Synthesis, Characterization and Biological Evaluation of Schiff Base Transition Metal Complexes Derived from 4-Nitrobenzene-1,2-diamine and 5-Chloroisatin

Article abstract of DOI:10.14233/ajchem.2020.22724

A series of transition metal complexes of the type [MLX2], where M = Mn(II), Fe(II), Co(II), Ni(II), X = Cl^–/CH3COO^– and L = Schiff base derived from 4-nitrobenzene-1,2-diamine and 5-chloroisatin have been synthesized and characterized by elemental analysis, molar conductance, IR, UV-visible, magnetic moments measurement, ¹H & ¹³C NMR and mass spectral studies. On the basis of physico-chemical studies and spectral evaluation, an octahedral geometry have been proposed for all metal(II) complexes. The antimicrobial activity of ligand and its metal complexes have been additionally screened against bacteria and fungi. Metal(II) complexes show good activity as compared to ligand towards studied microorganisms and also metal complexes checked for their catalytic properties for benzoylation of phenol.

Full text of DOI:10.14233/ajchem.2020.22724

Asian Journal of Chemistry; Vol. 32, No. 9 (2020), 2324-2328
A
SIAN
J
OURNAL OF HEMISTRY
C
https://doi.org/10.14233/ajchem.2020.22724
Synthesis, Characterization and Biological Evaluation of Schiff Base Transition
Metal Complexes Derived from 4-Nitrobenzene-1,2-diamine and 5-Chloroisatin
1,*,
2
3,
2
NETRA PAL SINGH
, KAUSHAL KUMAR , GAJENDRA KUMAR
and ANUROOP KUMAR
1Department of Chemistry, Deen Dayal Upadhyay Gorakhpur University, Gorakhpur-273009, India
2Department of Chemistry, Meerut College, Meerut-250001, India
3Department of Chemistry, Krishna College, Bijnor-246701, India
*Corresponding author: E-mail: npsmcm.in@gmail.com
Received: 18 March 2020;
Accepted: 18 June 2020;
Published online: 20 August 2020;
AJC-20033
A series of transition metal complexes of the type [MLX2], where M = Mn(II), Fe(II), Co(II), Ni(II), X = Cl–/CH3COO– and L = Schiff base
derived from 4-nitrobenzene-1,2-diamine and 5-chloroisatin have been synthesized and characterized by elemental analysis, molar conductance,
1
IR, UV-visible, magnetic moments measurement, H & 13C NMR and mass spectral studies. On the basis of physico-chemical studies and
spectral evaluation, an octahedral geometry have been proposed for all metal(II) complexes. The antimicrobial activity of ligand and its metal
complexes have been additionally screened against bacteria and fungi. Metal(II) complexes show good activity as compared to ligand towards
studied microorganisms and also metal complexes checked for their catalytic properties for benzoylation of phenol.
Keywords: Schiff base, Transition metal(II) complexes, 4-Nitrobenzene-1,2-diamine, 5-Chloroisatin, Antimicrobial activity.
of Schiff base has been found to be biological active against P.
aeruginosa [21]. It has been found that the nature of substituent
at 2- or 3-position of indole plays an important role in modu-
lating their anti-inflammatory action [22-26]. At present time
the coordination of Schiff bases with transition metal ions has
been extensively studied in medicine and diagnostics [27].
Substituted heterocyclic compounds in combination with transi-
tion metal salts generate coordination compound, which possess
enhance pharmacological properties [28], nucleolytic activity
[29], molecular magnets, catalysts [30-32], etc.
On account of these importance of metal complexes, herein,
the synthesis, characterization and antimicrobial activities of
transition metal(II) complexes of Schiff base obtained by the
condensation of 5-chloroisatin and 4-nitrobenzene-1,2-diamine
in molar ratio (2:1) in ethanol is reported. Moreover, two of
the synthesized Schiff base metal (II) (Cu2+ & Ni2+) complexes
were utilized as catalysis for benzoylation of phenol.
INTRODUCTION
Interest in the bioinorganic chemistry of transition metals
have increased recently, with the discovery of two new metallo-
enzymes which contain nickel at their active sites, bringing to
six the number of established metal containing enzymes [1].
Isatin (1H-indole-2,3-dione) is an endogenous polyfunctional
heterocyclic compound, which consist two type of carbonyl
groups i.e. keto and lactum [2,3]. Isatin due to its cis-α-dicarbonyl
moiety is a potentially good substrate for the synthesis of
transition metal complexes either alone or deprotonated, it has
also been found in mammalian tissues [4-6]. Isatin pharmaco-
phore is used to prepare large number of heterocyclic compound
and used as a starting material for synthesis of infinite drug
molecules [7,8].
Isatin is a good class of biologically active compounds with
tolerance to humans [9,10] and a good platform for structure
modification and derivatization of other compounds. Isatin
derivatives exhibit biological actions including anticancer [11],
antideprassant [12], antifungal [13], anti-HIV [14], anti-
inflammatory [15], anticonvulsant [16], antimicrobial [17],
antiviral [18] and antitubercular [19,20]. 5-Substituted isatin
EXPERIMENTAL
All the synthetic chemicals utilized were of reagent grade
and utilized as received. 4-Nitrobenzene-1,2-diamine and
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Vol. 32, No. 9 (2020)
Synthesis and Biological Evaluation of Schiff Base Transition Metal(II) Complexes 2325
5-chloroisatin were procured from Sigma-Aldrich. Hydrated
metal(II) salts, methanol, ethanol and diethyl ether were purc-
hased from Qualigens. IR spectra were recorded utilizing KBr
plate (4000-400 cm-1) on a Shimadzu 8300 IR spectrometer.
Electronic assimilation spectra in the range 200-900 nm were
acquired in ethanol on a Systronic UV-Visible spectrometer.
1H NMR of ligand (in DMSO-d6) was recorded on a Bruker
Advance II 400 NMR spectrometer regarding TMS. The mass
spectra were recorded onAgilent Q-TOF LC-MS mass spectro-
meter. The molar conductance estimation were resolved in
DMSO (10-3M) at room temperature utilizing Jenway Model
4070 conductivity meter.
Synthesis of Schiff base ((3′Z)-3,3′-(4-nitro-1,2-phenyl-
ene)-bis(azan-1-yl-1-ylidene)bis(5-chloroindolin-2-one) (1):
Ethanolic solution (50 mL) of 4-nitrobenzene-1,2-diamine
(0.755 g, 5 mmol) and ethanolic solution (50 mL) of 5-chloro-
isatin (1.81 g, 10 mmol) were mixed dropwise with constant
stirring. The subsequent arrangement was mixed for 0.5 h and
afterward refluxed in 100 mL round bottom flask at 60-80 ºC
for 3 h.The progress of the reaction response was observed by
TLC using chloroform:methanol (95:5). The solid compound
was separated off, washed with water, ethanol and diethyl ether
and finally dried in vacuum desiccator over anhydrous CaCl2
(Scheme-I).Yield: 65.5%, m.p.: 262 ºC, brownish solid.Anal.
calcd. (found) for C22H11N5O4Cl2 (m.w. 479.02): C, 55.02
(55.23); H, 2.31 (2.18); N, 14.58 (14.61).
(m.w.: 604.89): C, 43.53 (43.43), H, 1.83 (1.79); N, 11.54
(11.51); Fe, 9.20 (9.23); Cl, 23.36 (23.39). Molar conductance:
-1
7.9 Ω cm2 mol-1. µeff: 5.12 B.M. UV-Vis (DMF) λmax: 672 and
554 nm.
Synthesis of [CoL(OAc)2] complex (3): To hot ethanolic
solution of ligand (0.479 g, 1mmol) in 30 mL and the solution
of Co(OAc)2·2H2O (0.249, 1mmol) in 20 mL ethanol were
mixed for 0.5 h and then refluxed in round bottom flask for 6
h. The dark brown solid washed with ethanol, diethyl ether
and dried in desiccator over anhydrous CaCl2. Yield 66.1%;
m.p.: 295 ºC (dec.).Anal. calcd. (found) % for C26H17N5O8Cl2Co
(m.w.: 657.98): C, 47.51 (47.41); H 2.61 (2.56); N, 10.66
(10.57); Co, 8.97 (8.89), Cl, 10.79 (10.87). Molar conductance:
-1
3.5 Ω cm2 mol-1. µeff: 4.2 B.M. UV-Vis (DMF) λmax: 807,
610, 450 and 378 nm.
Synthesis of [NiLCl2] complex (4):An ethanolic solution
of NiCl2·6H2O (0.237 g, 1 mmol) in 30 mL was mixed to a hot
solution of ligand (0.479, 1mmol) in 30 mL ethanol. The solution
was refluxed in round bottom flask for 8 h. The light brown
coloured solid product was obtained and then washed with cold
ethanol, diethyl ether and finally dried in vacuum desiccator.
Yield 59.9%; m.p.: 292 ºC (dec.). Anal. calcd. (found) for
C22H11N5O4Cl4Ni (m.w.: 606.89): C, 43.33 (43.31), H, 1.82
(1.80), N, 11.48 (9.57); Ni, 9.62 (9.67), Cl, 23.25 (23.32).
-1
Molar conductance: 5.6 Ω cm2 mol-1. µeff: 3.31 B.M. UV-Vis
(DMF) λmax: 678, 490 and 373 nm.
Synthesis of [MnL(OAc)2] complex (1): Ligand (L)
(0.479 g, 1 mmol) in hot ethanol (30 mL) and ethanolic solution
of Mn(OAc)2·4H2O (0.245 g, 1 mmol) were mixed dropwise
for 1 h. The subsequent solution was refluxed in 100 mL round
bottom flask for 6 h and then separated out the dim dark grey
coloured solid, washed with cold ethanol and afterward with
diethyl ether, dried in vacuum desiccator over anhydrous CaCl2.
Yield: 64.5%; m.p.: 262 ºC (dec.). Anal. calcd. (found) % for
C26H17N5O8Cl2Mn (m.w: 653.98): C, 47.80 (47.67); H 2.62
(2.57); N, 10.72 (10.68); Mn, 8.41 (8.38); Cl, 10.85 (10.90).
Biological activities
Antimicrobial activity: Antimicrobial screening of all
the metal(II) complexes were evaluated using agar well diffusion
method [33]. The biological activity of ligand and its metal
complexes and standard drugs (antibacterial lmipenem and
antifungal miconazol) were studied against the Staphylococcus
aureus, Bacillus subtilis (Gram-positive) and Pseudomonas
aeruginosa, Escherichia coli, Salmonella typhi (Gram-negative)
and fungi Rizoctonia sp., Aspergillus sp., Penicillium sp. All
strains were obtained from Microbial Type Collection and Gene
Bank, Institute of MicrobialTechnology (IMTECH) Chandigarh,
India. The solution of different concen-tration 1, 1.5 and 2 mg/mL
of each compound (free ligand, its metal(II) complexes and
standard drug lmipenem and miconazole) in DMSO was prepared
for testing against spore germination of fungi and bacteria.
Centrifuged pellets of microorganism from a 24 h old culture
containing approximately 104 cfu/mL were spread on the surface
of Muller-Hinton agar media plates. Wells with 6 mm diameter
-1
Molar conductance: 8.2 Ω cm2 mol-1. µeff: 4.85 B.M. UV-Vis
(DMF) λmax: 625, 504, 482 and 375 nm.
Synthesis of [FeLCl2] complex (2): Hot ethanolic solution
of ligand (0.479 g, 1 mmol) in 30 mL and FeCl2·2H2O ( 0.1628 g,
1mmol) in 20 mL ethanol were mixed together. The subsequent
solution was refluxed in 100 mL round bottom flask for 6-7 h.
The dark black solid was washed with cold ethanol (5 mL) and
dried in vacuum desiccator over anhydrous CaCl2.Yield 49%;
m.p.: 285 ºC (dec.).Anal. calcd. (found) % for C22H11N5O4Cl4Fe
NO2
NO2
O
Cl
H2N
+
M(II) salt
Cl Cl
N
O
H2N
NO2
N
N
N
N
X
Cl
Cl
4-Nitrobenzene-1,2-diamine
H
M
5-Chloroindoline-2,3-dione
X
N
H
O
O
N
H
N
H
O
O
N
H
where, M = Fe(II), Mn(II), Co(II), Ni(II)
X = CH3COO–, Cl–
Scheme-I: Synthesis of Schiff base ligand and its transition metal(II) complexes

2326 Singh et al.
Asian J. Chem.
TABLE-1
made, then solution of test compound was filled to the wells.
The plates were incubated at 30 ºC for 24 h. The activity of
the compounds was determined by measuring diameter of the
inhibition zone (in mm) each test was carried in triplicate
[33,34].
Catalytic studies of cobalt(II) and nickel(II) complexes
towards benzoylation of phenol: The catalytic activities of
newly synthesized Co(II) and Ni(II) complexes were tested
for conversion towards the benzoylation of phenol. Both the
complexes indicated great reactant action. The activity of cobalt
(II) complex was by one way or another more noteworthy than
that of nickel(II) complex. So as to show up at reasonable response
conditions for most extreme change to phenyl benzoate, an
ideal catalyst load was utilized. Likewise, the impact of response
temperature and time on the transformation productivity was
examined.
KEY IR SPECTRAL BANDS (cm–1) OF LIGAND
AND ITS METAL(II) COMPLEXES
(-OH/
H2O)
–
(C=N)
azo
Compound
L
(C=O) (M-N) (M-O)
1615
1609
1606
1608
1610
1711
1698
1702
1704
1695
–
–
[MnL(OAc)2]·2H2O 3428
455
460
473
479
530
507
518
522
[NiLCl2]
[FeLCl2]
–
3432
[MnL(OAc)2]·2H2O 3435
TABLE-2
1H NMR SPECTRAL DATA OF THE LIGAND (DMSO-d6)
1H NMR (δ, ppm)
6.33-7.72 (m, 9H, Ar-H), 7.8 (d, 1H, N-H)
Compound
Ligand L
(G) transition, respectively which indicate the octahedral geometry
of the complex [35]. The magnetic moment value for Mn(II)
complex was found to be 4.85 B.M.. The electronic spectrum
of Fe(II) complex displays two absorption bands at 710-672
RESULTS AND DISCUSSION
and 590-554 nm, which are assigned to 5T2g → Eg transitions.
5
Condensation reaction of 5-chloroisatin (2 mol) with 4-
nitrobenzene-1,2-diamine (1 mol) in ethanol at 60-80 ºC gives
Schiff base ligand in a moderate yield (Scheme-I). The synthe-
sized ligand and its metal complexes are stable at room
temperature in solid state. The ligand is soluble in common
organic solvents while metal(II) complexes are soluble in DMSO
and DMF.
Also the band at 390 nm is assigned to L → M charge transfer.
The observed magnetic moment of 5.12 B.M. is consistent
with an octahedral geometry. The electronic spectra of cobalt(II)
complex indicated three groups at 1200-1051, 700-622 and
489-433 nm, which might be due to 4T1g → T2g (F), 4T1g → T1g
4
4
(P) and 4T1g → A2g (F) , respectively, magnetic moment values
3
IR spectral studies: The key IR spectral bands of ligand
and its metal(II) complexes are given in Table-1. The IR spectra
of the ligand showed the absorption at 1615 cm-1, demons-
trating the nearness of azomethine group vibration ν(C=N).
There is no stretching of unreacted NH2 group in IR spectra of
ligand demonstrate the amalgamation of proposed ligand. The
IR spectra of metal(II) complexes show huge changes when
coordinated with the free ligand. In the IR spectra of all the
metal(II) complexes, groups of azomethine group (-C=N) moved
by 5-10 cm-1, proposing coordination through nitrogen atom
of azomethine group. This is additionally upheld by the nearness
of new groups in the range of 490-475 cm-1, which demonstrate
the coordination of nitrogen to the metal ν(M-N) vibration.
No band was appeared 1711 cm-1 in the IR spectra of metal(II)
complexes. The coordination of oxygen molecule of carbonyl
group is additionally demonstrated by the apearance of new
band at 540-506 cm-1, which might be due to ν(M-O) vibration.
In the IR spectra of complexes of [MnL(OAc)2]·2H2O and
[CoL(OAc)2]·2H2O, the two characteristic bands appeared in
the range 1565-1350 cm-1, which might be due to ν(COO−). A
contrast between the frequencies is 215 cm-1, which is more
than 144 cm-1 and proves the coordination of acetate group as
unidentate ligand to the metal.
in the range 3.2-3.5 B.M. suggesting an octahedral geometry
around Co(II) ion [36-38]. The nickel(II) complex displayed
three bands at 1145-1054, 706-695 and 461-443 nm attributed
3
3
due to 3A2g (F) → T2g (F) (ν1) , 3A2g (F) → T1g (F) (ν2) and
3
3A2g (F) → T2g (P) (ν3) and magnetic moment is 3.12 B.M.,
which indicate that nickel(II) complex also exhibits the octa-
hedral geometry.
Mass spectral studies: The proposed atomic fragments
of synthesized complexes were confirmed by contrasting their
sub-atomic weight and m/z values. The molecular weight of
ligand and its metal(II) complexes were found to be: (i) m/z =
479.02 (ligand); (ii) m/z = 652.98 [Fe(II) complex], (iii) m/z =
651.98 [Mn(II) complex], (iv) m/z = 655.97 [Co(II) complex],
(v) m/z = 654.98 [Ni(II) complex]. These information in great
concurrence with proposed sub-atomic ratio for these complexes.
Molar conductance: All the metal (II) complexes were
dissolved in DMSO and molar conductivity of 10-3 M at room
temperature. The molar conductance values of all the complexes
lies in the range 15-30 ohm-1 cm2 mol-1 related to non-electrolytic
nature of all complexes [38].
Impact of catalyst amount on the reaction kinetics of
phenol benzoylation: The impact of catalyst using different
concentration at different temperature on the yield of phenyl
benzoate is shown in Tables 3 and 4. The catalyst load which
indicated the most elevated reaction during the test response
was utilized for the fixed amount of phenol (0.01 mol, 0.94 g)
and benzoyl chloride (0.01 mol, 1.41 g). At concentration of
2.5 × 10-5 mol gave similar results in the two cases with about
58.33% and 36.73% transformation to phenyl benzoate at 313 K
for Co(II) and Ni(II) complexes, respectively. Lower catalyst
amount yields poor transformation. The transformation incre-
1H NMR spectral studies: The 1H NMR analysis of ligand
was recorded in DMSO-d6 and its values are given in Table-2.
In 1H NMR range of the ligand, no sign was observed related
to essential amine proton, which recommend the arrangement
of ligand.
Electronic spectral studies: The electronic spectra of
Mn(II) complex shows an absorption band in the region 486-
4
4
441 and 540-510 nm attributed to 6A1g → T2g and 6A1g → T1g

Vol. 32, No. 9 (2020)
Synthesis and Biological Evaluation of Schiff Base Transition Metal(II) Complexes 2327
were more effective towards Gram-positive strains than Gram-
TABLE-3
EFFECT OF CATALYST AMOUNT ON % YIELD OF
PHENYL BENZOATE (REACTION TEMPERATURE
313 K) AND REACTION TIME 30 min
negative strains because the walls of Gram-negative cells are
more complexed than Gram positive cells.Antibacterial activity
of all the complexes towards Gram-positive and Gram-negative
bacteria is quite significant. Further, the ligand showed moderate
while its metal(II) complexes exhibited moderate to high activ-
ities as compared to standard drug towards the all organism
(Table-6). This may be due to the presence of -NH group, which
plays an important role in the biological activity and this group
is believed to impart the transformation reaction in biological
system. Coordination reduces the polarity of the metal ions due
to the partial sharing of its positive charge with the donor group
within the chelate ring system [40]. This process, in turn increases
the lipophilic nature of the central metal atom, which subse-
quently favours it's permeability through the lipid layer of cell
membrane and blocking the metal binding sites on enzymes of
microorganism [41,42]. In the present study, low activity of the
some metal(II) complexes is due to their low lipophilicity, because
of which penetration of the complex through the lipid membrane
was decreased and hence, they could neither block nor inhibit
the growth of the microorganism.
Catalyst load (mol)
1.0 × 10-5
[CoL(OAc)2]
26.14
[NiLCl2]
30.73
32.45
2.0 × 10-5
45.23
65.25
2.5 × 10-5
36.73
TABLE-4
EFFECT OF TEMPERATURE ON CONVERSION
% YIELD OF PHENYL BENZOATE, REACTION
TIME 30 min, CATALYST LOAD 1 × 10–5 mol
Temperature (K)
[CoL(OAc)2]
41.85
[NiLCl2]
300
313
318
32.48
37.12
33.02
92.88
45.21
ments with catalyst however in the long run reduces at high
temperature.
Biological activity studies
Antifungal activity:The antifungal activity of synthesized
Schiff base ligand and its metal(II) ion complexes exhibited a
considerable enhancement against Aspergillus sp., Rizoctonia
sp. and Penicillium sp. at 1.0, 1.5 and 2.0 mg/mL concentration
(Table-5). The activity is greatly enhanced at the higher concen-
tration. The metal complexes show better activity than the ligand
[39]. The antifungal results of the compounds were also compared
with the standard antifungal drugs miconazole.
Antibacterial activity: The Schiff base ligand, its metal
complexes, standard drug Imipenem and DMSO solution control
were screened for their antibacterial activity against the bacteria
Staphylococcus aureus and Bacillus subtilis and Pseudomonas
aeruginosa, Escherichia coli and Salmonella typhi. From the
bactericidal activity, it is apparent that all the metal(II) complexes
Conclusion
In this work, four transition metal(II) complexes of Schiff
base have been synthesized and characterized by elemental
1
analysis, spectral techniques such as FTIR, H & 13C NMR,
UV/visible and mass spectral studies. The spectral data of newly
synthesized compounds are in the favour of an octahedral geo-
metry of the complexes. The antimicrobial (antibacterial and
antifungal) studies revealed that the metal(II) complexes were
more biologically active than free ligand.Among the synthesized
metal(II) complexes, Ni(II) complex [Ni(C22H11N5O4Cl2)OAc2]
shows best antimicrobial activity against the tested micro-
organisms. The industrial applications of Co(II) and Ni(II)
TABLE-5
FUNGICIDAL SCREENING DATA OF THE SYNTHESIZED LIGAND AND ITS METAL(II) COMPLEXES
Inhibition of spore germination (%)
Compound
C22H11N5O4Cl2
[Mn(C22H11Cl2N5O4)OAc2]
[Ni(C22H11Cl2N5O4)OAc2]
[Co(C22H11Cl2N5O4)OAc2]
[Fe(C22H11Cl2N5O4)OAc2]
Miconazole (standard)
Aspergillus sp. (mg/mL)
Penicillium sp. (mg/mL)
Rizoctonia sp. (mg/mL)
1.0
1.5
50
61
86
66
85
69
2.0
1.0
1.5
31
59
77
59
70
78
2.0
1.0
44
48
68
56
59
76
1.5
50
51
72
58
64
82
2.0
53
60
79
60
66
94
42
51
82
62
75
57
55
78
93
71
87
23
54
72
55
65
65
36
71
86
67
82
83
100
TABLE-6
BACTERICIDAL SCREENING DATA OF THE SYNTHESIZED LIGAND AND ITS METAL(II) COMPLEXES (INHIBITION ZONE IN mm)
Mn(II) complex
Ni(II) complex
Co(II) complex
Fe(II) complex
Microorganism
Ligand
Imipenem (std. drug)
Gram-positive
Staphylococcus aureus
Bacillus subtilis
32
33
41
40
82
80
52
48
58
56
100
100
Gram-negative
Escherichia coli
Salmonella typhi
Pseudomonas aeruginosa
09
09
06
36
38
32
59
54
51
22
21
30
48
31
35
100
100
100
Excellent activity (90-100% inhibition), Good activity (60-70% inhibition), Significant activity (30-50% inhibition), negligible activity (08-20%
inhibition).

2328 Singh et al.
Asian J. Chem.
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