Synthesis, spectral and structural study of sulfur-containing copper(II) complexes

Article abstract of DOI:10.1080/17415993.2010.499567

A series of four new copper(II) complexes [Cu(H₂L)(L1)] 1, [Cu(H₂L)(PMDT)] 2, [Cu(H₂L)(Dien)] 3 and [Cu(H ₂L)(L²)] 4 have been synthesized by template condensation (H₂L=thiodiglycolic acid,

Full text of DOI:10.1080/17415993.2010.499567

This article was downloaded by: [Korea University]
On: 28 December 2014, At: 08:30
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
Synthesis, spectral and structural
study of sulfur-containing copper(II)
complexes
R. N. Patel a , A. Singh a , K. K. Shukla a , D. K. Patel a , V. P.
Sondhiya a & S. Dwivedi a
a Department of Chemistry , A.P.S. University , Rewa, Madhya
Pradesh, India
Published online: 12 Aug 2010.
To cite this article: R. N. Patel , A. Singh , K. K. Shukla , D. K. Patel , V. P. Sondhiya & S. Dwivedi
(2010) Synthesis, spectral and structural study of sulfur-containing copper(II) complexes, Journal of
Sulfur Chemistry, 31:4, 299-313, DOI: 10.1080/17415993.2010.499567
To link to this article: http://dx.doi.org/10.1080/17415993.2010.499567
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. 4, August 2010, 299–313
Synthesis, spectral and structural study of sulfur-containing
copper(II) complexes
R.N. Patel*, A. Singh, K.K. Shukla, D.K. Patel, V.P. Sondhiya and S. Dwivedi
Department of Chemistry, A.P.S. University, Rewa, Madhya Pradesh, India
(Received 31 March 2010; final version received 5 June 2010)
A series of four new copper(II) complexes [Cu(H2L)(L1)] 1, [Cu(H2L)(PMDT)] 2, [Cu(H2L)(Dien)] 3 and
[Cu(H2L)(L2)] 4 have been synthesized by template condensation (H2L = thiodiglycolic acid, L1 = N-
[(1)-1-(4-methylphenyl)ethylidene]benzohydrazide, PMDT = N,N,Nꢀ,Nꢀ,Nꢀꢀ-pentamethyldiethylene-
triamine, Dien = diethylenetriamine L2 = N-[(1)-pyridin-2-ylmethylidene]benzohydrazide). The bonding
and stereochemistry of the complexes have been characterized by molar conductance, elemental analy-
sis, magnetic susceptibility, infrared, UV–visible, electron paramagnetic resonance structural studies and
electrochemical studies. g-Values were calculated for all complexes in polycrystalline form as well as in
DMSO solution. The magnetic and spectral data indicate square pyramidal geometry for 1 and octahedral
geometry for 2–4 complexes. Cyclic voltammograms for all the complexes are similar and involve two
irreversible redox processes. Their biological properties have also been studied. The thio complexes show
more antibacterial activity than the controlled one. The antibacterial activities of the compounds have also
been tested against Escherichia coli with different concentrations.
Keywords: copper(II) complexes; antibacterial activity; SOD activity; EPR; CV
1. Introduction
Copper is an essential element for life, as it actively participates in biological events (1). This
transition metal is the second important element involved in the electron transfer process (2–4)
and copper ions present in proteins play a crucial role as electron carrier in many vital processes.
The large family of copper proteins includes one group of particular interest, the so-called type-1
or “blue” copper protein (TlCu). A number of publications, either experimental or theoretical,
have been devoted to TlCu proteins, due to their special features such as their ability to transport
electrons over large distances and hence to catalyze selected chemical reactions. Copper protein
possess well-designed active centers that finally tune metal ion redox properties (5, 6).
Thiodiglycolic acid and its metal complexes have received considerable attention over the past
few years. The chemistry of such ligands warrants further study because thiodiglycolic acid forms
an interesting series of copper(II) complexes with the help of other tridentate/bidentate ready-
made ligands/Schiff base ligands. Some of the metal complexes may be expected to be biologically
*Corresponding author. Email: rnp64@ymail.com
ISSN 1741-5993 print/ISSN 1741-6000 online
© 2010 Taylor & Francis
DOI: 10.1080/17415993.2010.499567
http://www.informaworld.com

300 R.N. Patel et al.
active. Indeed, carcinogenic activities (7) have already been found for some metal complexes of
thiodiglycolic acid.The synthesis of these complexes continues to be of interest in order to evaluate
their coordination chemistry and their potential as antimicrobial and anti-cancer agents.
In the present work, we describe four low molecular weight copper(II) complexes of thiodigly-
colic acid focussing on their possible application as a superoxide scavenging agent. The ability of
these copper(II) complexes to scavenge O−2 was evaluated by NBT method. Spectroscopic studies
were performed in order to correlate the structure feature of the complexes with their scavenging
activity.
2. Results and discussion
H2L forms square pyramidal 1 and octahedral complexes 2–4 with Cu(NO3)2·3H2O in methanol.
All the complexes were synthesized by the following sequential route (Scheme 1).
H3C
H3C
H
N
CH3
N
N
C
N
H3C
H3C
CH3
CH3
O
N
Cu
Cu
S
O
O
O
O
S
O
O
O
O
1
2
L1/ MeOH
at RT
PMDT/MeOH
at RT
Cu(NO3)2·3H2O
+
TDGA
Dien/MeOH
at RT
L2 /MeOH
at RT
O
O
S
O
O
HN
NH
O
2
Cu
N
NH
O
O
2
Cu
S
N
NH
O
O
3
4
Scheme 1. Synthesis of complexes 1–4.
All the copper(II) complexes are hygroscopic in nature. These are insoluble in common organic
solvents but soluble in DMF and DMSO. The elemental analysis shows that the copper(II)

Journal of Sulfur Chemistry 301
Table 1. The important IR frequencies (in cm−1) of Schiff bases and their metal complexes.
=
=
Compound ν(OH) ν(C–O) ν(C O) ν(C N) ν(C–S) ν(N–H) ν(NH2) ν (Cu–Npy) ν(Cu–N) ν(Cu–O) ν(Cu–S)
H2L
L1
L2
1
2
3
3060
1106
1650
1632
1635
1630
1635
1625
1630
1324
–
–
1338
1337
1336
1331
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
525
520
526
520
–
–
–
350
353
352
349
–
–
–
–
–
–
–
–
–
–
–
–
1558
1560
1580
–
3273
3274
3260
3268
3265
3266
3385
3370
–
465
460
463
–
–
280
4
1582
complexes have non-stoichiometric ratio of the type [M(H2L)(A)], where H2L stands for a sulfur
donor ligand containing SO2-bonding moiety. Several attempts were made to develop the single
crystal of the complexes but failed due to the insolubility of the complexes in common organic
solvents. All the complexes are non-electrolytic in nature.
2.1. Infrared spectral studies
The important IR spectral data of Schiff bases and their Cu(II) complexes are presented in Table 1.
The free ligand displays a broad band at 3030–3065 cm−1 due to O–H vibrations of the alcoholic
hydroxyl oxygen. This band disappears in the spectra of complexes indicating that the ligand
is coordinated to metal through deprotonated form (8). The ring vibrations and C–O stretching
modes of the ligand appear in the 1440–1513 and 1100–1190 cm−1 ranges, respectively. In the
spectra of complexes, these bands shift to higher wavenumbers as a result of coordination through
the hydroxyl oxygen atoms. A strong band in the region 1558 and 1560 cm−1 in the free ligands
1
2
(L and L ) assigned to (N C-CH3) exhibits 10–20 cm−1 shifting (9–11) in the spectra of
complexes (1 and 4) indicating (12) coordination through azomethine nitrogen of Schiff bases.
This can be explained by the donation of electrons from nitrogen to the empty d-orbitals of the
central metal atom. Formation of M–N(azo) bond (12) is further supported by the presence of
a band in the region 460–465 cm−1. A new band appearing at ∼750 cm−1 which is assigned to
C–S indicates the coordination through the sulfur atom in these complexes. Metal–sulfur bond
formation (13–15) is further confirmed by a band in the region 349–353 cm−1 in the far IR spectra
and confirms the complexation. The IR spectra of the ligand H2L shows characteristic bands
=
due to C–S and C O in the regions 1324 and 1650 cm−1, whereas NH stretching absorption
=
in free ligands (L1 and L2) occurs at ∼3273 cm−1 (16, 17). The N–H vibration bands of the
complexes 1, 3 and 4 are observed between 3260–3268 cm−1. In the complexes, these bands are
shifted to lower wavenumbers, indicating the involvement of nitrogen atoms in coordination. This
is also confirmed by the presence of new bands at 500–581 cm−1 in the spectra of complexes
corresponding to N–N vibration bands (18). In complex 4, a strong band is observed in the region
280 cm−1, which is consistent with the Cu–N of pyridine suggested by Clark and Williams (19).
In all the complexes, a strong band is observed in the region 349–353 cm−1, which has been
assigned to the Cu–S band (20).
2.2. Electronic spectra
It has been established that six coordinate copper(II) complexes possess elongated tetrahedral or
rhombic distortions in an octahedral field and display three spin allowed transitions (Figure 1)
2
2
2
assignedto2B1g → B1g (ν1), 2B1g → B2g (ν2)and2B1g → Eg (ν3)absorption(21, 22). However,
the first transition usually appears as shoulder and sometimes overlaps with the later transition
(ν2). The complexes 1–4 exhibited three bands around 15,050–26,400 cm−1. The broadness of

302 R.N. Patel et al.
0.20A
(0.020
/div)
250
500nm
0.01A
550.0nm
(100/div)
1100.0nm
Wavelength (nm)
Figure 1. The UV–visible spectrum (0.003 mol−1 dm−3) of complex 4.
band is due to ligand-field and the John-Teller distortions (23). Additional bands observed for all
complexes in the range 25,000–27,777 cm−1 are assigned to S→Cu transition (24, 25).
2.3. Magnetic moment studies
The magnetic susceptibility measurements for complexes 1–4 were measured in the solid state.
They showed the paramagnetic behavior at room temperature. The observed magnetic moments
of these complexes are quite close to the value expected for other copper(II) complexes. The
magnetic moment value (μeff ) of complexes 1–4 are 1.89, 1.87, 1.88 and 1.91 B.M., respec-
tively. Magnetic moment values lie within the range normally found for other magnetically dilute
copper(II) complexes (26–28).
2.4. Molar conductivity
The molar conductance values of the compounds 1–4 were measured in DMSO solution (3 ×
10−3 M). On the basis of observed values, the complexes are found to be nonconductors (29)
which indicates that the anionic ligand is coordinated to the central copper(II).
2.5. Electron paramagnetic resonance spectra
The powder and solution spectra of complexes showed g and g patterns only, and the corre-
ꢁ
⊥
sponding values (∼2.0) were found to be consistent with the distorted octahedral coordination
2
2
(30) around copper(II) in complexes 2–4 with the dx −y ground state (31). However, superhy-
perfine splitting is only observed in complex 4, whereas it could not be observed in the rest of
the complexes. The spectra of 4 have five nitrogen superhyperfine lines on the high-field copper
hyperfine splitting component, which arises from the coupling of the electron spin with the nuclear
spin of the two nitrogen atoms, i.e. one azomethine nitrogen and one nitrogen from the pyridine
ring coordinated to the copper(II) center (Figure 2).
The electron paramagnetic resonance (EPR) spectra of a polycrystalline sample at 298 K were
recorded in the X band using the 100 kHz field modulation, and g-factors were quoted relative to
the standard marker TCNE (g = 2.00277). The frozen solution EPR spectra and polycrystalline
sample EPR spectra are shown in Figures 2–5. The derived EPR parameters for copper(II) com-
plexes are presented in Table 2. The spectra of complex 4 in the polycrystalline state at 298 K

Journal of Sulfur Chemistry 303
Table 2. EPR spectral parameters of the copper(II) complexes.
EPR parameters
1
2
3
4
Polycrystalline state (298 K)
g1
g2
g3
2.222
2.059
–
2.214
2.124
2.073
2.260
2.141
2.073
2.192
2.141
2.050
DMSO (77 K)
g
2.207
2.050
160
2.196
2.012
170
2.108
2.050
195
2.2184
2.059
170
ꢁ
g
⊥
A (G)
G
α2
β2
γ 2
ꢁ
4.1
3.9
4.3
3.7
0.678
0.989
0.947
0.648
0.664
147
0.693
0.953
0.948
0.657
0.661
139
0.772
0.918
0.881
0.680
0.709
122
0.719
1.067
1.016
0.731
0.768
139
K
K
⊥
ꢁ
f (cm)
show only one broad signal isotropic, and hence only one g-value (2.0863) arises between differ-
ent molecules in the unit cell. This is suggestive of the presence of spin–spin interaction, which
may be the only intermolecular type arising due to the solid effect. These types of spectra unfor-
tunately give no information on the electronic ground state of the copper(II) ion present in the
complexes.
The low-temperature (77 K) DMSO-frozen glass EPR spectra of these complexes display
four-line copper hyperfine lines, characteristic of monomeric copper(II) complexes with a g
⊥
component. Kivelson and Nieman (32) have pointed out that compounds having g > 2.3 are
ꢁ
ionic in nature while those with g < 2.3 are covalent in character. The g values for complexes
ꢁ
2
2
1–4 reveal appreciable covalency with dx −y as the ground state. The complexes show similar
features with g > g . It is interesting that the relationship g > g typical of axially sym-
ꢁ
⊥
ꢁ
⊥
metric d9 copper (SCu
=
1/2) having unpaired dx −y orbital (33, 34). Similar observations
2
2
were made earlier (35) for mixed-ligand copper(II) complexes. The g value of the complexes
ꢁ
is found to be g < 2.3 which indicates considerable covalent character of the M→L bond (36).
ꢁ
In complexes 1–4, all EPR signals are shifted slightly towards higher magnetic field and there-
fore leading to smaller g and g values. This finding is in line with the increased ligand field
ꢁ
⊥
TCNE
TCNE
3300
2600 2700
2800
2900
3000
3100
3200
3400
Figure 2. EPR spectra (LNT) of complex 4 in 100% DMSO.

304 R.N. Patel et al.
TCNE
2700 2800
2900
3000
3100 3200
3300
3400
Figure 3. EPR spectra (LNT) of complex 3 in 100% DMSO.
TCNE
2700
2800
2900
3000
3100 3200
3300
3400
Figure 4. EPR spectrum of complex 1 in a polycrystalline state at RT.

Journal of Sulfur Chemistry 305
TCNE
2700
2800
2900
3000
3100 3200
3300
3400
Figure 5. EPR spectrum of complex 2 in a polycrystalline state at RT.
operating through the G = 2.0023 + nξ [E0 − En] relationship (35, 36). The geometric param-
eter G, which is a measure of the exchange of interaction between the copper centers in a
polycrystalline solid, has been calculated. According to Hathaway and coworkers (37, 38), if
G > 4, the exchange interaction is negligible and G < 4 indicates the exchange interaction. The
value of G for complexes 1–4 are 4.1, 3.9, 4.3 and 3.7, indicating that exchange interaction is
negligible for 1 and 3, whereas complexes 2 and 4 show exchange interaction in solid state. From
the low-temperature EPR spectra, various bonding parameters such as in-plane σ-bonding, in-
plane π-bonding as well as out-of-plane π-bonding can be evaluated (39) by using the following
expression (40)
ꢀ
ꢁ
A
3
ꢁ
α2 =
+ (g − 2.0023) + (g − 2.0023) + 0.04.
ꢁ
⊥
0.036
7
The orbital reduction factors K and K were estimated from the expression (40)
ꢁ
⊥
Ed−d
8λ0
K2 = (g − 2.0023)
,
ꢁ
ꢁ
Ed−d
2λ0
K⊥2 = (g − 2.0023)
,
⊥
where K = α2β2, K = α2γ 2 and λ0 represents the one-electron spin–orbit coupling constant
ꢁ
⊥
for the free ion, equal to −828 cm−1. Significant information about the nature of bonding in
the copper(II) complexes can be derived from the magnitude of K and K . In the case of
ꢁ
⊥
pure σ-bonding, K ≈ K ≈ 0.77, whereas K < K implies considerable in-plane bonding,
ꢁ
⊥
ꢁ
⊥
and for out-of-plane bonding, K > K . In all the present copper(II)complexes, it is observed
that K > K , which indicates the presence of a significant out-of-plane bonding. The eval-
ꢁ
⊥
ꢁ
⊥
uated values of α2, β2 and γ 2 of the complexes are consistent with both strong in-plane
σ- and in-plane π-bonding. The computed values of α2 and β2 (Table 2) are compared with
those of other copper(II) complexes which are ionic in nature (41). Therefore, the present
complexes may be regarded as ionic complexes. The f -values of these complexes are found
to be 147 for 1, 139 for 2, 122 for 3 and 139 for 4, indicating significant distortion from
planarity.

306 R.N. Patel et al.
2.6. Cyclic voltammetry
The cyclic voltammogram for copper(II) complexes exhibit a metal-centered electrochemical
process.All the copper(II) complexes show a similar electrochemical behavior. The cyclic voltam-
mogram (Figure 6) of the representative complex is discussed here. The representative cyclic
voltammogram and relative parameter are given in Figure 6 and Table 3. Inspection of this figure
indicates that the reduction wave (Peak B) and its oxidation counterpart (Peak C) are related to
the Cu(II)/Cu(I) reduction process in the range 0 to −1.4 V while on the anodic side (range 0 to
+1.2 V), there exists an oxidation curve (Peak D) with its cathodic peak (Peak A). Analysis of
the cyclic voltammetric response of peak B/C indicates that this process originates from an irre-
versible Cu(II)/Cu(I) redox couple with a peak-to-peak separation (ꢀEp) of more than 350 mV
and the ratio of Ipa/Ipc is also more than unity. It is expected that the Cu(II)/Cu(I) couple expe-
riences some structural reorganization barrier while undergoing the reduction process. Patterson
and Holm (42) have shown that softer ligands tend to favor more positive E1/2 values while hard
acids give rise to more negative values.
The cyclic voltammetric behavior of all complexes between −0.250 to +1.2 V shows cathodic
response with its oxidation counterpart in the range −0.250 to −0.325 V. This feature corresponds
to an irreversible couple Cu(III)/Cu(II) process (43), as indicated by ꢀEp values. The redox
process associated with the oxidation of Cu(II) to Cu(III) may probably originate due to the
presence of the thio center. During the reverse scan, the oxidation of Cu(I)/Cu(II) skips over and
passes to the Cu(III) state. This was confirmed by the ratio of the anodic to the cathodic current
value of the Cu(II)/Cu(III) couple (Ipa/Ipc = 2). Since the thiodiglycolic acid is a flexible ligand,
it can adopt different conformations so as to fit the smaller size Cu(III) ion, thus favoring the
oxidation process. Moreover, this oxidation step results in the formation of a low-spin d8 Cu(III)
state with a preference for a square planar geometry (44).
Figure 6. Cyclic voltammogram of complex 2 in DMSO (0.1 M NaClO4 as the supporting electrolyte, scan rate:
100 mV/s).

Journal of Sulfur Chemistry 307
Table 3. Cyclic voltammetric data for 1 mM solution of the Cu(II) complexes in DMSO containing 0.1 M NaClO4 as
supporting electrolytes.
ꢀ
Scan
rate
Epc
(mV)
Ipc
(μA)
Epa
(mV)
Ipa
(μA)
ꢀEp
(mV)
E0
Compound
(mV)
Ipa/Ipc(μA)
1
100
200
300
−284
−308
−320
0.979
1.379
2.142
275
318
336
1.958
2.771
4.348
559
626
656
−4.5
2.0
2.0
2.0
−5.0
−8.0
2
3
100
200
300
−301
−363
−394
4.3965
6.624
7.558
239
285
324
8.880
13.446
15.040
540
648
718
−31
2.0
2.0
1.9
−39
−35
100
−344
2.606
−40
5.290
−304
−152
2.0
200
300
−350
2.789
3.802
−12
5.8569
7.718
−338
−169
2.1
2.0
−358
31
−327
−163
4
100
200
300
275
253
231
1.944
4.913
6.296
351
373
395
3.907
9.727
12.654
75
119
164
313
313
313
2.0
1.9
2.0
Note: ꢀEp = Epa − Epc; E0ꢀ = (Epa + Epc)/2.
2.7. SOD activity
The SOD-like activities of all the complexes were investigated by NBT assay, and the catalytic
activity toward the dismutation of superoxide ion was measured. The coordination arm with two
hydroxyethyl arms provide a stable and flexible environment similar to that in the active sites of
the native enzymes, insuring the stable existence of the native enzyme and the stable existence of
the complexes. In this work, the SOD-like activities for the four complexes were measured.
The chromophore concentration required to yield 50% inhibition of the reduction of NBT(IC50)
was determined by the following literature method (45). The representative graph showing IC50
value for complex 1 is given in Figure 7. The IC50 data of the SOD activity assay along with
kinetic catalytic constants of 1–4 complexes (46, 47) are presented in Table 4. The IC50 values
for complexes 1–4 are 44, 59, 53 and 65 μM, respectively. The activities of these complexes are
similar to those of the other mononuclear complexes (48–50). They are among the most active
model compounds but are somewhat less active than the native enzyme (IC50 = 0.04 μM).
Figure 7. SOD activity of 1.

308 R.N. Patel et al.
Table 4. IC50 values and kinetic constant of 1–4.
Compound
IC50 (μmol)
kMcCF(M−1 s−1)b × 104
1
2
3
4
44
59
53
65
2.16
1.61
1.79
1.46
Note: kMcCF were calculated by K = kNBT × [NBT]/IC50, kNBT
(pH 7.8) = 5.94 × 104 M−1 s−1 (46, 47).
Figure 8. A representative photograph of the size of inhibition diameter of control against E. coli bacteria.
Figure 9. A representative photograph of the size of inhibition diameter of 2 against E. coli bacteria.

Journal of Sulfur Chemistry 309
The difference in IC50 values for the complexes should be ascribed to the evident discrepancy
in the structures between them, especially in the confirmation of the ligand. Especially the two
labile hydroxyl arms, which are proposed to be easily substituted by the substrate, O−2 , in the
catalytic process, just like the O−2 in place of the water molecule bound to the copper site in the
mechanism of dismutation of superoxide ion by native SOD.
2.8. Antimicrobial activity
The biological and medicinal potency of coordination compounds has been established in their
antitumor, antiviral and antimalarial activities. This characteristic property has been related to
the ability of the metal ion to form complexes with a ligand containing sulfur and oxygen donor
atoms. The synthesized ligands and their complexes were screened for their antibacterial activity
Table 5. Antibacterial results of Schiff base and their metal complexes.
Compound
Concentration (μg/l)
Diameter of inhibition zone (in mm) E. coli
L1
L2
1
0.003
0.003
0.001
0.002
0.003
1
1
1
Not clear inhibition zone
2
2
3
0.001
0.002
0.003
3
3
5
0.001
0.002
0.003
1
1
3
4
0.001
0.002
0.003
Not clear inhibition zone
2
3
DMSO (control)
No inhibition zone
Note: Key to interpretation (for 100 μg/l): less than 12 mm, inactive; 12–16 mm, moderately active; above
16 mm, highly active.
E. coli
7
6
5
4
3
2
1
0
1
2
3
Concentraꢀon (mM)
Figure 10. Antibmicrobial activity of complex 2.

310 R.N. Patel et al.
(51) against Escherichia coli. Their activity was determined by measuring the diameter of zone
of inhibition (in mm) (Figures 8 and 9, Table 5). All the complexes showed a high antibacterial
activity against E. coli (Figure 10). In particular, all complexes showed higher activity than the
respective Schiff bases. This higher activity of the metal complexes compared with the Schiff
bases may be due to the change in the structure due to coordination.
3. Conclusion
The elemental analysis, magnetic susceptibility and electronic, IR and ESR spectral observa-
tions suggest the square pyramidal geometry for the complex 1 and an octahedral geometry for
complexes 2–4. They show a high antibacterial activity against E. coli.
4. Experimental
4.1. Materials
Copper(II) nitrate trihydrate was purchased from S.D. Fine Chemicals, India. All other chemicals
used were of synthetic grade and used without further purification.
4.2. Synthesis of Schiff base L1
The Schiff base was prepared by the reaction of 4-methylacetophenone and benzoylhydrazine
(Scheme 2). A solution of 4-methylacetophenone (2.70 g, 20.0 mmol) in ethanol (10 ml) was
mixed with the stirred solution of benzoylhydrazine (2.70 g, 20.0 mmol). The resulting solution
was refluxed for 4 h after the addition of one to two drops of acetic acid. On cooling the solution
at room temperature, pale yellow crystals were separated, filtered and washed with methanol.
The product was recrystallized in high yield from hot ethanol. Yield: 4.136 g (88%). Anal. Calcd
for C16H16N2O: C, 76.16; H, 6.39; N, 11.10%. Found: C, 76.06; H, 6.25; N, 11.02%. FAB Mass
(m/z) Found: 251.95, Calcd: 252.31.
CH3
O
NH
H2N
H3C
4-Methylacetophenone
O
Benzoylhydrazine
Ethanol
Reflux, at 60°C for 4h
CH3
NH
N
O
H3C
L1, N-[(1)-1-(4-Methylphenyl)ethylidene]benzolhydrazide
Scheme 2. Synthesis of ligand L1.

Journal of Sulfur Chemistry 311
4.3. Synthesis of Schiff base L2
N-[(1)-Pyridin-2-ylmethylidene]benzohydrazide was prepared according to the method
reported (52) in the literature. L1 was synthesized by reacting benzohydrazide and 2-
pyridenecarboxaldehyde in ethanol. Yield 2.06 g (85%). Anal. Calcd for C13H11N3O: C,
69.25; H, 4.88; N, 18.64%. Found: C, 69.02; H, 4.56; N, 18.45%. FAB mass (m/z) calcd:
225.26. Found: 225.26. Details of the synthesis are described as the supporting information in
Scheme 3.
N
O
HN
O
NH2
Benzoylhydrazine
2-Pyridinecarboxaldehyde
Reflux, 4h, at 60°C
Ethanol
O
N
N
NH
L2 N-[(1)-Pyridin-2-ylmethylidene]benzohydrazide
Scheme 3. Synthesis of ligand L2.
4.4. Synthesis of [Cu(H2L)(L1)] (1)
To a methanolic solution (10 ml) of cupric nitrate trihydrate (1.0 mmol, 0.241 g), a solution of
L1 (1.0 mmol, 0.252 g) in methanol was added with constant stirring at room temperature for
30 min. After 1 h of stirring, a methanolic solution (10 ml) of thiodiglycolic acid (1.0 mmol,
0.116 g) was added. The resultant solution was stirred for 4 h. The solution was filtered and
allowed to stand at room temperature for a few days. The brownish sticky complex was collected
and stored in a CaCl2 desiccator. Yield 0.481 g (79%). Anal. Calcd for C19H20CuN2SO (1): C,
52.7; H, 4.63; N, 6.48%. Found: C, 51.89; H, 3.98; N, 5.98%. FAB mass (m/z) found: 432.0.
Calcd: 431.88.
4.5. Synthesis of [Cu(H2L)(PMDT)] (2), [Cu(H2L)(Dien)] (3) and [Cu(H2L)(L2)] (4)
Complexes 2–4 were synthesized following the same procedure as 1, only PMDT (1.0 mmol,
0.173 g) for 2, Dien (1.0 mmol, 0.103 g) for 3 and L2 (1.0 mmol, 0.225 g) for 4 were added. The
resultant solution was stirred for 4 h. The solution was filtered and allowed to stand at room
temperature for a few days. The brownish sticky complex was collected and stored in a CaCl2
desiccator.Yield 0.435 g (82%). Anal. Calcd for C12H27CuN3S (2): C, 40.70; H, 7.63; N, 11.89%.
Found: C, 40.55; H, 7.45; N, 11.67%. FAB mass (m/z) found: 353.3. Calcd: 351.89.Yield 0.368 g
(80%). Anal. Calcd for C7H17CuN3S (3): C, 29.67; H, 6.01; N, 14.83%. Found: C, 29.45; H, 5.85;
N, 14.55%. FAB mass (m/z) found: 283.17. Calcd: 282.86. Yield 0.480 g (84%). Anal. Calcd for
C16H15CuN3SO (4): C, 47.37; H, 3.70; N, 10.36%. Found: C, 46.89; H, 3.65; N, 10.95%. FAB
mass (m/z) found: 405.26. Calcd: 404.86.

312 R.N. Patel et al.
4.6. Physical measurements
Elemental analyses of the complexes were performed on an Elementar Vario EL III Carlo
Erba 1108 analyser. FAB mass spectra were recorded on a JEOL SX 102/DA 6000 mass
spectrometer/data system using xenon (6 kV, 10 mA) as the FAB gas. The accelerating voltage
was 10 kV and the spectra were recorded at room temperature. UV–visible spectra were recorded
at 298 K on a Shimadzu UV–visible recording spectrophotometer UV-160 in quartz cells. IR spec-
tra were recorded in a KBr medium on a Perkin-Elmer spectrophotometer. X-band EPR spectra
were recorded with a Varian E-line Century Series Spectrometer equipped with a dual cavity
and operating at X-band (∼9.4 GHz) with a 100 kHz modulation frequency. TCNE was used as
a field marker. The frozen solutions at liquid nitrogen temperature used for EPR spectra were
in 3 × 10−3 M DMSO solution. The Varian quartz tubes were used for measuring EPR spectra
of polycrystalline samples and frozen solutions. The EPR parameters for copper(II) complexes
were determined accurately from a computer simulation program (53). Magnetic susceptibility
measurements were made on a Gouy balance using a mercury(II) tetrathiocyanato cobaltate(II) as
the calibrating agent (χg = 16.44 × 10−6 cgs units). Cyclic voltammetry was carried out with a
BAS-100 Epsilon electrochemical analyzer having an electrochemical cell with a three-electrode
system. Ag/AgCl was used as a reference electrode, glassy carbon as a working electrode and
platinum wire as an auxiliary electrode; 0.1 M NaClO4 was used as the supporting electrolyte and
DMSO as the solvent. All measurements were carried out at 298 K under a nitrogen atmosphere.
Molar conductivities of the freshly prepared 2 × 10−3 M DMSO solutions were measured on a
Systronics conductivity TDS meter 308.
4.7. In vitro antibacterial assay
The in vitro antimicrobial (antibacterial) activities of these complexes were tested using the paper
disk diffusion method (54). The chosen strain was E. coli. The liquid medium containing the
bacterial subculture was autoclaved for 20 min at 121◦C and at 15 lb pressure before inoculation.
The bacteria were then cultured for 24 h at 36◦C in an incubator. Nutrient agar was poured into a
plate and allowed to solidify. The test compounds (DMSO solutions) were added dropwise to a
10 mm diameter filter paper disk placed at the center of each agar plate. The plates were kept at
5◦C for 1 h and then transferred to an incubator maintained at 36◦C. The diameter of the growth of
inhibition zone around the disk was measured after 24 h incubation. Three replicates were made
for each treatment.
Acknowledgements
Our grateful thanks are due to the National Single Crystal X-ray Diffraction Facility, X-ray Division and RSIC (SAIF), IIT
Mumbai, for EPR measurements. The Head RSIC (SAIF), Central Drug Research Institute, Lucknow, is also thankfully
acknowledged for providing analytical and spectral facilities. Financial assistance from UGC [Scheme no. 36-28/2008
(SR)] and DRDO [Scheme no. ERIP/Er/06357/M/01/1118], New Delhi, are also thankfully acknowledged.
References
(1) Malamstrom, B.G. ZeitschriftfurNaturwissenschaFtlichmedizinische Grundlagen Forschung 1965, 2, 259–266.
(2) Gray, H.B. Proc. Natl Acad. Sci. USA 2003, 100, 3563–3568.
(3) Finney, L.A.; O’Halloran, T.V. Science 2003, 300, 931–936.
(4) Cantars, G.W.; Dennision, C. Biochimi. 1995, 77, 506–515.
(5) Alcaraz, L.A.; Gomez, J.; Ramirez, P.; Carlvente, J.J.; Andreu, R.; Donaire, A. BioInorg. Chem. Appl. 2007, 16, 1–9.
(6) Paraskevopoulos, K.; Sundararajan, M.; Surendran, R. J. Chem. Soc. Dalton Trans. 2006, 25, 3067–3076.
(7) Majumder, S.M.M.H.; Ali, M.A.; Smith, F.E.; Mridha, M.A.U. Polyhedron 1988, 7, 2183–2187.

Journal of Sulfur Chemistry 313
(8) Nakamoto, K. Infrared Spectra of Inorganic and Coordination Compounds, 2nd ed.; J. Wiley: New York, 1970;
p 376.
(9) Gavr, S.; Sharma, B. J. Indian Chem. Soc. 2003, 8, 841–842.
(10) Daniel, T.T.; Natarajan, K. Transition Met. Chem. 2000, 25, 347–351.
(11) Sharma, B.D.; Bailar, J.C. J. Am. Chem. Soc. 1955, 77, 5476–5480.
(12) Singh, K.; Singh Barwa, M.; Tyagi, P. Eur. J. Med. Chem. 2006, 41, 147–153.
(13) Sengupta, S.K.; Pandey, O.P.; Shrivastava, A.K.; Rai, R.; Mishra, K.D. Indian J. Chem. Sec. A 1999, 38, 956–960.
(14) Verma, R.S.; Garg, P.K. J. Indian Chem. Soc. 1981, 58, 980–981.
(15) Sen, A.K.; Singh, G.; Singh, K.; Hunda, R.N.; Dubey, S.N. Proc. Indian Acad. Sci. (Chem Sci.) 1998, 110, 75–81.
(16) Singh, G.; Singh, D.A.; Singh, K.; Singh, D.P.; Hunda, R.N.; Dubey, S.N. Proc. Indian Acad. Sci. Ind. 2002, 72A,
87–94.
(17) Agrawal, R.K.; Sarin, R.K.; Agrawal, H. Bull. Chem. Soc., Ethiopia 1995, 9, 23–29.
(18) Nakamoto, K. Infrared and Raman Spectra of Inorganic and Coordination Compound, 5th ed.; J. Wiley: NewYork,
1997.
(19) Clark, R.J.; Williams, C.S. Inorg. Chem. 1965, 4, 350–357.
(20) Kumar, A.; Kulkarni, D.; Patil, S.A.; Badami, P.S. J. Sufur Chem. 2009, 30, 145–159.
(21) Chikate, R.C.; Padhye, S.B. Polyhedron 2005, 24, 1689–1700.
(22) Lever, A.B.P. Inorganic Electronic Spectroscopy, 2nd ed.; Elsevier: Amsterdam, 1984.
(23) Kneubunl, F.K. J. Chem. Phys. 1960, 33, 1074–1077.
(24) Ainscough, E.W.; Brodie, A.M.; Larsen, N.G. Inorg. Chim. Acta 1982, 60, 25–34.
(25) Dedert, P.L.; Thompson, J.S.; Ibers, J.A.; Marks, T.J. Inorg. Chem. 1982, 21, 969–977.
(26) Nonoyama, M.; Yamasaki, K. Inorg. Chim. Acta 1971, 5, 124–128.
(27) El-Shatzly, M.F.; EI-Dissowky, A.; Salem, T.; Osman, M. Inorg. Chim. Acta 1980, 40, 1–6.
(28) Patil, N.; Patil, B.R. Oriental J. Chem. 2002, 18, 547–550.
(29) Geary, W.J. Coord. Chem. Rev. 1971, 7, 81–122.
(30) Hathaway, B.J. In Comprehensive Coordination Chemistry: Wilkinson, G., Gillard, R.G., McCleverty, J.A., Eds.;
Pergamon Press: Oxford, 1987; Vol. 5, p 533.
(31) Zoroddu, M.A.; Pilo, M.T.; Seeber, R.; Pogni, R.; Basosi, R. Inorg. Chim. Acta 1991, 183, 185–189.
(32) Kivelson, D.; Nieman, R. J. Chem. Phys. 1961, 35, 149–155.
(33) Patel, R.N.; Gundla, V.L.N.; Patel, D.K. Polyhedron 2008, 27, 1054–1060.
(34) Patel, R.N.; Singh, N.; Gundla, V.L.N. Polyhedron 2006, 25, 3312–3318.
(35) Chandra, S.; Sangeetika, W.; Thakur, S. Transition Met. Chem. 2004, 29, 925–935.
(36) Symons, M.C.R.; West, D.X.; Wilkinson, J.G. J. Chem. Soc. Dalton Trans. 1975, 16, 1996–1700.
(37) Rudley, R.J.; Hathaway, B.J. J. Chem. Soc. 1970, 10, 1725–1728.
(38) Hathaway, B.J.; Billing, D.E. Coord. Chem. Rev. 1970, 5, 143–207.
(39) Chikate, R.C.; Belapure, A.R.; Padhye, S.B.; West, D.X. Polyhedron 2005, 24, 889–899.
(40) West, D.X. Inorg. Nucl. Chem. 1981, 43, 3169–3174.
(41) Malmstrom, B.G.; Vanngard, T. J. Mol. Biol. 1960, 2, 118–124.
(42) Patterson, G.S.; Holm, R.H. Bioinorg. Chem. 1975, 4, 1257–1275.
(43) Franco, E.; Lopez-Torres, E.; Mendiola, M.A.; Sevilla, M.T. Polyhedron 2000, 19, 441–445.
(44) Bu, X.H.; Cao, X.; An, D.L.Ch.; Zhang, R.H.; Thomas, C.; Kimura, E. J. Inorg. Chem. Soc. Dalton Trans. 1998, 3,
433–437.
(45) Bielski, B.H.J.; Shiue, G.G.; Bajuk, S. J. Phys. Chem. 1980, 84, 830–833.
(46) Pasternack, R.F.; Halliwell, B. J. Am. Chem. Soc. 1979, 101, 1026–1031.
(47) Liao, Z.-R.; Zheng, X.-F.; Luo, B.-S.; Shen, L.-R.; Li, D.-F.; Liu, H.-L.; Zhao, W. Polyhedron 2001, 20, 2813–2821.
(48) Patel, R.N.; Gundla, V.L.N.; Patel, D.K. Indian J. Chem. 2008, 47A, 353–360.
(49) Han, J.; Xing, Y.; Wang, C.; Hou, P.; Bai, F.; Zeng, X.; Zhang, X.; Ge, M. J. Coord. Chem. 2009, 62, 745–751.
(50) Bhirud, R.G.; Shrivastava, T.S. Inorg. Chim. Acta 1991, 179, 125–130.
(51) Simoncini, F.; Rangone, R.; Calanni, C. Farmaco, Edizione, Pratica, Prat. 1968, 23, 559–570.
(52) Kotschy, A.; Farago, J.; Csampai, A.; Smith, D.M. Tetrahedron 2004, 60, 3421–3425.
(53) Giugliarelli, G.; Cannistraro, S. Nuovolimento 1984, 4D, 194–205.
(54) Gray, H.B.; Ballhausen, C.J. J. Am. Chem. Soc. 1963, 85, 260–265.