New 2-pyridinealdehyde N4-hydroxyethyl thiosemicarbazone and their Cd(II) and Cu(II) complexes: Synthesis, spectral, in vitro antibacterial activity and molecular and supramolecular structure study

Article abstract of DOI:10.1080/17415993.2010.507815

N4-hydroxyethyl-pyridinealdehyde thiosemicarbazone (HL, 1) as a tridentate Schiff base has been synthesized by 1:1 reaction of S-methyl-3-((pyridyl)methyl) dithiocarbazate and 2-aminoethanol. Complexes [Cd(HL)2](NO3)2 (2), [Cd(HL)I2] (3), [Cd(HL)Cl2] (4), [Cu(HL)2](NO3)2 (5) and [Cu(HL)Cl2] (6) have been obtained and characterized by elemental analyses, molar conductivities, and spectroscopic studies. The ligand molecule binds the metal ion using pyridyl nitrogen, azomethine nitrogen and the sulfur atoms. The crystal structure analysis of 3 has been determined and showed to be a distorted square pyramidal geometry complex. The inter- and intramolecular interactions give rise to a supramolecular network. Compounds 2, 3, 5 and 6 were assayed for their bioactivities against selected pathogens. Copper(II) complexes 5 and 6 showed antimicrobial activities against Gram-positive (Bacillus anthracis) and Gram-negative (Pseudomonas aeruginosa and Yersinia pseudotuberculosis) bacteria, complexes 2-4 showed antimicrobial activities against Bacillus atrophaeus, while the ligand itself showed antimicrobial activities against Escherichia coli and Y. pseudotuberculosis.

Full text of DOI:10.1080/17415993.2010.507815

This article was downloaded by: [University of Chemical Technology and Metallurgy -
Sofia]
On: 24 November 2014, At: 04:27
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Journal of Sulfur Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/gsrp20
New 2-pyridinealdehyde N 4-
hydroxyethyl thiosemicarbazone and
their Cd(II) and Cu(II) complexes:
synthesis, spectral, in vitro
antibacterial activity and molecular
and supramolecular structure study
Reza Takjoo a , Mohammad Hakimi b , Mohammad Seyyedin c &
Mozhgan Abrishami b
a Department of Chemistry, School of Sciences , Ferdowsi
University of Mashhad , Mashhad, 91775-1436, Iran
b Department of Chemistry , Payame Noor University (PNU) ,
Mashhad, Iran
c Department of Quality Control , Razi Vaccine and Serum
Research Institute , Mashhad, Iran
Published online: 28 Sep 2010.
To cite this article: Reza Takjoo , Mohammad Hakimi , Mohammad Seyyedin & Mozhgan Abrishami
(2010) New 2-pyridinealdehyde N 4-hydroxyethyl thiosemicarbazone and their Cd(II) and Cu(II)
complexes: synthesis, spectral, in vitro antibacterial activity and molecular and supramolecular
structure study, Journal of Sulfur Chemistry, 31:5, 415-426, DOI: 10.1080/17415993.2010.507815
To link to this article: http://dx.doi.org/10.1080/17415993.2010.507815
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,

proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &
Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Journal of Sulfur Chemistry
Vol. 31, No. 5, October 2010, 415–426
New 2-pyridinealdehyde N4-hydroxyethyl thiosemicarbazone
and their Cd(II) and Cu(II) complexes: synthesis, spectral,
in vitro antibacterial activity and molecular and supramolecular
structure study
Reza Takjooa*, Mohammad Hakimib, Mohammad Seyyedinc and Mozhgan Abrishamib
aDepartment of Chemistry, School of Sciences, Ferdowsi University of Mashhad, Mashhad 91775-1436,
Iran; bDepartment of Chemistry, Payame Noor University (PNU), Mashhad, Iran; cDepartment of Quality
Control, Razi Vaccine and Serum Research Institute, Mashhad, Iran
(Received 25 March 2010; final version received 4 July 2010)
N4-hydroxyethyl-pyridinealdehyde thiosemicarbazone (HL, 1) as a tridentate Schiff base has been syn-
thesized by 1:1 reaction of S-methyl-3-((pyridyl)methyl) dithiocarbazate and 2-aminoethanol. Complexes
[Cd(HL)2](NO3)2 (2), [Cd(HL)I2] (3), [Cd(HL)Cl2] (4), [Cu(HL)2](NO3)2 (5) and [Cu(HL)Cl2] (6) have
been obtained and characterized by elemental analyses, molar conductivities, and spectroscopic studies.
The ligand molecule binds the metal ion using pyridyl nitrogen, azomethine nitrogen and the sulfur atoms.
The crystal structure analysis of 3 has been determined and showed to be a distorted square pyramidal
geometry complex. The inter- and intramolecular interactions give rise to a supramolecular network. Com-
pounds 2, 3, 5 and 6 were assayed for their bioactivities against selected pathogens. Copper(II) complexes
5 and 6 showed antimicrobial activities against Gram-positive (Bacillus anthracis) and Gram-negative
(Pseudomonas aeruginosa and Yersinia pseudotuberculosis) bacteria, complexes 2–4 showed antimicro-
bial activities against Bacillus atrophaeus, while the ligand itself showed antimicrobial activities against
Escherichia coli and Y. pseudotuberculosis.
Keywords: thiosemicarbazone; transition metal complex; antibacterial activity; crystal structure;
supramolecular
1. Introduction
Thecoordinationchemistryofsubstitutedthiosemicarbazoneswithtransitionmetalshasdisplayed
various bonding properties in their complexes and has shown their use in a variety of different
applications (1–3). The presence of hard N- and soft S-donor atoms in the backbones of these
ligands enables them to react readily with both transition and main group metal ions yielding
stable metal complexes. Owing to this biological activity, there is a considerable interest in metal
complexes of heterocyclic thiosemicarbazones (4).
*Corresponding author. Email: rezatakjoo@yahoo.com
ISSN 1741-5993 print/ISSN 1741-6000 online
© 2010 Taylor & Francis
DOI: 10.1080/17415993.2010.507815
http://www.informaworld.com

416 R. Takjoo et al.
Figure 1. Structure of 2-pyridinealdehyde N4-hydroxyethyl thiosemicarbazone (HL, 1).
In many cases, the pharmacological activity has been found to be highly dependent on the
=
identity of the metal, chemical nature of the moiety attached to the C S carbon atom and the donor
sequence of the ligands. Furthermore, various ligands widely show different biological activities
while their molecular structure may slightly vary; the mechanism is yet to be determined (5–6).
The development of the pathways that control the architecture of artificial supramolecular systems
is one of the major goals in the field of supramolecular chemistry (7). In some thiosemicarbazones,
there are suitable hydrogen bonds to form supramolecular structures which make them appealing
for study. Various columbic and hydrogen interactions between suitable species can create a
supramolecular network. The hydrogen bonds between a donor atom couple and an acceptor atom
couple in adjacent molecules will increase the probability of the formation of the supramolecular
network. Although generally considered weak, the hydrogen bonding involving the sulfur atom
takes a significant place among the stabilizing factors (8).
In the work reported here, the new tridentate thiosemicarbazone ligand N-(2-hydroxyethyl)-
2-(pyridin-2-ylmethylene)hydrazinecarbothioamide (HL, 1) (Figure 1) and its Cd(II) and Cu(II)
complexes have been synthesized. The HL molecule is designed as two parts. The first part
hydroxyethyl increases the supramolecular formation by providing hydrogen bonds. The second
part, pyridyl ring, is selected according to its expected biological activities.
1
These compounds were characterized by H NMR, 13C NMR, Infrared (IR), UV–VIS, and
carbon hydrogen nitrogen sulfur (CHNS) analyses. The structure of [Cd(HL)I2] (3) complex
has been determined by X-ray crystallography. Furthermore, the biological activities of a set of
synthesized thiosemicarbazones compounds against a panel of Gram-positive bacteria including
Staphylococcus aureus, Bacillus anthracis and Bacillus atrophaeus and Gram-negative bacteria
includingYersinia pseudotuberculosis, Escherichia coli and Pseudomonas aeruginosa have been
studied.
2. Results and discussion
The thiosemicarbazone ligand and complexes were prepared as described in Section 4. N-(2-
hydroxyethyl)-2-(pyridin-2-ylmethylene)hydrazinecarbothioamide (HL, 1) like most thiosemi-
carbazones can exhibit thione–thiol tautomerism (Figure 1).
HL interacts with metal ions in a molar ratio of 2:1 or 1:1, in the presence of appropriate
anions, yielding complexes with the empirical formula of [Cd(HL)2](NO3)2 (2), [Cd(HL)I2] (3),
[Cd(HL)Cl2] (4), [Cu(HL)2](NO3)2 (5) and [Cu(HL)Cl2] (6). This tridentate ligand acts as a
thione form in all complexes. The color, yield, molar conductance and elemental analysis data of
all the complexes are presented in Section 4. All of the compounds are stable in air and can be
kept in a desiccator for a long time without any signs of decomposition. The molar conductivities
of 10−3 M solutions in dimethylformamide (DMF) of the complexes indicate that the molar
conductance of compounds 3, 4 and 6 falls well below the value expected for a 1:1 electrolyte
and they are non-electrolytes. Conductivity data for 2 and 5 point to their electrolytic nature.
According to the reports of similar structures (9–15) and following results, compounds 2 and 5
have a distorted octahedral geometry and the other complexes have a distorted square pyramidal
geometry.

Journal of Sulfur Chemistry 417
2.1. IR spectra
The IR spectra of the free ligand and metal complexes were studied and assigned based on their
comparison. The assignments of main IR bands of the compounds in 400–4000 cm−1 region are
presented in Section 4. The strong bands at 3222 and 3151 cm−1 in the spectra of the ligand have
4
3
−
−
been assigned to ν( N H) and ν( N H), respectively (Figure 1).
4
−
In the complexes, the stretching bond of ν( N H) shift to both higher and lower energies,
4
suggesting differences in hydrogen bonding of NH between the uncomplexed and complexed
thiosemicarbazone (16). The ligand displays no band at ca. 2800–2550 cm−1 region associated
−
with ν(S H) (17), indicating that it exists in the thione form in the solid state. The out-of-
plane bending vibrations of the pyridine ring at 634 cm−1 in the spectrum of 1 are shifted on
complexation, suggesting the coordination of the ligand to the metal ions via the pyridine nitrogen
(18). A strong band at 1068 cm−1 in the compound 1 is assigned to the ν(N N) vibration which
−
is observed in the range of 1074–1047 cm−1 after coordination (19). In the spectrum of the free
base 1, the absorption at ca. 879 cm−1 is attributed to the δ(CS) vibration, and in the spectra of
the complexes it shifts to lower frequencies (823–777 cm−1). This indicates the coordination via
=
the sulfur atom (20, 21). Furthermore, the ν(C S) stretching vibration is observed as a band at
1365 cm−1 incompound 1whichrevealsanegativeshiftaftercomplexation(22). Inthecomplexes,
the band around 1383 cm−1 is attributed to D3h mode of the free NO−3 group which is not involved
in coordination, suggesting the uncoordination of nitrate groups as counter-ions (23). Finally, the
broad band at 3445–3390 cm−1 is assigned to the OH moiety stretching.
−
2.2. Nuclear magnetic resonance studies
The 1H NMR is a useful method for the identification of organic and diamagnetic compounds with
the help of other spectrometric data. The spectra of 1 and some metal complexes were carried out
in DMSO-d6 because this is the only solvent which dissolves all the above compounds. The chief
1H NMR data discussed based on the atom labeling in Figure 1 are listed in Section 4.
A sharp singlet signal at δ = 11.70 ppm in the 1H NMR spectrum of uncomplexed thiosemi-
carbazone is attributed to 3NH. This proton shows a downfield shift due to the decreases in the
electron density of proton in the intra- or intermolecular hydrogen-bonding interaction in the
solvent, suggesting Z-form configuration in the solution (24). A triplet is centered at 4.80 ppm
which can be assigned to the proton of the nitrogen atom 4N. The resonance splits as a triplet due
to quadrupole splitting (17). The signals of 3NH, 4NH and OH peaks disappear by the addition
of D2O, suggesting that they are easily exchangeable.
For pyridyl ring, a doublet at δ = 8.55 ppm is assigned to the 1CH proton. The presence of the
electronic effect of the adjacent electronegative pyridyl nitrogen shifts 1CH proton to downfield.
1
3
2
4
2CH is coupled with CH and results in forming a doublet. CH, CH and CH are found in
8.15, 7.83, and 7.35 ppm, respectively, and all are triplets. The methine proton 6CH is observed
at 8.1 ppm as a singlet. The absence of any peak around 1.6–2.2 ppm corresponding to the SH
proton in 1 indicates that the ligand is present in the thione form in solution (2).
The 1H NMR spectra of the complexes are less resolved than those of the ligand, perhaps due
to the low solubility of the complexes (17). Thus, these spectra show that the resonance peaks are
shifted from their corresponding values in the ligand as a result of coordination. The existence of
the 3NH resonance in the 1H NMR spectra of complexes indicates that the nitrogen atoms remain
as protonated and HL coordinates as neutral ligand. The pyridyl ring signals after coordination
exhibit a low intensity of the multiplets that may be attributed to the delocalization of electron
density due to coordination in the complex. The 1CH signal (at 8.5 ppm in HL) shifts downfield
in complexes because coordination through the pyridine nitrogen atom prevents 1CH from being
deshielded, as it is in the free ligand, due to the anisotropy of the C(6) = N(2) bond and the

418 R. Takjoo et al.
proximity of the sp2 nitrogen (25). However, protons in CH2CH2OH, which do not take part in
coordination, remain more or less unchanged in the complexes. There are perhaps slight variations
in their resonances due to the delocalization of electron density in the system.
2.3. Electronic spectra
The assignments of the significant electronic spectral bands of the ligand and its complexes are
presented in Section 4. Electronic spectra were obtained in DMF solution.
The electronic spectrum in the methanol solution of HL shows two bands corresponding to
n → π∗ transition of the pyridyl ring which is observed at 274 nm; however, the n → π∗ transition
of azomethine and thioamide functions of the thiosemicarbazone moiety are observed at 324 nm,
in which both the latter moieties overlap under the same envelop (26). Furthermore, the molar
absorptivity for n → π∗ transitions for the solution spectrum is >104, which is consistent with
the previously studied heterocyclic thiosemicarbazones (27). In the electronic spectra of the
complexes, the n → π∗ transitions are shifted as a result of coordination. The electronic spectra
of complexes show n → π∗ transitions at 383–245 nm. The band in the range of 420–409 nm
observed in the spectra is assigned to ligand to metal charge transfer (LMCT) (S → Cu and
py → Cu) transition. For all colored complex solutions, we expect to observe bands at visible
regions. The d–d transitions occur at much lower energy regions and are weak in nature. The
broad CT band, tailing into the visible region, causes to hide some weak d → d transitions in
Cu complexes and only one d–d transition is observed at 626 and 607 nm for compounds 5
and 6, respectively. The absence of d → d band in Cd complexes spectra is relevant to the d10
configuration of CdII (28).
2.4. Crystal structure
The oak ridge thermal ellipsoid plot (ORTEP) diagram of the [Cd(HL)I2] molecule with its atom
numbering scheme is shown in Figure 2. Selected bond lengths and bond angles are given in
Figure 2. Molecular plot of [Cd(HL)I2] (3) with the thermal ellipsoids representing 50% probability.

Journal of Sulfur Chemistry 419
Table 1. Bond lengths (Å) and angles (◦) for 3.
Cd(1)–I(2)
Cd(1)–I(1)
Cd(1)–S(1)
Cd(1)–N(2)
Cd(1)–N(1)
N(4)–C(8)
N(3)–C(7)
N(1)–C(1)
N(2)–N(3)
N(1)–C(5)
N(4)–C(7)
N(2)–C(6)
O(1)–C(9)
S(1)–C(7)
C(8)–C(9)
C(1)–C(6)
C(2)–C(3)
C(4)–C(5)
C(1)–C(2)
C(3)–C(4)
2.7805(9)
2.7443(8)
2.620(2)
2.399(6)
2.356(6)
I(1)–Cd(1)–I(2)
N(1)–Cd(1)–N(2)
N(2–Cd(1)–S(1)
S(1)–Cd(1)–I(2)
N(1)–Cd(1)–I(2)
N(1)–Cd(1)–I(1)
S(1)–Cd(1)–I(1)
N2–Cd(1)–I(1)
N(1)–Cd(1)–S(1)
N(2)–Cd(1)–I(2)
C(1)–N(1)–Cd(1)
C(5)–N(1)–C(1)
C(6)–N(2)–Cd(1)
N(2)–N(3)–C(7)
C(6)–N(2)–N(3)
N(3)–N(2)–Cd(1)
C(7)–N(4)–C(8)
C(5)–N(1)–Cd(1)
C(7)–S(1)–Cd(1)
N(4)–C(8)–C(9)
O(1)–C(9)–C(8)
N(4)–C(7)–N(3)
N(1)–C(1)–C(6)
N(2)–C(6)–C(1)
C(4)–C(3)–C(2)
C(1)–C(2)–C(3)
C(3)–C(4)–C(5)
C(2)–C(1)–C(6)
N(1)–C(1)–C(2)
N(4)–C(7)–S(1)
N(3)–C(7)–S(1)
N(1)–C(5)–C(4)
108.74(3)
68.1(2)
72.09(17)
95.50(5)
102.42(16)
104.96(16)
106.55(5)
112.34(16)
136.14(17)
138.91(16)
117.4(5)
118.0(7)
119.1(6)
120.0(7)
120.1(7)
120.4(5)
123.9(7)
124.1(5)
101.7(3)
110.8(6)
112.2(7)
115.7(7)
116.6(7)
117.8(7)
118.1(7)
119.2(8)
120.2(8)
121.5(7)
121.9(8)
122.1(6)
122.1(6)
122.5(8)
1.460(10)
1.368(10)
1.367(10)
1.350(9)
1.328(10)
1.300(10)
1.267(10)
1.419(10)
1.696(8)
1.497(11)
1.459(11)
1.392(12)
1.388(11)
1.387(11)
1.368(11)
Table 1. The compound crystallized with one monomer per asymmetric unit into triclinic crystal
¯
system with a space group P1. The structure shows that the complex is a monomer in which the
Cd(II) atom adopts a five-coordinate geometry with the neutral Schiff base being coordinated to
it as a tridentate chelating agent via the pyridyl nitrogen atom (N(1)), the azomethine nitrogen
atom (N(2)), the thione sulfur atom (S(1)) and two iodine atoms.
This five-coordinate geometry can adopt either a square pyramidal or a trigonal bipyramidal
structure. To determine such structures, the formula of Addison et al. (29) is applied in which
the angular structural parameter (τ) is represented as the index of trigonality. The parameter
τ = β − α/60, where α and β are the two largest angles, belongs to the cadmium atom. An ideal
square pyramid will have β = 180◦ and α = 180◦, and therefore τ = 0%, but an ideal trigonal
bipyramidal structure will have β = 180◦ and α = 120◦ and therefore τ = 100%. The τ-value
is calculated to be 4.62%, indicating the slightly distorted square pyramidal geometry around
Cd(II) ion.
The donor atoms of thiosemicarbazone (N(1), N(2), and S(1)) together with an iodine atom
(I(2)) form the basal plane of the square pyramid and the other iodine atom (I(1)) occupies the
apical position. The molecule exists in the Z conformation with respect to the C(6)–N(2) bond
and the S(1) and N(2) atoms are in the E conformation with respect to the N(3)–C(7) bond; hence,
the thiosemicarbazone moiety, as a whole, exists in the ZE conformation. This conformation may
be due to the steric effects of the ligand and is not attributed to electronic effects because Cd(II),
as a metal center, has d10 configuration and does not feel the ligand field stabilization effects.
The C(6)–N(2) (1.267(10)Å) and C(7)–S(1) (1.696(8)Å) bond distances are indicative of a
considerable double bond character. Cd–Npy (2.356(6)Å) distance in this complex is shorter than

420 R. Takjoo et al.
Cd–Nimine (2.399(6)Å) distance, whereas the azomethine nitrogen atom is typically a stronger
donor than that of pyridine. This observation can be found in some kind of Cd complexes
(9). The two Cd–I distances are different and their discrepancy (0.04Å) is bigger than that of
[Cd(HAm4DH)I2] (0.002Å) (10).
The angle between root mean square (rms) planes of thiosemicarbazone moiety and I(2)–Cd(1)–
I(1) is about 2.6◦, which indicates that these planes are nearly perpendicular. In this case, the
steric effect causes an angle difference (6.71◦) between the two rms planes of thiosemicarbazone
moiety and pyridyl ring. This angle value is smaller and bigger than that of [Cd(HAm4DH)I2]
and [Cd(HAm4E)I2], respectively (15).
Furthermore, comparative X-ray structure of 1 with similar compounds demonstrates that
Cd(1)–I(1) distance is shorter and Cd(1)–S(1) and Cd(1)–N(2) are longer in 1 than that of the
others ([Cd(HAm4DH)I2], [Cd(HAm4DH)I2] and [Cd(HAm4E)I2]).
The hydrogen bonds and other intermolecular interactions play an important role in this com-
pound lattice. The presence of appropriate donor and acceptor atoms in the molecule gives rise to
the formation of supramolecular. The hydrogen bonds N(3)–H(3)· · · O(1) and N(4)–H(4)· · ·O(1)
joint two molecules which form a dimer (Figure 3). These dimers are connected to each other via
O(1)–H(1)· · · I(2) hydrogen bond, causing the expansion of crystal chain growth in one dimension
along [1,−1,0] vector (Figure 4). Hydrogen bond parameters are given in Table 2.
Figure 3. Intermolecular hydrogen bonds in dimer formation (symmetry position i: −x, 2 − y, 2 − z).
Figure 4. The effect of O1–H1· · · I2 interactions in 1D development (symmetry position i: 1 + x, −1 + y, z; ii: −1 + x,
1 + y, z; iii: 2 + x, −y, 2 − z; iv: 1 − x, 1 − y, 2 − z; v: −x, 2 − y, 2 − z).

Journal of Sulfur Chemistry 421
Table 2. Hydrogen bonds for 3.
D–H· · ·A
d(D–H)
d(H· · ·A)
d(D· · ·A)
<(DHA)
O(1)–H(1)· · · I(2)#a1
N(3)–H(3)· · · O(1)#2
N(4)–H(4)· · · O(1)#2
0.84
0.88
0.88
2.64
2.15
2.03
3.404(6)
2.922(11)
2.848(10)
152
147
155
Note: aSymmetry transformations used to generate equivalent atoms: #1: x − 1, y + 1, z; #2: −x, −y + 2, −z + 2.
Table 3. Agar disk diffusion test (diameter of growth inhibitory zone by mm).
Gram-positive bacteria
Gram-negative bacteria
Compound
B. atrophaeus S. aureus B. anthracis P. aeruginosa E. coli Y. pseudotuberculosis
HL (1)
11
24
20
23
17
16
11
0
0
18
17
20
10
18
17
0
13
17
18
22
0
24
22
0
10
0
0
0
0
0
17
0
10
0
0
0
0
0
10
0
15
0
0
0
0
0
10
0
[Cd(HL)](NO3)2 (2)
[Cd(HL)I2] (3)
[Cd(HL)Cl2] (4)
Cd(NO3)2
[Cu(HL)2](NO3)2 (5)
[Cu(HL)Cl2] (6)
Cu(NO3)2
2.5. Antimicrobial activity study
The thiosemicarbazone (TSC) (1) and its complexes have been tested for in vitro inhibitory activity
against the growth of several selected pathogens to evaluate their antibacterial properties. For
tetracycline and streptomycin with a concentration of 1.5 mg/disk, d ≥20 mm, 14≤ d <20 mm,
and 9≤ d ≤13 mm show high, moderate and slight sensitivities, respectively (30). As the results
collected in Table 3 indicate, the complexes are intermediately to strongly active against Gram-
positive bacteria and have a weak activity against Gram-negative bacteria (except 6 which has an
intermediate activity against P. aeruginosa).
The results of disc diffusion method studies given in Table 3 indicate that only compounds 1
and 6 are active against Gram-negative bacteria. The data of quantitative antimicrobial analyses in
Table 4 (minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC))
show that metal complexes have generally better antibacterial activity against Gram-positive
bacteria than that of the free ligand and metal nitrate salts. It seems that the antibacterial activities
of the ligand are significantly enhanced by their chelation to the metal. Compound 3 does not show
any activity against the organism P. aeruginosa. In Gram-positive bacteria, the Cu complexes have
a robust activity against B. anthracis, while Cd complexes are strongly active against B. atrophaeus
and B. anthracis. In Gram-negative bacteria, the free ligand (1) possesses a good antibacterial
activity, especially against E. coli and Y. pseudotuberculosis, perhaps due to its less hydrophilic
property and therefore its better passage across the cell wall. Moreover, compound 6 shows a good
inhibition againstY. pseudotuberculosis.The results obtained from nitrate salts tests indicate that in
comparison with metal complexes, the nitrate ions do not have any significant antibacterial activity.
3. Conclusion
We have prepared a new nitrogen nitrogen sulfur (NNS) Schiff base HL along with its Cd(II) and
Cu(II) complexes.
In the complexes, the ligand acts as a neutral-charged tridentate coordinated to the bivalent
metal ion via the pyridyl nitrogen, the azomethine nitrogen and thione sulfur atoms. The geometry

Table 4. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) tests by μg/μL.
Gram-positive bacteria
Gram-negative bacteria
B. atrophaeus
MIC MBC
S. aureus
MIC MBC
Ga
B. anthracis
P. aeruginosa
MIC MBC
E. coli
Y. pseudotuberculosis
Compound
MIC
MBC
MIC
MBC
MIC
MBC
HL (1)
0.25
1
2
0.125
0.25
1
4
0.125
1
G
G
G
G
2
0.125
1
1
1
2
1
0.5
G
G
G
G
2
[Cd(HL)2](NO3)2 (2)
[Cd(HL)I2] (3)
[Cd(HL)Cl2] (4)
Cd(NO3)2
[Cu(HL)2](NO3)2 (5)
[Cu(HL)Cl2] (6)
Cu(NO3)2
0.0625
0.0625
0.0625
0.5
0.0625
0.0625
0.0625
2
0.5
2
0.0625
0.0625
0.0625
0.0625
0.0625
0.0625
0.5
0.125
0.125
0.125
0.25
0.0625
0.0625
1
4
4
4
4
2
1
2
G
G
G
G
4
2
2
2
4
1
1
1
1
2
1
2
1
4
0.125
0.25
0.25
0.5
0.25
0.125
2
0.5
0.25
2
2
4
2
2
0.25
1
1
2
0.25
1
Note: aG: growth.

Journal of Sulfur Chemistry 423
around the central metal in compounds 2 and 5 is distorted octahedral and the others have distorted
square pyramidal geometries.
An X-ray crystal structure determination of [Cd(HL)I2] confirms a distorted square pyramidal
geometry. Although metal complexes are effective against Gram-positive bacteria (Cu complexes
against B. anthracis and Cd complexes against B. atrophaeus and B. anthracis), the free ligand
is effective against Gram-negative bacteria (E. coli and Y. pseudotuberculosis).
4. Experimental
4.1. Materials and techniques
All chemicals of AR grade for the synthesis of the thiosemicarbazone ligand and their complexes
were used as received.
C, H, N, and S analyses were obtained with a Thermo Finnigan Flash Elemental Analyzer,
model 1112EA. IR spectra were recorded from KBr pellets in the range of 4000–400 cm−1 on an
FT-IR 8400-SHIMADZU spectrophotometer. 1H NMR spectra were recorded on a Bruker BRX
100AVANCE operating at the frequency of 100 MHz and using DMSO-d6 and TMS as the solvent
and the internal standard with δ = 0, respectively. The 13C NMR spectrum of HL was recorded
on a Bruker BRX-300 AVANCE. Electronic spectra of the complexes in DMF solution (ca. 25◦C)
were recorded by a spectrophotometer SHIMADZU model 2550 UV–VIS spectrophotometer
(250–900 nm). Melting points were determined with a Barnsted Electrothermal 9200 electrically
heated apparatus.
4.2. Synthesis of the ligand (HL, 1)
S-methyl dithiocarbazate was prepared using a reported procedure (31). Preparation of S-methyl-
3-((pyridyl)methyl)dithiocarbazate: a solution of S-methyl dithiocarbazate (1.2 g, 1 mmol) in hot
ethanol (10 mL) was treated with pyridine 2-carbaldehyde (0.1 ml, 1 mmol) and the resultant
mixture was heated on a steam bath for 20 min. The solution was allowed to cool and the fine
yellowish needles of the compound separated out. It was filtered off, washed with cold ethanol
and dried over silica gel.
HL was prepared by refluxing an ethanolic solution of a 1:1 S-methyl-3-((pyridyl)methyl)
dithiocarbazate with excess amounts of 2-aminoethanol for ca. 24 h at water bath temperature
(until moistened lead nitrate paper indicated that the evolution of methyl mercaptan had stopped).
The warm solution was filtered; the resulting yellow solid was washed with MeOH and dried
in vacuo over silica gel at room temperature.
HL (1): yellow, Yield: 47%. m.p.: 198◦C. Anal. Calcd for C9H12N4OS (224.28 g mol−1): C,
48.20; H, 5.39; N, 24.98; S, 14.30. Found: C, 48.19; H, 5.42; N, 27.61; S, 14.16%. IR spec-
trum in KBr, cm−1: ν(NH) 3223, 3152m, ν(C N) +ν(C C) +δ(N H) 1539s, ν(C S) 1298m,
=
=
−
=
−
−
=
ν(C O) 1221m, ν(N N) 1070m, δ(C S) 927w, ρ(py) 634w. UV/VIS (CH3OH), λmax, nm
(log ε, L mol−1 cm−1): 211 (3.72), 232 (3.43), 276 (3.46), 324 (4.04). UV/VIS (DMF), λmax
,
1
nm (log ε, L mol−1 cm−1): 276 (3.61), 324 (4.22). H NMR (100 MHz, DMSO-d6): δ = 11.71
3
1
3
=
(s, 1H, N H; exchanges with D2O) 8.52 (d, 1H, CH N) 8.55 (d, 1H, Cpy) 8.53 (t, 1H, Cpy)
7.83 (t, 1H, C2py) 7.35 (t, 1H, Cp4y) 4.80 (s, br, 1H, N4H; exchanges with D2O) 3.60 (s, 5H,
CH2CH2OH; OH exchanges with D2O). 13C NMR (300 MHz, DMSO-d6): δ = 46.511 (C8),
59.615 (C9), 120.552 (C4), 124.554 (C2), 136.975 (C3), 142.704 (C1), 149.836 (C6), 153.667
(C5), 177.840 (C7).
The structure of the ligand is given in Figure 1.

424 R. Takjoo et al.
4.3. Synthesis of complexes
The complexes were prepared by the following procedure. A solution of HL (1 or 2 mmol) in
ethanol (10 mL) was added to a solution of appropriate metal salts (1 mmol) in 10 mL of ethanol,
and the mixture was refluxed for 3–6 h. The resulting solids were filtered off, washed with cold
ethanol and dried over silica gel.
[Cd(HL)2](NO3)2 (2): yellow,Yield: 60%. m.p.: 152◦C. Molar conductivity (1 × 10−3 mol L−1
;
DMF): 103.6 ꢀ−1 cm2 mol−1. Anal. Calcd for C18H24CdN10O8S2 (682.97 g mol−1): C, 30.75; H,
3.73; N, 19.92; S, 9.12. Found: C, 30.90; H, 3.51; N, 20.18; S, 8.94%. IR spectrum in KBr,
cm−1: ν(OH) 3402m, ν(NH) 3222m, ν(C N)+ν(C C)+δ(N H) 1583s, ν(NO3) 1381s, ν(C S)
=
=
−
=
−
−
=
1319m, ν(C O) 1240m, ν(N N) 1074m, δ(C S) 929w, ρ(py) 646w. UV/VIS (DMF), λmax, nm
(log ε, L mol−1 cm−1): 292 (3.97), 396 (4.03). 1H NMR (100 MHz, DMSO-d6): δ = 11.8 (s, 1H,
3
4
=
N H; exchanges with D2O), 8.2 (s, 1H, CH N), 7.4–8.5 (m, 4H, CHpy), 4.80 (s, br, 1H, N H;
exchanges with D2O), 3.51 (s, 5H, CH2CH2OH; OH exchanges with D2O).
[Cd(HL)I2] (3): yellow, Yield: 75%. m.p.: 242◦C. Molar conductivity (1 × 10−3 mol L−1
;
DMF): 19.70 ꢀ−1 cm2 mol−1. Anal. Calcd for C9H12CdI2N4OS (590.50 g mol−1): C, 18.34; H,
1.88; N, 9.50; S, 5.44. Found: C, 18.37; H, 1.98; N, 10.17; S, 5.27%. IR spectrum in KBr,
cm−1: ν(OH) 3433m, ν(NH) 3248, 3053m, ν(C N)+ν(C C)+δ(N H) 1564s, ν(C S) 1273m,
=
=
−
=
−
−
=
ν(C O) 1234m, ν(N N) 1047m, δ(C S) 920w, ρ(py) 687w. UV/VIS (DMF), λmax, nm (log ε,
L mol−1 cm−1): 322 (4.41), 396 (4.31). 1H NMR (100 MHz, DMSO-d6): δ = 11.8 (s, 1H, N3H;
4
=
exchanges with D2O), 8.7 (s, 1H, CH N), 7.8–8.6 (m, 4H, CHpy), 4.70 (s, br, 1H, N H; exchanges
with D2O), 3.60 (s, 5H, CH2CH2OH; OH exchanges with D2O). Crystals suitable for X-ray data
collection were obtained from DMF.
[Cd(HL)Cl2] (4): yellow, Yield: 78%. m.p.: 231.5◦C. Molar conductivity (1 × 10−3 mol L−1
;
DMF): 20.47 ꢀ−1 cm2 mol−1. Anal. Calcd for C9H12CdCl2N4OS (407.60 g mol−1): C, 30.75; H,
3.73; N, 19.92; S, 9.12. Found: C, 30.75; H, 3.51; N, 20.18; S, 8.94%. IR spectrum in KBr,
cm−1: ν(OH) 3445m, ν(NH) 3213, 3022m, ν(C N)+ν(C C)+δ(N H) 1564s, ν(C S) 1300m,
=
=
−
=
−
−
=
ν(C O) 1242m, ν(N N) 1068m, δ(C S) 899w, ρ(py) 631w. UV/VIS (DMF), λmax, nm (log
ε, L mol−1 cm−1): 322 (4.39), 396 (4.21). H NMR (100 MHz, DMSO-d6): δ = 11.8 (s, 1H,
1
3
4
=
N H; exchanges with D2O), 8.54 (s, 1H, CH N), 7.4–8.58 (m, 4H, CHpy), 4.50 (s, br, 1H, N H;
exchanges with D2O), 3.57 (s, 5H, CH2CH2OH; OH exchanges with D2O).
[Cu(HL)2](NO3)2 (5): green, Yield: 43.5%. m.p.: 159◦C. Molar conductivity (1 × 10−3
mol L−1; DMF): 114.5 ꢀ−1 cm2 mol−1. Anal. Calcd for C18H24CuN10O8S2 (636.12 g mol−1): C,
33.99; H, 3.80; N, 22.02; S, 10.08. Found: C, 30.64; H, 3.91; N, 23.22; S, 9.70%. IR spectrum in
KBr, cm−1: ν(OH) 3390m, ν(NH) 3327, 3269m, ν(C N) 1612s, ν(N C) 1529s, ν(C S) 1296m,
=
=
=
−
−
=
ν(C O) 1234m, ν(N N) 1055m, δ(C S) 925w, δ(NO3) 887w, ρ(py) 623w. UV/VIS (DMF),
λmax, nm (log ε, L mol−1 cm−1): 323 (4.35), 409 (3.81), 623 (1.93).
[Cu(HL)Cl2] (6): green, Yield: 88%. m.p.: 222◦C. Molar conductivity (1 × 10−3 mol L−1
;
DMF): 49.64 ꢀ−1 cm2 mol−1. Anal. Calcd for C9H12Cl2CuN4OS (358.73 g mol−1): C, 30.13; H,
3.37; N, 15.62; S, 8.94. Found: C, 30.17; H, 3.42; N, 15.59; S, 9.03%. IR spectrum in KBr,
cm−1: ν(OH) 3402m, ν(NH) 3335, 3202m, ν(C N)+ν(C C)+δ(N H) 1591s, ν(C S) 1308m,
=
=
−
=
−
−
=
ν(C O) 1238m, ν(N N) 1057m, δ(C S) 939w, ρ(py) 634w. UV/VIS (DMF), λmax, nm (log ε,
L mol−1 cm−1): 298 (4.1), 343 (3.9), 420 (3.9), 607 (2.12).
4.4. Qualitative and quantitative antimicrobial activity
The free ligand and the complexes were tested for antimicrobial activity. Six pathogenic bacteria
were used to test the antibacterial potentials of the thiosemicarbazone and its complexes.
The organisms chosen for antimicrobial activity were three Gram-positive (S. aureus,
B. anthracis and B. atrophaeus) and three Gram-negative (Y. pseudotuberculosis, E. coli and

Journal of Sulfur Chemistry 425
P. aeruginosa) bacteria. The antimicrobial activity of all compounds was screened qualitatively
by a modified disc diffusion method (6). Agar disc diffusion method was carried out using brain
heart agar media and 6 mm diameter paper discs of Whatman filter paper No. 1. The compounds
were dissolved in DMSO to give a concentration of ca. 1.5 μg/disc. One of the media was cultured
with Swab (sterile, nontoxic) containing 1:10 dilution of 0.5 McFarland suspensions of bacterial
broth media (107 CFU/mL). The plates were incubated at 35◦C for 24 h, and the inhibition zone
around each disc was measured.
All the Compounds were subjected to the broth dilution method for the quantitative measure-
ment of bacteriostatic (MIC) and bacteriocidal (MBC) activities. The lowest concentration, in
which visible microbial growth was completely inhibited, was recorded as the MIC (μg/μL).
The simplest method for determining the MBC is to perform a subculture from antibiotic con-
centrations with no visible growth in the MIC (μg/μL) test onto antibiotic-free agar. This will
determine whether the bacteria are growth-inhibited but still viable or they are killed.
4.5. Crystal structure solution
An appropriate yellow prism-shaped single crystal of 3, with approximate dimensions of 0.25 ×
0.25 × 0.12 mm, was mounted on a glass fiber and intensity data were measured at 100(2) K. The
unit cell parameters and the intensity data were collected on a BrukerAPEX-II CCD diffractometer
using graphite monochromated Mo-Kα radiation (0.71073Å) with ϕ- and ω-scan techniques.
The software SMART and SAINTPlus were applied for data acquisition and data abstraction,
respectively. Absorptions corrections on the data were made using SADABS (32). The structure
was solved by direct methods (33) and refined by full-matrix least squares based on F2 with weight
Table 5. Crystal data and structure determination details for 3.
Compound
3
Empirical formula
Formula weight
Temperature
C9H12CdI2N4OS
590.49
100(2) K
Wavelength
Crystal system
Space group
0.71073 Å
Triclinic
P 1
¯
Unit cell dimensions
a = 9.6129(11)Å, α = 64.313(2)◦
b = 9.7288(12)Å, β = 66.973(2)◦
c = 10.2245(12)Å, γ = 70.289(2)◦
Volume
776.67(16)Å3
Z
2
Density (calculated)
Absorption coefficient
F(000)
Crystal size
Theta range for data collection
Index ranges
Reflections collected
Independent reflections
Completeness to theta =29.63◦
Absorption correction
Max. and min. transmission
Refinement method
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I>2sigma(I)]
R indices (all data)
Largest diff. peak and hole
2.525 Mg/m3
5.509 mm−1
544
0.25 × 0.25 × 0.12 mm3
2.31–29.00◦
−13 <= h <= 13, −13 <= k <= 13, −13 <= l <= 13
9024
4082 [R(int) = 0.0665]
99.2%
Semi-empirical from equivalents
0.518 and 0.271
Full-matrix least-squares on F2
4082/0/163
0.996
R1 = 0.0508, wR2 = 0.0850
R1 = 0.0990, wR2 = 0.0968
1.740 and −1.660 eÅ−3

426 R. Takjoo et al.
w = 1/[σ2(Fo2) + (0.0300P)2 + 2.5P], where P = (Fo2 + 2Fc2)/3 using SHELXTL ver. 5.1
programs (34). A summary of crystal data, refinement details, and resultant refinement agreement
factors are given in Table 5.
5. Supplementary materials
Crystallographic data for the structural analysis have been deposited with the Cambridge Crys-
tallographic Data Centre, CCDC No., [Cd(HL)I2]: 745184. Copy of this information may be
obtained free of charge from The Director, CCDC, 12 Union Road, Cambridge CB2 1EZ, UK
(fax: 44-1223-336033; e-mail: deposit@ccdc.cam.ac.uk or http://www.ccdc.cam.ac.uk).
Acknowledgements
We are grateful to Payame Noor University (PNU) for financial support and thank Mohammad Reza Hassani for his help.
References
(1) Yazdanbakhsh, M.; Takjoo, R.; Frank, W.; Aghaei Kaju, A. J. Coord. Chem. 2009, 62, 3651–3660.
(2) Yazdanbakhsh, M.; Heravi, M.M.; Takjoo, R.; Frank, W. Z. Anorg. Allg. Chem. 2008, 63, 972–976.
(3) Lobana, T.S.; Sharma, R.; Bawa, G.; Khanna, S. Coord. Chem. Rev. 2009, 253, 977–1055.
(4) Mukesh Kumar, B.; Krishna, S.; Monika, S.; Nighat, F.; Ran Vir, S. Transit. Met. Chem. 2008, 33, 377–381.
(5) Chan, M.-H.E.; Crouse, K.A.; Tahir, M.I.M.; Rosli, R.; Umar-Tsafe, N.; Cowley, A.R. Polyhedron 2008, 27,
1141–1149.
(6) Seena, E.B.; Kurup, M.R.P. Spectrochim. Acta A 2008, 69, 726–732.
(7) Pedrido, R.; Bermejo, M.R.; Romero, M.J.; González-Noya, A.M.; Maneiro, M.; Fernández, M.I. Inorg. Chem.
Commun. 2005, 8, 1036–1040.
(8) Novakovic´, S.B.; Fraisse, B.; Bogdanovic´, G.A.; Spasojevic´-de Biré, A. Cryst. Growth Des. 2007, 7, 191–195.
(9) Bermejoa, E.; Carballob, R.; Castiñeiras, A.; Domingueza, R.; Maichle-Mössmer, C.; Stráhle, J.; West, D.X.
Polyhedron 1999, 18, 3695–3702.
(10) Castiñeiras, A.; Garcia, I.; Bermejo, E.; West, D.X. Polyhedron 2000, 19, 1873–1880.
(11) West, D.X.; Swearingen, J.K.; Romack, T.J.; Billeh, I.S.; Jasinski, J.P.; Li,Y.; Staples, R.J. J. Mol. Struct. 2001, 570,
129–136.
(12) Ali, M.A.; Mirza, A.H.; Monsur, A.; Hossain, S.; Nazimuddin, M. Polyhedron 2001, 20, 1045–1052.
(13) Labisbal, E.; Sousa-Pedrares, A.; Castiñeiras, A.; Swearingen, J.K.; West, D.X. Polyhedron 2002, 21, 1553–1559.
(14) García, I.; Bermejo, E.; El Sawaf, A.K.; Castiñeiras, A.; West, D.X. Polyhedron 2002, 21, 729–737.
(15) Bermejo, E.; Castiñeiras, A.; Fostiak, L.M.; Santos, I.G.; Swearingen, J.K.; West, D.X. Polyhedron 2004, 23,
2303–2313.
(16) Rapheal, P.F.; Manoj, E.; Prathapachandra Kurup, M.R. Polyhedron 2007, 26, 818–828.
(17) Suni, V.; Prathapachandra Kurup, M.R.; Nethaji, M. Polyhedron 2007, 26, 5203–5209.
(18) Suni, V.; Prathapachandra Kurup, M.R.; Nethaji, M. Spectrochim. Acta A 2006, 63, 174–181.
(19) Fostiak, L.M.; García, I.; Swearingen, J.K.; Bermejo, E.; Castiñeiras, A.; West, D.X. Polyhedron 2003, 22, 83–92.
(20) Gómez-Saiz, P.; Gil-García, R.; Maestro, M.A.; Pizarro, J.L.; Arriortua, M.I.; Lezama, L.; Rojo, T.; González-
Álvarez, M.; Borrás, J.; García-Tojal, J. J. Inorg. Biochem. 2008, 102, 1910–1920.
(21) Latheef, L.; Kurup, M.R.P. Spectrochim. Acta A 2008, 70, 86–93.
(22) John, R.P.; Sreekanth, A.; Prathapachandra Kurup, M.R.; Mobin, S.M. Polyhedron 2002, 21, 2515–2521.
(23) Qing, Y.; Hua, D.J.; Gang, Z.L.; Qing, Z.X.; Dong, B.H.; Hong, L. J. Mol. Struct. 2006, 794, 71–76.
(24) Sau, D.K.; Butcher, R.J.; Chaudhuri, S.; Saha, N. Polyhedron 2004, 23, 5–14.
(25) Bermejo, E.; Castiñeiras, A.; García, I.; West, D.X. Polyhedron 2003, 22, 1147–1154.
(26) Philip, V.; Suni, V.; Prathapachandra Kurup, M.R.; Nethaji, M. Polyhedron 2005, 24, 1133–1142.
(27) Joseph, M.; Suni, V.; Prathapachandra Kurup, M.R.; Nethaji, M.; Kishore, A.; Bhat, S.G. Polyhedron 2004, 23,
3069–3080.
(28) Castiñeiras, A.; Carballo, R.; Pérez, T. Polyhedron 2001, 20, 441–448.
(29) Addison, A.; Rao, T.; Reedjik, J.; Van Rijn, J.; Verschoor, G. J. Chem. Soc. Dalton Trans. 1984, 1349–1356.
(30) Li, Q.-X.; Tang, H.-A.; Li, Y.-Z.; Wang, M.; Wang, L.-F.; Xia, C.-G. J. Inorg. Biochem. 2000, 78, 167–174.
(31) Tarafder, M.T.H.; Chew, K.-B.; Crouse, K.A.; Ali, A.M.;Yamin, B.M.; Fun, H.K. Polyhedron 2002, 21, 2683–2690.
(32) Blessing, R.H. Acta. Crystallogr. Sect. A 1995, 51, 33–38.
(33) Sheldrick, G.M. Acta. Crystallogr. Sect. A 1990, 46, 467–473.
(34) Sheldrick, G.M. SHELX-97, SHELXS97: University of Gottingen: Germany, 1997.