STRUCTURE FEATURES AND PHARMACOLOGICAL PROPERTIES OF GERMANIUM(IV) COMPLEXES WITH 1-HYDROXYETHANE-1,1-DIPHOSPHONIC ACID(Review)
  The review article presents the results of systematic research by the authors of a number of heterometals and mixed-ligand 1-hydroxyethane-1,1-diphosphonatogermanates, their structure, biological and pharmacological properties. It was observed, that hexanuclear cyclic complex anions o...
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| Дата: | 2024 |
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V.I.Vernadsky Institute of General and Inorganic Chemistry
2024
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Репозитарії
Ukrainian Chemistry Journal| _version_ | 1871466074089717760 |
|---|---|
| author | Martsynko, Olena Seifullina, Inna Finik, Оlena Tsymbaliuk, Kyrylo |
| author_facet | Martsynko, Olena Seifullina, Inna Finik, Оlena Tsymbaliuk, Kyrylo |
| author_institution_txt_mv | [
{
"author": "Olena Martsynko",
"institution": "Odesa I. I. Mechnikov National University, Dvoryanska St., 2, Odesa, 65082, Ukraine"
},
{
"author": "Inna Seifullina",
"institution": "Doctor of Chemical Sciences, Professor, Professor of the Department of Inorganic Chemistry and Chemical Education; Odesa I.I. Mechnikov National University, Dvoryanska St., 2, Odesa, 65082, Ukraine."
},
{
"author": "Оlena Finik",
"institution": "Chemist, Limited Liability Company LLC "INSPECTORAT UKRAINE", Udilny Lane, 1, Odesa, 65044, Ukraine."
},
{
"author": "Kyrylo Tsymbaliuk",
"institution": "PhD-student, Odesa I.I. Mechnikov National University, Dvoryanska St., 2, Odesa, 65082, Ukraine and chemist in Limited Liability Company LLC "INSPECTORAT UKRAINE", Udilny Lane, 1, Odesa, 65044, Ukraine."
}
] |
| author_sort | Martsynko, Olena |
| baseUrl_str | https://ucj.org.ua/index.php/journal/oai |
| collection | OJS |
| datestamp_date | 2026-07-22T08:23:55Z |
| description |  
The review article presents the results of systematic research by the authors of a number of heterometals and mixed-ligand 1-hydroxyethane-1,1-diphosphonatogermanates, their structure, biological and pharmacological properties. It was observed, that hexanuclear cyclic complex anions of the general composition [Ge6(µ-OH)6-n(µ-O)n(µ-hedp)6](6+n)− were present in the aqueous solutions of investigated compounds. At the same time, the composition and charge of the anion in each compound obtained in the solid state depends on the nature of the cation. They all have a common hexameric structure, with germanium atoms connected in pairs by 1-hydroxyethane-1,1-diphosphonate, hydroxo-, or oxo- and hydroxo-bridges. The coordination polyhedron Ge is a curved octahedron with two six-membered GeO2P2C cycles and an eight-membered bimetallic Ge2O4P2 closing, and each ligand performs a tetradentate tris(chelate)-µ-bridging function. The ratio of formed oxo- and hydroxo-bridges and, as a result, the charge of the anion varies under the influence of cation parameters and electrostatic interactions. Acute and chronic toxicity studies proved the safety of 1-hydroxyethane-1,1-diphosphonatogermanates. Complexes show a wide spectrum of pharmacological activity: antihypertensive, antiarrhythmic, hepatoprotective, cerebroprotective etc.The pharmacological and biological activities of 1-hydroxyethane-1,1-diphosphonatogermanates(IV) are ensured by the combined action of all biologically active components, which do not compete but show synergistic action. It was concluded that the preparation of new complexes of germanium(IV) with etidronic acid by chemical modification of their composition is a promising area of research in the field of creating coordination compounds with a wide range of pharmacological effects. |
| doi_str_mv | 10.33609/2708-129X.90.9.2024.19-30 |
| first_indexed | 2025-09-24T17:43:58Z |
| format | Article |
| fulltext |
19
UDC 541.49+546.814 doi: 10.33609/2708-129X.90.9.2024.19-30
STRUCTURE FEATURES AND PHARMACOLOGICAL PROPERTIES
OF GERMANIUM(IV) COMPLEXES WITH
1-HYDROXYETHANE-1,1-DIPHOSPHONIC ACID.
Olena Martsynko1, Inna Seifullina1, Olena Finik2, Kyrylo Tsymbaliuk1,2
1Odesa I. I. Mechnikov National University, Dvoryanska St., 2, Odesa, 65082, Ukraine;
2LLC “INSPECTORAT UKRAINE”, Udilnyi lane, 1, Odesa, 65009, Ukraine
e-mail: lborn@ukr.net
The review article presents the results of systematic research by the authors of a number of hetero-
metals and mixed-ligand 1-hydroxyethane-1,1-diphosphonatogermanates, their structure, biological
and pharmacological properties. It was observed, that hexanuclear cyclic complex anions of the general
composition [Ge6(µ-OH)6-n(µ-O)n(µ-hedp)6]
(6+n)− were present in the aqueous solutions of investigated
compounds. At the same time, the composition and charge of the anion in each compound obtained
in the solid state depends on the nature of the cation. They all have a common hexameric structure,
with germanium atoms connected in pairs by 1-hydroxyethane-1,1-diphosphonate, hydroxo-, or oxo-
and hydroxo-bridges. The coordination polyhedron Ge is a curved octahedron with two six-mem-
bered GeO2P2C cycles and an eight-membered bimetallic Ge2O4P2 closing, and each ligand performs
a tetradentate tris(chelate)-µ-bridging function. The ratio of formed oxo- and hydroxo-bridges and,
as a result, the charge of the anion varies under the influence of cation parameters and electrosta
tic interactions. Acute and chronic toxicity studies proved the safety of 1-hydroxyethane-1,1-diphos-
phonatogermanates. Complexes show a wide spectrum of pharmacological activity: antihypertensive,
antiarrhythmic, hepatoprotective, cerebroprotective etc.The pharmacological and biological activities
of 1-hydroxyethane-1,1-diphosphonatogermanates(IV) are ensured by the combined action of all bio-
logically active components, which do not compete but show synergistic action. It was concluded that
the preparation of new complexes of germanium(IV) with etidronic acid by chemical modification of
their composition is a promising area of research in the field of creating coordination compounds with
a wide range of pharmacological effects.
Keywords: germanium(IV), 1-hydroxyethane-1,1-diphosphonic (etidronic) acid, nitrogen hetero-
cycles, coordination compounds, biological activity.
INTRODUCTION. As a result of years
of systematic research providedat the Ode-
sa I.I. Mechnikov National University, the au-
thors have synthesized a wide range of coor-
dination compounds of germanium(IV) and
implemented a new approach to developing
biocoordination chemistry of germanium(IV)
as an independent scientific field. The com-
plexes demonstrated significant advantages
compared to organic compounds of germa-
nium such as low toxicity, solubility in water
and environmentally friendly synthetic route.
20 ISSN 2708-129X. Укр. хім. журн., 2024
STRUCTURE FEATURES AND PHARMACOLOGICAL PROPERTIES OF GERMANIUM(IV) COMPLEXES
WITH 1-HYDROXYETHANE-1,1-DIPHOSPHONIC ACID.INORGANIC CHEMISTRY
The authors have synthesized germanium(IV)
coordination compounds with O, P, N-con-
taining chelating organic ligands with physi-
ological activity [1, 2]. It was shown that the
synergism of germanium and bioligands pro-
vides their pharmacological properties.
The uniqueness of germanium as a com-
plexing agent and biogenic element is most
clearly demonstrated by the example of 1-hyd
roxyethane-1,1-diphosphonic (etidronic) acid
(H4hedp), a well-known multifunctional phos-
phonic complex with various valuable proper-
ties used in pharmacy and cosmetology.
Etidronic acid, due to its specific stereo-
chemistry and mutual interaction of phos-
phonic fragments, is capable of forming both
monomeric complexes with s-, p-, d-, and
f-element ions and coordination di-, oligo-,
and polymers. Compared to other phospho
nic complexing agents, a considerable number
of coordination compounds of etidronic acid
with various metals have been synthesized
and structurally characterized using different
methods [3–9].
The uniqueness of germanium as a com-
plexing agent and biogenic element is most
clearly demonstrated by the example of 1-hyd
roxyethane-1,1-diphosphonic (etidronic) acid
(H4hedp), a well-known multifunctional phos-
phonic complex with various valuable pro
perties used in pharmacy and cosmetology.
H4hedp belongs to the class of moderately to
xic substances and does not possess sensitizing
or cumulative properties, which makes it suit-
able for use as a pharmaceutical agent [10–14].
The high efficacy of metal coordination com-
pounds with H4hedp has been demonstrated
in applications for pain relief in cases of bone
metastases (186Re) and the diagnosis (188Re) of
bone cancer [15].
The aim of this work is analysis of the array of
experimental data on the structure, biological
and pharmacological properties of homo- and
heterometallic, mixed-ligand 1-hydroxyethane-
1,1-diphosphonatogermanates(IV) and identify
promising areas of their application.
Structural insights into 1-hydroxyetha-
ne-1,1-diphosphonatogermanates. Previously
spectrophotometric measurements have pro
ved that an acidic complex with a molar ra-
tio Ge : ligand = 1:1 exists in solution in the
GeO2 - H4hedp - H2O system at pH = 2 [16].
Subsequently, methods were developed for
the isolation of germanium(IV) coordination
compounds with ethidronic acid. It was shown
that the interaction of germanium dioxide and
germanium tetrachloride with H4hedp in wa-
ter produces the same X-ray amorphous glassy
compound. As a result of complexation, hyd
rolysis of germanium tetrachloride is inhibit-
ed. Detailed methods for the synthesis of vari
ous types of 1-hydroxyethane-1,1-diphospho-
natogermanates(IV) are given in [1, 16–18].
The idea of introducing an outer-sphere (exo-)
ligand into the reaction medium, for example,
an organic molecule capable of protonation,
such as nicotinic acid, nicotinamide, piracetam,
etc., was proposed to obtain crystals [1]. Also,
alkali and alkaline earth metals were introduced
and bimetallic complexes were obtained.
X-ray crystallographic data of complexes with
nicotinic acid
(HNic)6[Ge6(µ-OH)6(µ-hedp)6]⋅12H2O,
magnesium
[Mg(H2O)6]2H2[Ge6(µ-OH)6(µ-hedp)6]⋅28H2O
and barium
Ва3[Ge6(µ-OH)6(µ-hedp)6]·25H2O
were received.
It was found that the crystals of the com-
pounds were based on identical hexanuclear
21https://ucj.org.ua
Olena Martsynko, Inna Seifullina, Olena Finik, Kyrylo Tsymbaliuk UCJ № 9 / Vol. 90
cyclic complex anions [Ge6(µ-OH)6(µ-hedp)6]
6−
(рис. 1) in which six germanium atoms are in-
terconnected by six bridging ligand molecules
(phosphonium groups are completely deproto-
nated, each of them is connected to different
germanium atoms), as well as six bridging hyd
roxo-groups. The coordination polyhedron is
a curved octahedron typical of tetravalent
germanium. The cations are cations of NicH+
protonated on the nitrogen atom of the nico-
tinic acid heterocycle and hexaquacations of
s-metals.
Fig. 1. Crystal structure of the anion [Ge6(µ-OH)6(µ-hedp)6]
6-[1].
In the structure Ва3[Ge6(µ-OH)6(µ-hedp)6]·
25H2O the barium atoms are coordinated ex-
clusively by the oxygen atoms of water mole-
cules. However, the significant disorder of all
Ba2+ cations and some water molecules pre-
vented the precise determination of the crystal
structure, coordination number and coordina-
tion polyhedron of barium atoms, and the way
the structural units are packed in the crystal.
The structure of 1-hydroxyethane-1,1-di
phosphonatogermanates(IV) of metals of other
electronic units was investigated. After obtain-
22 ISSN 2708-129X. Укр. хім. журн., 2024
STRUCTURE FEATURES AND PHARMACOLOGICAL PROPERTIES OF GERMANIUM(IV) COMPLEXES
WITH 1-HYDROXYETHANE-1,1-DIPHOSPHONIC ACID.INORGANIC CHEMISTRY
ing the structural data of the bimetallic complex
with zinc, Zn4[Ge6(µ-OH)4(µ-О)2(µ-hedp)6]⋅
38Н2О, it was found that there is a change
in the structure of the hexanuclear anion
(2 hydroxo-bridges out of 6 are converted to
oxo-bridges). This structure also contains oc-
tahedral complex zinc cations with different
ligand environments: hexaquacations and cati-
ons in which two of the six adjacent (cis) verti-
ces of the zinc octahedron are occupied by the
terminal ligand atoms of the two hexanuclear
anions, and the remaining four vertices contain
oxygen atoms of water molecules (Fig. 2). That is,
the molecular formula of these compound can
be written as [Zn4(H2O)18][Ge6(µ-OH)4(µ-О)2
(µ-Oedph)6]⋅20Н2О.
The complex cations and hexanuclear ani
ons are connected by an extensive network
of hydrogen bonds through coordinated and
crystallising water molecules. A single inde-
pendent hydrogen bond is also implemented,
which directly connects each hexanuclear ani-
on with four neighbouring ones, thus forming
a polymeric anionic layer.
Fig. 2. Fragment of the domain layer [Zn(2){Ge6(μ-OH)4(μ-O)2(μ-hedp)6}]n in the crystal
structure of [Zn4(H2O)18][Ge6(µ-OH)4(µ-О)2(µ-Oedph)6]⋅20Н2О.
Coordination compounds with lanthanides
are coordination polymers. The X-ray diffrac-
tion study of three heterometallic coordina-
tion polymers of general formula {Ln2[LnGe6
(μ-hedp)6(μ-O)3(μ-OH)3(H2O)4]·xH2O}n (Ln =
Nd, x ∼ 26; Er, x ∼ 24; Tm, x ∼ 20) is perfor
23https://ucj.org.ua
Olena Martsynko, Inna Seifullina, Olena Finik, Kyrylo Tsymbaliuk UCJ № 9 / Vol. 90
med. The basis element of structures is a hexa
nuclear complex anion [Ge6(μ-hedp)6(μ-O)3
(μ-OH)3]
9−, in which bridging hydroxo- and
oxo-ligands are statistically disordered with
equal probability. Hexameric units are con-
nected by Ln1(H2O)4 fragments into a frame-
work (fig. 3). In structures are channels accom-
modating disordered lanthanide atoms and
water molecules. The complete disordering of
lanthanide atoms in the channels and the al-
most complete disordering of water molecules
coordinating them do not allow us to deter-
mine the actualhydrate composition of com-
plexes.
Fig. 3. Fragment of thestructure of {Nd2[NdGe6(μ-hedp)6(μ-O)3(μ-OH)3(H2O)4]·26H2O}n.
The next step was the introduction of ad-
ditional ligands (1,10-phenanthroline, phen;
2,2’-bipyridine, bipy) and the preparation of
different-ligand and heterometal complexes
with 3d metals. The result demonstrated the
presence of the hexanuclear anion [Ge6(µ-OH)6
(µ-hedp)6]
6- (fig. 1) in the obtained compounds.
However, there is a diversity in the structure of
cations depending on the d-metal.
Complexes with structure [{Co(рhen)3}2
{Co(рhen)(H2O)4}2][{Ge(μ-OH)(μ-hedp)}6Cl2],
[{Cu(рhen)2(H2O)}2(Hрhen)2][Ge(μ-OH)
(μ-hedp)]6∙20H2O were synthesized byusing
the initial chlorides of 3d metals. According
to X-ray diffraction data, these compound-
sare cation–anion type complexes in which
the anions are represented by [Ge6(μ-OH)6
(μ-hedp)6]
6– (in the case of Co-complex two
additional Cl– ions too), while the cations are
[Co(phen)3]
2+,[Co(phen)(H2O)4]
2+in Co-com-
plex (fig. 4) and [Cu(phen)2(H2O)]2+, Hphen+
in Cu-complex (fig. 5).
24 ISSN 2708-129X. Укр. хім. журн., 2024
STRUCTURE FEATURES AND PHARMACOLOGICAL PROPERTIES OF GERMANIUM(IV) COMPLEXES
WITH 1-HYDROXYETHANE-1,1-DIPHOSPHONIC ACID.INORGANIC CHEMISTRY
(a) (b)
Fig. 4. Molecular structure of cations [Co(phen)3]
2+ (a) and [Co(phen)(H2O)4]
2+ (b).
(a) (b)
Fig. 5. Molecular structure of cations [Cu(phen)2(H2O)]2+ (a) and Hphen+ (b).
In the crystals of compounds the cations,
anions, andwater molecules are combined by
numerous intermolecular hydrogen bonds,
giving rise to a 3D network (fig. 6).
A distinction of these coordination com-
pounds from the previously studied 1-hydrox-
yethane-1,1-diphosphonatogermanates(IV)
[1] is the formation of supramolecular assem-
blies based on simple and complex cations and
anions, which mutually counterbalance their
charges. This is caused by both the replace-
ment of Co2+ by Cu2+ and the incorporation
of 1,10-phenanthroline, which can function
simultaneously as a bidentate chelating ligand
and an outer-sphere cation in the Hp hen+
monoprotonated form.
25https://ucj.org.ua
Olena Martsynko, Inna Seifullina, Olena Finik, Kyrylo Tsymbaliuk UCJ № 9 / Vol. 90
(a) (b)
Fig. 6. Crystal structure of compounds [{Co(рhen)3}2{Co(рhen)(H2O)4}2][{Ge(μ-OH)(μ-hedp)}6Cl2] (a)
and [{Cu(рhen)2(H2O)}2(Hрhen)2][Ge(μ-OH)(μ-hedp)]6∙20H2O (b).
The developed synthesis methods allowed
us to obtain Ge(IV)-3d-metals coordination
compounds with 1-hydroxyethane-1,1-diphos-
phonic acid and 2,2’-bipyridine. Complexes
are characterized by the methods of elemental
analysis, IR-spectroscopy, thermogravimetric
analysis. It was established that the obtained
compounds to the cation-anion type. They
consist of the hexanuclear cyclic anions [Ge6
(μ-OH)4(μ-O)2(μ-hedp)6]
8-, complex cations
[M(bipy)3]
2+ (М = Co, Ni), [Cu(H2O)(bipy)2]
2+
(Fig. 7) and crystallization water molecules. In
the cation of complexes with Co(II) and Ni(II)
the octahedral coordination polyhedron of the
3d-metals formed by the six nitrogen atoms of
three 2,2´-bipyridine. The coordination num-
ber of Cu atoms is five, and the polyhedron is
formed by the four nitrogen atoms of two mole-
cules of 2,2´-bipyridine and the oxygen atom of
the water molecule. The synthesized complex-
es correspond to the formulas [M(bipy)3]4[Ge6
(μ-OH)4(μ-O)2(μ-hedp)6]⋅nН2О (М = Co, n =
20; Ni, n = 12), [Cu(H2O)(bipy)2]4[Ge6(μ-OH)4
(μ-O)2(μ-hedp)6]⋅14Н2O [18].
Fig. 7. Scheme of structures of cations [M(bipy)3]
2+, [Cu(H2O)(bipy)2]
2+.
7
polyhedron is formed by the four nitrogen atoms of two molecules of 2,2´-bipyridine and the
oxygen atom of the water molecule. The synthesized complexes correspond to the formulas
[M(bipy)3]4[Ge6(μ-OH)4(μ-O)2(μ-hedp)6]nН2О (М = Co, n = 20; Ni, n = 12),
[Cu(H2O)(bipy)2]4[Ge6(μ-OH)4(μ-O)2(μ-hedp)6]14Н2O [18].
Fig. 7. Scheme of structures of cations [M(bipy)3]2+, [Cu(H2O)(bipy)2]2+.
Pharmacological and biological activity of 1-hydroxyethane-1,1-diphosphonatogermanates(IV).
The pharmacological activity of a number of 1-hydroxyethane-1,1-
diphosphonatogermanates(IV), which according to the results of acute toxicity testing are classified
as low-toxic, was investigated [19–22].
The specific effect of complexes with nicotinic acid and magnesium on the cardiovascular
system was established on the model of arrhythmia caused by intraperitoneal administration of
aconitine alkaloid to rats. The antiarrhythmic effect was found, and it was more pronounced in the
complex with magnesium [23–25].
In acute cerebral ischemia caused by carotid artery occlusion, 1-hydroxyethane-1,1-
diphosphonatogermanates(IV) with piracetam has a pronounced anti-ischemic effect and is also
characterised by high absorption and elimination rate constants in the body [26].
A high hepatoprotective effect of the complex with nicotinic acid was also determined; it
prevents changes in total cholesterol, phospholipids and maintains the qualitative and quantitative
composition of phospholipid fractions at the level of control values in erythrocyte membranes and
in the liver [27].
Studies of the in vitro interferonogenic activity of these compounds on a fibroblast cell
culture line showed that the complex with nicotinic acid induces interferon, and at a concentration
of 25 to 100 μg/ml leads to a 100% delay in the cytopathic effect of vesicular stomatitis virus in cell
culture, which is superior to the comparison drugs.
In the model of endotoxemia of post-traumatic genesis (which can occur, for example, in
peritonitis), the detoxifying effect of the complex with magnesium was shown, which is expressed
in a decrease in the level of medium-weight molecules in the blood serum – a universal marker of
endogenous intoxication and lipid peroxidation products in the liver homogenate, i.e. the degree of
damage to cellular and subcellular membranes [28].
The screening for hepatoprotective activity among compounds with 3d-metals revealed that
the administration of the complex with copper resulted in a significantly lower increase in the
activity of cytolysis and cholestasis enzymes than in untreated animals with hepatitis. The
compound also reduced bilirubin levels in blood serum and liver tissue. Importantly, it has low
toxicity with different types of administration: oral, intraperitoneal and subcutaneous [29–30].
It was studied the effect of mixed-ligand complexes of Ge(IV) – Co(II) (Ni(II), Cu(II)) with
1-hydroxyethane-1,1-diphosphonic acid and 2,2′-bipyridine on the activity of elastase and
fibrinogenase isolated from Bacillus sp. IMV B-7883. It has shown that complexes Co(II) and
Ni(II) inhibited the activity of elastase by 54 and 71% respectively, while complex Cu(II) enhanced
it by 30%. All three complexes have a stimulating effect on fibrinogenase activity in more than 50%
[18].
CONCLUSION. As a result of systematic studies of the structure of a number of mixed-ligand
1-hydroxyethane-1,1-diphosphonatogermanates(IV) with different metals, it was observed, that
N
N М
N N
N
N
2+
M = Co, Ni
N
N
Cu
N
N
H2O
2+
26 ISSN 2708-129X. Укр. хім. журн., 2024
STRUCTURE FEATURES AND PHARMACOLOGICAL PROPERTIES OF GERMANIUM(IV) COMPLEXES
WITH 1-HYDROXYETHANE-1,1-DIPHOSPHONIC ACID.INORGANIC CHEMISTRY
Pharmacological and biological activity of
1-hydroxyethane-1,1-diphosphonatogermana
tes(IV).
The pharmacological activity of a number
of 1-hydroxyethane-1,1-diphosphonatogerma
nates(IV), which according to the results of
acute toxicity testing are classified as low-toxic,
was investigated [19–22].
The specific effect of complexes with nico-
tinic acid and magnesium on the cardiovascular
system was established on the model of arrhyth-
mia caused by intraperitoneal administration of
aconitine alkaloid to rats. The antiarrhythmic
effect was found, and it was more pronounced
in the complex with magnesium [23–25].
In acute cerebral ischemia caused by carotid
artery occlusion, 1-hydroxyethane-1,1-diphos-
phonatogermanates(IV) with piracetam has
a pronounced anti-ischemic effect and is also
characterised by high absorption and elimina-
tion rate constants in the body [26].
A high hepatoprotective effect of the com-
plex with nicotinic acid was also determined; it
prevents changes in total cholesterol, phospho-
lipids and maintains the qualitative and quan-
titative composition of phospholipid fractions
at the level of control values in erythrocyte
membranes and in the liver [27].
Studies of the in vitro interferonogenic ac-
tivity of these compounds on a fibroblast cell
culture line showed that the complex with nic-
otinic acid induces interferon, and at a concen-
tration of 25 to 100 μg/ml leads to a 100% delay
in the cytopathic effect of vesicular stomatitis
virus in cell culture, which is superior to the
comparison drugs.
In the model of endotoxemia of post-trau-
matic genesis (which can occur, for example,
in peritonitis), the detoxifying effect of the
complex with magnesium was shown, which is
expressed in a decrease in the level of medi-
um-weight molecules in the blood serum – a
universal marker of endogenous intoxication
and lipid peroxidation products in the liver ho-
mogenate, i.e. the degree of damage to cellular
and subcellular membranes [28].
The screening for hepatoprotective activity
among compounds with 3d-metals revealed
that the administration of the complex with
copper resulted in a significantly lower in-
crease in the activity of cytolysis and cholesta-
sis enzymes than in untreated animals with
hepatitis. The compound also reduced bili
rubin levels in blood serum and liver tissue.
Importantly, it has low toxicity with different
types of administration: oral, intraperitoneal
and subcutaneous [29–30].
It was studied the effect of mixed-ligand
complexes of Ge(IV) – Co(II) (Ni(II), Cu(II))
with 1-hydroxyethane-1,1-diphosphonic acid
and 2,2′-bipyridine on the activity of elastase
and fibrinogenase isolated from Bacillus sp.
IMV B-7883. It has shown that complex-
es Co(II) and Ni(II) inhibited the activity of
elastase by 54 and 71% respectively, while
complex Cu(II) enhanced it by 30%. All three
complexes have a stimulating effect on fibrino-
genase activity in more than 50% [18].
CONCLUSION. As a result of systematic stu
dies of the structure of a number of mixed-li
gand 1-hydroxyethane-1,1-diphosphonatoger
manates(IV) with different metals, it was ob-
served, that hexanuclear cyclic complex ani-
ons of the general composition [Ge6(µ-OH)6-n
(µ-O)n(µ-hedp)6]
(6+n)− were present in the aque-
ous solutions of investigated compounds.
At the same time, the composition and
charge of the anion in each compound obta
ined in the solid state depends on the nature of
the cation (fig. 8).
27https://ucj.org.ua
Olena Martsynko, Inna Seifullina, Olena Finik, Kyrylo Tsymbaliuk UCJ № 9 / Vol. 90
Fig. 8. Synthetic route and structures of different types
of 1-hydroxyethane-1,1-diphosphonatogermanates.
8
hexanuclear cyclic complex anions of the general composition [Ge6(-OH)6-n(-O)n(-hedp)6](6+n)
were present in the aqueous solutions of investigated compounds.
At the same time, the composition and charge of the anion in each compound obtained in the
solid state depends on the nature of the cation (fig. 8).
Fig. 8. Synthetic route and structures of different types of 1-hydroxyethane-1,1-
diphosphonatogermanates.
They all have a common hexameric structure, with germanium atoms connected in pairs by
1-hydroxyethane-1,1-diphosphonate, hydroxo-, or oxo- and hydroxo-bridges. The coordination
polyhedron Ge is a curved octahedron with two six-membered GeO2P2C cycles and an eight-
membered bimetallic Ge2O4P2 closing, and each ligand performs a tetradentate tris(chelate)--
bridging function. The ratio of formed oxo- and hydroxo-bridges and, as a result, the charge of the
anion varies under the influence of cation parameters and electrostatic interactions. However, the
structure of complex anions is quite stable and is not destroyed even by interactions with complex
cations.
Most obtained compounds refer to the cation-anion type with various cations (protonated
organic molecules, hexaaqua-, bipyridine-, and phenanthroline metal cations). In the structure of
lanthanide compounds complex hexanuclear anions [Ge6(-OH)3(-O)3(-hedp)6]9 and Ln(H2O)4
fragments are combined into a 3D-framework.
The pharmacological and biological activities of 1-hydroxyethane-1,1-
diphosphonatogermanates(IV) are ensured by the combined action of all biologically active
components, which do not compete but show synergistic action.
In view of the above, it can be concluded that the preparation of new complexes of
germanium(IV) with etidronicacid by chemical modification of their composition is a promising
area of research in the field of creating coordination compounds with a wide range of
pharmacological effects.
GeO2 + Н4hedp
900C, H2O
+ L, pH 4
+ MHCO3, pH 5
+ M’CO3, pH 3.5 or 5
+ M’’Cl2 + phen (ethanol)
+ M’’(CH3COO)2 pH 3.5
+ M’’(CH3COO)2 + bipy
(ethanol)
+ Ln(CH3COO)3, pH 4
An = Ge6(µ-OH)4(µ-O)2(µ-hedp)6
8-
[M’’(H2O)6]4[An]
[Co/Ni(bipy)3]4[An]
[Cu(bipy)2(H2O)]4[An]
{Ln2[Ln(H2O)4Ge6(µ-OH)3(µ-O)3(µ-hedp)6]}n
[Ge6(µ-OH)6-n(µ-O)n(µ-hedp)6](6+n)- (in solution)
L= nicotinic acid, niacinamide, isoniazid, imidazole, piracetam;
M = Na, K; M’ = Mg, Ca, Sr, Ba; M’’ = Co(II), Ni(II), Cu(II), Zn; Ln = Nd(III), Er(III), Tm(III);
bipy – 2,2’-bipyridine; phen – 1,10-phenanthroline; *all compounds are hydrates
An = Ge6(µ-OH)6(µ-hedp)6
6-
(HL)6[An]*, M6[An]
[M’(H2O)6]2H2[An]
[M’(H2O)6]3[An]
[{Co(рhen)3}2{Co(рhen)(H2O)4}2][AnCl2]
[{Cu(рhen)2(H2O)}2(Hрhen)2][An]
They all have a common hexameric struc-
ture, with germanium atoms connected in
pairs by 1-hydroxyethane-1,1-diphosphonate,
hydroxo-, or oxo- and hydroxo-bridges. The
coordination polyhedron Ge is a curved oc-
tahedron with two six-membered GeO2P2C
cycles and an eight-membered bimetallic
Ge2O4P2 closing, and each ligand performs a
tetradentate tris(chelate)-µ-bridging function.
The ratio of formed oxo- and hydroxo-bridges
and, as a result, the charge of the anion varies
under the influence of cation parameters and
electrostatic interactions. However, the struc-
ture of complex anions is quite stable and is not
destroyed even by interactions with complex
cations.
Most obtained compounds refer to the ca
tion-anion type with various cations (proto-
nated organic molecules, hexaaqua-, bipyri-
dine-, and phenanthroline metal cations). In
the structure of lanthanide compounds com-
plex hexanuclear anions [Ge6(µ-OH)3(µ-O)3
(µ-hedp)6]
9− and Ln(H2O)4 fragments are com-
bined into a 3D-framework.
The pharmacological and biological acti
vities of 1-hydroxyethane-1,1-diphosphonato-
germanates(IV) are ensured by the combined
action of all biologically active components,
28 ISSN 2708-129X. Укр. хім. журн., 2024
STRUCTURE FEATURES AND PHARMACOLOGICAL PROPERTIES OF GERMANIUM(IV) COMPLEXES
WITH 1-HYDROXYETHANE-1,1-DIPHOSPHONIC ACID.INORGANIC CHEMISTRY
which do not compete but show synergistic
action.
In view of the above, it can be concluded
that the preparation of new complexes of ger-
manium(IV) with etidronicacid by chemical
modification of their composition is a prom-
ising area of research in the field of creating
coordination compounds with a wide range of
pharmacological effects.
This work was done according to the
theme “Chemical construction of or-
gano-inorganic ensembles of coordi-
nating, supramolecular, polymeric na-
ture for use as new materials and phar-
maceuticals”, No state registration:
0122U201403, 2022-2026.
ОСОБЛИВОСТІ БУДОВИ ТА ФАРМАКОЛОГІЧНІ
ВЛАСТИВОСТІ КОМПЛЕКСІВ ГЕРМАНІЮ(IV)
З 1-ГІДРОКСИЕТАН-1,1-ДИФОСФОНОВОЮ
КИСЛОТОЮ
О. Марцинко1, І. Сейфулліна1,
О. Фінік2, К. Цимбалюк1,2
1Одеський національний університет
імені І. І. Мечникова,
вул. Дворянська, 2, Одеса 65082, Україна;
2ТОВ «ІНСПЕКТОРАТ УКРАЇНА»,
провулок Удільний, 1, м. Одеса 65009, Україна
e-mail: lborn@ukr.net
В оглядовій статті представлено резуль-
тати систематичних досліджень авторів
низки гетерометалів і різнолігандних 1-гід
роксиетан-1,1-дифосфонатогерманатів, їх
ньої структури, біологічних і фармаколо-
гічних властивостей. Встановлено, що у
водних розчинах досліджуваних сполук
присутні шестиядерні циклічні комплекс
ні аніони загального складу [Ge6(µ-OH)6-n
(µ-O)n(µ-hedp)6]
(6+n)−. При цьому склад і
заряд аніона в кожній сполуці, отрима-
ній в твердому стані, залежить від при-
роди катіона. Усі вони мають спільну гек-
самерну структуру аніона, в якій атомами
германію попарно з’єднані 1-гідроксие-
тан-1,1-дифосфонатними, гідроксо- або
оксо- та гідроксомістками. Координацій-
ний поліедр Ge є викривленим октаедром
з двома шестичленними циклами GeO2P2C
та восьмичленним біметалічним циклом
Ge2O4P2, кожен ліганд виконує тетрадентат-
нутрис(хелатну)-µ-місткову функцію. Спів-
відношення утворених оксо- і гідроксоміст-
ків і, як наслідок, заряд аніона змінюється
під впливом параметрів катіонів і електро-
статичних взаємодій. Дослідження гострої
та хронічної токсичності довели безпеч-
ність 1-гідроксиетан-1,1-дифосфонатогер-
манатів. Комплекси виявляють широкий
спектр фармакологічної дії: антигіпертен-
зивну, антиаритмічну, гепатопротекторну,
церебропротекторну та ін. Фармакологіч-
на та біологічна активність 1-гідроксие-
тан-1,1-дифосфонатогерманатів(IV) забез-
печується спільною дією всіх біологічно
активних компонентів, які не конкурують,
а виявляють синергічний ефект. Зроблено
висновок, що отримання нових комплек-
сів германію(IV) з етидроновою кислотою
шляхом хімічної модифікації їхнього скла-
ду є перспективним напрямком досліджень
у галузі створення координаційних сполук
із широким спектром фармакологічної дії.
Ключові слова: германій(IV), 1-гідрок
сиетан-1,1-дифосфонова (етидронова) кис-
лота, нітрогенвмісні гетероцикли, коорди-
наційні сполуки, біологічна активність.
29https://ucj.org.ua
Olena Martsynko, Inna Seifullina, Olena Finik, Kyrylo Tsymbaliuk UCJ № 9 / Vol. 90
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Стаття надійшла 10.06.2024.
|
| id | oai:ojs2.1444248.nisspano.web.hosting-test.net:article-688 |
| institution | Ukrainian Chemistry Journal |
| keywords_txt_mv | keywords |
| language | English |
| last_indexed | 2026-07-23T01:12:08Z |
| publishDate | 2024 |
| publisher | V.I.Vernadsky Institute of General and Inorganic Chemistry |
| record_format | ojs |
| resource_txt_mv | ucjorgua/40/c71dda87a18e60dd33aa50ba0558b040.pdf |
| spelling | oai:ojs2.1444248.nisspano.web.hosting-test.net:article-6882026-07-22T08:23:55Z STRUCTURE FEATURES AND PHARMACOLOGICAL PROPERTIES OF GERMANIUM(IV) COMPLEXES WITH 1-HYDROXYETHANE-1,1-DIPHOSPHONIC ACID(Review) Martsynko, Olena Seifullina, Inna Finik, Оlena Tsymbaliuk, Kyrylo germanium(IV), 1-hydroxyethane-1,1-diphosphonic (etidronic) acid, nitrogen heterocycles, coordination compounds, biological activity.   The review article presents the results of systematic research by the authors of a number of heterometals and mixed-ligand 1-hydroxyethane-1,1-diphosphonatogermanates, their structure, biological and pharmacological properties. It was observed, that hexanuclear cyclic complex anions of the general composition [Ge6(µ-OH)6-n(µ-O)n(µ-hedp)6](6+n)− were present in the aqueous solutions of investigated compounds. At the same time, the composition and charge of the anion in each compound obtained in the solid state depends on the nature of the cation. They all have a common hexameric structure, with germanium atoms connected in pairs by 1-hydroxyethane-1,1-diphosphonate, hydroxo-, or oxo- and hydroxo-bridges. The coordination polyhedron Ge is a curved octahedron with two six-membered GeO2P2C cycles and an eight-membered bimetallic Ge2O4P2 closing, and each ligand performs a tetradentate tris(chelate)-µ-bridging function. The ratio of formed oxo- and hydroxo-bridges and, as a result, the charge of the anion varies under the influence of cation parameters and electrostatic interactions. Acute and chronic toxicity studies proved the safety of 1-hydroxyethane-1,1-diphosphonatogermanates. Complexes show a wide spectrum of pharmacological activity: antihypertensive, antiarrhythmic, hepatoprotective, cerebroprotective etc.The pharmacological and biological activities of 1-hydroxyethane-1,1-diphosphonatogermanates(IV) are ensured by the combined action of all biologically active components, which do not compete but show synergistic action. It was concluded that the preparation of new complexes of germanium(IV) with etidronic acid by chemical modification of their composition is a promising area of research in the field of creating coordination compounds with a wide range of pharmacological effects. V.I.Vernadsky Institute of General and Inorganic Chemistry 2024-10-25 Article Article Inorganic Chemistry Неорганическая химия Неорганічна хімія application/pdf https://ucj.org.ua/index.php/journal/article/view/688 10.33609/2708-129X.90.9.2024.19-30 Ukrainian Chemistry Journal; Vol. 90 No. 9 (2024): Ukrainian Chemistry Journal; 19-30 Украинский химический журнал; ##issue.vol## 90 ##issue.no## 9 (2024): Ukrainian Chemistry Journal; 19-30 Український хімічний журнал; Том 90 № 9 (2024): Ukrainian Chemistry Journal; 19-30 2708-129X 2708-1281 en https://ucj.org.ua/index.php/journal/article/view/688/342 Copyright (c) 2024 Olena Martsynko, Inna Seifullina, Оlena Finik, Kyrylo Tsymbaliuk https://creativecommons.org/licenses/by-nc/4.0 |
| spellingShingle | Martsynko, Olena Seifullina, Inna Finik, Оlena Tsymbaliuk, Kyrylo STRUCTURE FEATURES AND PHARMACOLOGICAL PROPERTIES OF GERMANIUM(IV) COMPLEXES WITH 1-HYDROXYETHANE-1,1-DIPHOSPHONIC ACID(Review) |
| title | STRUCTURE FEATURES AND PHARMACOLOGICAL PROPERTIES OF GERMANIUM(IV) COMPLEXES WITH 1-HYDROXYETHANE-1,1-DIPHOSPHONIC ACID(Review) |
| title_full | STRUCTURE FEATURES AND PHARMACOLOGICAL PROPERTIES OF GERMANIUM(IV) COMPLEXES WITH 1-HYDROXYETHANE-1,1-DIPHOSPHONIC ACID(Review) |
| title_fullStr | STRUCTURE FEATURES AND PHARMACOLOGICAL PROPERTIES OF GERMANIUM(IV) COMPLEXES WITH 1-HYDROXYETHANE-1,1-DIPHOSPHONIC ACID(Review) |
| title_full_unstemmed | STRUCTURE FEATURES AND PHARMACOLOGICAL PROPERTIES OF GERMANIUM(IV) COMPLEXES WITH 1-HYDROXYETHANE-1,1-DIPHOSPHONIC ACID(Review) |
| title_short | STRUCTURE FEATURES AND PHARMACOLOGICAL PROPERTIES OF GERMANIUM(IV) COMPLEXES WITH 1-HYDROXYETHANE-1,1-DIPHOSPHONIC ACID(Review) |
| title_sort | structure features and pharmacological properties of germanium(iv) complexes with 1-hydroxyethane-1,1-diphosphonic acid(review) |
| topic_facet | germanium(IV) 1-hydroxyethane-1,1-diphosphonic (etidronic) acid nitrogen heterocycles coordination compounds biological activity. |
| url | https://ucj.org.ua/index.php/journal/article/view/688 |
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