Synthesis, characterization and pioactivity study of bidentate NS schiff base of S-Benzyl dithiocarbazate and its Zn(II) and Pd(II) complexes

Article abstract of DOI:10.14233/ajchem.2020.21870

The bis-chelated four coordinate complexes (ML2, L = deprotonated ligand) of Zn(II) and Pd(II) ions were synthesized, derived from a new bidentate NS Schiff base called S-benzyl-β-N-(4-hydroxy-3-nitrophenyl)methylene dithiocarbazate (HL) which is the condensation product of S-benzyl dithiocarbazate (SBDTC) with 4-hydroxy-3-nitrobenzaldehyde. The synthesized ligand and complexes were characterized using conventional techniques like NMR, UV-visible, IR, mass spectroscopic techniques, magnetic susceptibility measurement and molar conductance. A single crystal X-ray crystallography data approved the proposed crystal structure of the ligand. Both in solid and solution phase, the ligand continues to exist in its thione tautomeric form. The chelates were formed by the reaction of ligand with the metal ions through the ligand azomethine nitrogen atom and the deprotonated thiolate sulfur anion. Magnetic susceptibility and electronic spectroscopic data suggested to have a tetrahedral geometry for ZnL2 complex whereas a square planar structure for PdL2 complex. The analgesic and anti-inflammatory bioactivity were assayed on both the ligand and its complexes by tail flick and carrageenan induced paw edema test. The ligand at the dose of 10 mg/kg, produced a significant (p < 0.001) increase in pain threshold in tail flick methods when compared to control but in case of complexes, it showed moderate activity. At the same dose, the ligand and complexes significantly (p < 0.001) reduced paw edema when compared to the control. Altogether, these results suggest that ligand and its complexes could be used as a potent anti-inflammatory agent.

Full text of DOI:10.14233/ajchem.2020.21870

Asian Journal of Chemistry; Vol. 32, No. 8 (2020), 2091-2098
A
SIAN
J
OURNAL OF HEMISTRY
C
https://doi.org/10.14233/ajchem.2020.21870
Synthesis, Characterization and Bioactivity Study of Bidentate NS Schiff
Base of S-Benzyl Dithiocarbazate and its Zn(II) and Pd(II) Complexes
1,*
2
3
4
1,
MD. HASIBUL ISLAM , MD. CHANMIYA SHEIKH , RYUTA MIYATAKE , RONOK ZAHAN and MD. AL-AMIN-AL-AZADUL ISLAM
1Department of Chemistry, Rajshahi University of Engineering & Technology, Rajshahi-6204, Bangladesh
2Department of Environmental Applied Chemistry, Faculty of Engineering, University of Toyama, 3190 Gofuku, Toyama 930-8555, Japan
3Water Quality Management Center, University of Toyama, 3190 Gofuku, Toyama 930-8555, Japan
4Department of Pharmacy, University of Rajshahi, Rajshahi-6205, Bangladesh
*Corresponding author: E-mail: mhislamchem.bsfic@gmail.com
Received: 27 January 2019;
Accepted: 30 June 2020;
Published online: 27 July 2020;
AJC-19996
The bis-chelated four coordinate complexes (ML2, L = deprotonated ligand) of Zn(II) and Pd(II) ions were synthesized, derived from a
new bidentate NS Schiff base called S-benzyl-β-N-(4-hydroxy-3-nitrophenyl)methylene dithiocarbazate (HL) which is the condensation
product of S-benzyl dithiocarbazate (SBDTC) with 4-hydroxy-3-nitrobenzaldehyde. The synthesized ligand and complexes were
characterized using conventional techniques like NMR, UV-visible, IR, mass spectroscopic techniques, magnetic susceptibility measurement
and molar conductance. A single crystal X-ray crystallography data approved the proposed crystal structure of the ligand. Both in solid
and solution phase, the ligand continues to exist in its thione tautomeric form. The chelates were formed by the reaction of ligand with the
metal ions through the ligand azomethine nitrogen atom and the deprotonated thiolate sulfur anion. Magnetic susceptibility and electronic
spectroscopic data suggested to have a tetrahedral geometry for ZnL2 complex whereas a square planar structure for PdL2 complex. The
analgesic and anti-inflammatory bioactivity were assayed on both the ligand and its complexes by tail flick and carrageenan induced paw
edema test. The ligand at the dose of 10 mg/kg, produced a significant (***p < 0.001) increase in pain threshold in tail flick methods when
compared to control but in case of complexes, it showed moderate activity.At the same dose, the ligand and complexes significantly (***p
< 0.001) reduced paw edema when compared to the control. Altogether, these results suggest that ligand and its complexes could be used
as a potent anti-inflammatory agent.
Keywords: Schiff base, S-Benzyl Dithiocarbazate, Metal(II) complexes, Analgesic activity, Anti-inflammatory activity.
chelate rings, molecular packing, π-electron delocalization and
lipophilicity [9,10].
INTRODUCTION
S-Benzyl dithiocarbazate (SBDTC) Schiff bases comprise
an essential part of nitrogen-sulfur donor ligands [1,2] occupied
four potential donor atoms which coordinated with metal ions
to create the chelate form approved by their structural formula.
Exactly, transition reactions were completed through the main
group of the metal with hard nitrogen and soft sulfur atoms
facilitated of these ligands [3,4]. Principlally, both NS and SS
complexes remain practicable [5].After all, dithiocarbazic acid
and its esters usually forming of five-membered chelate rings
[3-6]. Typically, the bioactivity nature of Schiff bases depend
on their stereochemistry, hydrogen bonding, substituents present
on either side of the N2S2 chromophore [7,8]while for complexes,
the bioactivity depends largely on its geometry, number of
Metal complexes of SBDTC Schiff bases have been reported
to exhibit significant antibacterial [11-18], antifungal [17] and
cytotoxic activities [17,18].The mechanism of anticancer activity
of SBDTC Schiff base and its metal complex has also been
reported [19]. Natural plants have been investigated as potential
source of anti-inflammatory and analgesic drugs [20]. Organo-
metalic compounds sometimes behave as anti-inflammatory
agents. Wide-ranging research supported that Au, Cu and Zn
metal complexes used as anti-inflammatory drugs which have
similar or higher efficacy with smaller side effects than the root
organic drugs commonly in use. A recent study reported that
bidentate NS Schiff base of SBDTC with 3-hydroxyacetophe-
none and its copper(II) and nickel(II) complexes showed signi-
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2092 Islam et al.
Asian J. Chem.
ficant analgesic and anti-inflammatory activities [21]. In conti-
nuation of our work, the coordination chemistry of a Schiff base
synthesized from S-benzyl dithiocarbazate (SBDTC) and 4-
hydroxy-3-nitro benzaldehyde with Zn(II) and Pd(II) ions is
discussed and tested of their anti-inflammatory and analgesic
activities.
Bangladesh (ICDDRB). Experimental mice were accomm-
odated in polypropylene cages containing clean wood chips
as bedding materials. Maximum six mice/cage were maintained
with controlled conditions (12:12 h light-dark with temperature
25 2 ºC) along with utmost hygiene. The animal ethics were
maintained under the conditions of Institute of Biological
Sciences (IBSc), University of Rajshahi, Bangladesh, approved
ethical clearance (license no: 225/320-IAMEBBC/IBSc).
Analgesic activity: Tail-flick method completed the anal-
gesic activity using by Swiss albino mice (25-35g). Random
sampling method was implemented to collect their sex [25,26].
When it was the comparison diclofenac sodium at a dose level
of 10 mg/kg was applied orally as indicator. The test samples
were applied orally at a dose level of 10 mg/kg body wt. It was
recorded at 0, 30, 60 and 90 min after the implement and cut
off time was 10 s.
Anti-inflammatory activity: The carrageenan induced
paw edema test facilitated to measure the anti-inflammatory
activity [27]. Only Group II received indomethacin (10 mg/kg,
p.o.).After 1 h, 0.1 mL, 1% w/v carrageenan suspension in normal
saline was injected into the subplantar tissue of the right hind
paw. The paw volume was measured at 1, 2 and 3 h after carrag-
eenan injection using the plethysmograph (Model: PLYAN;
Buxco Electronics, Inc., USA).
Synthesis of S-benzyl-β-N-(4-hydroxy-3-nitrophenyl)-
methylenedithiocarbazate (HL) (1): Schiff base was synthe-
sized according to literature method [28].Briefly, 4-hydroxy-
3-nitrobenzaldehyde (1.67 g, 10 mmol) in acetonitrile (20 mL)
was added in hot SBDTC (1.98 g, 10 mmol) in acetonitrile
(40 mL) and refluxed for about 0.5 h. The resulting solution
was cooled to room temperature (20-25 ºC). The orange-yellow
solid which formed was separated, washed with ethanol and
dried in vacuum over anhydrous CaCl2. Yield: 2.96g (81%),
m.p. 171-172 ºC. The synthesized compound was recrystal-
lized from a mixture of chloroform and petroleum ether (2:1;
v/v) as large orange pyramid shaped single crystals after 4 days
of dissolution and slow evaporation at room temperature. IR
(KBr, νmax, cm-1): 3273 (O-H), 3124 (N-H), 3082 (C-H, ring),
2985 (C-H, CH2), 1622 (C=N), 1518 (C=C, ring), 1419 (C-H,
CH2, bend), 1485, 1305 (NO2), 1236 (O-H, phenol), 1357 (O-H,
in plane bending), 1035 (C=S), 972 (N-N), 943 (CSS). 1H NMR
(500 MHz, CDCl3) δ ppm: 2.17 (s, 2H, H2O), 4.56 (s, 2H,
SCH2), 7.19-7.44 (m, 5H, SCH2Ph), 7.80 (s, 1H, H14), 8.07 (dd,
1H, J1 = 2.5 Hz, J2 = 2.0 Hz, H(15), 8.29 (d, 1H, J = 2.0 Hz,
H(11), 10.20 (s, 1H, OH), 10.80 (bs, 1H, NH), 7.42 (s, 1H, CH=N).
UV-vis [DMSO, 10-5 M, nm (log ε)] λmax: 248 (4.39), 282 (3.89),
348 (4.89). LRMS for C15H13N3O3S2 (EI+, 70 eV, %) m/z: 349
([M+2]+, 6.09), 247 (M-C3H2NO3, 13.90), 231 (M-C4H7NO3,
36.32), 215 (M-C4H9N2O3, 10.31), 132 (M-C4H13N3S2, 10.76);
HRMS (EI+) for C15H13N3O3S2 calcd.: (M+): 347.0398, found
(M+): 347.0395.
EXPERIMENTAL
The solvents and chemicals used for the condensation
reaction to form the Schiff base and metal complexes were of
reagent grade. All of these solvent and chemicals were used
without any further purification.Among these chemicals, metal
salts and standard drugs viz. 4-hydroxy-3-nitrobenzaldehyde,
palladium(II) nitrate hydrate, indomethacin were procured from
Sigma-Aldrich (USA) and benzyl chloride was purchased from
Sisco Research Laboratories (SRL) Pvt. Ltd, India.
Characterizations: IR spectra (4000-400 cm-1) and UV-
visible absorptions were scanned from Department of Chemistry,
Rajshahi University of Engineering & Technology, Rajshahi,
Bangladesh using IRAffinity 1S spectrometer, (Shimadzu, Japan)
as KBr pellet and on a T60 UV-visible spectrophotometer (PG
Instruments, UK) between 200-1100 nm in 10-5 M solution of
DMSO using Win5 software. 1H NMR (0-14 ppm, 500 MHz)
and mass spectra were obtained from Venture Business Labor-
atory, Department of EnvironmentalApplied Chemistry, University
of Toyama, Japan on a JNM-A500 spectrometer in CDCl3 and
DMSO-d6 (for complexes) using TMS as internal standard (for
1H NMR spectra) and on a JEOL-JMS-700V mass spectrometer
(scan range, mass-to-charge (m/z) ratio 0-850) (for mass spectra),
respectively. Molar conductance and magnetic susceptibility
measure-ments were also conducted at Department of Chemistry,
Rajshahi University of Engineering & Technology (RUET)
using molar conductance measurements with a heavy-duty
conductivity/temperature meter (Extech Instruments, USA,
model No. 407303) and on a magnetic susceptibility balance
(Sherwood Scientific, UK).
X-ray crystal structure: Molecular structure of Schiff
base (HL) was determined by single crystal X-ray crystallogra-
phy on a Rigaku R-AXIS RAPID diffractometer from Water
Quality Management Center, University of Toyama, Japan by
using filtered Cu-Kα radiation (λ = 1.54187 Å). X-ray quality
single crystals were grown at room temperature in to a mixture
of chloroform and petroleum ether (2:1; v/v). Preliminary exami-
nation and intensity analysis for the proposed structure reported
was taken at 173(1) K. The structure analysis was performed by
direct process [22] and progressive Fourier techniques by the
full-matrix least-squares techniques based onF2 with all approved
mirrors [23]. Hydrogen atoms were geometrically situated and
refined using the riding model. The calculations were completed
using the Crystal Structure package [24] without refinement
for which SHELXL-97 was implemented [23].
Synthesis of ML2 (M = Zn(II)andPd(II))complexes: A
mixture of Schiff base (0.174 g, 0.5 mmol) in ethanol (30 mL)
and appropriate amount of corresponding metal salt (0.25 mmol)
in ethanol (15 mL) was refluxed for 0.25 h.The precipitate formed
was collected by filtration and washed with hot ethanol (10 mL)
and chloroform (10 mL) and dried in vacuum (Scheme-I).
Animal ethics: In this research, synthesized compounds
were applied to the test adult Swiss albino mice in moral accep-
tation theory and justified under animal rights and utilitar-
ianism. The mice were collected from the animal resource branch
of the International Centre for Diarrhea Disease Research,

Vol. 32, No. 8 (2020)
Study of Bidentate NS Schiff Base of S-Benzyl Dithiocarbazate and its Zn(II) and Pd(II) Complexes 2093
CS2
+
H2N NH
Stirring at 0-5 oC
ETOH, 0.5 h
Stirring at 0-5 oC
ETOH, 0.5 h
S
NH2-NH2.H2O
NH2NHC(=S)-S-K+
+
S
KDTCA
KOH
SBDTC
CH3CN
4-Hydroxy-3-nitrobenzaldehyde
O2N
HO
NO2
HO
N
NH
S
S
N
N
S
S
HL
M
N
N
S
S
M(II), hot stirring 10-15 min
ETOH/H2O
ML2
OH
M(II) = Zn and Pd
NO2
Scheme-I: Synthesis of Schiff base (1) and its metal complexes (2-3)
bis[Benzyl-N′-(4-hydroxy-3-nitrophenyl)methylene
hydrazine carbodithioato-κ2-N′,S]zinc(II) (ZnL2) (2):Yield:
0.257 g (56 %), yellow powder, m.p. 143-146 ºC. IR (KBr,
RESULTS AND DISCUSSION
Schiff base ligand HL was synthesized by condensation
reaction of S-benzyl dithiocarbazate with 4-hydroxy-3-nitro
benzaldehyde in acetonitrile under reflux, which on further
reaction with respective divalent metal salts in 2:1 molar ratio,
yielded their consisted metal chelates (ML2).All spectroscopic
analysis data support their proposed structures. The ligand was
more or less soluble in most common organic solvents, whereas
its complexes were only fairly soluble in DMSO. The result
of molar conductivity of the complexes in solution referred
their non-electrolytic nature.
Characterization: The IR spectrum of free ligand as KBr
pellet exhibited a weak and broad absorption at 3273 cm-1 for
the phenolic ν(O-H) band as described by Joseph et al. [29].
This band was observed in significantly lower wave number
that exhibited no significant change in the corresponding comp-
lexes [21], suggesting its non-involvement during complexation.
The ligand exhibited another weak and sharp band at 3124
cm-1 and a medium to strong absorption at 1035 cm-1 assigned
to the N-H and C=S stretching, respectively, which were not
present in the complexes [21]. These indicated the coordination
of ligand through the deprotonated thiolate sulfur anion [21].
The shifting of C=N stretching in the free ligand from 1620
cm-1 to lower frequency (1595-1583 cm-1) in the complexes also
indicated its coordination through azomethine nitrogen atom
[21]. In addition, the ligand and its Zn(II) & Pd(II) complexes
contained a strong band at 1323-1305 cm-1, tentatively assigned
to the symmetric stretching of the NO2 group vibration [30].
In contrast, the asymmetric NO2 group stretching mode might
ν
max, cm-1): 3257 (O-H), 3063, 3030 (C-H, ring), 2979, 2837
(C-H, CH2), 1622 (C=C, ring), 1595 (C=N), 1436 (C-H, CH2,
bend), 1323 (NO2), 1171 (O-H, phenol), 1045 (N-N), 966 (CSS),
546, 494 (M-N), 420 (M-S). 1H NMR (500 MHz, CDCl3), δ
ppm: 4.47 (s, 4H, SCH2), 6.98-7.41 (m, 10H, SCH2Ph), 7.92-
7.99 (m, 6H, phenyl), 9.22 (s, 2H, OH), 8.20 (s, 2H, CH=N).
UV-vis [DMSO, 10-5 M, nm (log ε)] λmax: 259 (4.02), 358
(4.38), 455 (3.80). LRMS for C30H24N6O6S4Zn (FAB+, 70 eV,
%) m/z: 756 ([M+2]+, 0.21), 540 (M-C8N3O3S, 2.33), 307 (M-
C18H15N3O3S2Zn, 24.22), 289 (M-C18H17N3O4S2Zn, 13.45), 154
(M-C24H20N5O6S2Zn, 100). Λ (DMSO, 10-5 M, ohm-1 cm2 mol-1):
11.3 ; µeff = diamagnetic.
bis[Benzyl-N′-(4-hydroxy-3-nitrophenyl)methylene
hydrazine carbodithioato-κ2-N′,S]palladium(II) (PdL2) (3):
Yield: 0.353 g (75%), brown powder, m.p. 256-257 ºC. IR
(KBr, νmax, cm-1): 3302 (O-H), 1622 (C=C, ring), 1583 (C=N),
1419 (C-H, CH2, bend), 1321 (NO2), 1263 (O-H, phenol), 1001
(N-N), 964 (C=S), 509 (M-N), 418 (M-S). 1H NMR (500 MHz,
DMSO-d6), δ ppm: 4.50 (s, 4H, SCH2), 7.17-7.42 (m, 10H,
SCH2Ph), 8.11, 8.18 (s, 2H, H14), 7.81, 7.79 (dd, 2H, J1 = 2.0
Hz, H15), 8.11 (d, 1H, J = 2.0 Hz, H11), 9.22 (s, 2H, OH), 8.20
(s, 2H, CH=N). UV-vis [DMSO, 10-5 M, nm (log ε)] λmax: 261
(4.23), 341 (4.27), 452 (3.51). LRMS for C30H24N6O6S4Pd
(FAB+, 70 eV, %) m/z: 799 (M+, 0.12), 612 (M-C12H12S, 0.48),
460 (M-C12H12N2OSPd, 2.26), 307 (M-C15H17N2O2S2Pd, 25.56),
289 (M-C15H19N2O3S4Pd, 13.90), 154 (M-C22H24N3O5S4Pd, 100).
Λ (DMSO, 10-5 M, ohm-1 cm2 mol-1): 12.7; µeff = diamagnetic.

2094 Islam et al.
Asian J. Chem.
have overlapped with the azomethine C=N vibration [30]. The
1H NMR spectrum, of HL in CDCl3 contained a broad singlet
at 10.80 ppm for the imide (NH) proton that disappeared in its
complexes, suggesting its thione tautomeric form in solution
and coordinated with the metal ions via the deprotonation of
the thiol form [31-34]. Additionally, a singlet at δ 7.42 ppm
observed in the free ligand tentatively assigned to the azomethine
(CH=N) proton, deshielded (ca. 0.6 ppm) in its respective
complexes, also suggested its coordination through the β-
nitrogen atom [31-34]. In contrast, a singlet at δ 4.56 ppm for
SCH2 protons of S-benzyl moiety of HL showed no significant
change in its complexes [21]. The electronic spectrum of Schiff
base showed a medium band at 248 nm as well as an intense
broad band at 348 nm corresponding to the π→π* and n→π*
transitions of phenyl ring and dithiocarbazate moiety, respec-
tively that resulted in red shift in the complexes [21,31,32,34].
However, the ligand contained a shoulder band at 282 nm, assig-
nable to the π→π* (azomethine) transition [35]. Additionally,
the complexes showed a medium intensity absorption band in
the visible region between 445-455 nm, attributable tothe S→M
charge transfer transition [35]. Generally, the square planar
Pd(II) complexes are hoped to show three bands consisting to
observed thus generally this bis-chelated complex is tetrahedral.
The low resolution mass spectrum of HL was scanned by EI+
method, which showed the molecular ion peak at m/z of 347
followed by the formation of fragment ions at m/z of 247,
231, 215, 205, 133, 117, 105 and 91. However, its ML2 comp-
lexes were scanned for their low resolution mass spectrum by
using FAB+ method. The ZnL2 and PdL2 complexes exhibited
molecular ion peak at m/z of 761 and 799 for [M+2] and [M+]
ions respectively, suggesting the formation of bis-chelated four
coordinate complexes (Schemes II-IV).
Crystal structure: The Schiff base crystal and molecular
structure was determined by single crystal X-ray diffraction
analysis. The data collection of the ligand is shown in Table-1.
Moreover, selected bond distance and bond angles are shown
in Table-2. Fig. 1 represents ORTEP drawing of Schiff base
with atom numbering scheme. The single crystal X-ray diffra-
ction study indicated that the ligand crystallizes in monoclinic
system with space group P21/c. In ligand, dithiocarbazate group
adopts an E-configuration with respect to the C=N bond of
phenyl group. The β-nitrogen and the thioketo sulphur are trans-
located with respect to the C(8)-N(2) bond. The molecule is in
its thione tautomeric form with C(8)=S(1) bond length of 1.656(8)
Å and the entire species has coplanar atoms with the exception
of S-benzyl phenyl ring indicating an electron delocalization
within it.An angle between the dithiocarbazate moiety and the
S-benzyl phenyl ring is 0.56º. The bond lengths involving the
dithiocarbazate moiety namely C(8)–S(1), C(8)–S(2), C(9)–
the 1A1g→ A2g, 1A1g→ B1g and 1A1g→ Eg transitions, respecti-
vely, however with dithiocarbazate ligands, a long tail of strong
charge transfer transitions invariably interfere with the obser-
vation of these bands was also observed [36]. The d-d transitions
for zinc(II) complex with d10 configuration are normally not
1
1
1
+.
NO2
S
HO
N
S
N
S
-[C3H2NO3]
-100
H
N
N
S
H
C12H11N2S2; m/z: 247
C15H13N3O3S2; m/z: 347
[M+2]: m/z: 349
-[CH4 + H]
-17
+.
S
N
N
H
S
C11H7N2S2; m/z: 231
-16
-[NH2]
S
-[NH2 +H2S + S]
-82
N
S
[C11]; m/z: 132
C11H5NS2; m/z: 215
Scheme-II: Mechanism of fragmentation of Schiff base (1) by mass spectroscopy

Vol. 32, No. 8 (2020)
HO
Study of Bidentate NS Schiff Base of S-Benzyl Dithiocarbazate and its Zn(II) and Pd(II) Complexes 2095
NO2
H
S
S
N
S
S
S
N
S
Zn
-[C8O3N3S]
-218
Zn
N
.+S
N
N
N
H
H
OH
OH
[C30H25N6O6S4Zn]; m/z: 759
NO2
NO2
[M+2] = 761
[C22H24N3O3S3Zn]; m/z: 540
-[C10H15SZn]
-233
O2N
O2N
HO
N
N
S
S
S
-[H2O]
-18
-[C6H3N2O2]
-135
N
N
S
S
H2N
S
[C12H7N3O2S2]+.; m/z: 289
[C6H4NS2]+.
Scheme-III: Mechanism of fragmentation of Zn(II) complex (2) by low resolution mass spectroscopy
; m/z: 154
[C12H9N3O3S2]+.; m/z : 307
TABLE-1
TABLE-2
CRYSTALLOGRAPHIC DATA AND
DETAILS OF REFINEMENT FOR (HL)
SELECTED BOND LENGTHS (Å) AND ANGLES (°) FOR (HL)
Bond lengths
C(8)–S(1)
C(8)–S(2)
C(9)–S(2)
C(8)–N(2)
N(1)–N(2)
C(7)–N(1)
C(1)–C(7)
Bond angles
C(8)-S(2)-C(9)
S(1)–C(8)–S(2)
S(1)–C(8)–N(2)
S(2)–C(8)–N(2)
C(8)–N(2)–N(2)
N(2)–N(1)–C(7)
N(1)–C(7)–C(1)
Empirical formula
C15H15N3O4S2
365.42
173
1.656(8)
1.755(7)
1.820(8)
1.337(10)
1.377(9)
1.292(10)
1.454(10)
100.7(4)
126.0(5)
120.2(6)
113.8(6)
122.7(7)
114.3(6)
121.1(7)
Formula weight
Temperature (K)
Wavelength (Å)
Crystal colour, habit
Crystal system
Space group
1.54187
Orange, prism
Monoclinic
P21/c
Unit cell dimensions
a (Å)
4.63369(9)
9.6529(2)
36.1123(8)
90.0000
b (Å)
c(Å)
α (°)
90.1162(13)
90.0000
1615.24(6)
4, 1.503
3.228
760.00
β (°)
γ (°)
V (Å3)
Z, calculated density (g cm–3)
Absorption coefficient (mm-1)
F(000)
Crystal size (mm)
θ range for data collection (°)
Limiting indices
0.85 × 0.18 × 0.03
4.58-68.21
-5 ≤ h ≤ 5; -11 ≤ k ≤ 11;
-43 ≤ l ≤ 43
17828/2965
0.0803
Reflections collected/unique
Rint
68.21
17828
0.908 and 0.726
2198/0/225
1.240
0.0908
0.2546
0.490, –0.460
θ max (°)
Fig. 1. ORTEP diagram (thermal ellipsoids at 40% probability level) of
HL with atom numbering scheme
No. of reflections collected
Maximum and minimum transmission
Data/restrains/parameters
Goodness-of-fit on F2
R1 indices [I > 2σ(I)]a
wR2
S(2), C(8)–N(2) and N(1)–N(2) were all in normal ranges of
typical dithiocarbazate compounds [11,21,31-33,37]. Similarly,
the bond angles in dithiocarbazate moiety like C(8)–S(2)–C(9),
S(1)–C(8)–S(2) and C(8)–N(2)–N(1) were found at 100.7(4),
126.0(5) and 122.7(7)º, respectively and are comparable to the
Largest difference peak and hole (e/Å3)
aR1 = S||Fo| – |Fc|| / S |Fo| , wR2 = [S(w(Fo2 – Fc2)2)/Sw(Fo2)2]1/2

2096 Islam et al.
NO2
Asian J. Chem.
NO2
HO
HO
H
H
S
N
S
S
S
N
N
S
S
S
Pd
N
N
Pd
S
N
N
N
-[C12H12S]; m/z: 188
H
H
OH
OH
NO2
[C30H24N6O6S4Pd]; m/z: 799
NO2
[C18H12N6O6S3Pd]+.; m/z: 611
NO2
[N2+ PdO ]
-152
HO
A
B
H
+.
NO2
H
-[C7H6NO3]; m/z: 152
HS
S
S
N
+.
H
N
N
S
S
N
Pd
N
S
N
OH
H
NO2
[C18H12N4O5S3]+.; m/z: 460
OH
NO2
-[C3H5OS3]
-153
[C11H7N5O3S3Pd]; m/z: 460
NO2
HO
N
N
-[C7H7NO3]; m/z: 153
O2N
+.
+.
NO2
N
S
S
S
N
Pd
N
[C15H7N4O4]+.;m/z: 307
N
[C4N4S3Pd]; m/z: 307
-18
-[H2O]
N
N
N
N
-[C7H5NO2]
-135
O2N
+.
N
O
+.
[C8N3O]+.; m/z: 154
N
[C15H5N4O3]+.;m/z: 289
O
Scheme-IV: Mechanism of fragmentation of Pd(II) complex (3) by low resolution mass spectroscopy

Vol. 32, No. 8 (2020)
Study of Bidentate NS Schiff Base of S-Benzyl Dithiocarbazate and its Zn(II) and Pd(II) Complexes 2097
TABLE-3
ANALGESIC ACTIVITY OF HL AND ITS ZnL2 AND PdL2 COMPLEXES WITH A DOSE OF 10 mg/Kg BODY wt.
Tail flick time (s)
Compound
0 min
30 min
60 min
90 min
Control (vehicle)
HL
ZnL2
PdL2
2.60 0.008
3.16 0.008
2.77 0.317
2.80 0.237
2.81 0.005
2.64 0.005
3.47 0.088
3.12 0.305
3.10 0.305
3.31 0.005
2.67 0.005
4.33 0.300**
3.24 0.363
3.57 0.146
5.85 0.020***
2.73 0.018
5.33 0.369***
3.75 0.456
3.67 0.142
12.37 0.035***
Positive control (diclofenac-Na)
All values expressed as mean SEM (n = 6) one way analysis of variance (ANOVA) followed by Tucky test, *p < 0.05, **p < 0.01, ***p < 0.001
significant compared to control.
TABLE-4
ANTI-INFLAMMATORY ACTIVITY OF THE TEST COMPOUNDS WITH A DOSE OF 10 mg/Kg BODY wt.
Paw edema volume (mm)
Compound
0 h
1 h
2 h
3 h
4 h
Control (vehicle)
HL
ZnL2
PdL2
1.92 0.012
0.42 0.008
0.42 0.034
0.44 0.020
1.54 0.008
1.96 0.008
2.07 0.035
2.22 0.014
2.22 0.014
0.37 0.031***
0.40 0.023***
0.40 0.003***
1.44 0.008***
0.37 0.029***
0.39 0.026***
0.38 0.013***
1.35 0.014***
0.36 0.030***
0.36 0.014***
0.36 0.018***
0.81 0.005***
0.32 0.014***
0.36 0.011***
0.33 0.027***
0.49 0.039***
Positive control (indomethacin)
All the values indicated as mean SEM (n = 6) by one-way analysis of variance (ANOVA) followed by Tukey test. *p < 0.05, **p < 0.01, ***p <
0.001 significant compared to control.
literature values [11,21,38,39]. In contrast, S(2)–C(8)–N(2) bond
angle is 7 to 14º smaller than values measured in other reported
ligands [11,21,40].A lattice water molecule was also detected
in the crystal as shown in the ORTEP drawing (Fig. 1), thereby
showing a variation in the molecular weight between mass and
X-ray data (Table-1).
Conclusion
The results of the present study, indicate that the ligand HL
afforded four coordinate bis-chelated neutral ML2 complexes
with zinc(II) and Pd(II) ions, respectively, binding through
azomethine nitrogen atom and deprotonated thiolate sulfur
anion. The Schiff base and its complexes showed significant
analgesic and anti-inflammatory activities. As the OH group
remains uncoordinated, it may play a vital role in biological
activity of the test compounds.
Supplementary data: The supplementary crystallographic
data for this article vide No. CCDC 972875 can be obtained
free of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.
html or from the Cambridge Crystallographic Data Centre.
Analgesic activity: Table-3 depicted the analgesic activity
and the test samples showed analgesic activity against radiant
heat induced algesia. The brain and spinal cord play a major
role in central pain mechanisms. The dorsal horn of the spinal
cord is endowed with several neurotransmitters and receptors
including: substance P, somatostatin, neuropeptideY, inhibitory
amino acid, nitric oxide, endogenous opioids and the mono-
amines, which are the major targets for pain and inflammation
[41]. The tail immersion test was considered to be selective to
examine compounds acting through opoid receptor; the ligand
increased pain threshold, which mean basal latency which indi-
cates that it may act via centrally mediated analgesic mechanism.
Anti-inflammatory activity: Table-4 indicated that the
compounds significantly inhibited anti-inflammatory activity
in second phase. Carrageenan induced oedema has been com-
monly used as an experimental animal model for acute inflam-
mation and is believed to be biphasic. The early phase (1-2 h)
of the carrageenan model is mainly mediated by histamine,
serotonin and increased the synthesis of prostaglandins in the
damaged tissue surroundings. The late phase is sustained by
prostaglandin release and mediated by bradykinin, leukotri-
enes, polymorphonuclear cells and prostaglandins produced
by tissue macrophages [42,43]. Since the ligand and complexes
significantly inhibited paw edema induced by carrageenan in
the second phase and this finding suggests a possible inhibition
of cyclooxygenase synthesis by the test samples and this effect
is similar to that produced by non-steroidal anti-inflammatory
drugs such as indomethacin, whose mechanism of action is
inhibition of the cyclooxygenase enzyme.
ACKNOWLEDGEMENTS
The authors are grateful to the authorities of Institute of
Biological Sciences (IBSc), University of Rajshahi, Rajshahi,
Bangladesh for their kind research support for this research
work. Thanks are also due to Mr. Atish Dipankar, University
of Science & Technology, Dhaka, Bangladesh for conducting
the biological activities.
CONFLICT OF INTEREST
The authors declare that there is no conflict of interests
regarding the publication of this article.
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