CEREBROPROTECTION BY GERMANIUM COORDINATION COMPOUNDS IN EXPERIMENTAL ACUTE GLOBAL BRAIN ISCHEMIA

Background. Stroke is among the leading causes of death and disability worldwide with rising incidence among young people today. This is the third most common cause of disability-adjusted life-years worldwide Objective. The present study evaluated the cerebroprotective action of coordination compounds of germanium with underlying global cerebral ischemia in rats. Methods. Global cerebral infarction was induced by bilateral common carotid artery occlusion. For primary screening we used numerous bis(citrate) germanates (stannates) compounds, which contained different metals: OL1-8, and VITAGERM-1,2,3 and 4. All germanium complexes used were injected intraperitoneally (1 % aqueous solution at a dose of 50 and 100 mg/kg in 35 min after bilateral common carotid artery occlusion). Piracetam was used as a reference drug. Criteria of cerebroprotection efficacy: survival of rats (%), ET50 (median effective time), observational Irwin’s test. Results. Almost all bis(citrate) germanates (stannates), which contained different metals, possessed anti-ischemic activity of different intensity. The exceptions were cobalt-containing OL-6 and OL-2 compounds. The most significant efficacy of all investigated indices (which exceeded even reference drug) was evidenced for VITAGERM-1 – a coordination compound of germanium, diethylenetriaminepentaacetic acid and lithium. Conclusions. Results of our experiments are the substitution for further more profound pharmacological investigation of VITAGERM-1 for stroke cerebroprotection and its implementation into clinics

The influence of coordinative tartrate and malatogermanate compounds on the activity of α-L-rhamnosidase preparations from Penicillium tardum, Eupenicillium erubescens and Cryptococcus albidus

Recently enzyme preparations of microbial origin become increasingly important in different industries. Preparations of α-L-rhamnosidase are used in the pharmaceutical industry as well as in scientific work as a tool for analytical research. We have obtained purified α-L-rhamnosidase preparations from Penicillium tardum, Eupenicillium erubescens and Cryptococcus albidus microorganism strains which are effective enzyme producers. The aim of the study was to estimate the ability of germanium coordination compounds to enhance enzyme catalytic activity. The effects of 11 heterometal mixed ligand tartrate (malate-)germanate compounds at 0.01 and 0.1% concentration on the activity of α-L-rhamnosidase preparations from Penicillium tardum IMV F-100074, Eupenicillium erubescens and Cryptococcus albidus 1001 were studied at 0.5 and 24 h exposition. The inhibitory effect of [Ni(bipy)3]4[{Ge2(OH)2(Tart)2}3Cl2]·15H2 on P. tardum α-L-rhamnosidase was revealed. All studied compounds except [CuCl(phen)2][Ge(OH)(HMal)2] were shown to increase activity of P. tardum α-L-rhamnosidase at a longer term of exposition. Activity of E. erubescens α-L-rhamnosidase was shown to be stimulated by d-metal cation-free compounds. C. albidus α-L-rhamnosidase occurred to be insensitive to all compounds studied

Противосудорожное действие нового ксиларатного комплекса германия (IV) с калием на моделях острого судорожного синдрома

Целью нашей работы была оценка противосудорожной активности нового комплекса ксигерма-3 на моделях острой судорожной активности: генерализованных максимальных электрошоковых судорог, острых миоклонических пентилентетразоловых, а также пикротоксиновых, бикукуллиновых и стрихниновых судорог. Обнаружено, что соединение бис(µ-ксиларато)дигидроксодигерманат (IV) калия (ксигерм-3) в этих условиях достоверно уменьшает частоту возникновения и интенсивность проявлений судорожного синдрома, а также увеличивает латентный период проявления первых судорог (в сравнении с референс-препаратами – карбамазепином, вальпроевой кислотой и диазепамом), выраженность которого зависит от дозы.The purpose of our work was an estimation of anticonvulsive activity of new complexes of xygerm-3 under the conditions of the different models of acute seizure activity. It is discovered that bis(µ-xylarato)dihydrogermanate (IV) with potassium (xygerm-3) has diminished frequency of origin and intensity of the seizure syndrome under these conditions and has increased duration of the latent period of the first seizures (as compared to drug-references carbamazepin, valproic acid and diazepam), the manifestation of which depends on a dose

(2S, 3R, 4S, 5R) -2,3,4,5-TETRAHYDROXYHEXANEDIOIC (GALACTARIC) ACID: STRUCTURAL FEATURES, ISOMERS, COMPLEXING PROPERTIES

A review article describes the features of structure and properties of galactaric acid (H6Gala) as a representative of polyhydroxydicarboxylic acids, which is widely used in analytical chemistry, medicine and agriculture. Galactaric acid (mucic acid) has an unusually low solubility in water for an unsubstituted carbohydrate. This property is accompanied by a relatively high melting-point, 206 C. Crystal-structure analysis was conducted in order to determine the intermolecular forces associated with the low aqueous solubility and high crystal-density of galactaric acid. Its coordination-chemical behavior in reactions with ions of s-, p- and d-metal has been characterized. The FT-IR spectra of compounds of galactaric acid and K+, NH4+, Ca2+, Ba2+, La3+have been interpreted. Spectroscopic evidence shows that the dimeric carboxylic groups of the free acid are dissociated upon formation of the compounds, and the asymmetric and symmetric stretching vibrations of the anionic COO-group in these complexes are observed at about 1600 and 1400 cm-1, respectively. The two carboxylic groups of the galactarate coordinate with Ca2+ions in a monodentate form. One of the carboxylic groups in the Ba2+compounds coordinates in a monodentate state; another group interacts with three cations in a tetradentate form. In the K+, NH4+, and La3+compounds, the COO-groups coordinate in a polydentate manner with the cations. Prospects of research of this acid as a ligand upon complexation with germanium (IV) and tin (IV) has been demonstrated

SYNTHESIS AND STRUCTURE OF BIS(XYLARATO )GERMANATES OF MAGNESIUM, CALCIUM AND BARIUM

A procedure for the synthesis of the heterometallic germanium(IV) and magnesium, calcium and barium complexes with xylaric acid (H5Xylar) [Ge(μ-HXylar)2{Mg(Н2О)2}2]·4H2O(І), [Ge(μ-HXylar)2{Ca(Н2О)2}2]·3H2O(ІІ), [Ge(μ-HXylar)2{Ba(Н2О)4}2]·3H2O(ІІІ) were developed and the complexes isolated for the first time in the solid state. The first stage of synthesis portions of GeО2 (2.092 g, 0.02 mol) and xylaric acid С5H8О7 (7.2 g, 0.04 mol) were inserted in hot water (500 ml), heated (рН 1,5-2) and concentrated on a water bath to 150 ml (~4.5 h). Then the resulting solution was cooled to room temperature and MgCO3 (І), СаСO3 (ІІ) or ВаCO3 (ІІІ) added to рН=5. The heteronuclear coordination compounds were characterized by elemental analysis, powder X-ray diffraction, thermogravimetry, IR spectroscopy. Complexes I-III are X-ray amorphous compound with the molar ratio Mg(Ca, Ba) : Ge : ligand = 2 : 1 : 2. A study of the thermal stability of complexes has shown that its thermolysis is stepwise. Analysis of the IR spectra of complexes І-III showed that spectrums does not contain bands at 3590-3650 cm-1 and ν(С=О) = 1720 cm-1 typical of stretching vibrations of free OH and COOH. Bands detected at ν(С–О)~1000-1139 cm-1 typical of alkoxides, and nas(СОО–)~1678-1684 and ns(СОО–)~1356-1413 cm-1 of carboxylate ions. The scheme of structure of compounds I-IІІ was offered

2-HYDROXYPROPYL-1,3-DIAMINTETRAACET AGERMANATICS:SYNTHESIS, PROPERTIES, STRUCTURAL FEATURES

We generalized the experimental data and proposed optimal synthesis techniques and methods for growing crystals 25 homo- and heteronuclear complex of germanium (IV) and a series of s-, d-, f-metals with 2-hydroxypropylene-1,3-diamine-N,N,Nʹ,Nʹ-tetraacetic acid (H5Hpdta). Determined their spectral properties and thermal stability are described features of the structure. We compared characteristics of the synthesized 2-hydroxypropylene-1,3-diamine- N,N,Nʹ,Nʹ-tetraacetagermanatics depending on the electronic structure of the second metal. Have been discovered laws of formation on the basis of the complex anion [Ge(Н2О)(ОН) (Hpdta)]2– different types of supramolecular compounds: cation-anion, heterobinuclear and tetranuclear

COORDINATION COMPOUNDS Sn (IV) WITH HYDROXYCARBOXYLIC ACIDS

This article presents a review of the literature, related to complex compounds of tin (IV) with hydroxycarboxylic acids. Results of investigations of complexing ability of a Lewis acid – tin tetrachloride (IV) in combination with the s-, d-metals ions relative to hydroxycarboxylic acids, obtained in recent years at the Department of General chemistry and polymers ONU I. I. Mechnikov

СИНТЕЗ, БУДОВА ТА ТЕРМІЧНА СТІЙКІСТЬ КОМПЛЕКСІВ ГЕРМАНІЮ(IV), СТАНУМУ(IV) З RS-МИГДАЛЬНОЮ КИСЛОТОЮ

Germanium(IV) and tin(IV) coordination compounds [Ge(Mand)2(H2O)2]∙2H2O (1), (H3O) [Ge(OH)(Mand)2] (2), [Sn(Mand)(HMand)2] 5Н2О (3) were synthesized for the first time with the RS-mandelic acid. Thermogravimetric analysis of 1-3 shows, that compounds are crystalohydrates. Thermal destruction of 1 and 2 is gradational. In the thermal interval 80-160°С an endothermic effect with the maximum at 140°С and weight loss, which corresponds to two molecules of crystalline water, is observed. At 160-220°С two more water molecules are deleted from the inner sphere of the complex. On the thermogram of 2 in the thermal interval 140-240°С the first endoeffect with the weight loss of two water molecules, that are bonded more fixedly, then crystalline ones, is observed. In contrast with 1 and 2, during the heating of 3 in the thermal interval of 80-170°С, an endothermic effect, which is followed by elimination of 5 crystalline water molecules, is observed. Disappearing of ν(С=О) = 1716 сm-1 absorption band and presence of νas(СОО–) = 1690 сm-1 in 1 (pic. 2.4 б), νas(СОО–) = 1688 сm-1, νs(СОО–) = 1323 сm-1 in 2 and νas(СОО–) = 1654 сm-1, νs(СОО–) =1322 сm-1 in 3 shows the presence of bonding between carboxyl group and germanium (tin) in 1-3. The bonding between hydroxyl group and metals is confirmed by presence of ν(С-О) absorption band at 1064 сm-1. Herewith in the spectra of complexes 1 and 2 deformation vibrations С-ОН are absent, and in spectrum of 3 they are presented at 1494 сm-1. The bonding is also confirmed by presence of valence vibrations bands of the Ge-O bond equal 744 сm-1 in 1 and 737 сm-1 in 2, and in the spectrum of 3 by presence of ν(Sn-О) = 567 сm-1. In the spectrum of 2 the clear absorption band at 834 сm-1, which corresponds to the deformation vibrations of Ge-O-H-group, is found. Consequently, germanium is presented in the compound in the hydrolyzed form. The schemes of structures are presented.Вперше було отримано координаційні сполуки германію(IV) і стануму(IV) з RS-миндальною кислотою [Ge(Mand)2(H2O)2]∙2H2O (1), (H3O)[Ge(OH)(Mand)2] (2), [Sn(Mand)(HMand)2] 5Н2О (3). Термогравіметричне дослідження 1-3 показало, що комплекси є кристалогідратами. Терморозклад 1 і 2 носить ступінчатий характер. В температурному інтервалі 80-160°С спостерігається ендотермічний ефект з максимумом при 140°С і убутком маси, який відповідає двом молекулам кристалізаційної води, а при 160-220°С відбувається видалення ще двох молекул води, які входять до внутрішньої сфери комплексу. На термогравіграмі 2 в інтервалі температур 140-240°С спостерігається перший ендоефект з убутком маси, що відповідає видаленню двох молекул води, яка зв’язана більш міцно, ніж кристалізаційна. На відміну від 1 і 2, при нагріванні комплексу стануму 3 при 80‑170°С спостерігається ендотермічний ефект, який супроводжується видаленням п’яти молекул кристалізаційної води. Про зв’язування карбоксильної групи кислоти з германієм і станумом комплексах 1-3 свідчить зникнення смуги коливань ν(С=О) = 1716 см-1 і поява смуг νas(СОО–)=1690 см-1 для 1, νas(СОО–) =1688 см-1 , ν s(СОО–)=1323 см-1 для 2 і ν as(СОО–) =1654 см-1 , νs(СОО–) =1322 см-1 для 3, а також ν(С-О) гідрокисильної групи алкоголятного типу при 1064 см-1. В ІЧ-спектрах комплексів 1 і 2 відсутні деформаційні коливання С-ОН, в спектрі 3 – вони зберігаються при 1494 см-1. Це підтверджується і наявністю в ІЧ-спектрах 1 і 2 смуг валентних коливань зв’язку Ge-O = 744 см-1 для 1 і 737 см-1 для 2, а в спектрі 3 – ν(Sn-О) = 567 см-1. В той же час в спектрі комплексу 2 виявлена чітка смуга при 834 см-1, яка відноситься до деформаційних коливань групи Ge-O-H, отже, германій до складу цього комплексу входить в гідролізованій формі. Запропоновано схеми будови комплексів

SYNTHESIS, STRUCTURE AND THERMAL PROPERTIES OF GERMANIUM(IV), TIN(IV) COMPLEXES WITH RS-MANDELIC ACID

Germanium(IV) and tin(IV) coordination compounds [Ge(Mand)2(H2O)2]∙2H2O (1), (H3O) [Ge(OH)(Mand)2] (2), [Sn(Mand)(HMand)2] 5Н2О (3) were synthesized for the first time with the RS-mandelic acid. Thermogravimetric analysis of 1-3 shows, that compounds are crystalohydrates. Thermal destruction of 1 and 2 is gradational. In the thermal interval 80-160°С an endothermic effect with the maximum at 140°С and weight loss, which corresponds to two molecules of crystalline water, is observed. At 160-220°С two more water molecules are deleted from the inner sphere of the complex. On the thermogram of 2 in the thermal interval 140-240°С the first endoeffect with the weight loss of two water molecules, that are bonded more fixedly, then crystalline ones, is observed. In contrast with 1 and 2, during the heating of 3 in the thermal interval of 80-170°С, an endothermic effect, which is followed by elimination of 5 crystalline water molecules, is observed. Disappearing of ν(С=О) = 1716 сm-1 absorption band and presence of νas(СОО–) = 1690 сm-1 in 1 (pic. 2.4 б), νas(СОО–) = 1688 сm-1, νs(СОО–) = 1323 сm-1 in 2 and νas(СОО–) = 1654 сm-1, νs(СОО–) =1322 сm-1 in 3 shows the presence of bonding between carboxyl group and germanium (tin) in 1-3. The bonding between hydroxyl group and metals is confirmed by presence of ν(С-О) absorption band at 1064 сm-1. Herewith in the spectra of complexes 1 and 2 deformation vibrations С-ОН are absent, and in spectrum of 3 they are presented at 1494 сm-1. The bonding is also confirmed by presence of valence vibrations bands of the Ge-O bond equal 744 сm-1 in 1 and 737 сm-1 in 2, and in the spectrum of 3 by presence of ν(Sn-О) = 567 сm-1. In the spectrum of 2 the clear absorption band at 834 сm-1, which corresponds to the deformation vibrations of Ge-O-H-group, is found. Consequently, germanium is presented in the compound in the hydrolyzed form. The schemes of structures are presented

DESIGN AND SYNTHESIS OF NEW HOMO- AND HETEROMETAL COORDINATION COMPOUNDS OF GERMANIUM(IV) FOR PREPARATION OF LOW TOXIC DRUGS WITH A WIDE THERAPEUTIC ACTION

Coordination compounds of essential microelement germanium(IV) with metals (Mg, Na, K, Ca, Cu, etc.) and organic ligands – biocatalysts, antidotes at intoxications and regulators of mineral metabolism in living organism (nicotinic, citric, tartaric, 1-hydroxyethylidendiphosphonic acids, nicotinamide) are synthesized for the first time on the Department of General Chemistry and Polymers of Odessa Mechnikov National University. The favorable activity of the synthesized compounds on cardiovascular and chronic respiratory diseases, senile pneumonia, neuropsychiatric and metabolic disorders, ischemic heart diseases, etc. is described. Thus, the influence of 1-hydroxyethylidendiphosphonatogermanate (medgerm) on CNS, its anxiolytic activity and absence of both hypnotic and myorelaxant effects has been shown. Cardioprotector properties of magnesium hydroxyethylidendiphosphonategermanate as a potential effective and safe drug with the high antihypertensive and antiarrhythmic activity have been found out. The interferoninductive and immunostimulatory activity of germanium(IV) compounds with 1-hydroxyethylidendiphosphonic, nicotinic acids, nicotinamide, pyracetam has been studied. Injection of these drugs (concentration 100-125 μg/ml) causes the 100 % delay of cytopathic action of vesicular stomatitis virus in the cell cultures that demonstrates the ability of compounds to increase essentially cells stability. The perspectives of germanium coordination compounds as interferon inductors and as immune pharmaceuticals for prevention the disbalance of the immune system are reviewed