Dimethyl sulfoxide containing platinum(II) and palladium(II) chelate complexes of glyoxylic and pyruvic acid thiosemicarbazones. A new class of cytotoxic metal complexes

Article abstract of DOI:10.1515/znb-2006-0909

The complexes [Pt(DMSO)(GT)]·DMSO (1), [Pt(DMSO)(PT)]·1/2DMSO (2) and [Pd(DMSO)(PT)] (3), where DMSO = dimethyl sulfoxide, H₂GT = glyoxylic acid thiosemicarbazone and H₂PT = pyruvic acid thiosemicarbazone, have been synthesized and characterized by elemental analysis, molar electric conductivity, IR, electronic and NMR (¹H and ¹³C) spectra. The single crystal X-ray diffraction analysis has revealed for 1 (orthorhombic, Pnma, a = 12.941(3), b = 7.108(2), c = 15.148(3) A?, Z = 4) that the doubly deprotonated thiosemicarbazone molecule is coordinated to Pt(II) via the carboxylato O, azomethine N and thiolato S atoms forming two condensed five-membered chelate rings. The fourth coordination site of Pt(II) is occupied by the S atom of DMSO. All the atoms of the complex molecule are coplanar except the methyl groups. The O atom of DMSO is in cis-position towards the thiolato-S atom (point group C_s). A system of hydrogen bonds of the type N-H?O links the complex molecules between them and with the lattice DMSO molecules. Similar structures have been deduced for the remaining two complexes on the basis of spectroscopic data. The three complexes and the ligand H₂GT exhibit cytotoxic activity against F4N leukemia cells, whereas the ligand H₂PT is inactive.

Full text of DOI:10.1515/znb-2006-0909

Synthesis, Spectral and Thermal Properties, and Crystal Structure of
Bis(ethylenediamine)(aqua)copper(II) (Bis)syringate Ethylenediamine
Dihydrate [Cu(en) (H O)](sy) (en)(H O)
2
2
2
2
2
a
b
b
a
Zerrin Heren , H u¨ meyra Pa s¸ ao g˘ lu , G o¨ khan Ka s¸ ta s¸ , Leyla Vurucu , and
b
Orhan B u¨ y u¨ kg u¨ ng o¨ r
a
Ondokuz Mayis University, Faculty of Arts and Sciences, Department of Chemistry,
TR-55139, Kurupelit, Samsun, Turkey b Ondokuz Mayis University, Faculty of Arts and Sciences,
Department of Physics,
TR-55139, Kurupelit, Samsun, Turkey
Reprint requests to Dr. H. Pa s¸ ao g˘ lu. E-mail: hpasa@omu.edu.tr
Z. Naturforsch. 61b, 287 – 291 (2006); received October 5, 2005
The complex [Cu(en) (H O)](sy) (en)(H O) has been synthesized and characterized by its elec-
2
2
2
2
2
tronic and vibrational spectra. The molecular structure of the complex has been determined by X-ray
diffraction methods. The complex crystallizes in the orthorhombic space group Pnma with unit-cell
˚
parameters a = 10.7236(5), b = 20.4660(10), c = 14.4523(11)A and Z = 4. In the cation, the Cu(II)
ion has a distorted square pyramidal coordination with two bidendate (en) ligands forming the basal
plane and a H O molecule in the apical position. The complex cations and syringate anions consti-
2
tute chains along the b axis in –A–B–A– fashion. The members of the chains are linked by through
N–H···O hydrogen bonds. The (en) molecules are responsible for connecting adjacent layers.
Key words: Syringic Acid, Ethylenediamine, Copper (II) Complex, Thermal Properties
Introduction
structure. In this study, we report the preparation and
structural characterization of the new square pyrami-
dal Cu(II) complex [Cu(en) (H O)](sy) (en)(H O) .
Major types of natural antioxidants are the pheno-
lic acids which are derivatives of benzoic and cinamic
acids [1]. There is a definite relationship between the
structures of the phenolic acids and their antioxidant
activities. The inhibitory effectiveness of monophe-
nols is substantially increased by one or two methoxy
groups. Syringic acid, 4-hydroxy-3,5-dimethoxybenz-
oic acid [syH], is one of the most active antioxidants
with two methoxy roups [2, 3]. Furthermore, syringic
acid has been identified as an active ingredient which
contributes to the prevention of cancer, inhibiting tu-
mour initiation, promotion and progression and heart
disease [3, 4]. The salts of 4-hydroxy-3,5-dimethoxy-
benzoic acid with various cations and mixed ligand
complexes of d-block elements have not been studied.
Ethylenediamine is an N-donor chelator and has been
studied intensively, both structurally and spectroscopi-
cally for many years [5, 6]. Therefore, we selected sy-
ringic acid as primary ligand and prepared Cu(II) eth-
ylenediamine complexes and examined their thermal
stability in air, IR spectral characteristics and crystal
2
2
2
2
2
Results and Discussion
Spectral and magnetic properties
The coordination sphere of the complex can be
treated in terms of C2v molecular symmetry. In the IR
spectrum, the region of the NH stretching vibrations
2
is relatively broaden by partial superposition with the
O-H vibrations of the coordinated and uncoordinated
−1
water molecules. The bands at 3370 and 3050 cm
are due to the symmetric and asymmetric stretching
vibrations of the NH groups of the coordinated and
2
uncoordinated en ligands. The vibrational frequencies
−1
the CH groups of the en ligands appear at 800 cm
.
2
This is in agreement with literature data [7, 8]. The
−1
Cu–N stretching frequency was observed at 750 cm
.
In the IR spectrum of free syringic acid there is a strong
−1
absorption band at 1700 cm for the COOH group,
which is absent for the complex, and the bands due
to the asymmetric and symmetric stretching of car-
−
1
boxylate groups occur at 1575 and 1373 cm , respec-
tively [9]. The bands of the C-H asymmetric stretching
Syringic acid = 4-hydroxy-3,5-dimethoxybenzoic acid.
0
932–0776 / 06 / 0300–0287 $ 06.00 ꢀc 2006 Verlag der Zeitschrift f u¨ r Naturforschung, T u¨ bingen · http://znaturforsch.com
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2
88
Z. Heren et al. · Bis(ethylenediamine)(aqua)copper(II)
˚
◦
Table 1. Crystal data and structure refinement parameters for Table 2. Selected bond lengths (A) and bond angles ( ) for
[
Cu(en) (H O)](sy) (en)(H O) .
[Cu (en) (H O)](sy) (en)(H O) .
2
2
2
2
2
2
2
2
2
2
˚
Bond lengths (A)
Cu1–N1
Cu1–N2
Empirical formula
Formula weight
Temperature [K]
Wavelength [A]
Crystal system
Space group
C24H48CuN6O13
692.22
296
0.71073 Mo-Kα
orthorhombic
Pnma
2.014 (3)
2.012 (3)
1.266 (4)
Cu1–O1
O6–C11
2.285 (3)
1.255 (4)
˚
O5–C11
◦
Bond angles ( )
N2–Cu1–O1
N2–Cu1–N1
92.00 (11)
84.10 (12)
N1–Cu1–O1
95.35 (12)
171.55 (15)
i
˚
N2 –Cu1-N1
Unit cell dimensions [A]
Symmetrie Code i x, 1/2−y,z.
a,
b,
c
10.7236 (5),
20.466 (1),
14.452 (1)
3171.8 (3)
4
Table 3. Hydrogen bonds ( A˚ , ) for [Cu(en) (H O)](sy) -
◦
2
2
2
˚
3
V [A ]
(en)(H O) .
2
2
Z
D–HA···A
D–H
H···A
D···A
D–HA
Absorption coefficient [mm 1]
−
0.760
1.450
i
N1–H1···O6
N2–H8···O2
0.93 (3)
0.89 (3)
0.83 (3)
2.06 (4)
2.11 (4)
1.84 (3)
2.960 (4) 165 (3)
2.996 (4) 174 (3)
2.663 (3) 167 (3)
−
3
Dcalcd. [Mg m
Crystal size [mm ]
Theta range for
]
ii
3
0.310×0.180×0.060
iii
iv
iv
v
O7–H23···O6
N4–H10···O2
N4–H10···O4
N3–H11···O2
O1–H9···O5
O8–H24···O5
O2–H22···O3
O2–H22···N3
1.41 – 27.14
0.914 (17) 1.860 (19) 2.740 (3) 161 (3)
0.914 (17) 2.40 (3)
0.865 (17) 1.90 (2)
0.92 (4)
0.98 (5)
0.820
data collection [deg]
Measured reflections
Independent reflections
Absorption correction
3.007 (2) 124 (3)
2.730 (4) 160 (3)
2.762 (3) 175 (4)
2.853 (3) 141 (5)
2.659 (3) 114.89
2.730 (4) 153.30
iii
38715
3575
Integration
Full-matrix least-squares on F
R1 = 0.043, wR2 = 0.078
R1 = 0.112, wR2 = 0.092
0.810
1.85 (4)
2.02 (5)
2.207
2
Refinement method
2
2
Final R indices [F > 2σ(F )]
R Indices (all data)
v
0.820
1.973
i
ii
2
Symmetry codes: x, 1/2 − y, z; 3/2 − x, y − 1/2, 1/2 + z; x −
Goodness-of-fit on F
i
v
v
1
/2, y, 1/2−z; 3/2−x, 1−y, z−1/2; 1−x, 1−y, 1−z.
Largest difference peak
0.420; −0.573
˚
−3
)
and hole (e A
netic moment value of the complex is 1.22 BM corre-
sponding to one unpaired electron.
Thermal properties
The crystals contain water of crystallization and
copper-coordinated water. The thermal dehydration
◦
occurred in two steps with endothermic effects at 40 C
◦
and 132 C (Fig. 1). One mole of coordinated water
and two moles of crystallization water are removed
at these stages (exp. 8.89%; calcd. 7.81%). A color
change from black to brown was noted on removal
of the water molecules. Further heating causes evap-
oration of one of the ethylenediamine molecules, re-
◦
sulting in an endothermic DTA peak at 154 C (exp.
1
2.89%; calcd. 12.18%). The product is very unsta-
Fig. 1. TG and DTA curves of the [Cu(en) (H O)](sy) (en)
2
2
2
ble and undergoes further decomposition by release of
the remaining ethylenediamine and decomposition of
the syringiato ligands. The exothermic peak at 481 C
can be explained by the burning of the organic residue
formed in the previous stages. The final solid product
of thermal decomposition was identified as CuO (exp.
(
H O) complex.
2 2
◦
of the CH groups appear at similar frequencies as in
3
−
1
free syringic acid (2850 cm ).
The electronic d-d transition spectrum of Cu(en)2
(
H O)](sy) (en)(H O) is compatible with the dis-
2 2 2 2
8
6.85%; calcd. 88.50%).
torted square pyramidal configuration. The maximum
−
1
−1
absorption is at 567 with ε = 61.0 Lmol cm
.
Crystal structure
This band is assigned to the a → b d-d transition
1
1
[
1
10– 14]. The band observed around 299 nm (ε =
The crystallographic analysis confirmed that the
− −1
362 Lmol cm ) is attributed to MLCT. The mag- complex consists of discrete [Cu(en) H O] cations,
2 2
1
2+
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Z. Heren et al. · Bis(ethylenediamine)(aqua)copper(II)
289
Fig. 2. Perspective view and atom label-
ing scheme of [Cu(en) (H O)](sy) (en)
2
2
2
(
H O) . Atomic displacement ellipsoids
2 2
are drawn at the 50% probability level.
Symmetry transformation used to gener-
ate equivalent atoms (i) x, −y+1/2, z.
One of the interesting features of the structure is
that the en molecules exhibit chemically different func-
tions. While in one form they coordinates to metal
cation, in the other form they are molecules of sol-
vation (Fig. 3). In the latter, they provide bifurcated
(
three-centered) hydrogen bonds (Table 3). The sy-
−
ringate anions [sy] do not act as ligands, but are incor-
porated into the crystal structure by hydrogen bonds.
The bond distances in the carboxylate group of de-
−
protonated [sy] are nearly equal (Table 2). This is
responsible for the shifting and splitting of the vibra-
tional bands of the carboxylate group.
˚
The Cu–N distances are 2.014(3) and 2.012(3) A,
similar to those found in related structures [15– 17].
The trans angles N–Cu–N at the Cu(II) ion devi-
◦
ate from linearity with a value of 171.55(15) . The
˚
Cu1–O1 distance is 2.285(3) A, and thus in agree-
ment with the reported values for square pyramidal
structures [18 – 20]. It is found that the apical Cu–O
bond is larger than the basal Cu–N bonds. This is be-
cause the short Cu–N bonds prevent the water mole-
cules from approaching the copper atom, and keep it
Fig. 3. A view of the complex, [Cu(en) (H O)](sy) (en)
2
2
2
(
H O) , normal to (100), showing different types of hydro-
gen bonding interactions responsible for the layered struc-
ture. Refer to Table 3 for symmetry codes.
2 2
˚
at a distance of 2.285 (3) A. The (en) chelate ring
Cu1 N2 N1 C2 C1) is close to planar, with an r. m. s
(
˚
two deprotonated syringate anions, one neutral (en) deviation of 0.1918 A. The Cu(II) cation departs from
molecule and two water molecules of solvation. The the mean plane defined by the four nitrogen atoms of
Cu(II) ion has a distorted square-pyramidal coordina- the pyramidal basis by 0.0358(18) A towards the axial
˚
tion. The basal coordination plane is formed by two water ligand.
symmetry-related, chelating (en) groups. The coordi-
nation is completed by a water molecule located at the moderate hydrogen bonding. These intermolecular in-
pyramid apex (Fig. 2).
teractions are depicted in Fig. 3, and are included in
The packing in the crystal is stabilized by strong and
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90
Z. Heren et al. · Bis(ethylenediamine)(aqua)copper(II)
Synthesis of Cu (II) syringate
The complex was prepared by mixing an aqueous solu-
tion of Cu(II) acetate (1 mmol) with a methanolic solution
of syringic acid (2 mmol). The reaction mixture was stirred
◦
overnight at 50 C and the brown product was isolated by
filtration, washed with cold distilled water and diethyl ether
and dried in air.
Synthesis of the Cu(II) syringate ethylenediamine complex
A solution of ethylenediamine (2 mmol) in distilled wa-
ter (20 ml) was added dropwise with stirring to a solution of
Cu(II) syringate (1 mmol) in distilled water (40 ml). The so-
◦
lution was heated and stirred for 5 h at 70 C and then the
mixture was cooled to room temperature. The black crystals
were filtered and washed with 10 ml of cold distilled water
Fig. 4. The unit-cell packing of the complex, [Cu(en) (H O)]
2
2
and acetone and dried in vacuo. UV/vis (H O): λmaxε) =
(
sy) (en)(H O) , normal to (100).
2
2
2
2
−1
5
67 nm (4.11). –IR (KBr): ν˜ = 3370 and 3050 cm (NH2).
–C24H CuN O (692.2): calcd. C 41.64, H 6.94, N 12.14;
2
+
Table 3. As shown in Fig. 4, [Cu(en) H O] complex
48
6
13
2
2
−
found C 41.05, H 7.43, N 12.82.
cations and [sy] anion constitute a chain which is re-
peated along the b axis in a –A–B–A– fashion, with a
dihedral angle of 24.14 (10) between the (en) chelate
X-ray structure determination
◦
Diffraction experiments were carried out at 296 K on a
Stoe IPDS diffractometer. The structure was solved by di-
rect methods using the program SHELXS97 [21]. All non-
hydrogen atoms were refined anisotropically by full-matrix
least-squares methods [SHELXL-97]. Hydrogen atoms at-
tached to C9, C10 and O2 were placed in geometrically ide-
alized positions and refined as riding atoms. Therefore, the
ring (Cu1 N2 N1 C2 C1) and the (C3 C4 C5 C6 C7 C8)
plane. The neighbouring chains are linked by uncoor-
v
dinated en ligands through N3–H11···O2 (v: 1 − x,
iv
1
− y, 1 − z) and N4–H10···O2 (iv: 3/2 − x, 1 − y,
z − 1/2) hydrogen bonds (Fig. 3). This arrangement
leads to a layered structure. It can be seen from Fig. 4
that the uncoordinated en and water molecules form
standart uncertainty (s.u) values for O2–H22···O3 and O2–
v
bridges between the layers through inter-molecular hy- H22···N3 hydrogen bondings is not included in Table 3. All
drogen bonds. The aqua ligands are linking adjacent other H atoms were located in a difference map, and their co-
−
[
sy] anions through O1–H9···O5 hydrogen bonds, ordinates andUiso(H) values were refined freely. The relevant
and are effective in forming a layered structure.
crystal data and experimental conditions along with the final
parameters are summarised in Table 1. Data collection: X-
Area, cell refinement: X-Area, data reduction: X-RED [21];
program(s) used to refine structure: SHELXL97 [22]; molec-
ular graphics: ORTEP-3 for Windows [23]; software used to
prepare material for publication: WinGX [24].
Experimental Section
Materials and measurements
All chemicals used were analytical reagent products.
Copper(II)acetatetetrahydrate and ethylenediamine were ob-
tained from Merck. Syringic acid was purchased from
ACROS Organics. The elemental analysis for C, H and N
Supplementary data
Crystallographic data for the structural analysis have
been deposited with the Cambridge Crystallographic Data
Centre, CCDC No. 271102. Copies of this information
may be obtained free of charge from the Director, CCDC,
¨
˙
were carried out at TUBITAK Marmara Research Centre.
The magnetic susceptibility measurement at room tempera-
ture was performed using a Sherwood Scientific MXI model
Gouy magnetic balance. The UV/vis spectrum was obtained
for the aqueous solutions of the complexes with a Unicam
UV2 spectrometer in the range 900 – 190 nm. The IR spec-
1
1
2 Union Road, Cambridge CB2 1EZ, UK (fax: +44-
223-336033; e-mail: deposit@ccdc.cam.ac.uk or www:
http://www.ccdc.cam.ac.uk).
−1
Acknowledgements
trum was recorded in the 4000 – 400 cm region with a
Mattson 1000 FT-IR spectrometer using KBr pellets. Ther-
The authors wish to acknowledge the Faculty of Arts and
mal analysis curves (TG and DTA) were recorded simultane- Sciences, Ondokuz Mayis University, Turkey, for the use of
ously in a static air atmosphere with a Rigaku TG8110 ther- the Stoe IPDS-II diffractometer (purchased under grant No.
◦
−1
.
mal analyzer. The heating rate was 10 C min
F279 of the University Research Fund).
-
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Z. Heren et al. · Bis(ethylenediamine)(aqua)copper(II)
291
[
[
[
[
1] S. Z. Dzicdzic, B. J. F. Hudson, Food Chemistry 14, 45
[14] C. Y. Wu, C. C. Su, Polyhedron 163, 383 (1997).
[15] I. M. Procter, B. J. Hathway, P. J. Nicholls, J. Chem.
Soc. A, 1678 (1968).
[16] K. Canan, T. Y. Veysel, K. Y. Turan, Acta Crystallogr.
E60, m593 (2004).
[17] A.-Y. Fu, D.-Q. Wang, F.-M. Wang, Acta Crystallogr.
E60, m1527 (2004).
[18] R. M. K. Deng, K. B. Dillion, A. E. Goeta,
M. Mapolelo, Inorg. Chim. Acta. 315, 245 (2001).
[19] G. Jovanovski, P. Naumov, O. Grup cˇ e, Eur. J. Solid
State Inorg. Chem. 35, 231 (1998).
[20] P. Naumov, G. Jovanovski, G. B. D. Michael, W. S. Ng,
Inorganica Chimica Acta 314, 154 (2001).
[21] Stoe & Cie, X-AREA and X-RED. Stoe& Cie, Darm-
stadt, Germany (2001).
(1984).
2] M. E. Cuvelier, H. Richard, C. Berst, Bioscience
Biotechnology Biochemistry 56, 324 (1992).
3] E. M. Marinova, N. N. Yarishlieva, Food Chemistry 81,
1
89 (2003).
4] E. H. Siemann, L. L. Creasy, Am. J. Enol. Vitic. 43, 49
1992).
(
[5] A. A. Bertelli, Int. J. Tiss. React. 17 (1995).
˙
[6] H.I c¸ budak, T. K. Yazıcılar, V. Y. Yılmaz, Thermochim.
Acta 93, 335 (1999).
˙
¨
[
[
[
7] O. Z. Ye s¸ ilel, H. I c¸ budak, H. Olmez, P. Naumov, Synth.
React. Inorg. Metal-Org. Chem. 33, 77 (2003).
˙
8] H. I c¸ budak, V. T. Yılmaz, Synth. React. Inorg. Met-
Org. Chem. 27, 1517 (1997).
9] S. Oksuz, A. Ulubelen, A. Barla, W. Voelter, Turk. J.
Chem. 26, 457 (2002).
[22] G. M. Sheldrick, SHLEXS-97 and SHELXL-97. Pro-
gram for Refinement of Crystal Structures, University
of G o¨ ttingen, Germany (1997).
[
[
[
[
10] B. J. Hathaway, A. A. G. Tomlison, Coor. Chem. Rev.
5
, 1 (1970).
[23] L. J. Farrugia, ORTEP-III. Program For Molecular
Drawing. J. Appl. Crystallogr. 30, 565 (1997).
[24] L. J. Farrugia, WinGX Suite for Single Crystal Small
Molecule Crystallography, J. Appl. Crystallogr. 32,
837 (1999).
11] B. J. Hathaway, in Comprehensive Coordination
Chemistry, Vol. 5, p. 594, Pergamon, Oxford (1987).
12] C. C. Su, J. S. Lin, S. L. Lin, S. L. Wang, F. L. Liao, J.
Coord. Chem. 30, 91 (1993).
13] F. A. Cotton, Advanced Inorganic Chemistry, pp. 642,
Wiley-Interscience, New York (1980).
-
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via free access