Synthesis, spectroscopic characterization, biological screening and in vitro cytotoxic studies of 4-methyl-3-thiosemicarbazone derived Schiff bases and their Co (II), Ni (II), Cu (II) and Zn (II) complexes

Article abstract of DOI:10.1002/aoc.5154

A series of twenty compounds inclusive of bidentate Schiff bases derived from condensation of 4-methyl-3-thiosemicarbazide with substituted derivatives of napthaldehyde/benzaldehyde/salicylaldehyde and their mononuclear Co (II), Ni (II), Cu (II) and Zn (I

Full text of DOI:10.1002/aoc.5154

Received: 31 May 2019
DOI: 10.1002/aoc.5154
Revised: 2 July 2019
Accepted: 13 July 2019
F U L L P A P E R
Synthesis, spectroscopic characterization, biological
screening and in vitro cytotoxic studies of 4‐methyl‐3‐
thiosemicarbazone derived Schiff bases and their Co (II),
Ni (II), Cu (II) and Zn (II) complexes
1
1
2
3
4
J. Devi
| M. Yadav | D.K. Jindal | D. Kumar | Y. Poornachandra
1
Department of Chemistry, Guru
Rameshwar University of Science and
Technology, Hisar 125001, India
A series of twenty compounds inclusive of bidentate Schiff bases derived from
condensation of 4‐methyl‐3‐thiosemicarbazide with substituted derivatives of
napthaldehyde/benzaldehyde/salicylaldehyde and their mononuclear Co (II),
Ni (II), Cu (II) and Zn (II) complexes in molar ratio (1:1) were synthesized
and characterized. The coordination behavior, modes of bonding and overall
geometry of the compounds was known from the elemental analysis, spectral
2
Department of Pharmaceutical Sciences,
Guru Rameshwar University of Science
and Technology, Hisar 125001, India
3
School of Pharmaceutical Sciences,
Shoolini University, Bajhol, Solan 173229,
India
1
13
techniques (IR, UV–Vis, H NMR, C NMR, ESR and ESI‐mass), magnetic
moment measurements, molar conductance, thermal and powder XRD stud-
ies. The studies revealed octahedral geometry for all the complexes where
ligands coordinated in a neutral bidentate manner (NS) via nitrogen atom of
azomethine group and sulphur atom of thione group with the metal centre.
In vitro biological effects of the compounds were tested against four bacterial
species and two fungal strains. The results indicated that the metal complexes
showed a marked enhancement in biocidal activity in comparable with the
parent Schiff bases. In vitro anticancer activity against the malignant tumor
cell lines; human alveolar adenocarcinoma epithelial cell line (A549), human
breast adenocarcinoma cell line (MCF7), human prostate cancer cell line
4
Applied Biology Division, CSIR‐Indian
Institute of Chemical Technology,
Hyderabad 500007, India
Correspondence
Jai Devi, Department of Chemistry, Guru
Rameshwar University of Science and
Technology. Hisar‐125001, India.
Email: jaya.gju@gmail.com
Funding information
Department of Chemistry of Guru
Rameshwar University of Science &
Technology; University Grant Commis-
sion, New Delhi, India, Grant/Award
Number: 23/06/2013(i)EU‐V dated 23/12/
(DU145) and human normal lung cell line (MRC‐5) using MTT assay, exposed
compound 16 as a leading member with lowest IC50 value of 10.6 ± 0.14 μM
2
013
against (A549) cell line.
KEYWORDS
anticancer activity, antimicrobial screening, Schiff bases, spectroscopic techniques, transition metal
complexes
1
| INTRODUCTION
permeates in the normal body tissues and travel through
blood and lymphatic systems, and lodge in other organs
There is a significant solitary throughout the globe; can-
cer is one of the primary health qualms, confronting
humankind which may be defined as the abandoned
growth of abnormal cells anywhere in the body. These
unusual cells are termed as malignant cells which get
where they can again replicate the uncontrolled growth
cycle. It is not restricted to humans only; animals and
other living organisms can also get cancer. Cisplatin (cis
diamminedichloroplatinum (II)) discovered in 1845 and
licensed for medical use in 1979, is a vivid and glowing
Appl Organometal Chem. 2019;e5154.
wileyonlinelibrary.com/journal/aoc
© 2019 John Wiley & Sons, Ltd.
1 of 23
https://doi.org/10.1002/aoc.5154

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DEVI ET AL.
[
1]
metal based drug for cancer therapy but currently some
other platinum‐based drugs are being screened through
clinical trials in an effort to find a substitute for cisplatin,
mainly due to development of resistance in tumor cells
and dose‐related adverse effects such as bone marrow
suppression, impairment, kidney problems, vomiting,
numbness, trouble walking, allergic reactions, heart dis-
2 | EXPERIMENTAL
2.1 | Materials and methods
In the present work, all the chemicals used were of
analytical reagent grade obtained from Sigma. They
included 4‐methyl‐3‐thiosemicarbazide, 2‐hydroxy‐1‐
[2,3]
ease etc.
naphthaldehyde,
4‐hydroxy
benzaldehyde,
3,5‐
On the other hand, a lot of synthesized transition
metal‐based compounds are already in use in clinical
practice for treatment of cancer while some are undergo-
dichlorosalicylaldehyde, propargyl bromide, bromomethyl
benzene, (2‐bromo‐ethyl)‐benzene, anhydrous potas-
sium carbonate and transition metal (II) acetates Co
[4,5]
ing clinical trials.
Hence, huge number of transition
(CH
3
COO)
and Zn (CH
2
.4H
2
O, Ni (CH
3
COO) .4H
.2H O. Organic solvents
2
2
2 3 2
O, Cu (CH COO) .
metal complexes are developed and tested for antitumor
activities and are considered as most hopeful substitute
H
O
2
3
COO)
2
like methyl alcohol, hexane, chloroform and
dimethylformamide were of spectroscopic purity and
used as such without further purification. The starting
[6,7]
to cisplatin as antitumor agents.
The transition metal
complexes hold unique characteristics like variableness
in coordination modes, redox activity and reactivity to-
wards the organic substrate.
materials
2‐phenethyloxy‐naphthalene‐1‐carbaldehyde
(a), 2‐benzyloxy‐naphthalene‐1‐carbaldehyde (b), 4‐
prop‐2‐ynyloxy‐benzaldehyde (c) and 2‐benzyloxy‐3,5‐
dichloro‐benzaldehyde (d) were prepared by the methods
N‐substituted thiosemicarbazones and their deriva-
tives, containing nitrogen and sulphur donor atoms with
imino functionality (‐C=N‐), have received stunning
[
30]
reported in the literature.
[8,9]
attention of researchers since 1950s
because of their
copious properties in physiochemical processes and
[
10–12]
diverse biological applications
like anticancer,
2.2 | Physicochemical measurements
anticonvulsant, antidiabetic, antifungal, antiviral, anti-
bacterial, anti‐inflammatory, antitubercular, anti‐HIV,
The melting points (°C) were observed in open capillaries
and are uncorrected. The Fourier transform infrared
(FTIR) spectra were recorded on Shimadzu IR affinity‐I
8000 FT‐IR spectrometer using KBr pellets in the wave-
[13–19]
antiamoebic,
idant and as antifertility agents.
as herbicides, insecticides and plant growth regula-
antimalarial, antihypertensive, antiox-
[20–22]
These are also used
[23,24]
−1
1
13
tors.
These thiosemicarbazones also behaves as long
length range of 4000–400 cm . H and C NMR spectra
were recorded on Bruker Avance II 400 MHz NMR spec-
trometer in CDCl and DMSO‐d by using TMS as an
acting and slow releasing drugs in diet, helps in studies of
[25]
metabolism,
acts as model for biological oxygen carrier
3
6
transport systems, used as corrosion inhibitors, designing
internal standard (chemical shift (δ) in ppm, coupling
constant J in (Hz)). Electronic spectra were recorded in
DMF on UV–VIS–NIR Varian Cary‐5000 spectrometer
at room temperature. Magnetic susceptibilites of the
complexes were measured at room temperature by using
[26]
of warehouses, catalyse enzymatic reactions,
exhibits
structure‐redox relationships, possess magnetic properties
[27,28]
and mesogenic characteristics.
These complexes
act as model molecules for biological oxygen carrier
systems, radiopharmaceutical, cancer targeting and
Gouy's method taking Hg [Co (SCN) ] as the calibrant.
4
[29]
dioxygen carriers.
Electron spin resonance spectra of the copper (II) com-
plexes were recorded by using tetracyanoethylene (TCNE)
as an internal standard on a Varian E112 X‐band spec-
trometer. Molar conductance measurements of metal
In extension of these investigations, it seemed ap-
pealing to develop such ligands which act as a backbone
to provide a prominent level of both antimicrobial
and cytotoxic activities, we report synthesis of novel
Schiff base thiosemicarbazones and their metal (II)
complexes of Co (II), Ni (II), Cu (II) and Zn (II) which
exhibits high antitumor activities and low toxicity.
For structural elucidations, various spectroscopic tech-
niques (IR, UV–Vis, NMR, mass), elemental analyses,
molar conductance, magnetic moment measurements
and thermal methods were used. The biological activi-
ties were also screened against some bacterial and
fungal organisms. Screening for antitumor activities
was also done.
−
3
complexes in DMF (concentration 10 M) at room tem-
perature were carried out using a model‐306 Systronics
conductivity bridge. Elemental analysis (C, H, N) was car-
ried out on the instrument Perkin Elmer 2400. Thermogra-
vimetric (TG) analysis of samples were carried out at a
−
1
heating rate of 10 °C min using Perkin Elmer Diamond
TG/DTA thermogravimetric analyzer instrument at a
−
1
flow rate of 20 mL min under high purity argon atmo-
sphere. Mass spectra were recorded on API 2000 (Applied
Biosystems) mass spectrometer equipped with an
electrospray source and a Shimadzu Prominence LC. Thin

DEVI ET AL.
3 of 23
layer chromatography (TLC) was run on the plates of
readymade silica gel (SIL G/UV254, ALUGRAM) and
visualized under ultraviolet light. The X‐ray powder dif-
fraction measurements were obtained using a Rigaku
Table Top X‐ray diffractometer at a scan rate of 2° min
in the range of 2θ = 20–80°.
the reaction mixture was further refluxed for 8 hr. The
solvent was evaporated and resulting off white solid (c)
was washed with ice‐cold water and recrystallized by
chloroform/hexane (scheme 1).
−
1
2
.4 | Synthesis of Schiff base ligands L ‐L
1
4
(1–4)
2
2
.3 | Synthesis of starting material ‐
‐Phenethyloxy‐naphthalene‐1‐
4
‐methyl‐3‐thiosemicarbazide (3.0 mmol, 3.15 g) dis-
solved in about 20 ml hot methanol was added slowly to
a magnetically stirred solution of above prepared deriva-
tives of napthaldehyde/benzaldehyde (a,b,c,d) in equi-
molar ratio in the presence of few drops of glacial acetic
acid and mixture was refluxed for 3–4 hr. Then, the
solution was concentrated to its half volume and the
obtained colored products were filtered off, washed sev-
eral times with methanol and recrystallized from chloro-
form (scheme 2).
carbaldehyde (a), 2‐Benzyloxy
naphthalene‐1‐carbaldehyde (b),
4
2
‐Prop‐2‐ynyloxy‐benzaldehyde (c) and
‐Benzyloxy‐3,5‐dichloro‐benzaldehyde (d)
To the solution of 2‐hydroxy‐1‐naphthaldehyde/3,5‐
dichlorosalicylaldehyde (1.0 mmol) in 20 ml DMF,
anhydrous potassium carbonate (2.0 mmol) was added
and stirred for 30 min. Then, slowly added (2‐bromo‐
ethyl)‐benzene (1.0 mmol) and bromomethyl‐benzene
(
1.0 mmol) in DMF for product a, b and d. The reaction
2.4.1 | (Z)‐N‐methyl‐2‐((2‐
mixture and was further stirred for 24–48 hr. Feasibility
of the reaction was frequently monitored by TLC.
The solvent was evaporated and the resulting dark
brown (a), light brown (b) and white colored (d) solid
were washed with ice‐cold water and recrystallized from
chloroform.
phenethoxynaphthalen‐1‐yl)methylene)
hydrazinecarbothioamide (L )
1
Dark brown; yield 80%; m.p. 125 °C; Anal. Calcd. for
C H N OS: C, 69.41; H, 5.79; N, 11.57. Found: C, 69.39;
21
21 3
−
1
2
−1
H, 5.82; N, 11.56. Conductivity: (ohm cm mol ) in
−
1
To the solution of 4‐hydroxy benzaldehyde (1.0 mmol)
in 20 ml acetone, anhydrous potassium carbonate
DMF: 12. IR (KBr, cm ): 1560 ʋ(C=N), 1270 ʋ(C=S),
1
3300 ʋ(N‐H). H NMR (400 MHz, CDCl ) δ (ppm): 8.81
3
(
2.0 mmol) was added and the resulting suspension was
(s, 1H, ‐C=NH), 8.77 (d, 1H, ‐NH, J = 8 Hz), 8.06 (s, 1H,
‐NH), 7.89(d, 1H, Ar‐H, J = 8 Hz), 7.82 (d, 1H, Ar‐H,
J = 8 Hz), 7.59–7.55(m, 1H, Ar‐H), 7.46–7.26(m, 6H,
stirred and refluxed for 30 min. Then, (2.0 mmol) propar-
gyl bromide (80% in toluene) was added to it slowly and
SCHEME 1 Synthesis of starting
aldehydic derivatives

4
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DEVI ET AL.
SCHEME 2 Scheme for synthesis of the
Schiff base ligands L ‐L (1–4)
1 4
Ar‐H), 4.41(t, 2H, ‐OCH ), 3.30(d, 3H, ‐CH ), 3.19 (t, 2H,
2.4.3 | (E)‐2‐(4‐(but‐3‐yn‐1‐yl)
benzylidene)‐N‐
2
3
13
‐
CH2), C NMR (400 MHz, CDCl ) δ (ppm): 178.49
3
(C=S), 157.43(C2), 140.61 (‐C=N‐), 138.12(C1),
methylhydrazinecarbothioamide (L )
3
1
1
1
32.69(C9), 131.17(C4), 129.45(C10), 129.12(C ,C ),
3 5
28.81(C5), 128.65(C ,C ), 128.13(C7), 127.07(C4),
White; yield 85%; m.p. 110 °C; Anal. Calcd. for
C H N OS: C, 51.50; H, 5.38; N, 7.23. Found: C, 51.51;
2
6
24.94(C ), 124.44(C ), 115.38(C ), 114.51(C ), 70.81(‐O‐
6
3
8
1
12 13 3
−
1
2
−1
CH ), 35.98 (‐CH ‐Ar), 31.36 (‐CH ), ESI‐MS (m/z):
H, 5.36; N, 7.21. Conductivity: (ohm cm mol ) in
DMF: 16. IR (KBr, cm ): 1565 ʋ(C=N), 1275 ʋ(C=S),
309 ʋ(N‐H). H NMR (400 MHz, CDCl ) δ (ppm):
.38(s, 1H, ‐C=NH‐), 7.78(s, 1H, ‐NH), 7.64(d, 2H, Ar‐H,
2
2
3
+
−1
3
64.11 (M + H) .
1
3
9
3
2
.4.2 | (Z)‐2‐((2‐(benzyloxy)naphthalen‐1‐
J = 8 Hz), 7.46(s, broad, 1H), 7.02(d, 2H, Ar‐H,
J = 8 Hz), 4.76(s, 2H, methylene), 3.28(d, 3H, CH group),
2.57(s, 1H, −alkyne group), C NMR (400 MHz, CDCl
yl)methylene)‐N‐
methylhydrazinecarbothioamide (L )
3
13
)
3
2
δ (ppm): 178.25 (C=S), 159.22(C ), 142.18 (‐C=N‐),
4
Light brown; yield 84%; m.p. 130 °C; Anal. Calcd. for
C H N OS: C, 68.72; H, 5.50; N, 2.04. Found: C,
128.77(C , C ), 127.01(C ), 115.21(C , C ), 78.01(‐O‐CH ‐
2
6
1
3
5
2
alkyne), 75.98(alkyne), 55.86(methylene), 31.06(‐CH ),
20
19
3
3
−
1
2
+
6
8.74; H, 5.48; N, 2.02. Conductivity: (ohm cm mol
ESI‐MS (m/z): 248.18 (M + H) .
−
1
−1
)
in DMF: 13. IR (KBr, cm ): 1565 ʋ(C=N), 1273
1
ʋ(C=S), 3302 ʋ(N‐H). H NMR (400 MHz, CDCl ) δ
3
(
1
ppm): 9.24(s, 1H, ‐C=NH‐), 8.79(s, 1H, ‐NH), 8.57(s,
H, ‐NH), 7.90(d, 1H, Ar‐H, J = 8 Hz), 7.83(d, 1H,
Ar‐H, J = 8 Hz), 7.61–7.57(m, 1H, Ar‐H), 7.46–7.39(m,
H, Ar‐H), 7.34(d, 1H, Ar‐H, J = 8 Hz), 5.27(s, 2H,
2.4.4 | (Z)‐2‐(3,5‐dichloro‐2‐
phenethoxybenzylidene)‐N‐
methylhydrazinecarbothioamide (L )
4
5
13
‐OCH ), 3.27(d, 3H, ‐CH ), C NMR (400 MHz, CDCl3)
White; yield 87%; m.p. 165 °C; Anal. Calcd. for
C H Cl N OS: C, 52.19; H, 4.12; N, 11.39. Found: C,
2
3
δ
1
1
1
1
3
(ppm): 178.43(‐C=S), 157.16(C2), 140.37(‐C=N‐),
36.21(C1), 132.71(C9), 131.36(C4), 129.34(C10),
16
15
2 3
−
1
2
52.18; H, 4.11; N, 11.41. Conductivity: (ohm cm mol
−
1
−1
28.86(C ,C ), 128.70(C5), 128.43(C ,C ), 128.17(C7),
) in DMF: 13. IR (KBr, cm ): 1568 ʋ(C=N), 1275
3
5
2
6
1
27.57(C4),
124.80(C6),
124.40(C3),
115.04(C8),
ʋ(C=S), 3308 ʋ(N‐H). H NMR (400 MHz, CDCl ) δ
3
14.10(C ), 71.67(‐O‐CH ), 31.36(‐CH ), ESI‐MS (m/z):
(ppm): 9.11(s, 1H, ‐C=NH‐), 7.69(s, 1H, Ar‐H), 7.68(s,
1H,‐NH, Ar‐H), 7.49(s, 1H, Ar‐H), 7.44–7.39(m, 4H, Ar‐
1
2
3
+
50.22(M + H) .

DEVI ET AL.
5 of 23
H), 7.35(s, broad, ‐NH), 5.03(s, 2H, methylene, 3.25(d, 3H,
2.5.2 | [Ni(L ).(CH COO) .2H O] (6)
1 3 2 2
13
‐
CH3), C NMR (400 MHz, CDCl ) δ (ppm): 178.49
3
(
1
‐C=S),
152.34(C2),
136.08(‐C=N‐),
135.34(C1),
Green; yield 76%; m.p. 258 °C; Anal. Calcd. for
C H F N NiO : C, 66.39; H, 4.64; N, 4.30; Ni, 9.01.
31.62(C ), 130.22(C , C ), 129.73(C ), 129.04(C ,C ),
4
3
5
6
2
6
36 30
2
2
4
1
28.86(C ), 128.83(C ), 124.37(C ), 117.57(C ), 72.09(‐
Found: C, 66.43; H, 4.63; N, 4.27; Ni, 9.04. Conductivity:
(ohm cm mol ) in DMF: 2.8. IR (KBr, cm ): 3460
5
4
3
1
+
−1
2
−1
−1
OCH ), 31.93(‐CH ), ESI‐MS (m/z): 368.23(M + H) .
2
3
ʋ(H‐O‐H), 1555 ʋ(C=N), 1254 ʋ(C=S), 3280 ʋ(N‐H),
1
740 ʋ (CH COO), 440 ʋ(M‐N), 410 ʋ(M‐S). ESI‐MS (m/
3
+
z): 651.86 (M + H) .
2.5 | Synthesis of transition metal (II)
complexes (5–20)
2
.5.3 | [cu(L ).(CH COO) .2H O] (7)
1 3 2 2
The different complexes of transition metals were pre-
pared by addition of metal acetates of Co (II), Ni (II),
Cu (II) and Zn (II) (1.0 mmol) dissolved in about 20 ml
methanol into 20 ml methanolic solution of above synthe-
sized ligands (1.0 mmol) in 1:1 molar ratio. The mixture
was stirred for 3–4 hr at room temperature by adjusting
pH 4–5 by adding some drops of aqueous base i.e. NaOH.
The different colored precipitates separated out were fil-
tered, washed with hexane and finally recrystallized from
chloroform and dried to get the pure product as repre-
sented in Scheme 3.
Brown; yield 69%; m.p. 245 °C; Anal. Calcd. for
C H CuN O S: C, 51.65; H, 5.40; N, 7.25; Cu, 10.95.
Found: C, 51.67; H, 5.38; N, 7.23; Cu, 10.93. Conductivity:
25
31
3 7
−
1
2
−1
−1
(
ohm cm mol ) in DMF: 11. IR (KBr, cm ): 3410
ʋ(H‐O‐H), 1543 ʋ(C=N), 1250 ʋ(C=S), 3285 ʋ(N‐H),
744 ʋ (CH COO), 442 ʋ(M‐N), 407 ʋ(M‐S). ESI‐MS (m/
1
3
+
z): 583.03 (M + H) .
2.5.4 | [Zn(L ).(CH COO) .2H O] (8)
1
3
2
2
White; yield 71%; m.p. 265 °C; Anal. Calcd. for
C H N O SZn: C, 51.49; H, 5.34; N, 7.23; Cu, 11.20.
25
31 3 7
Found: C, 51.51; H, 5.36; N, 7.21; Cu, 11.22. Conductivity:
−
1
2
−1
−1
2
.5.1 | [co(L ).(CH COO) .2H O] (5)
(ohm cm mol ) in DMF: 2.8. IR (KBr, cm ): 3505
1
3
2
2
ʋ(H‐O‐H), 1550 ʋ(C=N), 1258 ʋ(C=S), 3283 ʋ(N‐H),
1742 ʋ (CH COO), 439 ʋ(M‐N), 400 ʋ(M‐S). H NMR
(400 MHz, CDCl ) δ (ppm): 8.78(s, 1H, ‐C=NH‐), 8.74(d,
1
Brown Red; yield 72%; m.p. 265 °C; Anal. Calcd. for
C H N NiO S: C, 52.14; H, 5.43; N, 7.31; Co, 10.20.
3
25
31
3
7
3
Found: C, 52.10; H, 5.42; N, 7.29; Co, 10.18. Conductivity:
1H, ‐NH), 8.04(d, 1H, ‐NH‐), 7.89 (d, 1H, Ar‐H,
J = 8 Hz), 7.82 (d, 1H, Ar‐H, J = 8 Hz), 7.57(t, 1H,
Ar‐H, J = 8 Hz), 7.45–7.26(m, 6H, Ar‐H), 4.41(t, 2H,
‐OCH ), 3.30(d, 3H, ‐CH ), 3.19(t, 2H, ‐CH ), 2.38 (s,
−
1
2
−1
−1
(
ohm cm mol ) in DMF: 18. IR (KBr, cm ): 3457
ʋ(H‐O‐H), 1549 ʋ(C=N), 1259 ʋ(C=S), 3278 ʋ(N‐H),
736 ʋ (CH COO), 435 ʋ(M‐N), 403 ʋ(M‐S). ESI‐MS (m/
1
3
2
3
2
+
13
z): 576.02(M + H) .
6H, ‐CH COO). C NMR (400 MHz, CDCl ) δ (ppm):
3
3
SCHEME 3 Scheme for the synthesis of
Co (II), Ni (II), Cu (II) and Zn (II)
complexes (5–20)

6
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DEVI ET AL.
1
1
1
1
1
1
78.41 (C=S), 173.76(‐COO), 157.43(C ), 140.70 (‐C=N‐),
(‐C=N‐), 136.15(C ), 132.65(C ), 131.30(C ), 129.28(C ),
2
1
9
4
10
38.12(C1),
132.69(C9),
131.16(C4),
129.43(C10),
128.80(C ,C ), 128.64(C5), 128.37(C ,C ), 128.12(C7),
3
5
2
6
29.13(C ,C ), 128.81(C5), 128.66(C ,C ), 128.13(C7),
127.51(C4),
124.74(C6),
124.35(C3),
114.98(C8),
3
5
2
6
27.06(C4),
124.95(C6),
124.43(C3),
115.34(C8),
114.05(C ), 71.62(‐O‐CH ), 31.31(‐CH ), 18.49(acetate
1
2
3
+
14.48(C ), 70.80(‐O‐CH ), 35.97(‐CH ‐Ar), 31.38(‐CH ),
methyl). ESI‐MS (m/z): 568.30(M + H) .
1
2
2
3
+
8.57(acetate methyl). ESI‐MS (m/z): 265 (M + H) .
2
.5.9 | [co(L ).(CH COO) .2H O] (13)
3 3 2 2
2
.5.5 | [co(L ).(CH COO) .2H O] (9)
2 3 2 2
Brown Red; yield 77%; m.p. 280 °C; Anal. Calcd. for
C H CoN O S: C, 41.76; H, 5.02; N, 9.10; Co, 12.83.
Found: C, 41.74; H, 5.04; N, 9.13; Co, 12.80. Conductivity:
(ohm cm mol ) in DMF: 12. IR (KBr, cm ): 3487
ʋ(H‐O‐H), 1544 ʋ(C=N), 1241 ʋ(C=S), 3288 ʋ(N‐H),
Brown Red; yield 72%; m.p. 275 °C; Anal. Calcd. for
C H CoN O S: C, 51.23; H, 5.23; N, 7.43; Co, 10.45.
Found: C, 51.25; H, 5.20; N, 7.47; Co, 10.48. Conductivity:
16
23
3 7
24
29
3 7
−
1
2
−1
−1
−
1
2
−1
−1
(
ohm cm mol ) in DMF: 16. IR (KBr, cm ): 3467
ʋ(H‐O‐H), 1542 ʋ(C=N), 1256 ʋ(C=S), 3288 ʋ(N‐H),
744 ʋ (CH COO), 436 ʋ(M‐N), 408 ʋ(M‐S). ESI‐MS (m/
1744 ʋ (CH COO), 450 ʋ(M‐N), 412 ʋ(M‐S). ESI‐MS (m/
z): 461.30 (M + H) .
3
+
1
3
+
z): 563.21(M + H) .
2
.5.10 | [Ni(L ).(CH COO) .2H O] (14)
3 3 2 2
2
.5.6 | [Ni(L ).(CH COO) .2H O] (10)
2 3 2 2
Green; yield 72%; m.p. 290 °C; Anal. Calcd. for
C H N NiO S: C, 41.77; H, 5.07; N, 9.12; Ni, 12.78.
Found: C, 41.76; H, 5.04; N, 9.13; Ni, 12.76. Conductivity:
(ohm cm mol ) in DMF: 17. IR (KBr, cm ): 3500
ʋ(H‐O‐H), 1533 ʋ(C=N), 1240 ʋ(C=S), 3279 ʋ(N‐H),
Green; yield 73%; m.p. 290 °C; Anal. Calcd. for
C H N NiO S: C, 51.29; H, 5.16; N, 7.45; Ni, 10.41.
Found: C, 51.27; H, 5.20; N, 7.47; Ni, 10.44. Conductivity:
16
23
3
7
24
29
3
7
−
1
2
−1
−1
−
1
2
−1
−1
(
ohm cm mol ) in DMF: 13. IR (KBr, cm ): 3498
ʋ(H‐O‐H), 1540 ʋ(C=N), 1249 ʋ(C=S), 3286 ʋ(N‐H),
740 ʋ (CH COO), 442 ʋ(M‐N), 415 ʋ(M‐S). ESI‐MS (m/
1735 ʋ (CH COO), 446 ʋ(M‐N), 408 ʋ(M‐S). ESI‐MS (m/
z): 460.16 (M + H) .
3
+
1
3
+
z): 562.21 (M + H) .
2
.5.11 | [cu(L ).(CH COO) .2H O] (15)
3 3 2 2
2
.5.7 | [cu(L ).(CH COO) .2H O] (11)
2 3 2 2
Brown; yield 68%; m.p. 270 °C; Anal. Calcd. for
C H CuN O S: C, 41.32; H, 4.95; N, 9.06; Cu, 13.78.
Found: C, 41.33; H, 4.99; N, 9.04; Cu, 13.67. Conductivity:
(ohm cm mol ) in DMF: 13. IR (KBr, cm ): 3457
ʋ(H‐O‐H), 1548 ʋ(C=N), 1255 ʋ(C=S), 3280 ʋ(N‐H),
Brown; yield 68%; m.p. 268 °C; Anal. Calcd. for
C H CuN O S: C, 50.80; H, 5.12; N, 7.38; Cu, 11.23.
Found: C, 50.83; H, 5.15; N, 7.41; Cu, 11.21. Conductivity:
16
23
3 7
24
29
3 7
−
1
2
−1
−1
−
1
2
−1
−1
(
ohm cm mol ) in DMF: 18. IR (KBr, cm ): 3512
ʋ(H‐O‐H), 1556 ʋ(C=N), 1247 ʋ(C=S), 3290 ʋ(N‐H),
737 ʋ (CH COO), 445 ʋ(M‐N), 412 ʋ(M‐S). ESI‐MS (m/
1738 ʋ (CH COO), 438 ʋ(M‐N), 405 ʋ(M‐S). ESI‐MS (m/
z): 465.17 (M + H) .
3
+
1
3
+
z): 567.10 (M + H) .
2
.5.12 | [Zn(L ).(CH COO) .2H O] (16)
3 3 2 2
2
.5.8 | [Zn(L ).(CH COO) .2H O] (12)
2 3 2 2
White; yield 70%; m.p. 265 °C; Anal. Calcd. for
C H N O SZn: C, 41.15; H, 4.98; N, 9.02; Cu, 14.03.
Found: C, 41.17; H, 4.97; N, 9.00; Cu, 14.01. Conductivity:
(ohm cm mol ) in DMF: 19. IR (KBr, cm ): 3515
ʋ(H‐O‐H), 1536 ʋ(C=N), 1260 ʋ(C=S), 3283 ʋ(N‐H),
White; yield 73%; m.p. 270 °C; Anal. Calcd. for
C H N O SZn: C, 50.63; H, 5.17; N, 7.34; Cu, 11.51.
Found: C, 50.66; H, 5.14; N, 7.39; Cu, 11.49. Conductivity:
16
23 3 7
25
31 3 7
−
1
2
−1
−1
−
1
2
−1
−1
(ohm cm mol ) in DMF: 11. IR (KBr, cm ): 3425
1
ʋ(H‐O‐H), 1554 ʋ(C=N), 1258 ʋ(C=S), 3284 ʋ(N‐H),
1742 ʋ (CH COO), 449 ʋ(M‐N), 419 ʋ(M‐S). H NMR
(400 MHz, CDCl ) δ (ppm): 9.57(s, 1H, ‐C=NH‐), 7.81(s,
3
1
1
743 ʋ (CH COO), 441 ʋ(M‐N), 404 ʋ(M‐S). H NMR
3
3
(
1
7
(
400 MHz, CDCl ) δ (ppm): 9.22(s, 1H, ‐C=NH‐), 8.77(s,
H, ‐NH), 8.54(s, 1H, ‐NH), 7.87(d, 1H, Ar‐H, J = 8 Hz),
.80(d, 1H, Ar‐H, J = 8 Hz), 7.57(t, 1H, Ar‐H), 7.43–7.33
1H, ‐NH), 7.62(d, 2H, Ar‐H, J = 8 Hz), 7.47(s, broad,
1H), 7.02(d, 2H, Ar‐H, J = 8 Hz), 4.76(s, 2H, methylene),
3
3.29(d, 3H, CH group), 2.57(s, 1H, −alkyne group), 2.35
3
13
m, 6H, Ar‐H), 5.24(s, 2H, ‐OCH ), 3.24(d, 3H, ‐CH ),
(s, 6H, ‐CH COO). C NMR (400 MHz, CDCl ) δ
2
3
3
3
13
2
.38 (s, 6H, ‐CH COO). C NMR (400 MHz, CDCl ) δ
(ppm): 178.19 (C=S), 175.39(‐COO), 159.34(C ), 142.12
3
3
4
(
ppm): 178.37 (‐C=S), 173.70(‐COO), 157.10(C ), 140.31
(‐C=N‐), 128.85(C , C ), 126.78(C ), 115.27(C , C ),
2
2
6
1
3
5

DEVI ET AL.
7 of 23
7
3
4
7.98(‐O‐CH ‐alkyne), 76.02(alkyne), 55.87(methylene),
117.21(C1), 72.39(‐OCH2), 31.96(‐CH ), 19.23(acetate
methyl). ESI‐MS (m/z): 586.11(M + H) .
2
3
+
1.17(‐CH3), 19.62(acetate methyl). ESI‐MS (m/z):
+
67.39(M + H) .
2
2
.6 | Biophysical experiments
2
.5.13 | [co(L ).(CH COO) .2H O] (17)
4 3 2 2
.6.1 | Methodology of antimicrobial
activities
Brown Red; yield 77%; m.p. 275 °C; Anal. Calcd. for
C H Cl CoN O S: C, 41.33; H, 4.36; N, 7.25; Co, 10.13.
20
25
2
3 7
In vitro antimicrobial activity of the compounds were
tested by the standard serial dilution method against four
bacterial strains i.e. Gram‐positive bacteria Staphylococcus
aureus (MTCC 2901), Streptococcus gordonii (MTCC 822);
Gram‐negative bacteria Escherichia coli (MTCC 16521),
Pseudomonas aeruginosa (MTCC 424); two fungus strains
Candida albicans (MTCC 227) and Aspergillus niger
(MTCC 8189) which were cultured on nutrient broth
and potato dextrose broth as nutrient medium. Ciproflox-
acin and fluconazole were used as standards for antimi-
crobial studies and the minimum inhibitory
concentrations (MIC) were reported in μM/ml. MIC is
the lowest concentration of any antimicrobial agent that
will inhibits the visible growth of microorganisms after
incubation at the optimum conditions and calculated by
means of two fold serial dilution method using stock solu-
tion of test compounds having concentration 100 μg/ml in
Found: C, 41.32; H, 4.33; N, 7.23; Co, 10.14. Conductivity:
−
1
2
−1
−1
(
ohm cm mol ) in DMF: 20. IR (KBr, cm ): 3424
ʋ(H‐O‐H), 1549 ʋ(C=N), 1250 ʋ(C=S), 3287 ʋ(N‐H),
744 ʋ (CH COO), 442 ʋ(M‐N), 410 ʋ(M‐S). ESI‐MS (m/
1
3
+
z): 581.06 (M + H) .
2
.5.14 | [Ni(L ).(CH COO) .2H O] (18)
4 3 2 2
Light Brown; yield 70%; m.p. 285 °C; Anal. Calcd. for
C H Cl N NiO S: C, 41.37; H, 4,35; N, 7.24; Ni, 10.09.
20
25
2
3
7
Found: C, 41.34; H, 4.34; N, 7.23; Ni, 1o.10. Conductivity:
−
1
2
−1
−1
(
ohm cm mol ) in DMF: 14. IR (KBr, cm ): 3490
ʋ(H‐O‐H), 1542 ʋ(C=N), 1240 ʋ(C=S), 3290 (N‐H), 1739
ʋ (CH COO), 436 ʋ(M‐N), 420 ʋ(M‐S). ESI‐MS (m/z):
3
+
5
80.33 (M + H) .
[
31]
DMSO.
The stock solution was further diluted to make
2
.5.15 | [cu(L ).(CH COO) .2H O] (19)
4 3 2 2
concentrations of 50, 25, 12.5, 6.25, 3.12, 1.56 and 0.75 μg/
ml. The revived bacterial and fungal strains were inocu-
lated to each serially diluted solution and kept in incuba-
tor at 37 °C for 24 hr in the case of the bacteria and at
Green; yield 718%; m.p. 270 °C; Anal. Calcd. for
C H Cl CuN O S: C, 41.02; H, 4.27; N, 7.13; Cu, 10.86.
Found: C, 41.00; H, 4.30; N, 7.17; Cu, 10.85. Conductivity:
20
25
2
3 7
25 °C for 7 days in case of the fungi. Then, the results were
−
1
2
−1
−1
(
ohm cm mol ) in DMF: 11. IR (KBr, cm ): 3478
ʋ(H‐O‐H), 1534 ʋ(C=N), 1248 ʋ(C=S), 3281 ʋ(N‐H),
743 ʋ (CH COO), 440 ʋ(M‐N), 408 ʋ(M‐S). ESI‐MS (m/
compared with that of standard reference drug.
1
3
+
2.6.2 | Cytotoxic assay
z): 585.52 (M + H) .
All the synthesized complexes and ligands were assessed
for cytotoxicity against four different human cell lines:
A549 derived from human alveolar adenocarcinoma epi-
thelial cells (ATCC No. CCL‐185); MCF7 derived from
human breast adenocarcinoma cell line (ATCC No.
MDA‐MB‐231); DU145 derived from human prostate can-
cer cells (ATCC No. HTB‐81) and MRC‐5 derived from
human normal lung cells (ATCC No. CCL‐171) by means
of MTT colorimetric assay and using doxorubicin
2
.5.16 | [Zn(L ).(CH COO) .2H O] (20)
4 3 2 2
White; yield 69%; m.p. 265 °C; Anal. Calcd. for
C H Cl N O SZn: C, 40.88; H, 4.30; N, 7.18; Cu, 11.11.
Found: C, 40.87; H, 4.29; N, 7.15; Cu, 11.12. Conductivity:
20
25
2 3 7
−
1
2
−1
−1
(ohm cm mol ) in DMF: 16. IR (KBr, cm ): 3446
ʋ(H‐O‐H), 1537 ʋ(C=N), 1251 ʋ(C=S), 3290 ʋ(N‐H),
1
1
744 ʋ (CH COO), 445 ʋ(M‐N), 416 ʋ(M‐S). H NMR
3
[
32]
(400 MHz, CDCl ) δ (ppm): 8.84(s, 1H, ‐C=NH‐), 7.67(s,
(Adriamycin) as a standard.
The growth inhibition of
3
1
H, Ar‐H), 7.65(s, 1H,N‐NH‐), 7.47(d, 1H, Ar‐H,
J = 8 Hz), 7.42–7.38(m, 3H, Ar‐H), 7.36(s, 1H,N‐NH‐),
.01(s, 2H, methylene), 3.24(d, 3H, ‐CH ), 2.40 (s, 6H,
tumor cell lines was precise in different 96 well diffused
plates by cell mediated reduction of tetrazolium salt to
water insoluble formazan crystals. The consequence of dif-
ferent synthesized Schiff bases and metal complexes on the
probability of cancer cell lines along with normal cell line
was calculated on a multimode reader (InfiniteM200,
Tecan, Mannedorf, Switzerland) at 540 nm wavelength.
5
3
13
CH COO). C NMR (400 MHz, CDCl ) δ (ppm): 178.58
3
3
(
‐C=S), 173.89(‐COO), 152.34 (C2), 136.06(‐C=N‐),
1
35.34(C1), 131.62(C4), 130.23(C3, C5), 130.21(C6),
1
29.72(C ,C ), 129.05(C5), 128.84(C4), 124.37(C3),
2
6

8
of 23
DEVI ET AL.
The values obtained were corrected by subtracting the
absorbance of background from that of the blanks. The
dose response curves were plotted for the test compounds
along with controls and their IC values in μM were calcu-
the formation of different colored solid complexes, stable
at room temperature and non‐electrolytic in nature as the
molar conductance values of the complexes were found to
−
1
2
−1.[34,35]
be in between 11–20 ohm cm mol
All the com-
50
lated, which concerns with the concentration required to
cause toxic effects in 50% of cells. The entire experiment
was performed in triplicate.
pounds were soluble in MeOH, EtOH, CDCl , DMF and
3
DMSO but were insoluble in water. The ligands were che-
lated to all metal ions via nitrogen atom of azomethine
group and sulphur atom of thionyl group in thione form
without the replacement of hydrogen atom. The physical
measurements and analytical data of compounds 1–20
are depicted in Table 1.
[33]
3
| RESULTS AND DISCUSSION
The Schiff base ligands (L ‐L ) were obtained in good
1
4
yield
through
the
reaction
of
synthesized
napthaldehyde/benzaldehyde/salicylaldehyde derivatives
with 4‐methyl‐3‐thiosemicarbazide in dry methanol with
3.1 | FT‐IR spectra
1
–2 drops of glacial acetic acid. The homogeneity of these
compounds was regularly checked by TLC. Transition
metal complexes formulated as [M(L1–4).
CH COO) .2H O] were synthesized by refluxing metal
In order to know the nature of functional groups and to
interpret the coordinating mode of Schiff base ligands with
metal ions in complexes, IR spectrum of Schiff bases and
their complexes were recorded and compared with each
other and the values are listed in Table 2. The IR spectrum
of Schiff bases show bands in the region of 3300–
(
(
3
2
2
II) acetates with Schiff bases using methanol in 1:1
molar ratio. The mode of bonding, denticity and the
geometry of the complexes were elucidated by various
spectroscopic techniques like NMR, FT‐IR, mass, elec-
tronic spectra, ESR etc. The analytical data suggested
−
1
3308 cm assigned for υ (NH‐) stretching vibrations,
−
1
which shows downward shifting near 3278–3290 cm
indicating binding of Schiff bases through sulphur atom
TABLE 1 Analytical and physical data of the synthesized compounds
Found
(Calcd.)
N
%
−3
Sr. Molecular
No. formula
Yield
(%)
(Ω
Ω
M
) × 10
M.P.
−1
−1
2
Color
C
H
M
m/z
mol cm (°C)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
21
20
12
16
25
25
25
25
24
24
24
24
16
16
16
16
20
20
20
20
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
21
19
13
N
N
N
3
3
3
OS
OS
OS
80
84
85
87
72
76
69
71
72
73
68
73
77
72
68
70
77
70
71
Dark brown 69.39 (69.41) 5.82 (5.79) 11.56 (11.57)
Light brown 68.74 (68.72) 5.48 (5.50) 12.02 (12.04)
‐
‐
‐
‐
364.11 12
350.22 13
248.18 16
368.23 13
125
130
110
165
265
258
245
265
275
290
268
270
280
290
270
265
275
285
270
265
White
51.51 (51.50) 5.36 (5.38) 7.21 (7.23)
52.18 (52.19) 4.11 (4.12) 11.41 (11.39)
15Cl
31CoN
NiO
31CuN
2
N
3
OS
White
3
O
7
S
Brown red
Green
52.08 (52.09) 5.42 (5.41) 7.29 (7.28) 10.22 (10.19) 577.85 15
52.10 (52.14) 5.42 (5.43) 7.29 (7.31) 10.18 (10.20) 576.02 18
51.67 (51.65) 5.38 (5.40) 7.23 (7.25) 10.93 (10.95) 583.03 11
51.51 (51.49) 5.36 (5.34) 7.21 (7.23) 11.22 (11.20) 582.22 12
51.25 (51.23) 5.20 (5.23) 7.47 (7.43) 10.48 (10.45) 563.21 16
51.27 (51.29) 5.20 (5.16) 7.47 (7.45) 10.44 (10.41) 562.21 13
50.83 (50.80) 5.15 (5.12) 7.41 (7.38) 11.21 (11.23) 567.10 18
50.66 (50.63) 5.14 (5.17) 7.39 (7.34) 11.49 (11.51) 568.30 11
41.74 (41.76) 5.04 (5.02) 9.13 (9.10) 12.80 (12.83) 461.30 12
41.76 (41.77) 5.04 (5.07) 9.13 (9.12) 12.76 (12.78) 460.16 17
41.33 (41.32) 4.99 (4.95) 9.04 (9.06) 13.67 (13.78) 465.17 `13
41.17 (41.15) 4.97 (4.98) 9.00 (9.02) 14.01 (14.03) 467.39 19
41.32 (41.33) 4.33 (4.36) 7.23 (7.25) 10.14 (10.13) 581.06 20
31
N
3
7
S
3
O
7
S
Brown
31
N
3
O
7
SZn
White
29CoN
NiO
29CuN
3
O
7
S
Brown red
Green
0
1
2
3
4
5
6
7
8
9
0
29
N
3
7
S
3
O
7
S
Brown
29
N
3
O
7
SZn
White
23CoN
NiO
23CuN
3
O
7
S
Brown red
Green
23
N
3
7
S
3
O
7
S
Brown
23
N
3
O
7
SZn
CoN
NiO
CuN
White
25Cl
25Cl
25Cl
25Cl
2
2
2
2
3
O
7
S
Brown red
N
3
7
S
Light brown 41.34 (41.37) 4.34 (4.35) 7.23 (7.24) 10.10 (10.09) 580.33 14
3
O
7
S
Green
White
41.00 (41.02) 4.30 (4.27) 7.17 (7.13) 10.85 (10.86) 585.52 11
40.87 (40.88) 4.29 (4.30) 7.15 (7.18) 11.12 (11.11) 586.11 16
3 7
N O SZn 69

DEVI ET AL.
9 of 23
[
44]
in thione form without formation of thio‐enol tautomer or
no disappearance of υ(N‐H) band. The bands in the region
octahedral geometry.
In conclusion, the IR data sug-
gests a bidentate nature of ligands.
−
1
−1
1
560–1568 cm and 1270–1275 cm , were observed in
Schiff base spectra assigned for azomethine υ(‐C=NH)
[
36]
1
and thiocarbonyl υ(C=S) stretching vibrations,
underwent modest downward shifting (bathochromic
3.2 | H NMR spectra
−
1
1
shift) by 20–25 cm while comparing with the spectra of
complexes and observed in the range of 1535–1556 and
The H NMR spectrum of the Schiff bases and their
respective transition metal (II) complexes were carried
out in CDCl . The observed values of NMR data are given
−
1.[37]
1
260–1240 cm
This shifting divulges donation of
3
the lone pair of electrons available on azomethine
nitrogen to metal centers and confirms binding through
in experimental section and Figure 1. Schiff bases (L ‐L )
1
4
showed a characteristic signal due to azomethine nitro-
gen in the range of δ 9.38–8.81 ppm. Another signal due
to –NH proton adjacent to thionyl group appears near δ
8.79–7.68 ppm. Further, a broad signal in Schiff bases is
observed towards the upfield region in the range of δ
[38–40]
nitrogen and sulphur donor atoms.
In addition,
−
1
new broad bands displayed near 3515–3410 cm in all
complexes may be attributed for two coordinated water
molecules.
−
1
The bands observed near 435–450 cm
and 400–
8.57–7.35 ppm attributed to another –NH group which
−
1
[45]
4
20 cm which were not present in the free Schiff base
is attached to methyl group.
One sharp characteristic
ligands were assigned for formation of new bonds in the
spectra of complexes ascribed as ʋ(M–N) and ʋ(M–S),
reveals bidentate nature of Schiff bases and confirms
singlet near δ 5.27–4.41 ppm assigned for the protons of
methylene group attached to oxygen atom (O‐CH ). A
2
doublet in the range of δ 3.30–3.25 ppm was ascribed to
[41–43]
coordination via S and N donor atoms.
Further-
the protons of methyl (‐CH ) group was observed in all
3
[
46]
more, another sharp peak was observed in the region
ligands
and another triplet was observed in the case
−
1
~
1735–1744 cm in all the 1:1 metal complexes, attrib-
of ligand (L ) at δ 3.19 ppm certified the presence of
1
uted due to ʋ (OCOCH ) group which shows binding of
another methylene group. While in Schiff base L , a sharp
3
3
acetate groups to the metal centers to complete their
singlet at δ 2.57 ppm was observed, revealed the presence
−
1
TABLE 2 Characteristic IR frequencies (cm ) of Schiff bases and their respective transition metal (II) complexes
S. No Compounds υ(H‐O–H) water υ(N–H) υ(C=S) υ (CH COO) υ(‐C=NH‐) azomethine υ(M‐N) υ(M–S)
3
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
L
L
L
L
1
2
3
4
‐
‐
3300
3302
3309
3308
3278
3280
3285
3283
3288
3286
3290
3284
3288
3279
3280
3283
3287
3290
3281
3290
1270
1273
1275
1275
1259
1254
1250
1258
1256
1249
1247
1258
1241
1240
1255
1260
1250
1240
1248
1251
‐
‐
1560
1564
1565
1568
1549
1555
1543
1550
1542
1540
1556
1554
1544
1533
1548
1536
1549
1542
1534
1537
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
Co(L
1
).(CH
).(CH
).(CH
3
COO)
COO)
COO)
2
.2H
.2H
.2H
2
O
3457
3460
3410
3505
3467
3498
3512
3425
3487
3500
3457
3515
3424
3490
3478
3446
1736
1740
1744
1742
1744
1740
1737
1743
1744
1735
1738
1742
1744
1739
1743
1744
435
440
442
439
436
442
445
441
450
446
438
449
442
436
440
445
403
410
407
400
408
415
412
404
412
408
405
419
410
420
408
416
Ni(L
1
3
2
2
O
Cu(L
1
3
2
2
O
Zn(L
1
2
).(CH
3
3
COO)
2
2
.2H
2
O
O
Co(L
).(CH
COO)
.2H
2
0
1
2
3
4
5
6
7
8
9
0
Ni(L
2
).(CH
3
COO)
2
.2H
2
O
Cu(L
2
).(CH
3
COO)
2
.2H
2
O
Zn(L
2
).(CH
3
COO)
2
.2H
2
O
O
Co(L
3
).(CH
3
COO)
2
.2H
2
Ni(L
3
).(CH
3
COO)
2
.2H
2
O
Cu(L
3
).(CH
3
COO)
2
.2H
2
O
Zn(L
3
4
).(CH
3
3
COO)
2
2
.2H
2
O
O
Co(L
).(CH
COO)
.2H
2
Ni(L
4
).(CH
).(CH
).(CH
3
COO)
COO)
COO)
2
.2H
.2H
.2H
2
O
Cu(L
4
3
2
2
O
Zn(L
4
3
2
2
O

10 of 23
DEVI ET AL.
TABLE 3 Electronic spectral data and magnetic moment (BM) of Schiff bases and their respective transition metal (II) complexes
Absorption
(cm )
‐
1
−1
−1
Compounds
Band assignment
Dq (cm
)
B (cm
)
β
β %
υ
2/
υ
1
Geometry μ (BM)
L
1
L
2
L
3
L
4
28,770
n → π
π → π
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
*
3
9,300
27,980
8,850
27,820
9,950
28,980
n → π
π → π
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
*
3
n → π
π → π
‐
‐
‐
*
3
n → π
π → π
‐
*
40,000
4
4
Co(L
1
).(CH
3
COO)
2
.2H
2
O
9,740
7,610
2,580
T
T
1g(F) → T2g(F) (υ
1
)
1284
707.3
762.4
‐
0.728 27.2 2.31 Octahedral
0.732 26.8 1.76 Octahedral
4.45
4
4
1
2
1g(F) → A2g(F) (υ
2
)
4
4
T
3
1g(F) → T2g(P) (υ )
3
2
3
Ni(L
1
).(CH
3
COO)
2
.2H
2
O
10,396
A
3
2g(F) → T2g(F) (υ
1
)
1039
3.23
1.92
3
1
2
8,300
4,325
A
A
2g(F) → T1g(F) (υ
2g(F) → T1g(P) (υ
2
)
)
3
3
3
2
Cu(L
1
).(CH
3
COO)
2
.2H
2
O
15,475
4,450
B
1
2
g → A
1
2
g (ν
1
)
‐
‐
‐
‐
‐
‐
‐
‐
Octahedral
Octahedral
2
1 2 2
B g → E g (ν )
Zn(L
1
).(CH
3
COO)
2
.2H
2
O
O
23,600
9,810
LMCT
‐
‐
4
4
Co(L
2
).(CH
3
COO)
2
.2H
2
T
T
1g(F) → T2g(F) (υ
1
)
1268.4
1028
‐
709.6
0.731 26.9 2.29 Octahedral
4.43
4
4
1
2
7,585
2,494
2
1g(F) → A2g(F) (υ )
4
4
T
3
1g(F) → T2g(P) (υ )
3
3
Ni(L
2
).(CH
3
COO)
2
.2H
2
O
10,285
A
3
2g(F) → T2g(F) (υ
1
)
788.3
0.757 24.3 1.79 Octahedral
3.29
1.82
3
1
2
8,460
4,220
A
A
2g(F) → T1g(F) (υ
2g(F) → T1g(P) (υ
2
)
)
3
3
3
2
2
Cu(L
2
).(CH
3
COO)
2
.2H
2
O
15,330
4,850
B
1
2
g → A
1
2
g (ν
1
)
‐
‐
‐
‐
‐
‐
‐
Octahedral
Octahedral
2
1 2 2
B g → E g (ν )
Zn(L
2
).(CH
3
COO)
2
.2H
2
O
O
23,890
9,989
LMCT
‐
‐
‐
4
4
Co(L
3
).(CH
3
COO)
2
.2H
2
T
T
T
1g(F) → T2g(F) (υ
1
)
1228.6
669.5
0.689 31.1 2.22 Octahedral
4.48
4
4
4
1
2
7,635
2,275
2
1g(F) → A2g(F) (υ )
4
3
1g(F) → T2g(P) (υ )
3
2
3
Ni(L
3
).(CH
3
COO)
2
.2H
2
O
10,415
A
2g(F) → T2g(F) (υ
1
)
1041
788.6
0.758 24.2 1.78 Octahedral
3.22
1.89
3
3
1
2
8,590
4,485
A
A
2g(F) → T1g(F) (υ
2g(F) → T1g(P) (υ
2
)
)
3
3
3
2
Cu(L
3
).(CH
3
COO)
2
.2H
2
O
15,530
4,500
B
1
2
g → A
1
2
g (ν
1
)
‐
‐
‐
‐
‐
‐
‐
‐
Octahedral
Octahedral
2
1 2 2
B g → E g (ν )
Zn(L
3
).(CH
3
COO)
2
.2H
2
O
O
23,480
LMCT
‐
‐
‐
4
4
Co(L
4
).(CH
3
COO)
2
.2H
2
9,625
T
T
T
1g(F) → T2g(F) (υ
1
)
1276.5
722.0
0.743 25.7 2.32 Octahedral
4.46
4
4
4
1
2
7,350
2,390
2
1g(F) → A2g(F) (υ )
4
3
1g(F) → T2g(P) (υ )
3
3
3
Ni(L
4
).(CH
3
COO)
2
.2H
2
O
10,510
A
A
3
2g(F) → T2g(F) (υ
1
)
)
1051
752.4
0.723 27.7 1.75 Octahedral
3.25
3
18,420
4,390
2g(F) → T1g(F) (υ
2
3
2
A
2g(F) → T1g(P) (υ
3
)
2
2
Cu(L
4
).(CH
3
COO)
2
.2H
2
O
15,275
4,300
B
1
2
g → A
1
2
g (ν
g (ν )
2 2
1
)
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
Octahedral
Octahedral
1.84
2
B
1
g → E
Zn(L
4
).(CH
3
COO)
2
.2H
2
O
23,780
LMCT
‐
of alkyne proton. Further, some singlets, doublets and
multiplets for aromatic protons were observed near δ
On comparing the proton NMR of Schiff bases with
their Zn (II) complexes, it was found that no change in
the number of signals was observed, which confirms that
7
.90–7.02 ppm.

DEVI ET AL.
11 of 23
FIGURE 1 1H NMR spectra of (a) Schiff base 1 and (b) its zinc (II) complex (8)
the coordination of ligands to the metal ions has occurred
through sulfur atom in thione form which reveals that
there is no deprotonation of hydrazide nitrogen atom
methyl groups also gets slightly shifted in spectra of com-
plexes. Signals due to methyl, methylene, alkyne and aro-
matic protons were also slightly altered, resulting in
complexation of Schiff bases to the metal ions.
[47]
for thiolization of C=S group on complexation.
Fur-
ther, shifting in the peaks of azomethine group appears
in vicinity of δ 9.57–8.78 ppm indicates binding of ligands
through azomethine nitrogen atom to the central metal
ions. Moreover, the shifting without disappearance of sig-
nal assigned for –NH protons attached to thione group
confirms the chelation via sulphur atom as it is in thione
1
3
3.3 | C NMR spectra
13
C NMR spectra of Schiff bases and Zn (II) metal com-
plexes were recorded in CDCl3 and DMSO‐d6 using
tetramethylsilane (TMS) as an internal standard and the
[48]
form.
Another signal due to –NH group attached to

1
2 of 23
DEVI ET AL.
[50]
13
values are listed in experimental section and Figure 2.
C
in the complexes as a result of coordination with metals.
NMR spectrum of Schiff bases displayed characteristic sig-
nal in the range δ 152.34–159.22 ppm attributed to
azomethine carbon (‐C=N‐) which underwent shifting in
the complexes revealed binding of azomethine nitrogen
atom via lone pair of electrons to the central metal
A singlet in the vicinity of δ 31.93–31.06 ppm was observed
due to methyl carbons adjacent to –NH group. The peaks
for methylene carbons attached to oxygen atom appeared
near δ 55.86–72.09 ppm. In L ligand, an extra peak at δ
1
35.98 assigned for another methylene group present in
[
49]
ion.
A singlet near δ 178.49–178.25 ppm corresponding
the moiety, while in L , two more peaks were observed
3
to the thionyl (‐C=S) group gets shifted in the complexes
confirming ligation through sulfur atom of Schiff bases to
metal ions. The peaks due to aromatic carbons were
observed near δ 142.18–114.10 ppm, exhibits alternation
which were ascribed for alkyne carbons had been shifted
to δ 77.98 and 76.02 ppm in the complexes. All values
related to synthesized Schiff bases and their zinc (II) com-
plexes are depicted in supplementary data.
FIGURE 2 13C NMR spectra of (a) Schiff base (1) and (b) its zinc (II) complex (8)

DEVI ET AL.
13 of 23
3
.4 | Mass spectra
temperature, the magnetic moment values of the Co (II)
complexes lie in the range of 4.43–4.48 BM due to three
unpaired electrons and were in good agreement with
The mass spectral data of Schiff base ligands and their
metal chelates were specified in Table 1 and the peaks
are shown in Figure 3. The molecular ion peaks are found
in good agreement with the expected values. The mass
spectrum of ligand L gives a peak at 364.41 m/z, which
is assigned for [M + H] peak and is in good agreement
with the molecular weight of the compound 363.14. Co
[
53]
those reported for the octahedral structure.
Ni (II) complexes exhibited three bands in the vicinity
−
1
−1
of 10,285–10,510 cm , 18,300–18,590 cm and 24,220–
−
1
3
3
24,485 cm
attributed to the A g(F) → T2g(F),
1
2
3
3
3
3
A g(F) → T g(F), A g(F) → T g(P) transitions respec-
1
1
2
1
tively, and the value of υ /υ was found to be 1.75–1.79,
2
1
(
II) complex of Schiff base L gives molecular ion peak
which were in harmony with octahedral geometry
around nickel (II) ions. The Racah interelectronic repul-
sion parameters B, β were calculated for Ni (II) complexes
1
at m/z 577.85 assigned for [M + H] peak and was in good
agreement with that of its molecular mass 576.12. Thus,
the mass spectral results along with elemental analyses
agreed with the formation of the complexes of type
−
1
and were found to be in the range 752–788 cm and
0.723–0.758, respectively. The value of B was found to
[39]
−1
[
M(L)(CH COO) .2H O] in 1:1 stoichiometry.
be less than the free ion value (1041 cm ) because of
3
2
2
decreased interelectronic repulsions due to electron delo-
calization and shows covalent nature of bond between
[
54]
3.5 | Electronic spectra and magnetic
metal and ligand.
Further, the magnetic moment
measurements
values for Ni (II) complexes were found near 3.22–3.29
BM, expected for S = 1 due to two unpaired electrons
with small contribution of orbital motion also confirms
The electronic spectra and magnetic moment measure-
ments were recorded in solid state at room temperature
in DMF in order to acquire the geometry of the com-
plexes and the values obtained were summarized in
Table 3. The electronic spectra of all Schiff bases showed
two bands, one within the range of 27,820–28,980 cm
attributed to the n–π* transitions and another band
[
55]
octahedral geometry.
In the electronic spectra of Cu (II) complexes, UV spec-
−
1
tral bands were observed in vicinity of 15,275–15530 cm
−
1
and 24,300–24,850 cm
which were attributed for
B g → A g (ν ) B g → E g (ν ) transitions, respectively
−
1
2
2
2
2
1
1
1
1
2
2
and the magnetic moment values lies in the range of 1.82–
−
1
[56,57]
within the range of 38,850–40,000 cm is due to the
1.92 BM corresponds to octahedral geometry.
[51]
π–π* transitions.
The electronic spectra of the Co (II) complexes showed
Zn (II) complexes exhibited only one band in the
−
1
region of 23,480–23,890 cm due to ligand to metal
−
1
three bands around 9,625–9,989 cm , 17,350–
charge transfer transitions. Further, Zn (II) complexes
−
1
−1
10
1
7,635 cm and 22,275–22,580 cm have been assigned
are diamagnetic with fully filled d configuration and
4
4
4
4
for the T g(F)
→
T2g(F), T1g(F)
→
A g(F),
do not show any d‐d transitions. On the basis of the above
1
2
4
4
T1g(F) → T g(P) transitions, respectively which are
observations and spectral data, it was suggested that all
1
[
52]
[58]
characteristic of octahedral geometry.
The octahedral
the metal complexes possess octahedral geometry.
geometry for Co (II) complexes was further supported by
The figure representing electronic spectra of Schiff base
L2 and its metal (II) complexes is provided in supplemen-
tary data.
the values obtained by the ratio of υ /υ , which lies within
2
1
the range of 2.22–2.32 and various ligand field parameters
like Dq, B, β and β% calculated by using band fitting equa-
tion. The values of B and nephelauxetic parameter β were
−
1
found to be 669–722 cm and 0.689–0.743, respectively.
3.6 | ESR spectra
The B values were less than the free ion value (971 cm
−
1
)
calculated from B (complex)/B (free ion), indicated
Electron spin resonance (ESR) is a branch of spectroscopy
in which radiations in the range of microwave frequency
was absorbed by molecules possessing electrons with
unpaired spins. The solid state ESR spectrum of the Cu
covalent character between metal–ligand bonds. At room
TABLE 4 ESR spectral parameters of Cu (II) complexes
(
II) complex was recorded at room temperature from
Cu (II) complexes
g
||
g
┴
g
av
G
which, g and g⊥values of [Cu(L ).(CH COO) .2H O]
|
|
2
3
2
2
Cu(L
Cu(L
Cu(L
Cu(L
1
2
3
4
).(CH
).(CH
).(CH
).(CH
3
3
3
3
COO)
COO)
COO)
COO)
2
2
2
2
. 2H
. 2H
. 2H
. 2H
2
2
2
2
O
O
O
O
2.20
2.23
2.21
2.22
2.07
2.07
2.06
2.08
2.11
2.12
2.11
2.12
2.92
3.36
3.59
2.80
were calculated and shown in Figure 4. The spin
Hamiltonian parameters of Cu (II) complexes were
calculated and summarized in the Table 4. An intense
band is observed in the high field region of ESR spectra.
The ground state of the copper (II) complex is

14 of 23
DEVI ET AL.
FIGURE 3 Mass spectra of (a) Schiff base 1 (b) Cobalt (II) complex (5)
acknowledged from the g tensor values, g > g⊥ > 2.0023
between the Cu (II) centers in polycrystalline compounds
||
which are in accordance with octahedral geometry and
can be determined by using the following formula
2
2
[60]
indicates that unpaired electron resides in the d ‐ y
G = (g ‐2.0023)/(g⊥ − 2.0023).
If G < 4, it was
x
||
2
[59]
orbital and in the ground state as B1g.
The spin
considered the existence of some exchange interactions
between the Cu (II) centers and if G > 4, the exchange
interactions were negligible. In this complex, the G
value was found to be 3.36, indicative of very little
exchange interactions between the copper centers in
orbital coupling constant λ was calculated using the rela-
tion gav = 2(1– 2λ/10Dq) and gav was calculated by the
formulae: 1/3(g + 2 g⊥) which is less than free ion Cu
|
|
−
1
(
II) complex, λ value (832 cm ) supported the covalent
[
61]
character of M–L bond in complex. Further, the observed
the solid state.
g values for [Cu(L ).(CH COO) .2H O] complex were
2
3
2
2
g = 2.23, g⊥ = 2.07, g = 2.12, G = 3.36 were character-
|
|
av
istic of anionic and covalent environments respectively,
in metal–ligand bonding.
3.7 | X‐ray diffraction spectra
From the values of the g factors, geometric parameter
G, representing a measure of the exchange interaction
The X‐ray powder diffraction analysis of the compounds
has been carried out in order to determine whether the

DEVI ET AL.
15 of 23
FIGURE 4 ESR spectrum of copper complex [Cu(L2).(CH3COO)2.2H2O] (11) at room temperature
nature of the sample is crystalline or amorphous and is
performed by scanning the compound in the range
its zinc complex (12) is depicted in Figure 5. show well
defined sharp peaks due to their crystalline nature. The
crystallite size (D) of the compounds were calculated by
using Debye Scherrer's equation:
2θ = 0–80° at a wavelength of 1.54 Å at room tempera-
ture. The powder diffraction spectra of ligand L (2) and
2
FIGURE 5 XRD Spectra of (a) Schiff base 2 (b) zinc complex 12 [Zn(L2).(CH3COO)2.2H2O]

16 of 23
DEVI ET AL.
0
:9λ
1
2
decomposition in three steps. The first peak at 180 °C
with a weight loss of 6.5% (calcd. 6.3%) is assigned to
elimination of two coordinated water molecules, which
is accompanied by an endothermic peak. The second step
appeared as an exothermic peak at 250 °C, assigned for
ξ ¼ β cos θ
where, constant 0.9 is the shape factor, λ is the X‐ray
wavelength of 1.5406 Å, θ is the Bragg diffraction angle
and β is the full width at half maximum (FWHM). The
experimental average crystallite size of ligand and its
metal complex was found to be 33 and 34 nm suggesting
the nanocrystalline size of the particles. The another
loss of two CH COOH molecules with weight loss 20.4%
3
(
calcd. 20.8%). The third step appeared as an exothermic
peak at 570 °C, with a weight loss of 60.9% (calcd.
1.6%) implies complete decomposition of the complex
6
with the formation of ZnO in the end which is accompa-
nied by an exothermic peak.
[62,63]
parameter i.e. dislocation density (δ)
is the number
of dislocation lines per unit area of the crystal whose
value is related to the average particle diameter (D) and
is calculated by the relation
The TG and DTA thermogram of complex [Cu(L2).
(
CH COO) .2H O] (11) showed three decomposion steps.
3 2 2
The first peak at 200 °C with a weight loss of 6.1% (calcd.
.34%) represents the elimination of two coordinated
6
1
δ ¼
2
water molecule, accompanied by an endothermic peak.
The second step indicates weight loss of 20.2% (calcd.
ξ
XRD
2
0.8%) at 290 °C, assigned for the loss of two coordinating
The values of dislocation density (δ) was found to be in
the range 0.00086–0.00092 nm .
−
2
acetate molecules that is accompanied by an exothermic
peak. The third step appeared as an exothermic peak near
6
00 °C with a weight loss of 61.1% (calcd. 61.7%) referring
3
.8 | Molar conductivity values
to the complete decomposition of this complex that ended
with the formation CuO, that is accompanied by an exo-
thermic peak.
−
3
The molar conductivities of 10 M solution complexes
dissolved in DMF were recorded at room temperature
and the values reported in Table 1. The results obtained
for the conductivity measurements of the compounds
were found in the range of 11–20 Ω mol cm reveals
that all the metal complexes have very low conductivity
values which were characteristics for their non‐
The thermogram of the [Co(L ).(CH COO) .2H O] (9)
2
3
2
2
and [Ni(L ).(CH COO) .2H O] (10) complexes also
2
3
2
2
showed three steps of decomposition. The first peak
appeared as an endothermic peak near 170–180 °C with
a weight loss of 6.1 and 6.13% (calcd. 6.39 and 6.4%),
respectively, is assigned to removal of two coordinated
water molecules from each complex. The second peak
appeared at 260–280 °C with a weight loss of 20.3 and
20.6% (calcd. 20.95 and 21.0%) attributed for the loss of
two coordinated acetate molecules from each complex;
accompanied by an exothermic peak. In the third step,
an exothermic peak near 550–580 °C associated a weight
loss of 61.7 and 62.6% (calcd. 62.1 and 62.2%) get
appeared which was assigned for the elimination of
ligand moiety from each complex, implies for complete
decomposition of these complexes, respectively, ended
−
1
−1
2
[
64,65]
electrolytic nature.
3.9 | Thermal analysis
The thermal studies of ligands and their metal complexes
were characterized within a temperature range of 25 °C
to 1000 °C to elucidate the thermal stability of complexes,
to decide whether the water molecules (if present) are
inside or outside the coordination sphere of the central
metal ion and to recommend a common scheme for ther-
mal decomposition of these chelates. The temperature
intervals and the percentage of mass loss are depicted in
the graphs (Figure 6). Through IR spectral data
[
66]
with formation of metal oxides in the end.
(Table 2), it was found that two water molecules are pres-
3.10 | Biological studies
ent in the complexes; thermal analyses was carried out to
ascertain their nature, and to give an insight into the
thermal stability of the studied compounds. The results
showed that there is a good agreement in the weight loss
between the calculated and the proposed formulae. The
thermal analyses imply that all complexes generally
decomposed in three steps.
3.10.1 | In vitro antibacterial activity
The antibacterial activity of synthesized compounds and
the standard drug ciprofloxacin were screened against
two Gram +ve bacteria (S. aureus, S. gordonii) and two
Gram –ve bacteria (E. coli, P. aeruginosa). Serial dilution
method was used to evaluate antibacterial activity of com-
pounds and the data are given in Table 5 and graphical
The DTA and TGA thermogram of [Zn(L2).
(
CH COO) .2H O] complex (12) showed thermal
3 2 2

DEVI ET AL.
17 of 23
FIGURE 6 Thermogravimetric analysis plots of (a) complex 12 [Zn(L2).(CH3COO)2.2H2O] (b) complex 11 [Cu(L2).(CH3COO)2.2H2O]
representation in Figure 7. Antibacterial activity data
shows that the metal complexes were more venomous
than Schiff bases for the same strains under similar condi-
tions. Metal complexes show more toxicity towards Gram
aeruginosa. Compounds 5–8 and 14–20 were found to
be excellent bioactive against E. coli strains while against
P. aeruginosa, only complexes 16, 19 display very high
activity. The variation in the antimicrobial activity of dif-
ferent metal complexes against different microorganisms
depends on the impermeability of the cell wall or the
differences in ribosomes in microbial cell. The lipid
membrane surrounding the cell wall favors the passage
of any lipid soluble materials and it is known that
liposolubility is an important factor controlling antimi-
+
ve strains than Gram ‐ve strains and reason lies in the
difference in the complexity of structure of the cell walls
[67]
of Gram positive and Gram negative bacteria.
The order of antibacterial potency for Schiff bases (L1‐
L ) was L > L > L > L depending on the basis of
4
4
1
2
3
molecular weight. Further, the presence of two chloro
[
68,69]
groups in ligand L makes the compound highest active.
crobial activity.
3
The MIC values obtained indicate that the compounds
have significantly good inhibitory effect against S. aureus
but moderate effect against S. gordonii for Gram positive
bacterial strains. Furthermore, the compounds 4, 9, 11,
3.10.2 | In vitro antifungal activity
1
4, 16–20 were found to be very effective against strains
Antifungal activities of synthesized compounds were
tested against two fungal strains (C. albicans, A. niger)
and compared with standard antifungal drug fluconazole
at the same concentration. Antifungal activity data of the
compounds is summarized in Table 5 and Figure 7. The
of S. aureus and complexes 11, 19 were found to be effec-
tive for S. gordonii species.
In case of Gram negative bacterial strains, complexes
show more potency against E. coli as compared to P.

18 of 23
DEVI ET AL.
TABLE 5 Results of in vitro antimicrobial screening for Schiff bases (1–4), mononuclear metal complexes (5–20) and standard drugs (21,
2). (MIC in μM/ml)
2
Gram +ve bacteria
Gram –ve bacteria
Fungus
S. No.
Compounds
S. aureus
S. gordonii
E.coli
P. aeruginosa
C. albicans
A. niger
1
2
3
4
5
6
7
8
9
L
L
L
L
1
2
3
4
0.0343
0.0358
0.0253
0.0170
0.0217
0.0217
0.0215
0.0215
0.0111
0.0222
0.0110
0.0220
0.0272
0.0136
0.0269
0.0134
0.0108
0.0108
0.0107
0.0109
0.0047
‐
0.0343
0.0358
0.0506
0.0340
0.0217
0.0217
0.0215
0.0215
0.0222
0.0223
0.0110
0.0220
0.0271
0.0272
0.0269
0.0269
0.0215
0.0216
0.0107
0.0214
0.0047
‐
0.0343
0.0358
0.0506
0.0340
0.0108
0.0109
0.0108
0.0107
0.0222
0.0223
0.0221
0.0220
0.0272
0.0136
0.0135
0.0134
0.0108
0.0108
0.0107
0.0107
0.0047
‐
0.0343
0.0358
0.0506
0.0340
0.0217
0.0217
0.0215
0.0215
0.0222
0.0221
0.0221
0.0220
0.0272
0.0272
0.0269
0.0134
0.0215
0.0216
0.0107
0.0214
0.0047
‐
0.0343
0.0358
0.0253
0.0170
0.0217
0.0217
0.0108
0.0107
0.0111
0.0111
0.0110
0.0110
0.0136
0.0136
0.0135
0.0134
0.0108
0.0108
0.0107
0.0214
‐
0.0343
0.0358
0.0506
0.0340
0.0217
0.0217
0.0215
0.0215
0.0222
0.0223
0.0221
0.0220
0.0272
0.0272
0.0269
0.0134
0.0215
0.0216
0.0107
0.0107
‐
Co(L
1
).(CH
).(CH
).(CH
3
COO)
COO)
COO)
2
.2H
.2H
.2H
2
O
Ni(L
1
3
2
2
O
Cu(L
1
3
2
2
O
Zn(L
1
2
).(CH
3
3
COO)
2
2
.2H
2
O
O
Co(L
).(CH
COO)
.2H
2
10
11
12
13
14
15
16
17
18
19
20
21
22
Ni(L
2
).(CH
3
COO)
2
.2H
2
O
Cu(L
2
).(CH
3
COO)
2
.2H
2
O
Zn(L
2
).(CH
3
COO)
2
.2H
2
O
O
Co(L
3
).(CH
3
COO)
2
.2H
2
Ni(L
3
).(CH
3
COO)
2
.2H
2
O
Cu(L
3
).(CH
3
COO)
2
.2H
2
O
Zn(L
3
4
).(CH
3
3
COO)
2
2
.2H
2
O
O
Co(L
).(CH
COO)
.2H
2
Ni(L
4
).(CH
).(CH
).(CH
3
COO)
COO)
COO)
2
.2H
.2H
.2H
2
O
Cu(L
4
3
2
2
O
Zn(L
4
3
2
2
O
Ciprofloxacin
Fluconazole
0.0051
0.0102
metal complexes were more potent fungicides than the
respective Schiff bases and activity further got enhanced
at higher concentrations. DMSO control has shown a
negligible activity as compared to the metal complexes
and Schiff bases.
inhibition in the complexes was found to be in the order
Zn (II) > Cu (II) > Co (II) > Ni (II). The low activity of
some metal complexes may be due to their low lipophilic-
ity, 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
The trend of potency followed by Schiff base ligands
[
68]
(
L ‐L ) against fungal strains was also found to be
microorganism.
1
4
L > L > L > L as explained earlier for antibacterial
On conclusion, we can assert that copper complex 16
was the potent antimicrobial agent, while zinc complex
19 was the highest potent antimicrobial compound in
the series studied. While considering the overall order,
it was found that zinc complexes were the highest nox-
ious compounds among all the synthesized compounds
against all microbial strains.
The antimicrobial activity of synthesized Schiff bases
may be due to the existence of the (‐C=N‐) moiety which
have chelating properties. The mode of action of these
compounds may involve the construction of hydrogen
bond through azomethine/carbonyl group with the active
centers of the cell constituents, resulting in obstruction in
4
1
2
3
activity. All the metal complexes exhibit more potency
against C. albicans than A. niger. Against A. niger, com-
plexes 16, 19 and 20 were found to be excellent effective
with MIC values 0.0134 and 0.0107 μM/mL equivalent
with that of standard drug (MIC = 0.0102 μM/ml). Com-
pounds 5–15 and 18 were also found to be good antifun-
gal agent against A. niger with nearly half potency than
the standard.
Against C. albicans, the complexes 7–19 showed high
antifungal activity; almost half potency with MIC values
in the range 0.010 to 0.013 μM/ml than fluconazole
(MIC = 0.0051 μM/mL). The trend of fungal growth

DEVI ET AL.
19 of 23
FIGURE 7 Graphical representation of (a) Antibacterial activity (b) antifungal activity of Schiff base ligands and their complexes
normal life cell processes. The biological data divulges
that the coordination of Schiff bases to metal ions leads
to amplification in antimicrobial activity of complexes
than the free parent Schiff bases. The enhanced activity
of these metal complexes may be due to presence of an
additional factor of chelation through imine bond
3.11 | Anticancer activity
To evaluate the potential of the synthesized compounds
for growth inhibition of cancerous cells, the synthesized
compounds were screened in vitro against following
malignant tumor cell lines namely, human alveolar ade-
nocarcinoma epithelial cell line (A549), human breast
adenocarcinoma cell line (MCF7), human prostate cancer
cell line (DU145) and human normal lung cell line
(MRC5) using MTT assay and compared with the stan-
dard reference drug (doxorubicin). Accessed cytotoxicity
of all the test compounds was expressed as IC50 value
(i.e. the concentration which inhibits 50% growth)
obtained after exposure to 48 hours against four cell lines
and values summarized in Table 6 and Figure 8.
(
‐C=N‐) which certifies the increased lipophilic nature
[69]
of complexes.
On chelation, the polarity of the metal
ion will be reduced to a greater extent due to overlapping
of the ligand orbitals and partial sharing of the positive
charge of the metal ion with ligand donor groups. Fur-
ther, it increases the delocalization of p‐electrons over
the whole chelated ring and enhances the penetration of
the complexes into lipid membranes and blocking the
[
70]
metal binding sites in enzymes of microorganism.
These complexes also perturb the respiration process of
the cells and thus, blocks the synthesis of proteins, which
The synthesized Schiff base ligands and their com-
plexes having different substituents were tested for anti-
cancer activities and the calculated IC50 values
[71]
restricts further growth of microorganisms.
It was also
noted that the toxicity of the metal chelates increases on
increasing the concentration of metal ions, probably
owing to faster diffusion of these chelates as a whole via
cell membrane due to which further development of
organisms get caught up.
Apart from above considerations, the antimicrobial
activity of compounds also depends on the nature of the
ligands, their concentration, nature of metal ion, nature
of anions surrounding the metal ion, number and nature
of coordinating sites and geometry of complexes.
demonstrated that
(CH COO) .2H O] displayed highest activity among all
2
compound
(16)
[Zn(L3)
3
2
the synthesized compounds with an IC50 values of 10.6,
13.4 and 12.9 μM against A549, MCF7 and DU145 cancer
cell lines, respectively. Further, (8) and (12) zinc com-
plexes also showed very fine activity having IC50 value
<20 μM, while the compounds (1), (2), (3), (5), (6), (7),
(9), (10), (11), (13), (14) and (15) showed moderate anti-
cancer activity against A549, MCF7 and DU145 cell lines.
Moreover, the compounds (19) and (20) were found to be

20 of 23
DEVI ET AL.
TABLE 6 Cytotoxicity of Schiff bases and their respective complexes using three cancer cell lines (A549, MCF7, DU145) and one normal
cell line (MRC‐5) after revelation for 48 hrs
a
IC50 values (μM ± S.D.)
Sr. No.
Test compound
A549
MCF7
DU145
MRC5
1
2
3
4
5
6
7
8
9
L
L
L
L
1
2
3
4
20.5 ± 0.19
24.2 ± 0.25
20.3 ± 0.28
11.2 ± 0.44
27.7 ± 0.18
19.6 ± 0.22
21.4 ± 0.33
16.6 ± 0.22
26.1 ± 0.34
20.9 ± 0.22
21.0 ± 0.50
16.8 ± 0.21
25.1 ± 0.32
17.4 ± 0.12
18.8 ± 0.24
10.6 ± 0.14
‐
25.6 ± 0.50
27.1 ± 0.38
18.5 ± 0.43
14.7 ± 0.68
26.8 ± 0.20
22.1 ± 0.24
19.3 ± 0.25
17.8 ± 0.32
29.3 ± 0.54
23.7 ± 0.42
22.4 ± 0.37
20.0 ± 0.23
21.8 ± 0.41
16.5 ± 0.59
17.0 ± 0.45
13.4 ± 0.38
‐
30.4 ± 0.26
25.4 ± 0.61
21.9 ± 0.12
15.2 ± 0.21
25.2 ± 0.17
21.5 ± 0.63
23.2 ± 0.19
19.8 ± 0.35
25.9 ± 0.43
22.5 ± 0.64
26.3 ± 0.10
18.2 ± 0.24
24.1 ± 0.52
20.7 ± 0.44
20.8 ± 0.48
12.9 ± 0.53
57.4 ± 0.12
‐
96.9 ± 0.22
89.4 ± 0.25
94.2 ± 0.67
80.0 ± 0.37
97.1 ± 0.27
92.1 ± 0.71
84.1 ± 0.55
102.1 ± 0.43
95.3 ± 0.61
90.0 ± 0.51
80.2 ± 0.42
101.6 ± 0.52
90.2 ± 0.13
98.3 ± 0.67
109.2 ± 0.53
93.9 ± 0.56
‐
Co(L
1
).(CH
).(CH
).(CH
3
COO)
COO)
COO)
2
.2H
.2H
.2H
2
O
Ni(L
1
3
2
2
O
Cu(L
1
3
2
2
O
Zn(L
1
2
).(CH
3
3
COO)
2
2
.2H
2
O
O
Co(L
).(CH
COO)
.2H
2
10
11
12
13
14
15
16
17
18
19
20
Ni(L
2
).(CH
3
COO)
2
.2H
2
O
Cu(L
2
).(CH
3
COO)
2
.2H
2
O
Zn(L
2
).(CH
3
COO)
2
.2H
2
O
O
Co(L
3
).(CH
3
COO)
2
.2H
2
Ni(L
3
).(CH
3
COO)
2
.2H
2
O
Cu(L
3
).(CH
3
COO)
2
.2H
2
O
Zn(L
3
4
).(CH
3
3
COO)
2
2
.2H
2
O
O
Co(L
).(CH
COO)
.2H
2
Ni(L
4
).(CH
).(CH
).(CH
Doxorubicin
3
COO)
COO)
COO)
2
.2H
.2H
.2H
2
O
‐
‐
‐
Cu(L
4
3
2
2
O
43.2 ± 0.67
34.6 ± 0.19
0.7 ± 0.11
39.2 ± 0.86
45.4 ± 0.11
0.9 ± 0.08
48.3 ± 0.68
58.0 ± 0.23
0.8 ± 0.06
98.0 ± 0.27
87.2 ± 0.54
10.2 ± 0.18
Zn(L
4
3
2
2
O
Std
Not active
A549‐ Human lung carcinoma cell line
MCF7‐ Human breast carcinoma cell line
DU145‐ Human prostate carcinoma cell line
MRC5‐ Normal human lung cell line
a
(
IC50) = concentration of drug required to inhibit growth of 50% of tumor cells. The data are mean ± standard deviation and represents the average of three sets
of independent trials.
least potent with high IC50 values and compound (17)
was found inactive against all cancer cell lines except
DU145 with low potency. Further, the compound (18)
was found to be inactive against all the tested cell lines.
was found to be highly potent among its all the four com-
plexes followed by nickel and copper complexes. Simi-
larly, the zinc complex of ligand L was found to be
2
highest active against all tested strains followed by nickel,
copper and cobalt. These outcomes are expected as there
is difference of a single methylene group in the structures
of ligand L (1) and L (2). Further, zinc complex (16) of
It was found that the Schiff base ligand L (4) was
4
found to be highest active with IC50 values 11.2, 14.7
and 15.2 μM against A549, MCF7 and DU145 cancer cell
lines, respectively (owing to two chloro group present on
1
2
ligand L (3) was the highest active amongst the entire
3
benzene ring) and ligand L (2) is least active against
synthesized compounds against all the cancer cell lines
followed by the same pattern as discussed above which
may be attributed by the presence of the acetylenic group
in the structure. Further, the zinc and copper complexes
2
A549 and MCF7 while ligand L (1) is least active against
1
DU145 cell line. Further, the conclusions obtained from
the anticancer data revealed that complexes (5–8) of
ligand L (1) were found to be active against all the three
of ligand L (4) were somewhat active against all cell
1
4
cancer cell lines due to the presence of aromatic planar
ring system and hydrophobic nature but its zinc complex
lines, cobalt complex was active against only DU145 cell
line and nickel complex was found to be inactive against

DEVI ET AL.
21 of 23
FIGURE 8 Anticancer activities of Schiff bases and their transition metal complexes against (a) Human lung carcinoma cell line (A549), (b)
Human breast carcinoma cell line (MCF7), (c) Human prostate carcinoma cell line (DU145) and (d) Normal human lung cell line (MRC‐5)
all the cancer cell lines. The concluded trend of potency
followed by transition metal complexes (1–20) against
three cancer cell lines was found to be Zn > Ni >
Cu > Co.
Furthermore, the evaluation against human normal
cell line (MRC5), demonstrated that the compounds were
replication and transcription process ultimately leading
[
73,74]
to cell death.
Apart from this, the positive charge
of the metal increases the acidity of coordinated ligands
causing stronger hydrogen bonding resulting in enhanced
cytotoxic activity. The variation in substituents and the
metal ions clearly affects the binding ability to DNA
and corresponding alteration in biological activity is
observed in the present case also. Further, it was con-
cluded that electron‐withdrawing chloro groups on aryl
ring contributed significantly towards cytotoxic potential
8
–11 times less toxic as compared with the standard drug
[72]
doxorubicin,
except complexes (17) and (18) which
did not induce any toxicity against the normal cell line
which may be a buoyant and optimistic dot for the pres-
ent research work. But on the other hand they were also
found to be inactive against cancer cell lines. The other
important aspect for toxicity was that the compound
of ligand L against all the three cancer cell lines, but
4
the effect of the acetylinic group is even more pro-
nounced as is evident from the activity of compound
(16) zinc complex of ligand L3.
(
15) (IC50 value 109.2) was found to be almost 11 folds
less toxic than the standard drug doxorubicin (IC50 value
0.2) which along with its moderate activity, makes this
1
compound most appealing candidate among the entire
synthesized compounds for the curative purpose of can-
cer. Similarly, the complex (16) along with its uppermost
cytotoxicity in opposition to malignant cell lines was
found as 9 times least toxic than the standard drug for
normal human cell line and might be measured as the
compound of paramount importance amongst the present
tested compounds.
4 | CONCLUSIONS
In the current study of research, our booming efforts are
the synthesis of some novel mononuclear Schiff base com-
plexes of Co (II), Ni (II), Cu (II) and Zn (II). The Schiff
bases were obtained from condensation of substituted
napthaldehyde/benzaldehyde/salicylaldehyde derivatives
with 4‐methyl‐3‐thiosemicarbazide and were further
reacted by corresponding metal (II) acetates to form com-
plexes in 1:1 molar ratio. A comparative physicochemical
and spectral study of synthesized compounds has been
The cytotoxicity of compounds is dependent on their
ability to bind with DNA and subsequent impairment of
its structure and functions followed by interference in

22 of 23
DEVI ET AL.
done which provides excellent data and is in good agree-
ment with the proposed octahedral structure. The spectral
data studies revealed that Schiff bases coordinates in a
bidentate manner via nitrogen atom of azomethine group
and sulfur atom of thione group and does not exists in
thio‐enol tautomerism during complexation. The XRD
patterns designate the crystalline nature of complexes. In
vitro antimicrobial studies demonstrate enhancement in
metal complexes potency on complexation than parent
Schiff bases and zinc complexes were found as the most
potent. In addition to this, compounds were also evalu-
ated for cytotoxicity against three cancer cell lines and
one normal human cell line which displayed moderate
to good inhibitory activities and revealed that complex
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The author Ms. Manju Yadav (SRF) thanks to University
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instrumentation laboratory and Department of Chemistry
of Guru Rameshwar University of Science & Technology,
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