]∙20Н 2 О∙2C 2 h 5 OH) exerted a significant effect on the catalytic properties of α-L-rhamnosidase and α-galactosidase from P. restrictum. The activation and thermal stabilization of P. restrictum α-L-rhamnosidase in the presence of (7) is based on the combination of all constituents of the effector molecule: cation [Ni(bipy) 3 ] 2+ and anion [(OH) 2 Ge 2 (μ-HXylar) 4 Ge 2 (μ-OH) 2 ] 4- metal complex, as well as the location of aromatic amino acids in the enzyme molecule. Weak non-covalent bonds between P. restrictum α-L-rhamnosidase molecules and compound (7) appear to create the conformation that is most favorable for the convergence of the active sites of the enzyme with the substrate.

There have been developed a novel synthetic method that allowed to obtain raw of mixed-ligand heterometallic binuclear complexes of Ge(IV)-M2+ (Mn, Fe, Co, Ni, Zn) with 1,3-diamino‑2-hydroxypropane N, N, N’, N’-tetraacetic acid (H5hpdta). Compounds have been characterized by the set of methods: elemental analysis, thermogravimetry, IR‑spectroscopy, spectrum of diffuse reflection, magnetic suspensibility. According to the elemental analysis, the molar ratio Ge: M: H5hpdta: bipy= 1:1:1:1 in the obtained compounds 1‑5 corresponds to the formula [(H2O)(OH)Ge(m-hpdta)M(bipy)]·nН2О (M=Mn n=3 (1), Fe n=2 (2), Co n=4 (3), Ni n=4 (4), Zn n=3 (5). Complexes have yellow (1), red (2), orange (3), violet (4) and pink (5) colors and are stable on air. Compounds 1‑5 exist in the form of crystal hydrates, that contain certain amount of water molecules, that are eliminated into the gas phase while heating in the wide range of temperatures (t=80‑250 °C), which is accompanied with the low-temperature endothermic effect. This indicates the presence of a system of stable hydrogen bonds in their crystal structure. Analysis of the IR‑spectra 1‑5 revealed that form and coordination of ligands is similar. Deprotonation of all carboxylic groups in the ligands (H5hpdta) and their bonding to germanium and d-metal is confirmed with the absence in the IR‑spectra 1‑5 absorption bands characteristic for the free СООН H5hpdta (1716 сm‑1) and nas(СОО-) і ns(СОО-) bands. Disappearance of the ν(С-OН)-1210 сm‑1 and appearance of the ν(С-O)alk., νas(Ge-O-M), νs(Ge-O- M) absorption band indicates that OH‑group of H5hpdta is deprotonated and performs bridging function. 2,2`-bipyridine bidentatly coordinates to the d-metal, binds to the O, N‑atoms of hpdta5- ligand and reaches coordination number 6. The last ligand plays the bringing role between Ge-dmetal, shows itself as ditopic, octadentate in total. According to the magnetic moments of 3, 4 and their diffuse reflection spectra, polyhedrons of Co (II), Ni (II) are octahedrons, which are realized due to the bidentate coordination of bipyridine and four bonds with nitrogen and oxygen of hpdta5-. Structure of heterometallic binuclear complexes 1‑5 is similar. Ligand hpdta5- shows itself as octadentate ditopic, all carboxylate groups monodentatly coordinate to metals, oxygen atom of the deprotonated OH‑group performs the bridging function.

[Co(HydrHIz)] and [Ni(HydrHIz)]∙2H2O (М = Co, Ni) complexes have been obtained via the reaction of M(CH3COO)2 with 2-(7-bromo-2-oxo-5-phenyl-3H-1,4-benzodiazepin-1-yl)acetohydrazide (Hydr) and 1H-indole-2,3-dione (НIz). Structure and composition of the complexes have been confirmed by elemental analysis, thermogravimetry, IR spectroscopy, and mass spectrometry data. The electrical conductivity and magnetic susceptibility of the complexes have been determined. The local atomic structure of coordination centers has been established by X-ray absorption spectroscopy.

New xylatogermanates with the same homogermanate complex anion and various phenanthrolinecopper(II) cations, namely, [Cu(Phen)3]2[(OH)2Ge2(µ-HXylar)4Ge2(µ-OH)2] · 8H2O (I), [Cu(H2O)(Phen)2]2[(OH)2Ge2(µ-HXylar)4Ge2(µ-OH)2] · 8H2O (II), and [CuCl(Phen)2]4[(OH)2Ge2(µ-HXylar)4Ge2(µ-OH)2] · 8H2O (III), have been synthesized by the developed method and studied by IR spectroscopy and thermogravimetry. According to X-ray diffraction data, they represent ionic type complexes with the [(OH)2Ge2(μ-HXylar)4Ge2(μ-OH)2]4– tetranuclear germanium-containing complex anion and three complex cations: [Cu(Phen)3]2+ (I), [Cu(H2O)(Phen)2]2+ (II), and [CuCl(Phen)]+ (III). The Ge atoms in the complex anion have two types of coordination: they are five- or six-coordinated. Each Ge atom is linked to the deprotonated carboxylic and hydroxyl groups of two xylaric acid molecules. The five-coordinated Ge atom is additionally linked to one terminal hydroxyl ligand, and the six-coordinated Ge atom is linked to two bridging hydroxyl groups. In crystal structures I and II, cations and anions form alternating layers, which are interchangeably composed of cations and anions. In crystal structure III, cations form “porous” layers, whose cavities accommodate chains of anions. The layers of cations are linked by weak stacking-interactions between the π-systems of Phen.

New heteronuclear Germanium(IV)‑ Thulium (III) complex with 1,3‑diamino‑2‑propanoltetraacetic acid (H5hpdta) was synthesized for the first time. Comparative analysis of IR‑spectrum of complex and ligand proved the absence of free COOH‑groups in the structure of compound – there are no ν(СООН) absorption bands in the IR‑spectra of complex. The significant shift of the ν(С‑N) absorption band (about 45 cm-1), ν(СН) (about 5 cm-1) and presence of ν(Ge‑N) and ν(Tm‑N) bands evidences that protonized nitrogen atoms form coordination bonds with metals. Two pairs of νas(СОО) and νs(СОО) absorption bands of carboxylate ions together with stretching vibrations of Ge‑O and Tm‑O bonds confirm their coordination to metals. There are also presented νas(Ge‑O‑Tm), νs(Ge‑O‑Tm), δ(OH) and δ(Ge‑OH) absorption bands in the IR‑spectrum of complex that indicates the bridging nature of deprotonated hydroxy and hydroxyl group of ligand and also hydrolyzed form of germanium in the structure of compound. During thermal decomposition of the complex in the temperature range of 90‑150 °С as a result of the endothermic effect, two molecules of crystallization water are removed into the gas phase. The further endoeffects at around 150‑220° C are seen with the removal of three coordinated water molecules. The oxidative destruction of the complexes is accompanied by the three exoeffects in temperature range 220‑800 °С. The products of final thermal destruction at 1000°C are GeO2 and Tm2O3. According to the X‑Ray diffraction data of complex [Ge(ОН)(μ‑hpdta)(μ‑OH) Tm(H2O)3]*2H2O, the six‑coordinated atom of Germany and octa‑coordinated atom of Thulium are bound by the bridging oxygen atom of hydroxyl group and hydroxyl-anion. Thecoordination polyhedron of Ge(1) atom is a distorted octahedron formed by three O atoms of deprotonated carboxyl and hydroxyl groups, the nitrogen atom of the hpdta5– and two O atoms of two hydroxyl-anions. The coordination polyhedron of octa-coordinated atom of Thulium is formed by of the O atoms of deprotonated carboxyl, deprotonated hydroxyl groups of the hpdta5–, the bridging oxygen atom of hydroxyl‑anion, three O atoms of coordinated water molecules and one N‑atom of the hpdta5–.

This review article summarizes the results of the study of the composition, structure and pharmacological activity of related different-metal cation-anionic complexes with bis(citrato) germanate(stannate) anion and hexaquacation of the second metal M(H2O)6][Ge(HCit)2]·nH2O and [M(H2O)6][Sn(HCit)2]·nH2O, де М = Mg, Mn, Fe, Co, Ni, Cu, Zn, n=2-4. The inspire for this study were the features of citric acid as an intermediate product of the metabolic cycle of tricarboxylic acids, which plays a major role in the system of biochemical reactions of cellular respiration. Authors defined the conditions for the formation of heterometallic complexes in the systems GeО2 (GeCl4, SnCl4) – citric acid (H4Cit) – M(CH3COO)2 (FeSO4, AgNO3) – H2O (М=Mg2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+), obtained their complete physicochemical characteristics, and also established their molecular and crystalline structures. All compounds have low toxicity. They were proved to have a wide range of pharmacological activity (neurotropic, antistaphylococcal, antiviral, antihypoxic, cerebroprotective. The level and characteristics of a particular type of pharmacological action of the studied drugs is determined by the metal ions – parts of the complex cations and anions, as well as their synergetic effect. The relationship between the composition, structure and pharmacological activity of the complexes was established. The novelty of the approach allowed to obtain supramolecular salts with the structural blocks of opposite charges – complex cations and anions of different metals. Therefore, they do not compete with each other for binding to biosubstrates, but potentiate or enhance each other’s action.