Synthesis, characterization and biological activities of mercury(II) ternary complexes of 2-substituted benzothiazoles derivatives

Article abstract of DOI:10.14233/ajchem.2018.21301

Biological important ternary complexes of type [HgL(A-A)] [where L = 2-(2'-hydroxynaphthyl)benzothiazole (APBT), 2-(2'-hydroxyphenyl)benzothiazole (HPBT), 2-(2'-mercapto-phenyl)benzothiazole (MPBT)] (A = glycine or alanine) have been synthesized and characterized by m.w. determination, magnetic measurements, infrared and NMR studies. A tetrahedral geometry has been proposed for the present mercury(II) complexes. All the complexes are coloured, thermally stable, monomeric and non-electrolytic in nature. The ligands and their metal complexes showed biological activity against pathogenic fungi Aspergillus Niger and Fusarium oxysporum. The antifungal activity data revealed that mercury(II) complexes are found more fungi-toxic than the parent ligands.

Full text of DOI:10.14233/ajchem.2018.21301

Asian Journal of Chemistry; Vol. 30, No. 8 (2018), 1777-1780
A
SIAN
J
OURNAL OF HEMISTRY
C
https://doi.org/10.14233/ajchem.2018.21301
Synthesis, Characterization and Biological Activities of Mercury(II)
Ternary Complexes of 2-Substituted Benzothiazoles Derivatives
1
2
3
4
1,*
MANMOHAN SINGH CHAUHAN , MITLESH KUMARI YADAV , ARUNA SHARMA , SHRADHA BINANI and NARENDRA PAL LAMBA
1
2
3
4
ASAS, Department of Chemistry, Amity University Rajasthan, Jaipur-303 002, India
Department of Chemistry, Malaviya National Institute of Technology, Jaipur-302 017, India
Department of Chemistry, JECRC University, Jaipur-303 905, India
Hyderabad Institute of Technology and Management, Hyderabad-501 401, India
*
Corresponding author: E-mail: narenlamba5@gmail.com
Received: 23 February 2018; Accepted: 10 May 2018;
Published online: 30 June 2018;
AJC-18973
Biological important ternary complexes of type [HgL(A-A)] [where L = 2-(2'-hydroxynaphthyl)benzothiazole (APBT), 2-(2'-
hydroxyphenyl)benzothiazole (HPBT), 2-(2'-mercapto-phenyl)benzothiazole (MPBT)] (A = glycine or alanine) have been synthesized
and characterized by m.w. determination, magnetic measurements, infrared and NMR studies. A tetrahedral geometry has been proposed
for the present mercury(II) complexes. All the complexes are coloured, thermally stable, monomeric and non-electrolytic in nature. The
ligands and their metal complexes showed biological activity against pathogenic fungi Aspergillus niger and Fusarium oxysporum. The
antifungal activity data revealed that mercury(II) complexes are found more fungi-toxic than the parent ligands.
Keywords: Benzothiazole, Amino acids, Mercury(II) complexes, Antifungal activity.
applications of benzothiazole found in textile dyeing, proces-
sing of rubber, as an antioxidant, fungicide, etc. [20,21]. It has
been reported in literature that benzothiazole, its bio-sisters
have potential against bacteria’s such as Gram-negative, Gram-
positive and yeast [22]. Pal et al. [23] also reported the synthesis
of Zn(II) complex of benzothiazole derivatives having potential
antifungal and antibacterial activities. In this article, we reported
a synthetic protocol for the synthesis of 2-substituted benzo-
thiazoles viz. 2-(2′-hydroxynaphthyl)benzothiazole (APBT),
INTRODUCTION
In recent years, the synthesis of transition metal comp-
ounds, as important semiconductors materials, has attracted
wide attention due to their physical and chemical properties
in various fields, such as catalysis, sensors, solar cells, photo
detector, light emitting diodes, and laser communication, have
made them very attractive [1-4]. Linear complexes of mercury(II)
forms stable complexes with two sulfur donor ligands. However,
Hg -thiol bonds are labile and for higher Hg-S coordination
numbers, the structures are flexible, often with distorted trigonal
or tetrahedral coordination structures [5].
Benzothiazole derivatives played an important role in
structural formation of many biological, dye compounds and
pharmaceutical [6-10]. They used as cytotoxic agents [11],
cathepsin S inhibitors [12], HIV reverse transcriptase inhibitors
II
2
-(2′-hydroxyphenyl)benzothiazole (HPBT), 2-(2′-mercapto-
phenyl)benzothiazole (MPBT) and amino acids (glycine,
alanine) along with Hg(II) ternary complex.
EXPERIMENTAL
The chemicals and the solvents were purchased from CDH
and double distilled before use. Microanalysis was carried out
at Department of Chemistry, Rajasthan University, Jaipur, India.
IR spectra were recorded (using KBr pellets) on a SHIMADZU
8400 SPIR spectrophotometer. UV-visible spectrophotometer,
Gouy balance and Systronics Conductivity Bridge Model 305
were used for recording of electronic spectra, magnetic moments
and molar conductance, respectively. The rast camphor method
was used for determination of molecular weights. Gravimetric
analysis was used for estimation of mercury [24].
[
13], estrogen receptor agonists [14], selective peroxisome
proliferator activated receptor antagonists [15], anticancer
agents [16] and orexin-1 receptor antagonists [17]. Benzo-
thiazole derivatives are used as both natural and synthetic are
key components for radiolabeling of PET imaging for detecting
disease like alzheimer [18].
Furthermore, benzothiazole derivatives as ligand forms
stable complex with different transition metal ions [19] and
also showed promising biological activities [20]. Other industrial

1
778 Chauhan et al.
Asian J. Chem.
Synthesis of 2-substituted benzothiazoles: The synthesis
gillus niger and Fusarium oxysporum in the test solution of
dimethylformamide of concentration 50, 100 and 200 ppm.
Measuring the fungus colony diameter after 72 h, results in
linear growth. The calculated results of antifungal activity of
the ligands and Hg(II) ternary complex was compared with
the conventional fungicide bavistin.
of 2-(2′-hydroxynaphthyl)benzothiazole (APBT), 2-(2′-hydroxy-
phenyl)benzothiazole (HPBT), 2-(2′-mercapto-phenyl)benzothia-
zole (MPBT) was carried out by condensing o-aminothio-
phenol (0.01 mol) with salicylic acid (0.01 mol), thiosalicylic
acid (0.01 mol) and anthranilic acid (0.01) in polyphosphoric
acid (PPA) (25 mL). This mixture was heated under reflux with
constant stirring for 3 h at 250 °C and cooled at room tempe-
rature. The alkalinity of the resultant mixture is maintained
using NaOH. The final product filtered, washed, dried and
recrystallized from alcohol (Scheme-I).
RESULTS AND DISCUSSION
IR studies:The IR spectral bands and their tentative assigned
peaks are presented in Tables 1 and 2. The ligandsAPBT, HPBT,
MPBT with glycine or alanine amino acid act as bidentate
ligands in Hg(II) ternary complex using oxygen, sulfur and
X
-1
N
nitrogen as donor atoms. The broad band at 3340-3328 cm
NH2
COOH
H O
2
+
(Table-1) are attributed to ν(O-H) vibration of -OH group of
the free ligands (HPBT) disappears in the respective ternary
Hg(II) complex indicating the deprotonation of the -OH group
and simultaneous formation of Hg-O bonds. The formation of
Hg-O bond further support by the appearance of new bands
PPA
50 °C, 3h
+
S
2
X
SH
X = O H, SH, NH2
X = OH, SH, NH2
Scheme-I: Synthesis of benzothiazole derivatives
-1
of medium intensity in the region 535-521 cm (Table-2) due
Synthesis of Hg(II) ternary complexes: The correspon-
ding ligand viz., 2-(2′-Hydroxynaphthyl)benzothiazole
to ν(Hg-O) vibrations respectively. The IR peak in the region
-1
2
582 cm due to ν(S-H) vibration of -SH group of free ligand
(
APBT), 2-(2′-hydroxyphenyl)benzothiazole (HPBT) or 2-(2′-
mercapto-phenyl)benzothiazole (MPBT) (0.004 mol each) was
mixed with a solution of HgCl , amino acids (glycine or alanine)
MPBT, disappeared in the IR spectra of respective ternary Hg(II)
complexes, suggested the deprotonation of -SH group and simul-
taneously formation of Hg-S bonds due to the appearance of
non-ligand vibrations, respectively. This is further supported
by the appearance of bands of medium intensity in the region
2
and pyridine in dry alcohol (30 mL) and refluxed it with constant
stirring for 3 h and kept at room temperature for 12 h. This
solution was filtered, recrystallized from alcohol and dried
under vacuum (Scheme-II).
-1
3
57-352 cm assignable to ν(Hg-S) vibrations, respectively.
In the IR spectra Hg(II) complex the broad band's observed in
-1
the region 3355-3348 cm are assigned to ν(N-H) and ν(N-H)
vibrations of -NH group of glycine/alanine, indicating the
2
Hg Cl , Glycine
or Alanine
2
Y
H2N
N
S
coordination due to support by the appearance of non-ligand
Hg
Z
-1
bands of medium intensity in the region 455-437 cm due to
N
S
Ethyl alcohol,
reflux, 3h
O
ν(Hg←N) vibrations [25,26]. The absorption bands appeared
X
O
-1
in the region 1672-1655 cm of IR spectra for all these ternary
Hg(II) complexes, which is assignable to ν(C=O) stretching
vibration of coordinated carboxylate group of glycine/alanine
moiety. The IR spectra of free ligand (HPBT,APBT and MPBT)
X = OH, SH, NH2
Z = H, Gly
Z = CH , Ala
Y = O, S, NH
3
Scheme-II: Synthesis of Hg(II) ternary complex of benzothiazole deriva-
tives and amino acids
-1
exhibit medium intense bands in region 1615-1592 cm due to
Biological activity: Radial growth method is employed
for the biological activity of ligands (HPBT,APBT and MPBT)
and their Hg (II) ternary complexes using fungi, namely Asper-
ν(C=N) stretching vibration [27], are shifted to the lower wave
number by 10-20 cm and becoming larger and sharper in the
spectra of respective ternary Hg(II) complex, indicated the
-1
TABLE-1
KEY IR BANDS (cm ) OF 2-SUBSTITUTED BENZOTHIAZOLES
–
1
ν(C-O)
Exo)
ν(NH2)
asym/sym
Heterocyclic
breathing mode
Ligand
ν(O-H)
ν(S-H)
ν(C-S) (Exo)
ν(C=C)
ν(C=N)
(
HPBT
MPBT
APBT
3340
–
–
–
2570
–
1231
1214
–
–
–
–
1279
–
1586
1589
1591
1617
1621
1615
853
861
869
3369/3251
TABLE-2
KEY IR BANDS (cm ) OF TERNARY COMPLEXES OF Hg(II) OF 2-SUBSTITUTEDBENZOTHIAZOLES AND AMINO ACIDS
–1
Complex
ν(NH ) asym./sym.
ν(C=O)
1672
1669
1663
1665
1650
1655
ν(C=C)
1586
1581
1580
1576
1571
1579
ν(C=N)
1615
1608
1601
1597
1594
1592
ν(Hg←N)
455
ν(Hg-O)
535
529
519
521
ν(Hg←S)
363
2
[
[
[
[
[
[
Hg(HPBT)(Gly)]
Hg(HPBT)(Aly)]
Hg(MPBT)(Gly)]
Hg(MPBT)(Aly)]
Hg(APBT)(Gly)]
Hg(APBT)(Ala)]
3348, 3267
3342, 3267
3339, 3265
3337, 3258
3334, 3265
3331, 3255
445
443
441
433
360
359
346
365
526
511
437
361

Vol. 30, No. 7 (2018) Synthesis and Biological Activities of Mercury(II) Ternary Complexes of 2-Substituted Benzothiazoles Derivatives 1779
TABLE-3
1
H NMR DATA (δ) OF TERNARY COMPLEXES OF MERCURY(II) OF 2-SUBSTITUTED BENZOTHIAZOLES AND GLYCINE/ALANINE
Complexes
Hg(HPBT)(Gly)]
Hg(HPBT)(Ala)]
Hg(MPBT)(Gly)]
Hg(MPBT)(Ala)]
Hg(APBT)(Gly)]
Hg(APBT)(Ala)]
-NH (bs)
-CH (d)
-CH (s)
3.65
-
3.61
-
3.63
-
-CH (q)
Aromatic (m)
6.98-8.40
6.94-8.43
7.12-8.45
7.13-8.50
7.21-8.56
7.23-8.55
2
3
2
[
[
[
[
[
[
3.77
3.63
3.71
3.74
3.75
3.73
-
-
1.26
-
1.30
-
3.65
-
3.64
-
1.38
3.62
coordination through secondary oxygen atom of benzoxazolyl
moiety with Hg atom [28,29]. It is further confirmed by the
The toxicity increased as the concentration was increased. The
antifungal activity data also revealed that Hg(II) ternary com-
plexes of APBT and gly/ala showed more antifungal activity
than Hg complexes of HPBT and MPBT ligands with amino
acids, respectively. It also confirmed that complexes of soft acids
-1
appearance of non-ligand bands in the region 455-437 cm in
all these ternary complexes [30,31].
1
H NMR studies: The bonding pattern in the resulting
1
ternary Hg(II) complexes have been further confirmed by H
are more active because -NH group of APBT ligand can bind
2
NMR spectra of the ternary complexes and their ligands (substi-
to the cell enzyme more strongly. This can be explained by chela-
tion theory. Due to chelation, the lipophilic nature of metal incre-
ases which subsequently favour its permeation through the semi-
pereable defences of cell membrane of microorganisms and
thereby, impairing normal cell process [36,37].
tuted benzothiazoles and amino acids) in DMSO-d using tetra-
6
1
methylsilane as the internal standard. The H NMR spectra of
the free ligand glycine/alanine show a broad singlet (Table-3)
at δ 3.60-3.75 ppm due to -NH
δ 3.63-3.77 ppm) in the respective ternary Hg(II) complexes,
suggesting the coordination through nitrogen atom of -NH
group with Hg atom. The broad singlet in the region δ 10.28-
0.31 ppm assigned to -OH proton of the free ligand HPBT,
2
proton, is shifted to down field
(
TABLE-4
2
ANTIFUNGAL SCREENING DATA OF
-SUBSTITUTED BENZOTHIAZOLE LIGAND
2
1
1
Average % inhibition
APBT, MPBT and glycine/alanine disappearing in the H NMR
spectra of corresponding ternary Hg(II) complexes indicating
thereby the deprotonation of -OH group and coordination of
the phenolic oxygen to Hg atom.
Compound
HPBT
MPBT
APBT
Aspergillus niger
Fusarium oxysporum
50
100
45
44
51
46
42
48
42
54
56
96
200
62
63
69
52
58
61
63
71
73
103
50
37
34
48
31
37
38
36
47
45
87
100
47
56
68
43
45
47
49
71
74
99
200
64
68
76
56
52
59
61
79
81
105
36
38
46
32
31
30
34
47
46
86
1
The H NMR spectra of free ligand MPBT exhibited a
singlet at δ 4.48-4.50 ppm due to -SH (thiophenolic proton),
disappeared in the spectra of respective ternary Hg(II) complex,
suggesting the deprotonation of -SH group and coordination
[Hg(HPBT)(Gly)]
[Hg(HPBT)(Aly)]
[Hg(MPBT)(Gly)]
1
[Hg(MPBT)(Aly)]
[Hg(APBT)(Gly)]
[Hg(APBT)(Ala)]
of thiophenolic sulphur to Hg atom. The H NMR spectra of
ternary Hg(II) complex exhibited doublet at δ 1.26-1.30 ppm
due to -CH
3
proton, quintet at δ3.62-3.65 ppm due to -CH proton
proton
Bavistin (standard)
of alanine and singlet at δ 3.61-3.65 ppm due to -CH
2
of glycine. Aromatic protons observed at δ 6.98-8.55 ppm as
multiplet in the H NMR spectra of ligands (HPBT,APBT and
1
ACKNOWLEDGEMENTS
MPBT) shifted down field (δ 0.5-1.5ppm) in the spectra of
respective ternary Hg(II) complex, which may be possibly due
to deshielding on coordination of ligand molecules with Hg
atom [32,33].
Magnetic studies: The magnetic moment values ofternary
Hg(II) complex at room temperature indicates the diamagnetic
nature of Hg(II) ions. The zero value of magnetic moments of
the complex is the characteristic of Hg(II) in the distorted
tetrahedral structure.
The authors acknowledge the Department of Chemistry,
University of Rajasthan for providing research facility. Thanks
are also due to Amity University Rajasthan, Jaipur, India for
providing the financial support.
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