Complexes of 1-[2-[2-hydroxy-3-(propylamino)propoxy]phenyl]-3-phenyl-1-propanone (propafenone) with copper(II): Crystal structure of the mononuclear Cu(II) complex with propafenone

Article abstract of DOI:10.1016/j.poly.2006.01.027

Two new copper(II) complexes with the antiarrythmic drug propafenone (HPr) have been synthesized: the mononuclear complex CuPr₂ (1) and the binuclear one Cu₂Pr₂Cl₂ (2) and have been studied using electronic, IR and EPR spectra, magnetochemical, thermogravimetric and single-crystal X-ray diffraction methods. In the mononuclear complex 1, copper(II) is coordinated bidentately with the NH and deprotonated OH groups of two drug molecules forming a nearly square-planar structure of the type CuL₂, with a CuN₂O₂ chromophore. In complex 2 each copper atom is coordinated with one N atom from one ligand, one terminal chlorine atom and two oxygen atoms from two different ligand molecules which serve as bridges in the formation of the binuclear complex 2. Measurable antiferromagnetic interactions between the two paramagnetic Cu(II) centers are responsible for some interesting magnetic properties.

Full text of DOI:10.1016/j.poly.2006.01.027

Polyhedron 25 (2006) 2254–2260
www.elsevier.com/locate/poly
Complexes of 1-[2-[2-hydroxy-3-(propylamino)propoxy]phenyl]-
3-phenyl-1-propanone (propafenone) with copper(II): Crystal
structure of the mononuclear Cu(II) complex with propafenone
a
b
c
c,
*
V.T. Getova , R.P. Bontchev , D.R. Mehandjiev , P.R. Bontchev
a
Faculty of Chemistry, Sofia University, 1, J. Bourchier Blvd., Sofia 1164, Bulgaria
Sandia National Laboratories, P.O. Box 5800, MS 0779, Albuquerque, NM 87185-0779, USA
Institute of General and Inorganic Chemistry, Bulgarian Academy of Sciences, Acad. G. Bontchev Str., Bl. 11, Sofia 1113, Bulgaria
b
c
Received 20 September 2005; accepted 17 January 2006
Available online 6 March 2006
Abstract
Two new copper(II) complexes with the antiarrythmic drug propafenone (HPr) have been synthesized: the mononuclear complex
CuPr2 (1) and the binuclear one Cu2Pr2Cl2 (2) and have been studied using electronic, IR and EPR spectra, magnetochemical, ther-
mogravimetric and single-crystal X-ray diffraction methods. In the mononuclear complex 1, copper(II) is coordinated bidentately with
the NH and deprotonated OH groups of two drug molecules forming a nearly square-planar structure of the type CuL2, with a
CuN2O2 chromophore. In complex 2 each copper atom is coordinated with one N atom from one ligand, one terminal chlorine atom
and two oxygen atoms from two different ligand molecules which serve as bridges in the formation of the binuclear complex 2.
Measurable antiferromagnetic interactions between the two paramagnetic Cu(II) centers are responsible for some interesting magnetic
properties.
ꢀ 2006 Elsevier Ltd. All rights reserved.
Keywords: Cu(II) complexes; Propafenone; X-ray data; Magnetochemical properties
1. Introduction
the arterial blood pressure. A large number of such com-
plexes have been synthesized and studied in detail and
some interesting correlations have been found, for example
the relation between the concentration level of metallo-
thioneines and the arterial blood pressure [7–10] or the
complexation of noradrenaline (NA) with zinc and its
influence on the vasoconstriction effect of NA [11].
Special attention has been paid to the complexation
between copper and a series of medications used for nor-
malization of the arterial blood pressure – both antihypo-
tensives and antihypertensives such as vasodilators, ACE-
inhibitors, diuretics [1–4,12–15] and especially b-blockers
[1,16–22]. The first step of these investigations has been
to study the complexation processes of the metal with the
medicine, in order to obtain and characterize the complexes
formed, and then to study their biological effect in compar-
ison with that of the pure metal-free ligand. In several cases
we were able to show directly that such complexes could
During the last two decades we have found that many
drugs used in the treatment of hyper- and hypotension
form stable chelate complexes with copper and zinc (see
e.g. [1–4]), the two metals that participate in the regulation
of the arterial blood pressure [5,6]. Our investigations in
this field lead to the hypothesis that such complexation
can modify additionally the biological activity of the drugs
through changing the homeostasis of the metalloelements
and/or changing the reactivity of the medication when it
is bound in the form of a metal complex.
In order to verify this hypothesis we have studied the
complexation of copper and zinc with a variety of drugs
and other biochemically active agents capable of changing
*
Corresponding author. Tel.: +359 2 8161345; fax: +359 2 9625438.
E-mail address: prbontchev@chem.uni-sofia.bg (P.R. Bontchev).
0277-5387/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.poly.2006.01.027

V.T. Getova et al. / Polyhedron 25 (2006) 2254–2260
2255
have higher activity [3,11,23] or/and prolonged action as
compared to the free ligand [21].
was formed with participation of the same donor groups
of the ligand.
The present paper is part of this systematic study and it
is dedicated to complex formation between copper(II) and
1-[2-[2-hydroxy-3-(propylamino)propoxy]phenyl]-3-phenyl-
1-propanone, propafenone. The latter is an effective anti-
arrythmic agent with a moderate b-blocking activity and
an acceptable side effect profile for the acute and long-term
treatment of supraventricular arrythmias. From a chemical
point of view it represents an aminoalcohol and therefore it
is of interest to compare its behaviour as a ligand with that
of another group of aminoalcohol medications – that of the
b-blockers, which easily form stable complexes with cop-
per(II) [16–22]. Some of these complexes exhibit even better
pharmacological effects in comparison with the non-coor-
dinated free drugs that offer good perspectives for their
clinical application [3,11,21,22].
2. Experimental
2.1. Materials and synthesis
Propafenone was obtained from Sigma, Germany as the
hydrochloric salt, HPr Æ HCl and was used without further
purification. The metal salt CuCl2 Æ 2H2O and NaOH were
supplied by Riedel E. de Hae¨n AG and MeOH from Fluka.
All reagents and solvents used were of analytical grade.
The mononuclear complex 1 was obtained at room tem-
perature when 1.00 cm3 0.025 M solution of CuCl2 Æ 2H2O
(0.0426 g CuCl2 Æ 2H2O in 10.0 cm3 MeOH) was added to
10.00 cm3 0.025 M of the ligand in the same solvent
(0.0945 g Pr Æ HCl in 10.0 cm3 MeOH). Dropwise addition
of 5.0 cm3 0.10 M NaOH (0.0800 g NaOH in 20.0 cm3
MeOH) to the reaction solution resulted in a violet colora-
tion. From this solution violet crystals precipitated after 5
days. The crystals were filtered, washed with methanol,
recrystallized from EtOH and dried over P2O5 (yield ca.
35%). Anal. Calc. for CuPr2: C, 67.76; H, 7.04; N, 3.76;
Cu, 8.54. Found: C, 67.24; H, 6.86; N, 3.92; Cu, 8.45%.
M.p.: 146 ꢁC.
The binuclear complex 2 was synthesized at ambient
temperature when 10.00 cm3 0.025 M solution of Pr Æ HCl
(0.0945 g Pr Æ HCl in 10.0 cm3 MeOH) was mixed with
10.00 cm3 0.025 M solution of CuCl2 Æ 2H2O (0.0426 g
CuCl2 Æ 2H2O in 10.0 cm3 MeOH). The dropwise addition
of 5.0 cm3 0.10 M NaOH (0.0800 g NaOH in 20.0 cm3
MeOH) resulted in the formation of a green precipitate,
that was filtered, washed with MeOH and dried over
P2O5 (yield ca. 60%). Anal. Calc. for Cu2Pr2Cl2: C, 57.40;
H, 5.96; N, 3.19; Cl, 8.07; Cu, 14.46. Found: C, 57.31; H,
5.91; N, 3.28; Cl, 8.26; Cu, 14.06%. M.p.: 158 ꢁC. Unfortu-
nately, we were not able to obtain crystals of proper size
and quality in order to perform a direct X-ray single crystal
structure determination of complex 2.
H
OH
11
N
12
8
7
9
10
3
6
O
4
2'
3'
2
5
4'
1
1'
6' 5'
O
Propafenone, HPr
The aminoalcohol chain in propafenone is linked to the
phenyl ring through an oxygen atom as in the b-blockers
and thus one might expect to find similar coordination abil-
ity of these ligands. We have already discussed the role of
the oxygen for the chemical and biological properties of
other aminoalcohol drugs such as effortil, clenbuterol, sal-
butamol and sotalol [1,2,14,22]. On the other hand the
presence of bulky substituents in the aromatic ring of pro-
pafenone could create steric hindrance and decrease to
some extent the complexation with copper. Therefore, a
comparison between the coordination ability of propafen-
one and the other aminoalcohol drugs mentioned above
seems to be of interest.
We have found that, like many other aminoalcohols,
propafenone forms mono- and binuclear complexes,
depending mainly on the molar metal-to-ligand ratio in
the reaction system. Due to the relatively lower solubility
of the ligand in water, we used methanol as a reaction med-
ium for the synthesis of the complexes. In alkaline methan-
olic solution and with an excess of the ligand
(M:HPr Æ HCl 6 1:10; HPr Æ HCl:NaOH 6 1:2) the violet
mononuclear complex 1 was obtained, in which copper(II)
is coordinated via the NH and the deprotonated OH
groups of the ligand, forming a stable five-membered che-
late ring. With comparable amounts of the reagents
(M:HPr Æ HCl from 1:2 to 2:1) and the same alkalinity
(HPr Æ HCl:NaOH 6 1:2) the green binuclear complex 2
2.2. Instrumentation and analysis
Electronic spectra were obtained on a Specord UV–Vis
(Carl-Zeiss, Jena) instrument. IR spectra were recorded
in the range 4000–400 cmꢀ1 on a Specord-75 IR spectrom-
eter, and in the range 500–75 cmꢀ1 on a Bruker 113 V
instrument in polyethylene. Thermogravimetric analyses
were performed using a Perkin–Elmer TGS-2 instrument.
The EPR spectra in the X-band were obtained with
an ERS 220/Q instrument, using Mn/ZnS standard. Mag-
netic measurements were carried out under a helium
atmosphere on a SQUID magnetometer with a sensitivity
of ꢁ2 · 10ꢀ5 emu. The magnetic susceptibility was mea-
sured with an increment of 2 K over the whole temperature
range 2–300 K and the validity of the Curie–Weiss law was
estimated using the correlation coefficient, with values
higher than 0.9900. Elemental analyses were performed

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V.T. Getova et al. / Polyhedron 25 (2006) 2254–2260
according to classical methods: C, H were determined as
CO2 and H2O, N through the Dumas’ method, chlorine
by titration with Hg(NO3)2 after wet digestion of the sam-
ple. Copper was determined by atomic absorption after wet
digestion of the sample. The NMR spectra were recorded
in CDCl3 solutions on a JEOL EX-400 instrument (13C
3. Results and discussion
3.1. Mononuclear CuPr2 complex 1
3.1.1. X-ray data and crystal structure
The asymmetric unit of the title compound consists of
one copper atom and one propafenone molecule (Fig. 1).
The copper atoms are located on inversion centers occupy-
ing one special (2a: 0, 0, 0) position while all other atoms
occupy general (4e: x, y, z) positions. Each copper atom
is coordinated by two propafenone molecules acting as
bidentate ligands through O1 and N1 (Fig. 2). All five
atoms of the resulting CuO2N2 unit lie in the same plane
with CuAO1 and CuAN1 distances of 1.900(6) and
1
at 100 MHz, H at 400 MHz) and on a Varian 300 (13C
1
at 75 MHz, H at 300 MHz).
For the structure determination of 1, a transparent nee-
dle shaped pink crystal was mounted on a SIEMENS
SMART X-ray diffractometer with a 1 K CCD area detec-
tor. Data were collected at room temperature using graph-
˚
ite-monochromatized Mo Ka radiation (k = 0.71073 A). A
hemisphere of data (1271 frames at 5 cm detector distance)
was collected using a narrow-frame method with scan
widths of 0.30ꢁ in x and an exposure time of 30 s/frame.
The first 50 frames were measured again at the end of the
data collection to monitor instrument and crystal stability.
The data were integrated using the Siemens SAINT program
[23]. The program SADABS was used for the absorption cor-
rection [24]. The structure was solved by direct methods
and refined by full-matrix least-squares techniques with
the SHELX97 software package [25]. All non-hydrogen
atoms have been located and assigned directly from the
Fourier maps. The hydrogen atoms have been introduced
as riding models and their thermal parameters refined iso-
tropically [25]. The main crystallographic details are sum-
marized in Table 1.
˚
2.024(7) A, respectively, and a O1ACuAN1 angle of
86.9(3)ꢁ (Table 2). Hence, the copper coordination could
be described as a plain squared one (Fig. 2). All CAO,
CAN and CAC distances and angles in the propafenone
molecule are well within the corresponding limits.
The CuPr2 complexes are packed on top of each other
forming slabs that run parallel to the a-axis (Fig. 3). The
shortest intermolecular Oꢂ ꢂ ꢂH distances are of order of
˚
˚
˚
2.4 A (O3ꢂ ꢂ ꢂH11 = 2.35 A, O2ꢂ ꢂ ꢂH14 = 2.39 A and O2ꢂ ꢂ ꢂ
˚
H10 = 2.45 A) indicating the presence of only a small num-
ber of weak hydrogen bonds. No solvent molecules have
been detected in the structure.
3.1.2. Electronic and IR spectra
The electronic spectrum of the mononuclear complex 1
in methanol shows one broad asymmetric absorption band
at 520 nm (e ꢃ 100 l molꢀ1 cmꢀ1), and a shoulder at
650 nm, due to the d–d transition in the distorted octahe-
dral structure of the Cu(II) complex, where copper is
bound with nitrogen and oxygen donor atoms.
The IR spectrum of the ligand shows two bands at 3295
and 3160 cmꢀ1 assigned to the stretching vibrations of the
NH and OH groups, respectively, engaged in the formation
of H-bonds, as follows from the absorbance in the 2800–
Table 1
Crystal data and structure refinement for CuPr2 (1)
Complex 1
Empirical formula
Formula weight
Temperature (K)
Wavelength (A)
Crystal system, space group
C16.80H17.60Cu0.40N0.80O2.40
294.39
293(2)
0.71073
˚
monoclinic, P21/c (#14)
Unit cell dimensions
˚
a (A)
4.7106(9)
12.507(2)
˚
b (A)
˚
c (A)
31.979(6)
a (ꢁ)
b (ꢁ)
c (ꢁ)
90
92.858(4)
90
1881.7(6), 5
1.338
794
O3
C21
C15
C20
C19
3
˚
C13
C12
Volume (A ), Z
Calculated density (g cmꢀ3
F(000)
)
C11
C16
C17
C14
C5
C10
C9
Crystal size (mm)
h Range for data collection (ꢁ)
0.44 · 0.09 · 0.06
1.28–22.50
C18
O2
Limiting indices
ꢀ5 6 h 6 5, ꢀ13 6 k 6 13,
C7
ꢀ34 6 l 6 34
Reflections collected/unique
Refinement method
11218/2439
C4
N1
C8
full-matrix least-squares on F2
2439/239
C6
C3
Data/parameters
C1
C2
Goodness-of-fit on F2
Final R indices [I > 2r(I)]a,b
R indices (all data)
1.424
R1 = 0.1080, wR2 = 0.2681
R1 = 0.1111, wR2 = 0.2709
O1
P
P
a
Cu1
R1 = ||Fo| ꢀ |Fc|/ |Fo| (based on reflections with I > 2r(I)).
h
i
1=2
P
P
2
2
b
wR2 ¼
wðjF oj ꢀ jF cjÞ = wjF oj2
; w ¼ 1=½r2ðF 2oÞ þ ð0:0533PÞ
Fig. 1. Asymmetric unit, 50% thermal ellipsoids and labelling scheme in
þ28:15Pꢄ; P ¼ ½maxðF 2o; 0Þ þ 2F c2ꢄ=3 ðall dataÞ.
complex 1.

V.T. Getova et al. / Polyhedron 25 (2006) 2254–2260
2257
Fig. 2. Cu coordination in complex 1. Copper, nitrogen, oxygen, carbon and hydrogen atoms are shown as cross-hatched, hatched, open, filled and black
circles, respectively.
Table 2
3.1.3. EPR data
˚
Selected bond lengths (A) and bond angles (ꢁ) in the mononuclear complex
1
The X-band EPR spectrum of complex 1 in a methan-
olic solution frozen at 113 K presents an anisotropic sig-
nal with gi = 2.212, Ai = 170 G and an unresolved
perpendicular component. Qualitatively, these parameters
and the relation gi > g^ indicate that the unpaired d-elec-
tron is located mainly on the dx2ꢀy2 -orbital and a consid-
erable axial deformation is realized, leading practically to
a square-planar complex. The same spectra also exhibit
an unresolved SHSF from 14N in the perpendicular mag-
netic field, due to the coordination of the NH-function to
copper. A solid sample of complex 1 at the same temper-
ature (113 K) shows a broad signal for a magnetically
Cu(1)AO(1)#1
Cu(1)AO(1)
Cu(1)AN(1)#1
Cu(1)AN(1)
O(1)#1ACu(1)AO(1)
O(1)#1ACu(1)AN(1)#1
O(1)ACu(1)AN(1)#1
O(1)#1ACu(1)AN(1)
O(1)ACu(1)AN(1)
N(1)#1ACu(1)AN(1)
1.900(6)
1.900(6)
2.024(7)
2.024(7)
180.0(5)
86.9(3)
93.1(3)
93.1(3)
86.9(3)
180.0(5)
Symmetry transformations used to generate equivalent atoms: (#1)
ꢀx, ꢀy, ꢀz; (#2) ꢀx + 1, ꢀy, ꢀz.
concentrated sample of
complex.
a
paramagnetic copper(II)
2300 cmꢀ1 range. The coordination of the ligand with
Cu(II) and the formation of 1 lead to disappearance of
the m(OH) stretching vibration as a result of deprotonation
of the hydroxyl group and to a shift of the m(NH) to the
These experimental EPR data are in a good accordance
with those for other similar copper(II) complexes [1,22].
3.1.4. Magnetochemical data
3000–2800 cmꢀ1 range, where the bands due to m(ArCꢀH
)
The magnetochemical studies of the mononuclear com-
plex 1 in the temperature range 2–290 K revealed that the
magnetic susceptibility v decreases with increasing temper-
ature, which is indicative of the paramagnetic character of
the complex. The Curie–Weiss law is followed in the whole
of the aromatic ring are also present. At the same time
two new bands are observed in the far IR-spectrum at
600 and 430 cmꢀ1, assigned to the stretching vibrations
of m(CuAN) and m(CuAO) in the complex [26].
Fig. 3. Unit cell and 3D packing in complex 1.

2258
V.T. Getova et al. / Polyhedron 25 (2006) 2254–2260
temperature range studied with a correlation coefficient of
0.9943. The effective magnetic moment determined with a
value of the Weiss constant h = ꢀ16 was leff = 1.70leff/lB.
The fulfillment of the Curie–Weiss law indicates that the
Cu2+-ions are in an octahedral crystal field, as leff does not
depend on the temperature. The experimentally found
magnetic moment is lower than the theoretical one, which
for a crystal field of 10000 cmꢀ1 is about 2.01leff/lB [27].
The smaller value of the experimental magnetic moment
is probably due to a weak intermolecular antiferromagnetic
exchange interaction between the copper centers. This
assumption is in accordance with the X-ray data showing
The IR spectra of 2 show that the m(NH) band is shifted
110 cmꢀ1 to lower frequency, in comparison with the same
band in the free ligand, while m(OH) is absent, indicating that
the ligand is coordinated again through its NH group and
deprotonated OH function. This conclusion is supported
also by the appearance of new bands in the far IR-spectrum
at 590, 415 and 270 cmꢀ1 ascribed to the stretching vibra-
tions m(CuAN), m(CuAO) and m(Cu–Cl), respectively [26].
3.2.2. NMR spectra
Additional information about the coordination mode of
the ligand in 2 was obtained by a comparison between the
NMR spectra of the free ligand and complex 2. In the 13C
spectrum of 2 the signals for C7, C8, C9, C10, C11and C12 (at
70.40, 64.79, 49.73, 48.80, 18.71 and 10.97 ppm, respec-
tively) disappeared, due to the strong influence of the
adjacent paramagnetic copper(II) centers, bonded to Oꢀ
and NH functions. At the same time the intensities of
the signals for the other C-atoms remained practically
unchanged. Analogous results were revealed also by the
1H NMR spectra of the ligand and complex 2. Here again
a strong decrease in the intensities down to a complete dis-
appearance was observed for the proton signals of the NH-
and OH-groups (9.05 and 5.94 ppm) and for those bonded
with the carbon atoms C7, C8, C9, C10, C11 and C12 (at 4.12,
4.27, 3.08, 2.72, 1.64 and 0.04 ppm, respectively), while the
intensities for the protons at the other C-atoms were prac-
tically unchanged. Such effects have been already observed
with another copper(II) complex with an aminoalcohol
drug [1,16,30].
˚
a distance of 4.711 A between the copper ions in axial posi-
tions along the a-axis.
3.1.5. Thermogravimetric data
The thermogravimetric (TG) study confirmed the ele-
mental analysis, the IR and X-ray data that there is no sol-
vent included in the isolated mononuclear species 1.
3.2. Binuclear Cu2Pr2Cl2 complex 2
3.2.1. Electronic and IR spectra
The UV–Vis spectra of the complex 2 in methanol show
two absorption bands: a broad band of low intensity at
710 nm (e ꢃ 40 l molꢀ1 cmꢀ1) assigned to a d–d transition
in the near square-planar copper(II) structure, and a sec-
ond, more intense one at 385 nm (e ꢃ 1330 l molꢀ1 cmꢀ1),
that is typical for copper(II) polynuclear complexes with
oxygen bridges of the type CuAOACu. This band has been
attributed to a charge-transfer transition O ! Cu, which
explains its higher intensity [28,29].
These results confirmed again the coordination sites of
the ligand in the complexes formed with copper(II).
Fig. 4. Magnetic susceptibility vs. T for the binuclear complex 2, measured at 1kOe applied field: (a) in the range 2–300 K; (b) in the range 120–300 K, vg
being shown in a different scale.

V.T. Getova et al. / Polyhedron 25 (2006) 2254–2260
2259
Fig. 5. The X-band EPR-spectra of the methanolic green solution of complex 2.
3.2.3. Magnetochemical and EPR data
NH- and deprotonated OH-functions. In 1 only two
ligands are coordinated around copper(II), while in 2, each
one of the two metal centers are bound by one nitrogen, by
one terminal chlorine and by two deprotonated OH-groups
from two different propafenone molecules, forming oxygen
bridges between the metal centers in the Cu2Pr2Cl2 chro-
mophore. No solvent molecules have been detected in the
crystal structures of 1 and 2. The relatively short distance
between the two metal centers in 2, linked by the oxygen
The temperature dependence of the specific magnetic
susceptibility vg is given in Fig. 4a. In the range 2–150 K
the complex shows a typical paramagnetic character. At
temperatures above 150 K, vg begins to increase
(Fig. 4b). The Curie–Weiss law is not followed in the whole
temperature range (2–300 K). This complicated behaviour
of vg could be considered as a result of superposition of
the data for two different components. The first is a para-
magnetic one, present as a monomeric impurity. The sec-
ond component is an antiferromagnetic one, formed as a
result of an intramolecular indirect exchange interaction
between the copper(II) centers. An analogous course of
the vg/T plot is also observed for other copper(II) com-
plexes, described in the literature [31–35].
According to the theory [36,37] for complexes with clo-
sely located copper centers, the v versus T plot must have a
different course and is expected to pass through a maxi-
mum. In the present system such a maximum was not yet
reached in the temperature range studied.
Similar effect must be also expected for the EPR spectra,
measured at low and high temperatures. Fig. 5 shows the
EPR spectra of the complex at 113 and 293 K in solution.
Analogous spectra were obtained also with a solid state
sample. At low temperatures the typical broad signal for
paramagnetic Cu(II) has been observed. At higher temper-
atures the increased antiferromagnetic interaction leads to
the complete quenching of the signal.
bridges, leads to the appearance of
antiferromagnetism.
a measurable
5. Supplementary information
Full crystallographic details have been deposited in cif-
format with the Cambridge Crystallographic Data Centre,
CCDC 279128 for 1. Copies of this information could be
obtained free of charge from the Director, CCDC, 12
Union Road, Cambridge, CB2 1EZ, UK (fax: +44 1223
336 033, email: deposit@ccdc.cam.ac.uk, web: http://
www.ccdc.cam.ac.uk/conts/retrieving/html).
Acknowledgements
The authors greatly acknowledge the financial support
provided by the National Research Fund of Bulgaria. They
also thank Dr. V. Skumryev from the Universitat Auto-
noma de Barcelona, Spain, for checking some of the
magnetochemical data.
3.2.4. Thermogravimetric (TG) data
The TG study showed that, as in 1, there are no solvent
molecules included in the structure.
References
[1] P.R. Bontchev, I.N. Pantcheva, Transit. Met. Chem. 27 (2002) 1.
[2] P.R. Bontchev, B.B. Ivanova, R.P. Bontchev, D.R. Mehandjiev, D.S.
Ivanov, Polyhedron 19 (2000) 1843.
4. Conclusion
[3] P.R. Bontchev, Ch. Nachev, B. Evtimova, N.D. Yordanov, E.
Zhecheva, D. Mehandjiev, in: Proceedings of the 12th International
Conference on Coordination Chemistry, Smolenice, Slovakia, 1989,
p. 47.
Propafenone forms two complexes with copper(II) – the
mononuclear CuPr2 (1) and the binuclear Cu2Pr2Cl2 (2). In
both cases the drug acts as a bidentate ligand through its

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V.T. Getova et al. / Polyhedron 25 (2006) 2254–2260
[4] P.R. Bontchev, B.B. Ivanova, R.P. Bontchev, D. Mehandjiev,
Polyhedron 20 (2001) 231.
[21] P.R. Bontchev, I.N. Pantcheva, R.P. Bontchev, D.S. Ivanov, N.D.
Danchev, BioMetals 15 (2002) 78.
[5] M.J. Kendrick, M.T. May, M.J. Plishka, K.D. Robinson, Metals in
Biological Systems, Ellis Horwood, New York, 1992.
[6] J.J.R.F. da Silva, R.J.P. Williams, The Biological Chemistry of the
Elements, 2nd ed., Clarendon Press, Oxford, 1993.
[7] M. Apostolova, P.R. Bontchev, Ch. Nachev, I. Sirakova, Jpn. J. Med.
Sci. Biol. 45 (1992) 185.
[22] V.T. Getova, P.R. Bontchev, D.R. Mehandjiev, V. Skumryev, P.R.
Bontchev, Polyhedron 24 (2005) 1983.
[23] Siemens Analytical X-ray Instruments; SAINT, Version 4.05, Madison,
WI, 1995.
[24] G.M. Sheldrick, SADABS, v. 2.10. Program for Empirical Absorption
Correction of Area Detector Data, University of Go¨ttingen, Go¨ttin-
gen, Germany, 2003.
[8] M. Apostolova, P.R. Bontchev, Ch. Nachev, I. Sirakova, J. Chromat.
(Biomed. Appl.) 620 (1993) 191.
[25] G.M. Sheldrick, SHELX97 (Includes SHELXS97, SHELXL97, CIFTAB) –
[9] M. Apostolova, P.R. Bontchev, Ch. Nachev, I. Sirakova, Compt.
Rend. Bulg. Acad. Sci. 46 (1993) 75.
[10] M. Apostolova, Ch. Nachev, M. Koleva, P.R. Bontchev, I. Kehaiov,
Talanta 46 (1998) 325.
[11] Ch. Nachev, P.R. Bontchev, B. Evtimova, D. Ivanov, J. Clin.
Pharmacol. 28 (1988) 923.
[12] P.R. Bontchev, G. Gochev, B. Evtimova, H. Kadum, Ch. Nachev, J.
Inorg. Biochem. 46 (1992) 23.
[13] P.R. Bontchev, H. Kadum, G. Gochev, B. Evtimova, J. Macicˇeck,
Ch. Nachev, Polyhedron 11 (1992) 1973.
[14] P.R. Bontchev, B.B. Ivanova, D.R. Mehandjiev, Bulg. Chem.
Commun. 35 (2003) 21.
Programs for Crystal Structure Analysis (Release 97-2). Institut fur
¨ ¨
Anorganische Chemie der Universita¨t, Tammanstrasse 4, D-3400
Go¨ttingen, Germany, 1998.
[26] K. Nakamoto, Infrared and Raman Spectra of Inorganic and
Coordination Compounds, 5th ed., Wiley, New York, Toronto, 1997.
[27] A. Earnshaw, Introduction to Magnetochemistry, Academic Press,
London, New York, 1968.
[28] G.A. van Albada, M.T. Lakin, N. Veldman, A.L. Spek, J. Reedijk,
Inorg. Chem. 34 (1995) 4910.
[29] G.A. van Albada, W.J.J. Smeets, A.L. Spek, J. Reedijk, Inorg. Chim.
Acta 260 (1997) 151.
[30] W. Holzer, Molecules 6 (2001) 796.
[15] P.R. Bontchev, D.R. Mehandjiev, B.B. Ivanova, R.P. Bontchev,
Transit. Met. Chem. 28 (2003) 745.
[16] P.R. Bontchev, I.N. Pantcheva, T. Todorov, D.R. Mehandjiev, N.
Savov, J. Inorg. Biochem. 83 (2001) 25.
[17] P.R. Bontchev, B.B. Ivanova, R.P. Bontchev, D.R. Mehandjiev, J.
Coord. Chem. 54 (2001) 25.
[18] P.R. Bontchev, I.N. Pantcheva, G. Gochev, D.R. Mehandjiev, D.S.
Ivanov, Transit. Met. Chem. 25 (2000) 196.
[19] P.R. Bontchev, I.N. Pantcheva, B. Ivanova, D.R. Mehandjiev, Bulg.
Chem. Commun. 31 (1999) 59.
[20] P.R. Bontchev, H. Kadum, B. Evtimova, Ch. Nachev, E. Zhecheva,
D.R. Mehandjiev, D. Ivanov, J. Inorg. Biochem. 48 (1992) 153.
[31] Y. Nishida, S. Kida, J. Inorg. Nucl. Chem. 38 (1976) 451.
[32] R. Mergehenn, L. Merz, W. Haase, J. Chem. Soc., Dalton Trans. 9
(1980) 1703.
[33] N.F. Curtis, F.W.B. Einstein, K.R. Morgan, A.C. Willis, Inorg.
Chem. 24 (1985) 2026.
[34] S. Wang, S.J. Trepanier, J.C. Zheng, Z. Pang, M.J. Wagner, Inorg.
Chem. 31 (1992) 2118.
[35] T. Lindgren, R. Sillanpa¨a¨, K. Rissanen, L.K. Thompson, C.J. O’Con-
nor, G.A. VanAlbada, J. Reedijk, Inorg. Chim. Acta 171 (1990) 95.
[36] O. Kahn, Molecular Magnetism, Wiley, Chichester, UK, 1994.
[37] E.A. Boudreaux, L.N. Mulay, Theory and Applications of Molecular
Paramagnetism, Wiley, New York, 1976.