СOMPLEXES OF Nd(III) AND 3d-METALS BASED ON ETHYLENEDIAMINEDISUCCINIC ACID AS POTENTIAL ANTIFUNGAL AGENTS
Neodymium heterometallic complexes [(NdМIIEDDS)(H2O)6]∙n2H2O (МII=Zn, Co; n = 3; 2) were synthesized by the «block» synthesis method using protonated ethylenediaminedisuccinate of the 3-d metal and NdIII nitrate. The complexes were characterized by spectroscopic methods (UV-VIS electronic absorption...
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| author | Trunova, Olena Berezhnytska , Оleksandra Rohovtsov , Oleksandr Makotryk, Tamara Rusakova, Mariya |
| author_facet | Trunova, Olena Berezhnytska , Оleksandra Rohovtsov , Oleksandr Makotryk, Tamara Rusakova, Mariya |
| author_institution_txt_mv | [
{
"author": "Olena Trunova",
"institution": "V.I. Vernadsky Institute of General and Inorganic Chemistry NAS of Ukraine"
},
{
"author": " Оleksandra Berezhnytska ",
"institution": "V.I.Vernadsky Institute of General and Inorganic Chemistry of NAS of Ukraine, Akad. Palladin Avenue, 32\/34, Kyiv, Ukraine, 03142"
},
{
"author": "Oleksandr Rohovtsov ",
"institution": "V.I.Vernadsky Institute of General and Inorganic Chemistry of NAS of Ukraine"
},
{
"author": "Tamara Makotryk",
"institution": "V. I. Vernadskii Institute of General and Inorganic Chemistry of the Ukrainian National Academy of Sciences, Akad. Palladin Avenue 32\/34, Kyiv 03142, Ukraine"
},
{
"author": "Mariya Rusakova",
"institution": "Odessa I.I. Mechnikov National University"
}
] |
| author_sort | Trunova, Olena |
| baseUrl_str | https://ucj.org.ua/index.php/journal/oai |
| collection | OJS |
| datestamp_date | 2026-07-22T08:23:52Z |
| description | Neodymium heterometallic complexes [(NdМIIEDDS)(H2O)6]∙n2H2O (МII=Zn, Co; n = 3; 2) were synthesized by the «block» synthesis method using protonated ethylenediaminedisuccinate of the 3-d metal and NdIII nitrate. The complexes were characterized by spectroscopic methods (UV-VIS electronic absorption spectroscopy and FT-IR) and elemental analysis. It is shown that the f-d-complexes belong to the «folded» type complexes, in which the ligand-EDDS realizes the maximum dentateness to NdIII, and the coordination sphere of the 3-d cation is formed by chain carboxyl groups of EDDS and intraspherical water molecules. At the same time, the cations of 3d metals are in a distorted octahedral environment, and the coordination polyhedron of the neodymium ion corresponds to a square antiprism (C4v) with the coordination number NdIII = 8. In solutions and in the solid state, the complexes have the same type of structure. The sensitivity of various morphological forms of Candida albicans in Spider and Saburo media to neodymium complexes NdIII with ethylene diamine disuccinate: NdEDDS (I), NdEDDSZn (II) NdEDDSСo (III) in the range of concentrations of the studied compounds 1; 10 and 100 μM was studied. It is shown that the antifungal properties of the complexes vary in the range NdEDDSСo> NdEDDSZn ≥ NdEDDS. The inhibition index of C. albicans in the composition of the biofilm in the Saburo medium under the action of the complexes was 20–25% of the control value, and in the Spider medium the complexes led to 95% of cell death. |
| doi_str_mv | 10.33609/2708-129X.89.10.2023.85-99 |
| first_indexed | 2025-09-24T17:43:53Z |
| format | Article |
| fulltext |
85
UDC 541.49: 546.657 + 546.733 + 546.47– 54-386 doi: 10.33609/2708-129X.89.10.2023.85-99
СOMPLEXES OF Nd(III) AND 3d-METALS BASED
ON ETHYLENEDIAMINEDISUCCINIC ACID
AS POTENTIAL ANTIFUNGAL AGENTS.
Olena K. Trunova1*, Maria Yu. Rusakova2, Oleksandra S. Berezhnytska 1,3,
Oleksandr O. Rohovtsov1, Tamara O. Makotryk1
1V.I. Vernadsky Institute of General and Inorganic Chemistry of the National Academy
of Sciences of Ukraine,
32/34 Academic Palladin ave., 03142 Kyiv, Ukraine;
2 I.I. Mechnikov National University of Odessa, 65026 Odessa, Ukraine;
3 National Technical University of Ukraine «Igor Sikorsky Kyiv Polytechnic Institute»,
37 Peremohy ave., 03056 Kyiv, Ukraine
*е-mail: trelkon@gmail.com
Neodymium heterometallic complexes [(NdМIIEDDS)(H2O)6]∙n2H2O (МII=Zn, Co;
n = 3; 2) were synthesized by the «block» synthesis method using protonated ethylenediamine-
disuccinate of the 3-d metal and NdIII nitrate. The complexes were characterized by spectro-
scopic methods (UV-VIS electronic absorption spectroscopy and FT-IR) and elemental ana
lysis. It is shown that the f-d-complexes belong to the «folded» type complexes, in which the
ligand-EDDS realizes the maximum dentateness to NdIII, and the coordination sphere of the
3-d cation is formed by chain carboxyl groups of EDDS and intraspherical water molecules.
At the same time, the cations of 3d metals are in a distorted octahedral environment, and the
coordination polyhedron of the neodymium ion corresponds to a square antiprism (C4v) with
the coordination number NdIII = 8. In solutions and in the solid state, the complexes have the
same type of structure. The sensitivity of various morphological forms of Candida albicans in
Spider and Saburo media to neodymium complexes NdIII with ethylene diamine disuccinate:
NdEDDS (I), NdEDDSZn (II) NdEDDSСo (III) in the range of concentrations of the studied
compounds 1; 10 and 100 μM was studied. It is shown that the antifungal properties of the
complexes vary in the range NdEDDSСo> NdEDDSZn ≥ NdEDDS. The inhibition index of
C. albicans in the composition of the biofilm in the Saburo medium under the action of the
complexes was 20–25% of the control value, and in the Spider medium the complexes led to
95% of cell death.
Keywords: ethylenediaminedisuccinates complexes, neodymium, cobalt (II), zinc (ІІ),
antifungal properties.
86 ISSN 2708-129X. Укр. хім. журн., 2023
СOMPLEXES OF Nd(III) AND 3d-METALS BASED ON ETHYLENEDIAMINEDISUCCINIC ACID
AS POTENTIAL ANTIFUNGAL AGENTS.INORGANIC CHEMISTRY
INTRODUCTION. In recent decades, stu
dies of lanthanide (Ln) complexes have shown
that they play an important role in several bio-
chemical reactions [1, 2], and are widely used
in medical diagnostics as fluorescent labels for
biomolecular sensing, for the diagnosis and
therapy of cancer, and also as biosensors [3–7].
Cerium group lanthanides (La, Ce, Pr, Nd),
primarily used in biology, perform chemical
actions similar to other biologically useful met-
als and do so more efficiently due to their high-
er Lewis acidity. Ln have a high coordination
ability, allowing selective absorption, transport
and incorporation into enzymes similar to bio-
genic metals, especially CaII and FeIII [8].
Luminescent ions of some lanthanides are
used as labels that help to study the distribu-
tion of drugs and metabolites in vivo [9]. Al-
though lanthanides are not classified as bi-
metals, having great similarity with calcium,
they can replace it in biological systems. For
example, on the basis of Ln complexes, drugs
are created that regulate calcium metabolism
in the body, for example, blood anticoagulants
[10, 11]. Also, based on Ln, preparations have
already been developed that can affect calcium
metabolism in the body and inhibit the deve
lopment of tumor cells. The ionic radii of lan-
thanides are close to the ionic radius of Ca2+,
but due to their higher charge (Ln3+), lantha-
nide ions are characterized by a high affinity
for Ca2+ sites in biological molecules, which
determines their ability to block the corres
ponding channels. Thus, although Ln3+ ions
alone cannot penetrate cell membranes, they
can block the outer side of the calcium channel
[12, 13]. Complex compounds of polyamino-
carboxylic acids with lanthanides and iron can
be used in the therapy of oncological diseases,
immunodeficiencies and blood diseases. Nit
rates [LnL(NO3)2(H2O)2](NO3), (Ln = La, Pr,
Nd, Sm, Eu, Gd, Tb, Dy, Er) with polydentate
Schiff bases (L = N,N-bis(2-hydroxy-1-naph-
thylidene)-1,6-hexadimine), as well as hyd
razine complexes of 3,3'-thiodipropanoates
[M(N2H5)(tdp)2] (M = La, Ce, Sm, Pr, Nd) by
in vitro evaluation demonstrated high antimi-
crobial activity against six bacteria (Bacillus
cereus, Staphylococcus aureus, Proteus vulgaris,
Pseudomonas aeruginosa, Escherichia coli, Ser-
ratia species) and four fungi (Candida albicans,
Aspergillus niger, Aspergillus fumigatus, Penici
llium variance) [14–16].
The review [17] analyzed a large number of
studies devoted to the antimicrobial activity of
LnIII complexes. A fairly wide range of free or-
ganic ligands were found to be inactive against
various types of bacteria (except E. coli), while
complexes LaIII, PrIII, SmIII, TbIIIand YbIII-
showed some inhibitory activity against them.
It was concluded that the increase in the acti
vity of the complexes compared to free ligands
can be due to the effect of metal ions on the cell.
Moreover, most Ln complexes are more effec-
tive against gram-positive microorganisms, in
particular Staphylococcus aureus, than against
gram-negative ones, primarily Escherichia coli.
Comparing the effect on gram-positive micro-
organisms of free ligands and corresponding
complexes with lanthanides, it was determined
that the activity of the latter is 15–27% higher.
Based on the analysis, the authors concluded
that Ln complexes represent a possible alter-
native to antimicrobial agents currently used.
The use of nanomaterials based on lanthanides
in biomedicine has increased the likelihood of
their use in vivo [18].
Biocoordination compounds of metals as
medical and biological agents form the basis
of modern socially and technologically sig-
87https://ucj.org.ua
Olena K. Trunova, Maria Yu. Rusakova, Oleksandra S. Berezhnytska, Oleksandr O. Rohovtsov, Tamara O. Makotryk UCJ № 10 / Vol. 89
nificant innovative developments. Combining
metal ions with an organic compound enables
the production of supramolecular associates,
which are inherently close to the endogenous
coordination compounds that exist in the li
ving organism and in general in biosystems.
They are less toxic than their constituents and
usually have a wide range of biological activity.
The most promising chelating ligands are ami-
nopolycarboxylic acids containing carboxyl
(–C(O)O-) and amino (NH-) groups, which
makes it possible to obtain metal-containing
compounds in which metal ions are bound to
polydentate ligands using electron-donating
atoms (oxygen and nitrogen) with the forma-
tion of heterocyclic rings (metal chelate rings).
Among the wide variety of aminopolycarbo
xylic acids, a special place is occupied by ethy
lenediamine-N, N-disuccinic acid (EDDS),
which contains fragments of aspartic and suc-
cinic acids in the molecule, known as adapto-
gens. In a living organism, it performs not only
the function of delivering microelements but
also carries a biologically active load. Under
the action of enzymes in a living organism,
the organic part of the metal complex МEDDS
breaks down into essential amino acids (argi-
nine, leucine, isoleucine, valine, histidine, as-
paragine, alanine), which are components of
the metabolic chain [19].
For example, сomplexes of metals with
ethylenediaminedisuccinic acid has antimicro-
bial activity against fungi and bacteria [20] and
antiviral activity against cytomegalovirus [21].
In vitro ethylenediaminedisuccinic acid inhibi
ted viral replication in mice (EC50 8.6 mg/ml)
and reduced their mortality. The introduction
of EDDS may be an important immunopatho-
logical factor in terms of modulating the re-
sponse to cytomegalovirus infections. Ethyle
nediaminesuccinic acid is one of the effective
zincophores because it has a relatively high
affinity for removing zinc ions. Zincophores
are distinct from ionophores that transport
zinc across the membrane, such as pyrithione,
which forms a neutral ZnL2 complex. Zinco-
phores are commonly found in bacteria that
need to acquire Zn2+ in environments with low
zinc concentrations or high competition for
zinc [22.] A promising group of antimicrobial
compounds are metal pharmaceuticals based
on aminocarboxylate complexes of 3-d metals,
which are included in biomolecules (amino
acids, proteins, oligonucleotides or DNA) and
can interact with them [23]. Recently, interest
in cobalt coordination complexes has increased
due to their antimicrobial and antitumor pro
perties [24].
Thus, taking into account that complexes
of metals with ethylenediaminedisuccinic acid
have antimicrobial activity against fungi and
bacteria [19], the aim of this study was the syn-
thesis of new homo- and heterometallic ethy
lenediaminedisuccinate complexes of NdIII and
3-d metals (CoII, ZnII) and the study of their
antimicrobial activity by in relation to bacterial
strains of Candida albicans cultures.
EXPERIMENT AND DISCUSSION OF
THE RESULTS.
Neodymium nitrates Nd(NO3)3⋅6H2O and
zinc Zn(NO3)2⋅6H2O or cobalt Со(NO3)2⋅6H2O
were used as starting compounds for the syn-
thesis of homo- and heterometallic complex-
es of NdIII with ethylenediaminesuccinic acid.
Ethylenediaminediasuccinic acid was obtained
by the condensation reaction of maleic acid
with ethylenediamine [25]. All reagents were
of analytical grade and were used without fur-
ther purification. The strain Саndidа аlbiсапs
ATCC 18804 was obtained from the Museum
88 ISSN 2708-129X. Укр. хім. журн., 2023
СOMPLEXES OF Nd(III) AND 3d-METALS BASED ON ETHYLENEDIAMINEDISUCCINIC ACID
AS POTENTIAL ANTIFUNGAL AGENTS.INORGANIC CHEMISTRY
of Cultures of Microorganisms, Department
of Microbiology, Virology and Biotechno
logy, Odesa National University named after
I.I. Mechnikov (Ukraine). Solutions of salts
and H4EDDS of the required concentration
(0.01 mol/dm-3) were obtained by dissolving
the appropriate samples of reagents in bidis-
tilled water. Solutions were prepared imme-
diately before synthesis. The concentration
of metals in the solutions was determined by
complexometric titration with the indicators
murexide (for 3-d metal ions) and arsenazo 1
(for Nd3+ ions).
Neodymium ethylenediaminedisuccinate
homonuclear complex was obtained according
to the method [26]. The synthesis of heterome-
tallic complexes (НМС) in the NdIII-MIIEDDS
(MII=Zn, Co) systems was carried out by the
«block» method, which consists in sequential
complexation first with one and then with the
second metal. Homonuclear complexes of 3-d
metals obtained by the interaction of aqueous
solutions of EDDS and d-metal salts in an aci
dic medium were used as a «building block».
Нeterometallic complexes were obtained with-
out separating the «building block» from the
solution [26, 27].
The study of complexes in aqueous solu-
tions was carried out by the methods of UV-
VIS electronic absorption spectroscopy (EАS)
at an equimolar ratio of components and
СМ =1∙10-2mol/dm-3. Electronic spectra were
recorded on a spectrophotometer Specord
M∙40 in the range of 50,000–10,000 cm-1. The
pH value was monitored using a pH meter
pH – 150 MA.
In fig. 1, as an example, the UV-VIS spectra
of hono- and heterometallic ethylenediami
nedisuccinate complexes of NdIII is given, and
in Table. 1 position of the main absorption
bands of the NdIII ion in the spectra of the
complexes.
used without further purification. The strain Саndidа аlbiсапs ATCC 18804 was obtained from the
Museum of Cultures of Microorganisms, Department of Microbiology, Virology and Biotechnology,
Odesa National University named after I.I. Mechnikov (Ukraine). Solutions of salts and H4EDDS of
the required concentration (0.01 mol/dm-3) were obtained by dissolving the appropriate samples of
reagents in bidistilled water. Solutions were prepared immediately before synthesis. The
concentration of metals in the solutions was determined by complexometric titration with the
indicators murexide (for 3-d metal ions) and arsenazo 1 (for Nd3+ ions).
Neodymium ethylenediaminedisuccinate homonuclear complex was obtained according to
the method [26]. The synthesis of heterometallic complexes (НМС) in the NdIII-MIIEDDS (MII=Zn,
Co) systems was carried out by the «block» method, which consists in sequential complexation first
with one and then with the second metal. Homonuclear complexes of 3-d metals obtained by the
interaction of aqueous solutions of EDDS and d-metal salts in an acidic medium were used as a
«building block». Нeterometallic complexes were obtained without separating the «building block»
from the solution [26, 27].
The study of complexes in aqueous solutions was carried out by the methods of UV-VIS
electronic absorption spectroscopy (EАS) at an equimolar ratio of components and СМ =1∙10-
2mol/dm-3. Electronic spectra were recorded on a spectrophotometer Specord M∙40 in the range of
50,000–10,000 cm-1. The pH value was monitored using a pH meter pH – 150 MA.
In fig. 1, as an example, the UV-VIS spectra of hono- and heterometallic
ethylenediaminedisuccinate complexes of NdIII is given, and in Table. 1 position of the main
absorption bands of the NdIII ion in the spectra of the complexes.
The UV-VIS spectra of heterometallic complexes of NdIII with H4EDDS contain a set of
bands corresponding to f-f transitions of the Nd3+ ion from the ground state 4I9/2 to multiplets of
excited levels [L'S'J] (Table 1). The absorption band maxima of HMC are shifted to longer
wavelengths compared to the monometallic complex (∆νmax ≈ 90–250 cm-1 for NdZnEDDS and ≈
60–190 cm-1 for NdCoEDDS). In this case, the absorption intensity increases significantly. This
indicates both the formation of heterometallic metal complexes and a different coordination
environment of complex-forming ions (in particular, 3-d metal ions) in a heteronuclear complex
compared to mononuclear ones. In this case, the absorption intensity increases significantly. This
indicates both the formation of heterometallic metal complexes and a different coordination
environment of complex-forming ions (in particular, 3-d metal ions) in a heteronuclear complex
compared to mononuclear ones. For both heteronuclear neodymium complexes, the positions of the
supersensitive transitions 4I9/2 → 2P1/2 and 4I9/2 → 4G5/2,
2G7/2 are in a lower frequency range
compared to the corresponding bands in the spectrum of the NdEDDS complex.
30000 25000 20000 15000 10000
0.000
0.005
0.010
0.015
2P1/2
2K13/2,
4G9/2,
4G7/2
4G5/2,
4G7/2
4S3/2,
4F7/2
4F5/2,
2H9/2
4F3/2
4D3/2,
4D5/2,
2I11/2,
4D1/2,
2L15/2
4
I9/2
[L'S'J]
A
bs
or
ba
nc
e
,cm-1
2
1
Fig. 1. – UV-VIS spectra of homo- (1) and heterometallic (2) complexes of NdIII and ZnII with Н4EDDS (рН 7;
СNd=CZn=CEDDS=1·10-2mol/dm3).
Table 1.
Fig. 1. – UV-VIS spectra of homo- (1) and heterometallic (2) complexes of NdIII
and ZnII with Н4EDDS (рН 7; СNd = CZn = CEDDS = 1·10-2 mol/dm3).
89https://ucj.org.ua
Olena K. Trunova, Maria Yu. Rusakova, Oleksandra S. Berezhnytska, Oleksandr O. Rohovtsov, Tamara O. Makotryk UCJ № 10 / Vol. 89
The UV-VIS spectra of heterometallic com-
plexes of NdIII with H4EDDS contain a set of
bands corresponding to f-f transitions of the
Nd3+ ion from the ground state 4I9/2 to multiplets
of excited levels [L'S'J] (Table 1). The absorption
band maxima of HMC are shifted to longer
wavelengths compared to the monometallic
complex (∆νmax ≈ 90–250 cm-1 for NdZnEDDS
and ≈ 60–190 cm-1 for NdCoEDDS). In this
case, the absorption intensity increases signi
ficantly. This indicates both the formation of
heterometallic metal complexes and a different
coordination environment of complex-form-
ing ions (in particular, 3-d metal ions) in a
heteronuclear complex compared to mononu-
clear ones. In this case, the absorption intensity
increases significantly. This indicates both the
formation of heterometallic metal complex-
es and a different coordination environment
of complex-forming ions (in particular, 3-d
metal ions) in a heteronuclear complex com-
pared to mononuclear ones. For both hetero-
nuclear neodymium complexes, the positions
of the supersensitive transitions 4I9/2 → 2P1/2 and
4I9/2 → 4G5/2,
2G7/2 are in a lower frequency range
compared to the corresponding bands in the
spectrum of the NdEDDS complex.
Table 1.
Transition energies (cm-1) in UV-VIS spectra of NdIII and MII (MII=Co, Zn) complexes with
еthylenediaminedisuccinic acid.
Transition NdZnEDDS νNdL-νNdZnL NdEDDS NdCoEDDS νNdL-νNdCoL
4I9/2→
2P1/2 23254 216 23470 23358 112
4I9/2→
4G9/2 19502 186 19688 19537 151
4I9/2→
4G7/2 19017 247 19264 19113 151
4I9/2→
4G5/2 17196 255 17451 17261 190
4I9/2→
4F9/2 14621 91 14781 14712 69
4I9/2→
4F7/2 13388 242 13630 13440 190
4I9/2→
4F5/2 12475 268 12743 12588 155
4I9/2→
4F3/2 11567 159 11726 11549 177
The 4I9/2→2P1/2 transition is a singlet, which
indicates the existence of one type of con-
nection. However, the bathochromic shift of
the maximum of this band in the spectrum
of HMC (Fig. 2) relative to the monometallic
complex (∆νNdZnEDDS = 216 cm-1, ∆νNdCoZnEDDS =
112 cm-1) indicates a decrease in the coordina-
tion number of NdIII in hetero-complexes.
The general pattern of shifts of the main ma
xima of the f-f-transitions of the Nd3+ ion in the
synthesized heterometallic complexes compa
red to monometallic ones is as follows (Fig. 2).
The absorption bands of the NdIII ion at
≈.17200 cm-1 and 191200 cm-1 belong to the
transitions 4I9/2 → 4G5/2,
2G7/2, respectively, and
from their shape and position one can determine
the symmetry of the coordination environment
of the central atom. In the absorption spectra of
NdМІІEDDS, the half-width of the supersensi-
tive transitions band 4I9/2 → 4G5/2,
2G7/2 is +172
(+174) cm-1, and the band itself does not un-
dergo splitting, which is typical for compounds
with low symmetry [28, 29]. Since ethylenedi-
aminedisuccinic acid is a fairly bulky ligand,
90 ISSN 2708-129X. Укр. хім. журн., 2023
СOMPLEXES OF Nd(III) AND 3d-METALS BASED ON ETHYLENEDIAMINEDISUCCINIC ACID
AS POTENTIAL ANTIFUNGAL AGENTS.INORGANIC CHEMISTRY
no significant splitting of the spectral lines is
observed. It should be noted that the position
of the absorption bands of the f-f transitions of
the Nd3+ ion, as well as the shape of the spectra,
indicate the formation of an eight-coordinated
complex of C4v symmetry, and the NdIII coor-
dination polyhedron corresponds to a square
antiprism.
Fig. 2 – Diagram of shifts (cm-1) in the UV-VIS spectra of heterometallic complexes NdІІІ
with ethylenediaminedisuccinic acid compared to NdEDDS.
Transition energies (cm-1) in UV-VIS spectra of NdIII and MII (MII=Co, Zn) complexes with
еthylenediaminedisuccinic acid.
Transition NdZnEDDS NdL-NdZnL NdEDDS NdCoEDDS NdL-NdCoL
4I9/22P1/2 23254 216 23470 23358 112
4I9/24G9/2 19502 186 19688 19537 151
4I9/24G7/2 19017 247 19264 19113 151
4I9/24G5/2 17196 255 17451 17261 190
4I9/24F9/2 14621 91 14781 14712 69
4I9/24F7/2
13388 242 13630 13440 190
4I9/24F5/2
12475 268 12743 12588 155
4I9/24F3/2
11567 159 11726 11549 177
The 4I9/2→2P1/2 transition is a singlet, which indicates the existence of one type of connection.
However, the bathochromic shift of the maximum of this band in the spectrum of HMC (Fig. 2)
relative to the monometallic complex (∆νNdZnEDDS = 216 cm-1, ∆νNdCoZnEDDS = 112 cm-1) indicates a
decrease in the coordination number of NdIII in hetero-complexes.
The general pattern of shifts of the main maxima of the f-f-transitions of the Nd+3 ion in the
synthesized heterometallic complexes compared to monometallic ones is as follows (Fig. 2).
The absorption bands of the NdIII ion at ≈.17200 cm-1 and 191200 cm-1 belong to the
transitions 4I9/2 → 4G5/2,
2G7/2, respectively, and from their shape and position one can determine the
symmetry of the coordination environment of the central atom. In the absorption spectra of
NdМІІEDDS, the half-width of the supersensitive transitions band 4I9/2 → 4G5/2,
2G7/2 is +172 (+174)
cm-1, and the band itself does not undergo splitting, which is typical for compounds with low
symmetry [28, 29]. Since ethylenediaminedisuccinic acid is a fairly bulky ligand, no significant
splitting of the spectral lines is observed. It should be noted that the position of the absorption bands
of the f-f transitions of the Nd3+ ion, as well as the shape of the spectra, indicate the formation of an
eight-coordinated complex of C4v symmetry, and the NdIII coordination polyhedron corresponds to a
square antiprism.
2P1/2 4G9/2 4G7/2 4G5/2 4F9/2 4F7/2 4F5/2 4F3/20
50
100
150
200
250
177190
155
69
190
151151
112
159
216
268
91
255247
186
216
, c
m
-1
Transition
NdL- NdZnL
NdL- NdCoL
Fig. 2 – Diagram of shifts(cm-1) in the UV-VIS spectra of heterometallic complexes NdІІІ with
ethylenediaminedisuccinic acid compared to NdEDDS.
In both heterometallic complexes, the Nd3+
ion coordinates two nitrogen atoms, three oxy
gen atoms of the EDDS molecule and three
water molecules. The 3-d metal ions have
a distorted octahedral МІІO6 environment
formed by three oxygen atoms of the bridging
β-carboxyl groups of EDDS and three water
molecules. That is, the NdMІIEDDS complex
is a «folded» type complex, in which 3d-me
tal complexes play the role of exo-coordinated
ligands during the formation of heterometallic
complexes. It should be noted that the larger
bathochromic shift of the f-f transition maxi-
ma in the NdZnEDDS complex compared to
the NdCoEDDS complex is associated with
less distortion of the octahedron due to the
filled 3d10 zinc shell, which determines its re-
sistance to various deformations.
The synthesized NdMIIEDDS heterometallic
complexes were isolated from solutions using
the isothermal method (salting out with etha-
nol from aqueous solutions) at pH 7.5, which
corresponds to the maximum accumulation of
deprotonated complexes according to the dis-
tribution diagrams [26, 27]. Identification and
purity of НМС was established by elemental
analysis and IR spectroscopy. The elemental
analyzes for Carbon, Hydrogen and Nitrogen
were obtained on microanalyses Perkins – El
mer 2400. FT-IR spectra were recorded on a
spectrophotometer Specord M-80 in the region
of 4000–400 cm-1 in tablets with КВr.
91https://ucj.org.ua
Olena K. Trunova, Maria Yu. Rusakova, Oleksandra S. Berezhnytska, Oleksandr O. Rohovtsov, Tamara O. Makotryk UCJ № 10 / Vol. 89
NdZnEDDS: NO3[NdZn(C10N2O8H12)∙
6H2O]∙3H2O, found/calculated (%): Nd –
19,84/19,86; Zn – 8,95/8,96; С – 16,57/16,55;
N – 5,81/5,79; Н – 4,18/4,14. FT-IR (KBr, cm−1):
1635 [νаs(СОО)]; 1410, 1339, 1321 [νs(СОО)];
2952 [ν(С-Н)]; 3264, 3424 [ν(Н2О)]; 680, 612,
557, 500 [ν(МО)], 460[ν(МN)].
NdСоEDDS: NO3[NdСо(C10N2O8H12)∙
6H2O]∙2H2O, found/calculated (%): Nd –
19,84/19,86; Со – 8,95/8,96; С – 16,57/16,55;
N – 5,81/5,79; Н – 4,18/4,14. FT-IR (KBr,
cm−1): 1636,1620, 1548 [νаs(СОО)]; 1410, 1329,
1312 [νs(СОО)]; 2943. 2362 [ν(С-Н)]; 3242,
3454 [ν(Н2О)]; 687, 620, 576, 510 [ν(МО)],
456[ν(МN)].
The analysis of the given data proves that
the neodymium complexes have the same type
of structure in solutions and in the solid state.
Preliminary preparation and cultivation of
Саndidа аlbiсапs ATCC 18804 strain to test the
antifungal properties of synthesized neodymi-
um ethylene diamine disuccinate complexes
was carried out using Sabouraud dextrose agar
according to the standard method according
to [30]. The concentration range of the studied
compounds was 1, 10 and 100 µM. The starting
solutions were prepared using a water-ethanol
mixture (2–4% ethanol), after which they were
autoclaved at 0.5 atm.
To obtain a suspension of microorganisms,
they were washed with a sterile physiological
solution and standardized to 0.5 units accord-
ing to the McFarland standard [31]. To stim-
ulate changes in morphogenesis and the for-
mation of specific cell forms of C. albisaps, in
particular hyphae, in parallel with the liquid
version of Sabouraud's medium, Spider medi-
um containing mannitol was used. Sabouraud
liquid nutrient medium contained peptone
10 g/l, glucose 40 g/l, yeast extract 5 g/l. The
composition of the Spider medium with the
addition of mannitol corresponded to the fol-
lowing: meat-peptone broth 20 g, mannitol
20 g, K2HPO4 4 g, distilled water 1 l.
0.05 ml of the culture of the microorganism
was introduced into the wells of a sterile tab-
let containing 1.0 ml each of Saburo and Spy-
der liquid nutrient mediums, as well as corre-
sponding solutions of the studied compounds
(Fig. 3).
а b
Fig. 3 – General view of the tablet in which Candida albicans was cultivated (Sabureau or Spider medium): a
– polystyrene tablet; b – schematic arrangement of cells during cultivation.
Microorganisms were cultivated for 24–48 hours at a temperature of 370C, after which the
culture liquid containing the «suspension» culture of С. аlbiсапs was carefully removed from the
wells. Determination of the number of cells in the liquid medium was carried out using a
spectrophotometer «µQuant» BioTek at a wavelength of 540 nm, calculating the value of the optical
density in CFU/ml (CFU – colony-forming units)) using the appropriate calibration curve. Cultures
of the microorganism under study, grown in similar conditions with the addition of H4EDDS of the
appropriate concentration, served as controls After that, the wells of the tablets were washed with
physiological solution and filled with 96% ethyl alcohol, which fixed the biofilm formed by S.
albisaps. After 10 minutes, the alcohol was removed and the tablet was left to dry in the air. An
aqueous solution of crystal violet (0.1%) was used to stain the cells that make up the biofilm, which
was poured into the wells of the tablet and left for 10–20 minutes. For the quantitative analysis of the
intensity of biofilm formation, a dye was isolated that absorbed the cells, and the optical density of
the resulting solution was determined. An aqueous solution containing dodecyl sulfate and sodium
hydroxide was used for cell lysis. Cell lysis was performed for 60 min. The results were recorded
using a BioTek µQuant spectrophotometer at a wavelength of 592 nm. To obtain reliable results, all
experiments were performed in 5 repetitions. The Student's t-test [32] was used in the comparative
analysis of research results. A difference of p≤0.05 was considered significant.
The sensitivity of various morphological forms of Candida albicans to neodymium
complexes with ethylenediaminedisuccinate: NdEDDS (I), NdEDDSZn (II) NdEDDSСo (III) was
studied. The development of Candida albicans in vivo can take place in the form of several
morphological forms: in the form of budding yeast, pseudohyphae, and true hyphae [30]. The switch
between the yeast-like form and hyphae depends on various factors, but primarily on the composition
of the nutrient medium. Despite the fact that recent studies have shown that the «yeast-hyphae»
transition does not always occur during the development of systemic candidiasis, such dimorphism is
still considered as one of the factors of pathogenicity of S. albicans. [33]. In addition, the formation
of hyphae is necessary for C. albicans to avoid phagocytosis, penetration into body tissues, and also
to colonize medical devices by forming a biofilm [34]. The search for new compounds, as well as
elucidation of the mechanisms of resistance development of S. albicans during biofilm formation, is
one of the most urgent areas of research that will significantly increase the success of antibacterial
therapy [35].
At the first stage of the work, the antifungal activity of the studied compounds was
determined in relation to the planktonic culture of C. аlbiсапs, which contains cells of the same size
and physiological state (Fig. 4, 5). Comparing the inhibitory effect of the «Сontrol» (С=Н4EDDS)
Fig. 3 – General view of the tablet in which Candida albicans was cultivated (Sabureau or Spider
medium): a – polystyrene tablet; b – schematic arrangement of cells during cultivation.
92 ISSN 2708-129X. Укр. хім. журн., 2023
СOMPLEXES OF Nd(III) AND 3d-METALS BASED ON ETHYLENEDIAMINEDISUCCINIC ACID
AS POTENTIAL ANTIFUNGAL AGENTS.INORGANIC CHEMISTRY
Microorganisms were cultivated for 24–
48 hours at a temperature of 370C, after which
the culture liquid containing the «suspension»
culture of С. аlbiсапs was carefully removed
from the wells. Determination of the number
of cells in the liquid medium was carried out
using a spectrophotometer «µQuant» BioTek at
a wavelength of 540 nm, calculating the value
of the optical density in CFU/ml (CFU – colo
ny-forming units)) using the appropriate ca
libration curve. Cultures of the microorga
nism under study, grown in similar conditions
with the addition of H4EDDS of the appro-
priate concentration, served as controls Af-
ter that, the wells of the tablets were washed
with physiological solution and filled with 96%
ethyl alcohol, which fixed the biofilm formed
by S. albisaps. After 10 minutes, the alcohol
was removed and the tablet was left to dry in
the air. An aqueous solution of crystal violet
(0.1%) was used to stain the cells that make up
the biofilm, which was poured into the wells of
the tablet and left for 10–20 minutes. For the
quantitative analysis of the intensity of biofilm
formation, a dye was isolated that absorbed the
cells, and the optical density of the resulting
solution was determined. An aqueous solu-
tion containing dodecyl sulfate and sodium
hydroxide was used for cell lysis. Cell lysis was
performed for 60 min. The results were record-
ed using a BioTek µQuant spectrophotometer
at a wavelength of 592 nm. To obtain relia-
ble results, all experiments were performed
in 5 repetitions. The Student's t-test [32] was
used in the comparative analysis of research
results. A difference of p≤0.05 was considered
significant.
The sensitivity of various morphologi-
cal forms of Candida albicans to neodymium
complexes with ethylenediaminedisuccinate:
NdEDDS (I), NdEDDSZn (II) NdEDDSСo (III)
was studied. The development of Candida al-
bicans in vivo can take place in the form of
several morphological forms: in the form of
budding yeast, pseudohyphae, and true hy-
phae [30]. The switch between the yeast-like
form and hyphae depends on various factors,
but primarily on the composition of the nu-
trient medium. Despite the fact that recent
studies have shown that the «yeast-hyphae»
transition does not always occur during the
development of systemic candidiasis, such di-
morphism is still considered as one of the fac-
tors of pathogenicity of C. albicans [33]. In ad-
dition, the formation of hyphae is necessary for
C. albicans to avoid phagocytosis, penetration
into body tissues, and also to colonize medical
devices by forming a biofilm [34]. The search
for new compounds, as well as elucidation of
the mechanisms of resistance development of
S. albicans during biofilm formation, is one of
the most urgent areas of research that will sig-
nificantly increase the success of antibacterial
therapy [35].
At the first stage of the work, the antifungal
activity of the studied compounds was deter-
mined in relation to the planktonic culture of
C. аlbiсапs, which contains cells of the same
size and physiological state (Fig. 4, 5). Com-
paring the inhibitory effect of the «Сontrol»
(С=Н4EDDS) and neodymium complexes
based on it, it was established that the latter
were more effective against C. аlbiсапs cells at
all stages of cultivation in Saburo nutrient me-
dium (Fig. 4).
Neodymium-cobalt heterometallic complex
(III) at a concentration of 1 μM was the most
active, inhibiting the growth of C. аlbiсапs cells
in suspension culture by four times compared
to the control value. Lower concentrations of
93https://ucj.org.ua
Olena K. Trunova, Maria Yu. Rusakova, Oleksandra S. Berezhnytska, Oleksandr O. Rohovtsov, Tamara O. Makotryk UCJ № 10 / Vol. 89
Fig. 4 – Activity of NdІІІ complexes with H4EDDS against the planktonic culture
of Candida albicans cultivated in Saburo nutrient medium.
Fig. 5 – Activity of NdIII complexes against the planktonic culture
of Candida albicans cultivated in the Spider nutrient medium.
this complex had a less pronounced antimy-
cotic effect. Complexes I and II were char-
acterized by an antifungal effect, which was
about 50–55% compared to the Сontrol. When
the term of cultivation of the microorganism
was extended, the degree of inhibitory activi-
ty of all studied complexes decreased slightly,
accompanied by an increase in the number of
C. аlbiсапs cells in the suspension.
In the Spider nutrient medium, which
stimulated the formation of the hyphal form
of a yeast-like fungus, the effect of com-
plex compounds was also quite pronounced
(Fig. 5). At the same time, for complexes I and
II, the level of antifungal activity turned out
to be higher, by approximately 9–23%, com-
pared to the corresponding values in the Sa-
buro medium.
and neodymium complexes based on it, it was established that the latter were more effective against
C. аlbiсапscells at all stages of cultivation in Saburo nutrient medium (Fig. 4).
Fig. 4 – Activity of NdІІІ complexes with H4EDDS against the planktonic culture of Candida albicans
cultivated in Saburo nutrient medium.
Neodymium-cobalt heterometallic complex (III) at a concentration of 1 μM was the most
active, inhibiting the growth of C. аlbiсапscells in suspension culture by four times compared to the
control value. Lower concentrations of this complex had a less pronounced antimycotic effect.
Complexes I and II were characterized by an antifungal effect, which was about 50–55% compared
to the Сontrol. When the term of cultivation of the microorganism was extended, the degree of
inhibitory activity of all studied complexes decreased slightly, accompanied by an increase in the
number of C. аlbiсапscells in the suspension.
In the Spider nutrient medium, which stimulated the formation of the hyphal form of a yeast-
like fungus, the effect of complex compounds was also quite pronounced (Fig. 5). At the same time,
for complexes I and II, the level of antifungal activity turned out to be higher, by approximately 9–
23%, compared to the corresponding values in the Saburo medium.
Fig. 5. – Activity of NdIII complexes against the planktonic culture of Candida albicans cultivated in the
Spider nutrient medium.
With the continuation of cultivation of C. аlbiсапs in the Spider medium for up to 48 hours, the
activity of the studied complexes practically did not change. For complex III, on the contrary, it
increased: on average, it was about 35–50% of the control value. It was also recorded that complexes
II and III at 48 hours of cultivation of C. аlbiсапs were more active at the lowest concentration of
0.01 µM.
Therefore, in the course of the research, it was found that the sensitivity of the cells, which
are part of the suspension culture, is quite pronounced and turns out to be greater to the minimum
concentrations of the compounds. Obviously, this is due to the nature of the interaction of
complexonate molecules with C. аlbiсапs cells. It was also determined that the variant of the
and neodymium complexes based on it, it was established that the latter were more effective against
C. аlbiсапscells at all stages of cultivation in Saburo nutrient medium (Fig. 4).
Fig. 4 – Activity of NdІІІ complexes with H4EDDS against the planktonic culture of Candida albicans
cultivated in Saburo nutrient medium.
Neodymium-cobalt heterometallic complex (III) at a concentration of 1 μM was the most
active, inhibiting the growth of C. аlbiсапscells in suspension culture by four times compared to the
control value. Lower concentrations of this complex had a less pronounced antimycotic effect.
Complexes I and II were characterized by an antifungal effect, which was about 50–55% compared
to the Сontrol. When the term of cultivation of the microorganism was extended, the degree of
inhibitory activity of all studied complexes decreased slightly, accompanied by an increase in the
number of C. аlbiсапscells in the suspension.
In the Spider nutrient medium, which stimulated the formation of the hyphal form of a yeast-
like fungus, the effect of complex compounds was also quite pronounced (Fig. 5). At the same time,
for complexes I and II, the level of antifungal activity turned out to be higher, by approximately 9–
23%, compared to the corresponding values in the Saburo medium.
Fig. 5. – Activity of NdIII complexes against the planktonic culture of Candida albicans cultivated in the
Spider nutrient medium.
With the continuation of cultivation of C. аlbiсапs in the Spider medium for up to 48 hours, the
activity of the studied complexes practically did not change. For complex III, on the contrary, it
increased: on average, it was about 35–50% of the control value. It was also recorded that complexes
II and III at 48 hours of cultivation of C. аlbiсапs were more active at the lowest concentration of
0.01 µM.
Therefore, in the course of the research, it was found that the sensitivity of the cells, which
are part of the suspension culture, is quite pronounced and turns out to be greater to the minimum
concentrations of the compounds. Obviously, this is due to the nature of the interaction of
complexonate molecules with C. аlbiсапs cells. It was also determined that the variant of the
94 ISSN 2708-129X. Укр. хім. журн., 2023
СOMPLEXES OF Nd(III) AND 3d-METALS BASED ON ETHYLENEDIAMINEDISUCCINIC ACID
AS POTENTIAL ANTIFUNGAL AGENTS.INORGANIC CHEMISTRY
With the continuation of cultivation of
C. аlbiсапs in the Spider medium for up to
48 hours, the activity of the studied complex-
es practically did not change. For complex III,
on the contrary, it increased: on average, it was
about 35–50% of the control value. It was also
recorded that complexes II and III at 48 hours
of cultivation of C. аlbiсапs were more active at
the lowest concentration of 0.01 µM.
Therefore, in the course of the research, it
was found that the sensitivity of the cells, which
are part of the suspension culture, is quite pro-
nounced and turns out to be greater to the
minimum concentrations of the compounds.
Obviously, this is due to the nature of the inter-
action of complexonate molecules with C. аl-
biсапs cells. It was also determined that the
variant of the environment and, accordingly,
the predominant form of development of the
microorganism do not have a significant effect
on the effectiveness of the studied compounds.
According to numerous studies, C. аlbiсапs
as part of a biofilm is a less sensitive microor-
ganism to the action of antimycotic drugs com-
pared to plankton culture cells. In the work at
the second stage, the sensitivity of the cells of
the biofilm, which was formed in the Saburo
and Spyder media, to the action of the studied
complexes was determined (Fig. 6, а, b).
As for ethylenediaminedisuccinic acid, i.e.
Сontrol, this compound practically did not
show fungicidal activity in any version of bio-
film cultivation.
In the medium of Sabouro cells, the biofilm
consisted mainly of yeast-like cells, the part of
hyphal elements did not exceed 15–20% of the
total mass of the formation. In the experiment,
it was established that the studied complexes
practically did not affect the development of
this version of the biofilm. In this case, the re-
duction of microorganisms in the composition
of the association did not exceed 20–25% of
the control value. Another feature of the action
of the studied complexes was the preservation
of the level of antifungal activity, or its increase
on the second day of biofilm cultivation.
The biofilm that was formed in Saburo nu-
trient medium contained mostly cells in the
form of hyphae: almost 80% of the total num-
ber of structural elements (Fig. 6, b).
In contrast to the variant of the biofilm in
the Saburo environment, as well as the Сontrol,
the studied synthetic complexes in the Spider
environment led to 95% of the cell death in the
biofilm composition. At the same time, com-
pounds II and III turned out to be the most
active: at lower concentrations, the inhibitory
activity against the C. аlbiсапsass ociation was
higher. It was also determined that in most
concentrations the exposure level of the com-
pounds was maintained for 48 hours.
Compound I was less effective: the level of
its antifungal activity was approximately 50%
compared to the control. Only in the case of
0.1 μM and 1 μM during 24 h of cultivation, a
more pronounced inhibition of biofilm forma-
tion in the Spider medium was noted.
In general, the investigated complexes were
characterized by a significantly greater effect
on the cells of the biofilm formed in the Spi-
der nutrient medium, that is, on the hyphal
form of C. albicans development. Therefore,
the hyphal elements were more sensitive to
the action of the studied compounds than the
yeast-like elements of C. albicans. When using
almost all complexes, both in the early stages
of association cultivation and later stages, in-
hibition of the biofilm formation process was
observed. As for yeast-like elements, more
pronounced antifungal activity of the studi
ed compounds was observed at later stages of
biofilm formation.
95https://ucj.org.ua
Olena K. Trunova, Maria Yu. Rusakova, Oleksandra S. Berezhnytska, Oleksandr O. Rohovtsov, Tamara O. Makotryk UCJ № 10 / Vol. 89
Fig. 6 – Activity of NdIII complexes with H4EDDS against Candida albicans cells, which are part
of the biofilm, during cultivation in Saburo (a) and Spider (b) media.
environment and, accordingly, the predominant form of development of the microorganism do not
have a significant effect on the effectiveness of the studied compounds.
According to numerous studies, C. аlbiсапs as part of a biofilm is a less sensitive
microorganism to the action of antimycotic drugs compared to plankton culture cells. In the work at
the second stage, the sensitivity of the cells of the biofilm, which was formed in the Saburo and
Spyder media, to the action of the studied complexes was determined (Fig. 6, а, b).
As for ethylenediaminedisuccinic acid, i.e. Сontrol, this compound practically did not show
fungicidal activity in any version of biofilm cultivation.
In the medium of Sabouro cells, the biofilm consisted mainly of yeast-like cells, the part of
hyphal elements did not exceed 15–20% of the total mass of the formation. In the experiment, it was
established that the studied complexes practically did not affect the development of this version of
the biofilm. In this case, the reduction of microorganisms in the composition of the association did
not exceed 20–25% of the control value. Another feature of the action of the studied complexes was
the preservation of the level of antifungal activity, or its increase on the second day of biofilm
cultivation.
The biofilm that was formed in Saburo nutrient medium contained mostly cells in the form of
hyphae: almost 80% of the total number of structural elements (Fig. 6, b).
Fig. 6 – Activity of NdIII complexes with H4EDDS against Candida albicans cells, which are part of the
biofilm, during cultivation in Saburo (a) and Spider (b) media.
In contrast to the variant of the biofilm in the Saburo environment, as well as the Сontrol, the studied
synthetic complexes in the Spider environment led to 95% of the cell death in the biofilm
composition. At the same time, compounds II and III turned out to be the most active: at lower
concentrations, the inhibitory activity against the C. аlbiсапsass ociation was higher. It was also
determined that in most concentrations the exposure level of the compounds was maintained for 48
hours.
environment and, accordingly, the predominant form of development of the microorganism do not
have a significant effect on the effectiveness of the studied compounds.
According to numerous studies, C. аlbiсапs as part of a biofilm is a less sensitive
microorganism to the action of antimycotic drugs compared to plankton culture cells. In the work at
the second stage, the sensitivity of the cells of the biofilm, which was formed in the Saburo and
Spyder media, to the action of the studied complexes was determined (Fig. 6, а, b).
As for ethylenediaminedisuccinic acid, i.e. Сontrol, this compound practically did not show
fungicidal activity in any version of biofilm cultivation.
In the medium of Sabouro cells, the biofilm consisted mainly of yeast-like cells, the part of
hyphal elements did not exceed 15–20% of the total mass of the formation. In the experiment, it was
established that the studied complexes practically did not affect the development of this version of
the biofilm. In this case, the reduction of microorganisms in the composition of the association did
not exceed 20–25% of the control value. Another feature of the action of the studied complexes was
the preservation of the level of antifungal activity, or its increase on the second day of biofilm
cultivation.
The biofilm that was formed in Saburo nutrient medium contained mostly cells in the form of
hyphae: almost 80% of the total number of structural elements (Fig. 6, b).
Fig. 6 – Activity of NdIII complexes with H4EDDS against Candida albicans cells, which are part of the
biofilm, during cultivation in Saburo (a) and Spider (b) media.
In contrast to the variant of the biofilm in the Saburo environment, as well as the Сontrol, the studied
synthetic complexes in the Spider environment led to 95% of the cell death in the biofilm
composition. At the same time, compounds II and III turned out to be the most active: at lower
concentrations, the inhibitory activity against the C. аlbiсапsass ociation was higher. It was also
determined that in most concentrations the exposure level of the compounds was maintained for 48
hours.
CONCLUSIONS.
1. f-d-Нeteronuclear ethylenediaminedisu
ccinate complexes of NdIII with CoII and ZnII
were obtained by the «block synthesis» me
thod. The complexes belong to the «closed»
type complexes, in which the ligand-complex-
on realizes the maximum dentateness to NdIII,
and the octahedral coordination sphere of the
3-d cation is formed by the carboxyl groups of
EDDS and intraspherical water molecules. The
coordination polyhedron of NdIII corresponds
to a square antiprism (C4v) with a LnIII coordi-
nation number of 8. In solutions and in the solid
state, the complexants have a similar structure.
2. Experiments were conducted to detect the
antifungal activity of heterometallic complexes
of neodymium and 3-d metals against phyto-
pathogenic strains of myxomycetes Сandida
аlbicans. It was shown that, regardless of the
environment (Spider or Saburо), the complex-
es show a significantly greater inhibitory effect
than ethylenediaminediansuccinic acid, which
served as a control. It was established that in Sa-
buro nutrient medium, all investigated complex-
es are more effective against C. аlbiсаns cells at
all stages of cultivation than in Spider medium.
96 ISSN 2708-129X. Укр. хім. журн., 2023
СOMPLEXES OF Nd(III) AND 3d-METALS BASED ON ETHYLENEDIAMINEDISUCCINIC ACID
AS POTENTIAL ANTIFUNGAL AGENTS.INORGANIC CHEMISTRY
3. The yeast-like form of the C. albicans cell
was characterized by sensitivity to complexes,
the level of which was 4–6 times higher than
the sensitivity to pure complexone. Hyphal ele
ments turned out to be more sensitive to the
action of the studied compounds than yeast-
like cells of C. albicans. Regarding yeast-like
elements, the antifungal activity of the studied
compounds was observed at the beginning of
biofilm formation, in contrast to hyphal forms,
which were more sensitive in the composition
of associations.
4. The most active was the heterometallic
complex NdEDDSCo with a concentration of
1 µM, which inhibited the growth of C. albi-
cans cells in suspension culture by 4 times
compared to the control value. Lower concen-
trations of this complex had a less pronounced
antimycotic effect. Other studied complexes
(NdEDDS and NdEDDSZn) were charac-
terized by an antifungal effect that was about
50–55% compared to the control (EDDS). The
variant of the environment and, accordingly,
the predominant form of development of the
microorganism do not have a significant effect
on the effectiveness of the studied compounds.
5. The complexes were characterized by a
significantly greater effect on the cells of the
biofilm formed in the Spider nutrient medi-
um, that is, on the hyphal form of microcete
development. Therefore, hyphal elements were
more sensitive to the action of complexes than
yeast-like elements of C. albicans. When using
almost all complexes, both in the early stages
of association cultivation and later stages, in-
hibition of the biofilm formation process was
observed. As for yeast-like elements, more
pronounced antifungal activity of the studied
compounds was observed at later stages of bio
film formation.
AKNOWLEDGEMENT. The work was
carried out with the financial support
of the National Academy of Scienc-
es of Ukraine within the state budget topic
322E «Creation of new hybrid, composite and
polymer materials doped with coordination
compounds of 3d- and 4f-metals based on
β-diketonate and carboxylate acyclic ligands».
The state registration number of the work is
0122U001299.
КОМПЛЕКСИ Nd(III) І 3d-МЕТАЛІВ НА ОСНОВІ
ЕТИЛЕНДИАМІНДИБУРШТИНОВОЇ КИСЛОТИ
ЯК ПОТЕНЦІЙНІ АНТИФУНГАЛЬНІ ЗАСОБИ
Олена К. Трунова1*, Марія Ю. Русакова2,
Олександра С. Бережницька1,3,
Олександр О. Роговцов1,
Тамара О. Макорик1
1Інститут загальної та неорганічної хімії
ім. В. І. Вернадського НАН України,
просп. Академіка Палладіна, 32/34,
Київ 03142, Україна;
2 Одеський національний університет
ім. І. І. Мечникова, вул. Дворянська, 2,
Одеса 65026, Україна;
3 Національний технічний університет
України «Київський політехнічний
інститут імені Ігоря Сікорського»,
просп. Перемоги, 37, Київ 03056, Україна
*e-mail: trelkon@gmail.com
Методом «блокового синтезу» отримано
f-d-гетероядерні етилендиаміндисуксинат-
ні комплекси NdIII з CoII та ZnІІ. Комплекси
належать до комплексів «закритого» типу,
в яких ліганд-комплексон реалізує макси-
мальну дентатність до NdIII, а октаедрична
координаційна сфера 3d-катіону утворена
карбоксильними групами EDDS та внутріш-
97https://ucj.org.ua
Olena K. Trunova, Maria Yu. Rusakova, Oleksandra S. Berezhnytska, Oleksandr O. Rohovtsov, Tamara O. Makotryk UCJ № 10 / Vol. 89
ньосферними молекулами води. Координа-
ційний поліедр NdIII відповідає квадратній
антипризмі (C4v) із координаційним числом
LnIII 8. У розчинах і твердому стані комп-
лексанти мають близьку будову. Проведено
дослідження чутливості різних морфоло-
гічних форм Candida albicans до комплек-
сів неодиму з етилендиаміндисукцинатом:
NdEDDS(I), NdEDDSZn(II) NdEDDSСo(III)
у середовищах Сабуро та Спайдер. Штам
Candida albicans АТСС 18804 отримано з
музею культур мікроорганізмів кафедри
мікробіології, вірусології та біотехнології
ОНУ ім. І. І. Мечникова. Показано, що не-
залежно від середовища комплекси виявля-
ють значно більший пригнічуючий ефект,
ніж етилендиаміндибурштинова кислота,
яка слугувала як контроль. Встановлено,
що у поживному середовищі Сабуро всі до-
сліджені комплекси є більш дієвими щодо
клітин C. аlbiсаns на всіх стадіях культиву-
вання, ніж у середовищі Спайдер. Дріжджо-
подібна форма клітини C. albicans виявляла
чутливість до комплексів, рівень якої у 4–6
разів був вищим, ніж чутливість до чистого
комплексону. Гіфальні елементи виявилися
більш чутливими до дії досліджуваних спо-
лук, ніж дріжджоподібні клітини C. albicans.
Щодо дріжджоподібних елементів, то анти-
фунгальну активність досліджуваних спо-
лук спостерігали на початку формування
біоплівки на відміну від гіфальних форм, які
виявилися більш чутливими у складі асоці-
ацій. Найбільш активним виявився гетеро-
металічний комплекс NdEDDSСo з концен-
трацією 1 мкM, який пригнічував у 4 рази
ріст клітин C. albicans у суспензійній куль-
турі порівняно з контрольним значенням.
Менші концентрації цього комплексу мали
менш виражену антимікотичну дію. Іншим
досліджуваним комплексам (NdEDDS та
NdEDDSZn) притаманний антифунгаль-
ний ефект, який становив близько 50–55 %
порівняно з контролем (EDDS). Варіант се-
редовища та відповідно переважна форма
розвитку мікроорганізму не мають суттє-
вого впливу на ефективність досліджува-
них сполук. Комплекси здійснюють суттєво
більший вплив на клітини біоплівки, яка
утворювалася у поживному середовищі
Спайдер, тобто на гіфальну форму розвитку
мікроцетів. Отже, гіфальні елементи вияви-
лися більш чутливими до дії комплексів, ніж
дріжджоподібні елементи C. albicans. При
використанні практично всіх комплексів, як
на ранніх стадіях культивування асоціацій,
так й на більш пізніх, спостерігали гальму-
вання процесу утворення біоплівки. Щодо
дріжджоподібних елементів, то більш вира-
жену антифунгальну активність досліджу-
ваних сполук спостерігали на більш пізніх
стадіях формування біоплівки.
Ключові слова: етилендиаміндисукци-
натні комплекси, неодим, кобальт(ІІ), цинк
(ІІ), антифунгальні властивості.
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Стаття надійшла 12.11.2023.
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| id | oai:ojs2.1444248.nisspano.web.hosting-test.net:article-592 |
| institution | Ukrainian Chemistry Journal |
| keywords_txt_mv | keywords |
| language | English |
| last_indexed | 2026-07-23T01:10:52Z |
| publishDate | 2023 |
| publisher | V.I.Vernadsky Institute of General and Inorganic Chemistry |
| record_format | ojs |
| resource_txt_mv | ucjorgua/30/d4fb41166d676bb9e1d04a21f01d8030.pdf |
| spelling | oai:ojs2.1444248.nisspano.web.hosting-test.net:article-5922026-07-22T08:23:52Z СOMPLEXES OF Nd(III) AND 3d-METALS BASED ON ETHYLENEDIAMINEDISUCCINIC ACID AS POTENTIAL ANTIFUNGAL AGENTS Trunova, Olena Berezhnytska , Оleksandra Rohovtsov , Oleksandr Makotryk, Tamara Rusakova, Mariya ethylenediaminedisuccinates complexes, neodymium, cobalt (II), zinc (ІІ), antifungal properties. Neodymium heterometallic complexes [(NdМIIEDDS)(H2O)6]∙n2H2O (МII=Zn, Co; n = 3; 2) were synthesized by the «block» synthesis method using protonated ethylenediaminedisuccinate of the 3-d metal and NdIII nitrate. The complexes were characterized by spectroscopic methods (UV-VIS electronic absorption spectroscopy and FT-IR) and elemental analysis. It is shown that the f-d-complexes belong to the «folded» type complexes, in which the ligand-EDDS realizes the maximum dentateness to NdIII, and the coordination sphere of the 3-d cation is formed by chain carboxyl groups of EDDS and intraspherical water molecules. At the same time, the cations of 3d metals are in a distorted octahedral environment, and the coordination polyhedron of the neodymium ion corresponds to a square antiprism (C4v) with the coordination number NdIII = 8. In solutions and in the solid state, the complexes have the same type of structure. The sensitivity of various morphological forms of Candida albicans in Spider and Saburo media to neodymium complexes NdIII with ethylene diamine disuccinate: NdEDDS (I), NdEDDSZn (II) NdEDDSСo (III) in the range of concentrations of the studied compounds 1; 10 and 100 μM was studied. It is shown that the antifungal properties of the complexes vary in the range NdEDDSСo> NdEDDSZn ≥ NdEDDS. The inhibition index of C. albicans in the composition of the biofilm in the Saburo medium under the action of the complexes was 20–25% of the control value, and in the Spider medium the complexes led to 95% of cell death. V.I.Vernadsky Institute of General and Inorganic Chemistry 2023-11-24 Article Article Inorganic Chemistry Неорганическая химия Неорганічна хімія application/pdf https://ucj.org.ua/index.php/journal/article/view/592 10.33609/2708-129X.89.10.2023.85-99 Ukrainian Chemistry Journal; Vol. 89 No. 10 (2023): Ukrainian Chemistry Journal; 85-99 Украинский химический журнал; ##issue.vol## 89 ##issue.no## 10 (2023): Ukrainian Chemistry Journal; 85-99 Український хімічний журнал; Том 89 № 10 (2023): Український хімічний журнал; 85-99 2708-129X 2708-1281 en https://ucj.org.ua/index.php/journal/article/view/592/303 Copyright (c) 2023 Olena Trunova, Оleksandra Berezhnytska , Oleksandr Rohovtsov , Tamara Makotryk, Mariya Rusakova https://creativecommons.org/licenses/by-nc/4.0 |
| spellingShingle | Trunova, Olena Berezhnytska , Оleksandra Rohovtsov , Oleksandr Makotryk, Tamara Rusakova, Mariya СOMPLEXES OF Nd(III) AND 3d-METALS BASED ON ETHYLENEDIAMINEDISUCCINIC ACID AS POTENTIAL ANTIFUNGAL AGENTS |
| title | СOMPLEXES OF Nd(III) AND 3d-METALS BASED ON ETHYLENEDIAMINEDISUCCINIC ACID AS POTENTIAL ANTIFUNGAL AGENTS |
| title_full | СOMPLEXES OF Nd(III) AND 3d-METALS BASED ON ETHYLENEDIAMINEDISUCCINIC ACID AS POTENTIAL ANTIFUNGAL AGENTS |
| title_fullStr | СOMPLEXES OF Nd(III) AND 3d-METALS BASED ON ETHYLENEDIAMINEDISUCCINIC ACID AS POTENTIAL ANTIFUNGAL AGENTS |
| title_full_unstemmed | СOMPLEXES OF Nd(III) AND 3d-METALS BASED ON ETHYLENEDIAMINEDISUCCINIC ACID AS POTENTIAL ANTIFUNGAL AGENTS |
| title_short | СOMPLEXES OF Nd(III) AND 3d-METALS BASED ON ETHYLENEDIAMINEDISUCCINIC ACID AS POTENTIAL ANTIFUNGAL AGENTS |
| title_sort | сomplexes of nd(iii) and 3d-metals based on ethylenediaminedisuccinic acid as potential antifungal agents |
| topic_facet | ethylenediaminedisuccinates complexes neodymium cobalt (II) zinc (ІІ) antifungal properties. |
| url | https://ucj.org.ua/index.php/journal/article/view/592 |
| work_keys_str_mv | AT trunovaolena somplexesofndiiiand3dmetalsbasedonethylenediaminedisuccinicacidaspotentialantifungalagents AT berezhnytskaoleksandra somplexesofndiiiand3dmetalsbasedonethylenediaminedisuccinicacidaspotentialantifungalagents AT rohovtsovoleksandr somplexesofndiiiand3dmetalsbasedonethylenediaminedisuccinicacidaspotentialantifungalagents AT makotryktamara somplexesofndiiiand3dmetalsbasedonethylenediaminedisuccinicacidaspotentialantifungalagents AT rusakovamariya somplexesofndiiiand3dmetalsbasedonethylenediaminedisuccinicacidaspotentialantifungalagents |