Novel pyridinedicarboxamide derivatives and a polymeric copper(II) complex: Synthesis, structural characterization, electrochemical behavior, catalytic and cytotoxic studies

Article abstract of DOI:10.1016/j.ica.2017.02.023

Two new amide-based ligands, N,N′-bis(2-carboxylphenyl)-2,6-pyridinedicarboxamide (L1), N,N′-bis(2-carboxyphenyl ethyl ester)-2,6-pyridinedicarboxamide (L2) and a one-dimensional polymeric complex from reaction between (L1) and Cu(NO₃)₂·3H₂O with the formula of {[Cu(CPCP)](DMAP)·3H₂O}_n [where DMAP is 4-dimethylaminopyridine and CPCP is 6-(2-carboxylatophenylcarbamoyl) picolinate] were synthesized. These compounds have been characterized spectroscopically and their molecular structures were determined by single-crystal X-ray diffraction. Also, thermal analysis (TGA/DTA) was carried out on complex (3). Possible mechanisms were proposed for esterification and hydrolysis of (L1). Study of electrochemical behavior of compounds using cyclic voltammetry at E of ?1.0 to +1.0?V showed two redox couple for complex (3) corresponding to Cu(I)/Cu(0) and Cu(II)/Cu(I) at E^0′ of ?0.26 to 0.08?V versus Ag/AgCl. Ligands (L1) and (L2) did not exhibit any wave in the investigated potential range. Also, complex (3) was evaluated for catalytic activity on the oxidation of aromatic and aliphatic alcohols by changing parameters such as the amount of catalyst, oxidant and also reaction temperature. The outstanding catalytic performance of complex (3) was confirmed by selective conversion of alcohols to the corresponding aldehydes. The cytotoxic effect of compounds was evaluated using oxaliplatin as a positive control against MCF7 (a human breast cancer), HT29 (a human colon adenocarcinoma) and βTC (a mouse beta pancreatic) cell lines. The cancerous cells exhibited the highest sensitivity to compound (3) with IC50 values about 1–10?μM.

Full text of DOI:10.1016/j.ica.2017.02.023

Inorganica Chimica Acta 461 (2017) 221–232
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Research paper
Novel pyridinedicarboxamide derivatives and a polymeric copper(II)
complex: Synthesis, structural characterization, electrochemical
behavior, catalytic and cytotoxic studies
⇑
Sara Abdolmaleki, Mohammad Ghadermazi
Department of Chemistry, Faculty of Science, University of Kurdistan, Sanandaj, Iran
a r t i c l e i n f o
a b s t r a c t
0
0
Article history:
Received 10 August 2016
Received in revised form 16 February 2017
Accepted 19 February 2017
Available online 27 February 2017
Two new amide-based ligands, N,N -bis(2-carboxylphenyl)-2,6-pyridinedicarboxamide (L1), N,N -
bis(2-carboxyphenyl ethyl ester)-2,6-pyridinedicarboxamide (L2) and a one-dimensional polymeric complex
from reaction between (L1) and Cu(NO
3
)
2
ꢀ3H
2
O with the formula of {[Cu(CPCP)](DMAP)ꢀ3H
2 n
O} [where
DMAP is 4-dimethylaminopyridine and CPCP is 6-(2-carboxylatophenylcarbamoyl) picolinate] were syn-
thesized. These compounds have been characterized spectroscopically and their molecular structures
were determined by single-crystal X-ray diffraction. Also, thermal analysis (TGA/DTA) was carried out
on complex (3). Possible mechanisms were proposed for esterification and hydrolysis of (L1). Study of
Keywords:
Amide-based ligands
One-dimensional polymeric complex
Electrochemical behavior
Catalytic activity
electrochemical behavior of compounds using cyclic voltammetry at E of ꢁ1.0 to +1.0 V showed two
0
redox couple for complex (3) corresponding to Cu(I)/Cu(0) and Cu(II)/Cu(I) at E0 of ꢁ0.26 to 0.08 V versus
Ag/AgCl. Ligands (L1) and (L2) did not exhibit any wave in the investigated potential range. Also, complex
(3) was evaluated for catalytic activity on the oxidation of aromatic and aliphatic alcohols by changing
parameters such as the amount of catalyst, oxidant and also reaction temperature. The outstanding cat-
alytic performance of complex (3) was confirmed by selective conversion of alcohols to the corresponding
aldehydes. The cytotoxic effect of compounds was evaluated using oxaliplatin as a positive control
against MCF7 (a human breast cancer), HT29 (a human colon adenocarcinoma) and bTC (a mouse beta
pancreatic) cell lines. The cancerous cells exhibited the highest sensitivity to compound (3) with IC50 val-
Cytotoxicity
ues about 1–10 lM.
Ó 2017 Elsevier B.V. All rights reserved.
1
. Introduction
For a long time coordination chemistry of organic amides have
them to be investigated for the synthesis of supramolecular struc-
tures [8]. The steric environment and electronic properties of ami-
dic ligands are affected by changing acyl groups or substituents on
the nitrogen atom. Many amidic complexes of transition metals
and rare-earth metals were studied due to their high activities in
catalytic transformations, ring-opening polymerization of lactones,
oligomerization and polymerization of ethylene and insertion reac-
tions [9]. Formation of metal complexes with acidic organic
ligands, in which the acid group is usually a hydroxide, an amide
NH, or a thiol, is facilitated via the deprotonation of the ligand by
the addition of a base such as triethylamine, sodium hydride, or
use of the corresponding metal acetate [10]. The high donor ability
of tertiary amides such as DMA and DMF (which are usually used
as solvent) makes it possible for them to coordinate with metal
ions in many complexes, directly [11]. On the other hand, metal
ions with capability of substituting for amidic hydrogen can coor-
dinate strongly to the amide group [12]. The molecular geometries
are affected by the bulky amide groups in these structures [13].
been attracted much attention of inorganic chemists as an impor-
tant part of current chemical problems [1–3]. Molecules containing
the amide functionality are a class of compounds with variety of
applications in different fields of chemistry and biochemistry.
The favorable chemical properties which led to more accurate
study of these compounds include variable bonding modes for
complexation of metal ions [4], stabilization of metal ions in their
different oxidation states [5] and selective extraction of metal ions.
From the point of biochemistry, amidic linkages are investigated as
the main building units in natural macromolecules such as pro-
teins and polypeptides [6] and synthetic macromolecules such as
Ò
nylons and Kevlar [7]. The versatile coordination behavior and
potential hemilability of hybrid ligands containing (N, O) made
⇑
Corresponding author.
E-mail address: mghadermazi@yahoo.com (M. Ghadermazi).
http://dx.doi.org/10.1016/j.ica.2017.02.023
020-1693/Ó 2017 Elsevier B.V. All rights reserved.
0

2
22
S. Abdolmaleki, M. Ghadermazi / Inorganica Chimica Acta 461 (2017) 221–232
Multidentate heterocyclic ligands of pyridylcarboxamides have
AgCl/3 M KCl and platinum wire as reference and counter electrode
respectively and a GC as working electrode. The working electrode
was polished with aluminum oxide powder on chamois leather
and the electrolyte was deoxygenated with nitrogen gas prior to
the analysis.
an important position in biochemistry and coordination chemistry.
Several researches have been carried out on bonding and structural
motifs involving at this class of ligand; from isolated macrocycles
and helicates to dynamic porous frameworks [14]. The regular
hydrogen bonding of the amide groups can be used for a special
design contributing to the robustness of the frameworks and their
thermal stability [15]. A large number of high-valence copper com-
plexes with amide-based ligands were investigated as biomimetic
models and catalytic oxidants. The study of coordination structures
2
2
.2. Synthesis procedures
0
.2.1. Synthesis of N,N -bis(2-carboxylphenyl)-2,6-pyridine-
dicarboxamide (L1)
Synthetic route of compounds are displayed in Scheme 1. At
first, anhydrous thionyl chloride (25 mL) was added to pyridine-
2
+/3+
of Cu
complexes containing amidic ligands demonstrated that
N
amide donors are effective in bringing out and stabilizing the high
oxidation state of a metal ion [16].
2
,6-dicarboxylic acid (1 mmol, 0.167 g) and refluxed at 80–90 °C
Many transition metal complexes possess capability of enhanc-
ing cellular radiation damage both in vitro and in vivo. Copper(II)
ion was studied to modify the radiation response in both mam-
malian and bacterial cells. The radiosensitizing mechanism in
mammalian cells suggested the involvement in reduction of cop-
per(II) to copper(I). Recently, it was recognized that the radiosensi-
tization process may be related to the radiation induced DNA
damage, biological damage sensitized by copper ions involve
nucleobases and different structure of copper complexes which
might bind with double-helical DNA and promote double-strand
DNA damage [17]. Although many transition metal complexes
have been synthesized and their applications were investigated
in various fields [18–20], the biological relevance and rich catalytic
activity of copper complexes containing amidic nitrogen donors
encouraged us to prepare such compounds. For example copper
under argon atmosphere for 3 h until a clear yellow solution was
obtained. The excess thionyl chloride was removed under reduced
pressure. The product was dried in vacuum, cooled and obtained
white precipitate was dissolved in dichloromethane (15 mL) and
then, 2-aminobenzoic acid (2 mmol, 0.274 g) in dry pyridine
(
20 mL) was added to it. The color of the solution is changed slowly
from dark green to brown, with occasional stirring. The solution
was stirred overnight at room temperature and during the time
period light yellow precipitate was formed. The precipitate was fil-
tered off, washed with water, dried in the air and recrystallized
from methanol. Yield (89%). M.p: 279 °C. Found (calc. for
C
21
H
15
N
3
O
6
): C 62.11 (62.23), H 3.55 (3.70), N 10.49 (10.37)%.
ꢁ1
Selected IR bands (KBr pellet, cm ): 3446 m (
m
NH), 1693 s,
+
1
660 s (
m
3
CO), UV–Vis: kmax (CH OH, nm), 235. EI MS: m/z 405, M .
(
[
II) complexes in addition to their effects on cancer treatment
21–23], can be effective as catalysts for the oxidative organic
0
2
.2.2. Synthesis of N,N -bis(2-carboxyphenyl ethyl ester)-2,6-pyridine-
dicarboxamide (L2) compound (L1) (0.5 mmol, 0.203 g) was dissolved
in ethanol (30 mL) and sulfuric acid was added to it (100 L)
transformations involving the oxidation of alcohols, alkanes, alke-
nes and thioethers [24].
l
The solution was stirred 10 min at room temperature. The cubic
These results, along with our interest to design new compounds
with catalytic and cytotoxic activity, led us to synthesize and study
of new amidic ligands from the reaction of pyridine-2,6-dicar-
boxylic acid and 2-aminobenzoic acid and also, a Cu(II) complex
from (L1) [25]. It is noteworthy that despite high stability of amide
groups [26], X-ray studies exhibited that one of the amidic bonds
was hydrolyzed during the complexation of ligand (L1) [27] and
an unsymmetrically polymeric Cu(II) complex was synthesized.
In this paper, possible mechanisms and some effective factors on
the hydrolysis of amides are discussed.
yellow single crystals were formed after 15 days. Yield (70%). M.p:
2
87 °C. Found (calc. for C25
25 3 7
H N O ): C 62.81 (62.63), H 5.43 (5.21),
ꢁ1
N 8.64 (8.76)%. Selected IR bands (KBr pellet, cm ): 3351 m (
m
NH),
1
4
733 s, 1660 s (
79, M .
3
mCO), UV–Vis: kmax (CH OH, nm), 227. EI MS: m/z
+
2
.2.3. Synthesis of {[Cu(CPCP)](DMAP)ꢀ3H
Under aerobic conditions, aqueous solution of DMAP
0.48 mmol, 0.058 g) was added to a stirring aqueous solution of
2 n
O} (3)
(
ligand (L1) (0.12 mmol, 0.048 g). The obtained suspension was stir-
red at 70 °C for 2 h until a light yellow solution was produced. Then
2
. Experimental
aqueous solution of Cu(NO
3
)
2
ꢀ3H
2
O (0.12 mmol, 0.028 g) was
added and the mixture was refluxed at 100 °C for 2 h and evapo-
rated to dryness. The crude product was recrystallized from distil-
lated water as green needle-like crystals. Yield (71%). M.p: 289 °C.
2.1. Materials and apparatus
Pyridine-2,6-dicarboxylic acid, 2-aminobenzoic acid, 4-
23 4 8
Found (calc. for C21H N O Cu): C 48.15 (48.27), H 4.31 (4.40), N
dimethylaminopyridine (DMAP), thionyl chloride, hexanol, benzyl
alcohol and its derivatives were purchased from the commercial
sources and used as received. The solvents were distilled for all
synthetic works. Melting points were obtained on an Electrother-
mal IA-9100 apparatus. The FT-IR spectra were recorded on a Bru-
ker Vector 22 FT-IR spectrometer using KBr pellets. Electronic
spectra were recorded on Specord 210, Analytik Jena spectropho-
tometer in the range of 200–900 nm at room temperature. Micro-
analyses (C, H, N) were measured with a Perkin-Elmer 2004(II)
ꢁ
1
1
1
0.69 (10.72)%. Selected IR bands (KBr pellet, cm ): 1647 s,
+
3
604 s (mCO), UV–Vis: kmax (CH OH, nm), 231. EI MS: m/z 522, M .
2.3. X-ray crystallography
The X-ray measurement of single crystal of compounds (L1),
(L2) and (3) were carried out using a Bruker SMART APEX II diffrac-
tometer equipped with a CCD area detector at 298 K, with gra-
1
elemental analyzer. The H NMR spectra (400 MHz) were obtained
phite-monochromated Mo-K
a
radiation, k = 0.71073 Å. All
from Bruker Ultrashield 400 spectrometer. Thermal behavior was
measured with a PL-1500 TGA apparatus with heating rate of
refinements were done by the full-matrix least-squares method
on F using the SHELX-97 program and absorption corrections
2
1
0 °C/min in N
2
atmosphere. The mass spectroscopy (MS) was
were performed using the SADABS program [28a–e]. Software
including Bruker APEX II (data collection and cell refinement)
and WinGX (publication material) were properly employed [29].
The molecular graphic programs including DIAMOND [30] and
MERCURY were used [31]. The crystal and structural refinement
data for compounds are given in Table 1.
determined using an Agilent (USA) spectrophotometer. Electro-
chemical experiments were performed using a mAUTOLAB modular
electrochemical system (ECO Chemie, Ultrecht, the Netherlands)
equipped with a PGSTAT type III module driven by GPES software
in conjunction with a conventional three-electrode system an Ag/

S. Abdolmaleki, M. Ghadermazi / Inorganica Chimica Acta 461 (2017) 221–232
223
O
O
O
O
O
O
N
(i)
(ii)
N
N
NH
HN
OH
OH
Cl
Cl
COOH HOOC
(
L1)
)
i
O
O
i
(
i
i
(
v
)
N
H CH COOC
3
2
NH
H
HN
)
(b)
.
H O
a
(
2
3
CH
2
COOC
(
L2)
O
O
O
O
N
N
N
N
O
N
N
Cu
Cu
.
3H O
2
OOC
COO
OOC
N
n
(3)
Scheme 1. Synthesis route of ligands and polymeric Cu(II) complex. i: SOCl
a) Predicted complex, (b) Formed complex of {[Cu(CPCP)](DMAP)ꢀ3H O}
2
, ii: 2-aminobenzoic acid in dry pyridine, iii: recrystallized in ethanol, iv: Cu(NO
) ꢀ3H
3 2 2
O/DMAP.
(
2
n
.
Table 1
Crystallographic and structural refinement data for compounds (L1), (L2) and (3).
(L1)
(L2)
(3)
Formula
C
21
H
15
N
3
O
6
C
25
H
25
3
N O
7
21 23 4 8
C H N O Cu
Formula weight
Temperature (K)
Wavelength k (Å)
Crystal system
Space group
a (Å)
405.36
298 (2)
0.71069
Orthorhombic
Pbca
18.491(4)
7.5742(15)
26.016(5)
90.00
90.00(3)
90.00
3643.7(13)
8
1.478
2.70–25.00
1680
0.111
479.48
298 (2)
0.71073
522.96
298(2)
0.71073
Monoclinic
P2 /n
Monoclinic
P2 /n
1
1
10.286(2)
7.2038(14)
30.590(6)
90.00
94.80(3)
90.00
2258.7(8)
4
1.410
2.67–25.00
1008
0.104
ꢁ11 ꢂ h ꢂ 12, ꢁ8 ꢂ k ꢂ 8, ꢁ36 ꢂ l ꢂ 36
12,079/3943 [R(int) = 0.0419]
3943/1/326
15.636(3)
6.9522(14)
20.971(4)
90
100.44(3)
90
2242.0(8)
4
1.549
2.65–25.00
1080
1.030
ꢁꢁ18 ꢂ h ꢂ 18, ꢁ8 ꢂ k ꢂ 8, 0 ꢂ l ꢂ 24
7347/3949 [R(int) = 0.0695]
3949/0/312
b (Å)
c (Å)
a
(°)
b (°)
(°)
c
3
Volume (Å )
Z
Density (calc.) (g cmꢁ1)
h ranges for data collection (°)
F(000)
Absorption coefficient (mmꢁ1)
Index ranges
ꢁ21 ꢂ h ꢂ 20, ꢁ9 ꢂ k ꢂ 9, ꢁ30 ꢂ l ꢂ 30
20,731/3196 [R(int) = 0.1133]
3196/0/288
Reflections collected/unique
Data/restraints/parameters
Final R indices [I > 2sigma(I)] R
1
, wR
2
0.0391, 0.0668
0.0515, 0.1328
0.0558, 0.1416
R indices (all data) R
1
, wR
2
0.1288, 0.0827
1.009
0.161, ꢁ0.183
0.0854, 0.1418
0.922
0.210, ꢁ0.447
0.1149, 0.1498
0.921
0.431, ꢁ0.334
2
Goodness of fit on F (S)
Largest diff peak and Hole (e Åꢁ3)
2.4. Typical procedure for the study of catalytic properties
30
lL of hydrogen peroxide (30%) as an oxidant and benzyl alcohol
(
0.5 mmol, 0.05 g) was added to the mixture at room temperature.
To investigate the catalytic activity of complex (3), oxidation of
Also, the reaction was run in the absence of catalyst. Then, by
changing of parameters such as the amount of oxidant from 30
to 65 lL and temperature from 20 to 70 °C, optimized conditions
for oxidation of benzyl alcohol to benzaldehyde was evaluated.
After finding the optimized conditions for benzyl alcohol, oxidation
primary alcohols into the corresponding carbonyl compounds was
carried out [32]. Benzyl alcohol was selected as a model substrate
for oxidation process. As an initial test, different amounts of com-
plex from 0.01 to 0.05 g in acetonitrile solvent were mixed with

2
24
S. Abdolmaleki, M. Ghadermazi / Inorganica Chimica Acta 461 (2017) 221–232
of its derivatives and hexanol (0.5 mmol substrate) were studied in
the same way. The reaction progress was monitored by TLC in a
regular alternative time. After completion of the reactions and
removing of the solvent, the hemogeneous catalyst was separated
from the reaction mixture by addition of water (5.0 mL). Then, the
organic phase was separated by addition of chloroform (10.0 mL)
and dried over Na
phy on silica gel (ratio of eluent: hexane/ethyl acetate from 1:10 to
:5). Yields were obtained by weighting of isolated products. All
2 4
SO . The product was purified by chromatogra-
1
1
products were known by MS and H NMR spectroscopy [9,24].
2.5. Cell culture and cytotoxicity assays
MCF7 (a human breast cancer), HT29 (a human colon adenocar-
cinoma) and bTC (a mouse beta pancreatic) cell lines were pro-
vided from the Pasteur Institute (Iran), in this study. Cells were
2
grown in 25 cm culture flasks using DMEM (Gibco, Germany) sup-
plemented by 10% (v/v) FBS (fetal bovine serum) and penicillin/
streptomycin (100 U/mL, 100 mg/mL) at 37 °C in a humidified
0
Fig. 1. Ball and stick diagram of the X-ray crystal structure of N,N -bis(2-
atmosphere of 5% CO
trypsin–ethylenediamine tetra acetic acid (EDTA-PBS) solution
Ben Yakhte, Iran). MCF7, HT29 and bTC cells were incubated into
2
. They were sub-cultured regularly using of
carboxylphenyl)-2,6-pyridinedicarboxamide, (L1), showing atomic numbering
scheme with 50% probability.
(
9
2
4
6-well tissue culture plates at a density of 5 ꢃ 10 cells/well in
00 L of complete media at 37 °C and below 5% CO in a humid-
l
2
3. Results and discussion
ified incubator allowing the cell adhesion for 24 h. Stock solutions
of (L1), (L2) and (3) were prepared in DMSO (below 0.5%) [21] and
3.1. X-ray diffraction studies
diluted accordingly to concentrations 0.1 –100
water). Then 20 L of the solutions were added to each well and
plates were incubated for 48 h. Also, 20 L (5 mg/mL) of MTT (3-
4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide)
reagent was added to each well. The cells were incubated at
7 °C in a CO incubator for three or four hours. After the incuba-
tion period, the medium was removed and 200 L DMSO added
into each well to dissolve the produced formazan crystals by sev-
eral pipetting up and down. The absorbance values at 540 nm were
determined using an ELISA reader (Bio-Rad, Model 680, USA) [33].
The viability percent was obtained by dividing absorbance of the
treated group to the absorbance of the control group, multiplied
by 100 and results are expressed as IC50 (the concentration
required to kill 50٪ of cells). Oxaliplatin was chosen as a positive
reference. Untreated cells were run in each assay as the negative
control group. All the experiments were performed in triplicate
and data is registered as mean ± S.E.M [27].
lM (by distillated
l
3.1.1. Crystal structure of compound (L1)
l
To determinate the geometry of compounds, single crystal X-
ray analyses was performed for them. The procedure adopted in
the synthesis of compounds is outlined in scheme 1.
Ligand (L1) has been crystallized in orthorhombic Pbca space
group with eight molecules in the unit cell. A summary of crystal-
lographic data is indicated in Table 1. Selected bond lengths and
angles are presented in Table 2. The X-ray crystal structure of
(L1) with atomic numbering scheme is represented in Fig. 1. On
(
3
2
l
2.6. Statistical analysis
One-way analysis of variance (ANOVA) followed by Tukeyˊs test
(
GraphPad version 5.0; GraphPad Software Inc, San Diego, CA) was
used to obtain the difference between means. The value about
P < 0.05 was considered to be statistically significant. Data are pre-
sented as mean ± standard error in the results section.
Table 2
Selected bond lengths (Å) and angles (°) for (L1).
Bond lengths
#
1
N(3)–C(14)
1.350(4)
1.224(3)
1.302(4)
1.416(3)
N(1)–C(8)
N(1)–C(7)
C(3)–C(4)
O(4)–C(14)
1.347(4)
1.403(4)
1.380(4)
1.212(3)
O(2)–C(1)#
2
O(1)–C(1)#2
N(3)–C(15)
Bond angles
#
1
#1
O(4)–C(14)–N(3)
125.8(3)
120.9(3)
122.4(3)
123.7(3)
N(2) –C(9)–C(8)
118.2(3)
123.1(3)
124.8(3)
124.5(3)
O(5)# –C(21)–O(6)
3
#3
N(2) –C(9)–C(10)
#1
#4
O(2)# –C(1)–O(1)
2
#2
O(5) –C(21)–C(20)
O(3)–C(8)–N(1)
#3
O(2)#2–C(1)–C(2)
Fig. 2. Hydrogen bonds existing between layers in the unit cell and formation of
2
hydrogen bonding rings as
moieties (OAHꢀ ꢀ ꢀO), for N,N -bis(2-carboxylphenyl)-2,6-pyridinedicarboxamide,
R
2
0
(8) between carboxylic acid functional groups
Symmetry codes: #1: ꢁx + 1/2, y + 1/2, z; #2: ꢁx + 1, ꢁy, ꢁz + 1; #3: ꢁx + 1, ꢁy + 1,
z + 1; #4: ꢁx + 1/2, y ꢁ 1/2, z.
ꢁ
(L1).

S. Abdolmaleki, M. Ghadermazi / Inorganica Chimica Acta 461 (2017) 221–232
225
the base of crystallographic data, bis-amide structure of the com-
Table 3
Selected bond lengths (Å) and angles (°) for (L2).
pound (L1) reveals cis and trans geometries for the pyridine nitro-
gen to both NH and carbonyl groups, respectively. These groups are
anticlinal and dihedral angles of the O(3)–C(8)–C(9)–N(2) and O
Bond lengths
N(2)–C(8)
N(2)–C(7)#1
O(5)–C(21)
N(3)–C(9)
1.354(3)
1.398(3)
1.331(3)
1.347(3)
N(3)–C(13)
N(1)–C(15)
C(7)–C(2)#2
O(1)–C(8)
1.337(3)
1.420(3)
1.414(4)
1.219(3)
(
4)–C(14)–C(13)–N(2) were observed 167.50 and 174.93° respec-
tively, for them [34]. Also, the angles between the central pyridine
ring with two 2-carboxylphenyl rings are 34.88 and 21.93°. The
obtained angels between the aromatic rings indicate that the
ligand (L1) is not planar. The non-covalent interactions of hydro-
gen bonding in the crystal packing of the compound (L1) link the
fragments of the layer like structure. These bonds with DꢀꢀꢀA dis-
tances ranging from 2.214(3) to 3.625(3) Å are exhibited in the
crystal packing. Hydrogen bonding interactions have important
role in the creation of the supramolecular network in (L1). In this
structure, carboxylic acid functional groups moieties are held by
hydrogen bonds. These interactions lead to formation of hydrogen
Bond angles
O(2)–C(14)–N(1)
O(6)–C(21)–O(5)
O(3)–C(1)–O(4)
O(1)–C(8)–C(9)
124.9(2)
123.7(3)
121.8(2)
120.5(3)
N(2)–C(8)–C(9)
113.2(2)
122.0(3)
122.2(3)
112.9(2)
#1
N(2) –C(7)–C(6)
C(18)#2–C(19)–C(20)
O(4)–C(1)–N(2)#1
#2
Symmetry codes: #1: ꢁx + 1, ꢁy + 1, ꢁz + 1; #2: ꢁx + 1/2 + 1, y + 1/2, ꢁz + 1/2 + 1.
and carbonyl groups, respectively. Also, these groups are anticlinal
and dihedral angles of O(1)–C(8)–C(9|)–N(3) and O(2)–C(14)–C
bonding rings (synthons) as R2
(8) (R for ring, 8 the number of
2
(
13)–N(3) groups are 174.83 and 177.51°, respectively. On the
atoms in the pattern, superscript 2 is the number of acceptor atoms
and subscript 2 is the number of donor atoms) [27]. Hydrogen
bonds existing between layers in the unit cell and the cyclic inter-
actions are presented in Fig. 2. The organized hydrogen bonding
interactions between O(1)–H(1)ꢀ ꢀ ꢀO(2) [symmetry code: ꢁx + 1,
other hand, the angles 2.68 and 41.56° between the central pyri-
dine ring with two 2-carboxyphenyl ethyl ester rings showed that
compound (L2) is not planar [35].
The interactions of hydrogen bonding with DꢀꢀꢀA distances rang-
ing from 2.634(4) to 3.869 (5) Å are observed in the crystal packing
of (L2). These interactions between amide moieties and pyridine
ꢁ
y, ꢁz + 1], O(6)–H(6)ꢀ ꢀ ꢀO(2) and O(6)–H(6)ꢀ ꢀ ꢀO(5) [symmetry
code: ꢁx + 1, ꢁy + 1, ꢁz + 1] and C(18)–H(18)ꢀ ꢀ ꢀO(3) [symmetry
code: x, ꢁy + 1/2, z ꢁ 1/2] contribute to the supramolecular
arrangement (Fig. 2). The bonds of O(1)–H(1)ꢀ ꢀ ꢀO(2) and O(6)–H
fragments (CAHꢀ ꢀ ꢀO) led to the formation of hydrogen bond rings
2
as R
2
(10). The cyclic interactions are displayed in Fig. 4. The hydro-
gen bonding interactions characteristic to the supramolecular
arrangement are including C(10)–H(10)ꢀ ꢀ ꢀO(1) [symmetry code:
x, y, z] and C(4)–H(4)ꢀ ꢀ ꢀO(5) [symmetry code: ꢁx + 1, ꢁy + 2,
ꢁz + 1], in this structure. Also, co-crystallized one water molecule
was observed along with ligand (L2), as disorder.
(
6)ꢀ ꢀ ꢀO(5) are the strongest hydrogen bonds.
3.1.2. Crystal structure of compound (L2)
The crystallographic data indicated that the conversion of car-
boxylic acid groups to ester was done in accordance with predic-
tion for ligand (L2). This Ligand was crystallized in monoclinic
P2 /n space group with four molecules in the unit cell. The sum-
1
3
.1.3. Crystal structure of compound (3)
Compound of {[Cu(CPCP)](DMAP)ꢀ3H
2
n
O} was crystallized from
mary pertinent structural data is displayed in Table 1. The X-ray
crystal structure with atomic numbering scheme is represented
in Fig. 3. Selected bond distances and angles are shown in Table 3.
The configuration of the compound indicated rotation and ori-
entation toward the outside of the molecule in one of 2-car-
boxyphenyl ethyl ester groups. It may be caused by the larger
angle (54.71)° between two 2-carboxylphenyl rings than two 2-
carboxyphenyl ethyl ester rings (43.94)°. Like (L1), cis and trans
geometries are observed for the pyridine nitrogen with both NH
hot water as needle-like green single crystals in space group of
monoclinic P2
of crystallographic data is listed in Table 1. A schematic drawing
1
/n with four molecules in the unit cell. A summary
0
Fig. 4. Formation of hydrogen bonding rings as R2
(10) between amide moieties and
2
Fig. 3. Ball and stick diagram of the X-ray crystal structure of N,N -bis(2-
0
carboxyphenyl ethyl ester)-2,6-pyridinedicarboxamide, (L2), showing atomic num-
pyridine fragments (CAHꢀ ꢀ ꢀO), for N,N -bis(2-carboxyphenyl ethyl ester)-2,6-
bering scheme with 50% probability.
pyridinedicarboxamide, (L2).

2
26
S. Abdolmaleki, M. Ghadermazi / Inorganica Chimica Acta 461 (2017) 221–232
between monomers cause that geometry around each copper ion
to exhibit as a square pyramidal. In the overall structure of the
complex, connectivity and extending is along [010] direction and
polymeric chains are running parallel to the b axis. The intersected
mean planes of the N(1)-pyridine and the N(2)-phenylcarboxylate
rings were observed at 18.21 (4)° and the torsion angles values
indicated at N(2)–Cu–O(3)–C(14) = 1.66 (6), N(1)–Cu–O(1)–C(1) =
ꢁ
172.71(5), Cu–O(3)–C(14)–O(4) = ꢁ170.11(5) and Cu–O(1)–C
(
1)–C(1) = 6.23 (8)°. Also Cu–Cu–Cu angle between the layers was
observed at 81.24 (3)°.
The bond lengths Cu–N(1) = 1.887(5), Cu–O(3) = 1.889(5), Cu–N
(
1
(
1
2) = 1.982(5), Cu–O(1) = 2.039(4) Å and the angles N(1)–Cu–O(3) =
66.70(3), N(1)–Cu–N(2) = 82.30(2), O(3)–Cu–N(2) = 96.20(2), N
1)–Cu–O(1) = 80.70(2), O(3)–Cu–O(1) = 99.46(2), N(2)–Cu–O(1) =
62.50(2)° are comparable to other five-coordinated square pyra-
midal copper(II) complexes [1,36]. Selected bond lengths and
angles are given in Table 4. In the crystal structure, in addition of
the complex, co-crystallized one DMAP molecule and three water
molecules are observed. Hydrogen bonding interactions between
the complex with co-crystallized molecules of DMAP and water
(
OAHꢀ ꢀ ꢀO and OAHꢀ ꢀ ꢀN hydrogen bonds, range from 1.94 to 2.97
2
Å) led to the formation of the hydrogen bonding rings as R
2
(9),
(10). These interactions are shown in Fig. 6b. Strongest
hydrogen bonds are including [O(6)–H(6A)ꢀ ꢀ ꢀO(2){x, y, z}] and
stacking is
3
4
3 4
R (9), R
Fig. 5. Molecular structure of {[Cu(CPCP)](DMAP)ꢀ3H
2 n
O} , (3), showing the atom
numbering scheme with 50% probability of thermal ellipsoids.
[
O(6)–H(6B)ꢀꢀꢀN(3) {ꢁx + 1, ꢁy, ꢁz + 1}]. Also, CAHꢀ ꢀ ꢀ
p
of the complex and labeling of atoms is illustrated in Fig. 5. The
packing pattern is displayed in Fig. 6a. The obtained data of X-ray
investigations reveals that the formed complex is a one-dimen-
sional polymer built up from asymmetric monomeric units in
which the Cu(II) ion is surrounded by five donor atoms. The chela-
tion in each of monomeric units is through two nitrogen (N1, N2)
and two oxygen atoms (O1, O3) of the same monomer and one
oxygen atom (O5) on an adjacent monomer. The zigzag bridging
bonds of [Cu–O(5) = 2.493 (6) Å {ꢁx + 1/2, y ꢁ 1/2, ꢁz + 1/2 + 1}]
observed between C(20)–H(20C) and (N3, C15–C19) of DMAP rings
with distance of 3.686 Å and angle of 119.11° (Fig. 7).
3.2. Spectroscopic studies
The IR spectra of the ligands (L1) and (L2) exhibited that the
stretching vibrations of amide carbonyl groups were appeared as
ꢁ1
strong absorption band at 1660 cm
for both the ligands [1].
While, the carbonyl groups stretching vibrations of
Fig. 6. a) Hydrogen bonds existing between layers in the unit cell; b) Formation of hydrogen bonding rings as R2
DMAP molecule and three water molecules (OAHꢀ ꢀ ꢀO and OAHꢀ ꢀ ꢀN), for complex (3).
(9), R3 (9), R4
(10) between complex, co-crystallized one
3 4
2

S. Abdolmaleki, M. Ghadermazi / Inorganica Chimica Acta 461 (2017) 221–232
227
Table 4
Selected bond lengths (Å) and angle (°) for (3).
Bond lengths
Cu–N(1)
1.887(5)
1.982(5)
2.039(4)
1.889(5)
2.493(6)
1.255(8)
1.244(8)
1.272(8)
C (14)–O(4)
N(1)–C(6)
1.253(8)
1.322(8)
1.344(8)
1.356(8)
1.402(8)
1.315(10)
1.470(10)
1.475(10)
N(3)–C(17)#2
C(5)–H(5)
C(20)–H(20C)
C(2)–C (3)
1.366(11)
0.9300
0.9600
1.379(8)
1.390(9)
1.366(10)
0.8501
Cu–N(2)#1
Cu–O(1)
N(1)–C(2)
Cu–O(3)
N(2)–C(7)#1
N(3)–C(8)
Cu–O(5)#1
O(3)–C(14)
O(2)–C(1)
O(1)–C(1)
C(5)–C (6)
N(4)–C (19)
N(4)–C (21)
N(4)–C(20)
C(10)–C(11)#3
O(7)–H(7A)
O(8)–H(8B)
0.8499
Bond angles
N(1)–Cu(1)–N(2)#1
N(1)–Cu(1)–O(1)
N(2)#1–Cu(1)–O(1)
N(1)–Cu(1)–O(3)
N(2)#1–Cu(1)–O(3)
O(1)–Cu(1)–O(3)
C(14)#2–O(3)–Cu(1)
C(1)–O(1)–Cu(1)
82.30(2)
80.70(2)
162.50(2)
166.70(3)
96.20(2)
99.46(19)
128.00(5)
128.00(5)
C(7)#1–N(2)–Cu(2)#1
C(6)–N(1)–Cu(1)
C(2)–N(1)–Cu(1)
114.2(4)
118.4(4)
119.10(4)
123.50(6)
122.30(4)
123.50(6)
117.70
N(4)–C(21)–H(21B)
N(1)–C(6)–C(7)#1
N(1)–C(6)–C(5)
109.50
112.80(6)
120.30(6)
121.40(7)
123.20(8)
116.60(8)
120.70
#
1
#4
C(7) –N(2)–C(8)
N(4)–C(19)–C (18)
N (3)–C(15)–C(16)
#1
C(8)–N(2)–Cu(1)
#
1
#2
C(7) –N(2)–C (8)
N(3) –C(17)–H(17)
C(16)–N(3)–C(17)
#2
#4
C(17) –C(18)–H(18)
N(4)–C(21)–H(21A)
109.50
C(1)–C(2)–C(3)
128.70(6)
Symmetry codes #1: ꢁx + 1/2, y ꢁ 1/2, ꢁz + 1/2 + 1; #2: ꢁx + 1, ꢁy, ꢁz + 1; #3: ꢁx + 1, ꢁy, ꢁz + 2; #4: ꢁx + 1, ꢁyꢁ1, ꢁz + 1.
ꢁ5
tion 3 ꢃ 10 M in methanol, with an absorption maxima near 235
⁄
and 227 nm, assigned to
p?
p
transition of the aromatic ring and
⁄
shoulder at 327 and 311 nm corresponding to n?
p
transition of
the C@O chromophore for (L1) and (L2), respectively [42,43]. For
studies of metal complexation, electronic absorption spectrum of
ꢁ3
the compound (3) was performed at concentration 3 ꢃ 10 M in
methanol and it indicated only one broad d-d transition band at
ꢄ656 nm (e = 69 mol L cm ), corresponding to the 2
ꢁ
1
ꢁ1
E
g
? T2g
2
transition [41], that suggests octahedral configuration for the cop-
per ion. The change in configuration around the copper ion in solu-
tion with obtained square pyramidal geometry of X-ray in solid
state, can be justified by the coordination of one molecule of sol-
vent in axial position of copper ions [27]. The other expected band
at 345–391 nm is attributed to the charge transfer transitions. Also,
⁄
⁄
p?p and n?p intra-ligand charge transitions at 231 and 272 nm
were observed for the complex (3), which exhibited hypsochromic
⁄
shift about 55 nm in absorption band of n?
p
of the complex (3)
than the ligand (L1). The observed shift could be due to the dona-
tion of a lone pair of carbonyl electrons of pyridine-2,6-dicarbonyl
to copper(II) ion [26], corresponding to the obtained structure of X-
ray crystallography. The electronic impact mass spectrum provides
good evidence for the molecular formula of the synthetic com-
pounds [44]. The mass spectra of the ligands (L1) and (L2) showed
Fig. 7. CAHꢀ ꢀ ꢀ
p stacking between C(20)–H(20C) and (N3, C15-C19) of DMAP rings
for complex (3).
2
-carboxylphenyl and 2-carboxyphenyl ethyl ester rings were indi-
cated as a weak band close to amide carbonyl group at 1693 and
ꢁ1
3 6
m/z peaks at 405 and 479 that corresponded to C21H15N O and
C25H25N O moieties, respectively. The selected series of peaks
3 7
1
733 cm for (L1) and (L2), respectively. The broad absorption
ꢁ
1
bands in range 3229–3446 and 3138–3351 cm manifested the
presence of characteristic vibrations of –NH groups, for the com-
pounds (L1) and (L2) [35,37]. The overlapping with OH broad band
at this region causes that band of –NH seems as a weak doublet for
with values, i.e. 375, 342, 314, 286
], [C19 ], [C19 NO ], [C17
41, 417, 375, 341 corresponding to [C25
], [C20 ], [C20 ] for (L2) are attributable
u
H
corresponding to
NO ] for (L1) and
],
[
C
20
H
13
N
3
O
5
8
H N
3
O
4
H
8
4
4
4
4
u
19 3 5
H N O
[
C
23
H
19
N
3
O
5
H
13
N
3
O
5
9 2 4
H N O
(L1). Also a similar overlapping is observed for (L2) because of the
to different fragments of the ligands. Similarly, mass spectrum of
the complex (3) exhibited molecular ion peak [M] at m/z 522,
which agree well with the molecular formula that is {[Cu(CPCP)]
presence of hydrogen bonds and water molecules [27]. Meaningful
information can be obtained by comparing the IR spectra of the
complex (3) and the uncomplexed ligand (L1). Coordination of
the deprotonated carboxamide nitrogen and carboxylphenyl oxy-
gen to the Cu(II) center resulted a shift to lower frequencies in
the carbonyl vibrations. The carbonyl groups stretching vibrations
(
DMAP)ꢀ3H
plex (3) [45]. Also, fragments peaks at m/z 377, 341, 313, 264,
36 and 200 are corresponding to [C14 Cu],
2 n
O} and suggests the monomeric nature for the com-
2
10 4 5
H N O
ꢁ1
[C14H N O Cu], [C14H N O Cu], [C14H N Cu], [C13H NCu] and
of amide and acid were appeared at 1604 and 1647 cm respec-
6
4
3
6
2
3
5
2
3
[
C
10
3
H NCu], respectively. The obtained results of both elemental
tively, for (3). These vibrations shifted downward (about 46–
ꢁ1
analysis and mass spectra of the compounds are in good agreement
with the proposed formula for them.
5
6 cm ) compared to (L1), in agreement with the data reported
for related complexes [38,39]. The appeared band at 3200–
ꢁ1
3
446 cm was assigned to the presence of hydrogen bonds and
water molecules in the structure of complex [40]. The Cu–N and
Cu–O stretching vibrations are found at around 510–542 and
4
. Thermal studies of complex
ꢁ1
6
85–752 cm respectively, for complex (3) [41]. The compounds
The TGA/DTA scanning were carried out within a temperature
(L1) and (L2) displayed characteristic UV–Vis spectra at concentra-
2
range from 30 to 800 °C in N atmosphere at a rate of 10 °C/min

2
28
S. Abdolmaleki, M. Ghadermazi / Inorganica Chimica Acta 461 (2017) 221–232
during decomposition steps is in an excellent agreement with
together and also with the obtained structure of the crystallo-
graphic studies.
5
. Esterification and hydrolysis mechanisms of (L1)
The ligand (L1) was synthesized as compound with functional
groups of amide and carboxylic acid corresponding to prediction
and (L2) was prepared on the base of conversion of carboxylic acid
groups to ester in (L1), using acid (As catalyst) and alcohol (Fischer
esterification). Ethanol is used as solvent. So, it is in excess. Differ-
2 4
ent acids can be used for this conversion, but H SO (Sulfuric acid)
and TsOH (Tosic acid) are often used. In replacement of OH by OR,
many steps were exhibited including: protonation of the carbonyl
oxygen by acid for making the carbonyl carbon to much better
electrophile, 1,2-addition by the alcohol for transfer of the proton
from the alcohol to one of the OH groups, 1,2-elimination of water,
protonation of ester and then deprotonation of it. All these steps
are in equilibrium and byproduct of the reaction is water.
Fig. 8. Thermal behavior of complex (3).
Study of crystal structure of (3) confirmed that the ligand (L1)
was hydrolyzed during the reaction with the metal salt and one
of the N-carboxylphenyl bonds is broken in it. With regard to high
stability of amide bonds towards hydrolysis [47], no more studies
have been reported about the hydrolysis of amide ligands during
complexation. It seems that, the factors such as Cu(II) catalytic
effects, electrophilic (carbonyl) activation and intermolecular
metal hydroxide mechanisms [48], ligand architecture and its
coordination modes [49], the concentration of effective anions,
hydrogen ions and temperature [16] can be effective in the hydrol-
ysis rate. Generally, amides can be hydrolyzed depending on the
pH under either acidic or basic conditions and or from water-
assisted pathway [50,51], but the mechanism of the catalyzed
hydrolysis reaction is not still obvious [52]. With assuming the
water-assisted route, possible mechanism is shown in Scheme 2.
In this case, steric effects may be a barrier of same orientation
and interaction of the water molecules toward both amide groups
and as a result, one of the amide groups is not hydrolyzed. But
determination of the accurate route and effective factors on
hydrolysis of the ligand (L1) during formation of the complex is
difficult in this work and more accurate studies must be supported
by experimental works which is not within our goals.
to measure the percentage of mass loss as a function of tempera-
ture [46] on crystalline sample of the compound (3).
Thermogravimetric (TG) analysis exhibited three-step decom-
position processes for the complex (3) in which weight loss starts
at 60 and ends at 745 °C (Fig. 8). The first decomposition step at
0–100 °C with the loss weight of 6.01% is assignable to the
removal of co-crystallized two water molecules (H ) in structure
calcd 6.89%). The second decomposition step occurs at 100–405 °C
with total weight loss about of 65.90% due to the removal of co-
crystallized one water molecule, one DMAP molecule and also pyr-
15 4 4
idine 2-carboxylate-6-carboxamide molecule (C14H N O ) from
crystalline sample (calcd 62.34%). The third decomposition step
6
4 2
O
(
at 410–745 °C with mass loss of 17.92% can be attributed to the
elimination of two oxygen atoms (O
2
) in carboxylate phenyl (calcd
1
7.48%). The residual structure is expected to be copper uncoordi-
nated to phenyl ring as final product. The obtained curve of differ-
ential thermal analysis (DTA) indicates three distinct endothermic
peaks at 52, 84 and 264 °C and three distinct exothermic peaks at
8
1, 135 and 518 °C. The collected date of TGA-DTA curves of (3)
H
O
H
H
O
H
OH
O
H
H
O
O
H
O
O
O
N
N
H
NH
COOH
NH
HOOC
+
H O
2
NH
+H N
2
COOH
HOOC
(L1)
(L1)
NH2
O
O
HOOC
N
+
OH
NH
COOH
Scheme 2. Hydrolysis of water-assisted pathway in (L1).

S. Abdolmaleki, M. Ghadermazi / Inorganica Chimica Acta 461 (2017) 221–232
229
7
. Catalytic activity
Selective oxidation of alcohols into the corresponding carbonyl
compounds has occupied an outstanding part of the modern syn-
thetic organic chemistry [56,57]. Because of the importance of
aldehydes in the production of fine chemicals such as food addi-
tives or fragrances [58,59], conversion of primary alcohols to alde-
hydes has been attracting researchers’ attention. The catalytic
activity of the complex (3) with change in the amount of it has
been summarized in Table 5. As shown, the complex is active
enough on the oxidation of benzyl alcohol. It indicates that the
complex as catalyst is necessary to run the oxidation reaction.
The effect of hydrogen peroxide as oxidant on the oxidation of ben-
zyl alcohol is displayed in Table 6. The results show that the reac-
tion yield increased by increasing the amount of hydrogen
peroxide. The maximum yield is obtained of 81% by applying
0
.04 g of the complex and 60 mL of hydrogen peroxide. The effect
of temperature on the reaction yield is indicated in Table 7. The
investigations showed that the optimum temperature is 45 °C for
the reaction. It is seen that the reaction yield does not change by
rising the temperature. After realization of the optimized condi-
tions (amount of catalyst 0.04 g, reaction temperature 45 °C, used
Fig. 9. Cyclic voltammogram of complex (3), c = 4 ꢃ 10 mol/dm3 in H
ꢁ3
2
O medium,
KCl (0.1 M) at GCE, scan rate 0.05 V/s.
2 2
amount H O 60 mL), oxidation of a number of benzyl alcohol
derivatives and hexanol was studied in the presence of the com-
plex as catalyst. The obtained selectivity and yield of the com-
pounds are indicated in Table 8. In this study the complex
showed outstanding catalytic performance with selective conver-
sion of alcohols at 45 °C. This high activity and selectivity is likely
related to lewis acidity of the catalyst [60]. In conclusion, oxidation
of benzyl alcohol using hydrogen peroxide as mild oxidant in the
presence of synthetic complex as catalyst provides an efficient,
easy and safe approach for oxidation of alcohols to the correspond-
ing aldehydes.
6
. Electrochemical properties
The electrochemical behavior of the compounds (L1), (L2) and
3) were studied using cyclic voltammetry with potential in the
(
ꢁ
1
range ꢁ1.0 to +1.0 V and scan rate of 0.05 V s , in methanol solu-
tion containing 0.1 M LiClO as supporting electrolyte for the com-
4
pounds (L1), (L2) and in aqueous solution containing 0.1 M KCl as
supporting electrolyte for the complex (3). No redox response was
observed in the ligands (L1) and (L2). The cyclic voltammogram for
the compound (3) is displayed in Fig. 9.
8
. Stability testing of complex (3)
As seen, two anodic peaks appeared from ꢁ0.32 to +0.57 V at
E
A1 = ꢁ0.16 and EA2 = 0.32 V and in the reverse cycle, two
The stability of the complex (3) was evaluated by UV–Vis spec-
cathodic peaks are observed from 0.05 to ꢁ0.53 at EC2 = ꢁ0.16
tral analysis at different times in a mixture containing DMSO/H
2
O
(
as a wide wave with potential approx equal to anodic peak) and
0
at concentration of 100 M, 37 °C and pH 7.2. The degree of
l
E
E
C1 = ꢁ0.36 V. The first quasi reversible couple with E ˊ = ꢁ0.26 V,
C1 = ꢁ0.36 V and EA1 = ꢁ0.16 V was assigned to Cu(I)/Cu(0) redox
decomposition over time was determined by comparing the spec-
tra collected after 0, 1, 24, and 48 h. The results indicated that the
values of absorbance and wavelength were not affected, even after
system. The anodic peak height is attributed to the Cu(0) deposit
oxidation to Cu(I). The high value of the first anodic peak current
can be explained by the redissolution of copper electrodeposited
during the forward potential scan [53]. The peak separation
4
8 h and confirmed that the complex is stable in the solution for at
least 48 h under the test conditions [27].
(
ΔEp) is 0.20 V, for this couple.
The second couple with E0ˊ = 0.08 V,
E
C2 = ꢁ0.16 V and
9. Cytotoxicity
E
A2 = 0.32 V was corresponding to Cu(II)/Cu(I) redox process. The
peak separation (ΔEp) was 0.48 V, for this couple. Redox process
of Cu(I)/Cu(0) occurred at more negative E ˊ potential compared
The in vitro anticancer activity of the synthetic compounds was
studied on MCF7, HT29 and bTC cell lines by the MTT method and
using oxaliplatin as a positive control. The obtained results after
48 h of the treatment on the cell lines are displayed in Fig. 10
and Table 9. The cell proliferation was exhibited for all the three
compounds in the dose-dependent manner. The ligands (L1) and
(L2) indicated close anti-proliferative effect to oxaliplatin on
0
to Cu(II)/Cu(I) [54]. The obtained results of the investigation of
the cyclic voltammogram of the ligand (L1) confirm that it did
not exhibit any wave in the potential range of ꢁ1.0 to +1.0 V, thus
the observed redox couples have been assigned to single electron
transfer processes in the metal center of the complex [55].
Table 5
Catalytic effect of complex (3) on the oxidation of benzyl alcohol with different amounts of catalyst.
Entry
Oxidant (30 ml)
Complex (g)
Product
Selectivity (%)
Yield (%)
1
2
3
4
5
6
7
H
H
H
H
H
H
H
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
2
2
2
2
2
2
0.01
0.02
0.03
0.04
0.045
0.05
Not used
Benzaldehyde
Benzaldehyde
Benzaldehyde
Benzaldehyde
Benzaldehyde
Benzaldehyde
Benzaldehyde
>99
>99
>99
>99
>99
>99
>99
21
22
28
41
41
40
3

2
30
S. Abdolmaleki, M. Ghadermazi / Inorganica Chimica Acta 461 (2017) 221–232
Table 6
Effect of hydrogen peroxide on the oxidation of benzyl alcohol in the presence of optimized amount of catalyst.
Entry
H
2
O
2
(ml)
Complex (g)
Product
Selectivity (%)
Yield(%)
1
2
3
4
5
6
7
30
35
40
45
55
60
65
0.04
0.04
0.04
0.04
0.04
0.04
0.04
Benzaldehyde
Benzaldehyde
Benzaldehyde
Benzaldehyde
Benzaldehyde
Benzaldehyde
Benzaldehyde
>99
>99
>99
>99
>99
> 99
> 99
41
53
62
69
78
81
80
Table 7
Effect of temperature on the oxidation of benzyl alcohol in the presence of optimized amounts of catalyst and hydrogen peroxide.
Entry
H
2
O
2
(ml)
Complex (g)
Temperature(°C)
Product
Yield(%)
1
2
3
4
5
6
7
60
60
60
60
60
60
60
0.04
0.04
0.04
0.04
0.04
0.04
0.04
20
37
40
45
55
65
70
Benzaldehyde
Benzaldehyde
Benzaldehyde
Benzaldehyde
Benzaldehyde
Benzaldehyde
Benzaldehyde
47
64
86
93
92
90
84
Table 8
Oxidation of benzyl alcohol derivatives and hexanol in the presence of complex (3) as catalyst under the optimized conditions.
O
Catalyst (0.04 g)
H O
2 2
30% (60 µl)
R
OH
R
H
Temprature 45 °C, 40-45 min
Entry
1
Substrate
Product
Selectivity (%)
Isolated Yield (%)
92
HO
O
>99
Cl
Cl
2
Cl
Cl
>99
93
HO
O
O
3
4
HO
>99
>99
93
87
F
F
F
F
HO
O
O
5
7
HO
>99
>99
86
72
Br
OH
60 mL, reaction temperature 45 °C, 0.5 mmol substrate.
Br
O
Amount of catalyst 0.04 g, amount of H
2
O
2
MCF7 and bTC cell lines at the concentrations 0.1–100
HT29 cells exhibited the higher sensitivity to the ligand (L1) (with
IC50 equal to 10 M) compared to oxaliplatin at concentrations 10–
00 M. On the other hand, no significant difference was displayed
between (L2) and oxaliplatin on HT29 cells at all the tested concen-
trations (both with IC50 values about 100 M). The complex (3)
exhibited a significant cytotoxic effect (with IC50 = 1 M) com-
pared to oxaliplatin and both of the ligands on MCF7 and HT29
cells, also it had moderate anti-proliferative effect (with
IC50 = 10 M), than oxaliplatin on bTC cell line. This rate of
inhibitory is considerable with regarding to lack of response to
l
M, while
therapeutic agents in treatment of pancreatic cancer [61,62]. In
general, the complex (3) showed the highest cytotoxicity effect
compared to the ligands (L1) and (L2) on all the three cell lines.
Accordingly, it is reasonable to assume that inhibitory effect of
organic compounds can be increased by chelation with metal ions.
These results are comparable to those reported previously [63–65].
It should be noted that metal complexes as drug display enhanced
selectivity and novel modes of DNA interaction, like non-covalent
interactions that mimic the interaction mode of biomolecules
[66]. However to evaluate metal complexes as therapeutic agents
further studies are needed under biological conditions.
l
1
l
l
l
a
l

S. Abdolmaleki, M. Ghadermazi / Inorganica Chimica Acta 461 (2017) 221–232
231
Fig. 10. Cytotoxic effect of oxaliplatin and synthetic compounds (L1), (L2) and (3) against a) MCF7, b) HT29 and c) bTC cell lines. The incubated cells were treated with
concentrations 0.1, 1, 10 and 100
l
M of compounds. Cytotoxicity was determined under MTT method as explained. Data are registered as mean ± S.E.M (n = 3).
Table 9
The study of compounds electrochemical properties proved that
IC50 determination of compounds (L1), (L2) and (3) against MCF7, HT29 and bTC cell
lines.
only complex (3) is involved in redox reactions. According to the
obtained results, it is inferred that complex (3) as catalyst is active
enough on the oxidation of aromatic and aliphatic alcohols. Also,
after MTT assay, it was manifested that complex (3) has stronger
cytotoxicity than oxaliplatin and both ligands against all the three
cell lines.
IC50 (lM ± s.d.)
Compounds
MCF7
HT29
bTC
L1
L2
3
>100 ± 4.2
>100 ± 6.3
1 ± 3.1
10 ± 6.3
100 ± 4.1
1 ± 3.4
>100 ± 4.4
>100 ± 5.3
10 ± 4.2
Oxaliplatin
>100 ± 6.2
100 ± 5.1
>100 ± 5.6
Acknowledgments
%Viability ± standard error is expressed as an average of triplicates.
We would like to thank the University of Kurdistan and Faculty
of Pharmacy of Tehran University of Medical Sciences for financial
support.
1
0. Conclusion
Two novel ligands (L1), (L2) and a polymeric copper (II) com-
Appendix A. Supplementary data
plex (3) from (L1) were synthesized. X-ray crystallographic studies
of complex (3) revealed a square pyramidal geometry around cop-
per ion along with co-crystallized molecules of DMAP and water.
CCDC 1478768–1478770 contains the supplementary crystallo-
graphic data for compounds (1)–(3) respectively. These data can be

2
32
S. Abdolmaleki, M. Ghadermazi / Inorganica Chimica Acta 461 (2017) 221–232
obtained free of charge via http://www.ccdc.cam.ac.uk/conts/
retrieving.html, or from the Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (+44)
(b) M.C. Burla, R. Caliandro, M. Camalli, B. Carrozzini, G.L. Cascarano, L. De
Caro, C. Giacovazzo, G. Polidori, R. Spagna, J. Appl. Cryst. 38 (2005) 381–388;
(
c) G.M. Sheldrick, SHELXL97. Program for Crystal Structure Refinement,
University of Göttingen, Germany, 1997;
1
223-336-033; or e-mail: deposit@ccdc.cam.ac.uk.
Supplementary data associated with this article can be found, in
(d) SHELXT LN, Version 5.10, Bruker Analytical X-ray Inc., Madison, WI, USA,
1998.;
(
e) W. Shi, X.-Y. Chen, B. Zhao, A. Yu, H.-B. Song, P. Cheng, H.-G. Wang, D.-Z.
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