Structural and in vitro cytotoxicity studies on 1H-benzimidazol-2-ylmethyl- N-phenyl amine and its Pd(II) and Pt(II) complexes

Article abstract of DOI:10.1016/j.saa.2011.06.046

[MLCl₂]·zH₂O (L = (1H-benzimidazol-2-ylmethyl) -N-phenyl amine; M = Pd, z = 0; M = Pt, z = 1) and [PdL(OH₂) ₂]·2X·zH₂O (X = Br, I, NO₃, z = 0; X = SCN, z = 1) complexes were synthesized as potential anticancer compounds and characterized by elemental analysis, spectral and thermal methods. FT-IR and ¹H NMR studies revealed that the benzimidazole L is coordinated to the metal ions via the pyridine-type nitrogen (N_py) of the benzimidazole ring and secondary amino group (NH_sec). Quantum mechanical calculations of energies, geometries, vibrational wavenumbers, and ¹H NMR of the benzimidazole L and its complexes were carried out by density functional theory using B3LYP functional combined with 6-31G(d) and LANL2DZ basis sets. Natural bond orbitals (NBOs) and frontier molecular orbitals were performed at B3LYP/LANL2DZ level of theory. The synthesized ligand, in comparison to its metal complexes was screened for its antibacterial activity. The benzimidazole L is more toxic against the bacterium Staphylococcus aureus (MIC = 58 μg/mL) than the standard tetracycline (MIC = 82 μg/mL). The complexes showed cytotoxicity against breast cancer, Colon Carcinoma, and human heptacellular Carcinoma cells. The platinum complex (6) displays cytotoxicity (IC₅₀ = 12.4 μM) against breast cancer compared with that reported for cis-platin 9.91 μM.

Full text of DOI:10.1016/j.saa.2011.06.046

Spectrochimica Acta Part A 81 (2011) 529–543
Contents lists available at ScienceDirect
Spectrochimica Acta Part A: Molecular and
Biomolecular Spectroscopy
journal homepage: www.elsevier.com/locate/saa
Structural and in vitro cytotoxicity studies on
1H-benzimidazol-2-ylmethyl-N-phenyl amine and its Pd(II) and Pt(II) complexes
Nour T. Abdel Ghani, Ahmed M. Mansour∗
Chemistry Department, Faculty of Science, Cairo University, Gamaa Street, Giza 12613, Egypt
a r t i c l e i n f o
a b s t r a c t
Article history:
[MLCl2]·zH2O (L = (1H-benzimidazol-2-ylmethyl)-N-phenyl amine; M = Pd, z = 0; M = Pt, z = 1) and
[PdL(OH2)2]·2X·zH2O (X = Br, I, NO3, z = 0; X = SCN, z = 1) complexes were synthesized as potential anti-
Received 28 April 2011
Received in revised form 16 June 2011
Accepted 19 June 2011
cancer compounds and characterized by elemental analysis, spectral and thermal methods. FT-IR and 1
H
NMR studies revealed that the benzimidazole L is coordinated to the metal ions via the pyridine-type
nitrogen (Npy) of the benzimidazole ring and secondary amino group (NHsec). Quantum mechanical cal-
culations of energies, geometries, vibrational wavenumbers, and 1H NMR of the benzimidazole L and its
complexes were carried out by density functional theory using B3LYP functional combined with 6-31G(d)
and LANL2DZ basis sets. Natural bond orbitals (NBOs) and frontier molecular orbitals were performed
at B3LYP/LANL2DZ level of theory. The synthesized ligand, in comparison to its metal complexes was
screened for its antibacterial activity. The benzimidazole L is more toxic against the bacterium Staphylo-
coccus aureus (MIC = 58 ␮g/mL) than the standard tetracycline (MIC = 82 ␮g/mL). The complexes showed
cytotoxicity against breast cancer, Colon Carcinoma, and human heptacellular Carcinoma cells. The platinum
complex (6) displays cytotoxicity (IC50 = 12.4 ␮M) against breast cancer compared with that reported for
cis-platin 9.91 ␮M.
Keywords:
Benzimidazole
Biological studies
DFT
NBO
Thermal
© 2011 Elsevier B.V. All rights reserved.
1. Introduction
ability of azoles, the chelating ligands incorporating benzimidazole
groups have been extensively studied in the context of modeling
The great success of cis-platin as an antitumor drug has attracted
considerable attention in the search for new anticancer platinum
and other metal complexes with better pharmacological properties
[1]. Among the non-platinum compounds with potential for the
clinical treatment of human malignancies, palladium derivatives
have received considerable interest, because of the structural anal-
ogy between the Pt(II) and Pd(II) complexes. The design of Pd(II)
compounds with anticancer activity represents an exciting task,
since Pd(II) compounds exchange ligands 105 times faster than
analogous Pt(II) compounds [2]. Due to this rapid exchange, Pd(II)
derivatives do not maintain their structural integrity long enough
to reach the pharmacological target. To overcome their high lability,
chelating ligands have been used to afford high thermodynamic sta-
bile and kinetically inert Pd(II) complexes [2]. Recently, interest has
been directed towards developing of cis-platin analogs with hete-
rocyclic amine ligands [3], e.g. benzimidazole. The benzimidazole
scaffold is a useful structural motif for displaying chemical func-
tionality in biologically active molecules. Some of its derivatives
have potent biological activities as antitumor, anti-HIV, and antimi-
crobial agents [4]. At the same time, owing to the coordination
biological systems in recent years [5]. Thus, a considerable num-
ber of metal benzimidazole complexes including most transition
metals were studied as reported by Linert et al. [6].
Our aim was to take into account all the previously mentioned
properties of anticancer drugs and synthesize Pt(II) and Pd(II) com-
plexes of the benzimidazole ligand (L) (Fig. 1) that could be proved
to be potent antitumor agents. The structures of L and its complexes
were elucidated by elemental analysis, FT-IR, 1H NMR, MS, UV/vis,
X-ray powder diffraction, and thermal analysis. Quantum mechan-
ical calculations of energies, geometries, vibrational wavenumbers,
and 1H NMR of the benzimidazole L and its complexes were carried
out by using density functional theory (DFT). Natural bond orbital
(NBO) analysis was performed to provide details about the type of
hybridization and the nature of bonding in the complexes.
2. Experimental
2.1. Synthesis of the ligand (L) and its complexes
All chemicals used in the preparation and investigation of the
present study were of reagent grade (Sigma). The benzimida-
zole L was prepared by condensation of equimolar quantities of
2-chloromethylbenzimidazole [7] with aniline in ethanol in the
presence of small amount of sodium iodide for about 18–24 h. At
∗
Corresponding author. Tel.: +20 2 0122211253; fax: +20 2 35728843.
E-mail address: inorganic am@yahoo.com (A.M. Mansour).
1386-1425/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.saa.2011.06.046

530
N.T. Abdel Ghani, A.M. Mansour / Spectrochimica Acta Part A 81 (2011) 529–543
6.60–8.32 (10H, aromatic protons + NHsec), and ı 4.76, 5.18 (CH2).
UV/vis (DMF): 277, 284, and 367 nm. Molar Cond. (10−3, DMF):
431 ꢁ−1 cm2 mol−1
.
•
•
•
Data for Pd-L (X = SCN) (4) (C16H19N5O3S2Pd). Color: Deep yel-
low. Yield: 86%. Anal. Calc. %C, 37.10; %H, 4.09; %N, 13.52; %Pd,
20.55. Found: %C, 36.89; %H, 4.03; %N, 13.52; %Pd, 20.49. FT-IR:
3417 (ꢀ(NH)sec), 3359 (ꢀ(NH)Bz), 2114 ꢀ(C N), 1672 (ꢀ(C N)),
1455 (ꢀ(NHb)sec), 1310 (ꢀ(C–N)Bz), 1256 (ꢀ(C–N)sec), 866 ␳r(OH2),
and 629 ␳w(OH2). 1H NMR (DMSO): ı 13.46 (NHBz), ı 6.57–8.40
(9H, aromatic protons), ı 6.68 (NHsec), and ı 4.92 and 5.14 (CH2).
UV/vis (DMF): 276, 282, and 348 nm. Molar Cond. (10−3, DMF):
Fig. 1. The optimized structure of benzimidazole ligand (L).
449 ꢁ−1 cm2 mol−1
.
Data for Pd-L (X = NO3) (5) (C14H17N5O8Pd). Color: Grey-Green.
Yield: 80%. Anal. Calc. %C, 34.33; %H, 3.50; %N, 14.30; %Pd, 21.73.
Found: %C, 34.51; %H, 3.60; %N, 14.28; %Pd, 21.70. FT-IR: 3410
(ꢀ(NH)sec), 1657 (ꢀ(C N)), 1489 (ꢀass(NO2)), 1442 (ꢀ(NHb)sec),
1385 (ꢀss(NHb)sec), 1322 (ꢀ(C–N)Bz), 1283 (ꢀ(C–N)sec), 930
(ꢀ(NO)), 838 ␳r(OH2), 624 ␳w(OH2), and 510 ␳t(OH2). 1H NMR
(DMSO): ı 13.21 (NHBz), ı 6.20–8.96 (9H, aromatic protons), ı
6.93 (NHsec) and ı 5.18 and 5.36 (CH2). UV/vis (DMF): 277, 282,
the end of the reaction period, the mixture was neutralized and
the solid was separated by dilution with de-ionized water, and
re-crystallized from benzene/petroleum ether.
The solid Pd(II) (1), and Pt(II) (6) metal chlorides (X = Cl) com-
plexes were prepared by adding a hot ethanolic solution (60 ◦C)
of the ligand L (1 mmol) to a hot aqueous solution (60 ◦C) of the
metal ions (1 mmol; K2PdCl4, or K2PtCl4). The resulting mixtures
were stirred under reflux for about 1–2 h, whereupon the com-
plexes were precipitated. The palladium complexes with other
anions (X = Br, I, SCN and NO3) (2–5) were synthesized by adding
0.664 g KI, 0.408 g NaBr, 0.304 g NH4SCN, or 0.404 g KNO3 to
1 mM K2PdCl4 solution. Then, 1 mM of the hot ethanolic solu-
tion of the ligand L was added. The results of elemental analyses
are in a good agreement with those calculated for the suggested
formula and the melting point is sharp indicating the purity of
the prepared benzimidazole ligand. The molar conductance val-
ues of Pd-L (X = Cl) (1) and Pt-L (6) complexes in DMF indicate
the non-electrolytic nature of these complexes, while the higher
conductance values of the other complexes suggest their ionic
nature.
and 354 nm. Molar Cond. (10−3, DMF): 375 ꢁ−1 cm2 mol−1
.
Data for Pt-L (X = Cl) (6) (C14H13Cl2N3Pt). Color: Brown. Yield:
72%. Anal. Calc. %C, 34.37; %H, 2.68; %Cl, 14.49; %N, 8.59; %Pt,
39.87. Found: %C, 34.51; %H, 2.81; %Cl, 14.58, %N, 8.61; %Pt,
39.94. FT-IR: 3382 (ꢀ(NH)sec), 3245 (ꢀ(NH)Bz), 1625 (ꢀ(C N)),
1453 (ꢀ(NHb)sec), and 1278 (ꢀ(C–N)sec). 1H NMR (DMSO): ı 13.18
(NHBz), ı 6.56–8.48 (9H, aromatic protons), ı 7.01 (NHsec) and ı
4.80 and 4.96 (CH2). UV/vis (DMF): 274, 280, 351, and 422 nm.
Molar Cond. (10−3, DMF): 12.04 ꢁ−1 cm2 mol−1
.
2.2. Instruments
Infrared spectra were recorded as KBr pellets using FTIR-
460 plus, JASCO, in 4000–200 cm−1 region. The 1H NMR spectra
were run at 300 MHz in DMSO-d6 using Varian-Oxford Mercury
VX-300 NMR. The mass spectra were recorded by the aid of
SHIMADZU QP-2010 plus mass spectrometer at 70 eV. The X-ray
powder diffraction patterns were recorded over 2ꢂ = 5–60◦ range
using Philips X-ray diffractometer model PW 1840. Radiation was
•
Data for L (C14H13N3). Color: Orange-Yellow. Yield: 75%. MS:
M+ = 223 (calcd. 223.27). Anal. Calc. %C, 75.25; %H, 5.82; %N, 18.81.
Found: %C, 75.65%; %H, 5.72; %N, 18.73. FT-IR: 3427 (ꢀ(NH)sec),
3052 (ꢀ CHass/An), 2889 (ꢀ CH2ass), 2830 (ꢀ CH2ss), 1687 ꢀ(C N),
1599 (ꢀ CCss/An), 1421 ꢀ(C–N)Bz, and 1309 cm−1 ꢀ(C–N)sec 1H
.
NMR (DMSO): ı 12.20 (1H, s, benzimidazolic NH); 6.55 (2H), 6.65
(1H), and 7.05 (2H) (aniline protons, H26–30); 7.10, 7.12, 7.47, and
7.49 (benzimidazolic protons, H18–21); ı 6.23 (1H, t, NHsec), and
ı 4.46 (2H, d, CH2). UV/vis (ethanol): 204, 222, 242, 274, and
280 nm; (DMF): 263, 275, and 281 nm.
˚
provided by copper anode (K␣, ꢃ = 1.54056 A) operated at 40 kV
and 25 mA. The thermal analyses (TGA/DTA) were carried out in
dynamic nitrogen atmosphere (20 mL min−1) with a heating rate
of 10 ◦C min−1 in platinum crucible using DTG-60H SIMULTANEOUS
DTA-TG APPARATUS-SHIMADZU. Elemental microanalyses (C, H, N,
and X) were performed at the Micro-analytical Center, Cairo Uni-
versity. The analyses were repeated twice to check the accuracy of
the analyzed data. The metal content was determined gravimetri-
cally [8]. Digital Jenway 4330 Conductivity-pH meter with (1.02) cell
constant was used for pH and molar conductance measurements.
The UV/vis measurements were carried out using automated spec-
trophotometer UV/vis SHIMADZU Lambda 4B using 1 cm matched
quartz cells.
•
•
•
Data for Pd-L (X = Cl) (1) (C14H15Cl2N3OPd). Color: Yellow. Yield:
80%. Anal. Calc. %C, 40.17; %H, 3.61; %Cl, 16.94; %N, 10.04; %Pd,
25.42. Found: %C, 40.39; %H, 3.82; %Cl, 16.99, %N, 10.13; %Pd,
25.44. FT-IR: 3399 (ꢀ(NH)sec), 1614 (ꢀ(C N)), 1444 (ꢀ(NHb)sec),
1281 (ꢀ(C–N)sec), and 510 ␳t(OH2). 1H NMR (DMSO): ı 13.18
(NHBz), ı 6.56–8.48 (9H, aromatic protons), ı 7.46 (NHsec) and
ı 4.98 and 5.31 (CH2). UV/vis (DMF): 272, 278, and 372 nm. Molar
Cond. (10−3, DMF): 21.11 ꢁ−1 cm2 mol−1
.
Data for Pd-L (X = Br) (2) (C14H17Br2N3O2Pd). Color: Orange.
Yield: 85%. Anal. Calc. %C, 32.00; %H, 3.26; %Br, 30.41; %N, 8.00;
%Pd, 20.25. Found: %C, 31.89; %H, 3.23; %Br, 30.38, %N, 7.92; %Pd,
20.17. FT-IR: 3431 (ꢀ(NH)sec), 1659 (ꢀ(C N)), 1443 (ꢀ(NHb)sec),
1321 (ꢀ(C–N)Bz), 1281(ꢀ(C–N)sec) and 510 ␳t(OH2). 1H NMR
(DMSO): ı 13.17 (NHBz), ı 6.50–8.45 (9H, aromatic protons), ı
6.90 (NHsec) and ı 5.01 and 5.26 (CH2). UV/vis (DMF): 271, 281,
2.3. Theoretical calculations
The molecular structure of the benzimidazole (L) in the ground
state was optimized by a DFT method using B3LYP functional [9]
combined with 6-31G(d) and LANL2DZ basis sets. Calculations were
carried out using GAUSSIAN 03 [10]. The vibrational frequencies
and the corresponding normal modes were evaluated at the opti-
mized geometry [9] using the same basis sets. Vibrational modes
were analyzed using GAUSSVIEW software [11]. The main reason
in choosing the LANL2DZ basis set is its inclusion of relativistic
effect that is essential for heavy elements, e.g. Pd(II) and Pt(II), in
and 362 nm. Molar Cond. (10−3, DMF): 419 ꢁ−1 cm2 mol−1
.
Data for Pd-L (X = I) (3) (C14H17I2N3O2Pd). Color: Blue-Black.
Yield: 82%. Anal. Calc. %C, 27.14; %H, 2.77; %I, 40.97; %N, 6.78;
%Pd, 17.18. Found: %C, 27.07; %H, 2.74; %I, 40.93, %N, 6.71; %Pd,
17.11. FT-IR: 3414 (ꢀ(NH)sec), 3263 (ꢀ(NH)Bz), 1675 (ꢀ(C N)),
1454 (ꢀ(NHb)sec), 1311(ꢀ(C–N)Bz), 1263 (ꢀ(C–N)sec), 855 ␳r(OH2),
624 ␳w(OH2), and 466 ␳t(OH2). 1H NMR (DMSO): ı 13.14 (NHBz), ı

N.T. Abdel Ghani, A.M. Mansour / Spectrochimica Acta Part A 81 (2011) 529–543
531
order to compare between the optimized structures of the ligand
L and its complexes. The 1H NMR chemical shifts were computed
at the B3LYP/6-311+G(2d,p) level of theory in the gaseous state by
applying GIAO approach [12] and the values for the 1H isotropic
were referenced to TMS, which was calculated at the same level
of theory. The optimized structures, vibrational frequencies, 1H
chemical shifts, and the natural bond orbitals (NBOs) analysis of
the metal complexes were obtained at B3LYP/LANL2DZ level of
theory.
Benzimidazole ligand (L) has a strong intermolecular hydrogen
bond in the solid state, which makes the IR spectrum shows strong
and broad absorption band in the region 3500–2200 cm−1. Thus,
it is difficult to assign the benzimidazolic NH band (NHBz) experi-
mentally (Fig. 2). By using the B3LYP/6-31G(d) method, the scaled
calculated value at 3513 cm−1 is assigned to the ꢀ(NHBz). This group
is still masked in the spectra of metal complexes, due to the hydro-
gen bond effect generated by water molecules, whereas complexes
(3,4) have a sharp band at 3263 and 3359 cm−1, respectively [3]. The
theoretically scaled ꢀ(NHBz) in the benzimidazole (L) and its com-
plexes is found in the same position at 3570 cm−1 as calculated by
the LANL2DZ basis set. This confirms that the NHBz group remains
intact in the complexes.
2.4. Biological activity
2.4.1. Antimicrobial activity
The antimicrobial activities of the test samples were deter-
mined using a modified Kirby-Bauer disc diffusion method [13]
under standard conditions using Mueller-Hinton agar medium, as
described by NCCLS [14]. The antimicrobial activities were car-
ried out using culture of Bacillus subtilis, Staphylococcus aureus, and
Streptococcus faecalis as Gram-positive bacteria and Escherichia coli,
Pseudomonas aeruginosa, and Neisseria gonorrhoeae as Gram-
negative bacteria. Briefly, 100 ␮L of the test bacteria were grown
in 10 mL of fresh media until they reached a count of approxi-
mately 108 cells/mL. A 100 ␮L of microbial suspension was spread
onto agar plates corresponding to the broth in which they were
maintained. DMSO (0.1 mL) alone was used as control under the
same conditions for each microorganism, subtracting the diameter
of inhibition zone resulting with DMSO, from that obtained in each
case. The antimicrobial activities could be calculated as a mean of
three replicates. The results were compared with a similar run of
Tetracycline as an antibacterial.
The sharp band at 3427 cm−1 in the benzimidazole L is assigned
to ꢀ(NHsec) that is in a good agreement with the theoretically scaled
value. This band is still observed in the complexes, but it shifts to
lower frequency and/or becomes broad (3431–3382 cm−1), indicat-
ing its involvement in the coordination sphere. The scaled ꢀ(NHsec
)
is found at 3502, 3374, and 3353 cm−1 in the benzimidazole L, Pd-L
(1) and Pt-L (6) complexes, respectively. This confirms the partic-
ipation of this group in the coordination sphere. The stretching
mode of the C N group is observed at 1682 cm−1 in the free ligand
(theoretical value is 1683 cm−1) and is shifted to lower frequencies
by 12–63 cm−1 in its complexes. This confirms the participation
of the pyridine-type nitrogen in the coordination sphere. Other
vibration modes are shown in Table 1.
Unfortunately, the metal-nitrogen stretching bands could not
be distinguished experimentally from other ring skeleton vibra-
tions present in the same region [3]. However, the theoretically
scaled vibrations at 290 and 264 cm−1 in the Pd-L complex (1)
are assigned to Pd-Npy and Pd-NHsec, while the bands at 271 and
216 cm−1 are allocated for Pt-Npy and Pt-NHsec in the Pt-L complex
(6). The far-IR spectra of the palladium complexes (1–3) (X = Cl, Br
or I) show two medium bands only in case of X = Cl at 367 and
363 cm−1 due to ꢀ(Pd–Cl) in a cis-square planar structure [19].
Similarly, the platinum complex (6) shows these modes at 369
and 360 cm−1. In addition, the theoretical assignments of these
bands are easily assigned by the visualization of the normal mode
displacement vectors utilizing the GAUSSVIEW program. The the-
oretically scaled ꢀss(Pd–Cl) and ꢀass(Pd–Cl) modes are observed at
330 and 320 cm−1, while the scissoring bending mode of Cl–Pd–Cl
is found at 128 cm−1. For platinum complex (6), the theoretically
scaled ꢀss(Pt–Cl), ꢀass(Pt–Cl) and the scissoring Cl–Pt–Cl modes are
established at 322, 316 and 136 cm−1, respectively.
The IR spectrum of the palladium thiocyanato complex (4) dis-
plays ꢀ(C N) as strong band at 2114 cm−1. This value is higher
than that found in case of N-bonded and S-bonded complexes [20],
which indicates that the thiocyanate anions are out of the coordi-
nation sphere as suggested from the conductivity measurements.
The disappearance of M–N or M–S stretching modes confirms the
absence of SCN in the coordination sphere. Similarly, the nitrato
complex (5) shows three bands at 1489, 1385 and 930 cm−1 owing
to the ꢀ(NO2)asy, ꢀ(NO2)sy and ꢀ(NO) [20]. The IR spectra of com-
plexes (2–5) showed a very broad band centered at 3400 cm−1
associated by librational modes of water [20]. For example, the
nitrato complex (5) exhibits the librational modes (rocking (␳r),
twisting (␳t) and wagging (␳w)) at 838, 624 and 510 cm−1, respec-
tively.
2.4.2. Cell culture and cytotoxicity determination
Three human cancer cell lines were used for in vitro screen-
ing experiments; breast cancer (MCF7), Colon Carcinoma (HCT)
and human heptacellular Carcinoma (Hep-G2). They were obtained
frozen in liquid nitrogen (−180 ◦C) from the American Type Culture
Collection. The tumor cell lines were maintained in the National
Cancer Institute, Cairo, Egypt, by serial sub-culturing. Cell culture
cytotoxicity assays were carried out as described previously [15].
RPMI-1640 medium was used for culturing and maintenance of the
human tumor cell lines [15]. Cells were seeded in 96-well plates at
a concentration of 5 × 104 to 105 cell/well in a fresh medium and
left to attach to the plates for 24 h. Growth inhibition of cells was
calculated spectrophotometrically using a standard method with
the protein-binding dye sulforhodamine B (SRB) [16]. The results
were compared with a similar run of cis-platin as an antitumor
compound.
3. Result and discussion
3.1. IR spectral studies
The theoretical IR spectra of the benzimidazole (L) were
obtained at DFT/B3LYP level of theory using 6-31G(d) and LANL2DZ
basis sets. All band assignments are presented in Table 1. At this
level, the calculated harmonic force constants and frequencies are
higher than the corresponding experimental quantities, due to
basis set truncation, neglecting of electron correlation and mechan-
ical anharmonicity [17]. To compensate these shortcomings, scale
factors were introduced and an explanation of this approach was
discussed [18]. Two different methods were applied: (i) uniform
scaling [18], the scaling factors are 0.963 for 6-31G(d) and 0.970
for LANL2DZ basis sets, (ii) linear regression method [19], in this
method, the plot of the calculated frequencies versus their experi-
mental values resulted in a straight line, whose equation was used
to correct the calculated frequencies (ꢀcalc).
The RMS error of the frequencies between the un-scaled and
experimentally observed values in the benzimidazole L was found
to be 79.3 cm−1. After scaling, the RMS error are found to be 5.2
and 23.3 cm−1 for 6-31G(d) and LANL2DZ, respectively, suggest-
ing that the 6-31G(d) basis set gives more accurate results. Finally,
IR study reveals that the ligand coordinated to the metal ions via
the pyridine-type nitrogen (Npy) of the benzimidazole ring and
secondary amino group (NHsec).

532
N.T. Abdel Ghani, A.M. Mansour / Spectrochimica Acta Part A 81 (2011) 529–543
Table 1
Band assignment of experimental and theoretical IR spectra of benzimidazole (L).
No.
Exp. freq.
Calculated
un-scaled
frequency
B3LYP
Scaled
frequency
Uniform scaling
Scaled
Vibrational assignments
frequency
Linear regression
scaling
6-
LANL2DZ
6-
LANL2DZ
6-
LANL2DZ
31G(d)
31G(d)
31G(d)
1
2
3
4
5
6
7
8
3649
3563
3219
3211
3209
3203
3197
3191
3187
3180
3173
2999
2942
1683
1672
1643
1641
3681
3611
3238
3229
3224
3212
3209
3202
3196
3186
3180
2984
2963
1675
1664
3513
3431
3099
3092
3090
3084
3078
3072
3069
3062
3055
2888
2833
1620
1610
1582
1580
3570
3502
3140
3132
3127
3115
3112
3105
3100
3090
3084
2894
2874
1624
1614
3516
3433
3101
3093
3092
3086
3080
3074
3070
3064
3057
2889
2834
1621
1610
1582
1580
3516
3450
3093
3084
3080.
3068
3065
3059
3053
3043
3038
2850
2830
1599
1589
ꢀ NHss/Bz
ꢀ NHss/An
ꢀ CHss/Bz
ꢀ CHss/An
ꢀ CHass/Bz
ꢀ CHass/An
ꢀ CHass/Bz
ꢀ CHass/An
ꢀ CHass/Bz
ꢀ CHass/An
ꢀ CHass/An
3427
9
10
11
12
13
14
15
16
3052
2889
2830
1687
1599
ass
CH2
CH2
ss
ꢀ CC/Bz + ꢀ C N/Bz + ␤ NHsc/Bz
ꢀ CC/An
ꢀ CC/Bz + ꢀ CC/An + ␤ NH/Bz + ␤ NH/An
17
18
19
20
1635
1628
1582
1555
1585
1579
1534
1508
1561
1554
1510
1485
1466
ꢀ CC/Bz + ␤ NH/Bz
ꢀ CC/An + ␤ NHsc/An
1595
1564
1550
1543
1535
1535
1506
1492
1485
1478
1536
1506
1493
1486
1478
ꢀ CC/Bz + ␤ NH/Bz + ␤ NH/An + ısCH2 + ꢀ C N/Bz
ꢀ CC/An + ␤ NH/An + ısCH2
1505
21
22
23
24
25
26
27
28
ısCH2
ꢀ CC/Bz + ısCH2
ıs CH2 + ␤ NH/An
ꢀ CC/Bz (boat shape) + ␻ CH2
ꢀ CC/An + ␤ NH/An + ␻ CH2
ꢀ CC/Bz + ꢀ C N/Bz + ␻ CH2
ꢀ CC/An + ␤ NH/An + ␻ CH2
ꢀ C–NH/An + ␤ NH/An + ␤ NH/An + ␻ CH2
1535
1480
1528
1513
1477
1437
1431
1390
1372
1489
1413
1497
1493
1441
1437
1441
1438
1421
1339
1482
1467
1432
1394
1388
1348
1331
1459
1445
1410
1372
1366
1327
1310
1460
1377
1405
1326
1406
1326
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
ꢀ CC/An + ␤ CH/An
␤ CH/An
1370
1365
1332
1319
1314
1282
1319
1314
1282
␤ CH/An + ␤ CH/Bz + ␻ CH2 + ␤ NH/Bz
␤ CH/An + C–N/An + ␻ CH2
␤ CH/An + ␤ CH/Bz
␤ CH/An + ␤ CH/Bz + ␤ NH/An
ꢀ CC/Bz + ␤ NH/An
␤ CH/An + ␤ CH/Bz + ␤ NH/An + ␤ NH/Bz + ␻ CH2
ꢀ CC/Bz + ␻ CH2 + ␤ NH/An
␶ CH2 + ␤ NH/Bz + ␤ CH/Bz
␶CH2
1309
1266
1365
1326
1324
1286
1303
1266
1306
1257
1257
1302
1290
1263
1251
1243
1231
1295
1259
1247
1247
1212
1200
1247
1212
1200
1250
1247
1227
1220
1213
1209
1190
1183
1193
1190
1171
1165
␤ CH/Bz + ␤ NH/Bz
␤ CH/An + ␤ CH/Bz + ␤ NH/Bz + ␻ CH2
␤ CHsc/An
1186
1217
1206
1191
1183
1161
1144
1112
1058
1046
1040
674
1171
1161
1146
1139
1118
1101
1070
1018
1007
1001
649
1172
1161
1146
1139
1118
1101
1070
1018
1007
1001
648
␤ NH/Bz + ␤ CH/An + ␤ CH/Bz
1202
1193
1162
1140
1107
1166
1157
1127
1105
1073
1147
1139
1109
1088
1057
␤ CHsc/An
␤ CHsc/Bz
ꢀ CH/An + CH2-NH + ␤ NH/Bz
1107
1016
␤ CHsc/Bz
␤ CH/An
␤ CH/An
␤ CH/Bz
␳CH2
1050
675
1046
1035
1018
654
1014
1004
1002
644
998
988
52
53
1023
1008
985
970
985
970
Rtorsion/Bz
Rtrigd/An
975
947
874
822
762
705
1020
998
910
848
785
716
938
911
841
791
733
678
989
968
882
822
761
694
938
911
841
791
733
678
973
952
868
809
749
683
841
745
687
␥
54
55
CH/An
974
930
862
757
1024
982
896
786
937
895
830
728
993
952
869
762
937
895
830
728
977
937
855
750
␥
CH/Bz

N.T. Abdel Ghani, A.M. Mansour / Spectrochimica Acta Part A 81 (2011) 529–543
533
Table 1 (Continued)
No.
Exp. freq.
Calculated
un-scaled
frequency
B3LYP
Scaled
frequency
Uniform scaling
Scaled
Vibrational assignments
frequency
Linear regression
scaling
6-
LANL2DZ
6-
LANL2DZ
6-
LANL2DZ
31G(d)
31G(d)
31G(d)
56
57
58
59
60
871
912
1009
1004
909
878
978
973
881
651
878
963
958
867
605
Rtrigd/Bz
Rtrigd/An
Rtrigd/Bz
Rtrigd/An
Rtrigd/Bz
634
633
635
610
609
610
609
614
579
486
591
557
468
590
557
467
NH/An
NH/Bz
61
62
545
445
538
604
521
585
513
576
435
418
402
For 6-31G(d) basis set, the slope is equal 1.0384 and the linear coefficient is 0.9993.
For LANL2DZ basis set, the slope is equal 1.0464 and the linear coefficient is 0.9963.
R: ring; ss: symmetric stretching; ass: asymmetric stretching; ꢀ, stretching; ␤, in-plane bending; ␥, out-of-plane bending; ␳, rocking; ␻, wagging; ␶, torsion; trig: trigonal;
trigd: trigonal deformation.
3.2. 1H NMR studies
protons of the benzimidazole ring. In complexes, the aromatic
protons nearest to the coordination centers are found to suffer
maximum downfield shifts compared with the other aromatic
protons.
1. The NHBz signal appears at 12.20 ppm [21] in the benzimidazole
L and moves downfield in its complexes (13.14–13.46 ppm). This
shift is related to the charge density change in the benzimidazole
ring, which supports the fact that the coordination occurs via the
pyridine-type nitrogen.
2. The triplet signal at 6.23 ppm is due to the NHsec group (Fig. 3),
whereas the doublet signal at 4.46 ppm is assigned to the CH2
group. In complexes, both signals move downfield owing to the
participation of the NHsec group in the chelation. The methylene
group appears as a pair of quartet between 4.76 and 5.36 ppm
in the complexes, as the CH2 protons are no longer isochronous,
where the equatorial proton points away from the metal ion than
the axial one does [7].
The calculated chemical shift of the methylene group (4.46 ppm)
in the benzimidazole (L) by the 6-311+G(2d,p) basis set is in agree-
ment with the experimental value. The theoretical values at 7.53,
7.40, 7.10, 7.08, and 6.51 ppm are assigned to the aromatic pro-
tons of the aniline moiety, while the signals at 8.14, 7.59, 7.58, and
7.63 ppm are attributed to the benzimidazolic protons. Thus, the
experimental chemical shifts are slightly smaller than the calcu-
lated values. In addition, the experimental chemical shift of NHBz
proton is shifted towards higher magnetic field than the calculated
ones by 4.05 ppm, as previously reported by other authors [22]. In
addition, the calculated chemical shift of NHsec group is smaller
than that observed by 0.76 ppm. These may be due to neglect of
the non-specific solute–solvent interactions (in the gas phase), and
3. The protons of the aniline ring give rise to two doublets at 6.55,
7.05 ppm, and a singlet at 6.65 ppm. While, the four broader sig-
nals at 7.10, 7.12, 7.47, and 7.49 are attributed to the aromatic
Fig. 2. Infrared spectra of benzimidazole L (a) experimental, (b) 6-31G(d), (c) LANL2DZ.

534
N.T. Abdel Ghani, A.M. Mansour / Spectrochimica Acta Part A 81 (2011) 529–543
Fig. 3. 1H NMR spectrum of benzimidazole L in (a) DMSO, (b) DMSO/D2O.
the intermolecular hydrogen bond in our calculations as compared
with the experimental chemical shifts that are obtained from the
DMSO solutions (hydrogen-bonded solvent).
ment loses the NHBz group to give a peak at m/z 350. Fragments due
to 2-methylene benzimidazole, benzimidazole, and N-methylene
aniline are also observed.
Fragmentation pattern of the Pt-L complex (6) goes under three
complicated fragmentation routes as demonstrate in Scheme 1. It
was found that the participation of C Npy in the chelation intro-
duces a second weakness point through which the benzimidazole
ring decomposes to imidazole moiety with the appearance of a
fragment at m/z 365. The peak at m/z 417 is assigned to [PtL]2+
fragment. This fragment confirms the bidentate nature of the ben-
zimidazole ligand. The fragment at m/z 382 indicates the presence
of two chlorine atoms in the coordination sphere of Pt-L com-
plex.
3.3. Mass spectrometry
The benzimidazole L has a molecular ion peak at m/z 223, and
decomposes through the cleavage of the CH2–NH bond. The most
abundant fragment at m/z 131 is assigned to 2-methylene benzim-
idazole, while the fragment at m/z 93 is due to the aniline moiety.
The mass spectrum of the Pd-L complex (1) was characterized by
the appearance of the most abundant fragment at m/z 365 owing
to the removal of one chlorine atom from [PdLCl2]+. The latter frag-
A
Cl
Cl
Pt
N
B
NH
N
N
N
H
N
H
m/z = 488 ( 0 %)
B
m/z = 221 ( 16 %)
A
Pt
Pt
N
N
Cl
Cl
NH
N
NH
CH2
Pt
N
H
N
N
H
N
H
m/z = 365 ( 100 %)
m/z = 131 ( 32 %)
-CH
m/z = 417 ( 13 %)
N
H
2
2
m/z = 382 ( 15 %)
Pt
HN
Pt
N
N
N
N
N
NH
H
N
m/z = 287 ( 16 %)
H
m/z = 350 ( 34 %)
m/z = 105 (46 %)
m/z = 118 ( 18 %)
Pt
Cl
m/z = 91 ( 59 %)
NH
Pt
NH
N
m/z = 210 ( 23 %)
m/z = 259 ( 27 %)
Scheme 1. Fragmentation pattern of Pt-L (6) complex.

N.T. Abdel Ghani, A.M. Mansour / Spectrochimica Acta Part A 81 (2011) 529–543
535
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0005
0.0000
(b) 100
80
30
20
2.4
2.2
2.0
1.8
1.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0005
0.0000
-0.0005
-0.0010
-0.0015
-0.0020
-0.0025
(a)
DTG
60
10
-0.0005
-0.0010
-0.0015
-0.0020
-0.0025
-0.0030
TGA
40
0
20
-10
-20
-30
-40
-50
DTA
0
DTA
Pd-L (X = Br)
-20
-40
-60
TGA
Pd-L(X = SCN)
DTG
200
400
600
800
1000
Temp.oC
200
400
600
800
1000
Temp.oC
0.001
160
140
120
100
80
(c)
TGA
1.6
1.4
1.2
1.0
0.8
0.6
0.000
DTG
-0.001
-0.002
-0.003
-0.004
-0.005
Pt-L
60
40
20
DTA
0
-20
-40
200
400
Temp. o
600
800
C
Fig. 4. TGA, DTG and DTA curves of (a) Pd-L (X = Br), (b) Pd-L (X = SCN), (c) Pt-L.
3.4. Electronic absorption
3.5. Thermal analyses and kinetics studies
The electronic spectrum of the benzimidazole L displayed five
absorption bands in ethanol at 204, 222, 242, 274 and 280 nm. The
first two bands may be assigned to medium and low energy ␲–␲*
transitions within the phenyl rings of the aniline and benzimidazole
moieties, respectively [23]. The remaining bands at 242, 274 and
280 nm are assigned to ␲–␲* transitions in the benzimidazole ring
[24]. In addition, the bands at 274 and 280 nm appear doubled as
benzoic acid due to the existence of a tautomeric structure [25]. This
phenomenon is supported by comparing our spectrum with the
spectrum of 1-methyl-2-phenyl-benzimidazole [24], where this
fine structure is lost.
Discussing the simultaneous TGA/DTA curves constructed for
Pd-L complex (1), one can observe three endothermic mass loss
stages at 250, 409, and 467 ◦C. The 1st and 2nd decomposition steps
are accompanied by a mass loss, 53.34% (calcd. 53.83%) due to the
degradation of one ligand molecule. The 3rd stage involves a 17.35%
mass loss, owing to the releasing of chlorine gas (calcd. 16.90%)
leaving palladium oxide as a final residue at 507 ◦C.
The TGA/DTA curves of Pd-L (X = Br) complex (2) (Fig. 4a) exhibit
five decomposition steps maximized at 296, 379, 426, 506 and
800 ◦C. The 1st and 2nd pronounced peaks are accompanied by a
mass loss amounting to 22.19% (calcd. 21.99%) due to the removal of
one bromine atom and two coordinated water molecules. The 3rd
and 4th decomposition stages involve the loss of another bromine
atom and benzimidazole ring. The final stage is attributed to the
removal of N-methylene aniline with overall mass loss amount-
ing to 76.78% (calcd. 77.44%), leaving Pd metal as a final residue at
1000 ◦C. On the other hand, the thermogram of Pd-L (X = I) complex
(3) resembles complex (2) with four decomposition stages at 285,
419, 538 and 803 ◦C.
The two bands between 270 and 280 nm (35,714–37,000 cm−1
)
in the Pd(II) and Pt(II) complexes are assigned to internal lig-
and transitions (␲–␲* in the benzimidazole ring). The band near
26,000 cm−1 in Pd-L (1) is spin-allowed transition; a1g(dx 2 ) −
2
−y
b1g(dx 2 ) i.e. 1A1g
→
1B1g (ꢀ2). The first low energy spin allowed
2
−y
band at 23,696 cm−1 in Pt-L complex (6) has been assigned to
1
the transition b2g(dxy) − d1g(dx 2 ) i.e. A1g
→
1A2g (ꢀ1), compa-
2
−y
rable to the transition assigned by Jorgensen [31], for [PtCl4]2−
(21,500 cm−1). This blue shift is ascribed to the stereochemical
difference between the L and the chloride ion. Strong charge-
transfer transitions may interfere and prevent observation of all
the expected bands [26]. Strong bands between 350 and 380 nm
For Pd-L (X = SCN) complex (4), the degradation starts at 100 ◦C
with three decomposition stages centered at 261, 411 and 800 ◦C
(Fig. 4b). The first degradation step is due to the releasing of two
SCN, two coordinated water molecules and one hydrated molecule.
The 2nd and 3rd decomposition stages are attributed to the degra-
dation of one ligand molecule leaving Pd metal as a final residue
with overall mass loss amounting to 78.80% (calcd. 78.76%).
The first event in the Pd-L (X = NO3) complex (5) is a com-
posite one, which has three mutually endothermic overlapping
peaks, maximized at 51, 140 and 295 ◦C owing to the elimi-
(28,000–26,000 cm−1
) in the palladium complexes (2–5) are
assignable to a combination of MLCT and eg(dyz, dzx) − b1g(dx 2 ),
2
−y
i.e. 1A1g
→
1Eg bands (ꢀ3). Therefore, the electronic spectra of Pd(II)
and Pt(II) metal complexes are indicative of square planar geometry
[26,27].

536
N.T. Abdel Ghani, A.M. Mansour / Spectrochimica Acta Part A 81 (2011) 529–543
Table 2
Kinetic parameters, (E*, ꢄH*, ꢄG*, kJ/mol), A (s−1) and ꢄS* (J/K mol); determined using Coats–Redfern method and Horowitz–Metzger methods of the metal complexes
under study.
Compound
Decomp. range
Coats–Redfern
Horowitz–Metzger
E*
A
ꢄS*
ꢄH*
ꢄG*
E*
A
ꢄS*
ꢄH*
ꢄG*
30–310
310–420
420–507
89
44
128
2 × 106
2 × 105
5 × 105
−124
−151
−143
86
39
122
129
141
228
111
78
143
7 × 106
2 × 109
2 × 106
−96
111
78
144
144
127
240
[PdLCl2]·H2O
−72
−131
214–312
312–390
390–440
440–600
600–855
105
57
104
169
224
4 × 105
2 × 105
2 × 105
2 × 106
2 × 106
−143
−151
−151
−132
−137
100
52
98
163
215
182
149
204
265
362
122
70
113
181
224
3 × 106
3 × 106
1 × 105
5 × 106
2 × 106
−126
−126
−142
−124
−135
123
71
114
182
225
194
153
213
278
369
[PdL(H2O)2]·2Br
200–310
310–435
435–555
772–831
158
14
358
368
5 × 106
1 × 105
5 × 108
3 × 107
−121
−151
−87
153
9
351
360
220
113
422
479
194
26
381
389
2 × 108
2 × 109
2 × 109
8 × 107
−93
−74
−76
−104
194
26
381
389
246
77
443
502
[PdL(H2O)2]·2I
−111
225–360
360–1000
170
230
2 × 107
−112
−106
166
225
226
298
176
235
4 × 107
−105
−103
176
235
232
306
[PdL(H2O)2]·2SCN·H2O
4 × 107
6 × 107
30–91
91–215
215–350
350–512
725–862
20
32
55
176
291
2 × 105
1 × 105
1 × 105
5 × 106
7 × 106
−146
−149
−150
−123
−125
17
29
51
171
282
65
90
136
255
417
21
33
65
180
304
1 × 105
1 × 105
1 × 105
7 × 106
1 × 107
−139
−149
−137
−121
−119
22
34
66
181
304
67
95
144
263
433
[PdL(H2O)2]·2NO3
170–400
400–480
27
448
2 × 105
−149
−46
22
442
113
475
38
447
3 × 107
−108
−101
38
447
105
521
[PtLCl2]
8 × 107
8 × 107
nation of two-coordinated water molecules, two molecules of
nitrogen dioxide and oxygen gas. The 4th and 5th thermal
stages, centered at 409 and 808 ◦C, are due to the degrada-
tion of one ligand molecule with overall mass loss amounting
to 75.68% (calcd. 75.87%) leaving Pd metal as a final residue
[28].
The TGA/DTA curves (Fig. 4c) of the platinum complex (6) reveal
that the decomposition process proceeds via two main endother-
mic stages. The 1st step at 341 ◦C, is responsible for the elimination
of benzimidazole ring with mass losses 23.42% (calcd. 24.13%). The
2nd event is a composite one with two mutually overlapping peaks
at 420 and 455 ◦C. The mass loss for the 2nd event amounts to
36.30% (calcd. 35.99%). The thermal decomposition proceeds with
the formation of Pt as residue.
tice dynamics of these compounds. The values of 2ꢂ, interplanar
spacing d (Å) and the relative intensities (I/I◦) of benzimidazole
L and its complexes were tabulated in Table 3. The compari-
son between the obtained XRD patterns of L and its complexes
(Fig. 5), throws light on the fact that each complex represents a
definite compound with a distinct structure. This identification of
the complexes was done by the known method [31]. Such facts
suggest that the metal complexes are amorphous. The X-ray pow-
der diffraction pattern of benzimidazole (L) shows a degree of
crystallinity as the parent benzimidazole [32] with three low-
angle diffraction peaks (below 11.00◦) that are not observed in
the benzimidazole. Several peaks characterized to the benzim-
idazole moiety are also observed at 18.18◦, 34.09◦, 37.59◦, and
40.12◦.
The kinetics parameters are calculated by using Coats–Redfern
[29] and Horowitz–Metzger methods [30]. According to the
obtained data (Table 2), some complexes have negative entropy.
This indicates that the complexes are formed spontaneously and
are highly ordered in their activated states. In Pd-L (X = NO3)
complex (5), the values of activation energy increase on going
from one thermal stage to another for a given complex, indi-
cating that the rate of decomposition decreases in the same
order. While, the values of the free activation energy ꢄG*
increase significantly for the subsequent decomposition stages of
a given complex. This is due to increasing the values of TꢄS*
significantly from one-step to another, which override the val-
ues of ꢄH*. This may be attributed to the structural rigidity of
the remaining complex after the expulsion of one of the coordi-
nated anions or water molecules, as compared with the precedent
complex, which require more energy, TꢄS* for its rearrange-
ment before undergoing any compositional change. The positive
ꢄH* values mean that the decomposition processes are endother-
mic.
3.7. Theoretical calculations
3.7.1. Geometry optimization
Full geometry optimizations were performed at the DFT level of
theory [9]. The optimized N15C7 and N16C7 bond lengths in the lig-
˚
and L are 1.310 and 1.377 A (Table 4) as calculated by the 6-31G(d)
basis set. This confirms that the hydrogen atom is fixed at one
of the two nitrogen atoms through the intermolecular hydrogen
bonding. The benzimidazole L shows accumulation of the nega-
tive charge density on the pyridine-type nitrogen, which is a very
important structural feature related directly to the ability to bind
the metal ions. Several calculated thermodynamic parameters are
also presented in Table 4.
The fully optimized geometries of cis-PdLCl2 and cis-PtLCl2
and numbering of atoms are shown in Fig. 6 and their geomet-
ric parameters are listed in Table 5. The coordination sphere
around the metallic center in cis-PdLCl2 and cis-PtLCl2 complexes
is made up of Npy, NHsec and 2Cl completing the square planar
geometry. The four donor atoms are coplanar, while the phenyl
ring is bent out of the coordination plane by angle 112.765◦
(cis-PdLCl2) and 118.532◦ (cis-PtLCl2). It was found that the M-
NHsec (M = Pd or Pt) bond length is about 4.43% longer than the
M-Npy bond distance [33]. In addition, the optimized Pd-NHsec
3.6. X-ray powder diffraction
The X-ray powder diffraction patterns of the benzimidazole
L, Pd-L (X = Cl) (1), Pd-L (X = Br) (2) and Pt-L (6) complexes were
recorded over 2ꢂ = 5–60◦ in order to obtain an idea about the lat-
˚
˚
(2.167 A) and Pd-Npy (2.071 A) bond lengths are slightly longer

N.T. Abdel Ghani, A.M. Mansour / Spectrochimica Acta Part A 81 (2011) 529–543
537
Table 3
X-ray diffraction data of benzimidazole L, Pd-L (X = Cl) and Pt-L complexes.
L
Pd-L (X = Cl) (1)
Pd-L (X = Br) (2)
Angle (2ꢂ)
d-Value (Å)
Relative intensity (I/I◦) %
Angle (2ꢂ)
d-Value (Å)
Relative intensity (I/I◦) %
Angle (2ꢂ)
d-Value (Å)
Relative intensity (I/I◦) %
7.23
9.41
12.20
9.39
8.09
6.92
5.26
4.99
4.87
4.69
4.34
4.22
4.16
4.04
3.86
3.76
3.47
3.35
3.28
3.18
2.99
2.92
2.69
2.63
2.39
2.24
55.7
38.7
48.5
18.7
21.9
47.8
22.8
36.2
43.8
32.7
26.8
23.8
47.1
55.7
100.0
33.3
21.9
18.7
22.3
25.2
22.8
12.1
9.5
17.07
22.82
28.52
40.76
49.52
5.18
3.89
3.13
2.21
1.84
51.4
58.8
100.0
61.4
27.45
33.44
45.42
47.54
50.26
58.63
3.24
2.67
1.99
1.91
1.81 100.0
1.57 50.6
42.8
59.2
85.2
53.4
10.92
12.77
16.84
17.73
18.18
18.91
20.44
21.03
21.31
21.93
23.00
23.600
25.65
26.56
27.10
28.01
29.79
30.59
33.16
34.09
37.59
40.12
58.8
4.0
Table 4
Geometrical parameters optimized in L (bond length, and bond angle), theoretically computed energies, zero-point vibrational energies, rotational constants, entropies and
dipole moment.
Bond lengths (Å)
B3LYP/6-31G(d)
B3LYP/LANL2DZ
Bond angles (◦)
B3LYP/6-31G(d)
B3LYP/LANL2DZ
C1C2
C1C3
C3C4
C4C5
C2C6
C4C7
C7C8
C8C9
1.409
1.392
1.399
1.415
1.393
2.147
1.502
2.473
1.410
1.390
1.399
1.394
1.396
1.310
1.377
1.389
1.086
1.086
1.086
1.086
1.009
1.102
1.107
1.014
1.088
1.087
1.086
1.087
1.087
1.421
1.404
1.407
1.428
1.406
2.187
1.506
2.504
1.422
1.401
1.412
1.407
1.407
1.330
1.394
1.390
1.086
1.087
1.087
1.087
1.011
1.106
1.106
1.015
1.089
1.088
1.087
1.088
1.087
C3C1C2
C4C3C1
C5C4C3
C6C2C1
121.409
117.989
119.828
121.535
105.277
124.496
109.274
121.608
120.677
120.814
118.782
121.045
110.158
112.999
104.425
121.717
119.513
119.302
121.314
126.230
109.407
109.0856
116.544
119.124
119.147
120.577
119.997
119.385
121.336
117.892
120.136
121.527
105.791
124.623
109.274
121.608
120.591
120.886
118.739
121.064
109.691
112.279
104.807
121.679
119.586
119.175
121.019
126.061
109.293
109.318
120.764
119.254
119.223
120.585
119.850
119.243
C7N15C4
C8C7N15
N17C8C7
C9N17C8
C11C10C9
C12C11C10
C13C12C11
C14C13C12
N15C4C5
N16C7N15
N16C5C4
H18C3C1
H19C1C3
H20C2C1
H21C6C2
H22N16C7
H23C8C7
H24C8C7
H25N17C9
H26C10C9
H27C11C10
H28C12C11
H29C13C12
H30C14C13
C9C10
C10C11
C11C12
C12C13
C13C14
N15C7
N16C7
N17C9
H18C3
H19C1
H20C2
H21C6
H22N16
H23C8
H24C8
H25N17
H26C10
H27C11
H28C12
H29C13
H30C14
B3LYP/6-31G(d)
B3LYP/LANL2DZ
−705.470
E (a.u.)
−705.585
Zero-point E (kcal mol−1
)
153.676
154.516
Rotational constants (GHz)
1.975, 0.179, 0.161
1.980, 0.170, 0.157
Entropy (cal mol−1 K−1
Translational
Rotational
)
42.110
33.033
42.783
3.615
42.110
33.079
41.750
4.312
Vibrational
Total dipole moment (D)

538
N.T. Abdel Ghani, A.M. Mansour / Spectrochimica Acta Part A 81 (2011) 529–543
Fig. 5. X-ray diffraction pattern of (a) benzimidazole L, (b) Pd-L (X = Cl), (c) Pd-L (X = Br), (d) Pt-L complexes.
Fig. 6. Optimized structures of (a) cis-PdLCl2 complex, (b) cis-PtLCl2 complexes.

N.T. Abdel Ghani, A.M. Mansour / Spectrochimica Acta Part A 81 (2011) 529–543
539
Table 5
Selected bond lengths (Å), angles (◦) and charge for cis-PdLCl2 and cis-PtLCl2 complexes.
cis-PdLCl2
cis-PtLCl2
Bond lengths (Å)
Bond angles (◦)
Charge
Bond lengths (Å)
Bond angles (◦)
Charge
C6C7
C7C8
C8C9
1.422
C6C7C8
C7C8C9
C8C9C10
C9C10C11
C6C11C10
C7C6C11
C10N20C18
C9N2C18
N2C18N20
C18C19N3
C19N3C12
C12C13C14
C12N3Pd
C13C14C15
C14C15C16
C15C16C17
C13C12C17
Cl4PdC15
N2PdN3
121.733
116.990
121.013
122.121
116.487
121.655
107.673
107.548
111.184
108.461
116.787
119.613
112.765
120.492
119.462
120.568
120.278
95.065
Pd = 0.687
C1C2
C1C3
C3C4
C4C5
C5C6
C2C6
C7C8
C9C10
C10C11
C11C12
C12C13
C13C14
C9C14
N15C7
N16C7
N17C9
N15C4
N16C5
N17C8
Pt20Cl18
Pt20Cl19
N15Pt20
N17Pt20
1.421
1.402
1.407
1.425
1.404
1.404
1.496
1.405
1.404
1.410
1.407
1.408
1.403
1.338
1.376
1.480
1.415
1.408
1.522
2.368
2.386
2.071
2.168
C1C2C6
C2C6C5
C6C5C4
C5C4C3
C4C3C1
C3C1C2
121.488
116.525
122.322
120.731
117.086
121.847
107.690
107.332
111.345
108.907
81.207
Pt = 0.619
1.402
1.406
1.425
1.404
1.404
1.410
1.409
1.378
1.337
1.505
1.502
1.467
1.409
1.407
1.406
1.409
1.404
1.410
2.071
2.167
2.369
2.387
N2 = −0.603
N3 = −0.691
Cl4 = −0.505
Cl5 = −0.549
C6 = −0.213
C7 = −0.198
C8 = −0.251
C9 = 0.151
C10 = 0.149
C11 = −0.187
C12 = 0.163
C13 = −0.225
C14 = −0.189
C15 = −0.216
C16 = −0.194
C17 = −0.261
C18 = 0.473
C19 = −0.252
N15 = −0.561
N17 = −0.697
Cl18 = −0.496
Cl19 = −0.515
C1 = 0.153
C9C10
C10C11
C6C11
C10N20
C9N2
C18N20
C18N2
C18C19
C19N3
C12N3
C12C13
C13C14
C14C15
C15C16
C16C17
C12C17
N2Pd
C5N17C7
C4N15C7
N15C7N16
C7C8N17
N15PtN17
Cl18PtC19
N17C9C14
N17C9C10
C9C10C11
C10C11C12
C11C12C13
C12C13C14
C13C14C9
C10C9C14
C9N17Pt
C2 = 0.149
C3 = −0.186
C4 = −0.214
C5 = −0.198
C6 = −0.251
C7 = 0.472
90.479
119.301
119.658
119.195
120.400
119.855
120.025
119.490
121.026
118.532
C8 = −0.244
C9 = 0.164
C10 = −0.241
C11 = −0.197
C12 = −0.207
C13 = −0.188
C14 = −0.233
N16 = −0.599
80.673
N3Pd
Cl4Pd
Cl5Pd
E (a.u.)
−862.220
158.382
−854.633
Zero-point E (kcal mol−1
)
158.387
Rotational constants (GHz)
0.325, 0.195, 0.142
0.430, 0.158, 0.122
Entropy (cal mol−1 K−1
Translational
Rotational
)
43.843
34.837
62.814
14.915
44.443
34.920
64.332
15.445
Vibrational
Total dipole moment (D)
˚
Thus, 36 core electrons, 9.28 valence electrons (on 5s and 4d atomic
orbitals) and 0.04 Rydberg electrons (mainly on 5p, 5d, and 6p
orbitals) give the 45.31 electrons. This is consistent with the cal-
culated natural charge on Pd atom (+0.687) in cis-PdLCl2, which
corresponds to the difference between 45.31e and the total num-
ber of electrons in the isolated Pd atom (46e). In addition, the two
chlorine atoms (Cl4 and Cl5) have larger negative charge −0.505e
and −0.549e, respectively. Thus, the positive atomic charge upon
the Pd(II) was substantially reduced as a consequence of electron
density donation from the pyridine like nitrogen, secondary amino
group and two chlorine atoms. Table 6 lists the calculated occu-
pancies of natural orbitals. Three classes of NBOs are included, the
Lewis-type (s and p bonding or lone pair) orbitals, the valence non-
Lewis (acceptors, formally unfilled) orbitals and the Rydberg NBOs,
which originate from orbitals outside the atomic valence shell. The
calculated natural hybrids on atoms are also given in this table.
According to calculations, the palladium atom forms two sigma
bonds with two chlorine atoms, while the two bonds between
palladium and the nitrogen atoms can be described as donation
of electron density from a lone pair (LP) orbital on each nitrogen
atom to palladium molecular orbitals. As follows from Table 6, the
␴(Pd–Cl4) bond is formed from an sp0.01d1.04 hybrid on palladium
atom (which is a mixture of 48.80% s, 0.53% p and 50.67% d atomic
orbitals) and sp14.77 hybrid on the chlorine atom (93.66% p con-
tribution). Thus, the ␴(Pd–Cl4) bond is strongly polarized towards
the chlorine atom, with about 76.80% of electron density concen-
trated on the chlorine atom. The strength of this interaction can be
estimated by the second order perturbation theory.
than the Pt-NH3 bond distance in cis-platin by 0.16 and 0.06 A,
respectively, and are in agreement with that observed in some
benzimidazole complexes [34]. However, the Pd–Cl bonds are
˚
longer than Pt–Cl bond by 0.06 and 0.03 A for Pd–Cl5 and Pd–Cl4,
respectively, owing to the difference in sizes between the met-
als.
The optimized N2-Pd-N3 (80.673◦) is smaller than NH3-Pt-NH3
in cis-platin by 6.327◦ and this can be interpreted in terms of
CH2 group, which connects the two coordination sites (N2 and
N3) and prevent the opening of this angle. In addition, the calcu-
lated Cl4–Pd–Cl5 (95.065◦) angle is larger than the experimental
one in cis-platin by 3.165◦ [35], since the intramolecular hydrogen
˚
bonding N3–H28· · ·Cl5 (2.721 A) opens up Cl4–Pd–Cl5 angle. The
optimized N15PtN17 bond angle in the cis-PtLCl2 complex is close
to that found in cis-PdLCl2 complex, while the Cl18PtC19 is slight
different from that exists in cis-platin by 1.5◦. This indicates that
there is weak or no intramolecular hydrogen bonding as found in
the cis-PdLCl2 complex and this may be attributed to the signif-
icant difference in the bending angle of aniline ring as previously
mentioned. In addition, both C12N3 and C19N3 bond lengths in cis-
PdLCl2 complex were increased upon the coordination of secondary
amino group N3H to the metal center.
3.7.2. Natural bond orbital (NBO) analysis
The natural bond orbital (NBO) analysis of cis-PdLCl2 complex
was performed. The NBO analysis can be used to estimate the
delocalization of electron density between occupied Lewis-type
orbitals and formally unoccupied non-Lewis NBOs (antibonding
or Rydberg), which corresponds to a stabilizing donor–acceptor
interaction [36]. Table 5 collects the natural charges on atoms. The
largest negative charges are located on the two nitrogen atoms, Npy
(−0.603e) and NHsec (−0.691e). According to the NBO results, the
Table 7 lists the selected values of the calculated second order
interaction energy (E2) between donor–acceptor orbitals in cis-
PdLCl2. The strongest interactions are the electron donations from a
lone pair orbital on the nitrogen atoms, LP(1)N2 to the antibonding
acceptor ␴*(Pd–Cl5) orbitals, e.g. LP(1)N2 → ␴*(Pd–Cl5). As shown
in Table 6, the LP(1)N2 orbital has 69.35% p-character and is occu-
electron configuration of Pd is: [core]5s0.354d8.935p0.025d0.016p0.01
.

540
N.T. Abdel Ghani, A.M. Mansour / Spectrochimica Acta Part A 81 (2011) 529–543
Fig. 7. Molecular orbital surfaces and energy levels of (a) cis-PdLCl2 complex, (b) cis-PtLCl2 complexes.
Table 6
Occupancy of natural orbitals (NBOs) and hybrids calculated for cis-PdLCl2 complex.
Donora Lewis-type NBOs (A-B)
Occupancy
1.983
Hybridb
AO (%)c
Acceptord non Lewis NBOs
NBOs
0.036
sp1.84 (N2)
sp2.23 (C18)
s(35.23)p(64.77)
s(30.92)p(69.08)
␴*(C18-N2)
␴(C18-N2)
sp1.98 (N3)
sp2.83 (C12)
s(35.23)p(64.77)
s(26.09)p(73.91)
␴*(C12-N3)
␴*(C19-N3)
␴*(Pd–Cl4)
␴*(Pd–Cl5)
0.040
0.023
0.322
0.284
␴(C12-N3)
␴(C19-N3)
␴(Pd–Cl4)
␴(Pd–Cl5)
1.985
1.980
1.933
1.937
sp2.60 (N3)
sp3.40 (C19)
s(27.78)p(72.22)
s(22.73)p(77.27)
sp0.01d1.04 (Pd)
sp14.77 (C14)
s(48.80)p(0.53)d(50.67)
s(6.34)p(93.66)
sp0.01d1.09 (Pd)
sp13.32 (C15)
s(47.55)p(0.49)d(51.95)
s(6.99)p(93.01)
␴(N3-H28)
LP(1)N2
LP(1)N3
LP(1)Cl4
LP(1)Cl5
LP(1)Pd
LP(2)Pd
LP(3)Pd
1.981
1.730
1.713
1.990
1.990
1.995
1.991
1.990
sp2.99 (N3)
sp2.26
s(25.08)p(74.92)
s(0.02)p(99.98)
s(13.57)p(86.43)
s(79.62)p(20.38)
RY*(1)N2
RY*(1)N3
RY*(1)Cl4
RY*(1)Cl5
RY*(1)Pd
RY*(2)Pd
RY*(3)Pd
0.004
0.007
0.0003
0.0004
0.018
0.003
0.0025
sp6.37
sp0.26
sp0.41
s(71.11)p(28.89)
sp0.58d99.99
sp0.01d39.43
sp4.32d99.99
s(0.11)p(0.07)d(99.82)
s(2.47)p(0.01)d(97.51)
s(0.02)p(0.08)d(99.90)
a
LP(n)A is a valence lone pair orbital (n) on A atom.
Hybrid on A atom in the A–B bond or otherwise, as indicated.
Percentage contribution of atomic orbitals in NBO hybrid.
b
c
d
Asterisk (*) denotes antibonding, and Ry corresponds to the Rydberg NBO orbital.
Table 7
Second-order interaction energy (E2, kcal mol−1) between donor and acceptor orbitals in cis-PdLCl2 complex calculated at B3LYP/LANL2DZ level of theory (selected).
Donor → acceptor
E2
Donor → acceptor
E2
LP(1)N2 → ␴*(Pd–Cl5)
LP(1)N3 → ␴*(Pd–Cl4)
␴(Pd–Cl4) → ␴*(Pd–Cl5)
66.23
50.5
10.13
LP(1)Cl4 → ␴*(Pd–Cl4)
13.11
3.55
␴(N20-C18) → ␴*(Pd–Cl4)

N.T. Abdel Ghani, A.M. Mansour / Spectrochimica Acta Part A 81 (2011) 529–543
541
The benzimidazole L is active against both types of the bacteria,
which may indicate broad-spectrum properties. The remarkable
activity of this compound may be arising from the benzimidazole
ring, which may play an important role in the antibacterial activity.
The mode of action may involve the formation of a hydrogen bond
through the pyridine-type nitrogen of the imidazole ring with the
active centers of the cell constituents, resulting in interference with
the normal cell process. The benzimidazole L is more toxic against
Gram-positive than Gram-negative bacteria that is related to the
cell wall structure of the bacteria. It is important to point out that
the benzimidazole L is more toxic against the bacterium S. aureus
with a minimum inhibitory concentration (58 ␮g/mL) as compared
with the standard tetracycline (82 ␮g/mL).
35
30
25
Pd-L (X = Cl)
Pt-L
L
Tetracycline
20
15
10
5
Tetracycline
However, the Pd-L complex (1) was inactive against all the test
organisms, while the platinum complex (6) possesses lower activity
than that of the ligand itself as shown in Fig. 8. A possible expla-
nation for the poor activity of these complexes may be attributed
to their inability to chelate metals essential for the metabolism of
microorganisms and/or to form hydrogen bonds with the active
centers of cell structures, resulting in an interference with the
normal cell cycle. Furthermore, the low activity of these com-
plexes may be also due to their low lipophilicity, because of which
penetration of the complex through the lipid membrane was
decreased and hence, they could neither block nor inhibit the
growth of the microorganism. Therefore, the toxicity of the com-
plexes can be related to strength of the M–L bonds, besides other
factors such as size of the cation, receptor sites, diffusion, and a
combined effect of the metal and the ligands for inactivation of the
bio-molecules.
L
Pt-L
0
G1
G2
G3
Pd-L (X = Cl)
G4
G5
G6
Fig. 8. Antibacterial activities of benzimidazole L and its complexes; Pd-L (X = Cl) (1)
and Pt-L (6) against B. subtilis (G1), S. aureus (G2), S. faecalis (G3) as Gram-positive,
(G4) P. aeruginosa (G4), E. coli (G5), N. gonorrhoeae (G6) as Gram-negative bacteria.
pied by 1.731 electrons (this is consistent with a delocalization of
electron density from the idealized occupancy of 2.0e). The dona-
tion of electron density from the coordination sites in the ligand to
the Pd molecular orbitals has a clear correspondence to a chemical
picture of the coordination bonds.
3.7.3. Frontier molecular orbitals
The frontier molecular orbitals play an important role in the
electric and optical properties [37]. Fig. 7 shows the distributions
and energy levels of the HOMO, and LUMO orbitals computed at
the B3LYP/LANL2DZ level for cis-PdLCl2 and cis-PtLCl2 complexes.
The value of the energy separation between the HOMO and LUMO
is 0.130 and 0.141 eV for cis-PdLCl2 and cis-PtLCl2, respectively.
3.9.2. Cytotoxicity
To evaluate the potential usefulness of the studied complexes
synthesized as antitumor agents, three cell lines of different origin;
breast cancer (MCF-7), Colon Carcinoma (HCT) and human hepta-
cellular Carcinoma (Hep-G2) were treated. This experiment was
performed at 100 ␮M and compared with cis-platin. These com-
plexes showed activity against the studied cell lines. The IC50 (the
concentration that inhibited in 50% of the cellular proliferation)
of these compounds and cis-platin were determined. According
to Shier [38], the compounds exhibited IC50 activity in the range
10–25 ␮g/mL are considered weak anticancer drugs, while those of
IC50 between 5.00 and 10.00 ␮g/mL are moderate and compounds
of activity below 5.00 ␮g/mL are considered strong agents.
It was found that the Pd-L (1) and Pt-L (6) complexes have
moderate toxicity against Hep-G2 cells (according to Shier scale).
The palladium complex has IC50 value of 15 ␮M (equivalent to
6.27 ␮g/mL) as compared with the IC50 of cis-platin; 11.9 ␮M
(equivalent to 3.57 ␮g/mL). In addition, the Pd-L (1) is more toxic
than Pt-L (6) complex. This happens because the ligand-exchange
behavior of platinum compounds is quite slow, i.e. inert complexes,
which gives them a high kinetic stability and results in ligand-
exchange reactions of minutes to days, rather than microseconds
to seconds for many other coordination compounds. In addition,
another unusual phenomenon deals with the preferred ligands for
platinum ions is that Pt(II) has a strong thermodynamic preference
for binding to S-donor ligands and for this reason, one would predict
that platinum compounds would perhaps never reach DNA, with
many cellular platinophiles (S-donor ligands, such as glutathione,
methionine) as competing ligands in the cytosol [39].
3.8. Structural interpretation
The structures of the Pd(II) (X = Cl, Br, I, SCN and NO3) and Pt(II)
(X = Cl) complexes are elucidated by the elemental analyses, FT-
IR, 1H NMR, MS, UV/vis, thermal analysis (TGA/DTA) and molar
conductance data. From IR and 1H NMR data, it is concluded that
the benzimidazole L behaves as a neutral ligand with NNH sites
coordinating to the metal ions via the pyridine-type nitrogen (Npy
)
of the benzimidazole ring and the secondary amino group (NHsec).
From the molar conductance data of the complexes, it was found
that the Pd(II) (X = Cl) and Pt(II) complexes are non-electrolytes,
while the Pd(II) complexes (X = Br, I, SCN or NO3) are ionic. Based on
the above observations, square planar geometry is suggested for the
investigated complexes with the general formula; [MLCl2]·zH2O
(M = Pd, z = 0; M = Pt, z = 1) and [PdL(OH2)2]·2X·zH2O (X = Br, I, NO3,
z = 0; X = SCN, z = 1).
3.9. Biological activity
3.9.1. Antimicrobial activity
The data showed that the ligand L and its Pt-L complex (6)
have the capacity of inhibiting the metabolic growth of the inves-
tigated bacteria; B. subtilis, S. aureus, S. faecalis as Gram-positive
bacteria and E. coli, P. aeruginosa, N. gonorrhoeae as Gram-negative
bacteria; to different extents as shown in Fig. 8. The size of
the inhibition zone depends upon the culture medium, incuba-
tion conditions, rate of diffusion and the concentration of the
antibacterial agent (the activity increases as the concentration
increases).
The Pt-L complex (IC50 = 14.7 ␮M; 7.19 ␮g/mL) shows moder-
ate cytotoxicity against HCT cells as compared with cis-platin
(IC50 = 10.9 ␮M; 3.27 ␮g/mL). For MCF-7 cells, the Pt-L complex has
also moderate antitumor activity with IC50 = 12.4 ␮M; equivalent
to 6.06 ␮g/mL, while the IC50 of cis-platin is 9.91 ␮M (equivalent to
2.97, ␮g/mL).

542
N.T. Abdel Ghani, A.M. Mansour / Spectrochimica Acta Part A 81 (2011) 529–543
4. Conclusion
[6] M. Bocˇa, R.F. Jameson, W. Linert, Coord. Chem. Rev. 255 (2011) 290–317.
[7] N.T. Abdel-Ghani, A.M. Mansour, J. Mol. Struct. 991 (2011) 108–126.
[8] A. Skoog, D.M. West, Fundamentals of Analytical Chemistry, Thomson, Brooks,
Cole, New York, 2004.
Better approaches to the synthesis of the benzimidazole L and
its complexes were developed. On the basis of agreement between
the calculated and experimental results, assignments of all the
fundamental vibrational modes of benzimidazole L and its com-
plexes were examined and proposed at higher level of theory.
The inclusion of solvation to the 1H NMR calculations is nec-
essary especially for acidic protons in order to obtain accurate
values. The equilibrium geometries, and harmonic frequencies, of
the metal complexes were determined and analyzed at DFT level
of theory utilizing LANL2DZ basis set. NBO analysis reveals that
the strong coordination bonds result from donation of electron
density from a lone pair orbital on the nitrogen atoms to the
acceptor metal molecular orbitals, e.g. (LP(1)N2 → ␴*(Pt–Cl5)) and
(LP(1)N3 → ␴*(Pt–Cl4)). The studied ligand is more toxic against the
bacterium S. aureus with MIC (58 ␮g/mL) than the standard tetra-
cycline (82 ␮g/mL). The complexes show moderated cytotoxicity
against the investigated cell lines and represent an interesting class
of new compounds from the viewpoint of their physicochemical
and structural.
[9] A.D. Becke, J. Chem. Phys. 98 (1993) 5648.
[10] M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman,
V.G. Zakrzewski, J.A. Montgomery, R.E. Stratmann, J.C. Burant, S. Dapprich, J.M.
Millam, A.D. Daniels, K.N. Kudin, M.C. Strain, O. Farkas, J. Tomasi, V. Barone,
M. Cossi, R. Cammi, B. Mennucci, C. Pomelli, C. Adamo, S. Clifford, J. Ochterski,
G.A. Petersson, P.Y. Ayala, Q. Cui, K. Morokuma, D.K. Malick, A.D. Rabuck, K.
Raghavachari, J.B. Foresman, J. Cioslowski, J.V. Ortiz, A.G. Baboul, B.B. Stefanov,
G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. Gomperts, R.L. Martin, D.J. Fox, T.
Keith, M.A. Al-Laham, C.Y. Peng, A. Nanayakkara, C. Gonzalez, M. Challacombe,
P.M.W. Gill, B.G. Johnson, W. Chen, M.W. Wong, J.L. Andres, M. Head-Gordon,
E.S. Replogle, J.A. Pople, GAUSSIAN 03 (Revision A.9), Gaussian, Inc., Pittsburgh,
2003.
[11] A. Frisch, A.B. Nielson, A.J. Holder, GAUSSVIEW User Manual, Gaussian Inc.,
Pittsburgh, PA, 2000.
[12] R. Ditchfield, Chem. Phys. 76 (1972) 5688.
[13] (a) D. Greenwood, Antimicrobial Chemotherapy, Bailliere, Tindall, London. Part
II. Laboratory Aspects of Antimicrobial Therapy, 1983, p. 71;
(b) V. Lorian, Antibiotics in Laboratory Medicine, Williams & Wilkins, Baltimore,
1996.
[14] National Committee for Clinical Laboratory Standards, NCCLS Approval Stan-
dard Document M2-A7, Vilanova, PA, 2000.
[15] C.M. Lozano, O. Cox, M.M. Muir, J.D. Morales, J.L. Rodr␫´guez-Cabáin,
P.E. Vivas-Mejfa, F.A. Gonzalez, Inorg. Chim. Acta 271 (1998) 137–
144.
[16] (a) P. Skehan, R. Smreng, D. Scudiero, A. Monks, J. McMahon, D. Vistica, J.T. War-
ren, H. Bokesch, S. Kenney, M.R. Boyd, J. Natl. Cancer Inst. 82 (1990) 107–1112;
(b) A. Monks, D. Scudiero, P. Skehan, K. Paull, D. Vistica, C. Hose, J. Langley,
P. Cronise, A. Viagro-Wolff, M. Gra-Goodrich, J. Natl. Cancer Inst. 83 (1991)
757–766.
[17] (a) G. Rauhut, P. Pulay, J. Phys. Chem. 99 (1995) 3093–3100;
(b) J.A. Pople, H.B. Schlegel, R. Krishnan, J.S. Defrees, J.S. Binkley, M.J. Frisch,
R.A. Whiteside, Int. J. Quantum Chem.: Quantum Chem. Symp. 15 (1981)
269.
Acknowledgments
We would like to extend our grateful thanks to Dr. Mohamed
Elshakre, Chemistry Department, Faculty of Science, Cairo Univer-
sity for allowing us to use his version of the GAUSSIAN 03 package
of programs. Deep thanks to Prof. Dr. Samia Showman, professor
of Medical Biochemistry, National Cancer Centre, Cairo University,
for the great helps and support during the biological part.
[18] (a) M.W. Ellzy, J.O. Jensen, H.F. Hameka, J.G. Kay, D. Zeroka, Spectrochim. Acta
57A (2001) 2417;
(b) J.O. Jensen, A. Banerjee, C.N. Merrow, D. Zeroka, J.M. Lochner, J. Mol. Struct.:
Theochem. 531 (2000) 323;
References
(c) J.O. Jensen, D. Zeroka, J. Mol. Struct.: Theochem. 487 (1999) 267.
[19] O. Sala, N.S. Goncalves, L.K. Noda, J. Mol. Struct. 411 (2001) 565–566.
[20] K. Nakamoto, “Infrared and Raman Spectra of Inorganic and Coordina-
tion Compounds”, Part B: Applications in Coordination, Organometallic,
and Bioinorganic Chemistry, 6th ed., John Wiley & Sons Inc., New Jersey,
2009.
[1] (a) B.K. Keppler, Metal Complexes in Cancer Chemotherapy, VCH, Weinheim,
1993;
(b) G. Berthon, Handbook of Metal Ligand Interactions in Biological Fluids,
Marcel Dekker, New York, 1995.
[21] W. Nawrocka, B. Sztuba, M.W. Kowalaka, H. Liszkiewicz, Farmaco 59 (2004) 83.
[22] (a) E. Bednarek, J.C. Dobrowolski, K. Dobrosz-Teperek, L. Kozerski, W.
Lewandowski, A.P. Mazurek, J. Mol. Struct. 554 (2000) 233–243;
(b) F.S. Miranda, F.G. Menezes, J. Vicente, A.J. Bortoluzzi, C.Z. Ademir-Neves,
N.S. Gonc¸ alves, J. Mol. Struct. 938 (2009) 1–9.
[23] R.M. Issa, A.A. Hassanein, I.M. El-Mehasseb, R.I. Abed. El-Wadoud, Spectrochim.
Acta Part A 65 (2006) 206–214.
[24] (a) M. Krishnamurthy, P. Phaniraj, S.K. Dogra, J. Chem. Soc. Perkin Trans. II
(1986) 1917–1925;
[2] (a) K. Akdi, R.A. Vilaplana, S. Kamah, J.A.R. Navarro, J.M. Salas, F. González-
Vílcheza, J. Inorg. Biochem. 90 (2002) 51;
(b) A. Matilla, J.M. Tercero, N.H. Dung, B. Voissat, J.M. Pérez, C. Alonso, D. Martín-
Ramos, J. Niclós-Gutiérrez, J. Inorg. Biochem. 55 (1994) 235.
[3] (a) F. Gumus, G. Eren, L. Acik, A. Celebi, F. Ozturk, R. Ilikci Sagkan, S. Gur, A.
Ozkul, A. Elmali, Y. Elerman, J. Med. Chem. 52 (5) (2009) 1345–1357;
(b) M. Goekce, S. Utku, S. Guer, A. Oezkul, F. Gumus, Eur. J. Med. Chem. 40 (2)
(2005) 135–141;
(c) F. Gumus, O. Algul, G. Eren, H. Eroglu, N. Diril, S. Gur, A. Ozkul, Eur. J. Med.
Chem. 38 (5) (2003) 473–480;
(d) F. Gumus, A.B. Demirci, T. Oezden, H. Eroglu, N. Diril, Pharmazie 58 (5) (2003)
303–307;
(e) F. Gumus, I. Pamuk, T. Oezden, S. Yildiz, N. Diril, E. Oksuzoglu, S. Gur, A.
Ozkul, J. Inorg. Biochem. 94 (3) (2003) 255–262.
(b) A.K. Mishra, S.K. Dogra, Bull. Chem. Soc. Jpn. 58 (1985) 3587; A.K. Mishra,
S.K. Dogra, J. Photochem. 31 (1985) 333; A.K. Mishra, S.K. Dogra, Indian J. Phys.
Sect. B 54 (1984) 480; A.K. Mishra, S.K. Dogra, Spectrochim. Acta. Part A 39
(1983) 609.
[25] R.M. Issa, S.A. El-Daly, N.A. El-Wakiel, Spectrochim. Acta Part A 59 (2003)
723–728.
[26] (a) A.B.P. Lever, Inorganic Electronic Spectroscopy, 2nd ed., Elsevier, Amster-
dam, 1982, pp. 544–552;
(b) D.X. West, M.S. Lockwood, A. Liberta, X. Chen, R.D. Willet, Trans. Met. Chem.
18 (1993) 221.
[27] S.P. Perlepes, P. Jacobs, H.O. Desseyn, J.M. Tasangaris, Spectrochim. Acta 43A
(1987) 771.
[4] (a) V. Rajendiran, M. Murali, E. Suresh, S. Sinha, K. Somasundaram, M. Palanian-
davar, Dalton Trans. (2008) 148;
(b) J. Mann, A. Baron, Y. Opoku-Boahen, E. Johansson, G. Parkinson, L.R. Kelland,
S. Neidle, J. Med. Chem. 44 (2001) 138.
[5] (a) E. Bouwmann, W.L. Driessen, J. Reedijk, Coord. Chem. Rev. 104 (1990) 143;
(b) M.A. Puja, T.D. Bharamgouda, N.D. Sathyanarayna, Trans. Met. Chem. 13
(1988) 423.

N.T. Abdel Ghani, A.M. Mansour / Spectrochimica Acta Part A 81 (2011) 529–543
543
[28] N.T. Ghani, A.M. Mansour, Inorg. Chim. Acta 373 (2011) 249–258.
[29] A.W. Coats, J.P. Redfern, Nature 201 (1964) 68.
[30] H.H. Horowitz, G. Metzger, Anal. Chem. 85 (1963) 1464.
[31] B.D. Cullity, Elements of X-ray Diffraction, 2nd ed., Addison-Wesley Inc., 1993.
[32] N. Vijayan, R. Ramesh Babu, R. Gopalakrishnan, P. Ramasamy, W.T.A. Harrison,
J. Cryst. Growth 262 (2004) 490–498.
[33] D.N. Neogi, P. Das, A.N. Biswas, P. Bandyopadhyay, Polyhedron 25 (2006)
2149.
[34] (a) R.W. Hay, T. Clifford, P. Lightfoot, Polyhedron 17 (20) (1998) 3575–3581;
(b) X. Jing-Yuan, G. Wen, L. Ling, Y. Shi-Ping, C. Peng, L. Dai-Zheng, J. Zong-Hui,
J. Mol. Struct. 644 (2003) 23–27.
[35] R. Wysokin´ ski, D. Michalska, J. Comput. Chem. 22 (9) (2001) 901–912.
[36] A.E. Reed, L.A. Curtiuss, F. Weinhold, Chem. Rev. 88 (1988) 899.
[37] I. Fleming, Frontier Orbitals and Organic Chemical Reactions, Wiley, London,
1976.
[38] W.T. Shier, Mammalian Cell Culture on $5 a day: A Lab Manual of Low Cost
Methods, University of the Philippines, Los Banos, 1991.
[39] M. Pérez-Cabré, G. Cervantes, V. Moreno, M.J. Prieto, J.M. Pérez, M. Font-Bardia,
X. Solans, J. Inorg. Biochem. 98 (2004) 510–521.