Design, synthesis and spectroscopic characterization of metal (II) complexes derived from a tetradentate macrocyclic ligand: Study on?antimicrobial and antioxidant capacity of complexes

Article abstract of DOI:10.1016/j.micpath.2017.01.036

The paper presents the synthesis of Co(II), Ni(II) and Cu(II) complexes of macrocyclic Schiff base ligand derived from 1, 4-dicarbonyl-phenyl-dihydrazide and ethyl 3-oxobutanoate (2:2). The synthesized ligand and its metal complexes were characterized by elemental analyses, magnetic susceptibility measurements, FTIR, UV–Vis., mass ¹H NMR and X-ray diffraction. The Cu(II) complex exhibit distorted octahedral geometry, whereas an octahedral geometry is suggested for other complexes. The synthesized compounds were screened in?vitro for their antimicrobial activities to evaluate their inhibiting potential against bacterial species Pseudomonas aeruginosa, Escherichia coli, Salmonella typhimurium, Staphylococcus aureus and fungal species include Aspergillus flavus, Aspergillus fumingatus, and Candida albicans. The complexation led to a remarkable increase in antimicrobial activity. In addition, the antioxidant activity of the compounds was also investigated through scavenging effect on DPPH radicals. The obtained IC₅₀ value of the DPPH activity for the copper complex was higher than other compounds.

Full text of DOI:10.1016/j.micpath.2017.01.036

Accepted Manuscript
Design, synthesis and spectroscopic characterization of metal (II) complexes derived
from a tetradentate macrocyclic ligand: Study on antimicrobial and antioxidant
capacity of complexes
Parveez Gull, Manzoor Ahmad Malik, Ovas Ahmad Dar, Athar Adil Hashmi
PII:
S0882-4010(16)30792-6
10.1016/j.micpath.2017.01.036
YMPAT 2083
DOI:
Reference:
To appear in: Microbial Pathogenesis
Received Date: 16 November 2016
Revised Date: 5 January 2017
Accepted Date: 21 January 2017
Please cite this article as: Gull P, Malik MA, Dar OA, Hashmi AA, Design, synthesis and spectroscopic
characterization of metal (II) complexes derived from a tetradentate macrocyclic ligand: Study on
antimicrobial and antioxidant capacity of complexes, Microbial Pathogenesis (2017), doi: 10.1016/
j.micpath.2017.01.036.
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ACCEPTED MANUSCRIPT
Design, Synthesis and Spectroscopic characterization of metal (II)
complexes derived from a tetradentate macrocyclic ligand: Study on
antimicrobial and antioxidant capacity of complexes
Parveez Gull, Manzoor Ahmad Malik, Ovas Ahmad Dar, Athar Adil Hashmi*
Department of chemistry, Jamia Millia Islamia, New Delhi, India 110025
\
*Corresponding Address:
Prof. Athar Adil Hashmi
Department of Chemistry
Jamia Millia Islamia (Central University)
Jamia Nagar, New Delhi - 110025, India
Tel: 0091-11-26981717 Ext. 3269
E. mail: dr.aahashmi@yahoo.co.in
parveezgull@gmail.com
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GRAPHICAL ABSTRACT.
2

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Abstract
Present work reviews the synthesis of Co(II), Ni(II) and Cu(II) complexes of macrocyclic
Schiff base ligand derived from 1, 4-dicarbonyl-phenyl-dihydrazide and Ethyl 3-
oxobutanoate (2:2). The synthesised ligand and its metal complexes were characterized by
1
elemental analyses, magnetic susceptibility measurements, FTIR, UV–Vis., mass H NMR
and X-ray diffraction. The Cu(II) complex exhibit distorted octahedral geometry, whereas an
octahedral geometry is suggested for other complexes. The synthesised compounds were
screened in vitro for their antimicrobial activities to evaluate their inhibiting potential against
bacterial species Pseudomonas aeruginosa, Escherichia coli, Salmonella typhimurium,
Staphylococcus aureus and fungal species include Aspergillus flavus, Aspergillus fumingatus,
and Candida albicans. The complexation led to a remarkable increase in antimicrobial
activity. In addition, the antioxidant activity of the compounds was also investigated through
scavenging effect on DPPH radicals. The obtained IC50 value of the DPPH activity for the
copper complex was higher than other compounds.
Keywords: Metal complexes, Schiff base ligand, Spectroscopic studies, Antimicrobial
activity, and antioxidant activity
1. Introduction
Presently the synthetic macrocyclic complexes are most important from the biological point
of view as they are structurally comparable to some naturally occurring macrocyclic
complexes. The vital functions performed by these natural systems are attributed to the nature
of the metal ions enclosed in it such as iron-porphyrin core in haemoglobin, cobalt-corrin of
vitamin B12 and magnesium-hydroporphyrin in chlorophyll [1]. The prominence in designing
new macrocyclic schiff base ligands arises mainly from their use as models for protein-metal
binding sites in a substantial array of metalloproteins in biological systems, such as the
synthetic ionophores, models for the magnetic exchange phenomena, therapeutic reagents in
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chelate therapy for treatment of metal intoxication and the cyclic antibiotics that retain their
antibiotic actions to specify metal complexation [2-4]. The binding capacity of macrocyclic
ligands to various metal ions provides them a space in the emerging coordination chemistry
and are used as potential chelating agents in the field of coordination chemistry, catalysts,
anticorrosive in industries and in biological sciences [5-8]. There are number of macrocyclic
metal complexes which have shown a budding biological interest and are used as successful
models for biological compounds showing antibacterial, anticancer, herbicidal and anti-
inflammatory activities [9-12].
The research field dealing with macrocyclic Schiff base metal complexes is very broad
due to their potential interest for several interdisciplinary areas that include bioinorganic
chemistry [13-15]. Macrocyclic Schiff bases represent an important class of compounds
because they are employed as starting materials in the synthesis of industrial products
[16,17]. Antimicrobial diseases have become a threat even in the current century being still
very much problematic to diagnose. Metallorganic chemistry is becoming an emerging area
of research due to the demand of new metal based antibacterial and antifungal compounds
[18-19]. During the last century, various types of antibacterial and antifungal drugs have been
discovered. There are still various problems unsolved for various antimicrobial agents present
till date. To develop the more effective antimicrobial drugs is the need of an hour and the
macrocyclic metal complexes are also known to act as promising antimicrobial agents.
In this manuscript, the synthesis, spectral characterization and biological properties of the
new Co(II), Ni(II) and Cu(II) complexes of 1,4-dicarbonyl-phenyl-dihydrazide with Ethyl 3-
oxobutanoate have been described to shed more light on the structure and biological
properties of this new series of macrocyclic metal complexes.
2. Experimental
2.1. Materials and methods
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All the reagents were of the best grade available and used without further purification. Metal
salts CoCl2, NiCl2 and CuCl2 (Merck), Ethyl 3-oxobutanoate (Merck), diethyl terephthalate
and hydrazinhydrate (Aldrich) were used for the synthesis. All necessary precautions were
taken to exclude moisture during the synthesis and handling of the compounds. The FT-IR
spectra were recorded in the 4000–400 cm-1 region, on a Perkin Elmer Spectrum 100/ATR
Sampling Accessory. The 1H NMR spectra were recorded on a Varian 400 MHz spectrometer
in DMSO against tetramethylsilane (TMS) as internal reference. Electronic spectra were
recorded on a Perkin-Elmer spectrophotometer. X-ray diffraction of the synthesised
compounds were carried out in powder form using RIGAKU ULTIMA IV diffractometer
system at 25˚C in Cu anode material and the generator settings as 30 mA, 40 kV. The
microanalysis of C, H and N were estimated by Perkin-Elmer 2400 CHNSO elemental
analyser. Magnetic susceptibility measurements were done using Gouy balance.
2.2. Synthesis of 1, 4-dicarbonyl-phenyl-dihydrazide
Diethyl terephthalate (2.22 g) was dissolved in 30 mL mixture of ethanol. The solution of
diethyl terephthalate was added to a solution of hydrazine hydrate (98% 2 mL) dissolved in
20 mL ethanol. After complete addition, the solution was stirred for 4 h. After stirring the
solvent was removed by rotary evaporation under reduced pressure. The resulting dihydrazide
of terephthalic acid was collected, washed with water and then recrystallized from methanol
and dried in vacuum.
2.3. Synthesis of macrocyclic ligand
Ethyl 3-oxobutanoate (0.324 g, 2 mmol) in ethanol (25 mL) was added to a solution of 1,4-
dicarbonyl-phenyl-dihydrazide (0.388 g, 2 mmol) in ethanol (30 mL) containing a few drops
of concentrated HCl. Stirring was continued for 3-4 h at room temperature during which a
solid compound separated out as a precipitate. It was filtered, washed with methanol,
recrystallized from dichloromethane/methanol and dried in vacuum. (Scheme 1)
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Yield: 65%, Mol. wt. 576.6 g mol-1, Analytical data: calc. for C28H32N8O6 (L): C, 58.32; H,
5.59; N, 19.43. Found for C28H32N8O6 (L): C, 58.28; H, 5.52; N, 19.38. I.R. (KBr pellets, cm-
1): 3468 (N-H) str., 1710(C=O), 1495(C=C) aroma str. 1H NMR (DMSO, ppm): 10.43 (-NH,
s), 7.18–8.76 (-CH, m), 0.9 (-CH3, s), 1.1(-CH3, t), 3.89 (-CH2, q) E MS (m/z) 578.
2.4. Synthesis of the Co (II), Ni (II) and Cu (II) complexes
The Cobalt (II), Nickel (II) and Copper (II) complexes were synthesised by refluxing a
methanolic solution of macrocyclic Schiff base ligand and MCl2 metal salts. The reaction was
continued for 2 h during which a precipitate separated. The precipitate was filtered off,
washed with ethanol and dried under vacuum over anhydrous CaCl2. (Scheme 2)
CoL: Yield: 62%, Mol. wt.706.44. Analytical data: calc.: C, 47.60; H, 4.57; N, 15.86. Found:
C, 47.58; H, 4.52; N, 15.82. I.R (KBr pellets, cm-1): 3265 (N-H) str., 1605(C=N), 1490(C=C)
aroma str. and 524(Co-N). 1H NMR (DMSO, ppm): 10.30 (-NH, s), 7.18–8.76 (-CH, m), 1.2
(-CH3, s), 1.0(-CH3, t), 3.84 (-CH2, q) ESI MS (m/z) 728.16 [M+] UV-Vis (DMSO): (εmax/dm3
mol-1 cm-1): 13986 4T1g (F) →4T1g (P), 17921 4T1g (F) →4A2g (F)
NiL: Yield: Yield: 68%, Mol. wt. 706.2 Analytical data: calc.: C, 47.62; H, 4.57; N, 15.87.
Found: C, 47.57; H, 4.51; N, 15.80. I.R. (KBr pellets, cm-1): 3270 (N-H) str., 1610(C=N),
1489(C=C) aroma str. and 535 (Ni-N). 1H NMR (DMSO, ppm): 10.25 (-NH, s), 7.18–8.76 (-
CH, m), 1.0 (-CH3, s), 1.2(-CH3, t), 3.85 (-CH2, q). ESI MS (m/z) 704 [M+] UV-Vis
3
3
3
3
(DMSO): (εmax/dm3 mol-1 cm-1): 13966 A2g (F) → T2g (F), 16611 A2g (F) → T1g (F) and
20202 3A2g (F) → 3T1g (P)
CuL: Yield: Yield: 60%, Mol. wt. 711.06 Analytical data: calc.: C, 47.30; H, 4.54; N, 15.76.
Found: C, 47.26; H, 4.51; N, 15.71. I.R. (KBr pellets, cm-1): 3281 (N-H) str., 1625(C=N),
1490(C=C) aroma str. and 537 (Cu-N). 1H NMR (DMSO, ppm): 10.31 (-NH, s), 7.18–8.76 (-
CH, m), 0.9 (-CH3, s), 1.1(-CH3, t), 3.89 (-CH2, q) FAB MS (m/z) 710 [M+]. UV-Vis
→ 2
(DMSO): (εmax/dm3 mol-1 cm-1): 14880 2B1g A1g and 16339 2B1g → 2Eg)
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3. Results and discussion
3.1. IR spectra
The typical infrared spectrum of the Schiff base has been represented in figure S1. The IR
spectra of macrocyclic Schiff base shows the ligand exhibit sharp medium intensity bands at
3468 cm-1, which are assigned to the ʋ (N‒H) stretching vibration. In macrocyclic schiff base
ligand the imine >C=N band is superimposed with the >C=O group and appears as a strong
band at 1625 cm-1 [20]. These bands are slightly shifted to lower frequencies in the
complexes, and this change in the frequencies indicates that the imine nitrogen atom is
coordinated to the metal ions [22, 21]. The IR spectra of the metal complexes of the Schiff
base ligands were compared with those of the Schiff base ligand in order to determine the
coordination sites that may be involved in chelation. In the spectra of the complexes, the
occurrence of band at 525–546 cm-1(M‒N) provides evidence for the bonding of nitrogen to
the central metal ion [23].
3.2. Mass spectra
The ESI mass spectra of Cu (II), Co (II) and Ni (II) complexes have been recorded. The
molecular ion (M+) peaks obtained from various complexes are as follows: (1) m/z = 578
C28H32N8O6 (Figure S2), (2) m/z = 728 [Co (C28H32N8O6) Cl2] (Figure S3) (3) m/z = 704 [Ni
(C28H32N8O6) Cl2] (4) m/z = 711 [Cu (C28H32N8O6) Cl2]. This data is in good agreement with
the proposed molecular formula for these complexes. In addition to the peaks due to the
molecular ion, the spectra exhibit peaks assignable to various fragments arising from the
thermal cleavage of the complexes.
3.3. 1H NMR
A survey of literature reveals that the NMR spectroscopy has been proved useful in
establishing the structure and nature of many Schiff base ligand and its metal complexes. The
1H NMR spectra of macrocyclic ligand and its Ni (II) complex in deuterated DMSO show
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signals consistent with the proposed structure. (Figure S4) For ligand, the peak at 10.20 ppm
is assigned to proton of NH group [24]. Resonance appeared at 3.89 ppm is due to the protons
is due to the protons of methylene of the ethoxy group. Also, the spectrum showed a set of
peaks in the 0.9–2.47 ppm range which are assigned to the protons of methyl and methylene
protons attached to ethoxy and imino group respectively [25]. A multiplet in the region 7.18–
8.01 ppm may be assigned to aromatic ring protons [26, 27]. However, for Ni (II) complex,
the signal due to the NH proton is shifted to higher values 11.3 and 10.31 ppm.
3.4. Electronic spectral studies and magnetic measurements
The electronic spectrum of the Co(II) complex in DMSO shows two bands at 17, 921 cm-1
4
4
(558 nm) 13, 986 cm-1 (715 nm) assigned to T1g (F) →4A2g (F) and T1g (F) →4T1g (P)
transitions, respectively [28]. (Figure S5a) The value of magnetic moment (4.8 B.M.)
supports the presence of an octahedral geometry around the Co (II) ion [28]. The value of
magnetic moment (3.3 B.M.) falls in the range reported for octahedral geometry [29] around
the Ni (II) ion. The UV spectrum of Ni (II) complex in DMSO exhibits three bands at 20, 202
3
3
cm-1 (495 nm) 16, 611 cm-1 (602 nm) 13, 966 cm-1 (716 nm) assigned to A2g (F) → T1g (P),
3A2g (F) → 3T1g (F) and 3A2g (F) → 3T2g (F) transitions, respectively in an octahedral geometry
around Ni(II) ion [30].(Figure S5b) The spectrum shows also, a band at 33,003 cm-1 assigned
to L→M charge-transfer. The electronic spectrum of the copper (II) complex in DMSO
shows a two bands centered at 16339 cm-1 (612 nm) 14880 cm-1 (672 nm) which can be
2
2
2
2
assigned to B1g → Eg and B1g → A1g transitions in a distorted octahedral geometry [30].
(Figure S5c) The magnetic moment (2.2 B.M.) of copper complex is in the range expected for
monomeric copper (II) complexes [31]. (Table 1)
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Table 1. Spectral absorption bands of ligand and its metal complexes.
Compound
Band position (cm-1)
17921 (558nm)
13986 (715nm)
20202 (495nm)
16611 (602nm)
13966 (716nm)
16339 (612nm)
14880 (672nm)
Assignment
4T1g (F) →4A2g (F)
4T1g (F) →4T1g (P)
3A2g (F) → 3T1g (P)
3A2g (F) → 3T1g (F)
3A2g (F) → 3T2g (F)
2B1g → 2Eg
Geometry
Octahedral
[Co(C28H32N8O6)Cl2]
Octahedral
[Ni(C28H32N8O6)Cl2]
Distorted
[Cu(C28H32N8O6)Cl2]
2B1g → 2A1g
octahedral 30
3.5. X-Ray powder diffraction
X-ray diffraction is an essential instrumental technique that is utilized to detect crystalline
materials. The compounds studied show a good quality diffractograms and all the peaks has
been identified for h, k, l values using methods reported in the literature. The Braggs equation
nλ=2dsinθ has been used for obtaining the d values. The values of h, k and l and the cell
parameters were used to calculate the values of sin 2θ for each peak. The lattice constants a, b
and c for each unit cell have been found out and are given in Figure 1 and Figure 2. Based on
X-Ray diffraction studies, it has been found that the cobalt and copper macrocyclic
complexes are crystalline in nature having tetragonal and orthorhombic crystal systems
respectively. All the peaks match with the software JCPDF.
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50000
40000
30000
20000
10000
0
Crystal system: Tetragonal
W aveLength: 1.540598
Lattice Parameter: a= 19.24 b= 19.24 c= 13.42
10
20
30
40
50
60
70
80
2 theta
Figure 1. X-Ray diffractogram of [Co(C28H32N8O6)Cl2]
Crystal system: Orthorombic
WaveLength: 1.540598
Lattice Parameter: a= 8.180 b= 8.670 c= 17.906
Lattice Parameter: Alpha= 90 Beta= 90 Gama=90
10
20
30
40
50
2 theta
Figure 2. X-Ray diffractogram of [Cu(C28H32N8O6)Cl2]
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4. Biological Activity
4.1. Antimicrobial Activity
All the synthesised compounds were screened for their antimicrobial properties. MICs of the
compound (minimum concentration which inhibits the growth of tested microorganism) were
recorded. All the complexes showed good activities against the bacterial and fungal strains
(Tables 2 - 3).
4.1.1. Antibacterial studies
The newly synthesised macrocyclic ligand and its metal complexes were evaluated for their
antibacterial activity against some strains of bacteria like Pseudomonas aeruginosa,
Escherichia coli, Salmonella typhimurium, and Staphylococcus aureus by disc diffusion
method [32, 33]. The inhibition was measured in (mm) after 25 hours shown in Table 2. Two
different concentrations were used for screening process i.e., 1 µg/ml and 100 µg/ml and
ciprofloxacin was used as the standard. Broth dilution method was utilised for the
determination of Minimum inhibitory concentrations. The growths of the strains were
monitored spectrophotometrically after the cultures were incubated for 25 h at 37°C. The
lowest concentration (highest dilution) required to arrest the growth of bacteria was regarded
as minimum inhibitory concentration (MIC). To obtain the minimum bacterial concentration
(MBC), aliquot of 0.1 ml was taken from each tube, diluted by 2X with sterile distilled water
and spread on agar plates. The number of c.f.u. was counted after 25 h of incubation at 37°C.
The minimum inhibitory concentration and minimum bacterial concentration are given in
Table 3.
Table 2. Antibacterial activity of the synthesised compounds. {Zone of inhibition (mm)}
Compounds
Conc. (µg/ml)
C28H32N8O6 (L)
P. aeruginosa
E. coli
S. typhimurium
S. aureus
1
100
1
100
1
100
1
100
14
8
33
19
12
7
16
11
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19
0
11
0
0
0
19
0
15
0
12
14
0
7
5
0
[Co(C28H32N8O6)Cl2]
[Ni(C28H32N8O6)Cl2]
[Cu(C28H32N8O6)Cl2]
13
33
11
15
9
7
29
13
Table 3. MIC and MBC data of the synthesised compounds. (µgml-1)
P. aeruginosa
E. coli
S.
S. aureus
Complex
typhimurium
MIC MBC MIC MBC MIC MBC MIC MBC
12.5 25 6.25 6.25 12.5 25 6.25 12.5
6.25 12.5 6.25 6.25 12.5
C28H32N8O6 (L)
[Co(C28H32N8O6)Cl2]
[Ni(C28H32N8O6)Cl2]
[Cu(C28H32N8O6)Cl2]
ciprofloxacin
0
0
6.25
0
0
0
6.25 6.25
0
6.25 12.5
6.25 12.5 6.25 6.25 6.25
12.5 12.5 6.25 6.25 12.5
12.5
0
0
12.5 6.25 12.5
4.1.2. Antifungal studies
The macrocyclic ligand and its metal complexes were tested for their antifungal activity
against Aspergillus flavus, Aspergillus fumingatus, and Candida albicans by agar diffusion
method [34, 35]. Sabouraud’s agar media was prepared by dissolving peptone (1 g), D-
glucose (4 g) and agar (2 g) in distilled water (100 ml) and adjusting pH to 5.7. Normal saline
water was used to make suspension spore of fungal stain lawning. A loopful of particular
fungal stain was transferred to 3 ml saline to get suspension of corresponding species.
Twenty millilitres of agar media was poured into each petri dish. Excess of suspension was
decanted and plates were dried by placing in an incubator at 37°C for 1 h. Using an agar
punch, wells were made and each well was labelled. A control was also prepared in triplicate
and maintained at 37°C for 3–4 days. The fungal activity of each compound was compared
with Nystatin as standard drug. The fungal zones of inhibition are given in Table 4. The
cultures were incubated for 48 h at 35°C and the growth was monitored. The lowest
concentration (highest dilution) required to arrest the growth of fungus was regarded as
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minimum inhibitory concentration (MIC). To obtain minimum fungicidal concentration
(MFC), aliquot of 0.1 ml was taken from each tube, diluted by 2X with sterile distilled water
and spread on agar plates. The number of c.f.u. was counted as the lowest drug concentration
at which 99% of the inoculum was killed. The minimum inhibitory concentration and
minimum fungicidal concentration are given in Table 5.
Table 4. Antifungal studies of the synthesised compounds. {Zone of inhibition (mm)}
Complex
A. flavus
A. fumingatus
C. albicans
14
15
28
0
25
0
15
22
19
16
C28H32N8O6 (L)
[Co(C28H32N8O6)Cl2]
[Ni(C28H32N8O6)Cl2]
[Cu(C28H32N8O6)Cl2]
14
11
Table 5. MIC and MFC data of the synthesised compounds. (µgml-1)
Complex
A. flavus
A. fumingatus
C. albicans
MIC MFC
MIC
MFC
MIC
MFC
6.25
6.25
6.25
12.5
12.5
12.5
6.25
0
6.25
0
6.25
6.25
6.25
12.5
6.25
6.25
C28H32N8O6 (L)
[Co(C28H32N8O6)Cl2]
[Ni(C28H32N8O6)Cl2]
6.25
6.25
0
0
6.25
6.25
12.5
12.5
6.25
6.25
12.5
12.5
[Cu(C28H32N8O6)Cl2]
Nystatin
6.25
12.5
The results of the antimicrobial activity of synthesised compounds have revealed that
the macrocyclic metal complexes exhibit greater antimicrobial activity than that of the free
macrocyclic ligand. The examination of antibacterial screening data revealed that all the
tested compounds showed moderate to good bacterial inhibition [36]. Cobalt complex was
found to be inactive against E. coli. Nickel complex was found to be inactive against P.
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aeruginosa and S. typhimurium while copper complex showed no activity towards S. aureus.
Whereas the antifungal screening data showed that only nickel complexe exhibited good
activity while as Cobalt and copper complexes are inactive towards Aspergillus fumingatus
and Aspergillus flavus respectively. This progressive antimicrobial activity of the synthesised
metal complexes, compared with that of macrocyclic ligand, is conceivably owing to
modification in structure due to coordination, and chelating tends to make metal complexes
act as more influential and powerful bacteriostatic agents, thus inhibiting the growth of the
microorganisms. The Overtone’s concept and chelation theory explains the increased
antimicrobial effect as the chelation tend to make the ligand a more powerful and potent
bacterial agent [37]. On chelation, the polarity of the metal ion will be reduced to a better
range due to the overlap of the ligand orbital and partial sharing of the positive charge of the
metal ion with donor groups. Further, it increases the delocalization of p-electrons over the
whole chelate ring and enhances the penetration of the complexes into lipid membranes and
blocking of the metal binding sites in the enzymes of microorganisms. These complexes may
also disturb the respiration process of the cell and thus block the synthesis of proteins, which
restricts further growth of the organism [38]. In general metal complexes are more active than
the ligands because metal complexes may serve as a vehicle for activation of ligands as the
principle cytotoxic species.
4.1.3. Antioxidant activity
The synthesized macrocyclic compounds were evaluated for their antioxidant activity using
the scavenging ability of the stable DPPH (2, 2׳-diphenyl-1-picryl hydrazyl) radical. The
scavenging capacity of DPPH• was determined spectrophotometrically. DPPH (0.004%) was
prepared in methanol and 1 ml of 0.004% DPPH methanol solution was mixed with 2 ml of
(2 mg/ml) methanol compound mixture. The reaction tubes were wrapped in aluminium foil
and kept in dark for 30 min. The reduction of the DPPH• was monitored by observing the
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decrease in absorbance at 517 nm using UV–Vis spectrophotometer with solvent and DPPH
as blank. The percentage inhibition was calculated using the following formula
ꢂꢃꢄꢅꢆꢇꢄꢈ − ꢂꢉꢊꢋꢌꢈꢍ
ꢀ ꢁ
Percent % inhibition of DPPH activity =
× 100
ꢂꢃꢄꢅꢆꢇꢄꢈ
Where Acontrol = absorbance of DPPH• in methanol without an antioxidant, Asample
absorbance of DPPH• in the presence of an antioxidant.
=
The percentage antioxidant activity of the macrocyclic ligand and its metal complexes
are given in Table 6. The change in color of the DPPH from purple to yellow after reduction,
which can be quantified by its decrease of absorbance at wavelength 517 nm using UV–Vis
spectrophotometer. From the experimental results, the enhanced antioxidant activity is
observed for all the metal complexes than the free ligand. Among all the metal complexes,
[Ni(C28H32N8O6)Cl2] and [Cu(C28H32N8O6)Cl2] showed enhanced antioxidant activity. The
values imply that the activity of the compounds follows the order
[Ni(C28H32N8O6)Cl2] > [Cu(C28H32N8O6)Cl2] > [Co(C28H32N8O6)Cl2] > C28H32N8O6 (L).
Table 6. Antioxidant activity of Macrocyclic ligand and its metal complexes
Compound
Antioxidant activity (%)
C28H32N8O6 (L)
19.4
30.1
41.4
36.1
[Co(C28H32N8O6)Cl2]
[Ni(C28H32N8O6)Cl2]
[Cu(C28H32N8O6)Cl2]
5. Conclusion
The analytical data revealed a single metal ion mononuclear six coordinated octahedral
geometry for Co, Ni and Cu complexes as [Co(C28H32N8O6)Cl2], [Ni(C28H32N8O6)Cl2] and
[Cu(C28H32N8O6)] respectively. The ligand and their Co, Ni and Cu complexes were
synthesized, characterized and tested for their antimicrobial inhibition potential and the
studies reveals that metal complexes show enhanced biological activity than free ligand. The
process of chelation increases the lipophilicity of the metal complexes, metal complexes
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penetrate the bacterial membrane (Lipid membrane) more effectively thus increase the
inhibition potential of the complexes.
Acknowledgment
The authors are grateful to the University Grants Commission (UGC), New Delhi for
providing UGC-BSR Meritorious research fellowship to PG.
Supplementary Material
Supporting information for this article is available separately.
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H I G H L I G H T S
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•
•
Co(II), Ni(II) and Cu(II) macrocyclic complexes were synthesised and characterized
by various spectral characterizations.
Coordination of the metal and the azomethine nitrogen atoms were confirmed by IR
spectra.
Antimicrobial activities of the ligand and its complexes, as growth inhibiting agents,
have been screened in vitro against different species of bacteria and fungi.
The complexation led to a remarkable increase in antimicrobial activity.