Synthesis, spectroscopic characterization, and in vitro antimicrobial screening of 16-membered tetraazamacrocyclic schiff-base ligand and its complexes with Co(II), Ni(II), Cu(II), and Zn(II) ions

Article abstract of DOI:10.1080/15533174.2011.591331

A 16-membered tetraazamacrocyclic ligand has been synthesized by condensation reaction of 2-methyl acetoacetanilide with 1,8-diaminonaphthalene, and the metal complexes of the type [MLCl₂] [M = Co(II), Ni(II), Cu(II), Zn(II)] were prepared by i

Full text of DOI:10.1080/15533174.2011.591331

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Synthesis, Spectroscopic Characterization, and
In Vitro Antimicrobial Screening of 16-Membered
Tetraazamacrocyclic Schiff-Base Ligand and its
Complexes with Co(II), Ni(II), Cu(II), and Zn(II) Ions
Mohammad Shakir a , Sadiqa Khanam a , Mohammad Azam a , Asad U. Khan b & Farha
Firdaus a
a Department of Chemistry , Aligarh Muslim University , Aligarh, India
b Interdisciplinary Biotechnology Unit , Aligarh Muslim University , Aligarh, India
Published online: 04 Oct 2011.
To cite this article: Mohammad Shakir , Sadiqa Khanam , Mohammad Azam , Asad U. Khan & Farha Firdaus (2011)
Synthesis, Spectroscopic Characterization, and In Vitro Antimicrobial Screening of 16-Membered Tetraazamacrocyclic
Schiff-Base Ligand and its Complexes with Co(II), Ni(II), Cu(II), and Zn(II) Ions, Synthesis and Reactivity in Inorganic,
Metal-Organic, and Nano-Metal Chemistry, 41:8, 979-986, DOI: 10.1080/15533174.2011.591331
To link to this article: http://dx.doi.org/10.1080/15533174.2011.591331
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Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry, 41:979–986, 2011
Copyright ꢀ Taylor & Francis Group, LLC
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ISSN: 1553-3174 print / 1553-3182 online
DOI: 10.1080/15533174.2011.591331
Synthesis, Spectroscopic Characterization, and In Vitro
Antimicrobial Screening of 16-Membered
Tetraazamacrocyclic Schiff-Base Ligand and its Complexes
with Co(II), Ni(II), Cu(II), and Zn(II) Ions
Mohammad Shakir,1 Sadiqa Khanam,1 Mohammad Azam,1 Asad U. Khan,2
and Farha Firdaus1
1Department of Chemistry, Aligarh Muslim University, Aligarh, India
2Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India
corrins (vitamin B12), and antibiotics (valinomycin, nonactin).
These studies have revealed the development of supramolec-
ular chemistry and its enormous diversity.[1–5] Structural fac-
tors, such as the cavity size, type and number of donor atoms,
and stereochemical rigidity, have been shown to play signif-
icant roles in determining the binding features of macrocy-
cles toward metal ions.[6,7] Many of the more rational synthetic
routes of Schiff-base macrocyclic ligands involve the use of a
metal ion template to orient the reacting groups of linear sub-
strates in the desired conformation prior to the ring closure.[8]
Functionalized pendant-arm macrocyclic complexes have been
designed due to the fact that they can offer additional donor
groups to maintain the coordination requirement of metals in
the macrocycles, as well as mimic the structure and properties
of certain metalloenzymes and metalloproteins.[9] Macrocycles,
particularly the ones containing aromatic moieties, are known to
form charge-transfer complexes with a variety of guests. These
macrocycles were used to study complexation of diverse guests
to provide new insights into non-covalent binding interactions,
chiefly cation π-interactions, which involve the stabilization of
a positive charge by the face of an aromatic ring.[10]
A 16-membered tetraazamacrocyclic ligand has been synthe-
sized by condensation reaction of 2-methyl acetoacetanilide with
1,8-diaminonaphthalene, and the metal complexes of the type
[MLCl2] [M = Co(II), Ni(II), Cu(II), Zn(II)] were prepared by
interaction of the ligand with metal salts. The ligand and its com-
plexes were characterized by various spectroscopic studies. The
mode of bonding and the overall geometry of these complexes have
been deduced by elemental analysis, molar conductance values,
Fourier-transform infrared (FT-IR), 1H-nuclear magnetic reso-
nance (NMR), fast-atom bombardment (FAB) mass, electron para-
magnetic resonance (EPR), and ultraviolet–visible (UV-VIS) spec-
troscopy along with magnetic measurement studies. An octahedral
geometry has been envisaged for all these complexes, while a dis-
torted octahedral geometry has been noticed for the Cu(II) com-
plex. The cyclic voltammograme of the Cu(II) complex exhibits
a quasi-reversible one-electron transfer wave for the Cu(II)/Cu(I)
couple. The low conductivity data of all the complexes suggest their
nonionic nature. These complexes have also been screened against
pathogenic bacteria and fungi in vitro as growth-inhibiting agents.
Keywords antimicrobial, octahedral geometry, tetraazamacrocycle,
Schiff base
Acetoacetanilide, an important diketoanilide, has been re-
ported to form a variety of Schiff base complexes with
INTRODUCTION
Metal complexes containing synthetic macrocyclic lig- the different ligands,[11–13] such as o-phenylenediamine, 4-
ands have attracted considerable attention due to their aminoantipyrine, and isonicotinic acid. Metal chelates of ace-
mimicry with more intricate biological system: metallo- toacetanilide exhibit anticancer and antifungal activity. Cop-
porhyrins (hemoglobin, myoglobin, cytochrome, chlorophylls), per(II) complexes formed by the series of macrocyclic lig-
ands derived from diethylphthalate, o-phenylenediamine, and
2-methyl acetoacetanilide showed strong antifungal activi-
ties.[14] Several macrocyclic complexes have been synthe-
Received 9 February 2011; accepted 1 March 2011.
sized from 1,8-diaminonaphthalene and dicarbonyls via a
template method.[15–17] Tahir et al. recently reported 14- and
16-membered tetraazamacrocyclic Schiff-base ligands and their
transition metal complexes formed by 2-methyl acetoacetanilide
and diamines.[18] In view of the already mentioned appli-
cations of acetoacetanilide complexes, we thought it worth-
while to synthesize a tetraazamacrocyclic Schiff-base ligand
The Chairman, Department of Chemistry, Aligarh Muslim Uni-
versity, Aligarh, India, is acknowledged for providing necessary re-
search facilities. The authors thanks the Indian Institute of Technology,
Bombay, for recording the EPR spectra, and CDRI Lucknow for pro-
viding mass spectra and analytical data for the compounds.
Address correspondence to Mohammad Shakir, Department of
Chemistry, Aligarh Muslim University, Aligarh 202002, India. E-mail:
shakir078@yahoo.com
979

980
M. SHAKIR ET AL.
TABLE 1
MIC and MBC results of complexes with positive control ciprofloxacin
Gram-positive bacteria
S. pyogenes S. aureus
Gram-negative bacteria
K. pneumoniae
P. aeruginosa
E. coli
MBC
Compounds
MIC
MBC
MIC
MBC
MIC
MBC
MIC
MBC
MIC
L
100
25
100
25
50
6.25
200
50
200
25
100
12.5
50
25
50
25
50
100
50
100
50
100
12.5
50
25
50
25
25
100
50
100
50
50
12.5
50
25
50
25
50
100
100
100
50
100
12.5
50
25
50
25
50
100
10
100
25
50
12.5
[CoLCl2]
[NiLCl2]
[CuLCl2]
[ZnLCl2]
Standard
6.25
6.25
6.25
6.25
MIC (µg/mL) = minimum inhibitory concentration, i.e., the lowest concentration of the compound to inhibit the growth of bacteria
completely; MBC (µg/mL) = minimum bacterial concentration, i.e., the lowest concentration of the compound for killing the bacteria
completely.
by [2 + 2] condensation of 2-methyl acetoacetanilide and 1,8-
Synthesis of Ligand
diaminonaphthalene and its complexes. The biological activities
of the synthesized complexes have also been examined against
pathogenic bacterial strains, namely, Streptococcus pyogenes,
Staphylococcus aureus (gram-positive), Pseudomonas aerug-
inosa, Klebsiella pneumoniae, and Escherichia coli (gram-
negative), and some fungal strains, namely, Candida albicans,
Aspergillus fumigates, Trichophyton mentagrophytes, and Peni-
cillium marneffei.
2,10-Dimethyl-4,12-di(N-amino)-2-methyl Phenyl
1,5,9,13-Tetraazacyclohexadecane 1,4,9,12 Tetraene
-6,8:14,16-Bis(naphthalene)
A solution of 1,8-diaminonaphthalene (0.002 mol, 0.316 g)
taken in 20 cm3 of methanol was slowly added to a methanolic
solution (∼ 20 cm3) of 2-methyl acetoacetanilide (0.002 mol,
0.382 g) placed in a round-bottom flask. The reaction mixture
was stirred overnight, followed by refluxing for 6 h. The reaction
mixture was allowed to stand at room temperature, resulting in
the isolation of microcrystalline product after couple of days.
The product was washed several times with methanol and dried
in vacuo.
EXPERIMENTAL
Materials and Methods
The metal salts MCl2·6H2O (M = Co(II), Ni(II)),
CuCl2·2H2O, and ZnCl2 (all Merck) were commercially avail-
able pure samples. The chemicals 2-methyl acetoacetanilide
and 1,8-diaminonaphthalene (Acros) were used as received.
Analytical-grade methanol was used as solvent.
Synthesis of the Complexes [MLCl2] [M = Co(II), Ni(II),
Cu(II), and Zn(II)]
To a methanolic solution of hydrated metal chloride (0.001
mol) taken in round bottom flask was slowly added a methanolic
solution (∼20 cm3) of ligand, (0.001 mol, 0.626 g). The reaction
TABLE 2
MIC and MFC of complexes
CA
AF
TM
PM
Compounds
MIC
MFC
MIC
MFC
MIC
MFC
MIC
MFC
L
100
50
100
25
25
6.25
10
100
100
50
50
12.5
100
50
100
25
12.5
6.25
200
100
200
50
100
12.5
100
50
100
25
12.5
6.25
200
100
200
50
50
12.5
50
50
50
25
25
200
100
200
50
50
12.5
[CoLCl2]
[NiLCl2]
[CuLCl2]
[ZnLCl2]
Standard
6.25
CA, Candida albicans; AF, Aspergillus fumigates; TM, Trichophyton mentagrophytes; PM, Penicillium marneffei. MIC (µg/mL) = minimum
inhibitory concentration, i.e., the lowest concentration of the compound to inhibit the growth of fungus completely; MFC (µg/mL) = minimum
fungicidal concentration, i.e., the lowest concentration of the compound for killing the fungus completely.

16-MEMBERED TETRAAZAMACROCYLIC SCHIFF BASE LIGAND
981
CH3
Physical Measurements
NH
H3C
2
2
The elemental analyses were obtained from the microana-
lytical laboratory of Central Drug Research Institute (CDRI),
Lucknow, India. 1H-Nuclear magnetic resonance (NMR) spec-
tra were recorded on a Brucker Avance 400 NMR spectrome-
ter in DMSO-d6. Fast-atom bombardment (FAB) mass spec-
tra were recorded on a Joel SX-102 spectrometer. Electron
paramagnetic resonance (EPR) spectra were recorded on an
E-112 spectrometer from the Indian Institute of Technology,
Chennai. The Fourier-transform infrared (FT-IR) spectra
(4000–200 cm−1) of the complexes were recorded as KBr pellets
on an Interspec 2020 FT-IR spectrometer. The electronic spectra
in dimethyl sulfoxide (DMSO) were recorded on a Pye-Unicam-
8800 spectrophotometer at room temperature. Metals and chlo-
rides were determined volumetrically[19] and gravimetrically,[20]
respectively. Magnetic susceptibility measurement was carried
out on a Faraday balance at 25◦C. The cyclic voltammogram
was recorded on a CH-Instrument electrochemical analyzer
using KCl as supporting electrolyte at room temperature. A
three-cell electrode was used that contained a Pt microcylinder
working electrode, Pt wire as auxiliary electrode, and
Ag/AgCl as reference electrode. The molar conductance was
measured for 10−3 M solutions in DMSO using a Sys-
tronic type 302 conductivity bridge thermostated at 25
0.01◦C.
+
O
O
NH2 NH2
1,8-diaminonaphthalene
2-methyl acetoacetanilide
Stirring
Reflux
MeOH
CH3
H
CH3
N
N
N
N
N
N
H
H3C
CH3
MX2.nH2O
MeOH
CH3
H
CH3
N
N
X
N
X
M
N
N
N
H
H3C
CH3
[ M = Co(II), Ni(II) n=6, Cu(II) n=2, Zn(II) ; X = Cl ]
In Vitro Antimicrobial Activity: Determination
SCH. 1. Synthesis and proposed structure of macrocyclic ligand and its of Minimum Inhibitory Concentration
complexes.
Antimicrobial activities of the compounds were tested us-
ing the bacterial and fungal cultures by disc diffusion in agar
medium. Minimum inhibitory concentrations (MICs) were de-
mixture was stirred for 6 h, followed by refluxing for 4 h. Mi- termined by broth dilution technique. The nutrient broth, which
crocrystalline solid product was isolated on evaporation over a contained logarithmic serially twofold diluted amounts of test
period of a few days. The product was washed several times compound and controls, was inoculated with approximately 5 ×
with methanol and dried in vacuo.
105 CFU/mL of actively dividing bacterial cells. The cultures
TABLE 3
Elemental analyses, m/z value, color, yield, molar conductance, and melting point of complexes
Found (calcd.),%
Molar conductivity
m/z found
(ohm−1 cm2
Complexes
(calcd.)
Color
White
Yield (%)
52
M
Cl
C
H
N
mol−1)/m.p. (◦C)
C42H38N6
L
C42H38N6CoCl2
[CoLCl2]
C42H38N6NiCl2
[NiLCl2]
C42H38N6CuCl2
[CuLCl2]
C42H38N6ZnCl2
[ZnLCl2]
627.52
(626.80)
757.20
(756.63)
757.32
(756.39)
762.19
(761.24)
763.99
—
—
7.45
(7.78)
7.28
(7.75)
8.20
(8.34)
8.12
—
—
9.15
80.26
6.21
12.00
(80.48) (6.11) (12.40)
66.30 5.01 11.23
Black
40
46
50
42
13/>300
30/>300
34/>300
17/>300
(9.37) (66.67) (5.06) (11.01)
9.10 66.23 5.01 11.02
(9.37) (66.69) (5.06) (11.11)
9.22 66.29 5.00 11.18
(9.31) (66.26) (5.03) (11.03)
9.10 66.19 5.45 11.68
(9.29) (66.15) (5.02) (11.02)
Pale
Green
Dark
Green
Pinkish
(762.57)
(8.99)

982
M. SHAKIR ET AL.
TABLE 4
IR vibrational frequencies (cm−1) of complexes
Compounds
ν(C = N)
ν(N-H)
ν(M-N)
ν(M-Cl)
Phenyl ring vibrations
L
1640
1627
1612
1629
1629
3126
3123
3108
3118
3130
—
—
1422, 1025, 726
1455, 1013, 757
1401,1006, 763
1457, 1007, 748
1440, 1008, 752
[CoLCl2]
[NiLCl2]
[CuLCl2]
[ZnLCl2]
433
426
406
418
255
261
290
274
were incubated for 24 h at 37◦C and the growth was monitored IR Spectra
visually and spectrophotometrically. Fungal cultures were incu-
bated for 48 h at 35◦C and the growth was monitored. The lowest
concentration (highest dilution) required to arrest the growth of
bacteria and fungus was regarded as the minimum inhibitory
concentration (MIC). The values of MICs are given in Tables 1
and 2.
The binding mode of the ligand to metal ion in macrocyclic
complexes was studied by comparing the IR spectrum of free lig-
and with the spectra of macrocyclic complexes. The main bands
and their assignments are listed in Table 4. The IR spectrum
of the ligand shows a new strong-intensity band at 1640 cm−1
,
which may reasonably be assigned[21] to the imine function in the
macrocyclic framework. However, no band has been observed
characteristic of either free primary amine or carbonyl function
supportive of the formation of proposed macrocyclic skeleton.
A significant negative shift (15–20 cm−1) in ν(C = N) stretch-
ing mode has been observed for the complexes as compared to
free ligand, suggesting[22] the involvement of imine nitrogen of
the (C = N) group in coordination with metal ions (Figure 1).
The bands characteristic of aromatic ring vibrations appeared
in the 1457–1440, 1155–1008, and 750–748 cm−1 regions in all
the complexes. A broad medium-intensity band in the spectra
of ligand and its complexes in the 3130–3108 cm−1 region may
reasonably be assigned to the –NH stretching mode of anilide
group[12] on the macrocyclic skeleton, characteristic of a free
secondary amino group similar to that observed in the IR spec-
trum of 2-methyl acetoacetanilide. A weak absorption band in
the region 2920–2925 cm−1 may be assigned to the CH3 stretch-
ing vibration. The formation of macrocyclic complexes has been
further confirmed by appearance of a medium-intensity band in
the 418–406 cm−1 region, which may reasonably be ascribed
to ν(M-N) vibration.[23] However, a band in the 290–255 cm−1
region may be assigned to the ν(M-Cl) mode.[24]
RESULTS AND DISCUSSION
The 16-membered tetraaza Schiff-base macrocyclic ligand,
L, has been synthesized by [2 + 2] condensation reaction be-
tween 2-methyl acetoacetanilide and 1,8-diaminonaphthalene
(Scheme 1). The complexes of the type [MLCl2] [M = Co(II),
Ni(II), Cu(II), and Zn(II)] were synthesized by reaction of ligand
L and metal salts in 1:1 molar ratio in methanolic medium. The
purity of the ligand and complexes was checked by thin-layer
chromatography (TLC) run in 1:1 benzene–methanol. However,
in spite of all possible efforts a single crystal for both ligand and
complexes could not be successfully isolated. All the complexes
were stable to atmosphere and soluble in DMSO. The formation
of ligand framework and macrocyclic complexes was deduced
on the basis of results of elemental analyses, molecular ion peak
in mass spectra (Table 3), characteristic bands in FT-IR, and
resonance signals in the 1H-NMR. The overall geometry of the
complexes was inferred from the observed values of magnetic
moments and the position of the bands in electronic spectra.
The EPR spectrum of the Cu(II) complex exhibits a distorted
octahedral geometry. The molar conductance data of the 10−3
M solutions of the complexes measured in DMSO indicate the
non-electrolytic nature of all the complexes.
1H-NMR Spectra
1
The H-NMR spectra of macrocyclic ligand and its Zn(II)
complex recorded in DMSO-d6 show a sharp singlet at 2.35 and
2.11 ppm, respectively, which may be assigned to the methyl
protons (-CH3; 12H).[25] However, a singlet at 8.04 ppm may
be attributed to the pendant secondary amino protons (C-NH-C;
2H).[26] The proton resonance peaks expected for various aro-
matic moieties on the macrocyclic framework were observed as
multiplets in the region 6.61–7.09 ppm. However, the resonance
signals obtained for the Zn(II) complex show a downfield shift
as compared to the ligand, indicating the coordination of the
ligand to the Zn(II) ion.
FIG. 1. IR spectrum of Zn(II) complex.

16-MEMBERED TETRAAZAMACROCYLIC SCHIFF BASE LIGAND
983
copper(II) complex are less than 2.3, which is in agreement
with the covalent character of the M–L bond. The relationship
g|| > g > 2.0023 calculated for the Cu(II) complex suggests
that the unpaired electron is present in the dx2–y2 orbital and
the spectral features are characteristic of axial symmetry with
tetragonal elongation.[27]
G = (g|| – 2)/(g – 2), which measures the exchange inter-
action between the metal centers in polycrystalline solid, has
been calculated. According to Hathaway and Billing,[28] if G
>4 the exchange interaction is negligible but G < 4 indicates
considerable exchange interaction in the solid complex. The
calculated G value for the complex is 1.83 (G < 4), which in-
dicates considerable exchange interaction present between the
Cu(II) centers.
Mass Spectra
The mass spectrum of the ligand exhibits a molecular ion
peak [L]+ at m/z = 627.52. The mass spectra of all the syn-
thesized macrocyclic complexes exhibit molecular ion peaks
[M]+, m/z at 757, 757, 762, and 763 a.m.u., corresponding to
their molecular formulas [CoLCl2], [NiLCl2], [CuLCl2], and
FIG. 2. EPR spectrum of Cu(II) complex.
EPR Spectrum
The EPR spectrum of the polycrystalline Cu(II) complex was [ZnLCl2], respectively (Table 3). The proposed molecular for-
recorded at room temperature. The spectrum exhibits a single mula of these complexes were confirmed by comparing their
broad signal. The analysis of spectrum gives g|| = 2.15 and molecular formula weights with m/z values. The mass spectrum
g = 2.05 (Figure 2). The observed g|| and g values for the of macrocyclic Co(II) complex shows a series of peaks at m/z
FIG. 3. Mass spectrum of Co(II) complex.

984
M. SHAKIR ET AL.
TABLE 5
Antibacterial activity of the complexes
Diameter of zone of inhibition
Gram-positive bacteria
Gram-negative bacteria
Compounds
S. pyogenes
S. aureus
P. aeruginosa
K. pneumoniae
E. coli
L
10.2 0.3
14.2 0.3
11.5 0.7
16.1 0.3
13.1 0.3
23.0 0.2
—
11.9 0.5
12.9 0.5
9.1 0.3
17.8 0.8
11.1 0.5
22.0 0.2
—
19.9 0.3
21.9 0.3
17.2 0.5
20.2 0.3
14.3 0.6
32.0 0.3
—
11.2 0.2
13.2 0.2
15.2 0.4
19.2 0.4
15.2 0.9
20.5 0.3
17.8 0.4
27.0 0.2
—
[CoLCl2]
[NiLCl2]
[CuLCl2]
[ZnLCl2]
Standard
DMSO
11.1
0
14.1 0.2
10.3 0.6
19.0 0.2
—
Positive control (standard), ciprofloxacin, and negative control (DMSO) measured by the halo zone test (unit, mm).
722, 698, 626, 597, 514, 464, 442, 376, 350, 337, 274, 228, of the Cu(II) complex and may reasonably be assigned to the
2
2
2
195, 174, and 156 a.m.u., corresponding to various fragments 2B1g → Eg and B1g → B2g transitions, respectively, char-
(Figure 3).
acteristic of distorted octahedral geometry[31] around the Cu(II)
ion. The magnetic moment value of 1.85 B.M. further compli-
ments the electronic spectral results.
Electronic Spectra and Magnetic Data
The electronic spectrum of the Co(II) complex showed three
bands at 9,090 cm−1 16,750 cm−1, and 21,508 cm−1, which Electrochemical Studies
4
4
correspond[29] to 4T1g(F) → T2g(F), 4T1g(F) → A2g(F), and
The electrochemical redox behavior of the Cu(II) complex
has been studied with Ag/AgCl as reference electrode in the
potential range –1.0 to 1.0V at 0.05 VS−1 scan rate at room
temperature using KCl as solid electrolyte. The cyclic voltam-
mogram exhibited one quasireversible redox wave CuII/CuI at-
tributed to one electron transfer process with Epc = 0.35V and
Epa = –0.30V, and Ipa/Ipc ratio 1.4. For this couple, the dif-
ferences between cathodic and anodic peak potential ꢀEp and
formal peak potential E1/2 are 50 mV and 0.325V, respectively.
4T1g(F) → T1g(P) transitions, respectively, consistent with the
4
octahedral geometry around the cobalt(II) ion. The magnetic
moment value of 4.57 B.M. further supports the electronic data.
The absorption spectrum of Ni(II) complex showed three
spin-allowed transitions 3A2g(F) → 3T1g(P), 3A2g(F) →
3T1g(F), and A2g(F) → T2g(F) appearing at 11,250 cm−1
,
3
3
13,460 cm−1, and 24,450 cm−1, respectively, characteristic of
the octahedral nickel(II) complex.[30] The geometry has been
further confirmed by the observed value of magnetic moment of
3.12 B.M.
Biological Screening
A broad band centered at 19,000 cm−1 has been recorded
Antibacterial activity of the compounds was tested in vitro
along with a shoulder at 16,120 cm−1 in the electronic spectra against Escherichia coli, Staphylococcus aureus, Pseudomonas
TABLE 6
Antifungal activity of compounds, with positive control (greseofulvin) and negative control (DMSO), measured by the halo zone
test (unit, mm)
Diameter of zone of inhibition (mm)
Compounds
CA
AF
TM
PM
L
15.5 0.4
20.5 0.4
12.2 0.3
24.2 0.3
19.1 0.5
30.0 0.2
—
14.3 1.2
18.3 1.2
11.5 0.3
20.8 0–4
17.5 0.2
27.0 0.2
—
11.1 0.4
16.1 0.4
10.2 1.2
17.9 0.5
14.9 0.7
24.0 0.3
—
10.2 0.2
13.2 0.2
8.9 0.5
14.6 0.9
11.1 0.5
20.0 0.5
—
[CoLCl2]
[NiLCl2]
[CuLCl2]
[ZnLCl2]
Standard
DMSO
CA, Candida albicans; AF, Aspergillus fumigates; TM, Trichophyton mentagrophytes;
PM, Penicillium marneffei.

16-MEMBERED TETRAAZAMACROCYLIC SCHIFF BASE LIGAND
985
aeruginosa, Streptococcus pyogenes, and Klebsiella pneu-
moniae bacterial strains by a disc diffusion method.[32]
Ciprofloxacin (30 µg) was used as positive control, while the
disc poured in DMSO was used as negative control. The sus-
ceptibility was assessed on the basis of diameter of zone of
inhibition against gram-positive and gram-negative strains of
bacteria. Inhibition zones were measured and compared with
the controls. The bacterial zones of inhibition values are given
in Table 5. The results of antibacterial study suggest the maxi-
mum inhibition capacity of the copper(II) complex.
4. Fredericks, J.R.; Hamilton, A.D. In A.D. Hamilton (Ed.), Supramolecular
Control of Structure and Reactivity; Wiley: Chichester, 1996, chapter 1.
5. Steed, J.W.; Atwood, J.L. Supramolecular Chemistry; Wiley: Chichester,
2000.
6. Bazzicalupi, C.; Bencini A.; Berni, E.; Bianchi, A.; Borsari, L.; Giorgi, C.;
Vatancoli, B.; Lodeiro, C.; Lima, J.C.; Parola, A.J.; Pina, F. Protonation
and coordination properties towards Zn(II), Cd(II) and Hg(II) of a phenan-
throline containing macrocycle with an ethylamino pendant arm. J. Chem.
Soc., Dalton Trans., 2004, 591–597.
7. Formica, M.; Fusi, V.; Micheloni, M.; Poutellini, R.; Romani, P. Cryptand
ligands for selective lithium coordiantion. Coord. Chem. Rev., 1999, 184,
347.
Antifungal screening of the compounds was done in vitro on
Candida albicans, Aspergillus fumigatus, Penicillium marnef-
8. Radecka-Paryzck, W.; Patroniak, V.; Lisowski, J. Metal complexes of
polyaza and polyoxaaza Schiff base macrocycles. Coord. Chem. Rev. 2005,
249, 2156–2175.
9. Christensen, A.; Jensen, H.S.; McKee, V.; McKenzie, C.J.; Munch, M.
Tsalen- and tsalpn-based nickel complexes with two aldehyde functionali-
ties as potential synthons for thiphenolate-containing pi- and polynucleating
acyclic and macrocyclic ligands. Inorg. Chem. 1997, 36, 6080–6085.
10. Manjula, A.; Nagarajan, M. Synthesis and complexation studies on 1,4
dianphthacrown ether. Arkivoc 2001, 8, 165–183.
11. Raman N.; Pitchaikani Raja, Y.; Kulandaisamy, A. Synthesis and character-
ization of Cu(II), Ni(II), Zn(II) and VO(II) Schiff base complexes derived
from o-phenylenediamine and acetoacetanilide. Proc. Indian Acad. Sci.
(Chem. Sci.) 2001, 113, 183–189.
12. Raman, N.; Kulandiasamy A.; Shunmugasundaram, A. Synthesis, spectral,
redox and antimicrobial activities of Schiff base complexes derived from
1-phenyl-2,3-dimethyl-4-aminopyrazol-5-one and acetoacetanilide. Tran-
sition Metal Chem., 2001, 26, 131–135.
13. Deepa, K.P.; Aravindakshan, K.K. Synthesis, characterization and anti-
fungal studies of transition metal complexes of ω-bromoacetoacetanilide
isonicotinylhydrazone. Appl. Biochem. Biotechnol. 2004, 118, 283–
292.
14. Raman, N.; Joseph, J.; Senthilkumara Velan, A; Pothiraj, C. Antifungal
activities of biorelevant complexes of Copper(II) with biosensitive macro-
cyclic ligands. Microbiology 2006, 34, 214–218.
15. Singh, D.P.; Kumar, K.; Dhiman, S.S.; Sharma, J. Biologically active macro-
cyclic complexes derived from diaminonaphthalene and glyoxal: Template
synthesis and spectroscopic approach. J. Enzyme Inhib. Med. Chem. 2008,
1–9.
16. Muralidhar Reddy, P.; Prasad, A.; Shanker, K.; Ravinder, V. Synthesis,
spectral studies and antibacterial activity of novel macrocyclic Co(II) com-
pounds. Spectrochim. Acta A 2007, 68, 1000–1006.
17. Hori, A.; Yonemura, M.; Ohba, M.; Okawa, H. Template synthesis of macro-
cyclic dinuclear CuII complexes and conversion into mononuclear com-
plexes by site-selective copper elimination. Bull. Chem. Soc. Jpn. 2001, 74,
495–503.
18. Khan, T.A.; Naseem, S.; Khan, S.N.; Khan, A.U.; Shakir, M. Synthesis and
spectral chracterization of 14- and 16-membered tetraazamacrocyclic Schiff
base ligands and their transition metal complexes and a comparitive study
of interaction of calf thymus DNA with copper(II) complexes. Spectrochim.
Acta A, 2009, 73, 622–629.
19. Reilley, C.N.; Schmid, R.W.; Sadek, F.S. Chelon approach to analysis(II)
illustrative experiments. J. Chem. Ed. 1959, 36, 619–626.
20. Vogel, A.I. A Text Book of Quantitative Inorganic Analysis, 3rd ed.; Long-
mans: London, 1961, pp. 433–434.
fei, and Trichophyton mentagrophytes by using an agar diffusion
[33]
method.
The fungal activity of each compound was com-
pared with greseofulvin as standard drug. Inhibition zones were
measured and compared with the control. The fungal zones of
inhibition values are given in Table 6. Maximum fungal growth
inhibition was shown by the copper(II) complex and the mini-
mum by nickel(II) complex.
The reason for the high antimicrobial activity of copper com-
plex can be explained in terms of the effect of copper metal ion
on the normal cell process. The complexation reaction reduces
the polarity of the metal ion by the partial sharing of metal ion
positive charge with donor groups and electron delocalization
over the chelate ring.[34] Thus, the lipophilic character of the
central metal atom is enhanced, which results in a higher capa-
bility to penetrate the microorganisms through the lipid layer of
the cell membrane.
CONCLUSION
A series of novel 16-membered Schiff-base macrocyclic lig-
ands have been synthesized by condensation reaction between
2-methyl acetoacetanilide and 1,8-diaminonaphthalene, and its
macrocyclic complexes were prepared by interaction of ligand
with metal salts and have been characterized by various spec-
troscopic techniques. The ligand to metal stoichiometry and the
nature of the bonding were ascertained on the basis of elemental
analysis, position of molecular ion peaks in the mass spectra, and
conductivity data. An octahedral geometry has been assigned for
all the complexes on the basis of position of bands in electronic
spectra and magnetic moment data, while a slight distortion in
octahedral geometry has been observed in the Cu(II) complex on
the basis of EPR data. All the macrocyclic complexes showed
considerable antimicrobial activity and the relative order has
been estimated as Cu(II) > Co(II) > Zn(II) > Ni(II).
21. Kantekin, H.; Ocak, U.; Gok, Y.; Acar, I. The synthesis and characterization
of a novel vic-dioxime and its mononuclear complexes bearing an 18-
membered N2O2S2 macro-cycle and their characteristics as extractants for
transition metal ions. J. Inclusion Phenomenon Macrocyclic Chem. 2004,
48, 95–101.
22. Athapan, P.R.; Rajagopal, G. Synthesis, spectroscopic and redox behaviour
of copper(II), nickel(II) and cobalt(II) complexes of some macrocyclic
multidentates. Polyhedron 1996, 15, 527–534.
REFERENCES
1. Dietrich, B.; Viout, P.; Lehn, J.M. Macrocyclic Chemistry; VCH Verlags-
gesellschaft: Weinheim, 1993.
2. Lehn, J.-M. Supramolecular Chemistry; VCH Verlagsgesellschaft: Wein-
heim, 1995.
3. Constable, E.C. Metals and Ligand Reactivity; VCH Verlagsgesellschaft,
Weinheim, 1996.

986
M. SHAKIR ET AL.
23. Srinivasan, S.; Athappan, P.; Rajagopal, G. Synthesis, spectral and redox
properties of metal complexes of macrocyclic tetraaza chiral Schiff base.
Transition Metal Chem. 2001, 26, 588–593.
24. Nakamoto, K. Infrared Spectra of Inorganic and Coordination Compounds;
Wiley Interscience: New York, 1970, p. 317.
25. Prasad, R.; Kumar, A. An economical synthesis of dibenzocyclam nickel(II)
and a metal free macrocycle with tetramethyl substituent. Transition Metal
Chem., 2001, 26, 322–328.
1,4,8,11-tetraaza-5,7:12,14-dibenzocyclotetradeca-1,3,8,10-tetraene.
Spectrochim. Acta A 2005, 61, 1181.
30. Mruthyunjayaswamy, B.H.M.; Jadegoud, Y.; Ijare, O.B.; Patil, S.G.;
Kudari, S.M. Synthesis characterization and antimicrobial activ-
ity of macrocyclic phenoxo-bridged di- and tetra nuclear com-
plexes from N,N- bis[2,6-diiminomethyl-4-methyl-1-hydroxyphenyl] suc-
cinoyl/sebacoyldicarboxamides. Transition Metal Chem. 2005, 30,
234–242.
26. Raman, N.; Thangaraja, C. Synthesis and structural characterization
of a fully conjugated macrocyclic tetraaza (14)-membered Schiff base
and bivalent metal complexes. Transition Metal Chem., 2005, 30, 317–
322.
27. Chandra, S.; Gupta, L.K. EPR, IR and electronic spectral studies on Mn(II),
Co(II), Ni(II) and Cu(II) complexes with a few 22-membered azamacro-
cyclic [N4] ligands. Spectrochim. Acta A 2004, 60, 1751–1761.
28. Dudley, R.J.; Hathaway, B.J. Single crystal electronic and e.s.r spectra
of bis-(aquo)monoacetylacetonatocopper (II) picrate. J. Chem. Soc. 1970,
1725–1728.
31. Singh, D.P.; Kumar, R.; Malik, V. Synthesis and characterization
of complexes of Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) with
macrocycle 3,4,11,12-tetraoxo-1,2,5,6,9,10,13,14-octaazacyclohexadeca-
6,8,14,16-tetraene and their biological screening. Transition Metal Chem.
2007, 32, 1051–1055.
32. Collins, H.A. In Microbiological Methods, 2nd ed.; Butterworth: London,
1976.
33. Khan, Z.K. In vitro and vivo screening techniques for bioactivity screening
and evaluation, Proc. Int. Workshop UNIDO-CDRI, 1997, 210–211.
34. Arslan, H.; Duran, N.; Borekci, G.; Ozer, C.K.; Akbay, C. Antimicrobial
activity of some thiourea derivatives and their nickel and copper complexes.
Molecules, 2009, 14, 519–527.
29. Chandra, S.; Gupta, L.K. Spectroscopic studies on Co(II), Ni(II), and Cu(II)
complexes with a new macrocyclic ligand: 2,9-Dipropyl-3,10-dimethyl-