Synthesis, characterization and anticancer studies of bis(1-phenylpiperazine dithiocarbamato) Cu(II), Zn(II) and Pt(II) complexes: Crystal structures of 1-phenylpiperazine dithiocarbamato-S,S′ zinc(II) and Pt(II)

Article abstract of DOI:10.1016/j.molstruc.2018.05.068

Copper(II), zinc(II) and platinum(II) complexes of phenylpiperazine dithiocarbamate formulated as [CuL₂], [PtL₂] and [Zn₂(μ-L)₂(L)₂], where L = phenylpiperazine dithiocarbamate were prepared and characterized by elemental analysis IR, UV–Visible, ¹H and ¹³C NMR spectroscopy. Single crystal X-ray structures of the Zn(II) and Pt(II) complexes are also reported. The FTIR spectra of the complexes confirm the bidentate coordination of the ligand to the metal ions by the single band due to ν_(C–_S) observed in the range 1012–1014 cm^?1 compared to that of the ligand at 994 cm^?1. Electronic spectra of both the Cu(II) and Pt(II) complex are consistent with square planar geometry, this is further confirm in the case of the Pt(II) complex by the single X-ray crystal structure. The molecular structure of the Zn(II) complex indicate a centrosymmetric dimeric compound in which each of the zinc ion is bonded to two molecules of the ligands acting as either bidentate chelating or as bridging coordinating ligand resulting in a distorted octagonal cycle comprising of two zinc ions, two thioureide carbons and four sulphur atoms. The geometry around each zinc ion is a distorted tetrahedral geometry. The Pt(II) complex consist of a monomeric entity where the Pt(II) ion is surrounded by four sulphur donor atoms from the two phenylpiperazine dithiocarbamate ligands forming a slightly distorted square planner geometry around the Pt(II) ion. Anticancer potency of the complexes against three cancer cell lines indicates UACC62 > MCF7 > TK10 at IC₅₀ values of 3.34, 17.52 and 19.83 μM respectively for the Cu(II) complex. MCF7 > TK10 > UACC62 at IC₅₀ of 8.42, 13.40 and 15.14 μM respectively for Zn(II), whereas for the Pt(II) the activity stands at concentration (IC₅₀) >100 μM for all the cell lines.

Full text of DOI:10.1016/j.molstruc.2018.05.068

Accepted Manuscript
Synthesis, characterization and anticancer studies of bis(1-phenylpiperazine
dithiocarbamato) Cu(II), Zn(II) and Pt(II) complexes: Crystal structures of 1-
phenylpiperazine dithiocarbamato-S,S′ zinc(II) and Pt(II)
Fartisincha P. Andrew, Peter A. Ajibade
PII:
S0022-2860(18)30636-7
10.1016/j.molstruc.2018.05.068
MOLSTR 25241
DOI:
Reference:
To appear in: Journal of Molecular Structure
Received Date: 12 February 2018
Revised Date: 20 May 2018
Accepted Date: 21 May 2018
Please cite this article as: F.P. Andrew, P.A. Ajibade, Synthesis, characterization and anticancer studies
of bis(1-phenylpiperazine dithiocarbamato) Cu(II), Zn(II) and Pt(II) complexes: Crystal structures of 1-
phenylpiperazine dithiocarbamato-S,S′ zinc(II) and Pt(II), Journal of Molecular Structure (2018), doi:
10.1016/j.molstruc.2018.05.068.
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Graphical Abstract

ACCEPTED MANUSCRIPT
Synthesis, characterization and anticancer studies of bis(1-phenylpiperazine dithiocarbamato)
Cu(II), Zn(II) and Pt(II) complexes: Crystal structures of 1-phenylpiperazine dithiocarbamato-
S,S' zinc(II) and Pt(II)
Fartisincha P. Andrew, Peter A. Ajibade*
School of Chemistry and Physics, University of KwaZulu-Natal, Private Bag X01, Scottsville,
Pietermaritzburg 3209, South Africa
ABSTRACT
Copper(II), zinc(II) and platinum(II) complexes of phenylpiperazine dithiocarbamate formulated
as [CuL2], [PtL2] and [Zn2(ꢀ-L)2(L)2], where L = phenylpiperazine dithiocarbamate were
prepared and characterized by elemental analysis IR, UV-Visible, 1H and 13C NMR
spectroscopy. Single crystal X-ray structures of the Zn(II) and Pt(II) complexes are also reported.
The FTIR spectra of the complexes confirm the bidentate coordination of the ligand to the metal
ions by the single band due to ν(C-S) observed in the range 1012-1014 cm-1 compared to that of
the ligand at 994 cm-1. Electronic spectra of both the Cu(II) and Pt(II) complex are consistent
with square planar geometry, this is further confirm in the case of the Pt(II) complex by the
single X-ray crystal structure. The molecular structure of the Zn(II) complex indicate a
centrosymmetric dimeric compound in which each of the zinc ion is bonded to two molecules of
the ligands acting as either bidentate chelating or as bridging coordinating ligand resulting in a
distorted octagonal cycle comprising of two zinc ions, two thioureide carbons and four sulphur
atoms. The geometry around each zinc ion is a distorted tetrahedral geometry. The Pt(II)
complex consist of a monomeric entity where the Pt(II) ion is surrounded by four sulphur donor
atoms from the two phenylpiperazine dithiocarbamate ligands forming a slightly distorted square
planner geometry around the Pt(II) ion. Anticancer potency of the complexes against three
cancer cell lines indicates UACC62 > MCF7 > TK10 at IC50 values of 3.34, 17.52 and 19.83 ꢀM
respectively for the Cu(II) complex. MCF7 > TK10 > UACC62 at IC50 of 8.42, 13.40 and 15.14
ꢀM respectively for Zn(II), whereas for the Pt(II) the activity stands at concentration (IC50) >100
ꢀM for all the cell lines.
Keywords: Phenylpiperazine dithiocarbamate; metal (II) complexes; anticancer; crystal
structure.
*Corresponding author E-mail: ajibadep@ukzn.ac.za
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1. Introduction
Cancer is the second leading cause of death worldwide after cardiovascular diseases [1-4].
Although, platinum-based compounds are the main metal-based compounds used at present for
the treatment of various type of cancers but various side effects such as; nephrotoxicity,
neurotoxicity and drug resistance [5-7], these have, plague them significantly limit their clinical
applications. Consequently, there has been a consistent search for anticancer agents with reduced
toxicity, broader spectrum of activity and effectiveness against resistant cancer cells. The use of
transition metal complexes as anticancer agents is increasing since the successful clinical
integration of cisplatin in 1978 [8, 9]. Metal dithiocarbamates for instance has received much
attention in developing anticancer agents [10-13]. In addition to their stable bonding
configuration and various structural arrangement in solid state due to delocalized lone pair of
electrons on carbon -nitrogen and carbon-sulphur (NCSS-) backbone of the thioureide moiety
[14]. Metal dithiocarbamates of various transition elements such as copper, platinum and zinc,
are potential sources for effective anticancer agents [15, 16]. They have shown various degrees
of DNA binding affinity and potential cytotoxic and antiproliferative activity [17-19]. They have
been used to combat platinum drug resistance and toxicity [20, 21]. NF-κB that is known to
promote tumor cell proliferation, suppresses apoptosis, attracts angiogenesis, and induces
epithelial mesenchymal transition [22], is significantly inhibited by metal dithiocarbamates [23,
24]. In view of these potential properties of metal dithiocarbamates and the growing interest in
alternative therapeutic compounds, we present the synthesis, characterization and anticancer
screening of copper(II), zinc(II) and platinum(II) phenylpiperazine dithiocarbamate complexes.
The single crystal X-ray structures of the Zn(II) and Pt(II) complexes are also presented and
discussed.
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2.
Experimental
2.1 Material and method
All the starting materials used in this synthesis were of commercial source (from Aldrich and
13
Merck) and were used as obtained. NMR spectra (1H and C) of the ligand and the complexes
were obtained using Bruker Avance III 400 MHz spectrophotometer with TMS as internal
standard. The proton and carbon shifts are presented in parts per million in relation to the
relevant solvent signals. FT-IR spectra were obtained using Perkin Elmer spectrum 100 FTIR
spectrophotometer (between 4000-500 cm-1). The UV-Visible spectrum were recorded using
Cary100-UV-Vis spectrophotometer Agilent Technology. Elemental analysis was carried out
using Thermoscientific Flash 2000. Molar conductivity were measured in Jenway 4510
conductivity meter using 0.01M DMSO solution of the ligand and the complexes. The cell lines
TK10, UACC62 and MCF7 were acquired from National Cancer Institute (NCI) in collaboration
with Council for Scientific and Industrial Research (CSIR) South Africa. In vitro cytotoxic
activity of the compounds was tested using sulforhodamine assay.
2.2 Synthesis of sodium salt of phenylpiperazine dithiocarbamate
2 mL cold aqueous solution of NaOH (2.0 g, 50 mmol) was added to 15 mL cold methanolic
solution of 1-phenylpiperazine (8.0712 g, 50 mmol) followed by the addition of cold carbon
disulfide (3.798 g, 50 mmol). It was stirred for 4 hrs under ice bath (0-4 °C), a precipitate (white)
was obtained, filtered and washed with diethyl ether and dried in a desiccator over silica gel. %
Yield
=
78%, melting point; 159 °C, Λm(ꢁ-1cm2mol-1), 68, Anal. Cal for
Na(S2CNC4H8NC6H5)·2H2O: C, 44.58; H, 5.78; N, 9.45; S, 21.64. Found: C, 44.28; H, 5.82; N,
1
9.35; S, 21.92, H NMR (400 MHz, D2O, δ, ppm); 7.41 (t, 2H), 7.17 (d, 2H), 7.08 (t, 1H), 4.50
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(t, 4H), 3.23 (t, 4H), 13C NMR (400 MHz, D2O, δ, ppm), 209.01 (CS), 49.70, 50.45 (N-
CH4CH4N-) 117.98, 122.16, 129.59, 150.34 (-C6H5), UV-Vis (H2O, λmax, nm) 261, 286
(shoulder), Selected IR (solid state, cm-1) (ѴC-N), 1462, (Ѵ(C-S2 ), 994.
2.3 Synthesis of phenylpiperazyldithiocarbamato-S,S’ copper(II) [Cu(L)2]
10 mL aqueous solution of CuCl2·2H2O (0.3410 g, 2 mmol) was added slowly to aqueous
solution of the sodium salt of phenylpiperazine dithiocarbamate (1.040 g, 4 mmol) and was
stirred at room temperature for 3 hrs. The brown precipitate formed was filtered and washed
many times with distilled water thereafter with methanol and was dried in a desiccator over silica
gel to give a brown solid. % Yield = 66 %, melting point; 265 °C, Λm(ꢁ-1cm2mol-1), 0.17 Anal.
Cal for [Cu(S2CNC4H8NC6H5)2]: C, 48.74; H, 5.21; N, 10.33; S, 23.66. Found: C, 49.09; H,
4.87; N, 10.41; S, 23.83, Selected IR (solid state, cm-1): (ѴC-N), 1480, (Ѵ(C-S)) 1014, UV-Vis
(CHCl3, λmax, nm); 272, 292 (shoulder), 440, 640.
2.4 Synthesis of phenylpiperazyldithiocarbamato-S,S’ platinum(II) [Pt(L)2]
Aqueous solution of K2PtCl4 (0.1245 g, 0.3 mmol) was slowly added to aqueous solution of
sodium salt of phenylpiperazine dithiocarbamate (0.1562 g 0.6 mmol). The mixture was allow to
stirred for 6 hrs under room temperature, a yellow precipitated was obtained, it was filtered,
washed many times with water and methanol and dried over silica to give a yellow solid. %
Yield
=
72 %, melting point; 346 °C, Λm(ꢁ-1cm2mol-1), 2.4, Anal. Cal for
[Pt(S2CNC4H8NC6H5)2]: C, 39.45; H, 3.91; N, 8.36; S, 19.15. Found: C, 39.82; H, 3.56; N, 8.14;
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S, 19.53, Selected IR (solid state, cm-1): (ѴC-N), 1498, (Ѵ(C-S)) 1013, UV-Vis (CHCl3, λmax, nm):
258, 293 (shoulder), 354, 408.
2.5 Synthesis of phenylpiperazyldithiocarbamato-S,S’ zinc(II) [Zn2(L)4]
0.1363 g (1 mmol) of ZnCl2 dissolved in 10 mL ethanol was slowly added to 0.520 g (2 mmol)
of sodium salt of phenylpiperazine dithiocarbamate dissolved in water and stirred under room
temperature for 3 hrs, a white precipitated was formed, filtered and wash many times with water
and ethanol, and dried over silica gel. Slow evaporation of chloroform solution of the complex at
room temperature result in a crystal for x-ray crystallography. %Yield = 89 % , melting point;
296 °C, Λm(ꢁ-1cm2mol-1), 1.8, Anal. Cal for [Zn(S2CNC4H8NC6H5)2]: C, 48.92; H, 4.85; N,
10.37; S, 23.75. Found: C, 48.77; H, 4.98; N, 10.13; S, 24.02, 1H NMR (400 MHz, (CD3)2SO, δ,
ppm); 7.23(t, 2H), 6.96(d, 2H), 6.79(t, 1H), 4.21(s, 4H), 3.21(t, 4H) 13C NMR (400 MHz,
(CD3)2SO, δ, ppm) 195.35 (CS), 49.71, 47.82 (N-CH4CH4N-) 115.55, 119.10, 128.92, 150.33 (-
C6H5) Selected IR (solid state, cm-1): (ѴC-N) 1501, (Ѵ(C-S)) 1012, UV-Vis (CHCl3, λmax, nm);
265, 286 (shoulder).
2.6. In vitro anticancer studies
Sulforhodamine B assay [25] was used to probe the cell viability of the compounds in vitro
against UACC62, TK10 and MCF7 human cancer cell lines. The cell lines were cultured in
RPMI augmented with 5% fetal bovine serum, 2 mM L-glutamine and 50µg/ml gentamicin
under the following condition; 37 ºC, 100 % humidity, 5 % CO2 and 95 % air. The cells were
lodged in 96 wells plates at 7-1 x 104 cells/well and incubated for 24 hours. It was then treated
with the test compounds prepared in DMSO and made to 5 x 10-fold serial dilutions (50-0.005
ꢀM) in medium. Blank was made of complete medium only without cells. Parthenolide and cells
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without drug serve as standard and control respectively. The plates treated with the test
compounds were cultured for 48 hours. Viable cell were sedimented by 50 % cold trichloroacetic
acid. It was dyed with sulforhodamine when dried. The protein bound dye was then extracted
with Tris base (10 mM) and optical density determined at 540 nm by multiwell
spectrophotometer. GraphPad prism software was used in analyzing the data. IC50 was then
determined by nonlinear regression.
[26-28].
2.7
X-ray crystallography
Single crystals of the Zn (II) and Pt(II) complexes were obtained by slow evaporation of
chloroform and dichloromethane solution of their complexes respectively. Suitable crystals
(0.460 x 0.280 x 0.200 and 0.27×0.16×0.09) mm3 of the Zn(II) and Pt(II) respectively were
selected and mounted on a MITIGEN holder in paratone oil on a Bruker APEX-II CCD
diffractometer. The crystal was kept at T = 100(2) K during data collection. Using Olex2 [29],
The structure was solved in the space group P-1 and P21/c by Direct Methods using SHELXS-
2013 [30] structure solution program and refined by Least Squares using version 2016/6 of
SHELXL [31] All non-hydrogen atoms were refined anisotropically. Hydrogen atom positions
were calculated geometrically and refined using the riding model.
3.
Results and discussions
3.1 Synthesis and characterization
The synthesis of phenylpiperazine and its corresponding Cu(II), Pt(II) and Zn(II) complexes are
presented in Scheme 1. The air stable complexes are soluble in chloroform, diethyl sulfoxide and
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melt in the range 265-346 °C. The value of the molar conductivity 0.17 -2.4 ꢁ-1cm2mol-1
recorded at room temperature in 0.01M DMSO solution of the compounds indicate non-
electrolytic nature of the complexes. The results obtained from spectroscopic studies are
consistent with the proposed four coordinate geometry for Cu(II) and Pt(II) complexes in which
two molecules of phenylpiperazine dithiocarbamate bond the central metal ions as bidentate
chelating ligand. Single crystal X-ray crystallographic studies of the Zn(II) complex confirmed a
dimeric molecular structure, whereas the molecular structure of the Pt(II) complex is a
monomeric structural entity.
Scheme 1. Preparation of phenylpiperazine dithiocarbamate and its Cu(II), Zn(II) and Pt(II)
complexes
3.2 Single crystal structures of [Zn2(ꢀ-L)2(L)2] and [Pt(L)2]
The single crystal structures and unit cell packings of the Zn(II) and Pt(II) complexes are
presented in Figure 1, 2, 3 and 4 respectively. Their crystal data and refinements are shown in
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Table 1, some selected bond lengths and bond angles are shown in Table 2 and 3 respectively.
The molecular structure of the Zn(II) complex exhibit a centrosymmetric dimeric entity with the
zinc centers residing on crystallographic inversion center. Each of the zinc ion is bonded to two
molecules of the dithiocarbamate ligand, with one acting as bidentate chelating ligand and the
other as bridging coordinating ligand forming interconnected distorted octagonal cyclic ring
consisting of two zinc ions, two thioureide carbons and four sulphur donor atoms all together
forming a chair like configuration. The unequal bond length (Zn-S) and angle (S-Zn-S) (Table 2
and 3) around the zinc centers indicate an asymmetric bidentate coordination of the ligand to the
zinc ions, this indicate the geometry around the zinc ions is distorted tetrahedral. The values of
the Zn-S bond lengths and S-Zn-S bond angles (Table 2 and 3) are in the range of dinuclear bis-
(dithiocarbamato-S,S′) Zn(II) complexes reported in literature [32-38].
The Pt(II) complex crystallized in monoclinic P21/c space group. The crystal structure display
monomeric structural entity where the Pt(II) ion is surrounded by four sulphur donor atoms from
the two bidentate phenylpiperazine dithiocarbamate ligands forming a centrosymmetric slightly
distorted square planner geometry. The bond lengths Pt1—S1 and Pt1—S2 are 2.3199(5) Å and
2.3275(5) Å respectively. The C1—S1 (1.722(2) Å) bond length is slightly shorter than typical
C—S (1.815 Å) single bond and longer than C=S (1.671 Å) this suggest a partial double bond
character as a consequence of delocalization of electron density in the S—C—S group [39]. The
slight distortion of the geometry around the Pt(II) ion from a perfect square planner can be
attributed to the small bite angle; S1—Pt1—S2 (75.057 19°) of the dithiocarbamate ligand. This
is consistent with mononuclear bis-dithiocarbamate complexes [40-42]
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Figure 1. Molecular structure of [Zn2(ꢀ-L)2(L)2] showing atomic labelling displacement
ellipsoid at 50% probability
Figure 2. Molecular structure of [Pt(L)2] showing atomic labelling displacement ellipsoid at
50% probability
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Figure 3. Unit cell packing diagram of [Zn2(ꢀ-L)2(L)2]
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Figure 4. Unit cell packing diagram of [Pt(L)2]
Table 1. Crystal data and structure refinement for [Zn2(ꢀ-L)2(L)2] and [Pt(L)2]
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Compound
[Zn2(C11H13N2S2)4]·(HCCl3)2
[Pt(C11H13N2S2)2]
Formula
Dcalc./ g cm-3
C45 H54 Cl6 N8 S8 Zn2
1.577
C22H26N4PtS4
1.977
ꢀ/mm-1
1.495
6.627
Formula Weight
Size/mm3
676
669.80
0.27×0.16×0.09
100(2)
monoclinic
P21/c
0.460 x 0.280 x 0.200
100(2) K
Triclinic
P -1
T/K
Crystal System
Space Group
a/Å
b/Å
c/Å
α/°
β/°
γ/°
7.969(3)
11.538(4)
16.318(6)
100.623(14)
97.165(16)
106.519(14)
1388.5(9)
1
7.2456(2)
6.12860(10)
25.3873(6)
90
93.7290(10)
90
V/Å3
1124.95(4)
2
Z
Wavelength/Å
0.71073
1.293
0.71073
2.817
°
Θmin
/
°
Θmax
/
27.531
27.999
16695
Measured Refl.
Independent Refl.
Reflections Used
Rint
18975
6200
2708
5755
2447
0.0194
0.0223
142
Parameters
Restraints
316
3
2
Largest Peak
Deepest Hole
GooF
0.375
0.627
-0.208
-0.514
1.039
1.070
wR2 (all data)
wR2
0.0524
0.0333
0.0322
0.0512
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R1 (all data)
0.0234
0.0210
0.0183
0.0151
R1
Table 2. Selected bond lengths (Å) for [Zn2(
ꢀ
-L)2(L)2] and [Pt(L)2]
[Zn2(ꢀ-L)2(L)2] Bond
S1—Zn1
Length
[Pt(L)2] Bond
Length
2.3400(8)
2.4558(9)
2.3554(7)
Pt1—S1
2.3199(5)
2.3275(5)
1.722(2)
1.724(2)
1.321(3)
1.467(3)
1.458(3)
1.467(3)
1.462(3)
1.414(2)
S2—Zn1
S3—Zn1
S4—Zn11 2.3282(9)
Pt1—S2
S1—C1
S2—C1
C1—N1
N1—C5
C3—N2
N1—C2
N2—C4
N2—C6
C1—S1
C1—S2
C1—N1
1.7397(14)
1.7261(15)
1.3275(19)
C12—N3 1.3221(18)
C12—S4
C12—S3
1.7213(14)
1.7514(15)
Table 3. Selected bond Angles (°) for [Zn2(
ꢀ
-L)2(L)2] and [Pt(L)2]
[Zn2(ꢀ-L)2(L)2] Bond
S1—Zn1—S2
Angle (°)
75.84(3)
122.17(2)
116.60(8)
111.05(3)
129.27(2)
85.40(6)
[Pt(L)2] Bond
Angle (°)
S11—Pt1—S1 180
S11—Pt1—S2 104.943(19)
S1—Pt1—S2 75.057(19)
S11—Pt1—S21 75.057(19)
S1—Pt1—S21 104.943(19)
S1—Zn1—S3
S2—C1—S1
S3—Zn1—S2
S4—Zn1—S1
C1—S1—Zn1
C1—S1—Pt1
C1—S2—Pt1
S1—C1—S2
87.29(7)
86.99(8)
110.46(11)
C12—S3—Zn1 101.10(5)
N1—C1—S2
121.82(10)
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N3—C12—S4
S41—Zn1—S2 106.95(2)
119.10(10)
N1—C1—S1
N1—C1—S2
124.26(17)
125.25(17)
3.3 Infrared spectra studies of the complexes
The FTIR spectrum of phenylpiperazine dithiocarbamate and the Cu(II), Zn(II) and Pt(II)
complexes were compared and carefully assigned. There are two significant region of FTIR
vibrational frequencies in metal dithiocarbamates, one lies in the region 1580 - 1450 cm-1 due to
thioureide C-N stretching vibration and the second one lies in the region 1060 – 940 cm-1 due to
C-S stretching vibration [43, 44]. The absorption at 1462 cm-1 is due to ν(C-N) of the thioureide.
A shift to higher frequencies in all the complexes upon coordination was observed at 1480, 1498
and 1501 cm-1 for [CuL2], [PtL2] and [Zn2(L)4] respectively. The shift could be due to the
electron flow towards the metal center consequence of ν(C-N) double bond character [43]. Single
band observed at 994 cm-1 in the free ligand was assigned to ν(C-S) stretching vibration. This band
also shift to appreciably higher frequency
̴
20 cm-1 difference upon complexation. Usually
absorption observed in this region defines the coordinated denticity of dithiocarbamates. Single
band at 950-1050 cm-1 according to Ugo and Bonati indicates bidentate chelation of the
dithiocarbamate, whereas double band suggest a monodentate coordination of dithiocarbamate
ligands to metal ions [45]. A single band at 1014, 1013 and 1012 cm-1 for [CuL2], [PtL2] and
[Zn2(L)4] respectively were assigned to ν(C-S) stretching vibration, indicating a bidentate
coordination of the ligand to the metal ions via the two sulphur atoms [46-48]. The vibrational
frequencies reported here are in agreement with a typical dithiocarbamate complexes previously
reported in literature [49-52].
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3.3 Electronic spectra
Electronic spectrum of the phenylpiperazine dithiocarbamate ligand in water exhibit absorption
at 261 nm (38314.18 cm–1) and a shoulder at 286 nm (34965.03 cm–1) (Table 4) assigned to
intraligand π-π* transition corresponding to S–C=S and N–C=S of the dithiocarbamate moiety
[53]. The electronic spectrum of the Cu(II) complex (Fig. S9) exhibit four bands, the first and
second bands at 272 nm (36740.73 cm-1) and shoulder at 292 nm (34246.58 cm-1) are ascribed to
intraligand π-π* transitions [53]. The third and fourth absorption bands at 440 nm (22727.27 cm-
2
1) and 640 nm (15625 cm-1) are assigned to metal to ligand charge transfer (MLCT) and B1g →
2A1g transitions respectively of the Cu(II) ion in a square planner environment [54-56].
Similarly, the spectrum of the Pt(II) complex (Fig. S10) exhibit four absorption bands, the first
and second bands at 257 (38910.51 cm–1) and a shoulder at 293 (34129.69 cm–1) are due to
intraligand π-π transitions. The third and fourth transitions at 354 (28248.59 cm–1) and 408
1
1
(24509.80 cm–1) are assigned to metal to ligand charge transfer (MLCT) and A1g → Eg
transitions respectively of Pt(II) ion in a square planner geometry [57-58] this is in agreement
with the crystal structure (Fig. 2). The Zn(II) complex being a d10 system there is no LFSE
associated with its compounds the d-orbital is fully filled as a result d-d bands are not observed.
Bands observed in their spectra are normally due ligand and/or MLCT transition. Therefore,
absorption at 265 nm (37735.85 cm–1) is assigned to π-π* and MLCT transition [59].
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Table 4. Electronic spectra of ligand and complexes
Compound
Free Ligand
Wavelength, λmax nm/(cm-1)
261 (38314.18 cm–1)
Assignment
n-π*/π-π* intraligand
286 (34965.03 cm–1) (shoulder)
272 (36740.73 cm-1),
[CuL2] (1)
n-π*/π-π* intraligand
292 (34246.58 cm-1) (shoulder)
440 (22727.27 cm-1)
MLCT
640 (15625 cm-1)
2B1g → 2A1g
[PtL2] (2)
257 (38910.51 cm–1),
n-π*/π-π* intraligand
293 (34129.69 cm–1) (shoulder)
354 (28248.59 cm–1)
MLCT
408 (24509.80 cm–1)
1A1g → 1Eg
[Zn2(ꢀ-L)2(L)2] (3)
265 (37735.85 cm–1)
Ligand band and MLCT
3.4. NMR spectra studies
The aromatic protons of the phenyl moiety in the free ligand appeared in the range 7.41 – 7.08 as
two triplets and a doublet. The four methylene -CH2 protons of the piperazine moiety appeared at
4.50 ppm and 3.23 ppm as triplets. There is an upfield shift upon coordination to the Zn(II) ion
with respect to those of the ligand. Consequently, the aromatic protons appeared in the range
7.23 – 6.76 ppm as two triplets and one doublet and the methylene -CH2 proton appeared at 4.21
and 3.21 ppm as triplets.
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13
Similarly, in the C NMR spectrum of the free ligand, the quaternary thioureide (CS2) carbon
resonate at 209.01 ppm. This signal appeared at 195.35 upon complexation, the upfield shift with
respect to that of the ligand could be due to the movement of electron density from the thioureide
moiety to the Zn(II) ion upon complexation that could have because the thioureide carbon nuclei
to be deshielded hence the upfield shift [60]. The aromatic carbons of the free ligand, which
resonate in the range 117.98-150.34 ppm, appeared also at upfield upon complexation in the
range 115.55-150.33 ppm. This is similar with the methylene carbons they appeared at 49.70 and
50.45 ppm; however, upon complexation there was an upfield shift to 47.83ppm and 49.70 ppm
respectively.
3.5. Anticancer studies
All the three complexes were evaluated in vitro by testing for inhibition extent of cell
proliferation against three human carcinomas; TK10 (renal), UACC62 (melanoma) and MCF7
(breast) using Sulforhodamine B (SRB) assay. The growth inhibition effect of the Cu(II)
complex against the cell lines followed the order UACC62 > MCF7 > TK10 at concentrations
(IC50) of 3.34, 17.52 and 19.83 ꢀM respectively, whereas for the Zn(II) complex followed the
order MCF7 > TK10 > UACC62 at concentration (IC50) of 8.42, 13.40 and 15.14 respectively.
However, the platinum(II) complex is active at a higher concentration (IC50) > 100 ꢀM. The
growth inhibition activity exhibited by Cu(II) and Zn(II) complexes may be because copper and
zinc are essential elements and have excellent biological activity [61].
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Table 5. IC50 (ꢀM) values of the against TK10, UACC62 and MCF7 cell lines
Complex
[CuL2]
TK10
19.83
>100
13.40
UACC62
3.34
MCF7
17.52
>100
8.42
[PtL2]
>100
[Zn2(ꢀ-L)2(L)2]
15.14
4.
Conclusion
Divalent copper, platinum and zinc phenylpiperazine dithiocarbamate complexes were
Synthesized and characterized by FTIR, UV-Visible, and NMR spectroscopy. Spectroscopic
studies indicate that the metal ions are bonded to two molecules of the phenylpiperazine
dithiocarbamate in bidentate coordination mode. The crystal structures of the Zn(II) complex
revealed dinuclear zinc centers with two phenylpiperazine ligands acting as bidentate chelating
ligands and the other two as bridging coordinating ligands between the two Zn(II) ions forming a
chair like eight membered ring consisting of two zinc ions, two thioureide carbon and four
sulphur donor atoms. The crystal structure of the Pt(II) complex consist of a monomeric
structural entity in which the Pt(II) ion is surrounded by four sulphur donor atoms from the two
bidentate phenylpiperazine dithiocarbamate ligands forming a centrosymmetric slightly distorted
square planner geometry. All the three complexes were screened against three cancer cell lines:
TK10 (renal), UACC62 (melanoma) and MCF7 (breast). The copper(II) was active against
UACC62 at a concentration as low as (IC50) 3.34 ꢀM and zinc(II) was active against MCF7 at a
concentration as low as (IC50) 8.42 ꢀM.
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Supplementary crystallographic data
CCDC 1585991 and 1841548 contain supplementary crystallographic data can be obtained from
the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif or from
The Director, CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK (Fax: + 44-1223-336-033; e-
mail: deposit@ccdc.cam.ac.uk).
Acknowledgements
The authors acknowledge the financial support of Sasol and National Research foundation, South
Africa for financial support. FPA acknowledge Tertiary Education Trust Fund (TETfund) and
Modibbo Adama University of Technology, Nigeria for the award of PhD scholarship.
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