Synthesis of Schiff base ligand from N-substituted benzenesulfonamide and its complexes: Spectral, thermal, electrochemical behavior, fluorescence quenching, in vitro-biological and in-vitro cytotoxic studies

Article abstract of DOI:10.1016/j.molstruc.2019.127029

Convenient synthesis of new octahedral complexes from 4-amino-N-(1,3-thiazol-2-yl) benzenesulfonamide and 2-hydroxybenzaldehyde with the molecular formula [M(L)₂Cl₂] (where M = Mn(II), Co(II) and Cu(II) ions) have been described. The

Full text of DOI:10.1016/j.molstruc.2019.127029

Journal of Molecular Structure 1199 (2020) 127029
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: http://www.elsevier.com/locate/molstruc
Synthesis of Schiff base ligand from N-substituted
benzenesulfonamide and its complexes: Spectral, thermal,
electrochemical behavior, fluorescence quenching, in vitro-biological
and in-vitro cytotoxic studies
Govindaraj Valarmathy a , Ramanathan Subbalakshmi , Rajendran Sumathi ,
,
**
a
a
b, *
Rajalingam Renganathan
PG and Research Department of Chemistry, Seethalakshmi Ramaswami College, Tiruchirappalli, 620 002, Tamil Nadu, India
School of Chemistry, Bharathidasan University, Tiruchirappalli, 620024, Tamilnadu, India
a
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 10 December 2018
Received in revised form
Convenient synthesis of new octahedral complexes from 4-amino-N-(1,3-thiazol-2-yl) benzenesulfona-
mide and 2-hydroxybenzaldehyde with the molecular formula [M(L)
2
Cl
2
] (where M ¼ Mn(II), Co(II) and
Cu(II) ions) have been described. The Schiff base behaves as a bidentate ligand with oxygen and nitrogen
donors and coordinates via phenolic oxygen and azomethine nitrogen. Structural features and bonding
mode of the Schiff base have been proposed by magnetic properties and spectral methods. All the
complexes exhibit d-d transitions, photo emissive and one electron quasi reversible redox behavior. The
Schiff base ligand and its complexes have been screened for antimicrobial screening towards some
27 August 2019
Accepted 2 September 2019
Available online 4 September 2019
Keywords:
Schiff base ligand
clinically important microorganisms. The quenching studies were carried out for the [Cu(L)
by the alizarin red S dye in DMSO using fluorescence measurements. The thermodynamic parameter
et to predict feasibility of the transfer of electrons in the excited state was evaluated by employing the
2 2
Cl ] complex
4
-amino-N-(1,3-thiazol-2-yl) benzene
sulfonamide
-hydroxybenzaldehyde
D
G
2
well-known Rehm-Weller expression. The evaluated highly biologically active complex [Cu(L)
excellent cytotoxicity towards (MCF -7) cancer cell line.
2 2
Cl ] shows
In-vitro biological evaluation
In-vitro cytotoxic activity and fluorescent
quenching
©
2019 Elsevier B.V. All rights reserved.
1. Introduction
sulfonamides are the most widely used antibacterial agents in the
world mainly because of low cost and low toxicity [8].
Schiff base ligands containing nitrogen and oxygen donors are
unique and multifaceted, known for their selectivity and sensitivity
towards the metal ions. The chelation with suitable metal ion leads
for several medical applications as active analgesic, anti-
inflammatory, cytotoxic, antiviral and antitubercular activity
Previously a number of biologically important complexes have
been reported by our group [9e11]. To broaden the scale of in-
vestigations on the Schiff bases, the present investigation records
the synthesis followed by characterization of Mn(II), Co(II) and
Cu(II) complexes derived from 4-amino-N-(1,3-thiazol-2-yl) ben-
zene sulfonamide and 2-hydroxybenzaldehyde. The structures of
the ligand and its metal complexes were structured by molar
conductance, elemental analysis, Infra Red spectra, electronic
spectra magnetic moment, proton-NMR, C NMR, mass spectra,
ESR, and TGA/DTA. The biological activities are also studied against
gram positive and gram negative bacterial and fungi organisms for
Schiff base ligand and their complexes. The Cu(II) complex shows
excellent cytotoxicity towards breast (human) cancer cell (MCF -7).
The fluorescence quenching behavior were carried out for the
[
1e5]. Nowadays there is an increasing interest in the development
of fluorescence sensors for the enantioselective recognition of
chiral organic compounds and drug molecule [6]. An interesting
application of Schiff bases, is their use as an effective corrosion
inhibitor. It can also be key points in the development of inorganic
biochemistry, catalysis and optical materials [7]. N-substituted
13
*
Corresponding author.
2 2
[Cu(L) Cl ] complex by the alizarin red S dye in DMSO using fluo-
** Corresponding author.
rescence measurements.
E-mail addresses: valarchola@gmail.com (G. Valarmathy), rrengas@gmail.com
(
R. Renganathan).
https://doi.org/10.1016/j.molstruc.2019.127029
022-2860/© 2019 Elsevier B.V. All rights reserved.
0

2
G. Valarmathy et al. / Journal of Molecular Structure 1199 (2020) 127029
hydroxybenzaldehyde(0.01 mol) was added and the mixture was
refluxed for 4e5 h. A dark orange coloured solid mass separated out
on cooling is filtered, washed and dried over anhydrous CaCl in
2
desiccator.
2.2. Synthesis of complexes
To a warm solution of metal (II) (0.025 mol) chlorides in ethanol,
ethanolic/DMF mixture solution of Schiff base 4-((2-
hydroxybenzylidene) amino)-N-(1,3-thiazol-2-yl)benzenesulfona-
mide (L) (0.005 mol) was added. The mixture was refluxed for 9 h
and the precipitate obtained on partial evaporation was collected in
suction pump washed with ethanol several times and finally with
small amount of ether.
3. Results and discussion
3.1. Synthesis
Fig. 1. Formula of Schiff base [4-((2-hydroxybenzylidene) amino-N-(1,3-thiazol-2-yl)
benzenesulfonamide (L)].
The interaction of 4-amino-N-(1,3-thiazol-2-yl) benzenesulfo-
namide and 2-hydroxybenzaldehyde in equimolar proportion and
the complexes using metal chlorides according to the following
equations
2
. Experimental section
All chemicals and reagents used were of AR grade except
h
ꢁ ꢂ ꢁ ꢂ i
ethanol\DMF
reflux
ethanol which was purified prior to use. Conductance measure-
ments were studied using Elico Conductivity Bridge and a dip
conductivity cell. Solvents were purified and dried according to the
standard procedures. Elemental analysis of the ligand and com-
plexes were obtained using Elementar Vario EL CHN rapid analyzer.
All metal (II) compounds were used as chloride salts. IR spectra of
the complexes were recorded as KBr pellets on a SHIMADZU 8000-
MCl nH Oþ2Lꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ!
¼ MnðIIÞ;CoðIIÞand CuðIIÞ
M L
Cl
2
2
2
2
þnH oM
2
The structure of Schiff base ligand confirmed in the present
work is given in Fig. 1. The composition of the ligand and its com-
plexes were consistent with the microanalytical data were given in
Table 1. The conductance of metal complexes suggesting the (non-
electrolytic) nature [12] and indicate that no anions are present
outside the coordination sphere.
13
1
FT IR spectrophotometer. The C NMR and H NMR spectra of the
ligand was recorded with a Bruker Spectro spin advance (DPX-400)
6
using TMS as internal standard and DMSO‑d [6] as solvent. Melting
points were determined by open capillary method (silicon bath
electric melting point apparatus) and uncorrected. The EI Mass
spectra of the ligand and its metal complexes were recorded on
JEOL GCMATE II GC-MS model and analysed in EI mode at room
temperature. Fluorescence spectra were detected using Perki-
nElmer LS 45 Spectrofluorometer. Magnetic susceptibility mea-
surement was carried out on solid complex using Gouy balance at
room temperature.
3.2. FTeInfra Red spectra
The FTeIR spectra of the free ligand was compared with those of
the complexes in order to find out the binding modes of the ligands
to the M(II) centre.
The ligand used in the present investigation contains five
possible donor sites.
2
2
.1. Synthesis of Schiff base ligand
i) phenolic oxygen
ii) azomethine nitrogen
iii) sulfonamide nitrogen
iv) sulfonamide oxygen
v) ring nitrogen
.1.1. 4-((2-hydroxybenzylidene) amino)-N-(1,3-thiazol-2-yl)
benzenesulfonamide
To a stirred ethanolic solution of 4-amino-N-(1,3-thiazol-2-yl)
benzenesulfonamide (0.01 mol), ethanolic solution of 2-
Table 1
Physical characteristics and analytical data of Schiff base and its complexes.
ꢀ
ohm cm2 mol
ꢁ1
ꢁ1
Schiff base & Complexes Molecular Formula
Color
Yield % M.Pt
C
L
m
Elemental analysis %
Found (Calcd.)
C
H
N
S
% Metal
L
C
C
C
C
16
H
32
H
32
H
32
H
13
N
26
N
26
N
26
N
3
O
6
O
6
O
6
O
3
S
6
S
6
S
6
S
2
Dark orange 85
220
230
232
242
e
52.93
3.30
10.81
17.45 (17.82
e
(53.48) (3.62) (11.69)
[Mn(L)
[Co(L)
[Cu(L)
2
Cl
Cl
Cl
2
]
4
Cl
Cl
Cl
2
2
2
Mn Dark yellow 65
11.5
14.8
13.6
45.03
2.74
9.63 (9.96) 15.84 (16.18) 5.56 (5.93)
9.64 (9.91) 15.97 (16.11) 5.98 (6.37)
9.58 (9.85) 15.62 (16.02) 6.45 (6.80)
(45.55) (3.08)
2
2
]
4
4
Co
Cu
Pale yellow
Green
70
75
45.09
2.82
(45.33) (3.06)
2
2
]
44.54
3.01
(45.07) (3.05)

G. Valarmathy et al. / Journal of Molecular Structure 1199 (2020) 127029
3
1
coordination to the metal atom [16].
The two bands (non-ligand) occurring at
n
(M ꢁ N) 510-554 cmꢁ
ꢁ1
and
n
(M ꢁ O) 451-489 cm are confirmed from the far-IR spectra.
The characteristic bands due to
n
as(SO
2
) and
n
s
(SO
2
) sulfonamide
(SeN) (972-
ꢁ
1
oxygen,
n
(NH) amido nitrogen (2844-2869 cm ),
n
ꢁ
1
ꢁ1
973 cm ) and
n
(CeS) (857-864 cm ) shows no significant change
in the complexes and there by indicating the non-participation of
sulfonamide oxygen, amino nitrogen in the coordination [17]. The
ꢁ
1
phenolic
turned to 1209-1213 cm
n(CeO) stretching frequency of Schiff base at 1225 cm
ꢁ1
in all the complexes confirming the
coordination through oxygen.[18] Thus, the IR spectrum indicates
that the Schiff base ligand in all complexes under investigation is
bidentate and the binding sites are azomethine and phenolic OH
group.
3.3. Electronic spectra and magnetic susceptibility measurements
The nature of the ligand field around the metal ion and geom-
etry of the complexes have been ascertained from the electronic
spectra and magnetic susceptibility measurements. The prominent
bands with absorption maxima of the ligand and Cu(II) complex are
shown in Figs. 2 and 3.
Ligand (
ILCT
Mn(L)
l
max nm (cmꢁ1)): 279 (35842)
p
-
p
*; 345(28985) n-
p*
Fig. 2. UV spectrum of 4-((2-hydroxybenzylidene) amino-N-(1,3-thiazol-2-yl)benze-
nesulfonamide (L).
-
[
2
6
Cl
2
] (
l
max nm (cmꢁ1)): i)347 (28818) e ILCT ii)407
4
18
(
24570) - A1g/ T2g [5.82 BM]
Schiff base IR (solid state, cmꢁ1):
as(SO ) 1417; (CeO)1225.
Mn(L) Cl
] (solid state, cmꢁ1):
(M ꢁ O) 554; (M ꢁ N) 489; as(SO
56.
Co(L)
] (solid state, cmꢁ1):
(M ꢁ N) 478; as(SO
n
(>C]N) 1616;
n
(OeH) 3462;
ꢁ1
[Co(L) Cl ] (
2
2
l
max
nm (cm )): i)262 (38167), 303 (33003) -ILCT
4
4
n
2
n
1g 2g
ii)473 (21141) - T (F) / T (P) [19] [4.89 BM]
ꢁ1
[
2
2
n
(>C]N) 1603;
n
(OeH) 3460;
[Cu(L) Cl ] (
l
max
nm (cm )): i)351 (28490) eILCT ii)411
2
2
2
2
,
n
n
n
2
) 1414; (CeO)1212;
n
n
(M ꢁ Cl)
1g 2
(24331)- L M iii)511 (19569)- B / A g [20] [1.92 BM]
3
[
2
Cl
2
n
(>C]N) 1614;
) 1413;
n
(OeH) 3459;
3
.4. 1H NMR spectra and 13C NMR spectra
n
(M ꢁ O) 557;
n
n
2
n
(CeO)1209;
n
(M ꢁ Cl)
3
47.
[
Multiplet observed in the region
d
6.5e7.8 ppm for all the
Cu(L)
(M ꢁ O) 518;
2
Cl
2
] (solid state, cmꢁ1):
(M ꢁ N) 451; as(SO
n
(>C]N) 1609;
n
(OeH) 3419;
complexes have been assigned to the aromatic protons of the
ligand. The azomethine proton signal appears as a sharp singlet in
the region 8.96 ppm. The sharp singlet that appeared for the eOH
proton of the free ligand in the region 12.61 ppm remains unaf-
fected in complexes supporting coordination of the ligand to the
metal(II) ion via the phenolic OH group. The positions of the azo-
methine signal in the complexes are at downfield in comparison
with those of the free ligands, suggesting deshielding of the azo-
n
n
n
2
) 1416;
n
(CeO)1213;
n
(M ꢁ Cl)
3
44.
Coordination of the ligand to the M(II) ion through azomethine
nitrogen is expected to reduce the electron density on the azo-
methine nitrogen and thus lowers the (>C]N-) absorption fre-
n
ꢁ
1
quency after complexation by 3e13 cm
in all the complexes
(OH)
[
13,14]. The complexes show the appearance of phenolic
n
mode in all the complexes in the same region suggesting the co-
ordination of phenolic oxygen without deprotonation [15]. The
1
methine proton due to its coordination to metal [21]. The H NMR
spectrum of the complexes therefore confirm the bidentate coor-
dination mode of the ligand to metal (II) ion. Other peaks un-
changed: 6.98e7.53pm (m, H-phenolic ring), 7.45 ppm (d, 2H,
ꢁ
1
assignment of the
n
(M ꢁ Cl) stretching vibration at 344 cm in
Cu(II) complex from far - IR spectrum confirms the chloride ion
2 2
Fig. 3. UV and Diffuse reflectance spectrum of [CuL Cl ] complex.

4
G. Valarmathy et al. / Journal of Molecular Structure 1199 (2020) 127029
2 2
Fig. 4. ESR spectrum of [Cu(L) Cl ] complex at 77 K
2 2
Fig. 5. TGA/DTA curve of [Mn(L) Cl ] complex.

G. Valarmathy et al. / Journal of Molecular Structure 1199 (2020) 127029
5
Table 2
Electrochemical data of complexes.
Complexes
-(Epa) (V)
-(Epc) (V)
D
E
p
(mV)
-(E1/2
)
ipa/ipc
[
[
[
Mn(L)
Co(L)
Cu(L)
2
Cl
Cl
Cl
2
]
0.450
1.259
1.262
1.213
0.809
0.9
0.8
0.7
0.84
0.66
0.59
2
2
]
ꢁ0.498
ꢁ0.771
2
2
]
0.326
0.887
Supporting electrolyte: [Bu4N](ClO4) (0.05 M); Solvent ¼ DMF.
ꢁ
4
Concentration of complexes ¼ 10
M; Scan rate:200 mV se1.
All potentials referenced to SCE; E1/2 ¼ 0.5(Epc þ Epa).
Where Epa and Epc are anodic and cathodic peak potentials
and ipc are anodic and cathodic peak current.
DEp¼ (Epae Epc) and ipa
13
thiazole moiety). C NMR spectra(DMSO‑d6.): Downfield shifting of
the eCH]N- signal from 165.1 ppm in the ligand to 172.2 ppm in
the metal(II) complexes revealed the coordination of the azome-
thine nitrogen to the metal atom [22].
1
3
C NMR (DMSO- d
Schiff base (DMSO- d
phenolic CeOH), 168.8(C1, thiazole), 112.4 (C
thiazole),122.4 (C , C , N-phenyl), 127.6 (C , C , N-phenyl),140.1 (C
6
,
d
, ppm:
6
, d, ppm): 165.1 (eCH]N-), 150.6
(
3
, thiazole),147.9 (C
4
4
4
,
,
,
2
6
3
5
3
N-phenyl), 119.1 (C1, phenolic), 124.4 (C2, phenolic), 116.0 (C ,C
phenolic)
[
Mn(L)
phenolic CeOH), 168.4 (C1, thiazole), 111.8 (C , thiazole), 147.9 (C
5
thiazole),122.4 (C , C , N-phenyl),127.9 (C , C , N-phenyl),140.5 (C
2 2 6
Cl ] (DMSO- d , d, ppm): 170.4 (eCH]N-), 151.2
(
3
4
4
4
,
,
,
2
6
3
3
N-phenyl), 119.5 (C1, phenolic), 124.8 (C2, phenolic), 116.4 (C ,C
phenolic)
[
Co(L)
CeOH), 167.8 (C1, thiazole), 112.7 (C
22.4 (C , C , N-phenyl), 126.9 (C
2
Cl
2
] (DMSO- d
6
,
d
, ppm):172.2 (eCH]N-),150.2 (phenolic
, thiazole), 147.9 (C , thiazole),
, C , N-phenyl), 140.7 (C , N-
,C
3
4
1
2
6
3
5
4
phenyl), 119.8 (C1, phenolic), 123.4 (C2, phenolic), 116.6 (C
phenolic)
3
4
,
[
Cu(L)
CeOH), 168.3 (C1, thiazole), 112.9 (C
22.4 (C , C , N-phenyl), 127.1 (C
2
Cl
2
] (DMSO- d
6
,
d
, ppm): 171.1(eCH]N-), 150.4 (phenolic
, thiazole), 147.9 (C , thiazole),
, C , N-phenyl), 140.9 (C , N-
4
,C ,
3
4
1
2
6
3
5
4
phenyl), 118.9 (C1, phenolic), 124.7 (C2, phenolic), 115.7 (C
phenolic)
3
Fig. 6. Proposed Formula of the complexes.
Fig. 7. Cyclic voltammogram of the complexes.

6
G. Valarmathy et al. / Journal of Molecular Structure 1199 (2020) 127029
Table 3
Antimicrobial activity of Schiff base and its complexes.
Name of the Microorganisms
Zole of inhibition in mm
Ligand (ppm)
Mn(L
25
2
)Cl
2
(ppm)
75
Co(L
25
2
)Cl2 (ppm)
Cu(L
25
2
)Cl
2
(ppm)
75
25
50
75
100
50
100
50
75
100
50
100
SC
Std
Staphylococcus aureus (NCIM 2079)
Candida albicans (NCIM 3102)
14
16
16
16
16
18
21
20
13
12
14
16
16
18
18
20
13
14
14
20
18
20
22
24
12
15
15
15
15
18
20
24
e
e
35
32
Fig. 8. In vitro antibacterial screening of Schiff base and its metal complexes against Staphylococcus aureus.
3.5. EPR spectra
nitrogen temperature. The spectrum of Cu(II) complex at frozen
state shows two peaks (Fig. 4). The complex exhibits the gjj
ꢁ
4
EPR spectrum of copper complex provides information about
the metal ion environment. The X-band EPR spectra of the copper
and manganese complexes were recorded at room and at liquid
value ¼ 2.1532, g value ¼ 2.0382, Ajj ¼ 341.2 ꢂ 10 . These values
⊥
indicate that the unpaired electron in the ground state of copper(II)
2
þ
is predominantly in dx2ey2 orbital and the Cu ion being located in

G. Valarmathy et al. / Journal of Molecular Structure 1199 (2020) 127029
7
Fig. 9. In vitro antifungal screening of Schiff base and its metal complexes against Candida albicans.
distorted octahedral site elongated along the z-axis. The
l
value
spectra of Mn(II) complex show giso value of 2.0034.
.6. EI-mass spectra
ꢁ1
(
ꢁ469.12 cm ) calculated using the relations, gav ¼ 1/3[g
k
þ2 g
⊥
]
/10Dq), is less than the free Cu(II) ion (ꢁ832 cm 1)
ꢁ
and gav ¼ 2(1-2
l
3
which also supports covalent character of M-L bond in the complex
[
23]. The g value is very close to those reported for a number of
The EI-Mass spectra of the ligand show a molecular ion peak at
m/z 359.45 which corresponds to calculated value. The mass
spectra of C34 Cl Mn and C34 Cl Cu show peaks
distorted Cu(II) complex. gjj<2.3 which indicates significant degree
of covalency in the metal-ligand bond [24]. From the axial sym-
metry (G) parameter ¼ 4.01, there is no CueCu interaction and thus
the complex is monomeric in nature [25]. The covalency parameter
30
H N
6
O
8
S
4
2
H
30
N
6
O
8
S
4
2
at m/z ¼ 843 and m/z ¼ 852.54 corresponds to M and [Mþ2] peaks.
These peaks support the expected molecular masses of the com-
a
⊥
[2] are related to gjj and g and can be calculated using the
2 2
plexes and confirm the formulae of metal chelates as [M(L) Cl ]
following equation
type. The spectra of the Schiff base and its complexes show char-
acteristic molecular ion peaks at their expected m/z values con-
firming their stoichiometry as suggested.
2
a
¼
ꢁ
ðA k = 0:036Þ¥ þ ðg k ꢁ 2:0023Þ þ 3=7ðg⊥ ꢁ 2:0023Þ þ 0:04
3.7. Thermal analysis
The observed value of (
is less than unity indicates the covalent nature of the complex. The
a
[2] ¼ 0.69) of the Cu(II) complex which
TGA/DTA curve for complexes (Fig. 5) show first stage of

8
G. Valarmathy et al. / Journal of Molecular Structure 1199 (2020) 127029
2 2
Fig. 10. Anticancer activity of [Cu(L) Cl )] against human breast cancer cell line (MCF-7).
ꢀ
ꢀ
ꢀ
decomposition in the temperature range of 185e230 C. All the
300 Ce400 C (observedz 44.56%, calculated z44.23%) which
correlated with the removal of one molecule of Schiff base ligand in
all the complexes [26]. The horizontal thermal curve observed
ꢀ
complexes is stable up to 350 C. This excludes the possibility of
lattice as well as coordinated water molecules in the complexes.
The overall mass loss was observed in the temperature range of
ꢀ
above 540 C corresponds to the step by step decomposition of

G. Valarmathy et al. / Journal of Molecular Structure 1199 (2020) 127029
9
Table 4
Anticancer Activity of [Cu(L
2
)Cl
2
] complex.
25
Conc
ABS
6.25
m
M
2.5
m
M
m
M
50
mM
100
m
M
Cont
0.411
0.401
0.411
0.409
0.407
0.348
0.342
0.351
0.344
0.26
0.009
0.007
0.004
0.006
0.425
0.407
0.413
0.413
0
0
.415
.413
0.278
0.277
0.271
Avg
0.413
2 2
Fig. 13. Photo induced electron transfer from [Cu(L) Cl ] complex to alizarin red S.
3.8. Electrochemical behavior
Fig. 11. Plot of between % Cell inhibition and log concentration.
Cyclic voltammetry measurements were made over a potential
range between ꢁ2.1 V and þ3.1 V for all the complexes with a scan
another molecule of the ligand in all the complexes. The DTA curve
-
1
rate of 0.2 Vs . The redox processes are quasiereversible in nature,
ꢀ
of the complexes shows endothermic peaks around 360 C and
characterized by a rather large peaketoepeak separation (
D
Ep) of
ꢀ
small peak at 570 C which are attributed to phase transition
80e150 mV as shown in Fig. 7. The observed cyclic voltammograms
accompanied by decomposition of the complex. Based on the above
studies, it is concluded that all the complexes possess octahedral
geometry displayed by the Formula (Fig. 6).
for complexes are characterized as reversible where (DEp) < 100.
The difference between forward and backward peak potential can
provide a rough evaluation of one electron transfer reaction. The
0
Fig. 12. Fluorescence quenching of [Cu(L)
2
Cl
2
] complex by alizarin red S. Inset: plot of 1/(F eF) Vs 1/[Q].

10
G. Valarmathy et al. / Journal of Molecular Structure 1199 (2020) 127029
potential midway between the peak potentials is formal reduction
potential (E1/2)(Table 2). The ratio of anodic and cathodic current
for all the complexes (ipa/ipc<1) confirms the quasireversible pro-
cess [27]. From the peak separation value and peak potentials, the
electrode process is found to be consistent with the
quasiereversibility of the M(II)/M(I) and M(I)/M(II) couple.
1
1
1
ꢁ
ꢂ ¼ ꢁ
ꢂ þ
ꢁ
ꢂ
F0 ꢁ F
F0 ꢁ F0
0
K F ꢁ F ½Qꢃ
0
where K is the binding constant, F is the initial fluorescence in-
tensity of the complex, F is the fluorescence intensity of alizarin red
0
S adsorbed Cu(II)complex and F is the observed fluorescence in-
0
3.9. In-vitro biological activities of the complexes
tensity at its maximum. The plot of 1/(F eF) versus 1/[Q] gives a
straight line (inset Fig. 12) and from the slope, the calculated
4
ꢁ1
0
Antibacterial and antifungal activity of Schiff base and its com-
plexes (Table 3) have been tested by disc diffusion technique
28,29]. The various gram positive and gram-negative bacterial
binding constant (K
b
) are found to be 2.22 ꢂ 10 M . There is a
good linear relationship [R ¼ 0.996] between 1/(F eF) and the
reciprocal concentration of alizarin red S. The overlap between
emission spectrum of donor Cu(II) complex and absorption spec-
trum of the acceptor (alizarin red S) indicates the energy transfer.
Since there is no wavelength overlap between absorption of
acceptor (alizarin red S) and emission of donor (complex), energy
transfer between donor and acceptor is negligible. The thermody-
namic feasibility of the excited state electron transfer reactions was
calculated by employing the well-known Rehm-Weller expression
[33].
[
organisms such as gram-negative bacteria (Staphylococcus aureus)
and fungi (candida albicans) are used to find out the antimicrobial
assay. The results were compared with standard drug Ciprofloxa-
cin ¼ 5mg/disc and Nystatin ¼ 100 mg/disc for fungi. All the new
complexes showed a remarkable biological activity against bacteria
and fungus as indicated in Figs. 8 and 9. Thus the complexes were
observed to be more active against Staphylococcus aureus and
candida albicans. The enhancement in antimicrobial activity of the
metal complexes as compared to Schiff base may be explained on
the basis of Tweedy's chelation theory [30].
ðoxÞ
:ðredÞ
1=2
D
Get ¼ E1 ꢁ E
ꢁ Es þ C
=2
3
.10. Invitro cell growth inhibition assay of [Cu(L)
2
Cl
2
] complex
*
E
¼ Es=sþ ꢁ Es;
s=sþ
The metal complexes may also be a vehicle for activation of the
The higher negative
electron transfer process is thermodynamically favourable. The
excited state oxidation potentials E* of the Cu(II)complex
D
Get values (ꢁ3.57 eV) indicate that the
ligand as the cytotoxic agent. The in vitro cytotoxicity of the newly-
synthesised complexes with remarkable antimicrobial activity
were carried out in human tumor cell lines. Cell line namely human
breast cancer cell line (MCF-7) were assayed by the.
s/sþ
is ꢁ2.9 V the oxidation potential of complexes is E
s/sþ
is 0.49 V and
the excited state energy of the Cu(II) complex is 3.4eV. The transfer
of electron from excited state of the complex to CB of dye is ener-
getically favourable [34,35]. (Fig. 13).
3
-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide
MTT) assay [31]. The complexes were initially dissolved in neat
dimethyl sulfoxide (DMSO) to make a stock solution and additional
five series of dilutions (6.25 M, 12.5 M, 25 M, 50 M, 100 M)
were made to provide a total of five sample concentrations. The
concentration of the compounds at % cell inhibition growth (IC50
(
m
m
m
m
m
4. Conclusions
)
was calculated. The percentage cell inhibition was determined us-
ing the following formula.
In this work the synthesis of Co(II), Ni(II) and Cu(II) complexes of
the Schiff base 4-((2-hydroxybenzylidene)amino)-N-(1,3-thiazol-2-
yl)benzenesulfonamide has been described. The low molar
conductance values indicate the absence of anion outside the
sphere. From the spectral data, the structure of the complexes
corresponds to a six coordinate, the binding set includes phenolic
oxygen and imine nitrogen of the ligand to the metal (II) centre. The
absence of water molecules has been confirmed by thermal anal-
ysis. The metal ligand stoichiometry in all the complexes is 1:2.
Based on these facts, an octahedral structure has been proposed for
all complexes. The process of chelation affects the biological ac-
tivity of the complexes that are potent against pathogens. It is
observed that the potency to act against the cancerous cell is highly
influenced by the nature of the metal ion present in the chelate. The
feasibility of the reaction has been established from fluorescence
quenching studies. The fluorophore Cu(II) complex is effectively
quenched by alizarin in DMSO.
%
Cell Inhibition ¼ 100 ꢁ Abs ðsampleÞ = Abs ðcontrolÞ ꢂ 100
Cytotoxicity activity of [Cu(L) Cl ] complex is shown in Fig. 10.
2
2
The Cu(II) complex derived from 4-((2-hydroxybenzylidene)
amino-N-(1,3-thiazol-2-yl) benzenesulfonamide (L) shows excel-
lent cytotoxicity towards human breast cancer cell (MCF -7). The
complex exhibit considerable IC50 value 56.15 g/ml. The concen-
m
tration of the complex at 50% cell growth was inhibited and IC50
was calculated is shown in Table 4. The regression graph between %
cell inhibition and log concentration and shown in Fig.11. Nonlinear
regression graph was plotted between % cell inhibition and log
concentration and IC50 was determined using GraphPad Prism
software. The better cytotoxicity activity of Cu (II) complex against
(
MCF -7) may play a significant role in metallodrug formulation.
3.11. Fluorescence quenching studies of [Cu(L)
2 2
Cl ]
The excited state interaction of [Cu(L) Cl ] complex with alizarin
2
2
%
Cell Inhibition
red S dye was carried out through fluorescence measurements.
Fig. 12 show the emission spectrum of Cu(II) complex measured in
DMSO. It was observed that the Cu(II) complex were effectively
quenched by increasing the concentration of alizarin red S dye
0
2
2
50
100
.25
.5
5
0.08
1.53
16.69
34.27
98.38
IC 50
R2
56.15
mM
0.9636
ꢁ
5
(
0e5 ꢂ 10 M). The binding constant for this type of interaction
was calculated using fluorescence quenching data by from the
The % cell inhibition was determined using the following formula.
formula [32].
% Cell Inhibition ¼ 100- Abs (sample)/Abs (control) ꢂ100.

G. Valarmathy et al. / Journal of Molecular Structure 1199 (2020) 127029
11
Acknowledgements
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The authors are thankful to the Secretary, Seethalakshmi Ram-
aswami College, Tiruchirappalli, Tamil nadu for providing labora-
tory facilities and support. The authors also thankful to the
Director-STIC cochin, SAIF Madras for providing analytical support
and special thanks to Professor Dr. R. Renganathan, Bharathidasan
University, Tiruchirappalli, Tamil Nadu, India for rendering help
towards fluorescence quenching studies.
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