Synthesis, characterization, and cytotoxicity of binuclear copper(II) complexes with tetradentate nitrogen-containing ligands bis-5-(2-pyridylmethylidene)-3,5-dihydro-4H-imidazol-4-ones

Article abstract of DOI:10.1016/j.poly.2018.04.005

A treatment of the N₄-type organic ligands containing two 5-(2-pyridylmethylidene)-2-thio-3,5-dihydro-4H-imidazol-4-one fragments linked by (CH₂)₂ bridges between the sulfur atoms with CuCl₂ affords to binuclear

Full text of DOI:10.1016/j.poly.2018.04.005

Accepted Manuscript
Synthesis, Characterization, and Cytotoxicity of Binuclear Copper(II) Com-
plexes with Tetradentate Nitrogen-Containing Ligands bis-5-(2-Pyridylmethy-
lidene)-3,5-dihydro-4H-imidazol-4-ones
Elena K. Beloglazkina, Olga O. Krasnovskaya, Dmitry A. Guk, Viktor A.
Tafeenko, Anna A. Moiseeva, Nikolai V. Zyk, Alexander G. Majouga
PII:
S0277-5387(18)30172-4
https://doi.org/10.1016/j.poly.2018.04.005
POLY 13106
DOI:
Reference:
Polyhedron
To appear in:
Received Date:
Accepted Date:
4 March 2018
3 April 2018
Please cite this article as: E.K. Beloglazkina, O.O. Krasnovskaya, D.A. Guk, V.A. Tafeenko, A.A. Moiseeva, N.V.
Zyk, A.G. Majouga, Synthesis, Characterization, and Cytotoxicity of Binuclear Copper(II) Complexes with
Tetradentate Nitrogen-Containing Ligands bis-5-(2-Pyridylmethylidene)-3,5-dihydro-4H-imidazol-4-ones,
Polyhedron (2018), doi: https://doi.org/10.1016/j.poly.2018.04.005
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Synthesis, Characterization, and Cytotoxicity of Binuclear Copper(II)
Complexes with Tetradentate Nitrogen-Containing Ligands bis-5-(2-
Pyridylmethylidene)-3,5-dihydro-4H-imidazol-4-ones
Elena K. Beloglazkina*, Olga O. Krasnovskaya, Dmitry A. Guk, Viktor A. Tafeenko, Anna A.
Moiseeva, Nikolai V. Zyk and Alexander G. Majouga
M.V. Lomonosov Moscow State University, Chemistry Department, Moscow, Russia 119992
bel@org.chem.msu.ru
Abstract
A treatment of the N4-type organic ligands containing two 5-(2-pyridylmethylidene)-2-thio-3,5-
dihydro-4H-imidazol-4-one fragments linked by (CH2)2 bridges between the sulfur atoms with
.
CuCl2 affords to binuclear copper(II) complexes of corresponding ligands. A series of copper
complexes with L(CuCl2)2 composition were isolated and characterized by elemental analysis,
UV-vis spectra and cyclic voltammetry; the X-ray crystal structures of four synthesized
complexes showed the distored tetrahedral environment of both copper atoms; Cu-Cu distances
is about 4.5 Å, which is confirming the absence of interaction between copper ions.
Electrochemical studies of complexes demonstrated the simultaneous reduction of each of the
coordinated copper atoms at a potential of +0.39–+0.43 V.
Keywords: 2-alkylthio-3,5-dihydro-4Н-imidazole-4-ones; binuclear copper(II) complexes; X-
ray diffraction, cyclic voltammetry.
Introduction
The design and synthesis of complexes featuring two copper centers held in close
proximity has received considerable attention because of the potential application of such
complexes as catalysts that function through the concerted action of multiple metal centres (see,
for example, [1-3]), magnetic material due to possibility of magnetic exchange interactions
between paramagnetic metal centres [4-6], as selective receptors for different substrates [7-10]
and also as low-molecular models of metalloenzyme [11, 12]. Metalloproteins, requiring a metal
ion for their activity, are one of the most important class of enzymes. A specialized group of the
metalloproteins is the binuclear metalloenzymes, containing two closely spaced metals ions (≤4
Å apart) that are attached to the polypeptide scaffold. Binuclear copper complexes have some
features that make them favorable targets for drug design and discovery. Firstly, the metals are
highly charged; therefore strong ionic attractions to an inhibitor are feasible. Secondly,

metalloenzymes constitutes much less than one percent of an organism’s complete proteome;
this reduced risk the of off-target inhibition [13].
Copper is an essential element for all organisms living in oxygen-containing
environment. This redox active metal easily converts oxidation state from a Cu(I) to Cu(II), and
vice versa, as in chemical reactions and in physiological conditions [14]. Copper is essential for
the function of several enzymes and proteins, such as cytochrome oxidase, Zn, Cu-superoxide
dismutase, lysyl oxidase, tyrosinase, and dopamine-b-monooxygenase [14-16].
During the past decades copper complexes have gained a growing interest as
pharmaceuticals for the use as diagnostic agents or as chemotherapeutic drugs. Copper, as an
essential cofactor in a number of enzymes and physiological processes, may be less toxic than
non essential metals, such as platinum. At the current time, two copper complexes have reached
clinical assay, which paves the road to the first copper-based anticancer therapeutics [17]. Most
of the investigated anti-cancer copper coordination compounds belong to the family of copper(II)
complexes showing either five-coordinate environments comprising distorted square pyramidal
and trigonal bipyramidal geometries or distorted six-coordinate octahedral arrays. The majority
of these agents are mononuclear species, but there are few distinctive examples of dimeric
compounds exhibiting remarkable antitumor activity [18]. The anoxic character of cancer cells
promotes the reduction of Cu(II) to Cu(I), which is not possible in normal cells and thus provides
a therapeutic opportunity to target tumors [19]. The synthesis, design, and development of
copper complexes as anticancer agents have been presented in several reviews over the last
decade [18, 20-24].
We have recently synthesized and investigated a series of binuclear mixed valence
Cu(I,II) complexes containing substituted bis-5-(2-pyridylmethylidene)-3,5-dihydro-4H-
imidazol-4-ones as N4-coordinating ligands. These complexes are high cytotoxic for various cell
lines. We have found that these compounds did not intercalate DNA, inhibited number of
polymerases (telomerase predominantly), accumulated in the cell nucleus, and caused DNA
degradation [25]. In the work we describe the synthesis of new binuclear bis-5-
(pyridylmethylene)-2-thiohydantoin complexes Cu(II,II) complexes with isolated copper atoms
formed as the results of there ligand interaction with copper(II) chloride.
Experimental
All common reagents were purchased from commercial suppliers and used as received.
The melting points are uncorrected. 1H NMR spectra were recorded on a Bruker Avance recorder
1
(400 MHz for H) in DMSO-d6 or CDCl3. Chemical shifts are reported in parts per million
relative to the residual solvent signal. The IR spectra in nujol were recorded on a Perkin-Elmer

1430 spectrophotometer. Electronic spectra in 10-3 M DMF solution were obtained on a U2900
Hitachi UV–Vis spectrophotometer. High resolution mass spectra (HRMS) were recorded on an
Orbitrap Elite (Thermo Scientific) mass spectrometer with an IRET. To inject solutions with a
concentration of 0.1 to 9 μg/mL (in 1% formic acid in acetonitrile), direct injection into the ion
source using a syringe pump (5 μl/min) was used. The spray voltage was ± 3.5 kV, the
temperature of the capillary was 275ºC. Electrochemical measurements were performed on a IPC
Pro M potentiostat. Glassy-carbon (d = 2 mm) disks were used as the working electrodes, a 0.1
M Bu4NClO4 solution in DMF served as the supporting electrolyte, and Ag/AgCl/KCl(satur.)
was used as the reference electrode. The potential scan rates were 100 mV s–1 All measurements
were carried out under argon. The samples were dissolved in the pre-deaerated solvent.
Dimethylformamide (high purity grade) was purified by refluxing followed by successive
vacuum distillation over anhydrous CuSO4 and P2O5.
For single-crystal measurements of 4a, 4d, a suitable crystals was selected and tip-
mounted on a Bruker SMART diffractometer, Mo Kα radiation (0.71073 Å) platform with an
Apex 2-detector at 100 K. For compounds 4f, 4g the X-ray data was collected by using STOE
diffractometer Pilatus100K detector, focusing mirror collimation Cu Kα (1.54086 Å) radiation,
rotation method mode. STOE X-AREA software was used for cells refinement and data
reduction. Data collection and image processing was performed with X-Area 1.67 (STOE & Cie
GmbH, Darmstadt, Germany, 2013). Intensity data were scaled with LANA (part of X-Area) in
order to minimize differences of intensities of symmetry-equivalent reflections (multi-scan
method). The structures were solved and refined with SHELX program [26]. The non-hydrogen
atoms were refined by using the anisotropic full matrix least-square procedure. Molecular
geometry calculations were performed with the SHELX program, and the molecular graphics
were prepared by using DIAMOND software [27]. The crystal data one can see in the Table 1S
in Supplementary Information.
Synthesis of 3-substituted 2-thioxotetrahydro-4H-imidazol-4-ones (1) from glycine and
isothiocyanate (typical procedure). Glycine (1 eq.) was dissolved in a 1:1 water-pyridine
mixture. Then a 2 M sodium hydroxide solution was added to pH 9, and this pH was maintained
until the reaction was completed. The reaction mixture was warmed to 55 °C. At this
temperature, isothiocyanate (1.1 eq.) was added. The reaction mixture was stirred at 55 °C for 1
h, pH being monitored from time to time. Pyridine and excess of isothiocyanate were removed
by extraction with the same volume of toluene. Concentrated hydrochloric acid was added to the
aqueous phase to pH = 6-7 and the resulting solution was boiled 2.5 hours. The reaction mixture

was evaporated to half volume under reduced pressure and cooled to room temperature. The
formed precipitate was filtered off and recrystallized from methanol.
Synthesis of compounds 1-4e were described previously [28-31].
3-(But-2-yl)-2-thioxotetrahydro-4H-imidazol-4-one (1a). As a result of the reaction of
glycine (0.97 g, 7.9 mmol) and 2-butyl isothiocyanate (1 g, 1.1 mL, 8.7 mmol) 0.67 g (72%) of
1
compound 1a was obtained. M.p. 103 °C. H NMR (400 MHz, DMSO-d6, δ, ppm): 10.16 (bs,
1H, NH), 4.85 (m, 1H, -CH3CHCH2CH3), 4.05 (m, -CH2-), 1.95 (m, 1H, -CH3CHCH2CH3), 1.67
(m, 1H, -CH3CHCH2CH3), 1.35 (d, 3H, J = 6.91 Hz, CH3CH2CH2CH3), 0.79 (t, 3H, J = 7.08 Hz,
CH3CH2CH2CH3). IR (cm-1): 3180 (NH), 1730 (C=O). Calculated C, 48.83%; H, 6.97%; N,
16.27%; S-18.6%. C7H12N2OS. Found C, 48.79%; H. 6.91%; N. 15.88%; S, 18.95%.
(2-Methylbut-1-yl)-2-thioxotetrahydro-4H-imidazol-4-one (1b). As a result of the reaction
of glycine (0.528 g, 7 mmol) and (2-methylbutyl) isothiocyanate (1 g, 7.7 mmol) 1.1 g (90%) of
1
compound 1b was obtained. M.p. 116 °C. H NMR (400 MHz, DMSO-d6, δ, ppm): 10.15 (bs,
1H, NH), 4.15 (s, 2H, CH2), 3.49 (m, 2H, HCN), 1.95 (m, 1H, CH2CH3), 1.35 (m, 1H, CH2CH3),
1.05 (t, J = 7.45 Hz, 3H, CH3), 0.80 (d, J = 6.55 Hz, 3H, CH3). IR (cm-1): 3280 (NH), 1750
(C=O) Calculated C, 51.61; H, 7.52%; N, 15.05%; S, 17.2%. C7H12N2OS. Found C, 51.45%;
H, 7.44%; N, 15.00%; S, 16.88%.
3-Benzyl-2-thioxotetrahydro-4H-imidazol-4-one (1c). As a result of the reaction of glycine
(0.46 g, 6.1 mmol) and benzyl isothiocyanate (1 g, 0.9 mL, 6.7 mmol) 0.15 g (92%) of
1
compound 1c was obtained. M.p. 138 °C. H NMR (400 MHz, DMSO-d6, δ, ppm): 10.25 (bs,
1H, NH), 7.20-7.30 (m, 5H, Ph), 4.88 (s, 2H, HCN), 4.20 (s, 2H, CH2). IR (cm-1): 3280 (NH),
1750 (C=O). Calculated C, 58.25%; H, 4.85%; N, 13.59%; S, 15.56%. C10H10N2OS. Found C,
58.44%; H, 4.8%; N, 13.39%; S, 15.30%.
3-(2-Phenylethyl)-2-thioxotetrahydro-4H-imidazol-4-one (1d). As a result of the reaction
of glycine (0.44 g, 5.8 mmol) and 2-phenylethyl isothiocyanate (0.96 g, 6.2 mmol) 0.96 g (76%)
of compound 1d was obtained. M.p. 126 °C. 1H NMR (400 MHz, DMSO-d6, δ, ppm): 10.25 (bs,
1H, NH), 7.31 (d, 2H, J = 6.72 Hz, Ph), 7.20-7.25 (m, 3H, Ph), 4.11 (s, 2H, CH2), 3.85 (t, 2H, J =
7.34Hz, HCN), 2.86 (t, 2H, J = 7.41Hz, CH2-Ph). IR (cm-1): 3280 (NH), 1750 (C=O). Calculated
C, 60.0%; H, 5.45%; N, 12.72%; S,14.54%. C11H12N2OS. Found C, 60.31%; H, 5.61%; N,
12.81%; S, 14.49%.
3-Substituted 5-((Z)-2-pyridylmethylidene)-2-thiohydantoins 2a-е (typical procedure). 3-
Substituted 2-thiohydantoin 1a-d (1 eq.) was dissolved in a 2% ethanolic solution of KOH (1.2
eq.) with vigorous stirring. After complete dissolution of 2-thiohydantoin, (1 eq.) was added
dropwise and the reaction mixture was stirred for 12 h. The precipitate was filtered off and

dissolved in water. The solution was neutralized with vigorous stirring with dilute HCl to pH 7.
The formed precipitate was filtered off and washed with ethanol and then diethyl ether.
3-(2-Butyl)-5-((Z)-2-pyridylmethylidene)-2-thioxotetrahydro-4H-imidazol-4-one (2a). As
a result of the reaction of thiohydantoin 1a (0.5 g, 2.9 mmol) and 2-pyridinecarbaldehyde ( 0.34
1
g, 3.19 mmol) 0.96 g (76%) of compound 1d was obtained. M.p. 116 °C. H NMR (400 MHz,
DMSO-d6, δ, ppm):: 11.61 (bs, 1Н, NH), 8.73 (d, 1H, J = 5.48 Hz, Hα-Py), 7.90 (t, 1H, J = 7.68
Hz, Hβ-Py), 7.75 (d, 1H, J = 6.16 Hz, Hβ’-Py), 7.39 (t, 1H, J = 6.28 Hz, Hγ-Py), 6.67 (s, 1H,
=CH), 4.63 (m, 1H, CH3-CH-CH2-CH3), 2.03(m, 1H, CH3-CH-CH2-CH3), 1.72 (m, 1H, CH3-
CH- CH2-CH3), 1.41 (d, 3H, J = 5.89 Hz, CH3-CH- CH2-CH3), 0.76(t, 3H, J = 7.52 Hz, CH3-CH-
CH2-CH3). IR (cm-1): 3280 (NH), 1750 (C=O), 1600 (C=C). Calculated C, 59.77%; H, 5.74%;
N, 16.09%; S 12.26%. C13H15N3OS. Found C, 66.10%; H, 4.69%; N, 13.45%; S, 10.50%.
3-(2-Methylbutyl)-5-((Z)-2-pyridylmethylidene)-2-thioxotetrahydro-4H-imidazol-4-one
(2b). 1b (0.2 g, 1.1 mmol) and 2-pyridinecarbaldehyde ( 0.129 g, 1.2 mmol) 0.26 g (85%) of
1
compound 2b was obtained. M.p. 158 °C. H NMR (400 MHz, DMSO-d6, δ, ppm): 11.52 (bs,
1H, NH), 8.55 (m, Hα-Py), 7.90 (t, 1H, J = 7.79 Hz, H-Py), 7.78 (m, 1H, Hβ-Py), 7.38 (m, 1H,
Hγ-Py), 6.72 (s, 1H, =CH), 3.56 (m, 2H, CH2-CH(CH3)CH2CH3), 1.94 (m, 1Н, CH2-
CH(CH3)CH2СН3), 1.31 (m, 1H, CH2-CH(CH3)CH2СН3), 1.07 (m, 1H, CH2-CH(CH3)CH2СН3),
0.81 (m, 6H, CH2-CH(CH3)CH2СН3). IR (cm-1): 3290 (NH), 1750 (C=O), 1600 (C=C).
Calculated C, 61.09; H, 6.18%; N, 15.27%, S, 11.63. C14H17N3OS. Found C, 60.76%; H, 5.98%;
N, 15.04%; S, 11.57%.
3-Benzyl-5-((Z)-2-pyridylmethyidene)-2-thioxotetrahydro-4H-imidazol-4-one (2c). As a
result of the reaction of thiohydantoin 1c (0.3 g, 1.45 mmol) and 2-pyridinecarbaldehyde (0.171
1
g, 1.6 mmol) 0.4 g (95%) of compound 2c was obtained. M.p. 133 °C. H NMR (400 MHz,
DMSO-d6, δ, ppm): 11.81 (bs, 1H, NH) 8.77 (d, 1H, J = 4.38 Hz, Hα'-Py), 7.91 (td, 1H, J1 = 7.75
Hz, J2 = 1.46 Hz, Hβ-Py), 7.77 (d, 1H, J = 7.75 Hz, Hβ'-Py), 7.41 (dd, 1H, J1 = 4.79 Hz, J2 = 1.10
Hz, Hγ-Py), 7.34 (m, 3H, Ph), 7.29 (m, 2H, Ph) 6.76 (s, 1H, CH=), 5.03 (s, 2H, -CH2-Ph).
Calculated C, 65.08; H, 4.40%; N, 14.23%; S, 10.84. C16H13N3OS. Found C, 60.03%; H, 4. 55%;
N, 14.01%; S, 11.62%.
3-Phenylethyl-5-((Z)-2-pyridylmethylidene)-2-thioxotetrahydro-4H-imidazol-4-one (2d).
As a result of reaction of thiohydantoin 1d (0.185 g, 0.84 mmol) and 2-pyridinecarbaldehyde
(0.098 g, 0.92 mmol) 0.33 g (90%) of compound 2d was obtained. M.p. 143 °C (dec.) 1H NMR
(400 MHz, DMSO-d6, δ, ppm): 11.47 (bs, 1H, NH) 8.69 (d, 1H, J = 4.14 Hz, Hα'-Py), 7.76 (td,
1H, J1 = 7.96 Hz, J2 = 1.56 Hz, Hβ '), 3.42 (t, 2H, J = 7.69Hz, CH2), 3.06 (t, J = 7.70 Hz, 2H,
CH2). Calculated C, 66.01%; H, 4.85%; N, 13.59%; S, 10.35%. C17H15N3OS. Found C, 66.10%;
H, 4.69%; N, 13.45%; S, 10.50%.

3-(4-Ethoxyphenyl)-5-((Z)-2-pyridylmethylidene)-2-thioxotetrahydro-4H-imidazol-4-one
(2f). This compound was synthesized without isolation of thiohydantoins 1f. To a solution of 4-
ethoxyaniline (0.174 g, 1.27 mmol) in diethyl ether, ethyl isothiocyanatoacetate (0.184 g, 1.27
mmol) was added dropwise. Yhe resulting mixture was vigorously stirred overnight to obtain
white solid. The solid was filtered off, dried under reduced pressure and dissolved in 2% KOH
ethanol solution, than pyridine 2-carboxaldehyde (0.145 g, 1.35 mmol) was added dropwise.
After 3h stirring at room temperature the reaction mixture was diluted with water 1:1 and
acidified to pH 6 with 1M hydrochloric acid to give yellow precipitate. The yellow precipitate
was filtered off, washed with water, ethanol and diethyl ether. 0.305 g (74%) of Compound 2f
was obtained. M.p. 215 °C (dec.). HRMS: calculated for C17H14O3N3S (M-H)- 340.0756, found
340.0760; calculated for C17H16O3N3S+ (M+H)+ 342.0912, found 342.0909. 1H NMR (400 MHz,
DMSO-d6, δ, ppm): 8.75 (m, 1H, Hα'-Py) 7.88 (td, 1H, J1 = 1.65 Hz, J2 = 7.52 Hz, Hβ'-Py), 7.74
(d, 1H, J1 = 7.89 Hz, Hγ-Py), 7.38 (m, 1H, Hβ-Py), 7.26 (m, 2H, Hα, Hα'-Ph), 7.00 (m, 2H, Hβ,
Hβ'-Ph), 6.76 (s, 1H, CH=), 4.05 (q, 2H, J = 6.97 Hz, CH2), 1.32 (t, 3H, J = 6.97 Hz, CH3).
Calculated C, 62.75%; H, 4.65%; N, 12.91%; S, 9.85%. C17H15N3O2S. Found C, 63.00%; H,
4.50%; N, 13.08%; S, 9.88%.
3-(3,4-Dimethoxyphenyl)-5-((Z)-2-pyridylmethylidene)-2-thioxotetrahydro-4H-imidazol-
4-one (2g). This compound was obtained by a procedure analogous to 2f. As a result of reaction
of 3,4-dimethoxyaniline (0.182 g, 1.19 mmol), ethyl isocyanatoacetate (0.172 g, 1.19 mmol) and
2-pyridinecarbaldehyde (0.136 g, 1.27 mmol) 0.364 g (89%) of compound 2g was obtained. M.p.
206 °C. 2f: HRMS: calculated for C17H14O2N3S (M-H)- 324.0807, found 324.0812; calculated
for C17H16O2N3S (M+H)+ 326.0963, found 326.0960. 1H NMR (400 MHz, CDCl3, δ, ppm): 8.70
(d, 1H, J = 4.95 Hz, Hα'-Py) 7.78 (td, 1H, J1 = 1.65 Hz, J2 = 7.70 Hz, Hβ'-Py), 7.44 (d, 1H, J1 =
7.89 Hz, Hγ-Py), 7.28 (m, 1H, Hβ-Py), 6.95 (m, 2H, Hα, Hα'-Ph), 6.85 (m, 1H, Hβ-Ph), 6.60 (s,
1H, CH=), 3.91 (s, 3H, m-CH3), 3.89 (s, 3H, p-CH3). Calculated C, 59.81%; H, 4.43%; N,
12.31%; S, 9.35%. C17H15N3O3S. Found C, 59.38%; H, 4.18%; N, 12.33%; S, 9.29%.
Reactions of 5-((Z)-2-pyridylmethylidene)-2-thiohydantoins 2a-g witb dibromoethane
(typical procedure). 1,2-Dibromoethane (1 eq.) was added for 5 min with stirring to a mixture
of compound 2a-g (2 eq.) and dry K2CO3 (> 2 eq.) in DMF (10-15 mL) at –10 °C. The reaction
mixture was stirred for 2 h at –10 °C and then for 2 h at room temperature. Water (50 mL) was
added to the mixture. A formed precipitate was filtered off, washed with water, and
recrystallized from ethyl acetate.
(5Z,5´Z)-2,2´-(Ethane-1,2-diyldisulfanyldiyl)bis(3-(but-2-yl)-5-(2-pyridylmethylidene)-
3,5-dihydro-4H-imidazol-4-one) (3a), As a result of the reaction of thiohydantoin 2a (0.2 g, 0.76

mmol) with 0.033 mL (0.072 g, 0.14 mmol) of 1,2-dibromoethane and 0.16 g (1.1 mmol) of
1
K2CO3 0.25 g (61%) of compound 3a was obtained. M.p. 173 °C. H NMR (400 MHz, DMSO-
d6, δ, ppm): 8.75 (bs, 2H, Hα'-Py) 8.65 (d, 2H, J = 7.85 Hz, Hβ'-Py), 7.73 (m, 2 H, Hβ-Py), 7.26
(m, 2H, Hγ-Py), 7.07 (s, 2H, CH=), 3.96 (m, 6H), 1.98 (m, 4H), 1.50 (d, 6H, J = 6.87 Hz,
CH3CHCH2CH3), 0.93 (t, 6H, J = 7.13 Hz, CH3CHCH2CH3). IR (cm-1): 3400-3300 (OH), 1710
(C=O), 1670 (C=N), 1640 (C=C). Calculated C, 59.36%; H, 6.00%; N, 14.84%; S, 11.3%.
.
C36H32N6O2S2 H2O. Found C, 58.91%; H, 5.85%; N, 14.28%; S, 10.7%.
(5Z,5´Z)-2,2´-(Ethane-1,2-diyldisulfanyldiyl)bis(3-(2-methylbuthyl)-5-(2-
pyridylmethylidene)-3,5-dihydro-4H-imidazol-4-one) (3b). As a result of the reaction of
thiohydantoin 2b (0.2 g, 0.76 mmol) with 0.033 mL (0.072 g, 0.38 mmol) of 1,2-dibromoethane
1
and 0.31 g (2.3 mmol) of K2CO3, 0.54 g (56%) of compound 2b was obtained. M.p. 103° C. H
NMR (400 MHz, DMSO-d6, δ, ppm): 8.69 (m, 4H, Py), 7.68 (t, 2H, Py), 7.23 (t, 1H, J = 7.64Hz,
Py) , 7.12 (s, 1H, CH =), 3.94 (s, 1H, CH2), 3.49 (s, 4H, HCS), 1.93 (m, 2H), 1.45 (m, 2H), 1.22
(m, 2H), 0.94 (m, 12H, CH2-CH(CH3)CH2CH3). IR (cm-1): 1710 (C=O), 1670 (C=N), 1640
(C=C). Calculated C, 62.5%; H, 6.25%; N, 14.58%. C30H36N6O2S2. Found C, 62.40%; H, 6.36%;
N, 14.32%.
(5Z,5´Z)-2,2´-(Ethane-1,2-diyldisulfanyldiyl)bis(3-benzyl-5-(2-pyridylmethylidene)-3,5-
dihydro-4H-imidazol-4-one) (3c). As a result of the reaction of thiohydantoin 2c (0.15 g, 0.52
mmol) with 0.023 mL (0.048 g, 0.26 mmol) of 1,2-dibromoethane and 0.21 g (1.5 mmol) of
K2CO3, 0.2 g (61%) of compound 3c was obtained. M.p. 173 °C. 1H NMR (400 MHz, CDCl3, δ,
ppm): 8.65 (m, 4H, Hα'Hβ'-Py) 7.57 (td, 2H, J1 = 7.64 Hz, J2 = 1.67 Hz, Hβ-Py) 7.35 (m, 10H,
Ph), 7.19 (t, 2H, J = 4.66 Hz, Hγ-Py), 7.16 (s, 2H, CH=), 4.81 (s, 4H, HCS), 3.83 (s, 4H,
CH2Ph). IR (cm-1): 3450-3250 (OH), 1710 (C=O), 1670 (C=N), 1640 (C=C). Calculated C,
.
64.35%; H, 4.41%; N, 13.24%; S, 10.09%. C34H30N6O3S2 H2O. Found C, 64.52%; H, 4.49%; N,
12.84%; S, 9.59%.
(5Z,5´Z)-2,2´-(Ethane-1,2-diyldisulfanyldiyl)bis(3-(2-phenylethyl)-5-(2-
pyridylmethylidene)-3,5-dihydro-4H-imidazol-4-one) (3d). As a result of the reaction of 0.1 g
(0.28 mmol) of thiohydantoin 2d with 0.012 mL (0.027 g, 0.14 mmol) of 1,2-dibromoethane and
0.06 g (0.42 mmol) of K2CO3, 0.05 g (54%) of compound 3d was obtained. M.p. 175 °C (dec.).
1H NMR (400 MHz, CDCl3, δ, ppm): 8.82 (d, 2H, J = 8.12 Hz, Hα'-Py), 8.45 (d, 2H, J = 8.0 Hz,
Hβ-Py), 7.71 (td, 2H, J1 = 8.03 Hz, J2 = 1.58 Hz, Hβ '), 7.26 (m, 8H, Ph), 7.20 (t, 2H, J = 7.24
Hz, Hγ-Ph), 7.10 (t, 2H, J = 6.10 Hz, Hγ-Py), 6.67 (s, 2H, CH=), 4.02 (t, 4H, J = 4.51 Hz, HCN),
3.81 (s, 4H, HCS), 2.91 (t, J = 2.81Hz, 4H, CH2-Ph). IR (cm-1): 3450-3250 (OH), 1710 (C=O),
1670 (C=N), 1640 (C=C). Calculated C, 64.38%; H, 5.21%; N, 12.51%; S, 9.13%.
.
C36H32N6O2S2 1.5H2O. Found C, 64.38%; H, 5.21%; N, 12.51%; S, 8.88%.

(5Z,5´Z)-2,2´-(Ethane-1,2-diyldisulfanyldiyl)bis(3-(4-ethoxyphenyl)-5-(2-
pyridylmethylidene)-3,5-dihydro-4H-imidazol-4-one) (3f). As a result of the reaction of 0.1
g (0.30 mmol) of thiohydantoin 2f with 0.013 mL (0.028 g, 0.15 mmol) of 1,2-dibromoethane
and 0.06 g (0.42 mmol) of K2CO3, 0.054 g (53%) of compound 3f was obtained. M.p. 198 °C.
1
HRMS: calculated for C36H33O4N6S2 (M+H)+ 677.2005, found 677.1998. H NMR (400
MHz, CDCl3, δ, ppm): 8.70 (d, 2H, J = 7.83 Hz, Hα'-Py), 8.64 (d, 2H, J = 3.91 Hz, Hβ-Py),
7.57 (t, 2H, J = 7.83 Hz, Hβ '-Py), 7.15-7.25 (m, 8H, Ph), 6.99 (m, 4H, CH=, Hγ-Py), 4.08 (q,
4H, CH2), 3.82 (s, 4H, CH2CH2), 1.46 (t, 6H, J = 6.85 Hz,CH3). UV-vis (λ, nm/ε, l mol-1 cm-
1): 434/19336, 379/19336, 266/21289. Calculated C, 63.89%; H, 4.77%; N, 12.42%; S, 9.48%.
C36H32N6O4S2. Found C, 64.18%; H, 5.01%; N, 12.51%; S, 9.88%,
(5Z,5´Z)-2,2´-(Ethane-1,2-diyldisulfanyldiyl)bis(3-(3,4-dimethoxyphenyl)-5-(2-
pyridylmethylidene)-3,5-dihydro-4H-imidazol-4-one) (3g). As a result of the reaction of 0.1 g
(0.29 mmol) of thiohydantoin 2g with 0.012 mL (0.027 g, 0.14 mmol) of 1,2-dibromoethane and
0.06 g (0.42 mmol) of K2CO3, 0.053 g (53%) of compound 3g was obtained. M.p. 241 °C (dec.).
HRMS: calculated for C36H33O6N6S2 (M+H)+ 709.1903, found 709.1896. H NMR (400 MHz,
CDCl3, δ, ppm): 8.70 (d, 2H, J = 7.83 Hz, Hα'-Py), 8.65 (d, 2H, J = 3.91 Hz, Hβ-Py), 7.59 (t, 2H,
J = 7.82 Hz, Hβ '-Py), 7.20 (m, 2H, Ph), 6.87-6.97 (m, 4H, Ph), 6.80 (s, 2H, CH=), 3.95 (s, 6H,
p-CH3), 3.90 (s, 6H, m-CH3), 3.84 (s, 4H,CH2CH2). UV-vis (λ, nm/ε, l mol-1 cm-1): 362/10936,
277/7574. Calculated C, 61.00%; H, 4.55%; N, 11.86%; S, 9.05%. C36H32N6O6S2. Found C,
60.83%; H, 4.25%; N, 12.00%; S, 8.84%,
Coordination compounds of ligands 3a-g with copper(II) (typical procedure). To a
solution of ligand 3a-g (concentration ~10-5 M) in 1 mL of dichloromethane 0.1 mL of n-butanol
was added carefully to obtain two-phase system. A solution of copper(II) chloride dihydrate of
the same concentration in 1 mL of butanol was slowly added. The reaction mixture was sealed
tightly and left to precipitate.
[(5Z,5´Z)-2,2´-(Ethane-1,2-diyldisulfanyldiyl)bis(3-(but-2-yl)-5-(2-pyridylmethylidene)-
3,5-dihydro-4H-imidazol-4-one)]dicopper(II) tetrachloride (4a). From 0.012 g (0.021 mmol)
of ligand 3a and 0.0075 g (0.044 mmol) of CuCl2•2H2O, 0.0073 g (41%) of complex 4a was
obtained as black crystals. M.p. 180 °C. UV-vis (λ, nm/ε, L mol-1 cm-1): 371/9550, 281/5390.
Calculated C, 41.07%; H, 3.91%; N, 10.26%; S, 7.82%. C28H32N6O2S2Cu2Cl4. Found C, 41.08%;
H, 4.11%; N, 9.97%; S, 7.89%.
[(5Z,5´Z)-2,2´-(Ethane-1,2-diyldisulfanyldiyl)bis(3-(2-methylbutyl)-5-(2-
pyridylmethylidene)-3,5-dihydro-4H-imidazol-4-one)]dicopper(II) tetrachloride (4b). From

0.03 g (0.052 mmol) of ligand 3b and 0.018 g (0.1 mmol) of CuCl2•2H2O, 0.0097 g (54%) of
complex 4b was obtained as black crystals. M.p 165 °C. Calculated C, 42.55%; H, 4.25%; N,
9.92%. C30H36N6O2S2Cu2Cl4. Found C, 43.45%; H, 4.05%; N, 9.62%.
[(5Z,5´Z)-2,2´-(Ethane-1,2-diyldisulfanyldiyl)bis(3-benzyl-5-(2-pyridylmethylidene)-3,5-
dihydro-4H-imidazol-4-one)]dicopper(II) tetrachloride (4c). From 0.0135 g (0.021 mmol) of
ligand 3c and 0.0075 g (0.044 mmol) of CuCl2•2H2O, 0.01 g (54%) of complex 4c was obtained
as black crystals. M.p. 186 °C. Calculated C, 46.04%; H, 3.16%; N, 9.48%.
C34H28N6O2S2Cu2Cl4. Found C, 45.97%; H, 3.05%; N, 9.76%.
[(5Z,5´Z)-2,2´-(Ethane-1,2-diyldisulfanyldiyl)bis(3-phenylethyl-5-(2-pyridylmethylidene)-
3,5-dihydro-4H-imidazol-4-one)]dicopper(II) tetrachloride (4d). From 0.014 g (0.022 mmol)
of ligand 4d and 0.0075 g (0.044 mmol) of CuCl2•2H2O, 0.0062 g (32%) complex 4d was
obtained as black crystals. M.p. = 205 oС. UV-vis (λ, nm/ε, L mol-1 cm-1): 370/13490. 279/6890.
Calculated C, 47.26%; H, 4.59%; N, 9.19%; S, 7.00%. C36H32N6O2S2Cu2Cl4. Found C.47.26%;
H, 4.19%; N, 8.86%; S, 7.45%.
[(5Z,5´Z)-2,2´-(Ethane-1,2-diyldisulfanyldiyl)bis(3-(4-ethoxyphenyl)-5-(2-
pyridylmethylidene)-3,5-dihydro-4H-imidazol-4-one)]dicopper(II) tetrachloride (4f). From
0.015 g (0.022 mmol) of ligand 3f and 0.0075 g (0.044 mmol) of CuCl2•2H2O, 0.0053 g (26%)
complex 4f was obtained as black crystals. M.p. = 224 oС (dec). UV-vis (λ, nm/ε, l mol-1 cm-1):
431/23828, 388/60351, 273/19140.
[(5Z,5´Z)-2,2´-(Ethane-1,2-diyldisulfanyldiyl)bis(3-(3,4-dimethoxyphenyl)-5-(2-
pyridylmethylidene)-3,5-dihydro-4H-imidazol-4-one)]dicopper(II) tetrachloride (4g.). From
0.015 g (0.021 mmol) of ligand 3g and 0.0072 g (0.042 mmol) of CuCl2•2H2O, 0.0061 g (30%)
complex 4g was obtained as black crystals. M.p. = 215 oС (dec). UV-vis (λ, nm/ε, l mol-1 cm-1):
351/7617, 274/19276.
Results and discussion
Synthesis of ligands and copmplexes
The tetradentate N4 ligands 3a-g were synthesized by the three-step sequence of reactions
shown in Scheme 1. At the first step, 3-substituted 2-thiohydantoins 1a-g was synthesized using
one of two manners: reaction of the isothiocyanate with glycine or ethyl isothiocyanatoacetate
with an amine; the choice of the method was determined by the availability of corresponding
1
amines or isothiocyanates. Compounds 1a-e were isolated and characterized by H NMR, IR
spectroscopy and elemental analysis; thiohydantoins 1f, 1g were used into the following reaction
without further purification. The condensation of thiohydantoins 1a-g with 2-pyridine
carbaldehyde gave 5-pyridylmethylene-substituted derivatives 2a-g. All of these compounds

were obtained as single geometrical isomers which can in general be Z or E. It was shown earlier
1
[32] that the shifts of the vinyl protons in the H NMR spectrum of the Z and E isomers of 5-
arylidene-2-thiohydantoins are 6.40-6.85 and 6.10-6.35 ppm, respectively. Based on these data,
compounds 2a-g are the Z isomers. This fact was later confirmed by the X-ray diffraction study
of complexes 4a, d, f, g. The preferential generation of Z isomers for these compounds may be
the result of the formation of an intramolecular hydrogen bond between the pyridine nitrogen
atom and the N–H fragment of the thiohydantoin cycle.
Tetradentate ligands 3a-g were synthesized by the alkylation of thiohydantoins 2a-g with
1,2-dibromoethane in DMF solution, using K2CO3 as a base (Scheme 1). Coordination
compounds 4a-g were synthesized by the slow diffusion of copper(II) chloride dehydrate in n-
butanol into a ligand solution in CH2Cl2 (Scheme 2).
R
N
O
S
1) Py/H2O
2) HCl
+
R
R
NCS
NH2
H2N
SCN
COOH
COOEt
R
N
NH
O
S
1) KOH
2) HCl
K2CO3
DMF
or
+
N
NH
1a-g
2a-g
R
R
N
R
N
R
N
N
O
O
S
S
O
O
S
S
N
N
CuCl2 . 2 H2O
CH2Cl2/BuOH
N
N
N
N
Cl Cl
Cu
Cu
N
Cl Cl
N
3a-g
4a-g
R = sec-Bu (a), 2-Me-C4H8 (b), Bn (c), CH2CH2Ph (d), Ph (e), 4-EtO-CH4 (f), 3,4-(MeO)2-C6H3 (g)
6
Scheme 1. Synthesis of ligand and complexes.
All copper complexes were isolated as very dark green (near black) crystals with
moderate yields (26-54%). The UV-Vis spectra of coordination compounds contain intensive
broad adsorption bands in the UV region, which are similar to those in the UV spectrum of
corresponding ligands and refer, most likely, to the π—π* and n—π* transitions in the organic
fragment [33-35]. The peaks in the spectra of complexes are slightly shifted relatively to the
corresponding peaks of the free ligands, but their intensity changes significantly: the intensity of

the shorter-wave peaks increases, while the intensity of peaks at 340-400 nm decreases (Figure
1). The spectra of the complexes contain also very low-intensive absorption bands of d-d
transitions in the visible spectral region at ~ 700–850 nm. Such electronic spectra agree with the
tetrahedral or distorted tetrahedral coordination environment of copper(II) ions [36] and are
consistent with the previous data for the compounds of the same series [26, 37].
Figure 1. Electronic spectra of coordination compound 4g and corresponding ligand 3g in DMF,
2.35.10-6M.
X-ray crystallography
The structure of complexes 4a,d,f,g were established by X-ray diffraction. The molecular
structures of complexes are shown in Figure 2. The most important bond lengths and angles are
given in Table 1. The crystallographic data and refinement parameters are shown in the
Supplementary information Crystals available for structural investigation were obtained by slow
diffusion of the ethanolic solution of CuCl2 2H2O to the solution of corresponding ligand 3 in
CH2Cl2; if there was no crystal formation, the diethyl ether vapor was diffused into the resulting
solution.
Summarizing the results of X-ray structural studies for binuclear copper complexes with
bis-5-(2-pyridylmethylidene)-3,5-dihydro-4H-imidazol-4-ones the several typical features can be
noticed.
1. The complexes contain two structurally equivalent or almost equivalent copper cations.
2. The coordination polyhedron of the copper atom is N4 type, has a distorted tetrahedral
shape and is formed by two donor nitrogen atoms of pyridine and imidazolone fragments of
organic ligand and two chloride anions.
3. The Cu-Cu distances in complexes are about 4.5-4.6 Å, which is greater than the sum
of van der Waals radii. Thus, two copper atoms are not directly connected to one another.

4. The conjugated thiohydantoin and pyridine rings in organic ligand fragments are planar
and are virtually coplanar. Six-membered chelate rings of coordination polyhedra are virtually
coplanar. In molecules 3f and 3g, the carbon atoms of the benzene ring at the N(3) atom deviate
from the plane of the five-membered ring of the ligand; the angle of deviation is ~90°.
5. Aromatic fragments of the two "halves" of the ligand are arranged parallel or close to
parallel one above the other with a slight shift. The distance between centroids of pyridine rings
is approximately 3.5 A.
4a
4d
4f
4g
Figure 2. The molecular structures of 4a, 4d, 4f, 4g, showing the atom-numbering schemes.
Displacement ellipsoids are drawn at the 30% probability level. In (4f) two disordered solvate
molecules of CH2Cl2 have been omitted, for clarity. Symmetry related atoms in 4d, 4g are
labeled as Ni , symmetry code i= 1-x,y,1.5-z and 2-x,y,1.5-z for 4g, 4d respectively.
Table 1. Selected interatomic distances and bond angles for compounds 4a, 4d, 4f and 4g.
Atoms
Distance (Å) or angle (o)

Complex 4a
4.546
Complex 4d
4.559
Complex 4f
4.610
Complex 4g
4.536
Cu-Cu
1.972(5)
1.9699(17)
2.0413(19)
2.2218(5)
2.2266(6)
93.16(17)
141.84(5)
99.44(5)
1.999(6)
2.034(7)
2.205(3)
2.212(2)
94.2(3)
1.992(2)
2.064(2)
2.2111(8)
2.2143(7)
95.86(7)
142.94(7)
97.98(6)
94.95(16)
136.07(7)
99.00(3)
Cu(1)-N(1)
2.042(5)
Cu(1)-N(2)
2.2030(19)
2.2334(19)
93.5(2)
Cu(1)-Cl(1)
Cu(1)-Cl(2)
N(1)-Cu(1)-N(3)
N(1)-Cu(1)-Cl(2)
N(3)-Cu(1)-Cl(2)
N(1)-Cu(1)-Cl(1)
N(3)-Cu(1)-Cl(1)
Cl(1)-Cu-Cl(2)
145.14(17)
98.30(15)
94.95(16)
138.84(15)
97.32(8)
142.8(2)
98.5(2)
96.29(6)
93.6(2)
138.00(5)
97.91(2)
138.28(19)
98.5(2)
Electrochemistry
Ligands 3e-f and their complexes 4e-f were studied by cyclic voltammetry (CV) and
rotating disk electrode (RDE) voltammetry in DMF in the presence of 0.05 M Bu4NClO4 as the
supporting electrolyte. The electrochemical results and the experimental conditions are given in
Table 2 and Supplementary Information. The typical cyclic voltammograms of the complexes
and ligands are shown in Figure 6. Ligands undergo a two- of three step reduction at -1.19–-1.23
V and -1.76–-2.06 V (see Table 2); they oxidize in one irreversible step at 1.12-1.51 V. Our
previous calculations [30] suggest that both oxidation and reduction occur primarily at the
thiohydantoin moiety of the ligands (the orbital of the sulfur lone pair makes the major
contribution to HOMO, whereas the cross-conjugated methylidenehydantoin π-system
O=CC(=C)N=C makes the major contribution to LUMO).
Copper complexes 4 undergoes a quasi-reversible two-electron cathodic redox transition
at the potentials +0.39–+0.43 V; this processes are apparently copper based and correspond to
CuII → CuI reduction. Thus, in dinuclear complexes 4, both copper ions are reduced
simultaneously at the same potential. This is additional evidence that both copper ions in these
complexes are not bound to each other. The subsequent peaks in cathodic region at -0.85–-2.25
V apparently correspond to the reduction of organic ligand fragment, not copper(I). In favor of
this fact is the absence of peaks of Cu0 reductive desorption during the reverse anodic scans after
the potential of second and third cathodic peaks. In addition, there was no copper precipitation
on the electrode surface. These observations indicate that the reduced forms of complexes does
not break down with the release of Cu0. Note also, that the reduction of the organic fragment in
complexes occurs at less negative potentials that those for the free ligands, similar observed

earlier for copper coordination compounds, in which the ligand fragment reduction preceded the
reduction of copper(I). This is an additional argument in favor of the fact that the reduced
organic ligand remains attached to the positively charged metallic atoms [38].
Note, that for copper-containing complexes the peaks of the reduction of coordinated
ligand fragment are doubled (see Figure 3, right and Table 2). In our opinion, this may be due to
the formation of binuclear copper(I)-containing complexes with Cu-Cu bonding, analogous to
[28], under the first reduction stage. The pyridylmethylene-imidazolone fragments of these
intermediates, being bound to the conjugated via copper atoms, are reduced further stepwise and
one-electronically. A proposed scheme of the first steps of electrochemical reduction of
complexes 4 is shown on Scheme 2.
+ 1e
+ 2e
+ 1e
[L]CuII
[L2- ]CuI2
[L- ]CuI2
[L]CuI2
2
Scheme 2. The proposed sequence of the first steps of compounds 4 electrochemical reduction
The oxidation of complexes 4 takes place initially at 1.16–1.17 V, at potentials
corresponding to the oxidation all of the coordinated chloride anions at once. The subsequent
oxidation peak corresponds to oxidation of the organic ligand fragments (Figure 3).
Thus, during the initial reduction of complexes 4, both copper ions are reduced
simultaneously, during the initial oxidation all four chloride ions are also oxidized
simultaneously. As to further reduction, two symmetrical conjugate fragments of the ligand
moiety are reduced in stages, whereas they are oxidized at the same potential.
0.012
0.008
0.004
0
-0.004
-0.008
-2000
-1000
0
1000
2000
E, mV
Figure 3. Cyclic voltammograms for ligand 3f (left) and its complex 4f (right). GC electrode,
DMF, 5.10-4 M, Bu4NClO4.

Table 2. The electrochemical potentials (vs. Ag /AgCl /KCl (aq.,sat.)) of the compounds 3e-g,
4e-g in DMF in presence 0.1 M Bu4NClO4 at a GC electrode; potential scan rate 100 mV s -1
Epc, V
Epa, V
Compound
-1.19
-1.76
1.43
Ligand 3e
-2.06
+0.39/0.51
-0.85
-1.14
-2.25
-1.23
1.16
1.48
Complex 4e
Ligand 3f
1.12
-1.56
-1.82
+0.43/0.55
-1.03
-1.21
-1.55
-1.79
1.16
1.54
Complex 4f
Ligand 3g
-1.23
1.51
-1.84
+0.40/0.57
-1.01
-1.19
1.17
1.52
Complex 4g
-1.51
-1.76
Cytotoxicity
Ligands 3a,d,g and their copper complexes 4a,d,g were tested in terms of their in vitro
cytotoxicity against cell cancer cells lines, including human lung cancer (A549), breast
adenocarcinoma (MCF-7) and human embryonic kidney (HEK293) cells using a standard MTT
assay [39]. The results of this assay are shown in Table 4 together with the results obtained for
the clinically used drugs cisplatin and doxorubicin, which have been given for comparison.
Table 4. Cytotoxicity of ligands and complexes against A549, MCF7 and HEK293T cell lines
measured by MTT-assay (μM)
Сompound
HEK293T, μM
MCF7, μM
A549, μM
>100
2.06±0.8
59.5±9
1.27±0.8
18.7±6.4
3.4±0.5
2.0±0.8
>30
18.2±0.9
1.34±0.18
34.7±6
0.66±0.3
54.4±20.6
8.1±0.9
2.1±0.8
64.13±3.9
>100
3a
4a
3d
4d
3g
>100
1.38±0.13
101.9±47
19.3±2.5
1.1±0.1
12.4±3.9
>100
4g
Doxorubicin a
Cisplatin b
.
CuCl2 2H2O
>100

a according to [25].
b according to [40].
Based on the obtained data, the cytotoxicity of the free ligands were much higher than
those of the corresponding copper complexes. The nature of the substituent at the N(3) position
of the imidazolone ring had some impact on the cytotoxicity. All tested complexes demonstrate
significant cytotoxicity comparable to doxorubicine and greater than cisplatin. Note also that the
cytotoxicity of the investigated binuclear coordination compounds of copper(II) is higher than
the cytotoxicity of the previously studied binuclear mixed-valence (Cu(II)/Cu(I)) complexes of
the same ligands [25].
Conclusion
The present study involved the synthesis of binuclear copper(II) complexes obtained as a
results
of
(5Z,5´Z)-(2,2´-ethane-1,2-diyldisulfanyldiyl)bis(5-(2-pyridylmethylidene)-3,5-
.
dihydro-4H-imidazol-4-ones) interaction with CuCl2 2H2O. These complexes were characterized
by UV-vis spectroscopy, X-ray diffraction and cyclic voltammetry. Based on X-ray data
complexes contain two structurally equivalent and unconnected with each other copper atoms.
Both copper ions are electrochemically reduced simultaneously at the same potential. The
cytotoxicities of the copper containing complexes against MCF7, A549 and HEK293T cells were
comparable to those of doxorubicin and greater than those of cisplatin.
Appendix A. Supplementary data
CCDC entries: 1826604 (4a), 1826603 (4d), 1826602 (4f), 1826644 (4g) contain the
supplementary crystallographic data for this paper. These data can be obtained free of charge via
http://www.ccdc.cam.ac.uk/conts/retrieving.html, or from the Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (+44) 1223-336-033; or e-mail:
deposit@ccdc.cam.ac.uk.
Acknowledgements
This work (X-Ray and NMR study) was supported in part by M.V.Lomonosov Moscow
State University Program of Development We are also grateful to the Russian Foundation of
Basic Research (Projects 16-03-00921) for financial support of this work.
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