Synthesis, X-ray structures and biological properties of palladium(II) complexes of 1,2-dimethylimidazole and benzimidazole

Article abstract of DOI:10.1016/j.poly.2018.12.021

Three palladium(II) complexes (1–3) with imidazole derivatives; 1,2-dimethylimidazole, benzimidazole and 2-phenylimidazole were prepared and characterized by thermal and spectral analyses. The crystal structures for two of them (1 and 2) were determined b

Full text of DOI:10.1016/j.poly.2018.12.021

Accepted Manuscript
Synthesis, X-ray structures and biological properties of palladium(II) complexes
of 1,2-dimethylimidazole and benzimidazole
Haseeba Sadaf, Imtiaz-ud-Din, Syeda Saniya Zahra, Ihsan-ul-Haq, Shafqat
Nadeem, Muhammad Nawaz Tahir, Saeed Ahmad, Sohaila Andleeb
PII:
S0277-5387(18)30825-8
https://doi.org/10.1016/j.poly.2018.12.021
POLY 13637
DOI:
Reference:
Polyhedron
To appear in:
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Accepted Date:
16 September 2018
14 December 2018
Please cite this article as: H. Sadaf, Imtiaz-ud-Din, S.S. Zahra, Ihsan-ul-Haq, S. Nadeem, M.N. Tahir, S. Ahmad,
S. Andleeb, Synthesis, X-ray structures and biological properties of palladium(II) complexes of 1,2-
dimethylimidazole and benzimidazole, Polyhedron (2018), doi: https://doi.org/10.1016/j.poly.2018.12.021
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Synthesis, X-ray structures and biological properties of palladium(II)
complexes of 1,2-dimethylimidazole and benzimidazole
Haseeba Sadafa, Imtiaz-ud-Din*a, Syeda Saniya Zahrab, Ihsan-ul-Haqb, Shafqat Nadeema,
Muhammad Nawaz Tahirc, Saeed Ahmadd*, Sohaila Andleeba
aDepartment of Chemistry, Quaid-i-Azam University, Islamabad, Pakistan
bDepartment of Pharmacy, Quaid-i-Azam University, Islamabad, Pakistan
cDepartment of Physics, University of Sargodha, Sargodha, Pakistan
dDepartment of Chemistry, College of Sciences and Humanities, Prince Sattam bin Abdulaziz
University, Al-Kharj 11942, Saudi Arabia
_________________
*Corresponding authors (E.mail: saeed_a786@hotmail.com, drimtiazuddin@yahoo.com)

Abstract
Three palladium(II) complexes with imidazole derivatives, 1,2-dimethylimidazole (1),
benzimidazole (2) and 2-phenylimidazole (3) were prepared and characterized by thermal and
spectral analyses. The crystal structures for two of them (1 and 2) were determined by X-ray
crystallography. The palladium(II) ion in both complexes is bound to two nitrogen atoms of
imidazoles and two chloride ions at trans positions, adopting a nearly regular square planar
geometry. The complexes were screened for various biological activities including antimicrobial,
antioxidant and anti-diabetic properties. The biological activities of the complexes are more
effective as compared to the respective ligands. The complexes exhibited moderate antimicrobial
activities but they were not good as antioxidants. However, their anti-diabetic effects with
respect to the standard are significant.
Keywords: Palladium(II); 1,2-dimethylimidazole; benzimidazole; X-ray structure; biological
activity

1. Introduction
Imidazole and its derivatives are a class of heterocyclic compounds with a number of
pharmacological and industrial applications [1-5]. They represent the most dynamic class of
chemicals owning widespread anti-tumor, anti-bacterial, anti-fungal, anti-viral and anti-diabetic
activities with fewer side effects [2-4]. They can be viewed as models for metal-histidine
coordination in biological systems [6]. The resemblance between the chemistry of Pd(II) and
Pt(II) complexes triggers the significant interest in the study of palladium(II) complexes [7,8]
since the platinum(II) compounds are well-known for the treatment of various types of cancers
[9-14]. Palladium(II) complexes of imidazoles are known to exhibit significant anti-microbial
and anti-tumor activities [15-18] as well as promising catalytic applications [19-26]. Palladium
complexes bearing imidazole-based chelating ligands have been tested in the Heck reaction
[27,28]. The (CH3CN)2PdCl2/4mim system (where mim = 1-methylimidazole) catalyzed the
Suzuki reaction at room temperature. Although slower than the reaction at higher temperatures,
this can be useful for thermally sensitive substrates [23].
The potential applicability of palladium complexes containing imidazole ligands for
medicinal purposes prompted us to study their structure and biological activity. Therefore, in the
present work, we have synthesized palladium(II) complexes with three imidazole ligands,
namely, 1,2-dimethylimidazole, benzimidazole and 2-phenylimidazole. The complexes were
characterized by thermal analysis and, IR and NMR spectroscopy. The crystal structures of two
compounds, [Pd(1,2-dimethylimidazole)2Cl2] (1) and [Pd(benzimidazole)2Cl2] (2) are presented,
while that of [Pd(2-phenylimidazole)2Cl2] (3) as DMF solvate is known in the literature [24,25].
The biological properties of the complexes including anti-diabetic effects were also examined.
The study would be helpful to understand the nature of interactions of heavy metals with related
compounds having biological as well as industrial applications. The structures of ligands used
are shown in scheme 1.

1,2-dimethylimidazole benzimidazole
2-phenylimidazole
Scheme 1: Structures of the imidazole ligands used
2. Experimental
2.1. Chemical sources
Palladium chloride (PdCl2) was obtaimed from Degussa AG 40474, Dusseldorf, Germany. 1,2-
dimethylimidazole, benzimidazole and 2-phenylimidazole were purchased from Sigma Aldrich.
2.2. Preparation of Complexes
Potassium tetrachloridopalladate(II), K2[PdCl4] was prepared by reacting PdCl2 with an excess of
KCl in water-methanol medium as described earlier [29].
The palladium-imidazole complexes were obtained by adding 2 equivalents of an
imidazole ligand in 10 mL methanol to a solution of 0.326 g (1 mmol) K2[PdCl4] in 15 mL
water. Mixing resulted in the formation of yellow precipitates instantly or a clear solution in the
case of 2-phenylimidazole. For 1 and 2, a clear yellow solution was obtained upon addition of 5
mL acetonitrile. The solution was stirred for one hour. It was then filtered and kept at room
temperature for slow evaporation. After a few days yellow crystals were obtained, which were
washed with methanol to get fine crystals for analysis. Yield 85-88 %, melting points = 180 (1),
280 (2), 240 (3) °C (decomp.).

Spectroscopic data: - IR (cm-1): 1, ν = 3145, 3124, 2960 (C-H), 1551, 1510 (C=N, C=C), 1290
1050 (C-N);  = 754, 731 (C-H). (1,2-dimethylimidazole, ν = 3140, 3110, 2950 (C-H), 1530,
1505 (C=N, C=C), 1279 (C-N);  = 724, 676 (C-H)); 2, ν = 3202 (N-H), 3136, 2950 (C-H),
1597, 1417 (C=N, C=C), 1250 (C-N);  = 775, 750 (C-H); (benzimidazole, ν = 3112 (N-H),
3060, 2938 (C-H), 1587, 1406 (C=N, C=C), 1244 (C-N);  = 767, 744 (C-H)); 3, ν = 3205 (N-
H), 3115, 2915 (C-H), 1565, 1469 (C=N, C=C), 1111 (C-N);  = 771, 705 (C-H); (2-
phenylimidazole, ν = 3200 (N-H), 3100, 2900 (C-H), 1562, 1460 (C=N, C=C), 1104 (C-N);  =
768, 702 (C-H)).
1
- H NMR (DMSO, TMS, ppm): (1),  = 2.70 (C-CH3), 3.62 (N-CH3), 7.22 (N-CH); (1,2-
dimethylimidazole,  = 2.24 (C-CH3), 3.54 (N-CH3), 6.98 (N-CH); (2),  = 8.70 (N-C-CH), 8.98
(N2-CH), 13.40 (N-H); (benzimidazole,  =  = 7.60 (N-C-CH), 8.23 (N2-CH); (3),  = 7.38 (N-
CH), 13.10 (N-H); (2-phenylimidazole,  = 7.14 (N-CH), 12.5 (N-H).
- 13C NMR (DMSO, TMS, ppm): (1),  = 127.6 (N-CH), 145.9 (N2C); (1,2-dimethylimidazole, 
= 126.0 (N-CH), 144.6 (N2C); (2),  = 139.7 (N-CH), 144.3 (N2C); (benzimidazole,  = 138.6
(N-CH), 142.4 (N2C); (3),  = 126.9 (N-CH), 147.2 (N2C); (2-phenylimidazole,  = 128.3 (N-
CH), 146.0 (N2C).
2.3. Instrumentation
Infrared spectroscopy was performed on Thermo Shimadzu FT-IR spectrophotometer ranging
4000–500 cm-1. Thermogravimetric analysis was executed on Perkin Elmer USA TGA Diamond
1
13
Pyris. The H and CNMR spectra were recorded in DMSO-d using Bruker Avance 300 MHz
6
NMR spectrometer at the frequencies of 300.00 and 75.47 MHz respectively at 300 K. The
chemical shifts for both the nuclei were measured relative to TMS.
2.4. X-ray Structure Determination

Single crystal data collection for complexes 1 and 2 was performed at 296 K on a Bruker Kappa
APEXII CCD diffractometer equipped with a four-circle goniometer and using MoK graphite
mono-chromated radiation. The structures were solved by direct methods with SHELXS-97 [30]
and refined by full-matrix least squares procedures on F2 using the program SHELXL-97 [31].
Molecular graphics were performed using PLATON [32]. The crystal data and refinement details
are presented in Table 1.

Table 1.
Complex
Crystal data and the structure refinement details of compounds 1 and 2.
1
2
Formula
C10H16Cl2N4Pd
369.57
C14H12Cl2N4Pd
Formula Weight
Crystal system
Space Group
a, b, c (Å)
413.58
Orthorhombic
Monoclinic
P21/c
Pbca
6.9627(2),
12.3512(4)
8.4769(3), 13.2577(17), 8.4728(12),
13.7343(17)
, β, γ (o)
V (Å3)
Z
90, 102.3690(10), 90
712.07(4)
90, 90, 90
1542.8(4)
2
4
calc (g/cm3)
1.724
1.781

 (MoK) (mm-1)
F(000)
1.663
1.546
368
816
Crystal size (mm)
Temperature (K)
λ (MoK) (Å)
0.36 x 0.22 x 0.16
296(2)
0.34 x 0.28 x 0.20
296(2)
0.71073
0.71073
2θ range (o)
7.682-56.58
-9:9, -10:11, -13:16
6207, 1725, 0.0290
1725
7.804-51.98
-16:16, -3:10, -12:16
5001, 1470, 0.0264
1470
h, k, l limits
Reflns: Total, uniq., Rint
Observed data [I > 2σ(I)]
Tmin, Tmax
0.0220, 0.0529
1725, 0, 82
0.0193, 0.0504, 1.079
0.26, -0.29
0.0322, 0.0703
1470, 0, 97
0.0232, 0.0610, 1.091
0.40, -0.45
Data/restraints/parameters
R1, wR2, S [I > 2σ(I)]
Largest diff. peak, hole (eÅ–3)

2.5. Biological assessment
2.5.1. Free radical scavenging assay
The capability of the samples to quench the stable 2,2-diphenyl-1-picrylhydrazyl (DPPH) free
radical was also evaluated [33]. An aliquot of 20 µL from test sample (4 mg/mL DMSO) was
mixed with 180 µL of DPPH solution (9.20 mg/100 mL methanol) to attain the final
concentrations of 7.40, 22.22, 66.66, and 200 µg/mL in the reaction mixture. After 30 min of
incubation at 37°C, the absorbance was measured at 515 nm using microplate reader. The
following formula was used to compute % FRSA:
% FRSA = (1-Abs/Abc) ×100
Where Abs and Abc are the absorbance of sample and negative control respectively. The assay
was performed in triplicate by using ascorbic acid as a positive control.
2.5.2. Total antioxidant capacity (TAC)
The colorimetric assay based on Phospho-molybdenum was used to check the total antioxidant
capacity, which is represented as μg equivalent to ascorbic acid (μg AAE/mg of the sample) [34].
A volume of 100 µL of the test compound (4 mg/mL DMSO) was mixed with 900 µL of reagent
(0.6 M sulfuric acid, 28 mM sodium phosphate and 4 mM ammonium molybdate). DMSO was
used as a blank. Then the reaction mixture was incubated in a water bath for 90 min at 95°C.
Upon cooling, the absorbance of the test and standard solutions was measured at 695 nm via
PDA spectrophotometer (8354 Agilent Technologies, Germany). The experiments were
performed in triplicate. Calibration curve of the control (y = 0.0183x + 0.1198, R2 = 0.9597) was
made at absolute concentrations (50, 25, 12.5, and 6.25 μg/mL).
2.5.3. Antibacterial activity
To evaluate the antibacterial potential of the test compounds, disc diffusion method was used
[35]. The refreshed bacterial cultures of Staphylococcus aureus (ATCC-6538), S. epidermidis
(ATCC-12228), Bacillus subtilis (ATCC-6633), Escherichia coli (ATCC-25922) and Klebsiella

pneumoniae (ATCC-1705) with pre-adjusted turbidity were used to make lawns on nutrient agar
plates. Each test extract (5 μL from 10 mg/mL DMSO), standard (gentamicin and cefixime 5 μL
from 4 mg/mL DMSO) and negative control (DMSO, 5 μL) was loaded on sterile paper discs
and placed on the seeded plates. The average diameter of the zone of inhibition of the sample,
standards and control was measured after an incubation period of 24 hours at 37oC. An inhibition
zone ≥ 10 mm in diameter was considered active for the tested samples. The assay was
performed in triplicate.
2.5.4. Alpha amylase inhibition test
The alpha amylase inhibition test was executed to assess the anti-diabetic activity of test samples
according to the reported method with a slight change [36]. The reaction mixture containing 15
μL phosphate buffer (pH 6.8), 25 μL α-amylase enzyme (0.14 U/mL), 10 μL sample (1 mg/mL
DMSO) and 40 μL (2 mg/mL in potassium phosphate buffer) starch solution was incubated at
50oC for 30 min in 96 well plate followed by addition of 20 μL of 1M HCl to stop the reaction.
Afterwards 90 μL of iodine reagent (5 mM iodine, 5 mM potassium iodide in phosphate buffer)
was added to each well. Blank was prepared by adding DMSO and the phosphate buffer instead
of plant extract and enzyme solution respectively, whereas negative control was prepared by
adding DMSO in place of the test extract. Acarbose (250 µM) was used as positive control.
Absorbance of reaction mixture was measured at 540 nm. The activity was expressed as percent
α-amylase inhibition and calculated by the following equation:
% α-amylase inhibition = (Os-On) / (Ob-On) × 100
where 푂푛 = Absorbance of negative control, 푂푠 = Absorbance of sample and 푂푏 = Absorbance
of blank well.
3. Results and Discussion
3.1. Synthesis and Spectroscopic studies

The complexes were prepared by reacting K2[PdCl4] with imidazoles in 1:2 (metal:ligand) molar
ratio in methanol–water mixture using a little acetonitrile to crystallize the products of the
required composition, [PdL2Cl2]. All three complexes were isolated as air-stable and non-
hygroscopic solids. Information about the composition of complex 3 was obtained from thermal
analysis. The thermal decomposition pattern of complex 3 is shown in Figure 1. No weight loss
is observed up to 260 °C. After that the increase in temperature results in decomposition of the
complexes in two successive overlapped steps. The first step with a weight loss of about 60 %
ranges from 260 to 570 °C and this corresponds to the removal of imidazole ligands (calculated
61.9 %). The second step starts near 570 °C and completes at 800 °C. The weight loss of about
16 % (Calculated 15.2 %) indicates the removal of both the chlorine atoms. The end product with
a residual mass of 23.5 % represents the palladium metal (calculated value 22.8 %).
Fig. 1. TGA curve of complex 3

The selected IR frequencies of the ligands and their respective palladium(II) complexes
in the experimental section. In IR spectra of imidazoles, the representative bands are likely to
appear in three frequency regions: ν(N–H, C–H) around 3100 cm-1, ν(C=N) near 1600 cm-1 and ν(C–N)
between 1300 and 1100 cm-1. The C–H bending vibration is detected in the range of 800-700 cm-
1. A frequency swing in these bands reveals the formation of a metal-ligand complex. The
change in frequency is the highest for ν(C=N) bands as this nitrogen is directly involved in bonding
with metal.
13
The particular 1H NMR and C NMR chemical shifts of the ligands and their respective
1
complexes in DMSO-d
6
are listed in experimental part. The H NMR spectra of the complexes
showed less intense signals of imidazole after complex formation and downfield shifts were
observed as compared to the free ligands. The downfield shift is because of the decrease in the π
electron density in these bonds upon coordination.
13
In C NMR spectra of the complexes, the presence of a signal near 140 ppm assignable
to imino carbon is consistent with the coordination of imidazoles to palladium via that nitrogen
atom. The downfield shift in case of N2C resonance is because of a decrease in electron density
around the carbon nucleus after complex formation. The spectroscopic results are in agreement
with the reported data for similar type of compounds [20,21,24,25].
3.2. Crystal structure Description
The crystal structures of complexes 1 and 2 are presented in Figures 2 and 3 respectively. The
selected bond distance and bond angle data are given in Table 2. The Pd atoms in 1 and 2 are
positioned at inversion centers and adopt a square planar geometry attained by coordination of
two imidazole ligands and two chloride ions, oriented at the trans positions. The imidazole
groups behave as N-donors and show a terminal binding. Because of the inversion centers the
Pd/Cl1/N1/Cl1/N1 atoms lie in one plane. The cis-angles of 89.10(4)-90.90(4)o in 1 and
88.69(4)-91.31(4)o in 2, and the trans angles of 180 in both represent an almost ideal square
planar environment (Table 2). The Pd–Cl and Pd–N bond lengths are comparable to those
reported for similar palladium(II) complexes [20,21,25,37-41]. All the C–N bond distances in the
imidazole rings are intermediate between the expected single- and double-bond lengths. They are
shorter than the length of exocyclic N–CH3 bond. The structures of 1 and 2 are nearly matching

to the earlier reported structures of the trans-dichloridobis(1/2-methylimidazole-κN)
palladium(II) [40,41]. Similar to these, in compounds 1 and 2 the imidazole ligands bind through
pyridine nitrogen atoms rather than the pyrrole ones.
Crystal packing in 1 is stabilized by intermolecular C-H…Cl bonding, while in 2 by N-
H…Cl hydrogen bonds. The details of hydrogen bonds are given in Table 3. The bond
parameters are within the range as reported [21,41]. The arrangement of hydrogen bonds results
in the formation a two-dimensional sheet structures. The packing view of 2 is illustrated in
Figure 4.

Fig. 2. The molecular structure and numbering pattern of trans-dichloridobis(1,2-
dimethylimidazole-κN)palladium(II), 1
Fig. 3. The molecular structure and numbering pattern of trans-dichloridobis(benzimidazole-
κN)palladium(II), 2

Fig. 4. The crystal packing for 2 showing formation of a 2D-network with base vector [0 1 0]
and [0 0 1] in the plane (1 0 0). The H-atoms not involved in H-bonding are omitted for clarity.

Table 2. Selected bond lengths (Å) and bond angles (°) for 1 and 2
Bond Lengths
(1)
Bond Angles
Pd1-N1
Pd1-Cl1
N1-C1
2.0144(14)
2.3006(4)
1.380(2)
1.329(2)
1.350(2)
-
Cl1-Pd1-N1
Cl1-Pd1-N1´
Cl1-Pd1-Cl1
N1-Pd1-N1’
Pd1-N1-C1
Pd1-N1-C4
89.10(4)
90.90(4)
180.0
N1-C4
180.0
N2-C4
123.93(12)
128.61(11)
N2-C3
(2)
Pd1-Cl1
Pd1-N1
N1-C1
N1-C7
N2-C6
N2-C7
2.3046
2.008
1.387
1.322
-
Cl1-Pd1-N1
Cl1-Pd1-N1’
Cl1-Pd1-Cl1
N1-Pd1-N1’
Pd1-N1-C1
Pd1-N1-C7
88.69(4)
91.31(4)
180.0
180.0
126.69(15)
126.69(16)
1.338

Table 3. Hydrogen bond parameters for 1 and 2 (Å, o)a
Donor-H…Acceptor
D-H
H…A
D…A
 D-H…A
(1)
C2–H2…Cl11
C3–H3B…Cl12
C3–H3C…Cl11
C5–H5B…Cl13
0.93
0.96
0.96
0.96
2.94
2.76
2.95
2.91
3.7494(18)
3.654(2)
3.868(2)
3.488(2)
146.9
155.0
160.0
119.8
(2)
N2–H2A…Cl1
0.86
2.44
3.209(2)
149.6
aSymmetry codes: 11-X,-1/2+Y,1/2-Z; 2+X,3/2-Y,-1/2+Z; 32-X,1-Y,1-Z

3.3. Biological studies
The biological potential of complex 1 as well as the two related complexes, 2 and 3 was
estimated by measuring a number of biological activities, which are explained below.
3.3.1. Free radical scavenging assay (% FRSA) and total antioxidant capacity (TAC)
The results of anti-radical activity of compounds are presented in Table 4. This method depends
on the reduction of the purple colored DPPH, by accepting electron or hydrogen radical from
donor antioxidant, to a stable yellow-colored diphenylpicrylhydrazine molecule [42]. Overall,
the complexation has increased the free radical scavenging ability of the newly formed
compounds. The complex 1 showed the highest DPPH free radical scavenging potential with
complex 2 exhibiting slightly different value. The TAC (µg AAE/mg compound) of all the
ligands and their respective complexes is given in Table 4. The method relies on the reduction of
Mo(VI) to Mo(V) by the antioxidant mediators and the consequent formation of a green colored
phosphate/Mo(V) complex with a maximal absorption at 695 nm [42]. In total antioxidant
capacity (TAC) assay, complex 2 showed the highest potential (43.83±0.41 µg AAE/mg
compound), while no or negligible activity was shown by the other complexes. Our observation
is in conformity with a previous study, which reported the significant antioxidant behavior
against DPPH (2,2-diphenyl1-picrylhydrazylradical) by the palladium chloride complexes
bearing the nucleobases but not the nucleobases alone [43]. This proves that the complexation
enhances the formation of the required structural confirmation for DPPH scavenging assay.

Table 4. % Free radical scavenging activity data and total antioxidant capacity for 1-3
% FRSA (%)
TAC (μg AAE/mg DW)
Complexes/ ligands
1L
1
11.40±5.26
26.17±3.57
14.75±4.46
24.85±0.94
11.52±1.56
15.81±1.99
0
0
2L
2
0
43.83±0.41
15.73±0.68
4.94±0.59
3L
3
(Total antioxidant capacity (μg AAE/mg DW) and free radical scavenging activity (%) of compounds. IC50 of
ascorbic acid is found to be 21.8 μg/mL. Values are presented as mean ± Standard deviation (n = 3). 1 =
Pd(dimethylimidazole)2Cl2 and 1L is the corresponding ligand, 2 = Pd(benzimidazole)2Cl2 and 2L is the
corresponding ligand, and 3 = Pd(2-phenylimidazole)2Cl2 and 3L is the corresponding ligand.
3.3.2. Antibacterial activity
Out of all the compounds tested, the palladium complexes were found to be more active than
their respective ligand counterparts as shown in Figure 5. The antibacterial activity demonstrated
the following order of activity; complex 1 > complex 3 > complex 2. The most potent activity
was found against S. epidermidis by complex 1 with ZOI 17.33 ± 0.58 mm. The presence of
palladium metal has been linked with increase in antibacterial potential. This is in accordance
with another recent study [44], which showed palladium complexes of steroidal
thiosemicarbazones as potent antibacterials than steroidal thiosemicarbazones alone. The
antibacterial effect in case of complex 1 may be attributed to the presence of alkyl group on
imidazole ring which has been shown to be responsible in one of the structure activity
relationship studies performed previously [45].

Fig. 5. Antibacterial activities of the imidazoles and their respective palladium complexes(1-3).
Zone of inhibition (ZOI) includes the diameter of disc (6 mm). The positive control in case of S.
epidermidis is gentamicin while for all others is cefixime. Values are presented as mean ±
Standard deviation (n = 3).
3.3.3. Alpha amylase inhibition assay
Inhibitors of α-amylase reduce the glucose peaks that can occur after a meal, slowing the speed
with which amylase can convert starch to simple sugars until the body can deal with it. This is of
importance in people with diabetes, where low insulin levels prevent extracellular glucose from
being cleared quickly from the blood [46]. In alpha amylase inhibition assay significant results
were obtained. The % alpha amylase inhibition with the IC50 values of all the samples and
standard are compared in Figure 6. It was found that palladium complexes of imidazole
derivatives exhibited the promising antidiabetic potential as compared to their respective ligands.
Anti-diabetic activity of the complexes was found to increase considerably as compared to the
ligands. The complex 1, 2 and 3 demonstrated IC50 as low as 7.04, 11.11 and 7.06 μg/mL
respectively which is far less than the standard used (acarbose, IC50 = 33.73 μg/mL). The reason
might be associated with the specific configuration which is achieved after the complexation of

palladium chloride with the different imidazole derivatives. This has been reassured in a study of
imidazole derivative where in vivo model of diabetes was used but did not find any significant
antidiabetic effect but after complexation with the copper (II) acetate ligand the hypoglycemic
effect was dramatically increased [47].

Fig. 6. The α-amylase inhibition assay for (1-3) and their ligands. Acarbose is used as a standard.
Values are presented as mean ± Standard deviation (n = 3).
4. Conclusion
Here, we describe the synthesis and crystal structures of two palladium(II) complexes of
imidazole ligands. The crystal structures of the complexes (1 and 2) revealed a nearly regular
square planar geometry around palladium. The prepared complexes (as well as a known
complex, 3) were tested for various biological properties. Biological studies demonstrate the
enhancement of the activities after complexation of imidazole in case of antioxidant,
antibacterial and alpha amylase inhibition assays. The anti-diabetic property of the complexes is
far greater than acarbose, the standard drug for diabetes mellitus type II.
diabetic effects of the complexes
anti-
Supplementary Material

The crystal data of compounds 1 and 2 is deposited at the Cambridge Crystallographic Data
Centre and has been assigned the CCDC numbers 1832504-1832505 respectively. Crystal data
can be received free of charge on application to CCDC 12 Union Road, Cambridge CB21 EZ,
UK. (Fax: (+44) 1223 336-033; e-mail: data_request@ccdc.cam. ac.uk).
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Synthesis, X-ray structures and biological properties of palladium(II)
complexes of 1,2-dimethylimidazole and benzimidazole
Haseeba Sadaf, Imtiaz-ud-Din, Syeda Saniya Zahra, Ihsan-ul-Haq, Shafqat Nadeem, Muhammad
Nawaz Tahir, Saeed Ahmad, Sohaila Andleeb

Synthesis, X-ray structures and biological properties of palladium(II)
complexes of 1,2-dimethylimidazole and benzimidazole
Haseeba Sadaf, Imtiaz-ud-Din, Syeda Saniya Zahra, Ihsan-ul-Haq, Shafqat Nadeem, Muhammad
Nawaz Tahir, Saeed Ahmad, Sohaila Andleeb
Three palladium(II) complexes with imidazole derivatives, 1,2-dimethylimidazole (1),
benzimidazole (2) and 2-phenylimidazole (3) were prepared and crystal structures for two of
them (1 and 2) were determined by X-ray crystallography. The palladium(II) ion in both
complexes is bound to two nitrogen atoms of imidazoles and two chloride ions at trans positions,
adopting a nearly regular square planar geometry. The complexes were screened for various
biological activities including antimicrobial, antioxidant and anti-diabetic properties. The
complexes exhibited moderate antimicrobial activities but their anti-diabetic effects with respect
to the standard are significant.