Synthesis, spectroscopic, and thermal investigations of metal complexes with mefenamic acid

Article abstract of DOI:10.1155/2017/6172626

The novel metal complexes with empirical formulae M(mef)₂·nH₂O (where M = Mn(II), Co(II), Ni(II), Cu(II), Zn(II), and Cd(II); mef is the mefenamic ligand) were synthesized and characterized by elemental analysis, molar conductance, FTIR-spectroscopy, and thermal decomposition techniques. All IR spectra revealed absorption bands related to the asymmetric (as) and symmetric (s) vibrations of carboxylate group. The Nakamoto criteria clearly indicate that this group is bonded in a bidentate chelate mode. The thermal behavior of complexes was studied by TGA methods under non-isothermal condition in air. Upon heating, all compounds decompose progressively to metal oxides, which are the final products of pyrolysis. Cu(II), Zn(II), and Cd(II) complexes were also characterized by the coupled TG-FTIR technique, which finally proved the path and gaseous products of thermal decomposition. Additionally, the coupled TG-MS system was used to determine the principal volatile products of thermolysis and fragmentation processes of Mn(mef)₂·3H₂O and Co(mef)₂·2H₂O.

Full text of DOI:10.1155/2017/6172626

Hindawi
Journal of Chemistry
Volume 2017, Article ID 6172626, 7 pages
https://doi.org/10.1155/2017/6172626
Research Article
Synthesis, Spectroscopic, and Thermal Investigations of
Metal Complexes with Mefenamic Acid
Karolina Kafarska, MichaB Gacki, and Wojciech M. Wolf
Institute of General and Ecological Chemistry, Faculty of Chemistry, Lodz University of Technology,
116 Zeromskiego Street, 90-924 Lodz, Poland
Correspondence should be addressed to Karolina Kafarska; karolina.kafarska@p.lodz.pl
Received 18 September 2017; Revised 16 November 2017; Accepted 21 November 2017; Published 18 December 2017
Academic Editor: Maria F. Carvalho
Copyright © 2017 Karolina Kafarska et al. is is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
e novel metal complexes with empirical formulae M(mef) ⋅nH O (where M = Mn(II), Co(II), Ni(II), Cu(II), Zn(II), and Cd(II);
2
2
mef is the mefenamic ligand) were synthesized and characterized by elemental analysis, molar conductance, FTIR-spectroscopy,
and thermal decomposition techniques. All IR spectra revealed absorption bands related to the asymmetric (]as) and symmetric (]s)
vibrations of carboxylate group. e Nakamoto criteria clearly indicate that this group is bonded in a bidentate chelate mode. e
thermal behavior of complexes was studied by TGA methods under non-isothermal condition in air. Upon heating, all compounds
decompose progressively to metal oxides, which are the final products of pyrolysis. Cu(II), Zn(II), and Cd(II) complexes were also
characterized by the coupled TG-FTIR technique, which finally proved the path and gaseous products of thermal decomposition.
Additionally, the coupled TG-MS system was used to determine the principal volatile products of thermolysis and fragmentation
processes of Mn(mef) ⋅3H O and Co(mef) ⋅2H O.
2
2
2
2
1. Introduction
particular, divalent metal complexes with several NSAID are
better anti-inflammatory candidates then NSAIDs, because
they have unique structures that could interact with the
target enzymes more specifically. In addition, metal ions
introduce extra antioxidant activity [13] and antiproliferative
activity against cancer [14–16]. Furthermore gastrointestinal
toxicities associated with the administration of complexes
are much lower than those of the parent drug and improved
safety of these drugs [17].
Fenemates (N-arylated derivatives of anthranilic acid) are
pharmaceutical compounds with distinct anti-inflammatory
and analgesic, antipyretic activity. eir mode of biological
action is based on inhibiting prostaglandin synthetase [1,
2]. In particular, 2-(2,3-dimethyl-phenyl) aminobenzoic acid
(mefenamic acid: (CH ) C H NHC H COOH (Figure 1)) is
an effective nonsteroidal agent widely used for the treatment
of mild to moderate pains, inflammation, ache, and fever
[3–5]. Moreover mefenamic acid, as other anti-inflammatory
drugs, is emerging as novel chemopreventive agents against
cancer [6, 7]. It is an active ingredient of numerous drugs
which are present on the pharmaceutical market [8, 9].
However, NSAID-induced side effects, particularly in the
gastrointestinal tract and kidney, ofen limit their applica-
tions. For this reason, considerable efforts have been made
to increase their activity while minimizing side effects [10].
It is well known that several transition metal complexes
with nonsteroidal drugs are more effective and show signifi-
cantly lower toxicity than that of their parent drugs [11, 12]. In
3 2
5
3
5
4
Our studies were stimulated by the fact that majority
of anti-inflammatory drugs are carboxylic acids with their
carboxylate group prone to metal binding [11, 18–20]. Some
of mefenamate complexes have been described in the lit-
˙
erature. Brzyska and Ozga characterized complexes of rare
earth metals with mefenamic ligand [21]. Tapacli and Ide
described mefenamate compounds with Ca and Na ions [22].
Kovala-Demertzi et al. investigated the compounds with the
formulae: SnPh (mef) and SnBu (mef) [23].
3
2
2
e aim of the present work was to obtain the mefenamate
complexes of Mn(II), Co(II), Ni(II), Cu(II), Zn(II), and

2
Journal of Chemistry
(MO) cm−1; Anal. Calc. C H CuN O (%): C, 62.11; H, 5.56;
OH
O
30 32
2
6
N, 4.83; Cu, 10.95; Found (%): C, 62.08; H, 5.59; N, 4.85; Cu,
10.44.
H
N
Complex Zn(mef) ⋅2H O: color: white; IR (KBr, ]): 3338
2
2
(OH), 3066 (NH), 2858 (CH), 1651 (NH), 1576 (OCO−), 1506
(NH), 1466 (CH ), 1388 (OCO−), 1283 (CH ), 1183 (CH ),
3
3
3
1155 (CH), 1069 (CH), 1043 (CH ), 856 (CH), 748 (CH ),
3
3
677 (MO) cm−1; Anal. Calc. C H ZnN O (%): C, 61.92; H,
30 32
2
6
5.54; N, 4.81; Zn, 11.23; Found (%): C, 61.88; H, 5.50; N, 4.88;
Zn, 11.25.
Figure 1: Chemical structure of mefenamic acid.
Complex Cd(mef) ⋅2H O: color: white; IR (KBr, ]): 3312
2
2
(OH), 3067 (NH), 2858 (CH), 1651 (NH), 1576 (OCO−), 1499
(NH), 1452 (CH ), 1396 (OCO−), 1283 (CH ), 1190 (CH ), 1159
3
3
3
(CH), 1043 (CH ), 862 (CH), 750 (CH ), 679 (MO) cm−1;
3
3
Cd(II), determine their chemical properties, and study their
thermal decomposition patterns.
Anal. Calc. C H CdN O (%): C, 57.29; H, 5.13; N, 4.45; Cd,
30 32
2
6
17.86; Found (%): C, 57.30; H, 5.15; N, 4.53; Cd, 17.90.
2. Materials and Methods
2.3. Measurements. e chemical compositions of all com-
plexes were defined by the elemental analysis followed by
the atomic absorption spectrometry. Hydrogen, carbon, and
nitrogen contents were measured with the Vario EL III
Elemental Analyzer. e metal content was determined
in samples mineralized using the Anton Paar Multiwave
3000 closed system instrument. e mixture of concentrated
HNO (6 mL) and HCl (2 mL) was applied. Metal concen-
trations were measured by the FAAS with the GBC Scientific
Equipment 932 plus spectrometer.
2.1. Materials. Pure mefenamic acid was obtained as a gif
from Polfa Pabianice; metal chlorides MCl ⋅nH O (where M
2
2
= Mn, Co, Ni, Cu, Zn, and Cd), DMSO, DMF, and EtOH
p.a. were purchased from Aldrich and MeOH from Lab-Scan;
other chemicals were from POCh-Gliwice.
3
2.2. Synthesis. All complexes were obtained according to
similar procedures. e first step of synthesis was preparation
sodium salt of ligand by dissolution of mefenamic (1 mmol)
acid in 50 mL fresh precipitated aqueous-ethanol solution
(1 : 1) of NaOH (0,02 mol⋅L−1). e mixture was heated up
to 60∘C and added to aqueous solution of metal chlorides
(0,5 mol in 25 mL). e reaction mixture was kept in 60∘C for
2 hours. Afer several days the solid precipitates were isolated
by filtration, washed with hot water, and dried on air.
IR spectra were recorded on FTIR-8501 Shimadzu spec-
trophotometer over 4000–400 cm−1 range using KBr pellets.
e thermal stabilities of complexes were studied by means of
TGA techniques. e measurements were made with the Net-
zsch, TG 209 apparatus, and Q-1500 Derivatograph. Samples
(1⋅10−2 g) were heated (in ceramic crucibles) up to 1000∘C,
at a heating rate 10∘C min−1 in air atmosphere. e analysis
of solid decomposition products was performed using TG
and DTG curves and supported by the X-ray diffractograms
(Siemens D-5000 diffractometer, graphite monochromatized
Complex Mn(mef) ⋅3H O: color: pale pink; IR (KBr, ]):
2
2
3358 (OH), 3067 (NH), 2859 (CH), 1652 (NH), 1578 (OCO−),
1495 (NH), 1459 (CH ), 1394 (OCO−), 1283 (CH ), 1183
3
3
(CH ), 1159 (CH), 1093 (CH), 1043 (CH ), 852 (CH), 749
3
3
(CH ), 679 (MO) cm−1; Anal. Calc. C H MnN O (%): C,
CuK radiation) of sinters, obtained by heating the complex
ꢀ
3
30 34
2
7
samples up to temperatures defined from TG curves. A
coupled TG-MS system was applied for analysis of volatile
products of thermal decomposition and fragmentation pro-
cesses. Data were processed using online connected computer
system with commercial sofware (Derivatograph TG/DTA-
SETSYS-16/18, coupled to a Mass Spectrometer QMS-422
model ermoStart from Balzers); platinum crucible, mass
sample: 4–6 mg. Dynamic measurements were carried out
in argon atmosphere (at a flow rate 20 mL⋅min−1) with a
heating rate 10∘C⋅min−1 and an ion source temperature of ca.
150∘C using 70 eV electron impact ionization. e TG-FTIR
measurements were carried out in ceramic crucibles at flow-
ing argon atmosphere (20 mL⋅min−1) using the Netzsch TG
209 apparatus coupled with Bruker FTIR spectrophotometer.
e samples were heated up to 1000∘C at a heating rate
10∘C⋅min−1. Molar conductivity (Λ ) of all synthesized com-
pounds was measured in 1⋅10−3 moMl⋅L−1 solutions of MeOH,
DMSO, and DMF, according to procedure as described in
[24].
61.12; H, 5.81; N, 4.75; Mn, 9.32; Found (%): C, 61.00; H, 5.50;
N, 4.76; Mn, 9.36.
Complex Co(mef) ⋅2H O: color: pink; IR (KBr, ]): 3315
2
2
(OH), 3069 (NH), 1651 (NH), 1578 (OCO−), 1504 (NH), 1454
(CH ), 1393 (OCO−), 1283 (CH ), 1188 (CH ), 1159 (CH), 1097
3
3
3
(CH), 1043 (CH ), 854 (CH), 748 (CH ), 675 (MO) cm−1;
3
3
Anal. Calc. C H CoN O (%): C, 62.61; H, 5.60; N, 4.87;
30 32
2
6
Co, 10.24; Found (%): C, 62.67; H, 5.60; N, 4.88; Co, 10.22.
Complex Ni(mef) ⋅2H O: color: pale green; IR (KBr,
2
2
]): 3346 (OH), 3069 (NH), 2860 (CH), 1653 (NH), 1578
(OCO−), 1499 (NH), 1455 (CH ), 1391 (OCO−), 1285 (CH ),
3
3
1190 (CH ), 1159 (CH), 1097 (CH), 1043 (CH ), 851 (CH), 748
3
3
(CH ), 678 (MO) cm−1; Anal. Calc. C H NiN O (%): C,
3
30 32
2
6
62.64; H, 5.60; N, 4.87; Ni, 10.20; Found (%): C, 62.70; H, 5.49;
N, 4.98; Ni, 10.21.
Complex Cu(mef) ⋅2H O: color: green; IR (KBr, ]): 3321
2
2
(OH), 3077 (NH), 2910 (CH), 1647 (NH), 1578 (OCO−), 1506
(NH), 1458 (CH ), 1393 (OCO−), 1285 (CH ), 1188 (CH ),
3
3
3
1153 (CH), 1067 (CH), 1034 (CH ), 854 (CH), 746 (CH ), 680
3
3

Journal of Chemistry
3
Table 1: Molar conductivity of complexes ΛM/Ω−1 cm2⋅mol−1 for
0,001 mol⋅L−1 solutions in MeOH, DMF, and DMSO at−215∘C.
Table 2: Principal IR bands (cm−1) for carboxylate group in
investigated complexes.
Λ
[Ω−1 cm2 mol
DMF
]
Compound
Na(mef)
]
]
Δ] = ]asym − ]sym
200,0
M
asym
sym
Complex
MeOH
45.20
11.23
17.07
12.05
21.0
DMSO
16.90
3.07
1580,0
1577,7
1577,7
1577,7
1577,7
1575,7
1575,7
1380,0
1393,6
1392,5
1390,6
1392,5
1386,7
1396,4
Mn(mef) ⋅3H O
35.70
13.03
Mn(mef) ⋅3H O
184,1
185,2
187,1
2
2
2
2
Co(mef) ⋅2H O
Co(mef) ⋅2H O
2
2
2
2
Ni(mef) ⋅2H O
20.05
13.15
28.11
24.34
7.09
4.27
3.17
4.55
Ni(mef) ⋅2H O
2
2
2
2
Cu(mef) ⋅2H O
Cu(mef) ⋅2H O
185,2
189,0
178,7
2
2
2
2
Zn(mef) ⋅2H O
Zn(mef) ⋅2H O
2
2
2
2
Cd(mef) ⋅2H O
18.18
Cd(mef) ⋅2H O
2
2
2
2
0.00
100
90
80
70
60
50
40
30
20
3. Results and Discussion
−2.00
−4.00
−6.00
−8.00
−10.00
−12.00
e empirical formulae of complexes showing number of
water molecules and molar conductivities are presented in
Table 1. All synthesized solid complexes are stable in air.
ey are practically insoluble in water, but on the contrary
quite soluble in polar organic solvents (e.g., EtOH, MeOH).
Analysis of X-ray powder diffraction data reveals high level of
crystallinity and proves that neither pair of investigated
compounds is isostructural. e molar conductivity data
clearly indicate that all complexes in MeOH and DMSO as
well as Co(II), Ni(II), and Cu(II) compounds in DMF are
non-electrolytes. On the other hand, molar conductivities for
Mn(mef) ⋅3H O in MeOH and DMF and Zn(mef) ⋅2H O
100 200 300 400 500 600 700 800 900
Temperature (∘C)
Figure 2: ermoanalytical curves of Cd(mef) ⋅2H O in air, sample
2
2
mass 7,407 mg.
2
2
2
2
and Cd(mef) ⋅2H O point out that solutions of these com-
2
2
pounds according to the Geary criterion [25] are intermedi-
ates between those of nonelectrolytes and 1 : 1 electrolytes.
pattern investigations are collected in Table 3. e thermal
decomposition curves of Cd(mef) ⋅2H O are shown on Fig-
2
2
3.1. FTIR Spectra. e IR spectra of all complexes exhibit
a broad absorption band in the water stretching region
(3300–3600 cm−1). Additionally, bands related to the water
bending vibrations are observed (1615–1620 cm−1). In all
spectra the valence vibrations of monodissociated carboxylic
group are not observed. On the contrary, asymmetric
(1575–1578 cm−1) and symmetric (1386–1394 cm−1) vibration
of dissociated OCO− group are clearly observed (Table 2).
ese bands are affected by the coordination of mefenamic
ligand to metal ions. e separation Δ] = ]as(OCO) −
]s(OCO) and the direction of the shifs of these bands in
comparison to those values of sodium salt characterized the
nature of the metal–carboxylate bonds. e bathochromic
shifs of asymmetric (]as) and hypsochromic shifs of sym-
metric (]s) frequencies are also observed. e magnitude of
separation and the bands direction show that carboxylate
group of mefenamic ligand coordinated in bidentate chelate
mode [26].
ure 2. e thermal decomposition of the complexes is a multi-
stages process. All compounds started to decompose by dehy-
dration accompanied by the endothermic effect. Majority of
complexes lose their water molecules in one step. Only for
Co(II) and Zn(II) complexes water elimination is two-stage
transformation. ermolyses of these complexes are quite
similar. e two-stage dehydration (60–110∘C, 130–240∘C
and 100–160∘C, 160–190∘C for Co(II) and Zn(II) compound,
respectively) is followed by organic ligand thermodestruction
and metal carbonate formation. Further heating leads to
metal oxides: ZnO and CoO. e latter is obtained via Co O
3
4
intermediate. In the terminal step of pyrolysis the DTA curve
exhibits exoeffects. Formation of oxides was confirmed by the
powder X-ray diffraction technique (Figure 3).
Mn(mef) ⋅3H O and Cu(mef) ⋅2H O decompose in a
2
2
2
2
similar way. One-step dehydration takes place at 60–240∘C
and 100–180∘C for Mn(II) and Cu(II) complex, respectively.
Further increase of temperature results in high mass loss
(ca. 80%) caused by mefenamic ligand decomposition and
Mn O (via Mn O ) and CuO formation. e lowest thermal
Apart from carboxylate group the mefenamic anion has
amine group, available for coordination. e NH deforma-
tion vibrations in the IR spectra of mefenamic acid are very
close to those observed in the IR spectra of its complexes. at
indicates that the NH group does not participate directly in
coordination.
3
4
2
3
stability was determined for Ni(II) complex. Its decompo-
sition starts at 50∘C with 6,5% mass loss related to water
molecules elimination. In the following step, the anhydrous
compound decomposes (190–460∘C) to NiCO . is step is
3
represented as two distinct exothermic peaks at 340∘C and
430∘C on the DTA curve. Further heating leads to formation
of intermediate equimolar mixture of NiO and Ni, which
3.2. ermal Analysis. e data obtained from TG, DTG,
and DTA curves supported by chemical and X-ray diffraction

4
Journal of Chemistry
Table 3: ermal decomposition data of complexes in air.
Mass loss, %
Intermediate and final
solid products
Compounds
Ranges of decomp., ∘C
DTA peaks, ∘C
Found
9.0
78.0
1.0
3.0
3.0
Calc.
9.17
77.68
1.80
3.13
60–240
240–740
740–900
60–110
120 endo
320,600 exo
860 exo
100 endo
-
340 endo
470 exo
570 exo
920 exo
80 endo
Mn(mef)
2
Mn(mef) ⋅3H O
Mn O
2
2
2
3
Mn O
3
4
Co(mef) ⋅H O
2
2
130–240
3.13
Co(mef)
2
Co(mef) ⋅2H O
2
2
250–520
73.0
73.07
CoCO
3
530–660
>900
7.0
1.0
6.5
6.72
0.93
6.30
73.10
9.0
Co O
3
4
CoO
50–180
Ni(mef)
2
190–460
460–550
550–750
100–180
190–840
100–160
160–190
200–490
490–640
110–160
340, 430 exo
490 exo
570 exo
150 endo
550, 640 exo
130 endo
180 endo
420 exo
510 endo, 580 exo
73.0
8.5
NiCO
NiO+Ni
NiO
3
Ni(mef) ⋅2H O
2
2
1.5[a]
6.5
1.39[a]
6.66
80.08
3.10
3.10
72.26
7.56
Cu(mef)
CuO
2
Cu(mef) ⋅2H O
2
2
80.0
3.0
3.0
72,0
8.0
6.0
Zn(mef) ⋅H O
2
2
Zn(mef)
2
Zn(mef) ⋅2H O
2
2
ZnCO
3
ZnO
Cd(mef)
150 endo
300 endo,
340 exo
5.73
2
Cd(mef) ⋅2H O
210–380
470–760
67.0
7.0
66.86
6.59
CdCO
2
2
3
550 exo
CdO
[a]
Mass increase on TG curve.
complex. Dehydration is single-step process and started at
110∘C. e next mass loss (210–380∘C) as observed on TG
curve corresponds to destruction of organic ligand and leads
x
to formation of CdCO . e latter is associated with endo-
3
and exothermic effects as represented by two distinct DTA
peaks at 300 and 340∘C, respectively. Further weight loss is
observed at 470–760∘C and results from the CdO formation
(maximum on DTA curves at 550∘C).
x
x
x
x
x
x
x
x
x
x
x
3.3. TG-MS Measurement. Conventional thermoanalytic
studies such as TG/DTA ofen do not allow for unequivo-
cal identification of gaseous products. For this reason, the
TG/MS techniques were employed to characterize prod-
ucts of dynamic decomposition and fragmentation of
Mn(mef) ⋅3H O and Co(mef) ⋅2H O. e determination
x
10
20
30
40
50
60
70
80
 (degree)
x: ＃／3／4
2
2
2
2
Figure 3: X-ray powder diffraction patterns of decomposition
products of Co(mef) ⋅2H O heated up to 660∘C.
was carried out under an argon atmosphere. e m/z values
are given for 1H, 12C, 14N, and 16O. Figure 4 presents some
profiles of ion current detected by mass spectrometer as a
function of time for Co(II) complex. MS peaks of ion frag-
2
2
ments corresponding to H +, C+, CH + OH+, H O+, C H ,
+
subsequently is fully oxided to nickel oxide (mass increase on
the TG curve). Presence of NiO was confirmed by powder X-
ray diffraction of sinters prepared by heating compound to
750∘C. e highest thermal stability is shown by Cd(II)
complex. Its pyrolysis pattern closely resembles that of Ni(II)
2
3
2
2
2
+
+
+
+
HCN+, N , C H , NO+, CO , 13C16O , 13C16O18O+ (m/z
2
2
5
2
2
= 1, 12, 15, 17, 18, 26, 27, 28, 29, 30, 44, 45, 46) are monitored.
Recorded data clearly indicated that all investigated com-
plexes decompose progressively. For Mn(II) complex maxima

Journal of Chemistry
5
0
20
40
(3)
(1)
60
(4)
80
(5)
(2)
100
0
100 200 300 400 500 600 700 800 900
T (∘C)
Figure 4: TG and corresponding MS analysis of Co(mef) ⋅2H O (where: (1) m/z = 12; (2) m/z = 15; (3) m/z = 18; (4) m/z = 44; (5) TG).
2
2
2500
4500
4000
3500
3000
2500
2000
2000
1500
1000
1500
1000
500
500
Figure 5: e stacked plot TG-FTIR spectra of the evolved gases for Cd(mef) ⋅2H O.
2
2
of ion current intensities were observed for temperature
ranges 120–280∘C, 270–450∘C, and 600–900∘C.
3.4. TG-FTIR Measurement. e coupled TG-FTIR tech-
nique was applied to Cd(mef) ⋅2H O, Cu(mef) ⋅2H O, and
2
2
2
2
e peaks from H O+ and H + observed at 110 and 120∘C
2
2
Zn(mef) ⋅2H O complexes. All experiments were performed
2
2
in argon atmosphere. e IR spectra were recorded using
the Gramm-Schmidt curves. e respective stacked plot as
registered for Cd(mef) ⋅2H O is given in Figure 5.
are related to dehydration of complex. Subsequently, frag-
mentation of organic ligand occurred within the 120–180∘C
temperature range. e following molecular ions were
detected (respective temperature maxima are given in paren-
2
2
Analysis of IR spectra of gases evolved during the
thermal decomposition indicates that pyrolysis schemes of
all investigated complexes are similar and closely related to
those recorded in air atmosphere. All spectra clearly confirm
that the thermal decomposition begins from the dehydra-
tion process. On the TG curve in range 100–160∘C for
Cd(mef) ⋅2H O and Cu(mef) ⋅2H O and 100–190∘C for
theses): C H + (160∘C), CH + (150∘C), C H + (170∘C), C H
+
3
7
3
2
2
2
5
(165∘C), C+ (210∘C), CO + (215∘C), 13C16O + (180∘), (HCN+,
2
2
+
N ). ree major temperature ranges of gaseous prod-
2
ucts emissions 120–230∘C, 230–400∘C, and 500–900∘C were
+
recorded for Co(mef) ⋅2H O. In the first area, CH +, C H ,
2
2
3
2
5
2
2
2
2
C H + ions were detected (all maxima at 160∘C). e second
2
2
Zn(mef) ⋅2H O ca. 6% mass losses connected with water
2
2
+
is related to C+, CO including combination of isotopes
losing were observed. e IR spectra which recorded up to
120∘C for Cd(II) and Cu(II) complexes and up to 150∘C for
Zn(II) complex show bands in the wavenumbers 3750–3500
2
+
(ca. 300∘C) while the third range corresponds to C+, CH ,
3
C H , and CO + ions.
+
2
5
2

6
Journal of Chemistry
TG-DTG system. e differences are related to final products
and paths of dehydration.
Conflicts of Interest
N
H
e authors declare that they have no conflicts of interest.
HO
O
O
n（2／
M
Supplementary Materials
OH
e supplementary material includes the TG/DTG/DTA,
TG-MS, and TG-FTIR plots for synthesized complexes.
Figure 1A. TG/DTG/DTA curves of Mn(mef)2⋅3H2O. Figure
H
N
2A. TG/DTG/DTA curves of Co(mef)2⋅2H2O. Figure 3A.
TG/DTG/DTA curves of Ni(mef)2⋅2H2O. Figure 4A. TG/
DTG/DTA curves of Cu(mef)2⋅2H2O. Figure 5A. TG/DTG/
n
DTA curves of Zn(mef)2⋅2H2O. Figure 6A. TG/DTG/DTA
curves of Cd(mef)2⋅2H2O. Figure 7A. TG and corresponding
MS analysis of Mn(mef)2⋅3H2O (where: (1) m/z = 12; (2)
m/z = 15; (3) m/z = 18; (4) m/z = 44; (5) TG). Fig-
ure 8A. e stacked plot TG-FTIR spectra of the evolved
gases for Cu(mef)2⋅2H2O. Figure 9A. e stacked plot TG-
FTIR spectra of the evolved gases for Zn(mef)2⋅2H2O.
(Supplementary Materials)
Figure 6: Proposed formula of the mefenamic-metal complexes.
and 1750–1400 cm−1 corresponding to stretching and defor-
mation vibrations of liberating water molecules. Anhydrous
complexes are stable up to about 170∘C which is confirmed by
the lack of IR spectra of gaseous products. Further heating
leads to organic ligand degradation indicated by a significant
mass loss observed on the TG curve. e spectra recorded at
260∘C contain bands in frequencies ranging 3000–2600 cm−1
(assigned to the stretching vibrations of the CH bond from
the CH and CH groups); 1450–1350 cm−1 (corresponding to
References
[1] J. R. Vane and R. M. Botting, “Mechanism of action of nonster-
oidal anti-inflammatory drugs,” American Journal of Medicine,
vol. 104, no. 3 A, 1998.
[2] J. R. Vane, “Inhibition of prostaglandin synthesis as a mecha-
nism of action for aspirin-like drugs,” Nature: New biology, vol.
231, no. 25, pp. 232–235, 1971.
[3] F. A. Aly, S. A. Al-Tamimi, and A. A. Alwarthan, “Determination
of flufenamic acid and mefenamic acid in pharmaceutical
preparations and biological fluids using flow injection anal-
ysis with tris(2,2’-bipyridyl)ruthenium(II) chemiluminescence
detection,” Analytica Chimica Acta, vol. 416, no. 1, pp. 87–96,
2000.
[4] N. Cimolai, “e potential and promise of mefenamic acid,”
Expert Review of Clinical Pharmacology, vol. 6, no. 3, pp. 289–
305, 2013.
3
2
bending vibrations of the CH in the CH and CH groups);
3
2
1225–1000 cm−1 and 900–720 cm−1 (from bending vibration
of CH in aromatic ring). Additionally, this spectrum shows
the trace of water molecules in split of organic ligand destruc-
tion (tied in with NH vibration). Spectra which recorded up
to 290∘C contain the same patterns as described above aug-
mented by additional bands (in the range 2500–2250 cm−1
and 750–650 cm−1) corresponding to CO vibrations and
2
trace CO oscillations (2250–2050 cm−1). Heating the sample
above 450∘C resulted in rising intensity of bands related to
carbon oxides while in the same time decreasing those of
water and complete absence of aromatic ring vibrations.
[5] S. Cesur and S. Gokbel, “Crystallization of mefenamic acid and
polymorphs,” Crystal Research and Technology, vol. 43, no. 7, pp.
720–728, 2008.
[6] I. H. Sahin, M. M. Hassan, and C. R. Garrett, “Impact of non-
steroidal anti-inflammatory drugs on gastrointestinal cancers:
Current state-of-the science,” Cancer Letters, vol. 345, no. 2, pp.
249–257, 2014.
[7] P. Ghanghas, S. Jain, C. Rana, and S. N. Sanyal, “Chemopre-
ventive action of non-steroidal anti-inflammatory drugs on the
inflammatory pathways in colon cancer,” Biomedicine & Phar-
macotherapy, vol. 78, pp. 239–247, 2016.
4. Conclusions
All investigated complexes have been obtained as crystalline
hydrates. Majority of synthesized compounds in MeOH,
DMSO, and DMF solutions do not dissociate or dissociate
only in a very limited degree. IR spectra firmly confirmed that
mefenamic ligands are directly coordinated to metal ions
only through carboxylate group, in a bidentate chelate mode.
According to the chemical, spectroscopic, and thermal data,
we have proposed the formula of obtained complexes (Fig-
ure 6).
[8] I. Jasya and K. Hideo, Jpn. Patent No. 59-175220, 1986.
All compounds decompose progressively starting with
dehydration at the temperature range 60–150∘C. Anhydrous
compounds are stable up to almost 170∘C. e most temper-
ature persistence is Cd(II) complex, while the least one is
the Ni(II) compound. Results of the TG-MS and TG-FTIR
investigations correlate closely with those obtained by the
[9] K. Hirojuki, J. Mitihiro, and S. Enuhisa, Jpn. Patent No. 69-
134541, 1989.
[10] F. Dimiza, S. Fountoulaki, A. N. Papadopoulos et al., “Non-
steroidal antiinflammatory drug-copper(II) complexes: Struc-
ture and biological perspectives,” Dalton Transactions, vol. 40,
no. 34, pp. 8555–8568, 2011.

Journal of Chemistry
7
Applied Organometallic Chemistry, vol. 16, no. 7, pp. 360–368,
[11] S. B. Etcheverry, D. A. Barrio, A. M. Cortizo, and P. A. M.
Williams, “ree new vanadyl(IV) complexes with non-ster-
oidal anti-inflammatory drugs (Ibuprofen, Naproxen and Tol-
metin). Bioactivity on osteoblast-like cells in culture,” Journal
of Inorganic Biochemistry, vol. 88, no. 1, pp. 94–100, 2002.
[12] C. Nu´n˜ez, A. Ferna´ndez-Lodeiro, J. Ferna´ndez-Lodeiro, J.
Carballo, J. L. Capelo, and C. Lodeiro, “Synthesis, spectroscopic
studies and in vitro antibacterial activity of Ibuprofen and its
derived metal complexes,” Inorganic Chemistry Communica-
tions, vol. 45, pp. 61–65, 2014.
2002.
[24] D. Czakis-Sulikowska, A. Malinowska, and K. Kafarska, “Com-
plexes of Mn(II), Cu(II) and Cd(II) with bipyridine isomers and
lactates,” Polish Journal of Chemistry, vol. 80, no. 12, pp. 1945–
1958, 2006.
[25] W. J. Geary, “e use of conductivity measurements in organic
solvents for the characterisation of coordination compounds,”
Coordination Chemistry Reviews, vol. 7, no. 1, pp. 81–122, 1971.
[26] K. Nakamoto, Infrared and Raman Spectra of Inorganic and
[13] J. Feng, X. Du, H. Liu et al., “Manganese-mefenamic acid
complexes exhibit high lipoxygenase inhibitory activity,” Dalton
Transactions, vol. 43, no. 28, pp. 10930–10939, 2014.
C
oordination Compounds, John Wiley & Sons, Inc., New York,
NY, USA, 2009.
[14] X. Totta, A. A. Papadopoulou, A. G. Hatzidimitriou, A. Papadopoulos,
and G. Psomas, “Synthesis, structure and biological activity of
nickel(II) complexes with mefenamato and nitrogen-donor li-
gands,” Journal of Inorganic Biochemistry, vol. 145, pp. 79–93,
2015.
[15] A. Ashraf, W. A. Siddiqui, J. Akbar et al., “Metal complexes of
benzimidazole derived sulfonamide: Synthesis, molecular
structures and antimicrobial activity,” Inorganica Chimica Acta,
vol. 443, pp. 179–185, 2016.
[16] S. Ramzan, S. Saleem, B. Mirza, S. Ali, F. Ahmed, and S.
Shahzadi, “Synthesis, characterization, and biological activity of
transition metals complexes with mefenamic acid (NSAIDs),”
Russian Journal of General Chemistry, vol. 85, no. 7, pp. 1745–
1751, 2015.
[17] C. T. Dillon, T. W. Hambley, B. J. Kennedy et al., “Gastrointes-
tinal toxicity, antiinflammatory activity, and superoxide dismu-
tase activity of copper and zinc complexes of the antiinfiamma-
tory drug indomethacin,” Chemical Research in Toxicology, vol.
16, no. 1, pp. 28–37, 2003.
[18] K. Kafarska, D. Czakis-Sulikowska, and W. M. Wolf, “Novel
Co(II) and Cd(II) complexes with non-steroidal anti-inflam-
matory drugs: Synthesis, properties and thermal investigation,”
Journal of ermal Analysis and Calorimetry, vol. 96, no. 2, pp.
617–621, 2009.
[19] R. P. Sharma, S. Singh, A. Singh, and V. Ferretti, “Spectra-
structure relationship: Synthesis, characterization of cop-
per(II) complexes with ibuprofenate, o-methoxybenzoate, p-
ethoxybenzoate and single crystal X-ray structure determi-
nation of [trans-Cu(en)2(H2O)2](L)2 where en = ethylenedi-
ammine, L = o-methoxybenzoate/p-ethoxybenzoate,” Journal of
Molecular Structure, vol. 918, no. 1-3, pp. 188–193, 2009.
[20] C. Dendrinou-Samara, D. P. Kessissoglou, G. E. Manoussakis,
D. Mentzafos, and A. Terzis, “Copper(II) complexes with
anti-inflammatory drugs as ligands. Molecular and crystal
structures of bis(dimethyl sulphoxide)tetrakis(6-methoxy-ꢀ-
methyl-2-naphthaleneacetato)dicopper(II) and bis(dimethyl
sulphoxide)tetrakis[1-methyl-5-(p-toluoyl)-1H-pyrrole-2-
acetato]dicopper(II),” Journal of the Chemical Society, Dalton
Transactions, no. 3, pp. 959–965, 1990.
˙
[21] W. Brzyska and W. Ozga, “Preparation and properties of rare
earth element complexes with mephenamic acid,” Polish Journal
of Chemistry, vol. 67, p. 619, 1993.
[22] A. Topacli and S. Ide, “Molecular structures of metal complexes
with mefenamic acid,” Journal of Pharmaceutical and Biomedi-
cal Analysis, vol. 21, no. 5, pp. 975–982, 1999.
[23] D. Kovala-Demertzi, V. Dokorou, Z. Ciunik, N. Kourkoumelis,
and M. A. Demertzis, “Organotin mefenamic complexes-prep-
arations, spectroscopic studies and crystal structure of a triph-
enyltin ester of mefenamic acid: Novel anti-tuberculosis agents,”

International Journal of
Advances in
Organic Chemistry
International
International Journal of
Photoenergy
Medicinal Chemistry
Physical Chemistry
Hindawi Publishing Corporation
http://www.hindawi.com
Hindawi Publishing Corporation
Hindawi Publishing Corporation
http://www.hindawi.com
Hindawi Publishing Corporation
http://www.hindawi.com
Volume 2014
Volume 2014
http://www.hindawi.com
Volume 2014
Volume 201ꢀ
Carbohydrate
Chemistry
Journal of
Quantum Chemistry
Hindawi Publishing Corporation
http://www.hindawi.com
Volume 2014
Submit your manuscripts at
https://www.hindawi.com
Journal of
The Scientific
Analytical Methods
in Chemistry
World Journal
Hindawi Publishing Corporation
Hindawi Publishing Corporation
http://www.hindawi.com
http://www.hindawi.com
Volume 2014
Volume 2014
International Journal of
Journal of
International Journal of
Bioinorganic Chemistry
Spectroscopy
Inorganic Chemistry
Electrochemistry
and Applications
Hindawi Publishing Corporation
http://www.hindawi.com
Hindawi Publishing Corporation
Hindawi Publishing Corporation
Hindawi Publishing Corporation
Volume 2014
http://www.hindawi.com
Volume 2014
http://www.hindawi.com
Volume 2014
http://www.hindawi.com
Volume 2014
Journal of
Journal of
International Journal of
Chromatography
Journal of
Theoretical Chemistry
Research International
Catalysts
Chemistry
Spectroscopy
Hindawi Publishing Corporation
http://www.hindawi.com
Hindawi Publishing Corporation
http://www.hindawi.com
Hindawi Publishing Corporation
http://www.hindawi.com
Hindawi Publishing Corporation
http://www.hindawi.com
Hindawi Publishing Corporation
http://www.hindawi.com
Volume 2014
Volume 2014
Volume 2014
Volume 2014
Volume 2014