Antimicrobial relevance of Cu(II) complexes of thiophene-2-glyoxal-p-halogen substituted anils

Article abstract of DOI:10.13005/ojc/300314

Isomeric complexes of, p-chloro, p-bromo, and p-iodo-anils of 2-thiophene glyoxal ligands have been synthesized and characterized by metal analysis, molecular weight, infrared and UV-Visible spectroscopy, molar conductance and magnetic measurements. All n

Full text of DOI:10.13005/ojc/300314

ISSN: 0970-020 X
CODEN: OJCHEG
2014, Vol. 30, No. (3):
Pg. 1031-1036
ORIENTAL JOURNAL OF CHEMISTRY
An International Open Free Access, Peer Reviewed Research Journal
www.orientjchem.org
Antimicrobial Relevance of Cu(II) Complexes of
Thiophene-2-glyoxal-p-halogen Substituted Anils
FENTAHUN ADAMU1, SANIDHYA UPADHYAY2 and R.K.UPADHYAY1*
1Department of Chemistry, College of Natural and Computational Science, Jigjiga University, Ethiopia.
2Ranbaxy Research Laboretories, R & DV Department Plot No. 20, Section 18,Udyog, Gurgaon, India.
*Corresponding author E-mail: rkupadhyay14@gmail.com
http://dx.doi.org/10.13005/ojc/300314
(Received: May 10, 2014; Accepted: July 20, 2014)
ABSTRACT
Isomeric complexes of, p-chloro, p- bromo, and p-iodo – anils of 2-thiophene glyoxal ligands
have been synthesized and characterized by metal analysis, molecular weight, infrared and UV-
Visible spectroscopy, molar conductance and magnetic measurements.All non electrolytic complexes
are square planar paramagnetics. Among all of the compounds only p-bromo and p-iodo-anils of
2-thiophene glyoxal exhibited good antifungal activity against both test fungi but all products showed
moderate to good bactericidal effect against S.aures and X.holicicola bacteria.
Key words: Complexes, anils, antimicrobial, paramagnetics, 2- thiophene glyoxal.
INTRODUCTION
wide spectrum of biological properties, enhanced
biological properties of metal-based organic
compounds observed generally and alarming
problem of multi-drug resistance of several microbes,
bacteria and fungi, impelled us to design some
copper (II) – based Schiff,s bases antimicrobials
with the view to addess the problem of multi-
drug resistance of a few selected bacteria and
fungi. Therefore in the present communication we
report synthesis, structural characterization and
antimicrobial potential against Staphylococcus
aureus and Xanthomonas holicicola bacteria,
and Fusarium oxysporum and Aspergillus niger
fungi in vitro of copper (II) complexes of p-chloro-,
p-bromo and p-iodo-anils of 2-thiophene glyoxal16,
abbreviated asTGCA, TGBA andTGIA respectively.
Among the variety of organic compounds
Schiff’s bases have earned highest popularity owing
to their preparative accessibility and multifarious
applications, viz. in chemistry as analytical
reagents1,2, as starting materials in the synthesis
of hetercycles3-5 and as novel ligands in forming
complexes of unusual stereochemistries6,7 and
isomeric structures6,8,9, in agriculture as herbicides10,
in industries as dyes11 and catalytic agents11 and
in medical science as antimicrobial, anticancer,
antitumor, antimalarial, antituberculosis, analgesic
etc. agents13-15
.
High versality of Schiff’s bases in exhibiting

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ADAMU et al., Orient. J. Chem., Vol. 30(3), 1031-1036 (2014)
MATERIALS AND METHOD
displayed two spots with different Rf values in
several solvents. Owing to maximum Rf difference
Melting points determined in open glass of components of binary mixtures in benzene and
capillaries are uncorrected. Metal contents of chloroform (low Rf 0.00 and high Rf 0.83-0.97) they
complexes were estimated by atomic absorption were separated by column chromatography with
spectroscopy on Buck Scientific Model 210VGB. these solvents using silica gel (BHD 60 mesh).
Molecular weights were determined by Rast’s micro Low Rf products were eluted with acetone and on
method using camphor as solvent. IR spectra were evaporation of solvents from eluates solids were
recorded in 4000 – 200 cm-1 range on Perkin Elmer recovered and weighed. Quantity of high Rf products
1
R (FTIR) spectrophotometer in nujol and HNMR of CuCl2- TGCA and Cu (NO3)2-TGCA being very
spectra were recorded in CDCl3 on Bruker Ultrashield little, they could not be processed for structural
TM- 400 spectrometer using TMS as internal and antimicrobial investigations. In the synthesis of
standard. Electronic spectral measurements were compounds BDH/ Merck laboratory reagents were
done on UV/Vis- SP65 SYANO spectrophotometer used as supplied whereas in chromatographic work
in acetone, whereas conductometric measurements HPLC grade solvents were used.
were done on Jenway digital conductivity meter
in acetone. Magnetic susceptibility of powdered Evaluation of antimicrobial activities
samples was measured with MSB-AUTO, (Sherwood
Scientific) magnetic balance.
Antimicrobial, fungicidal and bactericidal,
activities of all the compounds were tested in vitro on
S aureus and X.holicicola bacteria and F.oxysporum
Synthesis of thiophene -2-glyoxal –p-halogen and A. niger fungi, using disc diffusion method.
substituted anils Isolates of both bacteria and fungi were cultured on
All the three ketoanils, TGCA, TGBA and nutrient agar (NA) and potato dextrose agar (PDA)
TGIA, were synthesized by reported procedure media respectively. Aliquots of 5, 10 and 20 µl of
[16].On mixing saturated solution of thiophene-2- 5mg/ml concentrated solutions of samples in acetone
glyoxal (0.04 mol) with saturated solution of each of were pipetted to the discs in three replications of
p-chloro-, p- bromo- and p-iodo- anilines (0.04 mol) each and transferred to NA plates seeded with
in diethylether with continuous stirring and allowing bacteria and PDA seeded with spore suspension of
the reaction mixtures to stand for half an hour at test fungi. For antifungal studies petri dishes were
room temperature, precipitates of products obtained incubated at 26°C for 5-7days whereas petri dishes
were filtered out, washed with ether and dried in air. containing bacteria for loaded discs incubated a 37°C
Thiophene -2- glyoxal was prepared by oxidation for A.ureus and at 28°C X.holicicola for 24 h.
of 2-acetyl thiophene (0.5mol) with an equimolar
quantity of selenium dioxide (0.5mol) in ethyl alcohol
by refluxing as reported16.
RESULTS AND DISCUSSION
Structural studies
Although synthesis and structures of TGCA,
Synthesis of complexes
For the synthesis of complexes saturated TGBA and TGIA have been reported [10,14] earlier
solution containing 0.01 mol of each of copper salts, but for further verification of reported structural results
CuCl2.2H2O and Cu (NO3)2.3H2O, was mixed with their UV, IR and 1HNMR spectra have been recorded
saturated solution of each ketoanil ligand (0.015mol) and analyzed.UV:C=O, ca.220 nm (Π→Π*) ca.327
in acetone and reaction mixtures were refluxed nm (n→Π*) ; C=N, ca. 243 nm (Π→Π*), 1HNMR : δ
for about 1h. On cooling the reaction mixtures 7.25- 8.20 (1H, CH=N) ; δ 7.1-7.9 (3H, thienyl ring);
precipitated products were filtered out, washed with δ 6.43- 7.74 (4H, benzene ring).
benzene/toluene, dried and finally washed with water
and dried in air.
Inallthethreeketoanils, halogensubstituent
in para position being electron donor could transfer
Homogeneity of the products was tested electron density to carbonyl oxygen which may lead
by thin-layer chromatography. All the three ketoanils to the molecular rearrangement of the benzenoid
exhibited single spot migration whereas complexes structures I to quinonoid form II. After acquiring

ADAMU et al., Orient. J. Chem., Vol. 30(3), 1031-1036 (2014)
1033
some negative charge quinonoid oxygen is more
activated for coordination than benzenoid oxygen
(structure I). Therefore structure II could offer three
coordinating sites, carbonyl oxygen, thienyl sulphur
and azomethine nitrogen (Fig.,1).
Formulation of complexes has been done
in accordance with their metal analysis, molecular
weight and conductance data (Tabe-1).
In order to study the binding modes of
ketoanil ligands in the complexes, IR spectra of
the free ligands are compared with their respective
metal complexes. Perusal of infrared spectra of
ligands and their respective complexes reveals that
stretching bands corresponding to C=C(aromatic),
1:4 disubstitution , and C-Cl, C-Br and C-I groups of
TGCA,TGBA and TGIA occurring at 1615, 1447 &
1436 cm-1, 820 cm-1 and 632 cm-1, 1587, 1470 & 1454
cm-1, 804 cm-1 and 550 cm-1 and 1584 & 1449 cm-1,
807 cm-1 and 500 cm-1 respectively are shifted to
higher frequency side at ca.1594, 1521 & 1462 cm-1,
ca.1585, 1498 & 1457 cm-1, ca.828 cm-1 and ca.552
cm-1, and ca. 1582, 1460 & 1452 cm-1, ca. 826 cm-1
and ca. 515 cm-1 of the spectra of their respective
complexes.. This increase in frequencies of these
groups of ligands on complexation clearly indicates
presence of quinonoid structure (II) of the ligands in
their complexes. The υC=O band of TGCA, TGBA
andTGIA occurring at 1775 cm-1,1675 cm-1 and 1650
cm-1 is observed at ca. 1688 cm-1, ca.1619 cm-1 and
ca.1619 cm-1 in their complexes respectively. The
lowering in carbonyl group stretching frequency of
ligands on complexation with copper is the strong
evidence of coordination of carbonyl group with the
metal.A new band in 475-530 cm-1 region of complex
spectra, attributed to Cu-O stretching, supports
the coordination of carbonyl group of ligands. The
lowering in υC=N frequency ofTGCA from 1675 cm-1
to ca. 1594 cm-1 in its chloro-and nitro complexes,
of TGBA from 1616 cm-1 to ca.1587 cm-1 in their
low Rf (a) complexes and of TGIA from 1613 cm-1
to ca. 1587 cm-1 in its low Rf (a) complexes and
appearance of a new band of Cu-N stretching in
405 - 431 cm-1 range of spectra of these complexes
indicate presence of azomethine group17 nitrogen
in the coordination zone of Cu(II) in them. The
undisplaced position of ÅC-S-C band of ligands in
these complexes reveals absence of thienyl sulphur
in coordination sphere of metal.

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ADAMU et al., Orient. J. Chem., Vol. 30(3), 1031-1036 (2014)
In high-Rf (b) complexes of TGBA and of υCu-N in 468-498 cm-1 region of spectra lead us
TGIA decrease in υC-S-C frequency of ligands from to propose monoligancy of nitrato ion through its
725 cm-1 and 721 cm-1 to ca.686 cm-1 and ca.664 nitrogen.
cm-1 respectively and appearance of a new low
frequency band in 238-250 cm-1 range of, υCu-S
Both isomeric complexes of CuCl2-TGBA
in complex spectra are suggestive of coordination display symmetric and antisymmetric stretching and
of thienyl sulphur17,18 whereas undisturbed C=N bending vibrations of lattice water19 at 3444 cm-1
stretching frequency of ligands in these complexes and ca.1669 cm-1 respectively whereas Cu(NO3)2-
indicates non- participation of azomethine group in TGBA (a) and CuCl2-TGIA (a) display only one band
coordination.
at ca.1650 cm-1 of symmetric and antisymmetric
bending vibration. Owing to absence of any band
A medium intensity band, characteristics characteristic of coordinated water, presence of
of υCu-Cl, occurring in 348-385 cm-1 region of all water in coordination zone of copper (II) is titally
the chloro complexes clearly exhibit coordination refruted.
of monodentate chlorine. All the nitrato complexes
display four bands at ca.1301 cm-1, ca.1037 cm-1,
Magnetic moments of the complexes
ca.1461 cm-1 and ca.885 cm-1 corresponding to [19] (1.78-2.18BM) close to spin-only value (1.73B.M),
υNO2 symmetric, υNO, υNO2 asymmetric and Ár NO2 correspond to d9 Cu(II) paramagnetics. Electronic
asymmetric out- of -plane respectively only out of the spectra of complexes display four or five bands
expected six bands and one pairs of combination in 18868-27778 cm-1 , 27778-30769 cm-1 , 30303 -
bands at ca.1771 cm-1 and ca.1748 cm-1 except 31746 cm-1 , 33898- 40000 cm-1 and 47619-48780
2
Cu(TGCA)(NO3)2 which displays two pairs of bands cm-1 .The first three bands are characteristic of B1g
as expected at 1775 cm-1 and 1750 cm-1, and 2434 → A1g → B1g → B2g and 2B1g → Eg d-d transitions
cm-1 and 2293 cm-1;the energy separation of first two of square planar geometry whereas other two bands
bands and last two of these bands is ca.24 cm-1 and of high energy could be due to ligand →metal charge
141 cm-.1 These results and a new additional band transfer.
2
2
2
2
Table 2: Antimicrobial activity of synthesized compounds
S.
Compound
Inhibition zone (mm)
Fungi
A. niger
5µl 10µl 20µl 5µl 10µl 20µl 5µl 10µl 20µl 5µl 10µl 20µl
No.
Bacteria
S. aureus X. holicicola
F. oxysporum
1
2
3
4
5
6
7
8
TGCA
Cu(TGCA)Cl2
Cu(TGCA)(NO3)2
TGBA
-
-
-
10
-
-
-
-
8
-
-
-
-
-
15
-
-
-
-
10
-
-
-
-
-
16
-
-
-
-
11
-
-
-
-
-
8
-
-
-
-
7
-
-
-
-
-
11
-
-
-
-
9
-
-
-
-
-
13
-
-
-
-
11
-
-
-
8
8
9
7
-
9
7
8
9
8
8
-
-
9
8
10
8
-
9
7
8
9
9
8
-
-
10
10
10
8
-
11
8
9
10
9
9
-
8
8
8
7
7
-
7
8
7
8
-
8
8
9
8
7
-
8
8
8
8
-
9
9
10
9
8
-
10
9
9
10
-
9
Cu(TGBA)Cl2.H2O”a
Cu(TGBA)Cl2.3H2O”b
Cu(TGBA)(NO3)2.3H2O”a
Cu(TGBA)(NO3)2"b
TGIA
Cu(TGIA)Cl2.3H2O”a
Cu(TGIA)Cl2"b
Cu(TGIA)(NO3)2"a
Cu(TGIA)(NO3)2"b
Bavistin(Standard)
Chloraphenicol (standard)
9
10
11
12
13
-
-
16
-
-
-
18
-
-
-
20
-
-
-
15
-
-
-
17
-
-
-
18
-
8
-
-
8
-
-
-
-
-
13
-
14
-
16
14 14 15

ADAMU et al., Orient. J. Chem., Vol. 30(3), 1031-1036 (2014)
1035
C
O
CH N
X
Benzenoid form (I)
S
X+
CH N
C
Quininoid form(II)
S
O -
Fig.1: Tautomeric structures of ketoanils, where X= Cl, Br or I
Where X= Cl, Br or I and Y= Cl- or NO3- n=0,1 or 3
Fig. 2(a): Structure of low Rf (a) complexes
Fig. 2(b): Structure of high Rf (b) complexes
Based on aforesaid studies following
structures of the complexes are proposed (Fig., 2 A
&B)
possibility of its use as selective antifungal drug.
Antibacterial data however reveals that all the test
compounds except Cu(TGBA)Cl2.3H2O (b) and
Cu(TGIA)(NO3)2 (b) are toxic against both bacteria
tested all the a-isomers involving NO donor sides
of ligands are better than b-isomers involving
SO coordination sides of ligands in bactericidal
properties.Higher inhibition levels of complexes than
their free ligands, observed in majority cases in all
the three doses applied, could be attributed to the
better lipophilic nature of complexes than ligands on
the basis of chelation theory20.
Antimicrobial studies
Fungicidal data (Table-2) clearly reveals
that all the complexes and TGCA are totally non-
toxic against both test fungi whereas TGBA and
TGIA exhibit dose dependant antifungal activity;
TGBA showing better activity than TGIA, almost
similar to Bavistin (standard fungicidal drug), could
be proposed for further investigation to look at the

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