Diaryl pyrazole-4-carbaldehyde benzoylhydrazones metal complexes: Synthesis and their antibacterial and antioxidant screening

Article abstract of DOI:10.14233/ajchem.2013.13131

Various heterocyclic ligands [1,3-diarylpyrazole-4-carbaldehyde benzoyl-hydrazones] and their metal complexes with Cu2+, Ni2+, Co2+, Pb ²⁺, Zn²⁺ and Fe²⁺ have been synthesized, characterized and screened for their antibact

Full text of DOI:10.14233/ajchem.2013.13131

Asian Journal of Chemistry; Vol. 25, No. 1 (2013), 419-423
http://dx.doi.org/10.14233/ajchem.2013.13131
Diaryl Pyrazole-4-carbaldehyde Benzoylhydrazones Metal Complexes:
Synthesis and Their Antibacterial and Antioxidant Screening
1
1
2,*
3
MUHAMMAD NASRULLAH , MISBAHUL AIN KHAN , MUHAMMAD NAEEM KHAN , MARK G. HUMPHREY ,
1
1
1
4
4
FAIZUL HASSAN NASIM , FARYAL CHAUDHRY , MOEENA GHAZAL ABIDI , UMAR FAROOQ and MUNAWAR ALI MUNAWAR
1Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
2Applied Chemistry Research Centre, PCSIR Laboratories Complex, Lahore, Pakistan
3Research School of Chemistry, Australian National University, Canberra, Australia
4Institute of Chemistry, University of the Punjab, Quaid-i-Azam Campus, Lahore, Pakistan
*Corresponding author: E-mail: changwani_1@yahoo.com
(Received: 28 November 2011;
Accepted: 28 July 2012)
AJC-11891
Various heterocyclic ligands [1,3-diarylpyrazole-4-carbaldehyde benzoyl-hydrazones] and their metal complexes with Cu2+, Ni2+, Co2+,
Pb2+, Zn2+ and Fe2+ have been synthesized, characterized and screened for their antibacterial and antioxidant activities. The synthesized
compounds were characterized through elemental analysis and spectroscopic techniques (FTIR, 1H NMR and Mass).
Key Words: Aryl pyrazoles, Vilsmeier-Haack reaction, Transition metal complexes, Antioxidant and antibacterial studies.
performed using Carlo Erba 1106 automatic analyzer. Melting
points were taken on a GallenKemp melting point apparatus
and were uncorrected.
INTRODUCTION
Derivatives of pyrazole are widely used as ligands in coor-
dination chemistry and are well known bioactive molecules.
The presence of metal in their complexes enhances the bioac-
tivity of these molecules. These metal based complexes have
attracted considerable interest in chemistry and biology owing
to their potentially beneficial biological activities which are
attributed to a chelation phenomenon with trace of metal ions1-5.
Hydrazones occupy unique position due to their diverse biolo-
gical activity which has been recently reviewed6.
Synthesis of ligands
1,3-Diarylpyrazole-4-carbaldehydes (1-4): A mixture
of an acetophenone (12 g, 0.1mol) and phenylhydrazine (10.8
g, 0.1 mol) in equimolar quantities along with a few drops of
acetic acid in ethanol (25 mL) was heated for a few minutes
on a hot plate to yield the corresponding acetophenone
phenylhydrazone (Scheme-I). These hydrazones, without
further purification, were treated withVilsmeier-Haack reagent
(POCl3, DMF). The temperature of the mixture was kept be-
low 10 ºC during addition, followed by heating on a water
bath for 1 h, poured into ice-cold water to give the precipitates
of the corresponding carbaldehyde. The precipitates were
washed with water and recrystallized from ethanol. The follo-
wing 1,3-diarylpyrazole-4-carbaldehydes were prepared in this
manner;
A number of hydrazones and their metal complexes have
been synthesized and reported to exhibit biological activity7,8.
In continuation of our previous studies of the metal complexes
related to diphenylpyrazole compounds9-11, we report the
synthesis of some novel metal complexes of diverse 1,3-
diarylpyrazole-4-carbaldehydes benzoylhydrazones.
EXPERIMENTAL
All the chemicals used in this study were of AR grade
and were purchased from Merck andAldrich and used without
1,3-Diphenylpyrazole-4-carbaldehyde (1): m.p. 141-143
ºC (Lit12. 138 ºC), yield; 7.4 g; 90 %.
1
further purification. The H NMR spectra were recorded on
3-(4′-Chlorophenyl)-1-phenylpyrazole-4-carbaldehyde
(2): m.p. 109-111 ºC (Lit12. 110 ºC), yield; 7.5 g; 88 %.
3-(4′-Nitrophenyl)-1-phenylpyrazole-4-carbaldehyde (3):
m.p. 120-122 ºC (Lit12. 120 ºC), yield; 6.9 g; 81 %.
3-(4′-Methylphenyl)-1-phenylpyrazole-4-carbaldehyde
(4): m.p. 160-162 ºC (Lit12. 165 ºC), yield; 6.9 g; 85 %.
Varian MR Instrument at 300 MHz in CDCl3 using
tetramethylsilane (TMS) as internal standard. Electronspray
ionization mass spectra (ESI MS) were recorded on VG
AutoSpec M series (EBE) MS spectrometer. FTIR spectra were
recorded on Bruker Tensor 27. Elemental analyses were

420 Nasrullah et al.
Asian J. Chem.
R
O
C
CH3
N
PhNHNH2
R
CH3
C
H
N
Ph
DMF / POCl3
R
R
O
C
H
C
H
N
CHO
N
PhCONHNH2
N
N
N
N
(1 - 4)
Ph
(5-8)
Ph
R = H, Cl, NO2, CH3
Scheme-I
1,3-Diarylpyrazole-4-carbaldehyde benzoylhydrazones
(5-8): General method: A mixture of 1,3-diarylpyrazole-4-
carbaldehyde (5 mmol), benzhydrazide (5 mmol) and 3-4 drops
of phosphoric acid in ethanol (30 mL), was refluxed for 0.5 h.
After cooling, the mixture was poured into distilled water (150
mL), off white precipitates were filtered off and recrystallized
from ethanol.
the nickel complex of 1,3-diphenyl-4-carbaldehyde thio-
semicarbazone13. The present work differs slightly from our
previous ones with respect to the aldehydic and hydrazide
functionalities which have been interchanged between the aryl
and diphenylpyrazole moieties. The results are as follows.
Synthesis: Scheme-I gives the general method for the
synthesis of the hydrazone ligands and their metal complexes
with various bivalent metal ions. During the synthesis of
aldehydes (1-4), it was found that some acetophenone phenyl-
hydrazones intermediates were very unstable and decomposed
on storage. Therefore, these were subjected to Vilsmeier-
Haack reaction without further purification. The ligands (5-8)
were obtained in good yields (75-80 %) by the condensation
of warm ethanolic solutions of corresponding aldehydes and
benzhydrazide. Their formation was confirmed from their
elemental analysis as well as mass and other spectra (Tables 1
and 2).
The following hydrazones were prepared in this manner:
1,3-Diphenylpyrazole-4-carbaldehyde benzoylhydrazone
(5): Off white crystals, m.p. 202 ºC, yield; 1.4 g; 77 %.
3-(4′-Chlorophenyl)-1-phenylpyrazole-4-carbaldehyde
benzoylhydrazone (6): Off-white crystals, m.p. 208 ºC, yield;
1.7 g; 85 %.
3-(4′-Nitrophenyl)-1-phenylpyrazole-4-carbaldehyde
benzoylhydrazone (7):Yellow crystals, m.p. 204 ºC, yield; 1.7
g; 82 %.
3-(4′-Methylphenyl)-1-phenylpyrazole-4-carbaldehyde
benzoylhydrazone (8): Off-white crystals, m.p. 201 ºC. yield;
1.6 g; 82 %.
Various metal complexes (9-32) prepared during this work
were also characterized through their elemental analysis and
spectroscopic data. The metal contents of these complexes were
determined with the help of AAS which showed that the
complexes had a metal to ligand ratio of 1:2. The mass spectral
data and elemental analysis (CHNS) also confirmed this
assumption.
Synthesis of metal complexes (9-32): General method:
Metal(II) chlorides (0.9 mmol) were dissolved in (10 mL)
ethanol and the solution was mixed with a warm ethanolic
solution (20 mL) containing equimolar quantity (0.9 mmol)
of ligands (5-8). The mixture was refluxed for 4 h, cooled to
room temperature and poured into distilled water (150 mL) to
give crystalline precipitates. These were washed successively
with water and ethanol, dried by vacuum suction and stored
in a desiccator containing anhydrous calcium chloride. The
physical and spectral data of complexes is tabulated in Tables
1 and 2.
FTIR analysis: The FTIR spectra (Table-2) were helpful
in determining the mode of bond formation between the ligands
and the metals. The ligand hydrazone seems to be predominantly
present in the enolic rather than the ketonic tautomeric form.
This is substantiated by the presence of a broad OH absorption
band for all the ligands (5-8) in the region of 3500-3000 cm-1
which is absent in all the complexes (9-32) pointing to an enolic
O bonding to the metal while there is a discreet shift in the
carbonyl frequencies of the hydrazone ligands (5-8) as com-
pared with their corresponding metal complexes. For (7, 21-
26), the bands in the region of 1550-1490 cm-1 and 1355-1315
cm-1 correspond to the asymmetric and symmetric stretching
of -NO2 group respectively14. The absorption bands around
RESULTS AND DISCUSSION
In continuation of our previous work on metal complexes
of 1,3-diphenylpyrazole-4-carbonyl hydrazones of aryl
aldehydes, we now report complexation studies of aroyl
hydrazones of 1,3-diphenylpyrazole-4-carbaldehyde. To our
best of knowledge, only one article has appeared describing

Vol. 25, No. 1 (2013)
Diaryl Pyrazole-4-carbaldehyde Benzoylhydrazones Metal Complexes 421
TABLE-1
PHYSICAL DATA FOR THE LIGANDS AND THE METAL COMPLEXES
Yield
Compd.
m.p.
(ºC)
Elemental analysis (%): Calcd. (Found)
H
Metal (%)
Calcd. (found)
MS†
m.f.
(%)
C
N
77.00
80.50
83.01
78.38
81.21
77.88
79.94
85.00
76.00
82.09
81.6
202
242 *
237*
248*
251*
236*
248*
208
366**
795
790
791
940
796
788
C23H18N4O
75.39 (75.31)
69.38 (69.33)
69.80 (69.83)
69.78 (69.74)
58.77 (58.72)
69.22 (69.19)
70.05 (69.10)
68.91 (68.97)
63.85 (63.89)
64.21 (64.27)
64.19 (64.13)
54.76 (54.71)
63.72 (63.79)
64.43 (64.49)
67.15 (67.09)
62.33 (62.34)
62.68 (62.61)
62.66 (62.61)
53.64 (53.61)
62.20 (62.27)
62.88 (62.83)
75.77 (75.71)
69.93 (69.87)
70.34 (70.30)
70.32 (70.25)
59.55 (59.60)
69.77 (69.72)
70.59 (70.63)
4.95 (4.88)
4.56 (4.52)
4.58 (4.55)
4.58 (4.55)
3.86 (3.90)
4 .55(4.10)
4.60 (4.07)
4.27 (4.25)
3.96 (3.99)
3.98 (3.94)
3.98 (3.93)
3.40 (3.47)
3.95 (3.98)
4.00 (4.35)
4.16 (4.11)
3.87 (3.92)
3.89 (3.83)
3.89 (3.87)
3.33 (3.31)
3.86 (3.82)
3.90 (3.92)
5.30 (5.25)
4.89 (4.94)
4.92 (4.94)
4.92 (4.96)
4.16 (4.10)
4.88 (4.83)
4.94 (4.99)
15.29 (15.32)
14.07 (14.08)
14.16 (14.15)
14.15 (14.18)
11.92 (11.95)
14.04 (14.00)
14.21 (14.14)
13.98 (13.92)
12.95 (12.98)
13.02 (12.95)
13.02 (13.08)
11.11 (11.19)
12.92 (12.98)
13.07 (13.03)
17.02 (17.08)
15.80 (15.87)
15.89 (15.93)
15.88 (15.82)
13.60 (13.67)
15.77 (15.72)
15.94 (15.99)
14.73 (14.69)
13.59 (13.54)
13.67 (13.72)
13.67 (13.72)
11.57 (11.51)
13.56 (13.60)
13.72 (13.78)
–
5
C46H36N8O2Cu
C46H36N8O2Ni
C46H36N8O2Co
C46H36N8O2Pb
C46H36N8O2Zn
C46H36N8O2Fe
7.98 (7.90)
7.42 (7.47)
7.44 (7.42)
22.04 (22.07)
8.19 (8.12)
7.08 (6.53)
–
9
10
11
12
13
14
6
400**, 402 C23H17N4OCl
244*
253*
271*
265*
243*
253*
204
863, 865
858, 860
859, 861
C46H34N8O2CuCl2
C46H34N8O2NiCl2
C46H34N8O2CoCl2
7.34 (7.39)
6.82 (6.89)
6.85 (6.89)
20.54 (20.48)
7.54 (7.60)
6.51 (6.50)
–
15
16
17
18
19
20
7
76.15
81.18
77.92
82.00
81.65
79.54
78.28
73.43
76.63
79.74
82.00
79.72
78.80
77.44
79.31
79.72
81.74
1008, 1010 C46H34N8O2PbCl2
864, 866
856, 858
411**
885
C46H34N8O2ZnCl2
C46H34N8O2FeCl2
C23H17N5O3
247 *
242*
263*
257*
248 *
270 *
201
C46H34N10O6Cu
C46H34N10O6Ni
C46H34N10O6Co
C46H34N10O6Pb
C46H34N10O6Zn
C46H34N10O6Fe
C24H20N4O
7.17 (7.12)
6.66 (6.61)
6.68 (6.64)
20.12 (20.08)
7.36 (7.32)
6.36 (6.32)
–
21
22
23
24
25
26
8
880
881
1030
886
878
380**
823
818
248*
255*
247*
261*
252*
257*
C48H40N8O2Cu
C48H40N8O2Ni
C48H40N8O2Co
C48H40N8O2Pb
C48H40N8O2Zn
C48H40N8O2Fe
7.71 (7.77)
7.16 (7.10)
7.19 (7.23)
21.40 (21.47)
7.91 (7.97)
6.84 (6.90)
27
28
29
30
31
32
819
968
824
816
*Decomposed; †Corresponding to [ML2+2H]+; **corresponding to [L+]
TABLE-2
FTIR AND 1H NMR DATA
1H NMR data δ (ppm)
Compd.
IR (cm-1)
3190 (OH), 1641 (C=O), 1597 (C=N-N=C)
10.30 (s, 1H, NHCO), 8.39 (s, 1H, CH=N), 8.34 (s, 1H, Pz), 7.21-7.85 (m, 15H,
Ar)
5
1672 (C=O), 1596 (C=N-N=C)
1642 (C=O), 1599 (C=N-N=C)
1650 (C=O), 1600 (C=N-N=C)
1641 (C=O), 1598 (C=N-N=C)
1642 (C=O), 1599 (C=N-N=C)
1672 (C=O), 1596 (C=N-N=C)
3160 (OH), 1652 (C=O), 1599 (C=N-N=C)
8.61 (s, 1H, CH=N), 8.36 (s, 1H, Pz), 7.26-7.91 (m, 15H, Ar)
8.41 (s, 1H, CH=N), 8.14 (s, 1H, Pz), 7.00-7.71 (m, 15H, Ar)
8.61 (s, 1H, CH=N), 8.31 (s, 1H, Pz), 7.26-7.89 (m, 15H, Ar)
8.36 (s, 1H, CH=N), 8.22 (s, 1H, Pz), 7.11-7.77 (m, 15H, Ar)
8.59 (s, 1H, CH=N), 8.33 (s, 1H, Pz), 7.26-7.90 (m, 15H, Ar)
8.46 (s, 1H, CH=N), 8.28 (s, 1H, Pz), 7.18-7.84 (m, 15H, Ar)
9.82 (s, 1H, NHCO), 8.54 (s, 1H, CH=N), 8.35 (s, 1H, Pz), 7.25-7.91 (m, 14H,
Ar)
9
10
11
12
13
14
6
1670 (C=O), 1597 (C=N-N=C)
1656 (C=O), 1599 (C=N-N=C)
1656 (C=O), 1605 (C=N-N=C)
1656 (C=O), 1601 (C=N-N=C)
1649 (C=O), 1592 (C=N-N=C)
1649 (C=O), 1598 (C=N-N=C)
8.68 (s, 1H, CH=N), 8.27 (s, 1H, NCH=), 7.34-7.83 (m, 14H, Ar)
8.69 (s, 1H, CH=N), 8.28 (s, 1H, Pz), 7.26-7.86 (m, 14H, Ar)
8.66 (s, 1H, CH=N), 8.23 (s, 1H, Pz), 7.26-7.88 (m, 14H, Ar)
8.59 (s, 1H, CH=N), 8.31 (s, 1H, Pz), 7.26-7.89 (m, 14H, Ar)
8.61 (s, 1H, CH=N), 8.29 (s, 1H, Pz), 7.25-7.90 (m, 14H, Ar)
8.63 (s, 1H, CH=N), 8.39 (s, 1H, Pz), 7.24-7.91 (m, 14H, Ar)
15
16
17
18
19
20
7
3210 (OH), 1649 (C=O), 1597 (C=N-N=C), 1502 & 10.34 (s, 1H, NHCO), 8.49 (s, 1H, CH=N), 8.41 (s, 1H, Pz), 7.11-7.93 (m, 14H,
1334 (NO2) Ar)
1641 (C=O), 1598 (C=N-N=C), 1492 & 1343 (NO2) 8.40 (s, 1H, CH=N), 8.29 (s, 1H, Pz), 7.25-7.88 (m, 14H, Ar)
1640 (C=O), 1598 (C=N-N=C), 1501 & 1341 (NO2) 8.46 (s, 1H, CH=N), 8.29 (s, 1H, Pz), 7.26-7.88 (m, 14H, Ar)
1646 (C=O), 1597 (C=N-N=C), 1500 & 1335 (NO2) 8.46 (s, 1H, CH=N), 8.27 (s, 1H, Pz), 7.26-7.87 (m, 14H, Ar)
1651 (C=O), 1597 (C=N-N=C), 1501 & 1334 (NO2) 8.45 (s, 1H, CH=N), 8.29 (s, 1H, Pz), 7.26-7.88 (m, 14H, Ar)
1651 (C=O), 1598 (C=N-N=C), 1500 & 1339 (NO2) 8.43 (s, 1H, CH=N), 8.30 (s, 1H, Pz), 7.26-7.91 (m, 14H, Ar)
1681 (C=O), 1596 (C=N-N=C), 1502 & 1341 (NO2) 8.57 (s, 1H, CH=N), 8.30 (s, 1H, Pz), 7.18-7.89 (m, 14H, Ar)
21
22
23
24
25
26
8
3237 (OH), 1640 (C=O), 1604 (C=N-N=C)
9.71 (s, 1H, NHCO), 8.57 (s, 1H, CH=N), 8.30 (s, 1H, Pz), 7.18-7.89 (m, 14H,
Ar), 2.35 (s, 3H, CH3)
1671 (C=O), 1597 (C=N-N=C)
1641 (C=O), 1600 (C=N-N=C)
1642 (C=O), 1607 (C=N-N=C)
1641 (C=O), 1600 (C=N-N=C)
1641 (C=O), 1600 (C=N-N=C)
1642 (C=O), 1598 (C=N-N=C)
8.61 (s, 1H, CH=N), 8.41 (s, 1H, Pz), 7.12-7.93 (m, 14H, Ar) 2.35(s, 3H, CH3)
8.60 (s, 1H, CH=N), 8.29 (s, 1H, Pz), 7.22-7.85 (m, 14H, Ar) 2.35(s, 3H, CH3)
8.63 (s, 1H, CH=N), 8.45 (s, 1H, Pz), 7.20-7.76 (m, 14H, Ar) 2.37(s, 3H, CH3)
8.55 (s, 1H, CH=N), 8.34 (s, 1H, Pz), 7.16-7.90 (m, 14H, Ar) 2.33(s, 3H, CH3)
8.56 (s, 1H, CH=N), 8.30 (s, 1H, Pz), 7.17-7.73 (m, 14H, Ar) 2.33(s, 3H, CH3)
8.51 (s, 1H, CH=N), 8.42 (s, 1H, Pz), 7.15-7.92 (m, 14H, Ar), 2.33(s, 3H, CH3)
27
28
29
30
31
32

422 Nasrullah et al.
Asian J. Chem.
1660-1590 cm-1 are designated to the azomethine (C=N-N=C)
group15. In the complexes, the frequencies of azomethine
groups appear mostly towards the lower region which strongly
indicates that the ligands coordinate to the metal through the
carbonyl oxygen and the azomethine nitrogen of the enolic
form of the ligand (Fig. 1). This is further confirmed on the
basis of 1H NMR studies (see below). Hence, the ligands act
as monobasic bidentate ligands in all the complexes.
Electron spray ionization mass spectra: The positive
ion ESI MS of the ligands (5-8) and their metal complexes
(9-32) in MeOH are dominated by the parent molecular ion
peaks. The m/z values shown in Table-1 are L+ molecular ion
peak for ligands (L for ligands) and monopositive complex
ion [ML2+2H]+ molecular ion peaks. The data support the
assumption that metal to ligand ratio is 1:2 in all the complexes.
Biological activities
Antibacterial activity: The method adopted here is based
on the principle that microbial cell number increases as the
microbial growth proceeds in the log phase of growth which
Ph
N
N
results in the increased absorbance of the broth medium16,17
.
Bacillus subtills was the bacterial strain used for the present
study.Ampicillin was used as the positive control and solvent/
nutrient broth as the negative control. The per cent inhibitions
of the synthesized compounds, in comparison with ampicillin,
were recorded in Table-3.
C
O
N
N
C
H
R
M+2
R
O
TABLE-3
BIOLOGICAL ACTIVITIES
H
C
N
N
C
Antibacterial activity*
Antioxidant activity**
(Inhibition %)
Bacillus subtills
(Inhibition %)
10.75
8.62
Compd.
N
N
I
31.48
10.38
39.74
55.58
18.44
23.37
03.11
31.21
74.00
12.98
65.45
52.20
17.40
71.94
33.33
18.44
28.31
15.00
76.88
33.24
68.31
14.81
7.27
5
9
Ph
13.46
27.58
15.35
12.47
12.56
32.09
16.91
12.72
16.25
14.69
32.51
6.15
10
11
12
13
14
6
Ph
N
N
H
N
C
O
N
CH
15
16
17
18
19
20
7
R
M+2
R
O
C
H
C
H
N
17.78
44.83
42.69
36.20
11.82
13.79
3.61
N
21
22
23
24
25
26
8
N
II
N
Ph
Fig. 1. Structure of metal complexes (9-32), R = H, Cl, NO2, CH3
20.67
28.98
36.29
33.66
5.17
27
28
29
30
31
32
1H NMR spectra: The chemical shift values for the
11.94
11.16
84.67
84.69
83.89
ligands (5-8) and the metal complexes are recorded in Table-
2. All the ligands differ only in substitution at 4′-position on
the 3-aryl substituent in the pyrazole (Pz) ring. The 3-aryl ring
protons show multiplets in the 7.11-7.93 ppm region. The
characteristic NHCO signal, observed at 10.30 ppm (5), is
conspicuously absent in the all the metal complexes (9-32). It
was further observed that the signals of the protons at NHCO,
H-5 proton of pyrazole (Pz) and 4'-substituted phenyl ring
were shifted from their original δ values from the respective
ligands (Table-2). Thus in the formation of complexes of these
bivalent metal ions, the NHCO signals disappeared due to
enolization of the ligands during complex formation with the
help of the carbonyl oxygen and azomethine nitrogen of the
enolic tautomer I (Fig. 1).
3.44
2.87
*Standard for antibacterial studies was ampicilin.
**Standard for antioxidant studies was ascorbic acid.
It is clear that most of the compounds showed significant
antibacterial activities. In case of ligand (5) and its metal
complexes, the metal complexation caused the activity to
increase except for Cu complex (9), where activity decreased
to some extent (10.75 to 8.62 %). The maximum activity was
found in cobalt complex (11) (27.58 %). For ligand (6)
(4′-chloro derivative) and its metal complexes, the complex

Vol. 25, No. 1 (2013)
Diaryl Pyrazole-4-carbaldehyde Benzoylhydrazones Metal Complexes 423
formation caused the activity to decrease. The zinc complex
(19) had almost similar activity as that of the ligand. In (7)
(4′-nitro derivative) and its complexes with metals, the anti-
bacterial activity was increased in complexes with Cu (21),
Ni (22) and Co (23), whereas it decreased in complexes with
Pb (24), Zn (25) and Fe (26). Similarly for (8) (4′-methyl
derivative) and the complexes, it was found that the activity
increased with Cu (27), Ni (28) and Co (29) complexes whereas
it decreased in complexes with Pb (30), Zn (31) and Fe (32) to
a significant extent.
presence of electron donating bulky group -CH3 decreased
the activity. In the complexes, the Cu (15) and Co (17) comp-
lexes with chloro substituted ligand showed the maximum
activity. Among Ni complexes, (10) exhibited the maximum
activity. It was found that the Pb (30), Zn (31) and Fe (32)
complexes with the 4′-methyl substituted ligand exhibited the
highest values among all the compounds/complexes studied.
Conclusion
The present study revealed the complexes formed from
ligands (5-8) have stoichiometry of 2:1 (ligand: metal) with a
possible structure showing chelation through carbonyl oxygen
and azomethyne nitrogen. These are evidenced by their IR,
1H NMR and elemental analytical data. The antibacterial
activity against Bacillus subtills showed that within a series,
the metal complexes are more active than corresponding
ligands. In ligands, on substitution of H with -Cl, -NO2 or
-CH3 at 4′-position, the antibacterial activity increased signi-
ficantly. The complexes of metals with ligands having electron
withdrawing group (-NO2) were the most active against the
gram positive bacteria. The antioxidant behaviour of the ligands
having -NO2 group increased than that with -H whereas the
presence of electron donating bulky group -CH3 decreased
the activity. The Cu and Co complexes with chloro substituted
ligand showed the maximum activity. It was found that Pb, Zn
and Fe complexes with 4′-methyl substituted ligand exhibited
the highest values among all studied compounds.
When the activities of the different ligands and their
complexes are compared, very interesting results are obtained.
In ligands, on substitution of H with -Cl, -NO2 or -CH3 at 4′
position in the parent ligand (5), the antibacterial activity
increased to significant extent. So, the presence of some group
at the specified position causes an increase in the activity; this
increase is greater in case of small sized group (-Cl) as com-
pared to large ones.
In Cu complexes (9, 15, 21, 27) of all four ligands, the
complex with a -NO2 group at 4′-position (7) showed the
maximum activity (44.83 %) of all the complexes. In Ni
complexes, (22) showed the second maximum activity (42.83
%). The similar result was observed in Co complex (23) (ligand
with nitro group). The complexes of Pb (12) and Fe (14)
showed the best results (highest activities) with ligand having
no group at 4′-position, rather the activities were decreased
with any of the substitution with electron withdrawing or
electron donating group. The Zn complexes showed a very
different behaviour. The -Cl substituted ligand showed the
maximum activity.
ACKNOWLEDGEMENTS
One of the authors (MN) acknowledged the financial support
by HEC Pakistan in the form of an indigenous Ph.D. fellow-
ship and assistance in the form of IRSIP to travel and work at
Australian National University. The author also acknowledged
the helpful discussion with Prof. Dr. Saeed Ahmed (University
of Engineering & Technology, Lahore).
It can be concluded that the complexes of metal with
ligand having the electron withdrawing group (-NO2) were
the most active against Bacillus subtills.
Antioxidant activity: Garret nitric oxide (NO) scavenging
method was used for the determination of antioxidant activity18.
The method is based on the principle that nitrate present in
the sample must be reduced to nitrite. This method involves
the determination of nitrite, instead of nitrate in the presence
of Griss reagent. The results are presented in Table-3.
The antioxidant activity of ligand (5) was substantially
increased on complexation with Ni (10) and Co (11) from
31.48 to 39.74 and 55.58, respectively. The complex with Fe
(14) seemed to be the least active, almost 10 times less than
the ligand. With 4′-chloro substituted ligand (6), the activity
increased with Cu (15), Co (17), Pb (18) and Fe (20) comp-
lexes whereas the activity of Ni (16) and Zn (19) complexes
was quite less than that of ligand (6). For 4′-nitro ligand (7),
Pb (24) and Fe (26) complex formation increased the anti-
oxidant behaviour of the compound and the complexes with
other four metals (Cu (21), Ni (22), Co (23) and Zn (25)) caused
the activity to decrease significantly. Similarly for 4′-methyl
substituted ligand (8), the activity increased after complex
formation with Pb (30), Zn (31) and Fe (32): the Zn (31)
complex showed the maximum antioxidant activity of all the
compounds studied.
REFERENCES
1. D.L. Klayman, J.F. Bartosevich, T.S. Griffin, C.J. Mason and J.P. Scovill,
J. Med. Chem., 22, 855 (1979).
2. D.X. West, S.B. Padhye and P.B. Sonawane, Struct. Bond., 76, 1 (1991).
3. A.E. Liberta and D.X. West, Biometals, 5, 121 (1992).
4. F.A. French, E.J. Blanz, J.R. DoAmaral and D.A. French, J. Med. Chem.,
13, 1117 (1970).
5. H. Beraldo and D. Gambino, Mini Rev. Chem., 4, 31 (2004).
6. S. Rollas and S.G. Kucukguzel, Molecules, 12, 1910 (2007).
7. E.W. Ainscough, A.M. Brodie, W.A. Denny, G.J. Finlay, S.A. Gothe and
J.D. Ranford, J. Inorg. Biochem., 77, 125 (1999).
8. D. Van Reyk, S. Sarel and N. Hunt, Biochem. Pharmacol., 60, 581 (2000).
9. I.Ahmad, M.A. Khan and M.Ather, Pak. J. Sci. Ind. Res., 43, 38 (2000).
10. I. Ahmad, M.A. Khan and M. Ather, J. Pure Appl. Sci., 17, 67 (1998).
11. I. Ahmad, M. A. Khan, M. Ather, Pak. J. Sci. Ind. Res., 44, 268 (2001)
12. O. Prakash, K. Pannu and A. Kumar, Molecules, 11, 43 (2006).
13. V.M. Leovac, S.B. Novakovic, G.A. Bogdanovic, M.D. Joksovic, K.M.
Szecsenyi and V.M. Cesljevic, Polyhedron, 26, 3783 (2007).
14. D.L. Pavia, G.M. Lampman and G.S. Kriz, Introduction to Spectroscopy,
Thomson Learning Inc. USA (2001).
15. R.T. Conley, Infrared Spectroscopy, Allyn and Bacom Inc. Boston,
USA (1972).
16. M. Kaspady, V.K. Narayanaswamy, M. Raju and G.K. Rao, Lett. Drug
Design Discov., 6, 21 (2009).
17. A.K. Patel, R.J. Patel, K.H. Patel and R.M. Patel, J. Chil. Chem. Soc.,
54, 228 (2009).
Among all the ligands (5-8), it was found that the substi-
tution at 4′-position with electron withdrawing bulky group
-NO2 caused the antioxidant activity to increase whereas the
18. D.C. Garret, QuantitativeAnalysis of Drugs, Chapman and Hall, Japan,
Vol. 3, p. 456 (1964).