molecules
Article
Synthesis, Characterization and Antibacterial Studies of
N-(Benzothiazol-2-yl)-4-chlorobenzenesulphonamide
and Its Neodymium(III) and Thallium(III) Complexes
Lawrence Nnamdi Obasi 1 , Uchechukwu Susan Oruma 1, *, Ibrahim Abdulrazak Al-Swaidan 2 ,
Ponnadurai Ramasami 3,4 , Chigozie Julius Ezeorah 1 and Alfred Ezinna Ochonogor 1
1
2
3
4
*
Department of Pure and Industrial Chemistry, University of Nigeria, Nsukka 410001, Nigeria;
[email protected] (L.N.O.); [email protected] (C.J.E.);
[email protected] (A.E.O.)
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457,
Riyadh 11451, Saudi Arabia; [email protected]
Computational Chemistry Group, Department of Chemistry, Faculty of Science, University of Mauritius,
Réduit 80837, Mauritius; [email protected]
Department of Applied Chemistry, University of Johannesburg, Doornfontein Campus,
Johannesburg 2028, South Africa
Correspondence: [email protected]; Tel.: +234-806-122-2297
Academic Editors: Panayiotis A. Koutentis and Andreas S. Kalogirou
Received: 9 November 2016; Accepted: 4 January 2017; Published: 22 February 2017
Abstract: N-(Benzothiazol-2-yl)-4-chlorobenzenesulphonamide (NBTCS) was synthesized by
condensation reaction of 4-chlorobenzenesulphonyl chloride and 2-aminobenzothiazole in acetone
under reflux. Neodymium(III) and thallium(III) complexes of the ligand were also synthesized.
Both ligand and metal complexes were characterized using UV-Vis, IR, 1 H- and 13 C-NMR spectroscopies,
elemental analysis and molar conductance measurement. IR studies revealed that the ligand is tridentate
and coordinates to the metal ions through nitrogen and oxygen atoms of the sulphonamide group and
nitrogen atom attached to benzothiazole ring. The neodymium(III) complex displays a coordination
number of eight while thallium(III) complex displays a coordination number of six. The ligand and
its complexes were screened in vitro for their antibacterial activities against Escherichia coli strains
(E. coli 6 and E. coli 13), Proteus species, Staphylococcus aureus and Pseudomonas aeruginosa using the
agar well diffusion technique. The synthesized compounds were found to be more active against the
microorganisms screened relative to ciprofloxacin, gentamicin and co-trimoxazole.
Keywords: N-(benzothiazol-2-yl)-4-chlorobenzenesulphonamide; neodymium(III) and thallium(III)
complexes; antibacterial activity
1. Introduction
Sulpha drugs, also known as sulphonamides, are compounds, which have a general structure
represented by Figure 1. Sulpha drugs were discovered in 1930s during a series of studies with
a bright red dye named prontosil [1,2]. Prontosil was found to be able to cure severe staphylococcal
septicemia in human [2]. After the discovery of prontosil, several drugs containing the sulphonamide
moiety have been prepared and put into diverse medical applications. They serve as antimicrobial
drugs (sulphacetamide) [3–5]; diuretic drugs (acetazolamide) [6]; anticonvulsants (sultiame) [6];
dermatological drugs (mafenide) [7]; anticancer [8–10]; anti-inflammatory [11,12]; antihypertensive
agent (bosentan) [13] and antiviral agents; and HIV protease inhibitors [14,15]. Their antimicrobial
activities arise due to competitive inhibition of the enzyme dihydropteroatesynthetase (DHPS),
an enzyme involved in folate synthesis. As such, the microorganism will be starved of folate and die.
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Molecules 2017, 22, 153
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The similarity
of As
thesuch,
structure
between sulphonamide
and p-aminobenzoic
acidThe
(PABA),
a molecule
folate
synthesis.
the microorganism
will be starved
of folate and die.
similarity
of the
found
in
bacteria
used
in
folic
acid
synthesis,
is
the
basis
for
the
inhibitory
activity
of
sulpha
drugs
structure between sulphonamide and p-aminobenzoic acid (PABA), a molecule found in bacteria
on dihydrofolate
biosynthesis
[1,6,16].
Sulpha
drugs are activity
associated
with antibiotic
and
used
in folic acid synthesis,
is the
basis for
the inhibitory
of sulpha
drugs onresistance
dihydrofolate
allergies [17,18].
TheSulpha
work drugs
done by
et al. 2012
insight
into sulpha
drug resistance
[1].
biosynthesis
[1,6,16].
areYun
associated
with gave
antibiotic
resistance
and allergies
[17,18]. The
They
revealed
that
the
binding
sites
of
PABA
and
sulpha
drugs
overlap,
but
those
of
sulpha
drugs
work done by Yun et al. 2012 gave insight into sulpha drug resistance [1]. They revealed that the binding
extend
the pocket
which
PABA binds.
Mutations
associated
with drug
resistance
cluster
sites
of beyond
PABA and
sulpha in
drugs
overlap,
but those
of sulpha
drugs extend
beyond
the pocket
in
aroundPABA
this extended
region of the
PABA pocket.
Thisresistance
explains how
they
can prevent
the drugs
from
which
binds. Mutations
associated
with drug
cluster
around
this extended
region
binding
without
seriously
affectinghow
the binding
PABA. the
Several
modifications
been seriously
made on
of
the PABA
pocket.
This explains
they canofprevent
drugs
from bindinghave
without
the general
in new
compounds
with
pharmacological
affecting
thestructure
binding of
ofsulphonamides,
PABA. Several resulting
modifications
have
been made
onvarying
the general
structure of
activities and reduced
sidein
effect
The work with
done varying
by Lawrence
et al. 2010 have
shownand
thatreduced
the best
sulphonamides,
resulting
new[2].
compounds
pharmacological
activities
therapeutic
results
were obtained
from the compounds
in which
onethat
hydrogen
atom
of the SOresults
side
effect [2].
The work
done by Lawrence
et al. 2010 have
shown
the best
therapeutic
2 NH2
groupobtained
was replaced
[19]. Previous
studies
by Obasi
al.2NH
have
led towas
discovery
of
were
from by
theheterocyclic
compoundsring
in which
one hydrogen
atom
of theetSO
2 group
replaced
ligands
and
complexes
with
varying
activities
against
multi-resistant
bacterial
strains
isolated
under
by heterocyclic ring [19]. Previous studies by Obasi et al. have led to discovery of ligands and complexes
clinical
conditions
and cultured
species using agar-well
method
[20–22].
Metal
complexes
of
with
varying
activities
against multi-resistant
bacterial diffusion
strains isolated
under
clinical
conditions
and
sulpha drugs
have
beenagar-well
reported diffusion
with appreciable
activities
[23–28].ofRecently,
there have
cultured
species
using
method biological
[20–22]. Metal
complexes
sulpha drugs
several reports
on neodymium(III)
and
thallium(III)
complexes
Mimouni
et al., 2014
[38]
been reported
with appreciable
biological
activities
[23–28].
Recently,[29–37].
there have
been several
reports
have
synthesized, characterized,
and studied
the [29–37].
antibacterial,
antifungal
activities
on
neodymium(III)
and thallium(III)
complexes
Mimouni
et al., and
2014antitubercular
[38] have synthesized,
of thallium complexes
of monensin
and lasalocid.
Their study
revealed that remarkable
characterized,
and studied
the antibacterial,
antifungal
and antitubercular
activities ofbioactivity
thallium
against different
pathogens
were achieved
and confirmed
that
the compounds
could
very likely
be
complexes
of monensin
and lasalocid.
Their study
revealed that
remarkable
bioactivity
against
different
used without
great
risk of
toxicity
in diverse
pharmaceutical
applications.
the crystal
pathogens
were
achieved
and
confirmed
that the
compounds could
very likelyInbeaddition,
used without
great
structures
of thallium
saltpharmaceutical
of Grisorixin and
antibiotic 6016
thallium
salt
have structures
been reported
[39,40].
risk
of toxicity
in diverse
applications.
In addition,
the
crystal
of thallium
In view
of the need
for a new
generation
of have
antibiotics
that would
cause
fewer
sideneed
effects,
salt
of Grisorixin
and antibiotic
6016
thallium salt
been reported
[39,40].
In view
of the
for
we
designed
a new
of inhibitors
namely:
a new
generation
of class
antibiotics
that would
causeN-(benzothiazol-2-yl)-4-chlorobenzenesulphonamide
fewer side effects, we designed a new class of inhibitors
(NBTCS)N-(benzothiazol-2-yl)-4-chlorobenzenesulphonamide
and its neodymium(III), and thallium(III) complexes.
Their in
vitro
activities
namely:
(NBTCS)
and
itsantibacterial
neodymium(III),
and
against Escherichia
coli Their
strains
coli
6 and E. coli
13), Proteus
Staphylococcus
thallium(III)
complexes.
in (E.
vitro
antibacterial
activities
against species,
Escherichia
coli strains (E.aureus
coli 6 and
Pseudomonas
aeruginosa
were
also investigated.
E.
coli 13), Proteus
species,
Staphylococcus
aureus and Pseudomonas aeruginosa were also investigated.
R
O
H2N
S
O
1
N
R
Figure 1.
1. General
of sulphonamides;
sulphonamides; R=R1=H
R=R1=H for
Figure
General structure
structure of
for sulphanilamide.
sulphanilamide.
2. Results and Discussion
2. Results and Discussion
The
reaction of 2-aminobenzothiazole with 4-chlorobenzenesulphonylchloride yielded
The reaction of 2-aminobenzothiazole with 4-chlorobenzenesulphonylchloride yielded
N-(benzothiazol-2-yl)-4-chlorobenzenesulphonamide (NBTCS) as shown in Scheme 1. The reaction of
N-(benzothiazol-2-yl)-4-chlorobenzenesulphonamide (NBTCS) as shown in Scheme 1. The reaction
Nd(NO3)3·5H2O and C6H9O6Tl with NBTCS yielded [Nd(NBTCS)2(H2O)2]NO3 and [Tl(NBTCS)2]CH3COO,
of Nd(NO3 )3 ·5H2 O and C6 H9 O6 Tl with NBTCS yielded [Nd(NBTCS)2 (H2 O)2 ]NO3 and
respectively. The ligand and complexes are air stable and have high melting points. They are soluble
[Tl(NBTCS)2 ]CH3 COO, respectively. The ligand and complexes are air stable and have high
in ethanol, methanol, acetic acid and DMSO. The analytical data of NBTCS and its complexes are shown
melting points. They are soluble in ethanol, methanol, acetic acid and DMSO. The analytical data
in Table 1. The elemental analysis of the NBTCS and its complexes show that the amount of carbon,
of NBTCS and its complexes are shown in Table 1. The elemental analysis of the NBTCS and its
hydrogen, nitrogen and sulphur (CHNS) are close to the experimentally determined values. The values
complexes show that the amount of carbon, hydrogen, nitrogen and sulphur (CHNS) are close to the
of molar conductance of the complexes in DMSO at room temperature were found to be 72 Ω−1·cm2·mol−1
experimentally determined values. The values of molar conductance of the complexes in DMSO at
and 88 Ω−1·cm2·mol−1 for the Nd(III) and −
Tl(III) complexes, respectively. These values indicate 1:1
room temperature were found to be 72 Ω 1 ·cm2 ·mol−1 and 88 Ω−1 ·cm2 ·mol−1 for the Nd(III) and
electrolytic nature of the complexes [41]. The ligand was found to be non-electrolyte with a molar
Tl(III) complexes, respectively. These values indicate 1:1 electrolytic nature of the complexes [41].
conductance value of 15.6 Ω−1·cm2·mol−1.
The ligand was found to be non-electrolyte with a molar conductance value of 15.6 Ω−1 ·cm2 ·mol−1 .
Molecules 2017, 22, 153
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Cl
N
NH2
S
130oC
+
S
S
NH
O acetone
N
+
HCl
S
O
2-aminobenzothiazole
O
O
Cl
4-chlorobenzenesulphonyl chloride
Cl
N-(benzothiazol-2-yl)-4-chlorobenzenesulfonamide
Scheme 1.
1. Synthesis of N-(benzothiazol-2-yl)-4-chlorobenzenesulphonamide.
Scheme
N-(benzothiazol-2-yl)-4-chlorobenzenesulphonamide.
Table1.1.Physical
Physical properties
properties and
Table
andelemental
elementalanalysis
analysisofofN-(Benzothiazol-2-yl)-4-chlorobenzenesulphonamide
N-(Benzothiazol-2-yl)-4-chlorobenzenesulphonamide
(NBTCS)
and
its
complexes.
(NBTCS) and its complexes.
Compound
Compound
Molar Weight
Molar Weight
(g/mol)
(g/mol)
NBTCS
NBTCS
324.5
324.5
[Nd(NBTCS)2(H2O)2]NO3
[Nd(NBTCS)2 (H2 O)2 ]NO3
891
891
[Tl(NBTCS)2]CH3COO
[Tl(NBTCS)2 ]CH3 COO
912
912
C
48.07
(48.11)
35.02
(34.99)
36.84
(36.40)
Cal. (Exp., %)
Molar Cond.
2·mol−1)
(Ω−1·cm
Molar
Cond.
C Cal. (Exp.,
H %)
N
S
−1
2
−1
48.07H
2.77N
8.63 S 19.72 (Ω ·cm ·mol )
15.6
(48.11)
2.77 (2.94)
8.63 (8.75)
19.72 (19.89)
15.6
(2.94) 2.47
(8.75) 7.86
(19.89) 14.37
35.02
72
2.47 (2.36)
7.86 (7.60)
14.37 (14.20)
(34.99)
72
(2.36)
(7.60)
(14.20)
36.84
2.30
6.14
14.04
88
2.30 (2.80)
6.14 (6.07)
14.04 (13.96)
(36.40)
88
(2.80)
(6.07)
(13.96)
Colour
Colour
White
Yield
(%)
Yield (%)
40.83
40.83
White
Yellow
32.24
32.24
Yellow
Brown
34.97
Brown
34.97
2.1. Electronic Spectra
2.1. Electronic Spectra
Electronic absorption spectra of the ligand and complexes in ethanol were recorded in the range
Electronic
of the in
ligand
complexes
ethanol were
recorded
in the range
200–700
nm andabsorption
the results spectra
are presented
Tableand
2. The
electronicinabsorption
spectra
of the compounds
200–700
nm
and
the
results
are
presented
in
Table
2.
The
electronic
absorption
spectra
of
the
show absorption bands between 230 and 282 nm, assigned to π–π* transitions. The bandcompounds
at 305 nm
show
absorption
bands
between
230
and
282
nm,
assigned
to
π–π*
transitions.
The
band
at 305 nm
is attributed to n–π* transition from conjugation between the lone pair of electrons on p-orbital
of
isnitrogen
attributed
to
n–π*
transition
from
conjugation
between
the
lone
pair
of
electrons
on
p-orbital
atom and conjugated π-bond of the benzene ring [42]. In the complexes, blue shifts wereof
nitrogen
conjugated
of thebe
benzene
ringof[42].
In the
shifts
observedatom
in theand
π–π*
transitionπ-bond
which could
as a result
removal
of complexes,
lone pair of blue
electron
onwere
the
observed
in the π–π*
which
could
be as a result
removal
lone pairdid
of not
electron
on the
electronegative
atomstransition
of the ligand
upon
coordination
[43].ofThe
Nd(III)ofcomplex
contribute
electronegative
atoms
of the ligand
[43].
complex
did not contribute
appreciably to the
electronic
spectraupon
sincecoordination
for lanthanide
ionsThe
f–f Nd(III)
transitions
are Larporte-forbidden
appreciably
the electronic spectra since for lanthanide ions f–f transitions are Larporte-forbidden
and weak intonature.
and weak in nature.
Table 2. UV-Vis spectral data λmax (nm) of NBTCS and complexes.
Table 2. UV-Vis spectral data λmax (nm) of NBTCS and complexes.
Compound
λmax (nm)
ε (L·mol-1·cm-1)
ῦ (cm-1)
Compound
NBTCS
NBTCS
[Nd(NBTCS)2(H2O)2]NO3
[Tl(NBTCS)
2]CH3COO
[Nd(NBTCS)
2 (H2 O)2 ]NO3
[Tl(NBTCS)2 ]CH3 COO
λmax
272,(nm)
282
(cm-1 )
υ̃
29,239,
30,314
(L·mol-1 ·cm-1 )
Assignment
6925, 6860
Assignment
π–π*
272,305
282
230,305
237, 250
32,787
29,239,
30,314
24,725,32,787
25,477, 26,875
6925,7363
6860
7363
8237,8333,8333
241,237,
248,250
261
230,
241, 248, 261
25,907,
26,659,26,875
28,057
24,725, 25,477,
8333,8333,8333
8237,8333,8333
8333,8333,8333
n–π*
π–π*
n–π*
π–π*
π–π*
π–π*
25,907, 26,659, 28,057
ε
π–π*
2.2. Infrared Spectra
2.2. Infrared
The IRSpectra
spectral data of NBTCS and its complexes are displayed in Table 3. The N–H stretching
−1, this can be seen in Figure 2. However,
vibration
for
NBTCSdata
was observed
a broad
band at 3407
The IR spectral
of NBTCSasand
its complexes
arecm
displayed
in Table 3. The N–H stretching
−
1 , this can
in Nd(III)for
and
Tl(III)was
complexes,
this
disappeared.
This
thatbe
the
N–H
deprotonated
vibration
NBTCS
observed
asband
a broad
band at 3407
cmsuggests
seen
inwas
Figure
2. However,
to complexation.
The IR spectrum
ofdisappeared.
Nd(III) complex
shown in
Figure
3 haswas
a broad
band at
inprior
Nd(III)
and Tl(III) complexes,
this band
Thisassuggests
that
the N–H
deprotonated
−1, assignable to water of hydration from the metal salt. This was further confirmed by the
3399
cm
prior to complexation. The IR spectrum of Nd(III) complex as shown in Figure 3 has a broad band
peak at
cm−1ofdue
to O–H bending
peak
around 3046
atpresence
3399 cmof−1a, sharp
assignable
to778
water
hydration
from thevibrations.
metal salt.The
This
wasobserved
further confirmed
by
−1
−
1
cm
in
the
Tl(III)
complex
was
assigned
to
aromatic
C–H
stretching
vibration.
The
peaks
at
1545
and
the presence of a sharp peak at 778 cm due to O–H bending vibrations. The peak observed around
1465cm
cm−−11ininthe
assigned
C=N stretching
vibration
benzothiazole
ring. InThe
the peaks
Nd(III)at
3046
theligand
Tl(III)were
complex
wastoassigned
to aromatic
C–Hofstretching
vibration.
−1 while in the Tl(III) complex a single peak at 1548 cm−1 was
complex,
these
shifted
to
1589
and
1410
cm
−
1
1545 and 1465 cm in the ligand were assigned to C=N stretching vibration of benzothiazole ring.
obtained.
This complex,
suggest that
the C=N
of benzothiazole
was involved
in theincoordination
[21,29]. This
was
In
the Nd(III)
these
shifted
to 1589 and 1410
cm−1 while
the Tl(III) complex
a single
−1. The medium peaks observed
further
supported
by
emergence
of
M–N
bands
between
392
and
420
cm
−
1
peak at 1548 cm was obtained. This suggest that the C=N of benzothiazole was involved in the
between 1154 and 1120 cm−1 in the compounds were assigned to SO2 stretching vibration. The observed
Molecules 2017, 22, 153
4 of 11
coordination [21,29]. This was further supported by emergence of M–N bands between 392 and
420 cm−1 . The medium peaks observed between 1154 and 1120 cm−1 in the compounds were assigned
2017, 22, 153
4 ofcm
11 −1
toMolecules
SO2 stretching
vibration. The observed decrease in wavenumber of the complexes up to 34
Molecules
2017, 22, 153
4 of 11
suggests coordination through SO2 group. Similar observation has been made in the literature [44].
−1
decrease
wavenumber
of
the
up
to
cm
coordination
through
SO
1 due
The
Nd(III)in
complex
showed
band
at 1349
ionic nitrate
[45]. A medium
assigned
decrease
in
wavenumber
ofnew
thecomplexes
complexes
upcm
to−34
34
cm−1tosuggests
suggests
coordination
throughband
SO22group.
group.
Similar
observation
has
been
made
in
the
literature
[44].
The
Nd(III)
complex
showed
new
band
−
1
observation
has been in
made
the literature
[44].
The cm
Nd(III)
complex
showed
newatband
to Similar
M–O stretch
was observed
the in
Nd(III)
complex
at 621
. The
medium
bands
953,atat
827,
−1 due to ionic nitrate [45]. A medium band assigned to M–O stretch was observed in the Nd(III)
1349
cm
−
1
−1
nitrate
[45]. A medium
band assigned
tobending
M–O stretch
was observed
in the Nd(III)
7501349
andcm
845due
cm to ionic
in
the
compounds
were
assigned
to
C–H
vibration
of
substituted
benzene
−1
−1 in the compounds were assigned
complex
at
cm
medium
bands
827,
750
complex
at621
621
cm−1. .The
The
medium
bandsat
at953,
953,
827,Supplementary
750and
and845
845cm
cm−1Materials.
in the compounds were assigned
ring
[46]. The
spectra
of
the
compounds
are
in the
to
toC–H
C–Hbending
bendingvibration
vibrationof
ofsubstituted
substitutedbenzene
benzenering
ring[46].
[46].The
Thespectra
spectraof
ofthe
thecompounds
compoundsare
arein
inthe
the
Supplementary
Materials.
Supplementary Materials.
Table 3. Infrared spectral data for NBTCS and its complexes.
Compound
Compound
Compound
NBTCS
NBTCS
Table 3. Infrared spectral data for NBTCS and its complexes.
δC–H
complexes.
−1
νNO3and
(ionic)
νC=N data νfor
νC–H spectral
νN–H Table
νO–H
SO2 NBTCS
3. Infrared
its
(cm−1 )
(cm−1 )
(cm−1 )
(cm−1 )
(cm−1 )
(cm−1 )
νO–H
νN–H
νO–H
νN–H
-(cm−1−1)
(cm )
(cm )
3407
- 3407 3399 -
3407(cm−1−1)
NBTCS
[Nd(NBTCS)
2 (H2 O)2 ]NO3
[Nd(NBTCS)
2(H2O)2]NO3
[Tl(NBTCS)
2 ]CH
3 COO
[Nd(NBTCS)
2(H
2O)2]NO3 [Tl(NBTCS)2]CH3COO
[Tl(NBTCS)2]CH3COO
-
-
νC–H
νC–H
(cm
- −1−1)
(cm )
- -
νC=N
νC=N
1545
(cm−1−1)
(cm )
1465
1545
1545
1589
1465
1465
1410
νSO2
νSO2
−1)
(cm
1154
(cm−1)
1154
1154
1120
νNO3 (ionic)
νNO3 (ionic)
(cm−1−1)
(cm )
(cm
δC–H
)
δC–H
953,
−1)
(cm827,
(cm
750−1)
953, 827, 750
953, 827,
1349
- 750
1589
1589
1120
1349
- 3399
1548
1128
845
3399 3142 1120
1349
1410
1410
ν- = stretching
δ = bending-vibrations. 845
3142 vibrations,
1548
1128
3142
1548
1128
845
ν = stretching vibrations, δ = bending vibrations.
ν = stretching vibrations, δ = bending vibrations.
δO–H
(cm−1 )
νM–O
(cm−1 )
νM–N
(cm−1 )
δO–H
δO–H
(cm
- −1)
(cm−1)
778-
νM–O
νM–O
(cm-−1−1)
(cm )
621
νM–N
νM–N
(cm−1-−1)
(cm )
392
778
778
621
621
-
392
420
392
420
420
Figure
IR
spectrumofofN-(Benzothiazol-2-yl)-4-chlorobenzenesulphonamide
N-(Benzothiazol-2-yl)-4-chlorobenzenesulphonamide (NBTCS).
Figure
2. 2.
IR
spectrum
(NBTCS).
Figure
2. IR
spectrum of N-(Benzothiazol-2-yl)-4-chlorobenzenesulphonamide (NBTCS).
Figure 3. IR spectrum of [Nd(NBTCS)2(H2O)2]NO3.
Figure3.3.IRIRspectrum
spectrumof
of[Nd(NBTCS)
[Nd(NBTCS)22(H
3. .
Figure
(H22O)
O)2]NO
2 ]NO
3
13
2.3.1 1H-NMR
1H-NMRand
and1313C-NMR
C-NMRSpectra
Spectra
2.3.2.3.
H-NMR
and
C-NMR
Spectra
In
the
ligand,
the
peaks
obtained
ppm
are
assigned
to
phenyl
and
In
theligand,
ligand,the
thepeaks
peaksobtained
obtained in
in the
the range
range 7.20–7.90
7.20–7.90
ppm
are
assigned
toto
phenyl
and
In
the
in
the
range
7.20–7.90
ppm
are
assigned
phenyl
and
benzothiazole
benzothiazoleprotons.
protons.This
Thisappeared
appearedas
asaacomplex
complexmultiplet
multiplethence
henceseparate
separateassignment
assignmentcould
couldnot
notbe
be
benzothiazole
protons.
This
appeared
as
a
complex
multiplet
hence
separate
assignment
could
made.
made.AAsingle
singlepeak
peakat
at9.35
9.35ppm
ppmisisalso
alsoassigned
assignedto
tobenzothiazole
benzothiazoleprotons.
protons.However,
However,in
inthe
thecomplexes,
complexes,
not
bepeaks
made.
A
single
peak at 9.35
ppm is also
assigned
benzothiazole
protons.
However,
in the
the
are
clearly
separated.
In
[Nd(NBTCS)
2(H
2O)2]NO3, to
the
peak
at
7.15
(2H,
d)
ppm
the peaks are clearly separated. In [Nd(NBTCS)2(H2O)2]NO3, the peak at 7.15 (2H, d) ppmand
and7.35
7.35ppm
ppm
complexes,
the peakstoare
clearly separated.
In [Nd(NBTCS)
peak atm)
7.15 (2H,
d) ppm
(2H,
of
2 (H2 O)
2 ]NO3 , the
(2H,d)
d)are
areassigned
assigned tophenyl
phenylprotons
protonswhile
whilethe
thepeaks
peaksatatthe
therange
range
of7.60–8.20
7.60–8.20ppm
ppm(4H,
(4H, m)are
areassigned
assigned
to
benzothiazole
protons.
In
[Tl(NBTCS)
2]CH3COO, the peaks at 7.10 (2H, d) ppm and 7.25 (2H, d)
to benzothiazole protons. In [Tl(NBTCS)2]CH3COO, the peaks at 7.10 (2H, d) ppm and 7.25 (2H, d)
ppm
ppmare
areassigned
assignedto
tothe
thetwo
twochemically
chemicallyequivalent
equivalentphenyl
phenylprotons
protonswhile
whilethe
thepeaks
peaksat
at7.28,
7.28,7.47,
7.47,7.52
7.52
and
7.79
ppm
(4H,
m)
are
assigned
to
benzothiazole
protons.
Similar
observation
has
been
and 7.79 ppm (4H, m) are assigned to benzothiazole protons. Similar observation has beenmade
madein
in
Molecules 2017, 22, 153
5 of 11
and 7.35 ppm (2H, d) are assigned to phenyl protons while the peaks at the range of 7.60–8.20 ppm (4H,
m) are assigned to benzothiazole protons. In [Tl(NBTCS)2 ]CH3 COO, the peaks at 7.10 (2H, d) ppm and
7.25 (2H, d) ppm are assigned to the two chemically equivalent phenyl protons while the peaks at 7.28,
Molecules
2017, 22,
153 (4H, m) are assigned to benzothiazole protons. Similar observation has been
5 of 11
7.47, 7.52
and 7.79
ppm
Molecules
2017, 22, 153
5 ofppm
11
made
in literature
[21,22,29,44,47]. The chemical shift due to the N–H proton is observed at 13.30
[21,22,29,44,47].
chemical
shift due to indicating
the N–H proton
is observed at
ppm
forIn
the
for theliterature
ligand but
disappeared The
in the
metal complexes
its replacement
by13.30
metal
ions.
literature
The
due to the
N–H proton
is observed by
at 13.30
ligand[21,22,29,44,47].
but disappeared
inchemical
the metalshift
complexes
indicating
its replacement
metalppm
ions.for
Inthe
Tl(III)
Tl(III) complex, peaks at 3.34 ppm (3H, s) are assigned to CH3 protons of acetate [22]. The spectra of
ligand
but disappeared
in ppm
the metal
complexes
indicating
its replacement
by[22].
metal
In Tl(III)
complex,
peaks at 3.34
(3H, s)
are assigned
to CH3 protons
of acetate
Theions.
spectra
of all the
all the compounds showed a multiplet centered at 2.50 ppm due to DMSO [46].
complex,
peaks at
3.34 ppm
(3H, s) are
assigned
to CH
3 protons
acetate
[22].13The spectra of all the
compounds
showed
a multiplet
centered
at 2.50
ppm
due to of
DMSO
[46].
Figure 4 gives the structure of the ligand showing carbon numbering. 13 C-NMR spectrum of
compounds
showed
a multiplet
centered
2.50 ppm
due to
DMSO
[46].
Figure
4 gives
the structure
of theatligand
showing
carbon
numbering.
C-NMR spectrum of the
the ligand
as
shown
in
Figure
5
has
a
peak
at
115.80
ppm
attributed
to benzothiazole
ring of
carbon
13C-NMR spectrum
Figureas4 gives
ligand
carbon
numbering.
the(C1).
ligand
shownthe
instructure
Figure 5 of
hasthe
a peak
atshowing
115.80 ppm
attributed
to benzothiazole
ring carbon
(C1).
Peaks
assigned
tobenzothiazole
benzothiazole
ring
carbon
(C2)
appear
at
ppm. Peaks
at
139.0
and
ligand
as shown
in to
Figure
5 has a peak
115.80
ppm
attributed
to 126.70
benzothiazole
(C1).
Peaks
assigned
ringat
carbon
(C2)
appear
at 126.70
ppm. Peaks atring
139.0carbon
and 140.0
ppm
140.0
ppm
are
assigned
to
benzothiazole
ring
carbon
(C3)
and
(C4)
respectively.
Peak
at
170.10
ppm
Peaks
at 126.70
ppm. Peaks
139.0 and
140.0
ppm
areassigned
assignedtotobenzothiazole
benzothiazolering
ringcarbon
carbon(C2)
(C3)appear
and (C4)
respectively.
Peak at 170.10
ppm
is attributed
is attributed
totobenzothiazole
ring
carbon
(C5).
Peaks
at
132.10
and
ppm
areis assigned
to
are assigned
benzothiazole
ring
carbon
(C3)
(C4)
respectively.
Peak
at 170.10
ppm
attributed
to benzothiazole
ring carbon
(C5).
Peaks
at and
132.10
and
143.60
ppm
are143.60
assigned
to
phenyl
ring carbon
phenyl
ringand
carbon
(C6)
and (C9)
respectively.
increase
inof
chemical
ofphenyl
C6 and
C9carbon
are in
due
to benzothiazole
carbon
(C5).
Peaks
at 132.10
and
143.60
ppm
are
to
(C6)
(C9)ring
respectively.
The
increase
inThe
chemical
shift
C6 assigned
and shift
C9 are
due
to ring
increase
the
to increase
in
the
electronegativity
of
the
atoms
attached
to
them.
C9
shows
a
higher
value
than
(C6)electronegativity
and (C9) respectively.
The increase
into
chemical
shift
of C6
and C9value
are due
increase
theC6
of the atoms
attached
them. C9
shows
a higher
thantoC6
becauseinchlorine
because
chlorine
which
to it to
is more
than
which
is attached
to
electronegativity
of the
attached
them. electronegative
C9
shows
a higher
value
than C6
because
chlorine
which
is attached
toisatoms
itattached
is more
electronegative
than
sulphur
which
issulphur
attached
to C6.
Peaks
assignable
C6.which
Peaks
toisphenyl
ring
and
(C8)
are observed
at to
130.30
and 130.60
ppm
is assignable
attached
it
more
electronegative
than
sulphur
which
is attached
C6. respectively.
Peaks
assignable
to phenyl
ringtocarbon
(C7)
and carbon
(C8) are(C7)
observed
at 130.30
and
130.60
ppm
Similar
13C-NMR
to phenyl
ring
carbon
(C7)made
and (C8)
are
observed
at literature
130.30
130.60 of
ppm
Similar
observations
have
been
in
literature
[21,22,29,44].
Theand
the respectively.
complexes
show
none
respectively.
Similar
observations
have
been
made
in
[21,22,29,44].
The 13 C-NMR
of
theof
13C-NMR of the complexes show none of
observations
have
been
made
in
literature
[21,22,29,44].
The
the peaks
forthe
thepeaks
solvent
peakfor
at the
40.0solvent
ppm. The
spectra
the compounds
areofinthe
the
complexes
show except
none of
except
peak
at 40.0ofppm.
The spectra
the Supplementary
peaksare
except
the solvent peak
at 40.0 ppm. The spectra of the compounds are in the
Materials.
compounds
in thefor
Supplementary
Materials.
Supplementary Materials.
2
1
1
2
3
1
3
S
4
1
2
4
2
S
5
NH
H
5N N
N
O
OS
SO
O
7
6
6
7
7
7
8
8 9
8
8
9
Cl
Cl
4. Structure
the ligand
showing
carbon
numbering.
FigureFigure
4. Structure
of theofligand
showing
carbon
numbering.
Figure 4. Structure of the ligand showing carbon numbering.
(ppm)
(ppm)
Figure 5. 13C-NMR spectrum of NBTCS.
13
Figure 5. C-NMR spectrum of NBTCS.
13 C-NMR spectrum of NBTCS.
Based on the spectral Figure
results,5.coordination
numbers of eight and six were proposed for Nd(III)
Based
on the
spectral respectively,
results, coordination
and
Tl(III)
complexes,
as shownnumbers
in Figureof6.eight and six were proposed for Nd(III)
and Tl(III) complexes, respectively, as shown in Figure 6.
Molecules 2017, 22, 153
6 of 11
Based on the spectral results, coordination numbers of eight and six were proposed for Nd(III)
and
Tl(III)
complexes,
respectively, as shown in Figure 6.
Molecules 2017,
22, 153
6 of 11
+
O
S
Molecules 2017, 22, 153
Molecules 2017, 22, 153
N
N
S
S
O
O
O
N S
N Tl S
O
O
N
N
N
S
N
N
S
S
O
Tl
NTl S
O
O
O
N S
N S
O
O
N
Cl
S
N
S
S
+
+
Cl
Cl
CH 3COO
-
CH 3COO CH 3COO
Cl
Figure 6. Proposed
Cl
Figure 6. Proposed
S
O
O
O
N S
N Nd S
O
O
N
N
H2O
H2O
6 of 11
6 of 11
Cl
+
+
O
Nd
NNd S
S
O
O
N
O
N
N S
structure of the complexes.
structure of the complexes.
N S
S
O
S
O
-
Cl
H2O
+
O
S
N
Cl
OH2 Cl
NO 3
OH2
OH2 Cl
NO 3 NO 3
-
-
Cl
Cl
2.4. Antibacterial Activity
2.4. Antibacterial Activity
Figure 6. Proposed structure of the complexes.
Figurewere
6. Proposed
structure
thetheir
complexes.
The ligand and its complexes
screened
in vitrooffor
antibacterial activity against multiThe
ligand
and
its
complexes
were
screened
in
vitro
for their
antibacterial
activity
against
resistant
bacterial
strains
isolated
under
clinical
conditions
namely:
Escherichia
coli strains
(E. coli
6
2.4. Antibacterial Activity
2.4.
Antibacterial
Activity
multi-resistant
bacterial
isolated
under clinical
namely:aeruginosa.
EscherichiaThe
coliantibacterial
strains (E. coli
and E. coli 13),
Proteusstrains
species,
Staphylococcus
aureus conditions
and Pseudomonas
The
and its species,
complexes
were screenedaureus
in vitro
forPseudomonas
their antibacterial
activityThe
against
multi6 and
E.
coliligand
13),
and
aeruginosa.
antibacterial
activities
of
the Proteus
compounds
wereStaphylococcus
determined
usinginthe
agar
diffusion
method
[48]. The
inhibitory
The
ligand
and its complexes
were screened
vitro
forwell
their
antibacterial
activity
against
multiresistant
bacterial
strains
isolated
under
clinical
conditions
namely:
Escherichia
coli
strains
(E.
coli 6
activities
of bacterial
the compounds
were determined
using
the agar well
diffusion
method
[48].
The(E.
inhibitory
zone
diameter
(IZD)
and minimum
inhibition
concentration
(MIC)
in μg/mL
of the
were
resistant
strains
isolated
under
clinical
conditions
namely:
Escherichia
colicompounds
strains
coli 6
anddiameter
E. coli 13),
Proteus
Staphylococcus
aureus
and Pseudomonas
aeruginosa.
Thethe
antibacterial
zone
(IZD)
andspecies,
minimum
inhibition
concentration
(MIC)
in
µg/mL
of
compounds
determined.
Co-trimoxazole,
ciprofloxacin
and gentamicin
used
as positive
control.
structure
and E. coli 13),
Proteus
species,
Staphylococcus
aureus
andwere
Pseudomonas
aeruginosa.
TheThe
antibacterial
activities of the compounds were determined using the agar well diffusion method [48]. The inhibitory
were
determined.
Co-trimoxazole,
ciprofloxacin
and
gentamicin
were
used [48].
as positive
of
these
drugs
shown
in were
Figures
7–9
respectively.
Gentamicin
belongs
tomethod
aminoglycosides
andcontrol.
their
activities
of theare
compounds
determined
using the
agar
well diffusion
The inhibitory
zone diameter (IZD) and minimum inhibition concentration (MIC) in μg/mL of the compounds were
mechanism
of
action
is
by
inhibition
of
protein
synthesis
by
preventing
the
synthesis
of
nucleic
acids
The
structure
these
are shown
inconcentration
Figures 7–9(MIC)
respectively.
Gentamicin
belongs
zone
diameterof(IZD)
anddrugs
minimum
inhibition
in μg/mL of
the compounds
were to
determined. Co-trimoxazole, ciprofloxacin and gentamicin were used as positive control. The structure
(DNA
replication
or RNA
thereby
blocking
transcription.
Ciprofloxacin
belongs
quinolones
determined.
Co-trimoxazole,
ciprofloxacin
gentamicin
were used
positive
control. to
The
structure
aminoglycosides
and
theirsynthesis),
mechanism
of and
action
is by
inhibition
of as
protein
synthesis
by
preventing
of these drugs are shown in Figures 7–9 respectively. Gentamicin belongs to aminoglycosides and their
inhibit
bacteria
growth
by
preventing
DNA or
synthesis
before
mitosis
Co-trimoxazole
is a
ofsynthesis
these
drugs
shown
in Figures
7–9
respectively.
Gentamicin
belongs
to [49].
aminoglycosides
and their
theand
of are
nucleic
acids
(DNA
replication
RNA
synthesis),
thereby
blocking
transcription.
mechanism of action is by inhibition of protein synthesis by preventing the synthesis of nucleic acids
sulphonamide,
known
to
prevent
the
growth
of
microorganisms
by
inhibiting
folic
acid
production.
mechanism
of
action
is
by
inhibition
of
protein
synthesis
by
preventing
the
synthesis
of
nucleic
acids
Ciprofloxacin
belongs to quinolones and inhibit bacteria growth by preventing DNA synthesis before
(DNA replication or RNA synthesis), thereby blocking transcription. Ciprofloxacin belongs to quinolones
Co-trimoxazole
contains
a fixed
combination
of sulphamethoxazole
andgrowth
trimethoprim.
(DNA[49].
replication
or RNA synthesis),
thereby blocking
transcription.
Ciprofloxacin
belongs
to quinolonesby
mitosis
Co-trimoxazole
sulphonamide,
to prevent
the
microorganisms
and inhibit bacteria growth is
bya preventing
DNAknown
synthesis
before mitosis
[49]. of
Co-trimoxazole
is a
and inhibit
growth by Co-trimoxazole
preventing DNAcontains
synthesisa fixed
beforecombination
mitosis [49]. of
Co-trimoxazole
is a
inhibiting
folicbacteria
acid
production.
sulphamethoxazole
sulphonamide,
known
to prevent
the
growth
of
microorganisms
by
inhibiting
folic
acid
production.
N
NH
2 growth of microorganisms by inhibiting folic acid production.
sulphonamide,
known
to
prevent
the
and
trimethoprim.contains a fixed combination of sulphamethoxazole and trimethoprim.
Co-trimoxazole
Co-trimoxazole contains a fixedNcombination of sulphamethoxazole and trimethoprim.
N
NH
N 2
NH2
NH2
N
N
NH
OCH
2 3
NH2
H3CO
H2N
SO2NH
H2N
H2N
SO2NH
SO2NH
N
OCH 3
Trimethoprim
OCH 3
CO
H3
H3CO
OCH 3
O
CH3
N
N
Sulphamethoxazole
O
O
CH3
CH3
Figure 7. Structure of co-trimoxazole.
OCH 3
OCH 3
Trimethoprim
Trimethoprim
Sulphamethoxazole
Sulphamethoxazole
O
O
Figure 7.
7. Structure of
Figure
of co-trimoxazole.
co-trimoxazole.
Figure 7.FStructure
Structure of
co-trimoxazole.
HN
HN
HN
NF
F
O
O
N
N
N
N
N
O
O
Figure 8. Structure of ciprofloxacin.
Figure 8. Structure of ciprofloxacin.
Figure8.
8. Structure
Structure of
Figure
of ciprofloxacin.
ciprofloxacin.
OH
OH
OH
Molecules 2017, 22, 153
Molecules 2017, 22, 153
7 of 11
7 of 11
H2N
O
HO
O
CH3
O
NH2
NH2
O
NH2
HO
OH
H3C
NH
H3C
Figure
Figure 9.
9. Structure
Structure of
of gentamicin.
gentamicin.
The result of the IZD (Table 4) shows that the metal complexes exhibit higher antibacterial
The result of the IZD (Table 4) shows that the metal complexes exhibit higher antibacterial activity
activity against the microorganisms relative to the ligand. It was also observed that the ligand did
against the microorganisms relative to the ligand. It was also observed that the ligand did not inhibit
not inhibit the growth of S. aureus and P. aeruginosa. Likewise, the thallium complex had no effect on
the growth of S. aureus and P. aeruginosa. Likewise, the thallium complex had no effect on P. aeruginosa.
P. aeruginosa. The increase in antibacterial activity of the metal chelates might be due to the effect of
The increase in antibacterial activity of the metal chelates might be due to the effect of the metal
the metal ion on the normal cell process. Chelation reduces the polarity of the metal ion because of
ion on the normal cell process. Chelation reduces the polarity of the metal ion because of partial
partial sharing of its positive charge with donor groups and the π-electron delocalization over the
sharing of its positive charge with donor groups and the π-electron delocalization over the whole
whole chelate ring. Such chelation could enhance the lipophilic character of the central metal atom,
chelate ring. Such chelation could enhance the lipophilic character of the central metal atom, which
which subsequently favours its permeation through the lipid layers of the cell membrane [50]. From
subsequently favours its permeation through the lipid layers of the cell membrane [50]. From the MIC
the MIC values (Table 5), it is observed that the synthesized compounds are more active against
values (Table 5), it is observed that the synthesized compounds are more active against Escherichia coli
Escherichia coli strains 6 and 13 relative to the standard drugs, since the lower the MIC value, the more
strains 6 and 13 relative to the standard drugs, since the lower the MIC value, the more effective the
effective the antibacterial activity of the drug. However, Ciprofloxacin has a higher antibacterial
antibacterial activity of the drug. However, Ciprofloxacin has a higher antibacterial activity against
activity against S. aureus and Proteus species compared to the compounds. It can also be inferred from
S. aureus and Proteus species compared to the compounds. It can also be inferred from Table 5 that the
Table 5 that the synthesized compounds have better antibacterial activity against the microorganisms
synthesized compounds have better antibacterial activity against the microorganisms screened relative
screened relative to Gentamicin and Co-trimoxazole.
to Gentamicin and Co-trimoxazole.
Table 4. Antibacterial activity of NBTCS, [Nd(NBTCS)2(H2O)2]NO3 and [Tl(NBTCS)2]CH3COO.
Table 4. Antibacterial activity of NBTCS, [Nd(NBTCS)2 (H2 O)2 ]NO3 and [Tl(NBTCS)2 ]CH3 COO.
Compounds
Compounds
NBTCS
[Nd(NBTCS)
2(H2O)2]NO3
NBTCS
[Nd(NBTCS)
2 O)3COO
2 ]NO3
[Tl(NBTCS)22(H
]CH
[Tl(NBTCS)2 ]CH3 COO
IZD Values (mm)
IZD Values (mm)
E. coli 6 E.
coli 13
S. aureus
P. aeruginosa
E. coli
E.10
coli 13
S.
P. aeruginosa
136
0 aureus
0
1410
17 0
120
1315
1512
1214
15 17
0 12
12
12
15
IZD: inhibitory zone diameter.
0
Proteus species
Proteus12
species
16
12
16
12
12
IZD: inhibitory zone diameter.
Table 5. MIC values of the compounds and standard drugs.
Table 5. MIC values of the compounds and standard drugs.
MIC Values (μg/mL)
Compounds
E. coli 6 MIC
E. Values
coli 13 (µg/mL)
S. aureus P. aeruginosa Proteus species
NBTCS
3.16
4.57
0.00
3.39
Compounds
E. coli 6
E. coli 13
S. aureus
P.0.00
aeruginosa
Proteus
species
[Nd(NBTCS)
2(H2O)2]NO3
1.78
2.19
1.45
3.31
1.26
NBTCS
3.16
4.57
0.00
0.00
3.39
[Tl(NBTCS)
2]CH
3.47
3.47
1.26
0.00
3.47
[Nd(NBTCS)
]NO3
1.78
2.19
1.45
3.31
1.26
2 (H
2 O)23COO
[Tl(NBTCS)
3.47
3.47
1.26
0.00
3.47
Ciprofloxacin
20.00
20.00
0.63
10.00
0.16
2 ]CH3 COO
Ciprofloxacin
20.00
20.00
0.63
10.00
0.16
Gentamicin
100.00
100.00
2.50
20.00
5.00
Gentamicin
100.00
100.00
2.50
20.00
5.00
Co-trimoxazole
100.00
100.00
50.00
170.00
30.00
Co-trimoxazole
100.00
100.00
50.00
170.00
30.00
MIC: minimum inhibition concentration; 0.00 = no antibacterial activity.
MIC: minimum inhibition concentration; 0.00 = no antibacterial activity.
Molecules 2017, 22, 153
8 of 11
3. Materials and Methods
3.1. Materials
All the reagents and solvents used were of analytical grade and were used as supplied unless
otherwise stated. The melting point of the ligand and the complexes were determined using a
Gallenkamp melting point apparatus (Weiss Technik, Loughborough, UK) and were uncorrected.
Electronic spectra (in ethanol) were recorded on a UV-2500PC series spectrophotometer (SHIMADZU,
Tokyo, Japan). The FTIR spectra were performed using FTIR-8400S Spectrophotometer (SHIMADZU),
in the range 4500–200 cm−1 using KBr. The 1 H- and 13 C-NMR of the ligand were recorded on Bruker
Spectrospin 250(Bruker, Billerica, MA, USA) using DMSO while the elemental analysis was done using
Euro EA 3000 Dual CHNS Analyzer (Eurovector S.P.A, Zurich, Switzerland) both at the Department of
Chemistry, University of Mauritius.
3.2. Synthesis of N-(Benzothiazol-2-yl)-4-chlorobenzenesulphonamide (NBTCS)
To a solution of 2-aminobenzothiazole (3.0 g; 20 mmol) in acetone (15 mL) was added
4-chlorobenzenesulphonylchloride (4.24 g; 20 mmol) with stirring. The mixture was refluxed for
45 min at 130 ◦ C. A white precipitate was formed, which was recrystallized from absolute ethanol,
dried and stored in a desiccator over anhydrous CaCl2 . This is shown in Scheme 1. The yield was
40.83% and the melting point 220–222 ◦ C.
3.3. Synthesis of [N-(Benzothiazol-2-yl)-4-chlorobenzenesulphonamide] Neodymium(III) Complex,
[Nd(NBTCS)2 (H2 O)2 ]NO3
To a solution of N-(benzothiazol-2-yl)-4-chlorobenzenesulphonamide (1.62 g; 5.17 mmol) in
acetone (10 mL) was added aqueous solution of neodymium(III) nitrate pentahydrate, Nd(NO3 )3 ·5H2 O
(1.05 g; 1.37 mmol). This was refluxed for 1 h at 120 ◦ C during which a yellow precipitate was formed.
The resulting yellow precipitate formed was filtered, dried in a stream of air and stored in a desiccator
over anhydrous CaCl2 . The yield was 32.24% and the melting point is 245–247 ◦ C.
3.4. Synthesis of [N-(Benzothiazol-2-yl)-4-chlorobenzenesulphonamide] Thallium(III) Complex,
[Tl(NBTCS)2 ]CH3 COO
To a solution of N-(benzothiazol-2-yl)-4-chlorobenzenesulphonamide (1.62 g; 5.17 mmol) in
acetone (10 mL) was added aqueous solution of thallium(III) acetate, C6 H9 O6 Tl (0.95 g; 1.14 mmol).
This was refluxed for 1 h at 120 ◦ C during which a brown precipitate was formed. The resulting brown
precipitate formed was filtered, dried in a stream of air and stored in a desiccator over anhydrous
CaCl2 . The yield was 34.97% and the melting point is 235–237 ◦ C.
3.5. Antibacterial Activity
The inhibitory activity of the ligand and its metal complexes were carried out on the following
microorganisms: Escherichia coli strains (E. coli 6 and E. coli 13), Proteus species, Staphylococcus aureus and
Pseudomonas aeruginosa. The bacteria strains used were isolated from clinical conditions. The method
used was the agar well-diffusion Technique [46]. Mueller-Hinton agar plates were inoculated with
0.1 mL of 3 h broth culture of the test microorganisms. Using a cork borer, wells (7 mm in diameter and
2.5 mm deep) were bored into the inoculated agar. Fresh solutions (1000 µg/mL) of all the synthesized
compounds were prepared in DMSO and 50 µL of each compound was delivered into the wells.
Wells containing 1000 µg/mL of ciprofloxacin, gentamicin and co-trimoxazole in DMSO were used as
positive controls. The plates were incubated at 37 ◦ C for 24 h and assessment of antibacterial activity
was based on the measurement of the diameter of inhibition zone (IZD) around the wells.
The minimum inhibitory concentrations (MIC) of the test compounds were determined using the
same method. Two-fold serial dilutions of test compound were made in DMSO. The final concentration
of the compounds ranged from 250 to 0.625 µg/mL. Inoculated plates were incubated at 37 ◦ C for 24 h
Molecules 2017, 22, 153
9 of 11
and observed for presence of visible growth. The minimum inhibition concentration was determined
as the value of the lowest concentration that completely suppressed the growth of the microorganisms.
4. Conclusions
NBTCS and its neodymium(III) and thallium(III) complexes were synthesized. Based on the UV,
IR and NMR spectral studies and elemental analysis, a coordination number of eight was proposed for
neodymium(III) complex and six for thallium(III) complex. The antibacterial activity revealed that
the synthesized compounds have better antibacterial activity against the microorganisms screened
relative to gentamicin and co-trimoxazole. The low MIC values observed for NBTCS and its complexes
indicate the potency of these compounds as antibacterial agents. This serves as a marker in drug
design, hence these compounds should be screened for in vivo antibacterial activity and the lethal
dose (LD50 ) determined.
Supplementary Materials: The following are available online at: http://www.mdpi.com/1420-3049/22/2/153/s1,
FTIR Spectra, electronic spectra, 1 H-NMR and 13 C-NMR of the ligand and complexes.
Acknowledgments: The authors acknowledge the facilities from their respective universities and the comments
to anonymous reviewers. Ibrahim Abdulrazak Al-Swaidan (I.A.A.-S.) and Ponnadurai Ramasami (P.R.) extend
their appreciation to the International Scientific Partnership Program ISPP at King Saud University for funding
this research work through ISPP# 0070.
Author Contributions: L.N.O. conceived, designed and supervised the experiment. U.S.O. performed the
experiment. I.A.A.-S. and P.R. carried out the elemental analysis and 1 H- and 13 C-NMR spectroscopy of the
synthesized compounds. A.E.O. contributed in proofreading of the entire work and made professional input.
C.J.E. contributed in proofreading of the entire work. U.S.O. wrote the paper.
Conflicts of Interest: The authors declare no conflict of interest.
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