New formamidine ligands and their mixed ligand palladium(II) oxalate complexes: Synthesis, characterization, DFT calculations and in vitro cytotoxicity

Article abstract of DOI:10.1016/j.saa.2015.07.076

A series of new ternary palladium(II) complexes of the type [Pd(L_1-4)ox]·xH₂O where L = formamidine ligands and ox = oxalate, were synthesized and characterized by elemental analyses, magnetic susceptibility, UV-Vis, infrared (IR) and mass spectroscopy and thermal analysis. The spectroscopic data indicated that the formamidine ligands act as bidentate N2 donors and the oxalate as O2 ligand. The complexes (1-4) are diamagnetic and the optimization of their structures indicated that the geometry is distorted square planer with O-Pd-O and N-Pd-N bond angles ranged 82.70-83.87° and 88.21-95.02°; respectively which is acceptable for the heteroleptic complexes. The dipole moment of the complexes (13.97-18.77 Debye) indicating that the complexes are more polarized than the ligands (1.93-4.96 Debye). The complexes are thermally stable as shown from their relatively higher overall activation energies (441-688 kJ mol^-1). The ligands and the complexes are proved to have good cytotoxicity with IC₅₀ (μM) in the range of (0.011-0.168) against MCF-7, (0.012-0.150) against HCT-116, (0.042-0.094) against PC-3 and (0.006-0.222) against HepG-2 cell lines, which open the field for further application as antitumor compounds.

Full text of DOI:10.1016/j.saa.2015.07.076

Accepted Manuscript
New formamidine ligands and their mixed ligand palladium(II) oxalate com-
plexes: Synthesis, characterization, DFT calculations and in vitro cytotoxicity
Ahmed A. Soliman, Othman I. Alajrawy, Fawzy A. Attabi, Mohamed R.
Shaaban, W. Linert
PII:
S1386-1425(15)30125-6
http://dx.doi.org/10.1016/j.saa.2015.07.076
SAA 13975
DOI:
Reference:
Spectrochimica Acta Part A: Molecular and Biomo-
lecular Spectroscopy
To appear in:
Received Date:
Revised Date:
Accepted Date:
17 April 2015
19 June 2015
16 July 2015
Please cite this article as: A.A. Soliman, O.I. Alajrawy, F.A. Attabi, M.R. Shaaban, W. Linert, New formamidine
ligands and their mixed ligand palladium(II) oxalate complexes: Synthesis, characterization, DFT calculations and
in vitro cytotoxicity, Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy (2015), doi: http://
dx.doi.org/10.1016/j.saa.2015.07.076
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

New formamidine ligands and their mixed ligand palladium(II)
oxalate complexes: Synthesis, characterization, DFT calculations
and in vitro cytotoxicity
Ahmed A. Soliman1*, Othman I. Alajrawy1, 2, Fawzy A. Attabi1 , Mohamed R.
Shaaban1 and W. Linert3
1Department of Chemistry, Faculty of Science, Cairo University, 12613 Giza, Egypt.
2College of Veterinary Medicine, Al-Anbar University, Fallujah, Iraq
3Institute of Applied Synthetic Chemistry, Vienna University of Technology, Getreidemarkt
9163-AC, A-1060 Vienna, Austria.
Abstract
A series of new ternary palladium(II) complexes of the type [Pd(L1-4)ox].xH2O where L= formamidine
ligands and ox=oxalate, were synthesized and characterized by elemental analyses, magnetic
susceptibility, UV-Vis, infrared (IR) and mass spectroscopy and thermal analysis. The spectroscopic data
indicated that the formamidine ligands act as bidentate N2 donors and the oxalate as O2 ligand. The
complexes (1-4) are diamagnetic and the optimization of their structures indicated that the geometry is
distorted square planer with O-Pd-O and N-Pd-N bond angles ranged 82.70°-83.87° and 88.21°-95.02°;
respectively which is acceptable for the heteroleptic complexes. The dipole moment of the complexes
(13.97-18.77 Debye) indicating that the complexes are more polarized than the ligands (1.93-4.96 Debye).
The complexes are thermally stable as shown from their relatively higher overall activation energies (441-
688 kJmol-1). The ligands and the complexes are proved to have good cytotoxicity with IC50 (µM) in the
range of (0.011-0.168) against MCF-7, (0.012-0.150) against HCT-116, (0.042-0.094) against PC-3
and (0.006-0.222) against HepG-2 cell lines, which open the field for further application as antitumor
compounds.
Keywords: ternary Pd(II) complexes, oxalate, formamidine, antitumor complexes.
*Correspondent author: Prof. Dr. Ahmed A Soliman, e-mail: ahmedsoliman61@gmail.com, Tel:
002 01110121379, Fax: 002 02 35676556.
1

1. INTRODUCTION
Over decades, pharmaceutical chemistry of anticancer drugs has been extensively reported
with the aim of design and test new anticancer drugs, potentially valuable in the treatment of a
lot of cancers [1-4]. The preparation of novel highly cytotoxic active both platinum and non-
platinum coordination compounds successfully use a combination of potentially active organic
compounds with a suitable transition metal [5]. Plenty of transition metal complexes, namely
iron(II/III), cobalt(II), nickel(II), copper(II), zinc(II), ruthenium(III), palladium(II), platinum(II)
and platinum(IV) [5], have been prepared, characterized and tested in vitro for their cytotoxic
activity against selected human cancer cell lines. Oxaliplatin is the most important representative
of platinum(II) oxalate complexes[6], because it belongs among the recently used platinum-
based anticancer drugs (approved in 1996) [4, 7]. The elements of platinum and palladium are
chemically very similar, that is why palladium complexes were tested for their cytotoxicity
among the first non-platinum compounds. However, cis-[PdCl2(NH3)2] and [PdCl2(dach)] the
analogues of the highly cytotoxic platinum(II) complexes, were found to be inactive on a
Sarcoma 180 tumor cell line [8]. Generally, the lower efficiency of palladium (II) complexes
than the platinum (II) analogues is attributed to the fact that palladium (II) complexes are of
about 105 times faster substitution of the leaving groups for the water molecules. Despite these
early failures, plenty of palladium complexes have been prepared to date and many of these
compounds were evaluated as substances with even higher cytotoxic activity against various
types of tumors as compared with cisplatin [7, 9].
On the other hand and up to the best of our knowledge, there are no reports on the metal
complexes of the used formamidine ligands except the study conducted in our group on the
binary complexes of palladium (II) and ruthenium(II) were prepared and investigated [10]. In
view of the above facts, it seems therefore to be of considerable interest to conduct investigations
of ternary complexes of palladium (II) with some formamidines and oxalate ligands as potential
antitumor complexes. In continuation of our published work on palladium complexes [10, 11],
we report in the present synthesis, characterization, structure optimization and antitumor activity
of palladium complexes of formamidine [10] and oxalate ligands. The formamidine ligands are
given in Scheme 1.
2

2. Experimental.
2.1. Materials.
All chemicals used in this study were of the highest purity available. Sodium
tetrachloropalladate(II), Na2[PdCl4] and potassium oxalate monohydrate, K2C2O4.H2O were
supplied by Aldrich. All solvents were of analytical grade and were purified by distillation
before use.
2.2. Measurements.
Infrared measurements of the solid complexes, as KBr pellets, were carried out using Jasco
FTIR-460 plus and Jasco FTIR-4000 (range 400-4000 cm-1), mass spectrometry measurements
were carried out using GCMS-QP1000EX Shimadzu. The magnetic susceptibility of the
complexes in the solid state was carried out using a Sherwood Scientific, Cambridge Science
Park Cambridge-England magnetic susceptibility balance. Thermal analysis of the complexes
were carried out using a Shimadzu thermo-gravimetric analyzer TGA-60H; under a nitrogen
atmosphere with a heating rate of 10 oC /min over a temperature range from room temperature up
to 1000 oC. UV-Vis spectra were recorded in a 1 cm path length quartz cell by using optizen UV-
Vis spectrophotometer.
2.3. Preparation of complexes
K2[Pd(ox)2].2H2O was synthesized using a slightly modified and previously published
procedure[12] and stored in dark and cold place throughout the study. Both sodium
tetrachloropalladate(II); Na2PdCl4, and potassium oxalate monohydrate; K2C2O4.H2O, were
o
dissolved separately in a minimum volume of distilled water, at 25 C, in a 1:2 (Pd: ox) molar
ratio. 1 mmol of L1(0.21 g), L2(0.19 g), L3(0.14 g) or L4(0.12 g) was dissolved in 10 mL of
ethanol and slightly added to a water solution (10 mL) of 1 mmol (0.40 g) K2[Pd(ox)2].2H2O.
o
The mixtures were stirred for 24 h at 40 C. The obtained yellow solids complexes
[Pd(L1)(ox)].H2O (1) (0.312 g; yield: 74.2%), [Pd(L2)(ox)].H2O (2) (0.289 g; yield: 72.2%),
[Pd(L4)(ox)].5/2H2O (4) (0.272 g; yield: 74.9%), and yellow-orange [Pd(L3)(ox)].4H2O (3)
(0.301 g; yield: 73.9%), ternary complexes were filtered off, washed with warm water, ethanol
and dried in vacuum dissector. Geometric parameters and energies of prepared complexes were
3

carried out using [GAUSSIAN 09W] software program. Molecular geometry of the singlet
ground state of complexes was fully optimized in the gas phase at the B3LYP level of theory.
3. Results and discussion
The analytical, physical and UV-Vis spectroscopic data of the ligands and their isolated metal
complexes are given in Table 1. The complexes are air stable and exhibit very poor solubility in
all solvents except DMSO in which complexes (1), (2) and (4) are soluble while (3) is not.
3.1. IR Spectra.
The IR spectra of the complexes were compared with those of the free ligands (L1-L4, ox) in
order to monitor the change in the vibration frequency of the coordination sites, which may be
involved in chelation. The characteristic peaks of all ligands and its complexes are listed in Table
2. The IR spectra of the free ligands showed a strong band at 1600-1640 cm-1 assignable to
ν(C=N) of the azomethine and a weak band at 1261-1276 cm-1 assignable to ν(C-N) [13]. The
IR spectra of complexes (1-4) showed strong bands at 1627-1641 cm-1 to ν(C=N) of the
azomethine and new bands at 1699-1712 cm-1 due to ν(C=O). Furthermore, in all cases, the
infrared spectra showed the typical patterns of dicarboxylate ligands bound in a bidentate fashion
to a metal center with shoulder of ν(COO-) in the range 1310-1400 cm-1 [14, 15]. Figure 1 shows
the calculated and experimental IR spectra of the complex 1 as representative example. The
calculated IR data are in good agreement with the experimental ones (Table 2). The relative error
is in the range (0.1-6.2%). The small deviation in the calculated vibrations may attributed to the
fact that the computed wavenumbers are corresponded to the isolated molecular state, whereas
the observed wavenumbers correspond to the solid state spectra;
3.2. Mass spectral analysis.
The mass spectral data of the complexes showing the major mass fragmentation peaks are
listed in Table 3. Mass spectrum of complex (1) (molecular weight equals 418) gave a parent
peak at m/z = 420 (M+2), a peak at m/z =402 assigned for (M+2-H2O) , a peak at m/z =334
assigned for (M+2-C2O4), a peak at m/z =215 assigned for (M+-L1), a peak at m/z =205
assigned for (L1). The mass spectrum of complex (2) (molecular weight equals 400.68), gave a
parent peak at m/z = 400 (M+), a peak at m/z =382 assigned for (M+-H2O) , a peak at m/z =307
4

assigned for (M+-C2O4)a peak at m/z =213 assigned for [M+-L2)] , and a peak at m/z =184
assigned for (L2). Mass spectrum of complex (3) (molecular weight equals 407), gave a
parent peak at m/z=408 (M+2), a peak at m/z=339 assigned for (M+2-4H2O), a peak at
m/z=326 assigned for (M+2-C2O4), a peak at m/z=264 assigned for (M+2-L3), and a peak at
m/z=139 assigned for (L3). The mass spectrum of complex (4) (molecular weight equals 361),
gave a parent peak at m/z = 363 (M+2), a peak at m/z =315 assigned for (M+2-5/2H2O), a peak
at m/z =273 assigned for [M+2- C2O4] , a peak at m/z =238 assigned for [M+2-L4] and a
peak at m/z =121 assigned for (L4), indicate that all complexes are separated as monomers
associated with at least one uncoordinated water molecule. It is interesting also to highlight the
contribution of the different isotopes of palladium to the molecular mass of complexes. The mass
spectra of the complexes showed the stable palladium isotopes peaks at 104, 105,106, 108 and
110 [16].
3.3. Electronic Spectra.
The electronic spectral data of the DMSO solutions of the free ligands, recorded in the 200 –
1100 nm are given in Table 1. The complexes (1, 2, 4) exhibited absorption bands in the range
300–340 nm and 340–400 assigned to the π→π* and n→π* transitions; respectively, of benzene
ring and the azomethine group respectively [11]. The spectra showed also shoulders at 400-420
nm which may be assigned to MLCT (metal to ligand charge transfer) within a square planar
moieties [17, 18]. It is worthy to mention that complex (3) is insoluble. The values of the
experimental absorption peaks were compared with the computed excitation energies (eV). The
computed main excitation, electronic transition configurations and oscillator strength of Pd
complexes are given in Table 4. The calculated electronic transitions for the complexes (1, 2, 4)
were of good agreement with the experimental values; Table 4 and Fig. 2. The assignment of the
calculated orbital excitations to the experimental bands was based on the relative energy of the
HOMO and LUMO orbitals involved in the electronic transitions which provides a better
estimation of excitation energies and oscillators strengths, especially for transitions with charge-
transfer character.
3.4. Magnetic Susceptibility Measurements.
5

Measurements of the magnetic susceptibility of palladium complexes (1-4) in the solid state
showed that they are diamagnetic. The diamagnetism of the complexes can be explained on the
fact that Pd(II) (with d8 configuration) in a square planner geometry may have the electronic
2
distribution eg4 a1g b2g2 with all electrons paired [19].
3.5. Thermal Analysis.
The thermal studies of the complexes were carried out using the thermogravimetric analysis
(TGA) and the derivative thermogravimetric analysis (DrTGA) to investigate the thermal
stability of the complexes and the type and number of water associated with the complexes. The
complexes decomposed in three to five steps and ended with Pd metal as the metallic residue,
Table 4. The decomposition of the complexes is consistent with the proposed formulae.
Calculation of thermodynamic parameters using Integral method using the Coats–Redfern and
Approximation method using Horowitz–Metzger [20,21]. The temperature ranges of
decompositions along with the corresponding mass loss of species are given in Tables 5. A
typical TGA and DrTGA plots for complexes (1) and (3) as representative example is shown in
Fig. 3. All thermodynamic parameters of the four complexes are given in Table 6. The
complexes showed high thermal stability which is reflected from the relatively higher overall
activation energies (441-688 kJmol-1). The entropy change, ∆S*, of the formation of the
activated complexes from the starting reactants varied from positive to negative values within the
decomposition steps. This variation in the sign of the entropy change from a decomposition step
to another one consistent with the variation in the degree of structural ‘complexity’
(arrangement, ‘organization’) of the activated complex as the starting reactants are different
[22-24].
3.6. Computational Studies
In the absence of a crystal structure and to obtain the molecular conformation of the complexes
(1-4), energy minimization studies were carried out using GAUSSIAN 09W software program (
institutional copy of the Faculty of Science, Cairo University). Molecular geometries of the
singlet ground state of complexes were fully optimized in the gas phase at the B3LYP level of
theory. The SDD basis set for all atoms was employed in the calculations [25, 26]. The
optimized geometries of the complexes are given in Scheme 2. Selected bond lengths and angles
6

are given in Table 7. A comparison of the calculated Pd-O and Pd-N bond lengths with those of
reported palladium(II) oxalato complexes involving bidentate N-donor ligands, whose average
values were found to be for Pd-O; (1.999-2.105 Å) range is consistent with the range of values
reported for five and six-membered chelates containing Pd-O bonds [27-29], and for Pd–N;
(2.03-2.09 Å) range [30-32], indicated that the mentioned parameters correlate well in the case of
the Pd-O bonds. The angles around central metal ion Pd(ΙΙ) with surrounded four atoms of two
ligands vary from 82.70° to 96.64°, these values deviated from those expected square planar
indicating that structures are distorted square planar [33]. The O-Pd-O bond angles whose
average values were found to be (82.70°-83.87°) within the chelating ring is comparable with the
other palladium(II) carboxylato complex, e.g. 82° in K2[Pd(C2O4)2].4H2O [34] and 81.1° in
oxalate cis-bis(triethylphosphine)palladium(II) [35]. The N-Pd-N bond angles whose average
values were found to (88.21 °-95.02 °) are deviating from the ideal value (90o). This may be
attributed to bulky nature of the ligand. The slight deviations in both bond lengths and bond
angles may be attributed to the nature of complexes (1-4) as heteroleptic formed by two
different ligand with two different groups of donor atoms (N2 and O2) while the reported
complexes used in comparison are homoleptic.
The calculation of atomic charges is a very important parameter that is used in the
application of quantum mechanical calculation to describe the electronic characteristics of
molecular system [29]. The charge densities were found on nitrogen atoms of all ligands in the
range (-0.060)-(-0.151); Scheme 1. This indicates that the suitability of the nitrogen atoms (L1-
L4) for coordination to the positively charged palladium. The positive charge on sulfur atom in
L1 (0.249) and in complex (1) (0.376) omits the possibility of sulfur as binding site. It has been
found that in the four complexes, the charges on the coordinated nitrogen atoms are increased to
the range (-0.273)-(-0.338) which indicates the back donation from the metal sites in a MLCT
mode to the π* orbitals of the ligand. The distribution of the atomic charges is also important in
the determination of the direction of the dipole moment vector in the complexes which depends
on the centers of negative and positive charges.
The dipole moment and the electronic energies of the ligands as well as complexes are
given in Table 8 . The dipole moment of the complexes (13.97-18.77 Debye) indicating that the
complexes are more polarized than the ligands (1.93-4.96 Debye). The electronic energies (a.u.)
of the complexes (- 902. 09 to -1455.04) and that of the ligands (-397.04- 949.99) indicate their
stability. The calculated energies of the highest occupied molecular orbital (HOMO) and the
7

lowest unoccupied molecular orbital (LUMO) of the ligands (L1-L4) and their palladium (II)
complexes (1-4) are listed in Table 8. The hardness (η) is defined as (η= (I-A)/2) where I is the
ionization energy and A is the electron affinity. On the other hand, the (I-A) equals the gap
between the HOMO and LUMO. Hence, the hardness of the present ligands and complexes can
be calculated as ((η= (EHOMO-ELUMO)/2). Hard molecules have high the HOMO-LUMO gap, and
soft molecules have smaller HOMO-LUMO gap [36, 37]. The values η and ∆E (HOMO-LUMO)
are given in Table 8. It is obvious from the table that the complexes are soft (η= (0.046-0.054),
where for ligands (η=0.053-0.155). It is also that the electronic transition within the complexes is
easy as indicated from the ∆E of complexes (0.092-0.108), where for ligands (0.106-0.310).
The frontier molecular orbitals (FMOs) can offer reasonable qualitative indication of the
excitation properties and the electron transport. The energies of the HOMO and LUMO orbitals
of the ligands and their complexes were negative which indicates that the ligands and the
complexes are stable compounds, the values of HOMO and LUMO orbitals and their energy gap
reflect also the chemical activity of the molecule [38]. The values of the energy separation
between the HOMO and LUMO for complexes (1-4) are in agreement with the values for stable
transition metal complexes [28, 39]. Figure 4 shows the isodensity surface plots of HOMO and
LUMO for L1 and complex (1); as example, the electron density of HOMO and LUMO in L1 are
mainly localized on the benzthoizole part of the ligand and the electronic transition could be
described as a mixed π→π* and n→π* transition. The energies of HOMO sates (H to H-4), the
% contribution and the main characters of Pd, oxalate (Ox) and formamidine ligand (L1-L4) in
complexes (1-4) are calculated and given in Table 8. The % contribution of Oxalate (Ox) to the
different HOMO states in Complex (1) varies from 34% to 95% and the main character is Ox
(π). The % Contribution of Oxalate to different LUMO states (L to L+4) is much lower (0%-
71%). The % contribution of L1 (complex (1)) in the different HOMO are low and varies from
1% to 18% through L1(π) as the main character while the % contribution to LUMO states are
much higher and varies from 29% to 90% through L1(π*) as the main character. It is obvious
from Table 8 that Ox has higher contribution to the different HOMO states than L1 which has on
contrary higher contribution to the LUMO states. Therefore the π−π* electronic transition within
the complexes may be arose from the transition from HOMO states of high Ox(p) character to
LUMO states of L1(π*) character. The % contribution of Pd to the HOMO states varies from 5%
8

to 33% by Pd(t2g) as the main character except H-3 which 61% contribution through Pd(eg)
which gives rise to the possibility of MLCT from Pd(eg) to either Ox(π*) and/or L1(π*). On the
other hand, the % contribution of Pd to the LUMO states varies from 1% to 7% except L+1 in
which the contribution of Pd is 48% which points to the possibility of LMCT from Ox(π*)
and/or L1(π*) to Pd(eg) [17]. The % contribution and the main characters of Pd , oxalate (Ox)
and formamidine ligand (L2-L4) to the different HOMO and LUMO states in complexes (2-4)
showed more or less the same trend as complex(1).
The molecular electrostatic potential (MEP) is used for predicting sites and relative
reactivity towards electrophilic and nucleophilic attack. The negative (red) regions of the MEP
are related to electrophilic reactivity and the positive (blue) regions of nucleophilic reactivity.
For the free ligands L1-L4 (Fig.5) the negative (red) regions are mainly localized over the
nitrogen atoms of the ligands and hence it would be predicted that the nitrogen atoms will be the
most reactive sites for electrophilic attack. In complexes, the negative (red) regions are mainly
localized over the carbonyl- oxygen atoms of the coordinated oxalate ligand (Fig.6).
3.7. In vitro cytotoxic
In vitro cytotoxic activities of the formamidine ligands (L1-L4) and their mixed ligand
complexes (1, 2, and 4) were tested against the, human breast adenocarcinoma (MCF-7), liver
carcinoma cell line (HEPG-2), and colon carcinoma cell line (HTC-116). For the evaluation of
the IC50, the cell lines (100 µL each) were incubated for 48 h with various concentrations of the
complexes, ranging from 0 to 100 µg/mL (100 µL volume) using doxorubicin as reference. As
the total volume of the well was 200 µL, the concentration was taken as the number of
micromoles (µM) were calculated from the micrograms of the complex. The complexes showed
higher cytotoxicity against MCF-7 and HCT-116 compared with HEPG-2 as inferred from their
%inhibition (Table 9). The IC50 values (µM) of the three tested complexes were compared with
the doxorubicin as reference; Table 10. In general the ligands as well as their Pd(II) complexes
have good IC50 values and the ligand L1-L4 has relatively lower IC50 values than those of the
complexes which may be attributed the bulkiness and limited solubility of complexes. L4 being
the simplest ligand has the lower IC50 with high potential to be applied as antitumor reagent.
Conclusion
9

Based on the spectroscopic, magnetic, thermal and theoretical data; the complexes (1-4) have
distorted square planer geometry in which the formamidine ligands act as bidentate N2 donors
and oxalate as bidentate O2 ligand. The distortion is indicated from the deviation of the O-Pd-O
and N-Pd-N angles from 90o. The distortion may be attributed to the heteroleptic nature of the
complexes with two different coordinated ligands. The energies of the HOMO and LUMO
orbitals of the ligands and their complexes were negative which indicates that the ligands and the
complexes are stable compounds. The complexes are thermally stable as shown from their the
relatively higher overall activation energies (441-688 kJmol-1). The ligands and complexes are
proved to have good cytotoxicity against some tumor cell lines which open the field for further
application as antitumor compounds.
10

References
[1]. C. Orvig, M. Abrams, Chem. Rev. 99 (1999) 2201- 2204.
[2]. I. Warad ,A. F. Eftaiha, M. A. Al-Nuri 1, A. I. Husein 1, M. Assal, A. Abu-Obaid, N. Al-
Zaqri, T. B. Hadda, B. Hammouti. J. Mater. Environ. Sci. 4 (4) (2013) 542-557.
[3]. B. Rosenberg, L. Van Camp and T. Krigas, Nature 205 (1965) 698–699.
[4]. L.R. Kelland, and N.P.Farrell, Platinum-Based Drugs in Cancer Therapy, Humana:Totowa,
2000.
[5] Z. Trávníček, I. Popa, M. Čajan, R. Zbořil, V. Kryštof and J. Mikulík, J. Inorg. Biochem.
104 (2010) 405–417.
[6]. Y. Kidani, K.Inagaki, M.Iigo, A.Hoshi and K.Kuretani, J.Med. Chem. 21 (1978) 1315–
1318.
[7]. M. Gielen and E.R.T. Tiekink, Metallotherapeutic Drugs and Metal-based Diagnostic
Agents, Willey: London, 2005.
[8]. J.L. Butour, S.Wimmer, F.Wimmer and P. Castan, Chem. Biol. Interact.104 (1997)165 178.
[9]. A. Garoufis, S.K. Hadjikakou, N. Hadjiliadis, Coord. Chem. Rev. 253(2009), 1384–1397.
[10]. A. M. Sayed, Synthesis, characterization and antitumor activity of palladium
complexes with some new formamidine ligands, M.Sc. Thesis, faculty of science, Cairo
university, 2013.
[11]. [11]. S. R. Majeed, analytical and inorganic studies of new antitumor palladium (II),
ruthenium (II) and platinum (IV) complexes, PhD. Thesis, faculty of science, Cairo
university, 2013.
[12]. P. Štarha, Z.K. Trávnícek , I. Popa, J. Inorg. Biochem. 103 (2009) 978–988.
[13]. N. Nakamoto, Infrared and Raman Spectra of Inorganic and Coordination Compounds,
Wiley, New York, 1986.
[14]. S.R. Ali Khan, I.Guzman-Jimenez, K.H. Whitmire, A.R. Khokhar, Polyhedron 19 (2000)
983.
[15]. J. D. Hoeschel, Oak Ridge, Tenn.; Alan R. Amundsen, Somerville, NJ. : Engelhard
Minerals & Chemicals Corp., Iselin, NJ. 106,439, 26, 1979
[16]. R. P. Bush, Recovery Of Platinum Group Metals From High Level Radioactive Waste
Possibilities Of Separation And Use Re-Evaluated, Platinum Metals Rev., 1991, 35, (4),
202-208
[17]. A. B. P. Lever “Inorganic electronic spectroscopy”, Elsevier, Amsterdam, 2nd ed, (1984)
544.
[18]. G. C. Pellacani, W. D. D. Malavasi, J. Inorg. Nucl. Chem. 37 (197 5)477-481.
11

[19]. Housecroft C. E., Sharpe A. G.. Inorganic Chemistry, 2nd ed, England, Pearson,2005, p.
579.
[20]. H. H. Horowitz, G. Metzger, Anal. Chem., 35 (1963) 1464-1468.
[21]. A. W. Coats, J. P. Redfern, Nature, 201 (1964) 68-69.
[22]. Soliman A. A., Samir M. E. and Omyma A. M. Ali, Thermal study of chromium and
molybdenum complexes with some nitrogen and nitrogen-oxygen donors ligands, J.
Thermal. Anal. &Cal., 2006;83(2):385-92.
[23]. A. A. Soliman, M. M. Khattab, R. M. Ramadan, Transit. Met. Chem., 32, 331(2007).
[24]. S.A. Ali, A.A. Soliman, M.M. Aboli, R.M. Ramadan, J. Coord. Chem. 55 (2002) 1161–
1170.
[25]. T. H. Dunning Jr., P. J. Hay, Modern Theoretical Chemistry, 3rd Ed., Vol. 3, Plenum,
New York, 1976, pp. 1–28.
[26]. D. Andrae, U. Häußermann, M. Dolg, H. Stoll, H. Preuß, Theor. Chem. Acc. 77 (1990) 123
[27]. Marwa G. Elghalban, Ahmed M. El Defarwy, Reem K. Shah, Mohamed A. Morsi,
Int. J. Electrochem. Sci., 9 (2014) 2379 – 2396.
[28]. Xavier Assfeld, J.L. Rivail, Chem. Phys. Lett. 263 (1996) 100–106.
[29]. A. M. Mansour, Inorganica Chimica Acta 394 (2013) 436–445.
[30]. Sadeek A. Sadeek, Walaa H. El-Shwiniy, Wael A. Zordok1 and Akram M. El-Didamony,
The Journal of the Argentine Chemical Society Vol. 97 N° 2, 128-148 (2009).
[31]. A. K. Singh, J. Sooriyakumar, S. Husebye, K. W. Tornroos, J. Organomet. Chem. 612
(2000) 46.
[32]. D. R. Billodeaux, F. R. Fronczek, A. Yoneda, G. R. Newkome, Acta Crystallogr. C C54
(1998) 1439.
[33] M. Kaplun, M. Sandström, D. Boström, A. Shchukarev, P. Peresson, Inorg. Chim. Acta
358 (2005) 527.
[34]. D. J. Robinson, C. H. L. Kennard, J. Chem. Soc. A (1970) 1008.
[35]. X.-M. Luo, X.-H. Chen, S. Shanmuga Sundara Raj, H.-K. Fun, L.-G. Zhu, Acta
Crystallogr. C 55 (1999) 1220.
[36]. K. Krogmann, Z. Anorg. Allg. Chem., 346, 188 (1966).
[37]. A.L. Rheingold, S. Yollies, R.M. Roat, W.C. Fultz and S.A. Kretchmar, Acta Crystallogr.
Sect. C (Cr. Str. Comm), 43, 167(1987).
[38]. J.G. Małecki , P. Zwolinski, Polyhedron 39 (2012) 85–90.
[39]. Pavel Štarha, Igor Popa and Zden k Trávní ek, Molecules 19, 2014, 3832-3847.
doi:10.3390/molecules19033832.
12

Scheme 1: Optimized molecular structure of formamidine ligands, Carbon (grey), Nitrogen
(blue), Sulfur (yellow), Hydrogen atoms are omitted for simplicity.
13

Scheme 2. Optimized molecular structure and atomic charges of prepared Pd(II) oxalate
complexes; by (Gaussian 09W software). Carbon (gray), Nitrogen (blue), Sulfur (yellow),
Oxygen (red), and Palladium (green). Hydrogen atoms are omitted for simplicity.
14

(a)
Wave number, cm-1
(b)
Fig. 1. IR spectra of Complex 1 experimental (a) and calculated (b).
15

Fig. 2. The UV-visible spectra of complex 1 experimental (blue), and calculated (red).
Fig. 3. The thermogram of complex (3)
16

Fig. 4. HOMO and LUMO orbitals and energy gap of L1 and Complex 1, Red regions (negative)
and green regions (positive).
17

Fig. 5. Total Density of Electron Distributions of formamidine ligands. Hydrogen atoms are
omitted for simplicity.
18

Fig. 6. Total Density of Electron Distributions of Pd(II) complexes. Hydrogen atoms are omitted
for simplicity.
19

Table 1
The analytical, physical and spectroscopic data of the ligands and Pd(II) complexe
Molar
mass
Solubility
UV-Vis absorption
peaks (nm)
Complexes
color
m.p
220
assignment
π-π*
n-π*
310-320
330-345
415
[Pd(L1)ox].H2O
Pale
yellow
417.73
DMSO
DMSO
MLCT
310-325
330-350
420
π-π*
n-π*
[Pd(L2)ox].H2O
[Pd(L3)ox].4H2O
400.68
405.66
yellow
245
226
MLCT
orange Insoluble
Insoluble
π-π*
n-π*
MLCT
[Pd(L4)ox].
5/2H2O
320-340
380-395
425
DMSO
yellow
360.62
180
20

Table 2
Most characteristic calculated and observed vibrational frequencies cm-1 for Pd(II) complexes
Compound
L1
Obs.
1618
1276
1632
1274
1634
1261
1631
1294
3441
1635
1272
1702
757
Calc.
1613
Relative error
-0.30
Assignment
υ(C=N) imin
υ(C-N)
1297
1607
1291
1730
1245
1642
1273
-
1.60
L2
-1.50
υ(C=N) imin
υ(C-N)
1.20
L3
L4
5,80
υ(C=N) imin
υ(C-N)
-1.20
0.60
υ(C=N) imin
υ(C-N)
-1.60
[Pd(L1)ox].H2O
υ(O-H) Hydrated
υ(C=N) imin
υ(C-N)
1678
1262
1701
765
2.60
0.70
-0.05
1.00
υ(C=O) oxalate
υ(M-O)
462
433
-6.20
υ(M-N)
[Pd(L2)ox].H2O
3446
1641
1283
1699
752
-
υ(O-H) Hydrated
υ(C=N) imin
υ(C-N)
1710
1265
1697
767
4.20
-1.40
-0.10
1.19
υ(C=O) oxalate
υ(M-O)
452
442
-2.20
υ(M-N)
[Pd(L3)ox].4H2O
3426
1636
1381
-
υ(O-H) Hydrated
υ(C=N) imin
υ(C-N)
1706
1391
4.20
0.70
21

1704
722
1698
769
470
-
-0.30
6.10
4.40
υ(C=O) oxalate
υ(M-O)
450
υ(M-N)
[Pd(L4)ox].5/2H2O
3415
1627
1298
1712
799
υ(O-H) Hydrated
υ(C=N) imin
υ(C-N)
1722
1304
1701
772
670
5.50
0.40
-0.60
-3.40
-3.10
υ(C=O) oxalate
υ(M-O)
691
υ(M-N)
Relative error = {(calc –exp)/exp} x 100
Table 3
Important mass data of Pd(II) complexes
Molar
complex
Important mass fragmentations (m/z) values
mass
420 (M+2), 400 (M-H2O), 330 (M-C2O4), 213 (M-L1), 205
(L1), 121 PdO, Pd isotopes 103, 105, 107,108,109
[Pd(L1)ox].H2O(1)
[Pd(L2)ox].H2O(2)
417.73
400 (M), 382 (M-H2O), 330 (M-(CO2, CO)), 213 (M-L2),
191 (L2), 121 (PdO), Pd isotopes 107, 109, 110
400.68
405.66
408 (M+2), 387 (M-H2O), 351 (M-3H2O), 333 (M-4H2O),
317 (M-C2O4), 265 (M-L3), 138 (L3), 122 (PdO), Pd
isotopes 110, 111
[Pd(L3)ox].4H2O(3)
[Pd(L4)ox].5/2H2O(4) 360.62
361 (M), 343 (M-H2O), 316 (M-5/2H2O), 272 (M-C2O4),
22

238 (M-L4), 121 (L4), Pd isotopes 105, 107, 108, 110
Table 4
Computed excitation energies (a.u), percent contribution from Pd, ox, ligands, and main
character of some frontier orbitals of the studied complexes obtained from the calculations
Complex
Orb.a Typeb
Energy (a.u)
ox
Ligand
Pd
Main character
[Pd(L1)ox)].H2O
(80)
H
O
O
O
O
-0.23
-0.26
-0.26
-0.27
94%
57%
57%
34%
1%
5%
ox(π)
(79) H-1
(78) H-2
(77) H-3
14%
10%
4%
29%
33%
61%
ox(π), Pd(t2g)
ox(π), Pd(t2g)
ox(π), Pd(eg)
23

(76) H-4
(81)
O
V
V
V
V
V
-0.27
-0.13
-0.09
-0.04
-0.04
-0.03
68%
4%
18%
90%
26%
86%
83%
29%
14%
7%
L1(π), ox(π)
L1(π*)
L
(82) L+1
(83) L+2
(84) L+3
(85) L+4
26%
10%
16%
71%
48%
4%
Pd(eg), L1(π*)
L1(π*)
1%
ox(π*), L1(π*)
L1(π*)
1%
[Pd(L2)ox)].H2O
(81)
H
O
O
O
O
O
V
V
V
V
V
-0.22
-0.24
-0.25
-0.26
-0.26
-0.11
-0.07
-0.03
-0.03
-0.02
94%
51%
59%
35%
77%
0%
1%
5%
ox(π)
(80) H-1
(79) H-2
(78) H-3
(77) H-4
18%
7%
31%
34%
62%
16%
2%
ox(π), Pd(t2g),
ox(π), Pd(t2g)
ox(π), Pd(eg)
ox(π), Pd(eg)
L2(π*)
3%
7%
(82)
L
98%
18%
70%
30%
100%
(83) L+1
(84) L+2
(85) L+3
(86) L+4
27%
27%
69%
0%
55%
3%
Pd(eg), ox(π*)
L2(π*), ox(π*)
ox(π*), L2(π*)
L2(π)
1%
0%
[Pd(L4)ox)].5/2H2O
(63)
H
O
O
O
O
O
V
V
V
V
-0.23
-0.25
-0.26
-0.27
-0.28
-0.12
-0.09
-0.07
-0.04
95%
70%
63%
82%
36%
2%
1%
4%
ox(π)
(62) H-1
(61) H-2
(60) H-3
(59) H-4
2%
28%
34%
12%
62%
5%
ox(π), Pd(t2g)
ox(π), Pd(t2g)
ox(π), Pd(eg)
Pd(eg), ox(π)
L4(π*)
3%
6%
2%
(64)
L
93%
65%
57%
37%
(65) L+1
(66) L+2
(67) L+3
12%
14%
55%
22%
29%
8%
L4(π*), Pd(t2g), Pd(eg)
Pd(eg), Pd(t2g), L4(π*)
L4(π*), ox(π*)
24

(68) L+4
V
-0.03
42%
53%
5%
L4(π*), L4(π*)
a H and L represent the HOMO and LUMO, respectively. H+n indicates the nth molecular orbital above the HOMO
and L-n indicates the nth molecular orbital below the LUMO.
b V, and O represent unoccupied (virtual), and doubly occupied molecular orbitals, respectively.
Table 5
Thermogravimetric analytical data for decomposition of palladium(II) complexes
Assignment of
the removed
species
[H2O,L1,CO]
CO2
½ O2
H2O
2CO
[L2,O]
½ O2
2H2O
Metallic
residue found
(cal. %)
Molar
mass
TG range DTA max Mass loss found
Complex
(K)
(K)
(cal. %)
374-530
542-584
611-1085
312-448
448-543
543-669
669-1046
343-497
479-558
558-677
677-800
1006-1036
501
60.56; (59.76)
10.13; (10.47)
4.09 ; (3.81)
4.39; (4.50)
14.31; (14.0)
50.53; (50.07)
4.64; (4.00)
8.64; (8.82)
19.77; (19.60)
7.01; (6.86)
Pd 25.22,
( 25.47)
[Pd(L1)ox].H2O 417.73
[Pd(L2)ox].H2O 400.68
565
1042
319
499
630
1030
479
540
671
Pd 26.13,
( 26.55)
[2H2O,CO2]
CO
L3
½ O2
Pd 26.97,
(26.23)
[Pd(L3)ox].4H2O 405.66
783
1024
33.70; (34.26)
3.91; (3.92)
315-408
408-460
460-567
567-1026
406
439
563
995
4.66; (4.95)
56.39; (56.47)
4.38; (4.40)
4.27; (4.40)
H2O
[Pd(L4)ox].
360.62
[3/2H2O,L4,2CO]
½ O2
½ O2
Pd 30.30,
(29.51)
5/2H2O
25

Table 6
Thermodynamic data of the thermal decompositions of Pd(II) complexes
Decomposition ∆E/ KJ
∆S/ J K-1
mol-1
∆H/ KJ
mol-1
∆G/ KJ
mol-1
Complex
R2
temperature (K)
mol-1
374-530
542 -584
611-1085
217
203
21
0.86
0.98
0.86
76
102
-271
-93
211
198
12
162
140
295
597
162
126
157
187
732
162
133
172
200
667
162
108
149
304
723
[Pd(L1)ox].H2O
441
421
211
102
141
8
312-448
448-543
543-669
669-1046
76
217
106
146
17
0.89
0.98
0.95
0.85
-48
[Pd(L2)ox].H2O
-26
-270
-268
76
486
217
200
92
462
211
196
86
343-497
479-558
558 -677
677-800
1006-1036
0.88
0.98
0.96
0.98
0.99
116
-127
-34
[Pd(L3)ox].4H2O
179
688
217
232
32
172
665
211
229
27
31
315-408
408-460
460-567
567-1026
76
0.91
0.98
0.87
0.85
301
-213
-294
-130
[Pd(L4)ox].5/2H2O
19
11
500
478
26

Table 7
Equilibrium geometric parameters bond lengths (Å), bond angles (°), dihedral angles (°), total
energy, and total dipole moment of optimized Pd(II) complexes by using DFT/B3LYP/SDD set
basis.
Bond Lengths o A
[Pd(L1)ox)].H2O
Bond Angles o
Pd(7)-O(3)
Pd(7)-O(4)
Pd(7)-N(14)
Pd(7)-N(19)
2.01
1.99
2.09
2.17
O(3)-Pd(7)O(4)
82.70
96.64
91.51
89.11
179.18
173.95
O(3)-Pd(7)-N(14)
O(4)-Pd(7)-N(19)
N(14)-Pd(7)-N(19)
O(4)-Pd(7)-N(14)
O(3)-Pd(7)-N(19)
[Pd(L2)ox].H2O
Pd(13)-O(17)
Pd(13)-O(16)
Pd(13)-N(9)
2.00
2.01
2.04
2.14
O(16)Pd(13)-O(17)
N(9)Pd(13)-O(16)
N(12)Pd(13)-O(17)
N(9)Pd(13)-N(12)
N(9)-Pd(13)-O(17)
N(12)-Pd(13)-O(16)
83.18
95.62
88.21
92.97
178.80
171.40
Pd(13)-N(12)
[Pd(L3)ox].4H2O
Pd(1)-O(3)
Pd(1)-O(2)
Pd(1)- N(8)
Pd(1)- N(9)
1.99
1.99
2.02
2.15
O(2)-Pd(1)-O(2)
O(2)-Pd(1)-N(8)
N(9)-Pd(1)-N(8)
O(3)-Pd(1)-N(9)
N(8)-Pd(1)-O(3)
N(9)-Pd(1)-O(2)
83.87
96.03
91.90
88.27
179.82
172.06
[Pd(L4)ox].5/2H2O
Pd(1)-O(2)
Pd(1)-O(3)
Pd(1)- N(8)
Pd(1)- N(14)
2.00
1.99
2.01
2.11
O(2)-Pd(1)-O(3)
O(2)-Pd(1)-N(8)
N(8)-Pd(1)-N(14)
O(3)-Pd(1)-N(14)
O(3)-Pd(1)-N(8)
84.48
93.98
90.63
90.86
178.41
27

Bond Lengths o A
Bond Angles o
O(2)-Pd(1)-N(14)
174.62
28

Table 8
Calculated physical parameters of ligands and complexes.
Compound
ELUMO
EHOMO
η
∆E
D.M
Total
energy
a.u
Debye
L1
4.90
3.66
4.96
1.93
-949.99
-607.19
-469.57
-397.04
-0.11
-0.03
-0.10
-0.03
-0.13
-0.42
-0.20
-0.21
-0.21
-0.23
0.16
0.31
L2
0.08
0.05
0.09
0.05
0.17
0.11
0.19
0.10
L3
L4
13.97 -1455.04
16.06 -1112.25
18.77 -974.62
15.76 -902.09
[Pd(L1)ox].H2O
-0.12
-0.13
-0.12
-0.23
-0.22
-0.23
0.05
0.05
0.05
0.11
0.09
0.11
[Pd(L2)ox].H2O
[Pd(L3)ox].4H2O
[Pd(L4)ox].5/2H2O
29