Imino-quinolyl palladium(II) and platinum(II) complexes: Synthesis, characterization, molecular structures and cytotoxic effect

Article abstract of DOI:10.1016/j.ica.2013.02.029

Imino-quinolyl ligands L1-L5 were synthesized by condensation reactions and obtained in good yields. Reactions of the ligands with either PdCl ₂(cod) or K₂[PtCl₄] gave the corresponding palladium(II) and platinum(II) complexes 1-10 also in good yields. All the compounds were characterized by elemental analysis, IR, ¹H and ¹³C NMR spectroscopy. X-ray crystallography was used to confirm the structures of these compounds. Molecular structures of 3 and 5 showed that the ligands coordinate to the metal center through the two nitrogen atoms, generating a distorted square planar geometry around the palladium atom. The new complexes exhibited remarkable cytotoxic activities against MCF-7 and HT-29 cancer cell lines.

Full text of DOI:10.1016/j.ica.2013.02.029

Inorganica Chimica Acta 400 (2013) 197–202
Contents lists available at SciVerse ScienceDirect
Inorganica Chimica Acta
journal homepage: www.elsevier.com/locate/ica
Imino-quinolyl palladium(II) and platinum(II) complexes: Synthesis,
characterization, molecular structures and cytotoxic effect
b
b
c
William M. Motswainyana a, Martin O. Onani a, , Abram M. Madiehe , Morounke Saibu , Jeroen Jacobs ,
⇑
Luc van Meervelt c
a Chemistry Department, University of the Western Cape, Private Bag X17, Bellville 7535, South Africa
b Department of Biotechnology, University of the Western Cape, Private Bag X17, Bellville 7535, South Africa
c Chemistry Department, KU-Leuven, Celestijnenlaan 200F, B-3001 Leuven (Heverlee), Belgium
a r t i c l e i n f o
a b s t r a c t
Article history:
Imino-quinolyl ligands L1–L5 were synthesized by condensation reactions and obtained in good yields.
Reactions of the ligands with either PdCl2(cod) or K2[PtCl4] gave the corresponding palladium(II) and
platinum(II) complexes 1–10 also in good yields. All the compounds were characterized by elemental
analysis, IR, 1H and 13C NMR spectroscopy. X-ray crystallography was used to confirm the structures of
these compounds. Molecular structures of 3 and 5 showed that the ligands coordinate to the metal center
through the two nitrogen atoms, generating a distorted square planar geometry around the palladium
atom. The new complexes exhibited remarkable cytotoxic activities against MCF-7 and HT-29 cancer cell
lines.
Received 7 November 2012
Received in revised form 3 February 2013
Accepted 14 February 2013
Available online 4 March 2013
Keywords:
Imino-quinolyl
Palladium
Ó 2013 Elsevier B.V. All rights reserved.
Platinum
Molecular structures
Cancer
Cytotoxicity
1. Introduction
group [5]. Reports have also demonstrated that varying the aniline
functionality allows the design of compounds with a wide range of
Transition metal complexes containing nitrogen-donor ligands
continue to be the subject of intense biological evaluations as the
search for less toxic and more selective anticancer drugs continues
[1]. The subtlety with which the ligands control the reactivity of
transition metal ions and the reciprocal effects that the metal ions
have on the properties of ligands are some of the interesting
dimensions being explored in the search for suitable ligands in
metallo-drugs [2]. Existing examples are seen in the use of pyridine
based platinum(II) complexes as mimics of cisplatin, because the
pyridine ligand gives rise to square planar complexes which are
structurally similar to cisplatin [3]. One important aspect relating
to planar ligands is that their complexes reduce the rate of deacti-
vation by thiol containing groups without interfering with DNA
binding [3]. The use of chelating, bidentate ligands has also been
viewed as important in preventing trans-labilization and undesired
displacement of the ligands by sulfur and nitrogen donors in
biomolecules [4].
physical and chemical properties that may provide desired steric
congestion around the coordinated metal atom [6]. The steric hin-
drance is favorable for this type of work because it prevents axial
approach to the metal atom, therefore inhibiting the formation of
a five-coordinate intermediate that would otherwise lead to a li-
gand substitution. This phenomenon permits high selectivity in
binding to DNA [6]. It is against this background that we report
the synthesis and characterization of sterically congested palla-
dium(II) and platinum(II) complexes derived from quinoline imine
bearing substituted aniline moiety. The new complexes were
investigated in vitro for their potential to exert cytotoxicity on
MCF-7 and HT-29 cancer cells and the results are herein discussed.
2. Experimental
2.1. Materials and methods
Recent research has shown that for a palladium drug to be
developed, it should be stabilized by a chelate or a strongly coordi-
nated, bulky monodentate nitrogen ligand and a suitable leaving
All reactions were carried out under nitrogen atmosphere using
a dual vacuum/nitrogen line and standard Schlenk techniques un-
less stated otherwise. Solvents were dried and purified by heating
at reflux under nitrogen in the presence of a suitable drying agent.
All the reagents and starting materials were purchased from
Sigma–Aldrich and were used without any further purification.
⇑
Corresponding author. Tel.: +27 21 959 3050; fax: +27 21 959 3055.
E-mail address: monani@uwc.ac.za (M.O. Onani).
0020-1693/$ - see front matter Ó 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.ica.2013.02.029

198
W.M. Motswainyana et al. / Inorganica Chimica Acta 400 (2013) 197–202
The palladium(II) precursor PdCl2(cod) was prepared following
literature method [7]. The 1H NMR experiments were performed
on a Varian XR200 MHz spectrometer. IR spectra in solution were
recorded with a Perkin-Elmer Spectrum 100 Series FT-IR instru-
ment using Nujol mulls on NaCl plates. Elemental analysis was
performed on Server 1112 Series Elemental Analyzer. X-ray diffrac-
tion data for the compound was collected on a Agilent SuperNova
1.99 mmol) and 2,6-diethylaniline (0.2972 g, 1.99 mmol). Reddish
brown oil was obtained [10]. Yield: 0.5509 g (96%); IR (Nujol
cmÀ1);
m(C@N imine) 1641, m(C@N quinolyl) 1596, m(C@C quinolyl)
1563, (C@C phenyl) 1504; 1H NMR (200 MHz, CDCl3): d 8.47 (s, 1H,
quinolyl); 8.39 (d, 1H, J = 8.4, quinolyl); 8.21 (dd, 1H, J = 8.4, quino-
lyl); 7.91–6.94 (m, 4H, quinolyl and imine); 6.76–6.69 (m, 5H,
phenyl); 2.52 (dd, 4H, Me); 1.57–1.09 (m, 6H, Me); 13C NMR
(50 MHz, CDCl3) d 154.55, 118.16, 136.70, 132.62, 147.92, 127.73,
125.96, 129.02, 127.73, 163.43 (imine), 149.54, 124.32, 129.89,
126.25, 129.76, 118.26, 24.65, 24.23, 14.53, 12.97. Anal. Calc. for
diffractometer using mirror-monochromated Mo K
a radiation
(k = 0.71073 Å). The crystal structures were solved by direct
methods using SHELX [8] and refined by full-matrix least-squares
methods based on F2 [8] using SHELX [8] and using the graphics
program OLEX2 [9].
C20H20N2: C, 83.30; H, 6.99; N, 9.71. Found: C, 83.54; H, 6.78; N,
9.99%.
2.2. Synthesis of the ligands
2.2.5. 2-(2,6-Diisopropylphenyl)iminomethylquinoline (L5)
The ligand was synthesized according to the procedure de-
scribed for L1 using 2-quinolinecarboxaldehyde (0.3318 g,
2.11 mmol) and 2,6-diisopropylaniline (0.3743 g, 2.11 mmol). Red-
dish brown oil was obtained. Yield: 0.6276 g (94%); IR (Nujol
2.2.1. 2-Phenyliminomethylquinoline (L1)
To
a
solution of 2-quinolinecarboxaldehyde (0.3830 g,
2.44 mmol) in CH2Cl2 (10 ml) was added aniline (0.2269 g,
2.44 mmol) dropwise. The reaction was stirred at room temperature
for 10 h, and a crude product was obtained after evaporation of the
solvent. The product was washed with water (10 ml) and the organ-
ic material extracted with CH2Cl2 (2 Â 10 ml), and dried over
anhydrous magnesium sulfate. Reddish brown oil was obtained
upon evaporation of the solvent. Yield: 0.5214 g (92%); IR (Nujol
cmÀ1);
m(C@N imine) 1642, m(C@N quinolyl) 1595, m(C@C quinolyl)
1562, (C@C phenyl) 1504; 1H NMR (200 MHz, CDCl3): d 8.45 (s, 1H,
quinolyl); 8.40 (d, 1H, J = 8.2, quinolyl); 8.21 (dd, 1H, J = 8.0, quino-
lyl); 7.91–7.04 (m, 4H, quinolyl and imine); 6.79–6.68 (m, 5H,
phenyl); 3.05–2.87 (m, 2H, Me); 1.22 (dd, 12H, J = 1.2, Me); 13C
NMR (50 MHz, CDCl3) d 154.57, 118.33, 136.78, 132.48, 148.03,
124.56, 129.86, 129.11, 163.44 (imine), 148.44, 127.81, 129.98,
23.08, 28.02, 23.44, 22.47. Anal. Calc. for C22H24N2: C, 83.50; H,
7.64; N, 8.85. Found: C, 83.25; H, 7.92; N, 8.59%.
cmÀ1);
m(C@N imine) 1626, m(C@N quinolyl) 1598, m(C@C quinolyl)
1560, (C@C phenyl) 1503; 1H NMR (200 MHz, CDCl3): d 8.79 (s, 1H,
quinolyl); 8.37 (d, 1H, J = 8.4, quinolyl); 8.27 (dd, 1H, J = 8.2, quino-
lyl); 7.93–7.10 (m, 4H, quinolyl and imine); 6.79–6.66 (m, 5H, phe-
nyl); 13C NMR (50 MHz, CDCl3) d 154.84, 115.07, 136.64, 129.92,
147.97, 127.72, 121.23, 128.90, 127.75, 160.89 (imine), 150.81,
118.65, 129.71, 126.95, 129.25, 118.53. Anal. Calc. for C16H12N2: C,
82.73; H, 5.21; N, 12.06. Found: C, 82.95; H, 4.91; N, 12.32%.
2.3. Synthesis of palladium(II) complexes
2.3.1. Dichloro-[2-(phenyliminomethyl)quinoline]palladium(II) (1)
To a solution of L1 (0.0748 g, 0.322 mmol) in dry CH2Cl2 (10 ml)
was added dropwise
a
solution of PdCl2(cod) (0.0925 g,
2.2.2. 2-(2-Methylphenyl)iminomethylquinoline (L2)
0.324 mmol) in CH2Cl2 (5 ml). The yellow solution was refluxed
for 4 h, resulting in the formation of yellow precipitate. The precip-
itate was filtered and washed with Et2O (2 Â 10 ml) to obtain a
pure yellow solid which formed single crystals suitable for X-ray
crystallography when it was recrystallized from a mixture of CH2-
Cl2:C6H14 solution [11]. Yield: 0.1082 g (82%); IR (Nujol cmÀ1);
The ligand was synthesized according to the procedure de-
scribed for L1 using 2-quinolinecarboxaldehyde (0.3266 g,
2.08 mmol) and 2-methylaniline (0.2227 g, 2.08 mmol). Reddish
brown oil was obtained. Yield: 0.4713 g (92%); IR (Nujol cmÀ1);
m(C@N imine) 1625, m(C@N quinolyl) 1595, m(C@C quinolyl) 1560,
(C@C phenyl) 1504; 1H NMR (200 MHz, CDCl3): d 8.68 (s, 1H, qui-
nolyl); 8.38 (d, 1H, J = 8.8, quinolyl); 8.19 (dd, 1H, J = 8.4, quinolyl);
7.88–6.98 (m, 4H, quinolyl and imine); 6.72–6.63 (m, 5H, phenyl);
2.42 (s, 3H, Me); 13C NMR (50 MHz, CDCl3) d 155.08, 114.89,
136.58, 132.59, 147.93, 127.65, 126.63, 128.88, 127.74, 160.01
(imine), 149.81, 118.65, 130.43, 126.92, 129.88, 117.48, 17.88.
Anal. Calc. for C17H14N2: C, 82.90; H, 5.73; N, 11.37. Found: C,
83.14; H, 6.02; N, 11.55%.
m(C@N imine) 1599, m(C@N quinolyl) 1588, m(C@C quinolyl) 1572,
(C@C phenyl) 1511; 1H NMR (200 MHz, DMSO): d 8.50 (d, 1H,
J = 8.4, quinolyl); 8.30 (d, 1H, J = 8.2, quinolyl); 8.11–7.28 (m, 4H,
quinolyl and imine); 8.77 (d, 1H, J = 8.0, quinolyl); 6.87–6.70 (m,
5H, phenyl). Anal. Calc. for C16H12Cl2N2Pd: C, 46.92; H, 2.95; N,
6.84. Found: C, 47.20; H, 3.11; N, 6.99%.
2.3.2. Dichloro-[2-(2-
methylphenyl)iminomethylquinoline]palladium(II) (2)
The compound was synthesized according to the procedure de-
scribed for 1 using L2 (0.0634 g, 0.257 mmol) and PdCl2(cod)
2.2.3. 2-(2,6-Dimethylphenyl)iminomethylquinoline (L3)
The ligand was synthesized according to the procedure de-
scribed for L1 using 2-quinolinecarboxaldehyde (0.2913 g,
1.85 mmol) and 2,6-dimethylaniline (0.2246 g, 1.85 mmol). Red-
dish brown oil was obtained. Yield: 0.4527 g (94%); IR (Nujol
(0.0744 g, 0.257 mmol).
0.0969 g (89%); IR (Nujol cmÀ1);
lyl) 1589,
(C@C quinolyl) 1561, (C@C phenyl) 1500; 1H NMR
A
yellow solid was obtained. Yield:
m
(C@N imine) 1599, (C@N quino-
m
m
cmÀ1);
m
(C@N imine) 1639,
m(C@N quinolyl) 1595,
m
(C@C quinolyl)
(200 MHz, DMSO): d 8.46 (d, 1H, J = 8.2, quinolyl); 8.36 (d, 1H,
J = 8.2, quinolyl); 8.16–7.04 (m, 4H, quinolyl and imine); 8.76 (d,
1H, J = 8.8, quinolyl); 6.85–6.68 (m, 5H, phenyl). Anal. Calc. for C17-
H14Cl2N2Pd: C, 48.20; H, 3.33; N, 6.61. Found: C, 48.48; H, 3.17; N,
6.52.
1562, (C@C phenyl) 1503; 1H NMR (200 MHz, CDCl3): d 8.50 (s, 1H,
quinolyl); 8.42 (d, 1H, J = 8.4, quinolyl); 8.22 (dd, 1H, J = 8.0, quino-
lyl); 7.91–6.92 (m, 4H, quinolyl and imine); 6.67–6.63 (m, 5H, phe-
nyl); 2.19 (s, 6H, Me); 13C NMR (50 MHz, CDCl3) d 154.62, 117.99,
136.71, 129.95, 145.53, 127.78, 124.15, 128.22, 128.14, 163.84
(imine), 150.30, 121.68, 129.77, 126.79, 129.05, 118.18, 18.31,
17.59. Anal. Calc. for C18H16N2: C, 83.04; H, 6.19; N, 10.76. Found:
C, 83.27; H, 6.45; N, 11.01%.
2.3.3. Dichloro-[2-(2,6-
dimethylphenyl)iminomethylquinoline]palladium(II) (3)
The compound was synthesized according to the procedure
described for 1 using L3 (0.0557 g, 0.214 mmol) and PdCl2(cod)
(0.0623 g, 0.218 mmol). A yellow solid was obtained. Suitable
crystals for X-ray crystallography were grown by slow evaporation
of CH3CN solution of the complex. Yield: 0.0805 g (86%) IR (Nujol
2.2.4. 2-(2,6-Diethylphenyl)iminomethylquinoline (L4)
The ligand was synthesized according to the procedure de-
scribed for L1 using 2-quinolinecarboxaldehyde (0.3130 g,

W.M. Motswainyana et al. / Inorganica Chimica Acta 400 (2013) 197–202
199
cmÀ1);
m
(C@N imine) 1599,
m
(C@N quinolyl) 1585,
m
(C@C quinolyl)
2.4.3. Dichloro-[2-(2,6-
dimethylphenyl)iminomethylquinoline]platinum(II) (8)
1565, (C@C phenyl) 1510; 1H NMR (200 MHz, DMSO): d 8.42 (d,
1H, J = 8.2, quinolyl); 8.34 (d, 1H, J = 8.2, quinolyl); 8.27–6.96 (m,
4H, quinolyl and imine); 8.72 (d, 1H, J = 7.8, quinolyl); 6.82–6.73
(m, 5H, phenyl). Anal. Calc. for C18H16Cl2N2Pd: C, 49.40; H, 3.68;
N, 6.40. Found: C, 49.16; H, 3.88; N, 6.22%.
The compound was synthesized according to the procedure de-
scribed for 6 using L3 (0.0643 g, 0.247 mmol) and K2[PtCl4]
(0.1035 g, 0.249 mmol). An orange solid was obtained. Yield:
0.1014 g (78%); IR (Nujol cmÀ1
lyl) 1589,
)
m
(C@N imine) 1607,
m(C@N quino-
m
(C@C quinolyl) 1561, (C@C phenyl) 1513; 1H NMR
(200 MHz, DMSO): d 8.44 (d, 1H, J = 8.0, quinolyl); 8.32 (d, 1H,
J = 8.6, quinolyl); 8.01–6.92 (m, 4H, quinolyl and imine); 8.73 (d,
1H, J = 8.4, quinolyl); 6.78–6.59 (m, 5H, phenyl). Anal. Calc. for C18-
H16Cl2N2Pt: C, 41.08; H, 3.06; N, 5.32. Found: C, 40.94; H, 2.77; N,
5.06%.
2.3.4. Dichloro-[2-(2,6-
diethylphenyl)iminomethylquinoline]palladium(II) (4)
The compound was synthesized according to the procedure de-
scribed for 1 using L4 (0.0640 g, 0.222 mmol) and PdCl2(cod)
(0.0650 g, 0.228 mmol). A yellow solid was obtained. Suitable crys-
tals for X-ray crystallography were grown by slow evaporation of
CH3CN solution of the complex [10]. Yield: 0.0848 g (82%) IR (Nujol
2.4.4. Dichloro-[2-(2,6-
cmÀ1);
m(C@N imine) 1602, m(C@N quinolyl) 1584, m(C@C quinolyl)
diethylphenyl)iminomethylquinoline]platinum(II) (9)
The compound was synthesized according to the procedure de-
scribed for 6 using L4 (0.0728 g, 0.252 mmol) and K2[PtCl4]
(0.1059 g, 0.255 mmol). An orange solid was obtained. Yield:
1563, (C@C phenyl) 1506; 1H NMR (200 MHz, DMSO): d 8.42 (d,
1H, J = 8.4, quinolyl); 8.36 (d, 1H, J = 8.2, quinolyl); 8.23–6.96 (m,
4H, quinolyl and imine); 8.77 (d, 1H, J = 7.4, quinolyl); 6.88–6.78
(m, 5H, phenyl). Anal. Calc. for C20H20Cl2N2Pd: C, 51.58; H, 4.33;
N, 6.02. Found: C, 51.89; H, 4.18; N, 5.83%.
0.1034 g (74%); IR (Nujol cmÀ1
1587,
)
m
(C@N imine) 1608,
m(C@N quinolyl)
m
(C@C quinolyl) 1566, (C@C phenyl) 1516; 1H NMR (200 MHz,
DMSO): d 8.43 (d, 1H, J = 8.6, quinolyl); 8.35 (d, 1H, J = 8.2, quinolyl);
8.19–6.89 (m, 4H, quinolyl and imine); 8.72 (d, 1H, J = 8.2, quinolyl);
6.76–6.56 (m, 5H, phenyl). Anal. Calc. for C20H20Cl2N2Pt: C, 43.33; H,
3.64; N, 5.05. Found: C, 43.09; H, 3.91; N, 5.22%.
2.3.5. Dichloro-[2-(2,6-
diisopropylphenyl)iminomethylquinoline]palladium(II) (5)
The compound was synthesized according to the procedure de-
scribed for 1 using L5 (0.0645 g, 0.204 mmol) and PdCl2(cod)
(0.0598, 0.209 mmol). A yellow solid was obtained. Suitable crys-
tals for X-ray crystallography were grown by slow diffusion of
C6H14 into a solution of the complex in CH2Cl2.Yield: 0.0856 g
2.4.5. Dichloro-[2-(2,6-
diisopropylphenyl)iminomethylquinoline]platinum(II) (10)
The compound was synthesized according to the procedure de-
scribed for 6 using L5 (0.0472 g, 0.149 mmol) and K2[PtCl4]
(0.0633 g, 0.152 mmol). An orange solid was obtained. Yield:
(85%) IR (Nujol cmÀ1);
m(C@N imine) 1606, m(C@N quinolyl)
1589,
m
(C@C quinolyl) 1562, (C@C phenyl) 1514; 1H NMR
0.0651 g (75%); IR (Nujol cmÀ1
1588,
)
m
(C@N imine) 1612,
m(C@N quinolyl)
(C@C quinolyl) 1564, (C@C phenyl) 1514; 1H NMR (200 MHz,
(200 MHz, DMSO): d 8.44 (d, 1H, J = 8.4, quinolyl); 8.35 (d, 1H,
J = 8.0, quinolyl); 8.22–6.98 (m, 4H, quinolyl and imine); 8.78 (d,
1H, J = 7.6, quinolyl); 6.78–6.71 (m, 5H, phenyl). Anal. Calc. for C22-
H24Cl2N2Pd: C, 53.51; H, 4.90; N, 5.67. Found: C, 53.28; H, 4.72; N,
5.93%.
m
DMSO): d 8.42 (d, 1H, J = 8.0, quinolyl); 8.37 (d, 1H, J = 8.4, quinolyl);
8.12–6.85 (m, 4H, quinolyl and imine); 8.75 (d, 1H, J = 8.6, quinolyl);
6.64–6.48 (m, 5H, phenyl). Anal. Calc. for C22H24Cl2N2Pt: C, 45.37; H,
4.15; N, 4.81. Found: C, 45.13; H, 4.35; N, 5.02%.
2.4. Synthesis of platinum(II) complexes
2.5. Cytotoxicity determination
2.4.1. Dichloro-[2-(phenyliminomethyl)quinoline]platinum(II) (6)
To a solution of L1 (0.0627 g, 0.270 mmol) in dry MeOH (10 ml)
was added dropwise an aqueous solution of K2[PtCl4] (0.1115 g,
0.269 mmol) (5 ml). The reaction was stirred at room temperature
for 15 h, resulting in the formation of an orange precipitate. The
precipitate was filtered and washed with Et2O (2 Â 10 ml) to ob-
2.5.1. Cell culture
The A2780 and MCF-7 cells were cultured in RPMI-1640 in
25 cm tissue culture flasks and were allowed to grow to 90% con-
fluency in an incubator set at 37 °C containing 5% CO2 atmospheric
pressure, before they were trypsinized and cultured in six tissue
culture plates. Stock and final concentrations of the complexes
were prepared in the culture media.
tain a pure orange solid. Yield: 0.1019 g (76%); IR (Nujol cmÀ1
)
m
(C@N imine) 1610, m(C@N quinolyl) 1586, m(C@C quinolyl) 1560,
(C@C phenyl) 1510; 1H NMR (200 MHz, DMSO): d 8.62 (d, 1H,
J = 9.2, quinolyl); 8.33 (d, 1H, J = 8.8, quinolyl); 8.12–7.03 (m, 4H,
quinolyl and imine); 8.71 (d, 1H, J = 8.4, quinolyl); 6.89–6.59 (m,
5H, phenyl). Anal. Calc. for C16H12Cl2N2Pt: C, 38.57; H, 2.43; N,
5.62. Found: C, 38.72; H, 2.62; N, 5.76%.
2.5.2. MTT assay
The cells were plated in 96-well tissue plates at a density of
2.0 Â 105 cells per well and treated with various concentrations
of the palladium complexes that ranged from 100 to 10 lM after
which they were incubated for 24 h. Triplicate wells were estab-
lished for each concentration. Just 5 h before the elapse of 24 h,
10
plates were further incubated. At the end of the incubation period,
the media was removed from each well and replaced with 50 l of
DMSO. The plates were shaken on a rotating shaker for 10 min be-
fore taking readings at 560 nm using a microplate reader.
ll of 5 mg/ml MTT solution was added to each well and the
2.4.2. Dichloro-[2-(2-
methylphenyl)iminomethylquinoline]platinum(II) (7)
The compound was synthesized according to the procedure de-
scribed for 6 using L2 (0.0679 g, 0.276 mmol) and K2[PtCl4]
(0.1146 g, 0.276 mmol). An orange solid was obtained. Yield:
l
0.1060 g (75%); IR (Nujol cmÀ1
lyl) 1588,
)
m
(C@N imine) 1612,
m(C@N quino-
m
(C@C quinolyl) 1557, (C@C phenyl) 1512; 1H NMR
3. Results and discussion
(200 MHz, DMSO): d 8.57 (d, 1H, J = 8.6, quinolyl); 8.34 (d, 1H,
J = 8.0, quinolyl); 8.25–7.17 (m, 4H, quinolyl and imine); 8.72 (d,
1H, J = 8.4, quinolyl); 6.79–6.58 (m, 5H, phenyl). Anal. Calc. for C17-
H14Cl2N2Pt: C, 39.86; H, 2.75; N, 5.47. Found: C, 40.08; H, 3.03; N,
5.33%.
3.1. Synthesis of the ligands and metal complexes
Imino-quinolyl ligands L1–L5 were successfully prepared by
reacting 2-quinolinecarboxaldehyde with substituted aniline and

200
W.M. Motswainyana et al. / Inorganica Chimica Acta 400 (2013) 197–202
obtained in very good yields. Ligand L4 has been previously
reported by our group, but it was not fully characterized [10].
The rest of the ligands have been reported by another research
group [12] but they were independently prepared by us. The new
corresponding palladium(II) and platinum(II) complexes 1–10
were subsequently prepared by equimolar reactions of the ligands
with either PdCl2(cod) or K2[PtCl4] (Scheme 1). All the compounds
were characterized using elemental analysis, IR, 1H and 13C NMR
spectroscopy.
The micro-analysis data are consistent with the proposed
molecular formulae. The IR spectra of the ligands showed three
strong absorption bands between 1625 and 1647 cmÀ1, which
confirmed imine formation [13–15]. The other strong bands ob-
served around 1595 cmÀ1 and 1559 cmÀ1 show the presence of
(C@N) and (C@C) quinolyl vibrations, respectively. Coordination
of the ligands to the metal center was confirmed by lower absorp-
tion frequencies between 1618 and 1599 cmÀ1 compared to their
corresponding free ligands [13–15]. The (C@N) and (C@C) quinolyl
vibrations did not show any significant shift in absorption
frequency from their corresponding free imines, confirming their
non involvement in coordination.
3.2. Single crystal X-ray diffraction studies
The molecular structures of some of the complexes were
confirmed by X-ray crystallography. Crystallographic data and
refinement parameters are summarized in Table 1, while selected
bond lengths and bond angles are summarized in Table 2. The
molecular structures are shown in Figs. 1 and 2, respectively.
ꢀ
Complex 3 crystallizes in the triclinic space group P1, with two
structurally identical molecules (A and B) in the asymmetric unit
(rms deviation of 0.173 Å when fitting inverted molecule B on mol-
ecule A), while 5 crystallizes in the monoclinic space group P21/c.
In the structures,
p–p interactions between quinoline rings link
two molecules into centro-symmetric dimers. The palladium atom
is four coordinated by two chloride anions and two nitrogen atoms
of the bidentate ligand, generating a distorted square planar coor-
dination geometry around the palladium metal center. The bond
angles around the palladium metal atom of N(2)–Pd(1)–N(1) and
Cl(2)–Pd(1)–Cl(1): 80.32(11)° and 88.75(3)° for molecule A in 3
and 80.45(12)° and 88.13(14)° in 5 showed significant deviations
from 90°, which confirms the distortion in the square planar geom-
etry. These bond angles are in agreement with those of closely re-
lated compounds [11,13,14]. The Pd(1)–C1(1) and Pd(1)–C1(2)
bond lengths of 2.2941(8) Å and 2.2788(9) Å for molecule A in 3
and 2.2769(10) Å and 2.3081(10) Å in 5 are in good agreement
In the 1H NMR spectra of the ligands, the signal for the imine
proton was obscured by the aromatic signals. The quinolyl protons
appeared as doublets or triplets between 8.79 and 8.13 ppm due to
vicinal proton–proton coupling. In the 13C NMR analysis, the
characteristic signals for the imine carbons appeared at around
163.00 ppm [13–15]. In the NMR spectra of the complexes, the
signals generally shifted downfield with respect to their position
in the free ligand due to coordination of the ligand.
Table 1
Crystallographic data and refinement for complexes 3 and 5.
Crystallographic data
3
5
Empirical formula
Formula weight
T (K)
2(C18H16Cl2N2Pd)ÁC2H3N C22H24Cl2N2Pd
916.31
100
492.72
100
R2
Crystal system
Space group
triclinic
P1
monoclinic
P21/c
ꢀ
Unit cell dimensions
NH2
a (Å)
b (Å)
c (Å)
b (°)
V (Å3)
Z
8.0349(5)
13.5623(8)
17.5006(10)
77.043(5)
1831.70(19)
2
11.4731(6)
13.0007(8)
14.8263(8)
106.356(6)
2122.0(2)
4
+
O
N
CH2Cl2
rt, 10 h
R1
Dcalc. (M gmÀ3
F(0 0 0)
)
1.661
1.542
916
1000
R2
Absorption coefficient (mmÀ1
Crystal size (mm3)
)
1.31
1.14
0.3 Â 0.3 Â 0.3
0.3 Â 0.2 Â 0.2
Number of data collected
7435
4344
Number of parameters refined
447
0.036
0.091
248
0.043
0.089
N
R[F2 > 2
wR(F2)
r
(F2)]
N
Theta range for data collection
2.8 to 26.4°
1.08
2.9 to 26.3°
1.09
Goodness-of-fit on F2
R1
Largest difference peak and hole 0.67 and À1.08
0.81 and
À0.82
PdCl2(cod)
K2[PtCl4]
(e ÅÀ3
)
R2
Table 2
Selected bond lengths and bond angles for compounds 3 and 5.
N
N
Compound
Bond length (Å)
Bond angle (°)
M
3
Pd(1)–N(2) 2.020(2)
Pd(1)–N(1) 2.074(3)
Pd(1)–Cl(2) 2.2788(9)
Pd(1)–Cl(1) 2.2941(8)
Pd(2)–N(3) 2.014(3)
Pd(2)–N(4) 2.110(3)
Pd(2)–Cl(3) 2.2736(8)
Pd(2)–Cl(4) 2.2956(9)
N(2)–Pd(1)–N(1) 80.32(11)
Cl(2)–Pd(1)–Cl(1) 88.75(3)
N(1)–Pd(1)–Cl(1) 98.36(7)
N(2)–Pd(1)–Cl(2) 91.94(8)
N(4)–Pd(2)–N(3) 80.23(11)
Cl(4)–Pd(2)–Cl(3) 87.53(3)
N(3)–Pd(2)–Cl(3) 90.81(8)
N(4)–Pd(2)–Cl(4) 101.50(8)
Cl
Cl
R1
R1 = R2 = H, M = Pd (1); M = Pt (6)
R1 = Me, R2 = H, M = Pd (2); M = Pt (7)
R1 = R2 = Me, M = Pd (3); M = Pt (8)
R1 = R2 = Et, M = Pd (4); M = Pt (9)
R1 = R2 = iPr, M = Pd (5); M = Pt (10)
5
Pd(1)–N(4) 2.026(3)
Pd(1)–N(2) 2.098(3)
Pd(1)–Cl(3) 2.2769(10)
Pd(1)–Cl(2) 2.3081(10)
N(4)–Pd(1)–N(2) 80.45(12)
Cl(3)–Pd(1)–Cl(2) 88.13(14)
N(2)–Pd(1)–Cl(2) 99.99(9)
N(4)–Pd(1)–Cl(3) 92.69(9)
Scheme 1.

W.M. Motswainyana et al. / Inorganica Chimica Acta 400 (2013) 197–202
201
Table 3
Cytotoxic activities for the free ligand and complexes tested against MCF-7 and HT-29
cancer cell lines.
Compound
MCF-7
HT-29
IC50
L1
(lM)
>100
>100
Palladium(II) complexes
1
2
3
5
63.87 0.23
62.76 2.36
47.58 1.66
46.01 0.95
58.96 2.98
57.88 1.85
43.89 0.74
42.79 1.69
Platinum(II) complexes
6
7
8
10
59.86 2.38
57.59 2.45
45.99 0.99
44.90 1.86
100
54.75 0.81
53.84 2.11
41.92 1.33
39.90 0.92
100
Cisplatin
IC50 is the concentration of the complex required to inhibit cell growth by 50%. Data
are presented otherwise specified as mean SD of IC50
pendent experiments.
(lg/ml) from three inde-
Fig. 1. X-ray crystal structure of complex 3.
same experimental conditions for comparison. The imino-quinolyl
ligand L1 was also evaluated to assess whether free imino-quinolyl
ligands could exert cytotoxicity on cancer cells. However, the
ligand did not return any appreciable activity (IC50 > 100 lM).
The imino-quinolyl palladium(II) and platinum(II) complexes
exhibited growth inhibitory activities against MCF-7 and HT-29
cancer cell lines which were superior to the reference compound
cisplatin, which returned IC50 values around 100
cytotoxic activities were pronounced in complexes 5 and 10 (IC50
46.01 and 39.90 M), which were approximately two times more
lM. The highest
l
active than cisplatin against the two examined cancer cell lines.
These complexes contain two iso-propyl groups substituted at
ortho-positions on the phenyl ring, making them more sterically
demanding. The trend confirms the importance of steric congestion
in preventing axial approach to the coordinated metal atom and
permitting high selectivity to DNA binding [6]. However, there
was insignificant difference in activities between complexes
containing two iso-propyl groups and those with two methyl
groups on the phenyl ring.
Fig. 2. X-ray crystal structure of complex 5.
with the average Pd–Cl bond distance of 2.298(15) Å for known
palladium complexes [16,17]. There is detectable trans- influence
taking place for the chloride ligands since the bond distance
Pd(1)–Cl(1) is slightly longer than Pd(1)–Cl(2), thus reflecting the
stronger trans-influence of the quinolyl group compared to the
secondary amine [18].
All the complexes generally exhibited higher cytotoxic activities
against human colon (HT-29) cell line (IC50 39.90–58.96 lM)
compared to the human breast (MCF-7) cell line. Furthermore,
imino-quinolyl platinum(II) complexes showed slightly superior
cytotoxic activities compared to their palladium(II) counterparts
across the examined cancer cell lines, probably due to the higher
lability of palladium(II) compared to their platinum(II) analogs,
which makes them to dissociate readily in solution, leading to very
reactive species that are unable to reach their pharmacological tar-
gets [22–23]. The complexes are also square planar with metal
chloride bonds in cis-position, and when considering the proposed
mechanism of action of cisplatin [24,25], it is reasonable to suggest
that cytotoxicity of these imino-quinolyl complexes is derived
from DNA binding. Our group has recently reported cytotoxic
activities of complex 4 showing similar trend [10].
3.3. Cytotoxicity studies
The aim of this study was to evaluate imino-quinolyl
palladium(II) and platinum(II) complexes as possible antitumor
agents. The complexes were derived from chelating, bidentate qui-
nolyl imine ligands containing substituted aniline, thereby making
them sterically congested. As indicated earlier, steric congestion
protects the central metal atom from deactivation, thereby permit-
ting high selectivity to DNA binding [6], while chelating, bidentate
ligands prevent trans-labilization and undesired displacement of
the ligands [4].
The free imino-quinolyl ligand L1 and some palladium(II)
complexes and platinum(II) complexes were evaluated for their
potential to exert cytotoxicity on highly invasive human breast
(MCF-7) and human colon (HT-29) tumor cells using 3-(4,5-di-
methyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT)
assay with minor modifications [19–21]. The compounds were first
solubilized in dimethylsulfoxide (DMSO). Cell growth inhibition
results, expressed as concentration of the complex required to
inhibit tumor cell growth by 50% (IC50) are summarized in Table 3.
They are reported with a measurement accuracy depicting a stan-
dard deviation. Cytotoxicity of cisplatin was evaluated under the
4. Conclusions
We have successfully synthesized and fully characterized
sterically congested palladium(II) and platinum(II) complexes
derived from chelating imino-quinolyl ligands. The complexes
were evaluated in vitro for their potential to exert cytotoxicity on
human breast (MCF-7) and human colon (HT-29) cancer cell lines.
The free ligand did not return any appreciable activity. However,
the complexes exhibited growth inhibitory activities that were
even better than cisplatin.

202
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The authors thank University of the Western Cape, National
Research Foundation and University of Leuven’s International
Admissions and Mobility Office (WMM) for financial support. The
authors also thank the Hercules Foundation for supporting the
purchase of the diffractometer through project AKUL/09/0035.
Appendix A. Supplementary material
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