Synthesis, structural characterization and biological screening of heteroleptic palladium(II) complexes

Article abstract of DOI:10.1016/j.ica.2016.03.014

Heteroleptic palladium(II) complexes of the type formula [(DTC)(Pd)(PR₃)Cl], where DTC = bis(2-ethylhexyl)dithiocarbamate (1, 8, 9, 10), bis(2-methoxyethyl)dithiocarbamate (2), di-n-decyldithiocarbamate (3, 6), di-n-hexyldithiocarbamate (4, 7), bis(2-methylbutyl)dithiocarbamte (5); PR₃ = diphenyl-t-butylphosphine (1), diphenyl-n-propylphosphine (2), triphenylphosphine (3, 4, 5, 10), diphenyl-p-tolylphosphine (6, 7, 8), diphenylbenzylphosphine (9); have been synthesized and characterized by FTIR, Raman, multinuclear and multinuclear NMR (¹H, ¹³C, ³¹P) spectroscopy and elemental analyses. The structures of complexes (1 and 2) were determined by single-crystal X-ray diffraction. The geometries around the metal centers are pseudo square-planar. The new complexes exhibit moderate anticancer and antibacterial activity.

Full text of DOI:10.1016/j.ica.2016.03.014

Accepted Manuscript
Synthesis, Structural Characterization and Biological Screening of Heteroleptic
Palladium(II) Complexes
Hizbullah Khan, Amin Badshah, Muhammad Said, Ghulam Murtaza,
Muhammad Sirajuddin, Jamil Ahmad, Ian S. Butler
PII:
S0020-1693(16)30106-2
http://dx.doi.org/10.1016/j.ica.2016.03.014
ICA 16949
DOI:
Reference:
Inorganica Chimica Acta
To appear in:
Received Date:
Revised Date:
Accepted Date:
13 October 2015
9 March 2016
10 March 2016
Please cite this article as: H. Khan, A. Badshah, M. Said, G. Murtaza, M. Sirajuddin, J. Ahmad, I.S. Butler, Synthesis,
Structural Characterization and Biological Screening of Heteroleptic Palladium(II) Complexes, Inorganica Chimica
Acta (2016), doi: http://dx.doi.org/10.1016/j.ica.2016.03.014
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Synthesis, Structural Characterization and Biological Screening of Heteroleptic
Palladium(II) Complexes
Hizbullah Khan1,2*, Amin Badshah2*, Muhammad Said3, Ghulam Murtaza2, Muhammad
Sirajuddin1, Jamil Ahmad4, Ian S. Butler5
1Department of Chemistry, University of Science and Technology, Bannu 28100, Khyber
Pakhtunkhwa, Pakistan
2Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan
3Department of Chemistry, Abdul Wali Khan University, Mardan 23200, Pakistan
4Department of Chemistry, Hazara University, Mansehra 21120, Pakistan
5Department of Chemistry, McGill University, Montreal, Quebec, Canada H3A 2K6
Email: hizbmarwat@yahoo.com; aminbadshah@yahoo.com
Abstract
Heteroleptic palladium(II) complexes of the type formula [(DTC)(Pd)(PR3)Cl], where DTC =
bis(2-ethylhexyl)dithiocarbamate (1,8,9,10), bis(2-methoxyethyl)dithiocarbamate (2), di-n-
decyldithiocarbamate (3,6), di-n-hexyldithiocarbamate (4,7), bis(2-methylbutyl)dithiocarbamte
(5); PR3 = diphenyl-t-butylphosphine (1), diphenyl-n-propylphosphine (2), triphenylphosphine
(3,4,5,10), diphenyl-p-tolylphosphine (6,7,8), diphenylbenzylphosphine (9); have been
13
synthesized and characterized by FTIR, Raman, multinuclear and multinuclear NMR (1H, C,
31P) spectroscopy and elemental analyses. The structures of complexes (1 and 2) were
determined by single-crystal X-ray diffraction. The geometries around the metal centres are
pseudo square-planar. The new complexes exhibit moderate anticancer and antibacterial activity.
Key words: Heteroleptic palladium(II) complexes; single crystal; XRD analysis; anticancer
activity; antibacterial activity; Spectroscopy
1

1.1 Introduction
Since the discovery of the antitumor activity of cisplatin in 1969, extensive research has been
performed on the antitumor potential of platinum(II) and palladium(II) complexes [1]. There has
been particular interest in the study of palladium (II) complexes because they behave similarly
to platinum(II) complexes but with faster kinetics[2]. Hydrolysis of palladium(II) complexes is
very rapid leading to reactive species that are unable to reach their pharmacological targets.
Moreover, some cis-palladium(II) complexes transform into the in active transderivatives. The
stabilization of Pd(II) complexes by strongly coordinating ligands and an appropriate leaving
group has been explored as a synthetic technique for the synthesis of antitumor palladium(II)
complexes[3],[4],[5]. Thus various compounds containing bidentate ligands (N-N, P-P, or mixed N-
O, N-S)[6], [7], monodentate bulky ligands[8], and organometallic derivatives have been
synthesized. Some new 9-aminoacridine palladium(II) complexes exhibit about 30-fold more
antitumor activity against the HL-60 human tumor cell line than does cisplatin [9].
Because palladium(II) chemistry is similar to that of platinum(II), it was speculated that
palladium(II) complexes may exhibit antitumor activity with fewer side effects [10]. Palladium(II)
complexes are expected to have less kidney toxicity than does cisplatin, which results from
binding of the sulfhydryl group of kidney tubule protein [11]. Genova et al. have reported that
Pd(II) complexes demonstrated significant activity against acyclovir-resistant viruses R-100
(HSV 1) and PU (HS V 2) and negatively influence the expression of key structural HSV-1
proteins (VP 23, gH, and gG/gD) hereby simultaneously suppressing virus entry, trans activation
of the virus genome, capsid assembly, and cell-to-cell spread of infectious HSV progeny [12]
.
Dithiocarbamates have received considerable attention recently owing to their ability to act as
bidentate ligands. Metal dithiocarbamates are currently used as lubricants, antioxidants,
accelerators for rubber vulcanization[13], and in biological applications[14]. Dithiocarbamates
derived from secondary amines have also been extensively studied because of their interesting
electrochemical and optical properties[15]
The synthesis of other metal-containing drugs, such as organometallic complexes[16] of
iron[17], iridium[18], copper[19], rhodium[20], ruthenium[21], gold[22] and titanium[23] has also
2

attracted much interest. More recently, heterometallic[24] complexes have been synthesized which
demonstrate the synergic effect of two different metals with known antitumor activity. A series
of Pd(II) complexes with a benzene alkyl dicarboxylate chain has been prepared in an attempt to
determine the effect of carbon chain length. The four complexes prepared exhibited cytotoxic
specificity and significant cancer cell inhibitory rates. Studies of the complexes have shown that
there is a substantial correlation between the carbon chain length and the DNA binding
properties and cytotoxicity- the longer the carbon chain length, the higher the efficiency of
DNA-binding and the greater the cytotoxicity[25]
.
In this article, we report the syntheses, characterization and biological activities of ten mixed
ligand dithiocarbamate and organophosphine palladium(II) complexes.
1.2 Experimental section
All the experiments were carried out at reflux temperature and normal pressure. The chemicals,
palladium chloride (Sigma-Aldrich), 2-ethylhexylamine (Sigma-Aldrich), diphenyl-t-
butylphosphine (Alfa Aesar), 2-methoxyethylamine (Alfa Aesar), diphenyl-n-propylphosphine
(Alfa Aesar), di-n-decylamine (Sigma-Aldrich), triphenylphosphine (Alfa Aesar), di-n-
hexylamine (Alfa Aesar), bis(2-methylbutyl)amine (Alfa Aesar), diphenyl-p-tolylphosphine
(Alfa Aesar), bis(2-ethylhexyl)amine (Alfa Aesar), diphenylbenzylphosphine (Alfa Aesar), and
hydrochloric acid (Sigma-Aldrich) were purchased from Sigma-Aldrich and Alfa Aesar and ere
used without further purification. The solvents used were dried and purified by standard
methods. All the dithiocarbamates used and their salts have been reported previously in the
literature and were prepared by the methods indicated[26]
.
NMR spectra were recorded on Mercury 200 MHz and Bruker 300 MHz spectrometers. 1H NMR
31
(300.13 MHz): CDCl3 (7.26 from SiMe4). 13C NMR (75.47 MHz), internal standard TMS; P
NMR (121.49 MHz): CDCl3. The splitting of proton resonances are shown as, s = singlet, d =
doublet, t = triplet and m = multiplet (showing a complex pattern). IR spectra were recorded on a
Nicolet 6700 FT-IR instrument in the range of 4000-400 cm-1 and Raman spectra ( 1 cm-1) were
measured with an InVia Renishaw spectrometer, using argon ion (514.5 nm) and near infrared
3

diode (785 nm) lasers. Wire 2.0 software was used for the Raman data acquisition and spectra
manipulations. The elemental analyses were conducted on a LECO-183 CHNS analyzer. Melting
points were measured on Stuart SMP10 apparatus and are uncorrected.
1.2.1 General synthesis of mixed ligand dithiocarbamate-organophosphine palladium(II)
complexes 1-10
The heteroleptic Pd(II) complexes were prepared in two steps. In the first step, the Pd(II)-
organophosphine complex was prepared by dissolving PdCl2 in methanol, along with 3-4 drops
of concentrated hydrochloric acid. The desired organophosphine was dissolved in dry acetone
and reacted with PdCl2 solution in 2:1 molar ratio. The reaction mixture was refluxed for 1 h
and the solid product was filtered off. In the second step, the dichloromethane solution of Pd-
organophosphine was reacted with dithiocarbamic acid or the potassium salt of the
dithiocarbamate ligand in 1:1 molar ration under reflux conditions, for 6 h. The resulting golden
yellow solid product was obtained by rotary evaporation. The solid product was recrystallized in
conical flask in 20 mL dichloromethane and n-hexane in a 4:1 by volume ratio. Golden yellow
crystals of complexes 1 and 2 were obtained by slow evaporation at room temperature and
pressure, while the other complexes did not crystallize.
1.2.2 [Pd(bis(2-ethylhexyl)dithiocarbamate)(PPh2C(CH3)3)Cl]
(1)
Quantities used were: 0.21g (0.59 mmol) bis(2-ehtylhexyl)dithiocarbamic acid, 0.39g (0.59
mmol) Pd-phosphine complex. Yield: 0.28 g (69%). M. p.:147-148 °C. MW = 700.76. FT-IR
(powder, cm-1): 3043 υ(C-H, aromatic), 2981, 2922 υ(C-H, aliphatic), 1514 υ(C N), 1096
υ(SCS). Raman (powder, cm-1): 260 υ(Pd-P), 296 υ(Pd-Cl), 416 υ(Pd-S).1H NMR (300 MHz,
CDCl3) δ-ppm: 0.78,(t, 3H, CH3(CH2)3CH(CH2CH3)CH2-,3JH-H
3H,CH3(CH2)3CH(CH2CH3)CH2-,3JH-H
7.2 Hz),
=
7.2 Hz)0.86 (t,
1.12-1.23 (m,
=
12H,CH3(CH2)3CH(CH2CH3)CH2-),1.69-1.75 (m, 4H, CH3(CH2)3CH(CH2CH3)CH2-), 1.82-1.89
(m, 2H, CH3(CH2)3CH(CH2CH3)CH2-) 3.55, 3.50 (d,4H, CH3(CH2)3CH(CH2CH3)CH2-), 1.45 (s,
9H, C(CH3)3), 7.41-7.91 (m, 10H, Ar-H).13C NMR (75.47 MHz, CDCl3) δ-ppm:135.5, 134.9,
130.3,
127.7
(ArC),
53.1,
52.7
(CH3(CH2)3CH(CH2CH3)CH2-),
37.4,
37.3
4

(CH3(CH2)3CH(CH2CH3)CH2-), 35.5, 35.3 (CH3CH2CH2CH2CH(CH2CH3)CH2-), 30.3, 30.4
(CH3CH2CH2CH2CH(CH2CH3)CH2-), 30.1, 30.0 (CH3(CH2)3CH(CH2CH3)CH2-), 29.5
(C(CH3)3), 28.5 (C(CH3)3), 23.8, 23.7 (CH3CH2CH2CH2CH(CH2CH3)CH2-), 14.1, 14.0
(CH3(CH2)3CH(CH2CH3)CH2-), 10.6, 10.5 (CH3(CH2)3CH(CH2CH3)CH2-), 208.6 (SCS),.31P
NMR (121.49 MHz, CDCl3) δ-ppm: 45.1. Elemental analysis, % Calculated (Found)
forC33H53ClNPPdS2: C, 56.56 (56.60); H, 7.62 (7.65); N, 2.00 (1.99); S, 9.15 (9.16).
1.2.3 [Pd(bis(2-methoxyethyl)dithiocarbamate)(PPh2-n-propyl)Cl]
(2)
Quantities used were: 0.03 g (0.12 mmol) potassium salt of bis-2-methoxyethyldithiocarbamate,
0.08g (0.12 mmol) Pd-phosphine complex. Yield: 0.05 g (63 %). M. p.: 177-178 °C. MW =
578.46. FT-IR (powder, cm-1): 3050 υ(C-H, aromatic), 2935, 2886 υ(C-H, aliphatic), 1517υ(C
N), 1089 υ(SCS). Raman (powder, cm-1): 200 υ(Pd-P), 299 υ(Pd-Cl), 413 υ(Pd-S).1H NMR
(300 MHz, CDCl3) δ-ppm: 3.29, (s, 3H, CH3OCH2CH2-), 3.30 (s, 3H, CH3OCH2CH2-), 3.86 (t,
3
3
2H, CH3OCH2CH2-, JH-H= 5.1 Hz), 3.98 (t, 2H, CH3OCH2CH2-, JH-H= 5.1 Hz), 3.51 (t, 2H,
CH3OCH2CH2-,3JH-H= 5.1 Hz), 3.61 (t, 2H, CH3OCH2CH2-,3JH-H= 5.1 Hz), 1.03 (t, 2H,
3
3
CH3CH2CH2-, JH-H= 7.2 Hz), 1.58-1.78 (m, CH3CH2CH2-), 2.47 (t, 2H, CH3CH2CH2-, JH-H
=
7.2 Hz), 7.26-7.69 (m, 10H, Ar-H). 13C NMR (75.47 MHz, CDCl3) δ-ppm: 59.0, 59.1
(CH3OCH2CH2-), 69.9, 70.0 (CH3OCH2CH2-), 50.2, 50.5 (CH3OCH2CH2-), 15.7 (CH3CH2CH2-
), 18.3 (CH3CH2CH2-), 28.0 (d, CH3CH2CH2-,2JC-P= 109.8 Hz), 206.6 (SCS).31P NMR (121.49
MHz, CDCl3) δ-ppm: 23.9. Elemental analysis, % Calculated (Found) for C22H31ClNO2PPdS2:
C, 45.68 (45.72); H, 5.40 (5.43); N, 2.42 (2.40); S, 11.09 (11.11).
1.2.4 [Pd(di-n-decyldithiocarbamate)(PPh3)Cl]
(3)
Quantities used were: 0.04g (0.10 mmol) potassium salt of di-n-decyldithiocarbamate, 0.08g
(0.10 mmol) Pd-phosphine complex. Yield: 0.06 g (71 %). M. p.: 183-184 °C. MW = 776.85.
FT-IR (powder, cm-1): 3053 υ(C-H, aromatic), 2922, 2850 υ(C-H, aliphatic), 1510 υ(C N),
1
1097 υ(SCS). Raman (powder, cm-1): 206 υ(Pd-P), 298 υ(Pd-Cl), 413 υ(Pd-S). H NMR (300
MHz, CDCl3) δ-ppm: 0.88 (t, 3H, CH3(CH2)8CH2-, 3JH-H= 7.0 Hz), 0.80 (t, 3H, CH3(CH2)8CH2-,
3JH-H= 7.0 Hz), 2.46 (t, 2H, NCH2-, 3JH-H= 7.0 Hz), 2.61 (t, 2H, NCH2-, 3JH-H= 7.0 Hz), 1.23-1.63
13
(m, 32H, CH3(CH2)8CH2-), 7.18-7.71 (m, 15H, Ar-H). C NMR (75.47 MHz, CDCl3) δ-ppm:
5

14.0, 14.2 (CH3(CH2)8CH2-), 49.1, 49.9 (NCH2-), 26.6, 27.1, 29.1, 29.2 29.3, 29.5, 31.8, 31.9 (-
(CH2)8-), 128.4, 128.5, 132.0, 136.1 (Ar-C), 206.8 (SCS).31P NMR (121.49 MHz, CDCl3) δ-
ppm: 21.5. Elemental analysis, % Calculated (Found) forC39H57ClNPPdS2: C, 60.30 (60.28); H,
7.40 (7.38); N, 1.80 (1.81); S, 8.26 (8.23).
1.2.5 [Pd(di-n-hexyldithiocarbamate)(PPh3)Cl]
(4)
Quantities used were: 0.04 g (0.13 mmol) potassium salt of di-n-hexyldithiocarbamate, 0.09 g
(0.13 mmol) Pd-phosphine complex. Yield: 0.06 g (73 %). M. p.: 190-191 °C. MW = 664.6. FT-
IR (powder, cm-1): 3040 υ(C-H, aromatic), 2975, 2930 υ(C-H, aliphatic), 1511 υ(C N), 1096
υ(SCS). Raman (powder, cm-1):218 υ(Pd-P), 311 υ(Pd-Cl), 388 υ(Pd-S).1H NMR (300 MHz,
CDCl3) δ-ppm: 0.79 (t, 3H, CH3(CH2)4CH2-, 3JH-H= 7.2 Hz), 0.85 (t, 3H, CH3(CH2)4CH2-, 3JH-H
=
3
7.2 Hz),1.15-1.24 (m, 16H, CH3(CH2)4CH2-),2.56 (t, 2H, CH3(CH2)4CH2-, JH-H= 7.1 Hz), 2.59
3
(t, 2H, CH3(CH2)4CH2-, JH-H= 7.1 Hz), 7.29-7.67 (m, 15H, Ar-H).13C NMR (75.47 MHz,
CDCl3) δ-ppm: 14.0, 14.3 (CH3(CH2)4CH2-), 22.4, 22.7 (CH3CH2CH2CH2CH2CH2-), 26.1, 26.3
(CH3CH2CH2CH2CH2CH2-),
27.0,
27.2
(CH3CH2CH2CH2CH2CH2-),
31.1,
31.3(CH3CH2CH2CH2CH2CH2-), 49.3, 50.1 (CH3CH2CH2CH2CH2CH2-), 206.4 (SCS). 31P NMR
(121.49 MHz, CDCl3) δ-ppm: 30.0. Elemental analysis, % Calculated (Found) for
C31H41ClNPPdS2: C, 56.02 (56.11); H, 6.22 (6.20); N, 2.11 (2.10); S, 9.65 (9.67).
1.2.6 [Pd(bis(2-methylbutyl)dithiocarbamte)(PPh3)Cl]
(5)
Quantities used were: 0.06g (0.22 mmol) of potassium salt of bis(2-methybutyl)dithiocarbamate,
0.16 g (0.22 mmol) of palladium triphenylphosphine complex. Yield: 0.11 g (76 %) M. p.: 201-
202 °C. MW = 636.59. FT-IR (powder, cm-1): 3072 υ(C-H, aromatic), 2957, 2925υ(C-H,
aliphatic), 1526υ(C N), 1093 υ(SCS).Raman (powder, cm-1): 238 υ(Pd-P), 293 υ(Pd-Cl), 430
υ(Pd-S).1H NMR (300 MHz, CDCl3) δ-ppm: 0.82 (t, 3H, CH3CH2CH(CH3)CH2-, 3JH-H= 5.3 Hz),
3
0.86 (t, 3H, CH3CH2CH(CH3)CH2-, JH-H= 5.3 Hz), 0.93, 1.06 (d, 6H, CH3CH2CH(CH3)CH2-),
1.50 (m, 4H, CH3CH2CH(CH3)CH2-), 1.61 (m, 2H, CH3CH2CH(CH3)CH2-), 3.45, 3.62 (d, 4H,
CH3CH2CH(CH3)CH2-), 7.26-7.70 (m, 15H, Ar-H). 13C NMR (75.47 MHz, CDCl3) δ-ppm: 22.3,
22.4
(CH3CH2CH(CH3)CH2-),
26.0,
26.1
(CH3CH2CH(CH3)CH2-),
30.8,
30.9
(CH3CH2CH(CH3)CH2-), 35.7, 35.8 (CH3CH2CH(CH3)CH2-), 47.7, 47.9 (CH3CH2CH(CH3)CH2-
6

31
), 207.0 (SCS). P NMR (121.49 MHz, CDCl3) δ-ppm: 30.1. Elemental analysis, % Calculated
(Found) forC29H37ClNPPdS2: C, 54.72 (54.68); H, 5.86 (5.87); N, 2.20 (2.21); S, 10.07 (10.04).
1.2.7 [Pd(di-n-decyldithiocarbamate)(PPh2-p-tolyl)Cl]
(6)
Quantities used were: 0.04 g (0.10 mmol) potassium salt of di-n-decyldithiocarbamate, 0.08g
(0.10 mmol) Pd-phosphine complex. Yield: 0.06 g (70%). M. p.:160-161 °C. MW = 790.88. FT-
IR (powder, cm-1): 3053 υ(C-H, aromatic), 2922, 2850 υ(C-H, aliphatic), 1510 υ(C N),
1097υ(SCS). Raman (powder, cm-1): 206 υ(Pd-P), 298 υ(Pd-Cl), 413 υ(Pd-S).1H NMR (300
MHz, CDCl3) δ-ppm: 0.88 (t, 3H, CH3(CH2)8CH2-, 3JH-H= 7.0 Hz), 0.83 (t, 3H, CH3(CH2)8CH2-,
3
3
3JH-H= 7.0 Hz) 2.46 (t, 2H, NCH2-, JH-H= 7.0 Hz), 2.61 (t, 2H, NCH2-, JH-H= 7.0 Hz), 2.65 (t,
3
2H, NCH2-, JH-H= 7.0 Hz),1.23-1.63 (m, 32H, CH3(CH2)8CH2-), 2.38 (s, 3H, Ph-CH3), 7.18-
13
7.71 (m, 14H,Ar-H). C NMR (75.47 MHz, CDCl3) δ-ppm: 14.0, 14.1 CH3(CH2)8CH2-), 49.1,
49.8 (NCH2-), 26.6, 27.1, 29.1, 29.2, 29.3, 29.5, 31.8, 31.9 (-(CH2)8-), 21.5 (Ph-CH3), 206.5
31
(SCS). P NMR (121.49 MHz, CDCl3) δ-ppm: 27.0. Elemental analysis, % Calculated (Found)
for C40H59ClNPPdS2: C, 60.75 (60.79); H, 7.52 (7.54); N, 1.77 (1.76); S, 8.11 (8.15).
1.2.8 [Pd(di-n-hexyldithiocarbamate)(PPh2-p-tolyl)Cl]
(7)
Quantities used were: 0.07 g potassium salt of di-n-hexyldithiocarbamate, 0.17 g of palladium
diphenyl-p-tolyl phosphine complex. Yield: 0.11g (68 %).M. p.: 230-231 °C. MW = 678.67. FT-
IR (powder, cm-1):3050 υ(C-H, aromatic), 2923, 2850 υ(C-H, aliphatic), 1510 υ(C N), 1097
υ(SCS).Raman (powder, cm-1): 206 υ(Pd-P), 298 υ(Pd-Cl), 413 υ(Pd-S).1H NMR (300 MHz,
CDCl3) δ-ppm: 0.86 (t, 3H, CH3(CH2)4CH2-, 3JH-H= 8.0 Hz), 0.83 (t, 3H, CH3(CH2)4CH2-, 3JH-H
=
3
8.0 Hz), 1.23-2.38 (m, 16H, CH3(CH2)4CH2-, 3.46 (t, 2H, CH3(CH2)4CH2-, JH-H= 7.1 Hz), 3.61
(t, 2H, CH3(CH2)4CH2-, 3JH-H= 7.1 Hz), 2.36 (s, 3H, Ph-CH3). 13C NMR (75.47 MHz, CDCl3) δ-
ppm: 13.7,13.9 (CH3(CH2)4CH2-), 21.5 (Ph-CH3), 22.4, 22.6 (CH3CH2CH2CH2CH2CH2-), 26.2,
26.5 (CH3CH2CH2CH2CH2CH2-), 27.0, 27.4 (CH3CH2CH2CH2CH2CH2-), 31.3, 31.5
(CH3CH2CH2CH2CH2CH2-), 49.3, 49.8 (CH3CH2CH2CH2CH2CH2-), 206.3 (SCS).31P NMR
7

(121.49 MHz, CDCl3) δ-ppm: 27.0. Elemental analysis,
%
Calculated (Found)
forC32H43ClNPPdS2: C, 56.63 (56.60); H, 6.39 (6.41); N, 2.06 (2.05); S, 9.45 (9.47).
1.2.9 [Pd(bis(2-ethylhexyl)dithiocarbamate)(PPh2-p-tolyl)Cl]
(8)
Quantities used were: 0.17g (0.48 mmol) bis(2-ehtylhexyl)dithiocarbamic acid, 0.35g (0.48
mmol) Pd-phosphine complex. Yield: 0.27 g (76%). M. p.:197-198 °C. MW = 734.77. FT-IR
(powder, cm-1): 3040 υ(C-H, aromatic), 2971, 2922 υ(C-H, aliphatic), 1510 υ(C N), 1096
υ(SCS). Raman (powder, cm-1): 223 υ(Pd-P), 312 υ(Pd-Cl), 391 υ(Pd-S).1H NMR (300 MHz,
3
CDCl3) δ-ppm:0.83 (t, 3H, CH3(CH2)3CH(CH2CH3)CH2-, JH-H= 7.2 Hz), 0.88 (t, 3H,
CH3(CH2)3CH(CH2CH3)CH2-, 3JH-H= 7.2 Hz), 1.16-1.30 (m, 12H, CH3(CH2)3CH(CH2CH3)CH2-
),
1.70-1.77
(m,
4H,
CH3(CH2)3CH(CH2CH3)CH2-),
1.83-1.90
(m,
2H,
2
CH3(CH2)3CH(CH2CH3)CH2-),3.56 (d, 2H, CH3(CH2)3CH(CH2CH3)CH2-, JH-H= 7.1 Hz), 3.60
(d, 2H, CH3(CH2)3CH(CH2CH3)CH2-, 2JH-H= 7.1 Hz), 2.36 (s, 3H, Ph-CH3), 7.18-7.71 (m, 14H,
Ar-H). 13C NMR (75.47 MHz, CDCl3) δ-ppm: 10.5,10.6 (CH3(CH2)3CH(CH2CH3)CH2-),
14.0,14.1 (CH3(CH2)3CH(CH2CH3)CH2-), 22.9, 23.7, 28.4, 30.4 (CH3(CH2)3CH(CH2CH3)CH2-),
37.4, 37.6 (CH3(CH2)3CH(CH2CH3)CH2-), 52.7,52.9 (CH3(CH2)3CH(CH2CH3)CH2-), 21.5 (Ph-
CH3), 127.8, 128.3, 128.8 129.3, 130.3, 134.4, 135.0, 140.8 (Ar-C), 207.7 (SCS). 31P NMR
(121.49 MHz, CDCl3) δ-ppm: 23.8. Elemental analysis, % Calculated (Found) for
C36H51ClNOPPdS2: C, 57.59 (57.65); H, 6.85 (6.87); N, 1.87 (1.88); S, 8.54 (8.57).
1.2.10 [Pd(bis(2-ethylhexyl)dithiocarbamate)(PPh2(benzyl))Cl]
(9)
Quantities used were: 0.15 g (0.42 mmol) of potassium salt of bis(2-ethylhexyl)dithiocarbamate,
0.31 g (0.42 mmol) of palladium benzyldiphenyl phosphine complex. Yield: 0.25 g (81 %). M.
p.: 203-204 °C. MW = 734.77. FT-IR (powder, cm-1): 3040 υ(C-H, aromatic), 2975, 2930 υ(C-H,
aliphatic), 1511 υ(C N), 1096 υ(SCS).Raman (powder, cm-1):218 υ(Pd-P), 311 υ(Pd-Cl), 388
1
3
υ(Pd-S). H NMR (300 MHz, CDCl3) δ-ppm: 0.78 (t, 3H, CH3(CH2)3CH(CH2CH3)CH2-, JH-H
=
3
7.2 Hz), 0.86 (t, 3H, CH3(CH2)3CH(CH2CH3)CH2-, JH-H= 7.2 Hz), 1.15-1.24 (m, 12H,
CH3(CH2)3CH(CH2CH3)CH2-), 1.53-1.69 (m, 4H, CH3(CH2)3CH(CH2CH3)CH2-), 1.81-1.89 (m,
3
2H, CH3(CH2)3CH(CH2CH3)CH2-), 3.93 (d, 4H, CH3(CH2)3CH(CH2CH3)CH2-, JH-H= 7.0 Hz),
4.01 (d, 2H, Ph-CH2-, 3JH-H= 7.0 Hz), 7.17-7.52 (m, 15H, Ar-H). 13C NMR (75.47 MHz, CDCl3)
8

δ-ppm: 10.5 (CH3(CH2)3CH(CH2CH3)CH2-), 14.0 (CH3(CH2)3CH(CH2CH3)CH2-), 22.9, 23.8
2
28.4, 30.6 (CH3(CH2)3CH(CH2CH3)CH2-), 32.9 (d, Ph-CH2-, JC-P[13C, 31P]), 37.4
(CH3(CH2)3CH(CH2CH3)CH2-), 52.7 (CH3(CH2)3CH(CH2CH3)CH2-), 207.1 (SCS). 31P NMR
(121.49 MHz, CDCl3) δ-ppm: 27.0. Elemental analysis, % Calculated (Found) for
C36H51ClNPPdS2: C, 58.85 (58.80); H, 7.00 (7.02); N, 1.91 (1.90); S, 8.73 (8.75).
1.2.11 [Pd(bis(2-ethylhexylhexyl)dithiocarbamate)(PPh3)Cl]
(10)
Quantities used were: 0.20g (0.56 mmol) bis(2-ehtylhexyl)dithiocarbamic acid, 0.39g (0.56
mmol) Pd-phosphine complex. Yield: 0.32 g (80%). M. p.:290-291 °C (decompose). MW =
720.75. FT-IR (powder, cm-1): 3040 υ(C-H, aromatic), 2975, 2930 υ(C-H, aliphatic), 1511 υ(C
N), 1096 υ(SCS). Raman (powder, cm-1): 218 υ(Pd-P), 311 υ(Pd-Cl), 388 υ(Pd-S).1H NMR
(300 MHz, CDCl3) δ-ppm: 0.79 (t, 3H, CH3(CH2)3CH(CH2CH3)CH2-, 3JH-H= 7.2 Hz),0.81 (t, 3H,
CH3(CH2)3CH(CH2CH3)CH2-, 3JH-H= 7.2 Hz), 0.84 (t, 3H, CH3(CH2)3CH(CH2CH3)CH2-, 3JH-H
=
3
7.2 Hz), 0.82 (t, 3H, CH3(CH2)3CH(CH2CH3)CH2-, JH-H= 7.2 Hz), 1.17-1.24 (m, 12H,
CH3(CH2)3CH(CH2CH3)CH2-), 1.54-1.68 (m, 4H, CH3(CH2)3CH(CH2CH3)CH2-), 1.80-1.89 (m,
3
2H, CH3(CH2)3CH(CH2CH3)CH2-), 3.91 (d, 2H, CH3(CH2)3CH(CH2CH3)CH2-, JH-H= 7.0 Hz),
3.94 (d, 2H, CH3(CH2)3CH(CH2CH3)CH2-, 3JH-H= 7.0 Hz), 7.29-7.67 (m, 15H, Ar-H). 13C NMR
(75.47 MHz, CDCl3) δ-ppm: 10.4, 10.6 (CH3(CH2)3CH(CH2CH3)CH2-), 14.1, 14.2
(CH3(CH2)3CH(CH2CH3)CH2-), 22.9, 23.6 28.3, 30.6 (CH3(CH2)3CH(CH2CH3)CH2-), 37.6, 37.7
(CH3(CH2)3CH(CH2CH3)CH2-), 52.7, 52.9 (CH3(CH2)3CH(CH2CH3)CH2-), 128.4, 130.7 132.1,
31
134.4 (Ar-C),207.1 (SCS). P NMR (121.49 MHz, CDCl3) δ-ppm: 30.2. Elemental analysis: %
Calculated (Found) for C35H49ClNPPdS2: C, 58.32 (58.25); H, 6.85 (6.84); N, 1.94 (1.95); S,
8.90 (8.92).
1.3 Structural studies of complexes 1 and 2
The needle shaped golden yellow crystals of the complexes 1 and 2 were developed in
dichloromethane and n-hexane in the volume ratio of 2:1 respectively. The crystals were
mounted on a glass fibre with the help of epoxy glue. The measurements were made at 293 K on
a STOE IPDS image plate detector diffractometer equipped with graphite mono-chromated
MoKα radiation. The cell parameters, data collection and data integration were performed with
9

the help of; S1TOE X-AREA [27]. The structures of the complexes were solved and refined by
using SHELXS-97 and SHELXL-97 (Sheldrick, 1997) and all the non-hydrogen atoms were
refined anisotropically, with the hydrogen atoms were placed at the idealized positions. The two
A level alerts in the CIF file of the complex 1 can be ignored, as these don’t disturb the geometry
around the metal centre.
1.4 Anti-bacterial assays
The antibacterial potential of the synthesized mixed ligand metal complexes was tested against
some Gram positive and Gram negative bacterial strains.
1.4.1 Antibacterial assays
The antibacterial activity of all the synthesized metal complexes has been investigated against
five strains of bacteria (Escherichia coli, Bacillus subtilis, Staphylococcus aureus, Klebsiella
pneumoniae and Staphylococcus epidermidis) by the agar well diffusion method[28]. Imipenem
was selected as a standard antibiotic. Four milligrams of the complexes were dissolved in 1 ml of
DMSO. Centrifuged pellets of bacteria were taken from 24h old culture containing
approximately 104–106 colony forming unit (CFU) per ml was spread on the surface of Muller
Hinton Agar (MHA) plates. Wells were created in medium with the help of a sterile metallic
borer and nutrients agar medium were prepared by suspending nutrient agar(Merck) 20 g in one
litre of distilled water (pH 7.0), autoclaved and cooled down to 45 °C. Then it was seeded with10
ml of prepared inocula to have 106 CFU/ml. Petri dishes were prepared by pouring 75 ml of
seeded nutrients agar. Experimental plates were incubated for 24 h and zones of inhibition (%)
were measured and compared with standard antibiotic Imipenem. The bactericidal assays were
performed in triplicate and results are shown in Table 1.2.
1.4.2 Anticancer assays
The human lung Fibroblast MRC-5 carcinoma cells were obtained from the American Type
Culture Collection. The cells were maintained in Roswell Park Memorial Institute medium
supplemented with 10 mM HEPES, 3 mM L-glutamine, 10% FBS and 100 µg/mL penicillin.
Prior to the drug treatment, all the assay cells were plated for 24 h. 100 mmol stock solutions of
10

the synthesized compounds were prepared in DMSO. Nine serial dilutions of the heteroleptic
palladium complexes were used to treat the cells.
The MRC-5 carcinoma cells were plated at 5000 cells/well in 96-well flat-bottom microtiter
plates. After 24 h incubation, cells were exposed to various concentrations of each compound for
five days. The remaining live cells were fixed using 60 µL of cold trichloroacetic acid (50%) for
60 minutes at 276 K , washed with water, stained with 0.4% sulphorhodamine B (SRB) for 5 h
at 298 K, rinsed with 1% acetic acid and allowed to dry overnight[29]. The resulting coloured
residue was dissolved in 200 µL Tris base (10 mM, pH 10.0) and optical density was recorded at
490 nm using a microplate reader ELx808 (Biotek instruments). The results were analysed by
Graph Pad Prism (Graph Pad Software, Inc., San Diego, CA) and the sigmoidal dose response
curve was used to determine 50% cell growth inhibitory concentration (IC50). The growth
inhibition assay was performed once in triplicate.
1.5 Results and discussion
Synthesis and characterization of mixed ligand palladium(II) complexes
The heteroleptic Pd(II) complexes were synthesized by reacting known Pd-phosphine complexes
[30]
[31]
with dithiocarbamate ligands
while stirring magnetically and under reflux conditions in
dichloromethane (Scheme 1.1). The synthesized compounds are stable at normal conditions of
temperature and pressure and soluble in common organic solvents.
The stretching frequencies of
and
, were of prime interest in the IR spectra of the
mixed ligand palladium(II) complexes. Both of these vibrations can be used to determine the
coordination mode of a dithiocarbamate ligand to metal moiety. The presence of a single band in
the range of 1089-1097 cm-1 due to υ(
coordinated to metal centre in a symmetrical bidentate fashion, otherwise two peaks are observed
in this region[30b]. The absorption peak is observed in the range of 1510-1526 cm-1, which
) is an indication that dithiocarbamate has been
is intermediate between a single bond C-N (1250-1350 cm-1) and a double bond C=N (1640-
1690 cm-1), and a very typical characteristic of dithiocarbamate complexes[32]. The intermediate
nature of the C-N bond showed the resonance phenomenon in the dithiocarbamate moiety and
11

has been confirmed using X-ray crystallography[33]. The disappearance of the S-H peak in the
metal complexes suggested the coordination of dithiocarbamate ligand with metal centre.
Raman spectroscopy was mainly used to identify the metal ligand bonds in the far IR region i.e.,
below 400 cm-1. The most explicit feature in the spectra of all of the complexes was the
appearance of a new band in the 388-430 cm-1 region, which was absent in the spectra of the free
ligands, this band is assigned to the Pd-S[34] stretching mode. The Pd-Cl stretching mode was
observed in the 296-312 cm-1 range, while the Pd-P stretching mode appeared in the 200-238 cm-
1, region for all the complexes. The observation of all of these bands demonstrates complex
formation between the Pd(II) moiety and the ligands.
S
R'
N
PR3
Cl
S
R'
SH/K
R'
R'
(PR3)2PdCl2
Pd
N
S
CH2Cl2, Reflux, 24 hr
PR3 = PPh2C(CH3)3 (1), PPh2-n-propyl (2), PPh3 (3,4,5,10), PPh2-p-tolyl
(6,7,8), PPh2(benzyl) (9)
R' = 2-ethylhexyl (1,8,9,10), 2-methoxyethyl (2), n-decyl (3,6), n-hexyl
(4,7), 2-methylbutyl (5)
Scheme 1.1: Synthesis of heteroleptic palladium(II) complexes
The proton NMR spectra of the synthesized compounds were recorded in CDCl3. The
assignments of the proton peaks were made from their multiplicity, chemical shift, intensity
pattern and comparison of the integration areas of the protons with the expected composition.
1
The H NMR data show the disappearance of the SH frequency- suggesting coordination of the
dithiocarbamate ligand to the metal centre by abstraction of H+ from the dithiocarbamic acid
1
moiety. Another characteristic feature of the H NMR spectra is the asymmetry in the alkyl
groups attached to the nitrogen atom of the dithiocarbamate moiety, caused by restricted rotation
around the C-N bond, which is known to have a barrier energy ranging from 65 to 92 kJ.mol-1[35]
.
The restricted rotation around the C-N bond can be attributed to the partial double bond character
12

in this bond owing to resonance in the dithiocarbamate group. The aromatic protons were
observed at 7.18-7.10 ppm. The rest of the proton frequencies in the metal complexes show no
distincive changes when compared to the spectra of their precursors. All these observations are
in agreement with the previously reported literature for Pd-dithiocarbamate complexes[31a, 36]
.
The 13C NMR spectra of the complexes were also recorded in CDCl3. The most important peak
in the carbon spectra of all the compounds is the carbon of SCS moiety of the dithiocarbamate
ligand. The slight up field shift of this signal can be attributed to the accumulation of electronic
density after complexation. It confirms coordination of the dithiocarbamate ligand with the metal
centre. The SCS carbon atom in the complexes investigated was observed in the 206.3-208.6
ppm range. Like the proton atoms of the alkyl groups attached to the nitrogen atom of the
dithiocarbamate, the carbon atoms of the alkyl groups are also asymmetrical in nature.
31P NMR data were collected for the synthesized complexes in CDCl3 and their precursors.
Generally, the 31P frequency shifted considerably downfield after the coordination of the
31
phosphine ligand to metal moiety. The downfield shift of the P frequency can be assigned to
the flow of electronic density from the phosphorus atom to the palladium centre after the
complex formation. The 31P shifts were observed in the range of 21.5-45.1ppm
1.6 Structural studies of complexes 1 and 2
The ball and stick diagrams of compounds 1 and 2 with selected bond lengths and angles are
shown in Figures 1.1 and 1.2 respectively. Both complexes crystallize in the P2(1)/c space group.
In both complexes, the central atom exhibits similar pseudo square-planar geometry with the
dithiocarbamate ligand occupying two adjacent coordination sites while the chloride ion and the
tertiary organophosphine ligand dwell in the two remaining sites. The largest deformation from
the normal square planar geometry comes from the bidentate ligand (S(1)-Pd-S(2) of
75.05(3)°and 75.37(3)° for 1 and 2, respectively) which causes the trans S-Pd-Cl (166.34(3)° (1)
and 170.71(4)° (2)) and P-Pd-S angles to be 169.14(3)° (1) and 170.89(3)° (2), smaller than the
expected value of 180°. The asymmetry observed in the Pd-S distances (∆S, 0.0502 Å (1) and
0.0777 Å (2)) is usual for square planar systems and reflects the trans influence of the attached
ligands. In both complexes, the Pd-S bond lengths trans to the phosphine ligands are longer
13

(2.3372(8) Å (1) and 2.3643(14) Å (2) than the Pd-S bond lengths trans to the chloride
(2.2870(9) Å (1) and 2.2854(9) Å (2). The largest inconsistency in the Pd-S bond lengths (0.0777
Å) for complex 2 demonstrates the better donating capability of the diphenyl-n-propylphosphine
than diphenyl-tert-butylphosphine ligand. The S-C bond distances (1.709(3), 1.727(3) (1) and
(1.732(4), 1.715(4) (2) are intermediate between single bond, C-S (1.82 Å) and double bond C=S
(1.60 Å) distances. In the same way, the C-N bond lengths of 1.323(4)Å for 1 and 1.322(4)Å for
2 are significantly shorter than a normal C-N bond distance (1.47 Å) and longer than a C=N bond
length (1.28 Å)[37]. These bond values clearly demonstrate the resonance phenomenon in N-CSS
moiety.
Figure 1.1: The ball and stick diagram (50% probability)of (1). The Hydrogen atoms have been
omitted for clarity. Selected bond lengths (Å) and angles (deg): 2.3372(8) (Pd-S, trans to
organophosphine), 2.2870(9) (Pd-S, trans to Cl-), 0.0502 (∆S),1.323(4) (C-N); 169.14(3) (P-Pd-S,S
14

trans to phosphorus atom), 166.34(3) (Cl-Pd-S, S trans to chloride ion), 75.05(3) (S-Pd-S), 110.1(2) (S-
C-S).
Complex 2
Figure1.2: The ball and stick diagram (50% probability)of (2). Hydrogen atoms have been
removed for clarity. Selected bond lengths (Å) and angles (deg): 2.3631(9) (Pd-S, trans to
organophosphine), 2.2854(9) (Pd-S, trans to Cl-), 0.0777 (∆S), 1.322(4) (C-N); 170.89(3) (P-Pd-S, S,
trans to phosphorus atom), 170.71(4) (Cl-Pd-S, S, trans to chloride ion), 75.37(3) (S-Pd-S), 111.1(2) (S-
C-S).
15

Table 1.1: Crystal data and structure refinement parameters for complexes 1 and 2
Compound No.
1
2
C33 H53 Cl N P Pd S2
C22 H31 Cl NO2 P Pd S2
Empirical
formula
Formula weight
Temperature
Wavelength
700.76
578.46
296(2) K
0.71073 Å
MoK\α
200 (2) K
1.54178 Å
CuK\α
Diffraction
radiation type
Space group
F(000)
P2(1)/c
1472.0
P2(1)/c
1184.0
Index ranges
-16<=h<=16, 0<=k<=12, 0<=l<=23
-16<=h<=16, -23<=k<=29, -
17<=l<=12
Unit cell
a = 12.3536(6) Å α = 90.00°
a = 13.3911(6) Å α = 90.00°
dimensions
b = 22.0280(9) Å β = 96.970(2)° b = 10.2874(5) Å β = 103.714(3)°
c = 13.4169(6) Å γ = 90.00°
c = 18.7804(9) Å γ = 90.00°
42458
30349
Reflections
collected
2
2
Refinement
method
Full-matrix least-squares on F
Full-matrix least-squares on F
1.7 Biological activity
1.7.1 Cell cytotoxicity assay
The synthesized compounds 1-10 were assayed for their cytotoxicities against the human lung
fibroblast MRC-5 cell line. The IC50 values of the compounds are given in the Table 1.1. The
16

complex 6, [Pd(di-n-decyldithiocarbamate)(PPh2-p-tolyl)Cl] showed the greatest cytotoxicity of
the ten complexes. The higher cytotoxicity of complex 6 may be assigned to the higher carbon
chain length of the dithiocarbamate ligand. The longer the carbon chain length, the higher the
efficiency of the DNA-binding and the greater the cytotoxicity [25]. Compound 3, which contains
the same ligand di-n-decyldithiocarbamate ligand also exhibited cytotoxic activity but less than
compound 6. The difference in activity may be due to the variation in the attached
organophosphine ligand. In general, the compounds exhibited low to moderate activity.
Table 1.2: Anticancer activity
Samples
1
2
3
4
5
6
7
8
9
10
IC50
[mM] SEM
36.7 2.9 >100 71.5 13.1 >100 81.6 13.1 22.8 2.4 >100 30.8 2.6 >100 65.3 12.5
1.7.2 Antibacterial activity
The synthesized metallodrugs were screened for their antibacterial activity against two Gram
positive (Bacillus subtilis, Staphylococcus aureus) and three Gram negative bacteria
(Escherichia coli, Klebsiella pneumoniae, Staphylococcus epidermidis). The antibacterial
activities are shown in Table 1.2. The antibacterial activities of the synthesized compounds
decrease in the order 1>3>10>8>9>2>7>6>4>5.A regular structure activity relationship cannot
be concluded from the available data. Generally, the compounds containing the 2-
ethylhexyldithiocarbamate ligand (1, 8, 9, and 10) showed higher antibacterial activity.
According to chelation theory, the polarity of the metal atom decreases upon complexation and
lipophilicity of the metallo drug is increased. The organophosphine ligands also have an
important role in the antibacterial activity of compounds. The two compounds, 4 and 5, which
contain triphenylphosphine, exhibit the lowest antibacterial activity; this may be assigned to the
electron-withdrawing nature of triphenylphosphine moiety.
17

Table 1.3: Antibacterial activity (diameter of inhibition zone in mm) of the synthesized
complexes
Samples
Bacillus
subtilis
(G +)
Staphylococcus
Escherichia
Klebsiella
pneumoniae
(G -)
Staphylococcus
aureus (G +)
coli (G -)
epidermidis (G -)
22 0.33
15 0.21
18 0.39
10 0.47
10 0.38
12 0.33
10 0.71
17 0.24
16 0.36
17 0.39
32 0.44
22 0.16
15 0.27
18 0.13
10 0.23
10 0.36
12 0.44
10 0.32
17 0.46
16 0.18
17 0.33
35 0.54
20 0.21 16 0.32
11 0.52 12 0.67
21 0.61 19 0.55
14 0.51 13 0.69
07 0.26 09 0.43
11 0.23 10 0.13
16 0.23 15 0.43
14 0.35 18 0.22
15 0.37 16 0.25
16 0.21 18 0.42
25 0.11 26 0.15
16 0.46
1
17 0.35
17 0.62
10 0.16
12 0.55
13 0.21
11 0.63
13 0.32
15 0.58
20 0.28
35 0.36
2
3
4
5
6
7
8
9
(10
Reference
drug
(Imipenem)
1.8 Conclusions
Ten heteroleptic palladium(II) compounds were synthesized and characterized by various
spectroscopic techniques. Metal-based compounds, such as these have exhibited promising
antitumor and antibacterial activity. All the synthesized complexes were prepared in good yield.
The spectroscopic results and single-crystal X-ray diffraction studies for two of the compounds
reveal that the compounds have distorted square-planar geometry around the metal moiety. The
compounds exhibited moderate antibacterial and antitumor activity.
18

1.9 Supplementary material
The crystallographic data for the structural analyses of complexes 1 and 2, have been deposited
with the Cambridge Crystallographic Data Centre, CCDC No. for 1 is CCDC 1420935 and for
complex 2 is CCDC 1420934. Copy of this information may be obtained free of charge from the
Director, CCDC, 12 Union Road, Cambridge, CBZ1EZ, UK (fax: þ44 1223 336 033;
email:deposit@ccdc.cam.ac.uk or www: http://www.ccdc.cam.ac.uk).
1.10 Acknowledgement
Dr Hizbullah Khan is highly grateful to Higher Education Commission (HEC) of Pakistan for
providing PhD scholarship under the “5000 Indigenous PhD Scholarships Programme”, at
Quaid-i-Azam University Islamabad and six months scholarship under the programme of
International Research Support Initiative Programme (IRSIP) as a Graduate Research Trainee at
Department of Chemistry, McGill University, Montreal, Quebec, Canada.
19

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Synopsis
Mixed ligand Pd(II) complexes have been synthesized in good yields. All the complexes were
characterized by analytical and spectroscopic techniques. The prepared compounds have shown
moderate antitumor and antibacterial activity.
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Graphical Abstract
Complex 1
Complex 2
S
R'
N
PR3
Cl
S
R'
SH/K
R'
R'
(PR3)2PdCl2
Pd
N
S
CH2Cl2, Reflux, 24 hr
PR3 = PPh2C(CH3)3 (1), PPh2-n-propyl (2), PPh3 (3,4,5,10), PPh2-p-tolyl
(6,7,8), PPh2(benzyl) (9)
R' = 2-ethylhexyl (1,8,9,10), 2-methoxyethyl (2), n-decyl (3,6), n-hexyl
(4,7), 2-methylbutyl (5)
Scheme:
Synthesis of heteroleptic palladium(II) complexes

Highlights
ꢀ Ten heteroleptic palladium(II) complexes have been synthesized in good yields
ꢀ The single crystal XRD analyses of the two prepared complexes have exhibited pseudo
square-planar geometry around the central metal atom
ꢀ The
absorption peak is observed in the range of 1510-1526 cm-1, which is
intermediate between a single bond C-N (1250-1350 cm-1) and a double bond C=N
(1640-1690 cm-1)
ꢀ The synthesized metallodrugs have shown moderate anticancer and antibacterial activity
23