Antimicrobial and antioxidant activities of new metal complexes derived from (E)-3-((5-phenyl-1,3,4-oxadiazol-2-ylimino)methyl)naphthalen-2-ol

Article abstract of DOI:10.1007/s00044-011-9880-1

(E)-3-((5-phenyl-1,3,4-oxadiazol-2-ylimino)methyl) naphthalen-2-ol (LH) has been synthesized and used as a ligand for the formation of V(IV), Cr(III), Mn(II), Co(II), Ni(II), and Cu(II) complexes. The chemical structures were characterized using different

Full text of DOI:10.1007/s00044-011-9880-1

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res (2012) 21:3204–3213
DOI 10.1007/s00044-011-9880-1
ORIGINAL RESEARCH
Antimicrobial and antioxidant activities of new metal complexes
derived from (E)-3-((5-phenyl-1,3,4-oxadiazol-2-
ylimino)methyl)naphthalen-2-ol
Ahmed A. Al-Amiery
Received: 26 July 2011 / Accepted: 4 November 2011 / Published online: 12 November 2011
ꢀ Springer Science+Business Media, LLC 2011
Abstract (E)-3-((5-phenyl-1,3,4-oxadiazol-2-ylimino)methyl)
naphthalen-2-ol (LH) has been synthesized and used as a
ligand for the formation of V(IV), Cr(III), Mn(II), Co(II),
Ni(II), and Cu(II) complexes. The chemical structures were
characterized using different spectroscopic methods. The
elemental analyses revealed that the complexes have the
general formula [ML2(H2O)2] [where M = Mn(II), Co(II),
and Cu(II)], while the Cr(III) complex has the formula
[CrL2(H2O)2]Cl, V(IV) complex has the formula [VO2L2],
and Ni(II) complex has the formula [NiL2]. The molar con-
ductance data revealed that all the metal chelates except the
Cr(III) are non-electrolytes. From the magnetic susceptibil-
ity measurement and UV–Visible spectra, it is found that the
structures of Cr(III), Mn(II), Co(II), and Cu(II) complexes
are octahedral, V(IV), complex is square pyramid and Ni(II)
complex is square planar. The stability of the prepared
complexes was studied theoretically using density function
theory. The total energy for the complexes was calculated
and it was shown that the copper complex is the most stable.
Complexes were tested against selected types of microbial
organisms and showed significant activities. The free radical
scavenging activity of metal complexes have been deter-
mined by their interaction with the stable DPPH-free
radicals. All the compounds have shown encouraging anti-
oxidant activities.
Introduction
Drug resistance has become a growing problem in the
treatment of infectious diseases caused by bacteria and
fungi (Raman et al., 2007). The serious medical problem
of bacterial and fungal resistance and the rapid rate at
which it develops has led to increasing levels of resistance
to classical antibiotics (Rice et al., 1999; Ironmonger
et al., 2007). The discovery and development of effective
antibacterial and antifungal drugs with novel mechanism
of action has become an urgent task for infectious disease
research programs (Kumar et al., 2011). Schiff bases and
their complexes are largely studied because of their
interesting and important properties such as their ability to
reversibly bind oxygen (Muhammad et al., 2011) to redox
system, biological systems (Park et al., 1998) and oxida-
tion of DNA (Landy, 1989). Antioxidants have become
one of the major areas of scientific research (Gursoy and
Yukse, 2010). Antioxidants are extensively studied for
their ability to protect organism and cell from damage that
are induced by oxidative stress. Scientists in many dif-
ferent disciplines become more interested in new com-
pounds, either synthesized or obtained from natural
sources that could provide active components to prevent or
reduce the impact of oxidative stress on cell (Hussain
et al., 2003). The synthesis of compounds incorporating
oxadiazole ring have been attracting widespread attention
due to their diverse pharmacological properties such as
antimicrobial, anti-inflammatory, analgesic, and antitumor
activities (Amir and Shikha, 2004; Holla and Shivananda,
2002; Neslihan, 2005; Hakan et al., 2010; Scovill and
Franchino, 1982). The preparation of a (E)-3-((5-phenyl-
1,3,4-oxadiazol-2-ylimino)methyl)naphthalen-2-ol, used as
a ligand for the formation of V(IV), Cr(III), Mn(II),
Co(II), Ni(II), and Cu(II) complexes, is presented in this
Keywords Antimicrobial ꢀ Complexes ꢀ DPPH ꢀ
Oxadiazol ꢀ Scavenging ꢀ Vanadium
A. A. Al-Amiery (&)
Biotechnology Division, Applied Science Department,
University of Technology, Baghdad 10066, Iraq
e-mail: dr.ahmed1975@gmail.com
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Med Chem Res (2012) 21:3204–3213
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Synthesis of the metal complexes
study. The chemical structures of the newly synthesized
complexes were confirmed by spectroscopic techniques
and CHN analysis. The microbial activities of all synthe-
sized compounds and their in vitro antioxidant activities
were also investigated.
Bis((E)-3-((5-phenyl-1,3,4-oxadiazol-2-ylimino)methyl)
naphthalen-2-ol)nickel (II) The ethanolic solution of
brown colored nickel (II) complex was obtained by mixing
the solutions of nickel chloride (0.28 g in 100 ml),and
ligand (0.63 g in 100 ml) in 1:2 molar ratio followed by
dropwise addition of 10% sodium acetate (pH 7.5) was
refluxed for 2 h over a water bath. On keeping the reaction
mixture overnight, dark brown solids separated out. The
adduct was filtered, washed with ethanol, and petroleum
ether and finally dried under vacuum.
Experimental
General
All chemicals used in this study were of reagent grade
(AR) supplied by either Sigma-Aldrich or Fluka, and used
without purification. The FT-IR spectra were recorded
in the (4,000–200) cm-1 range on Cesium iodide disks
using a Shimadzu FTIR 8300 Spectrophotometer. Proton
NMR spectra were recorded on Bruker-DPX 300 MHz
spectrometer with TMS as internal standard. The UV–
Visible spectra were measured in ethanol using a Shima-
dzu UV–Vis. 160A spectrophotometer in the range
(200–1,000) nm. Magnetic susceptibility measurement for
complexes was obtained at room temperature using a
Magnetic Susceptibility Balance Model MSB-MKI. The
flame atomic absorption of a Shimadzu AA-670 elemental
analyzer was used for metal determination. Elemental
microanalysis was carried out using a CHN elemental
analyzer model 5500-Carlo Erba instrument. A Gallenk-
amp M.F.B.600.010 F melting point apparatus was used
to measure the melting points of all the prepared
compounds.
Bis((E)-3-((5-phenyl-1,3,4-oxadiazol-2-ylimino)methyl)
naphthalen-2-ol)vanadium(II) LH (0.63 g, 0.002 mol) in
100 ml of ethanol was added with stirring to the
VOSO4ꢀ5H2O solution (0.001 mol, 0.253 g) in 2:1 molar
ratio. The pH of the solution was raised up to 7.0 by adding
5 ml of 10% sodium acetate solution. The reaction mixture
was refluxed for half an hour. Pink color complex was sep-
arated out then washed and filtered under suction. Further
washing with water, ethanol, and petroleum ether to remove
unreacted ligand and dried over anhydrous CaCl2.
Bis((E)-3-((5-phenyl-1,3,4-oxadiazol-2-ylimino)methyl)
naphthalen-2-ol)diaqua, cobalt(II), manganese(II), cop-
per(II) or chromium(III) chloride, complexes Acidic
solutions of metal (CrCl3ꢀ6H2O, MnCl2ꢀ4H2O, CoCl2ꢀ
6H2O, and CuCl2ꢀ2H2O) (1 mmol) in hot ethanol (20 ml)
were mixed with hot ethanolic solution 50 ml of the ligand
(2 mmol) and dropwise addition of 10% (w/v) sodium
acetate till the complexes precipitated out (pH 8.5). The
closed complexes were filtered, washed with water, etha-
nol, and dried under vacuum. Purity of the complexes was
checked by thin layer chromatography (TLC). The TLC
plate prepared with precoated silica gel aluminum pla-
te 60F-254 and the stationary face having a thickness of
about 0.5 mm. 5 ll each of test solution was applied on
silica gel plate (20 9 10 cm). The TLC plate was kept in a
developing chamber saturated ethyl acetate:methanol:
acetone (25:25:50) solvent systems (Kadhum et al., 2011).
Chemistry
Synthesis of the ligand
A mixture of equimolar quantity of 3-hydroxy-2-naph-
thaldehyde and 2-amino-5-phenyl-1,3,4-oxadizole in min-
imum amount of ethanol was refluxed for 2 h. After
cooling to room temperature the product was separated out
and washed with distilled water, ether and finally several
times with cold ethanol, dried, and then recrystallized from
acetone which gave yellow needle shaped crystals of (E)-3-
((5-phenyl-1,3,4-oxadiazol-2-ylimino)methyl)naphthalen-
2-ol (LH) (Al-Amiery et al., 2011a, b), yield 87%, m.p.
Study of complex formation in solution
The complexes of the ligand with metal ions were studied
in dimethylformamide (DMF), to determined M:L ratio in
the complex following the molar ratio method. Several
series of solutions were prepared having constant concen-
tration (10-3 M) of the metal ion and (L). The M:L ratio
was determined from the relationship between the
absorption of light (Al-Amiery et al., 2011a, b) and the
M:L molar ratio. The results of complexes formation in
solution are listed in Table 2.
1
216ꢁC; H-NMR (CDCl3): d 5.4 (s, 1H) for –O–H, d 6.3
(s, 1H) for –N=C–H), d 7.30 (m, 1H) for aromatic ring)
and d 7.90 (m, 1H) for aromatic ring); IR: 2400 m cm-1
(OH, hydroxy), 1630 cm-1 (C=N), 1570 cm-1 (C=C,
Alkene), 1050 and 1230 cm-1 (sym. and asym. C–O);
Anal. Calcd. for C19H13N3O2: C 72.37%, H 4.16%, N
13.33%. Found: C 72.10%, H 4.02%, N 13.30%.
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Med Chem Res (2012) 21:3204–3213
Pharmacology
Evaluation of antibacterial activities The in vitro biologi-
cal screening of all the compounds was carried out to evaluate
their antibacterial activity against Escherichia coli, Klebsi-
ella pneumoniae, Pseudomonas vulgaris, Pseudomonas
aeruginosa, Staphylococcus aureus, and Bacillus cereus by
the disk diffusion method, using agar nutrient as the medium
and ciprofloxacin as the standard. The antifungal activity of
the compounds was evaluated by the disk diffusion method
against the fungi Aspergillus niger and Candida albicans
cultured on potato dextrose agar as medium and ketoconazole
as the standard. The stock solution (10-2 M) was prepared by
dissolving the compounds in DMSO and the solutions were
serially diluted to find the minimum inhibitory concentration
(MIC) values. Inatypicalprocedure(Al-Amieryetal., 2009),
the disk was filled with the test solution using a micropipette
and the plate was incubated 24 h for bacteria and 72 h for
fungi. During this period, the test solution diffused and the
growth of the inoculated microorganisms was affected.
Fig. 1 The structure of (E)-3-((5-phenyl-1,3,4-oxadiazol-2-ylimi-
no)methyl)naphthalen-2-ol (LH)
Table 1 The atomic charges of LH
Atom
Charge
[C(1)]
C -0.175
C 0.257
[C(2)]
[C(3)]
C -0.004
C -0.063
C 0.018
[C(4)]
[C(5)]
[C(6)]
C -0.044
C -0.059
C -0.038
C -0.066
C 0.050
[C(7)]
[C(8)]
[C(9)]
[C(10)]
[O(11)]
[C(12)]
[N(13)]
[O(14)]
[C(15)]
[N(16)]
[N(17)]
[C(18)]
[C(19)]
[C(20)]
[C(21)]
[C(22)]
[C(23)]
[C(24)]
[H(25)]
[H(26)]
[H(27)]
[H(28)]
[H(29)]
[H(30)]
[H(31)]
[H(32)]
[H(33)]
[H(34)]
[H(35)]
[H(36)]
[H(37)]
Evaluation of antioxidant activity Stock solution (1 mg/
ml) was diluted to final concentrations of 20–100 lg/ml.
Ethanolic DPPH solution (1 ml, 0.3 mmol) was added to
sample solutions in DMSO (3 ml) at different concentra-
tions (50–300 lg/ml) (Chen et al., 1999). The mixture was
shaken vigorously and allowed to stand at room tempera-
ture for 30 min. The absorbance was then measured at
517 nm in a UV–Vis spectrophotometer. The lower
absorbance of the reaction mixture indicates higher free
radical scavenging activity. Ethanol was used as the solvent
and ascorbic acid as the standard. The DPPH radical
scavenger was calculated using the following equation:
O -0.206
C 0.148
N -0.213
O -0.107
C 0.469
N -0.324
N -0.266
C 0.350
C 0.043
C -0.052
C -0.027
C -0.055
C -0.028
C -0.051
H 0.026
A0 ꢁ A1
Scavenging effect ð%Þ ¼
ꢂ 100;
A0
where A0 is the absorbance of the control reaction and A1 is
the absorbance in the presence of the samples or standards.
A0 - A1.
H 0.021
H 0.022
H 0.025
H 0.025
Results and discussion
H 0.023
H 0.194
Chemistry
H -0.013
H 0.021
(E)-3-((5-Phenyl-1,3,4-oxadiazol-2-ylimino)methyl)naph-
thalen-2-ol (Fig. 1) is the key intermediate for the metal
complexes synthesized in this study.
H 0.025
H 0.025
H 0.025
These data shows that the atomic charges have been
affected by the presence of substituent of rings as shown in
Table 1. As a reference compound the (E)-3-((5-phenyl-
1,3,4-oxadiazol-2-ylimino)methyl)naphthalen-2-ol (Fig. 1),
data for minimized geometry and the 3D-geometrical
structure is shown in Fig. 2.
H 0.023
The data obtained shows that the highest atomic charge
in LH molecule is at [N(16) -0.324] the next charge value
is at [N(13) -0.213] and [O(11) -0.206]. These data
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Med Chem Res (2012) 21:3204–3213
3207
Fig. 2 The 3D structure of LH
Scheme 1 Formation of the
ligand
Table 2 Analytical data for the metal complexes
No.
Compounds
M:L
M.P. ꢁC/color
Elemental analysis found/calculated
C%
H%
N%
M%
C1
C2
C3
C4
C5
C6
[VO(L)2]
1:2
1:2
1:2
1:2
1:2
1:2
266d/light green
272d/green
65.42/65.62
60.51/60.68
63.42/63.42
63.24/63.07
66.47/66.40
62.72/62.68
3.44/3.48
3.71/3.75
3.89/3.92
3.86/3.90
3.49/3.52
3.84/3.88
12.05/12.08
11.15/11.17
11.68/11.68
11.65/11.61
12.24/12.23
11.54/11.54
7.60/7.32
7.16/6.91
7.60/7.63
7.90/8.14
8.40/8.54
8.71/8.73
[CrL2(H2O)2]Cl
[MnL2(H2O)2]
[CoL2(H2O)2]
[NiL2]
245/dark brown
280d/light pink
268d/orange
[Cu(H2O)2L2]
292d/green
(Table 1) show clearly that oxygen atom [N(16)] is the
most reactive toward the bonding with the metal. The
determined bond angle, twist angle, 3D geometrical
structure (Fig. 2), and stereochemistry [C(12)–N(13): (E)]
indicate that this molecule is planar.
bidentate ligand through its oxygen and nitrogen atoms.
The analytical data of these complexes are presented in
Table 2. All the complexes are fairly stable and can be
stored for long periods at room temperature. The solid
colored complexes are stable toward heat, air, and mois-
ture, and they dissolved in dimethyl formamide and
dimethyl sulfoxide. The analytical data of the complexes
are consistent with the proposed molecular structures
(Fig. 3), with molar metal to ligand ratio of (1:2). The
stability for the prepared complexes was studied theoreti-
cally using density function theory (DFT). The total energy
The synthesis of (E)-3-((5-phenyl-1,3,4-oxadiazol-2-yli-
mino)methyl)naphthalen-2-ol was performed by vigorously
refluxing 3-hydroxy-2-naphthaldehyde and 2-amino-5-phe-
nyl-1,3,4-oxadizole. 87% yield (Scheme 1).
The complexes were synthesized by the reactions of LH
with the metal ions, in which the ligand behaves as a
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Med Chem Res (2012) 21:3204–3213
Square pyramidal geometry V(IV) complex
Octahedral geometry Mn(II), Co(II) and Cu(II) complex
Square planer geometry Ni(II) complex
Octahedral geometry Cr(III) complex
Fig. 3 The proposed structures for the complexes
for the complexes was calculated and it was shown that the
copper complex is the most stable and the chromium
complex is the least stable as follows: Cu(II) [ Ni(II) [
Co(II) [ Mn(II) [ Cr(III) [ V(IV). In all our study on
metal complexes (in which we have used different ligands
with the ion metals Cu, Ni, Co, and Cr), we found out that
the copper complex is consistently the more stable.
the formula ML2(H2O)2, [M = Mn(II), Co(II), and Cu(II)]
while Cr(III) complex with formula [ML2(H2O)2]Cl,
Ni(III) complex with formula [NiL2], and V(IV) complex
with formula [VOL2] (Table 2). The complexes are gen-
erally soluble in common organic solvents.
Infrared spectra
Elemental analysis
A study and comparison of the infrared spectra of LH and its
complexes imply that LH is bidentate, with the oxygen and
nitrogen as the two coordination sites. The ligand (LH)
shows two moderately strong bands at 3,400 and 1,630 cm-1
assigned as m O–H and m C=N groups. On complex formation
The compositions of the complexes are summarized in
Table 2. The C, H, N, and M contents (both theoretically
calculated values and actual values) are in accordance with
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Med Chem Res (2012) 21:3204–3213
3209
the latter band shifts to lower energy while the phenolic O–H
group disappears in the prepared complexes, this supports
the deprotonation and linkage of Oxygen atom to the central
metal ion (Scovill and Franchino, 1982). However, the
exceptionally higher value of 1,030 cm -1 is in conformity
with the C–O group in oxadiazole ring. The absorption band
in the range (460–515) and (380–430) cm-1 were assigned
to (M–N) and (M–O) bands. Moreover, the strong absorption
at 970 cm-1 for C1 complex investigate the V=O group, as
well as the stretching of O–H groups for coordinated water
molecular are showed in the region 3,615–3,490 cm-1
(Hakan et al., 2010; Sreekanth and Kurup, 2003) as broad
band which indicates the participation of water molecular in
coordination with metal ion except for Ni(II) complex
(Table 3).
while the second band (which has higher intensity than the
first band due to conjugated system) appeared at 315 nm
(31,746 cm-1) and represents the (n ? p*) transition.
Generally, the bands of the newly synthesized complexes are
either shifted to shorter or longer wavelengths than that of the
ligand, but the high intensity of the band is an indication for
complex formation.
In these complexes the bands observed over 300 nm
could be assigned to nitrogen-metal charge transfer
absorption. The electronic absorption bands for the ligand
and complexes are classified into two distinct groups, first
those that belong to ligand transitions appeared in the UV
region while d–d transitions which appeared in the visible
region. These transitions are assigned in relevance to the
structures of the complexes (Table 4). The Cr(III) complex
showed a 3.2 B.M magnetic moment, which supports the
high spin octahedral geometry. The Cr(III) complex
showed four bands with absorbance maxima at 43478.2,
27777.7, 23809.5, and 16260.16 cm-1 which were
1H-NMR spectra
1
The H NMR spectrum of the ligand (LH) show charac-
4
4
teristic signals due to the (O–H) protons at 5.4 ppm.
Moreover, the peaks observed at 7.3 ppm (m) and 7.9 ppm
(m) were assigned to the (C–Haromatic) protons of the
ligand. The band located at 6.3 ppm may be assigned to
(=C–Hvinyl) proton for ligand.
assigned to the 4A2g(F) ? T2g(F)
,
4A2g(F) ? T1g(F)
,
4A2g(F) ? T1g(P) absorption bands, respectively. These
transitions suggest an octahedral geometry for the Cr(III)
complex.
4
The electronic spectrum of vanadyl complex shows an
absorption at 390 cm-1 of high intensity which refers to
LMCT transition of (O=V), this suggest the overlapping of
d–d transition at 413 nm with this change transform with
indicates the square pyramid geometry around V-ion,
Table 4. However, the spin forbidden transition at
2,000 cm-1 for Mn(II) complex investigates the octahedral
geometry (John and David, 1965).
Molar conductance
The molar conductance values of all the complexes
determined in nitrobenzene at room temperature are given
in Table 4. The value for the Cr(III) complex indicates that
one chloride ion is present outside the coordination sphere.
The molar conductance values V(IV), Mn(II), C(II), Ni(II),
and Cu(II) complexes are quite low to correspond to an
ionic complex; hence, these complexes are considered to
be neutral and the chloride ions are assumed to be situated
within the coordination sphere.
The nickel complex at a room temperature magnetic
moment of 0.0 B.M., which is consistent with an square
Table 4 Physical data of the synthesized compounds
No. kmax nm
(Emax
Magnetic
moment l
(B.M.)
K
Structure
)
ohm-1 cm2 mol-1
Magnetic moment and UV–Vis spectra
The ultraviolet spectrum of the synthesized ligand showed
two absorption bands, the position of the first band at 240 nm
(41,666 cm-1), which represents the (p ? p*) transition,
C1 240, 390, 413 0.00
18
90
30
Square
pyramid
C2 230, 360, 420, 3.20
615 (106)
Octahedral
C3 240, 375
(25000), 505
(80)
4.50
Octahedral
Table 3 FT-IR (cm-1) bands of metal complexes
No. C=N
C=C
mC–O M–O
mM–N
V=O H2O
C4 230, 325, 500, 2.90
625 (120)
24
28
Octahedral
C1
C2
C3
C4
C5
C6
1,570 1,572 1,025 395 (m) 460 (m) 970
3,660
3,490
3,515
–
C5 225, 380
(19500), 505
(118)
0.00
Square
planar
1,580 1,573 1,020 415 (m) 510
–
–
–
–
–
1,605 1,577 1,015 380
1,610 1,572 1,015 420
1,663 1,577 1,010 418
1,660 1,020 1,580 430
515
490
465
477
C6 230, 350
1.35
22
Octahedral
3,470
3,615
(3500), 525
(80)
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Med Chem Res (2012) 21:3204–3213
planar field. The electronic absorption spectrum showed
absorption band at 19,220 cm-1 which is considered as
A2g1 ? A2g2. The absence of any band below
10,000 cm-1 eliminates the possibility of a tetrahedral
environment in this complex. The room temperature
magnetic moment of 1.35 B.M. indicates an octahedral
structure for the Cu(II) ion complex. The electronic
absorption spectrum of Cu(II) complex shows only one
band at 20,500 cm-1 assigned to Eg2 ? T2g2, which is in
conformity with octahedral geometry (Hakan et al., 2010;
Sreekanth and Kurup, 2003).
the whole chelating space (Rohaya et al., 2005). This
increases the lipophilic character of the metal chelate and
favors its permeation through the lipoid layer of the bac-
terial membranes. The increased lipophilic character of
these complexes seems to be responsible for their enhanced
potent antibacterial activity. It may be suggested that these
complexes deactivate various cellular enzymes, which play
a vital role in various metabolic pathways of these micro-
organisms. It has also been proposed that the ultimate
action of the toxicant is the denaturation of one or more
proteins of the cell, which as a result, impairs normal
cellular processes. There are other factors which also
increase the activity, which are solubility, conductivity,
and bond length between the metal and the ligand. As a
result from the study of antibacterial of the prepared metal
complexes (Table 5), the following points were concluded.
The activity of the ligand and metal complexes was
tested against some human pathogenic bacteria including
Gram-positive (S. aureus and B. cereus) Gram negative
(E. coli, P. aeruginosa, K. pneumoniae, and P. vulgaris)
(Table 5). From the results obtained from the method, it
was found that the ligand and metal complexes were highly
active even at low concentrations as shown in Table 5.
Suggested stereostructures of the complexes
The proposed structures of complexes based on the above
mentioned data (UV–Vis, IR, and NMR spectra, conductiv-
ity, molar ratio, and magnetic properties) are depicted in
Fig. 3. The water molecules in the metal complexes of except
Ni(II) and V(IV) are in the octahedral coordination sphere,
but for the Cr(III) complex, the water molecules are in
spherical coordination and the chloride is in the outer of the
spherical coordination, as implied by the molar conductance.
Pharmacology
Antifungal activities
Antibacterial activity
Metal ions are adsorbed on the surface of the cell wall of
microorganisms and disturb the respiration process of the
cell and thus block the synthesis of the proteins that
restricts further growth of the organisms. So, metal ions are
essential for the growth-inhibitor effect (Dharmaraj et al.,
2001). According to Overtone’s concept of cell perme-
ability, the lipid membrane that surrounds the cell favors
the passage of only the lipid soluble materials due to which
liposolubility is an important factor, which controls the
antifungal activity. On chelation, the polarity of metal ion
will be reduced to a greater extent due to the overlap of the
ligand orbital and partial sharing of the positive charge of
The antibacterial screening data shows that the complexes
exhibit antimicrobial properties, and we note that the metal
chelates exhibit more inhibitory effects than the parent
ligand. The increased activity of the metal chelates can be
explained on the basis of chelation theory (Sengupta et al.,
1998). It is known that chelation tends to make the ligand
act as powerful and potent bactericidal agents, thus killing
more of the bacteria than the ligand alone. It is observed
that, in a complex, the positive charge of the metal is
partially shared with the donor atoms present in the
ligands, and there may be p-electron delocalization over
Table 5 The effect of tested compounds (LH and C1–C6) toward tested bacteria compare with ciprofloxacin as standard
Compounds
Zone of inhibition (mm)/concentration of compounds (10 lg/ml)
E. coli
K. pneumoniae
P. vulgaris
P. aeruginosa
S. aureus
B. cereus
LH
15
16
19
45
30
26
31
29
0
12
18
19
25
28
26
29
27
0
8
16
21
19
25
18
23
25
0
7
16
24
23
25
16
26
28
0
16
22
28
19
29
26
30
29
0
6
12
18
21
21
22
16
23
0
C1
C2
C3
C4
C5
C6
Ciprofloxacin
DMSO
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Med Chem Res (2012) 21:3204–3213
3211
the metal ion with donor groups. Further, it increases the
delocalization p-electrons over the whole chelate ring and
enhances the lipophilicity of the complexes. This increased
lipophilicity enhances the penetration of the complexes
into lipid membrane and restricts further multiplicity of the
microorganisms. The variation in the effectiveness of dif-
ferent compounds against different organisms depends
either on the impermeability of the cells of the microbes or
on differences in ribosome of microbial cells (Joseyphus
and Nair, 2008). Although, the exact mechanism is not
understood biochemically, mode of action of antimicrobi-
als may involve various targets in microorganisms.
(i) Interference with the cell wall synthesis, damage as a
result of which cell permeability may be altered (or) they
may disorganize the lipoprotein leading to the cell death.
(ii) Deactivate various cellular enzymes, which play a vital
role in different metabolic pathways of these microorgan-
isms. (iii) Denaturation of one or more proteins of the cell,
as a result of which the normal cellular processes are
impaired. (iv) Formation of a hydrogen bond through the
azomethine group with the active center of cell constitu-
ents, resulting in interference with the normal cell process
(Malhota et al., 1993). In vitro antifungal screening effects
of the investigated compounds were tested against some
fungal species (A. niger and C. albicans). The results of
antifungal activity show that the ligand it selves dose not
exhibit antifungal activities, but all complexes exhibit good
antifungal activities. The Cu(II) complex shows more
activity than Ni(II) and shows more activity than the Co(II)
complex, due to the higher stability of Cu(II) complex than
the Ni(II) and Co(II) complexes (Table 6).
the uncoordinated site and inhibit the growth of microor-
ganisms (Malhota et al., 1993).
Effect of azomethine ([C=N) group The mode of action
of the compounds may involve formation of a hydrogen
bond through the azomethine group ([C=N–) with the
active centers of cell constituents (Soares et al., 1997;
Mishra and Singh, 1993) resulting in interferences with the
normal cell process.
In vitro antifungal screening effects of the ligand and
metal complexes were tested against some fungal spices
(A. niger and C. albicans). Complex (C4) was found to
exhibit antifungal activity against all the fungi in this study.
Thus, complex (C6) displayed potential antifungal activity
against A. niger and C. albicans as shown in Table 6.
Radical scavenging activity
The 2,200-diphenyl-1-picrylhydrazyl (DPPH) radical assay
provides an easy and rapid way to evaluate the antiradical
activities of antioxidants. Determination of the reaction
kinetic types DPPHH is a product of the reaction between
DPPH• and an antioxidant:
DPPHꢃ þ AH ! DPPHH þ Aꢃ
The reversibility of the reaction is evaluated by adding
DPPHH at the end of the reaction. If there is an increase in
the percentage of remaining DPPH• at the plateau, the
reaction is reversible, otherwise it is a complete reaction.
DPPH was used as stable free radical electron accepts or
hydrogen radical to become a stable diamagnetic molecule
(Dharmaraj et al., 2001). DPPH is a stable-free radical
containing an odd electron in its structure and usually used
for detection of the radical scavenging activity in chemical
analysis (Nithiya et al., 2011). The reduction capability of
DPPH radicals was determined by decrease in its absor-
bance at 517 nm induced by antioxidants (Matthaus, 2002).
The graph was plotted with percentage scavenging effects
on the y-axis and concentration (lg/ml) on the x-axis. The
scavenging ability of the metal complexes was compared
with ascorbic acid as a standard. The metal complexes
showed good activities as a radical scavenger compared
with ascorbic acid, Fig. 4. These results were in agreement
with previous metallic complexes studies where the ligand
has the antioxidant activity and it is expected that the metal
moiety will increase its activity (Bukhari et al., 2009, 2008;
Gabrielska et al., 2006).
Effect of hetero atoms From the observation (Table 6),
the higher inhibition of microbial growth is due to unco-
ordinated hetero atom. In the complexes, the ligand has
uncoordinated donor atom (nitrogen atom) which enhance
the activity of the complexes by bonding with trace ele-
ments present in microorganisms. This may combine with
Table 6 The effect of tested compounds (LH and C1–C6) toward
tested fungi compare with ketoconazole as standard
Compounds Zone of inhibition (mm)/concentration of compounds
(10 lg/ml)
A. niger
C. albicans
LH
C1
C2
C3
C4
C5
C6
2
11
22
2
4
9
19
6
24
14
25
24
16
29
26
Conclusions
In this study, V(IV), Cr(III), Mn(II), Co(II), Ni(II), and
Cu(II) complexes of (E)-3-((5-phenyl-1,3,4-oxadiazol-2-
Ciprofloxacin 27
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3212
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