Synthesis, crystal structure, spectroscopic, and biological studies on Cu(II) complexes of N,O donor dimethyl isoxazole Schiff bases

Article abstract of DOI:10.1080/00958972.2012.755174

Cu(II) complexes with Schiff bases DMIIMP, DMIIMBD, DMIIMBP, DMIIMCP, DMIIMMP, and DMIIMNP (see Introduction for definitions) are derived from condensation of 3,4-dimethyl 5-amino-isoxazole with salicylaldehyde and substituted salicylaldehydes. The newly

Full text of DOI:10.1080/00958972.2012.755174

Journal of Coordination Chemistry
Vol. 66, No. 2, 20 January 2013, 274–286
Synthesis, crystal structure, spectroscopic, and biological
studies on Cu(II) complexes of N,O donor dimethyl isoxazole
Schiff bases
VIJAY KUMAR CHITYALA†, K. SATHISH KUMAR†, N.J.P. SUBHASHINI‡,
PALLEPOGU RAGHAVAIAHx and SHIVARAJ†*
†Department of Chemistry, Osmania University, Hyderabad, India
‡Department of Chemistry, University College of Technology, Osmania University,
Hyderabad, India
xSchool of Chemistry, University of Hyderabad, Hyderabad, India
(Received 27 November 2011; in final form 2 October 2012)
Cu(II) complexes with Schiff bases DMIIMP, DMIIMBD, DMIIMBP, DMIIMCP, DMIIMMP, and
DMIIMNP (see Introduction for definitions) are derived from condensation of 3,4-dimethyl
5-amino-isoxazole with salicylaldehyde and substituted salicylaldehydes. The newly synthesized
ligands were characterized by IR, UV-Vis, 1H NMR, 13C NMR, mass spectra, and elemental analy-
sis. The Cu(II) complexes were characterized by IR, UV-Vis, ESR, elemental analysis, magnetic
moments, thermogram, DTA, and single crystal analysis. The complexes have general formula [M
(L)2]. The Schiff bases are bidentate coordinating through the azomethine nitrogen and phenolic
oxygen of salicylaldehydes. Based on the analytical and spectral data, four-coordinate geometry is
assigned for all the complexes. ESR and single crystal analysis suggests square planar geometry
for all complexes. [Cu(DMIIMP)2] crystallizes in the orthorhombic system. Antimicrobial studies
of Schiff bases and their metal complexes show significant activity with the metal complexes show-
ing more activity than corresponding Schiff bases. Cytotoxicity of the copper complexes on human
cervical carcinoma cells (HeLa) was measured using the Methyl Thiazole Tetrazolium assay.
Keywords: Isoxazole Schiff base; Cu(II) complexes; Single crystal; Square planar; Antimicrobial
activity
1. Introduction
Heterocyclic rings containing Schiff bases and their analogs exhibit an important role in
several biological processes [1–4]. Schiff-based complexes were used as metal indicators
in complexometric titrations and as colorimetric reagents [5–9]. Generally, Schiff bases
exhibit good pharmacological properties such as antibacterial, antifungal, anticancer, anti-
HIV activity, and also have applications as pesticides and insecticides [9, 10]. Studies on
metal complexes of Schiff bases derived from 3-amino-5-methyl isoxazole and substituted
salicylaldehydes were reported earlier and their antimicrobial activity enhances upon metal
chelation [11–14]. Synthesis and characterization of 2-((3,4-dimethylisoxazol-5-ylimino)
methyl)phenol (DMIIMP) was reported earlier [15]. In continuation of this field of
*Corresponding author. Email: shivaraj_sunny@osmania.ac.in
Journal of Coordination Chemistry
ISSN 0095-8972 print/ISSN 1029-0389 online Ó 2012 Taylor & Francis
http://dx.doi.org/10.1080/00958972.2012.755174

Studies on Cu(II) complexes
275
CH3
H
DMIIMP: R=H
H3C
4'
3
6
DMIIMBD: R=OH
DMIIMBP: R=Br
DMIIMCP: R=Cl
DMIIMMP: R=OCH3
DMIIMNP: R=NO2
5'
3'
2
4
R
N
N
O
1'
2'
1
5
HO
Figure 1. Structure of Schiff bases.
study, we report herewith synthesis and characterization of Schiff bases (see figure 1)
of 2-((3,4-dimethylisoxazol-5-ylimino)methyl)benzene 1,4-diol) (DMIIMBD), 2-((3,4-dim-
ethylisoxazol-5-ylimino)methyl)-4-bromophenol (DMIIMBP), 2-((3,4-dimethylisoxazol-
5-ylimino)methyl)-4-chlorophenol (DMIIMCP), 2-((3,4-dimethylisoxazol-5-ylimino)methyl)
-6-methoxyphenol (DMIIMMP), 2-((3,4-dimethylisoxazol-5-ylimino)methyl)-4-nitrophenol
(DMIIMNP), and their Cu(II) complexes. [Cu(DMIIMP)2] was structurally characterized
by single crystal X-ray crystallography. The biological activity of the Schiff bases and their
metal complexes were carried out against bacteria and fungi. Cytotoxicity activity on
human cervical carcinoma cells (HeLa) was measured using the methyl thiazole
tetrazolium (MTT) assay.
2. Experimental
2.1. Physical measurements
1H and 13C NMR spectra of the ligands were recorded on a Bruker 400 MHz NMR instru-
ment using tetramethyl silane as internal standard. EI mass spectra were recorded on a
Vergleichdare Gerate (VG) micro mass 7070–H instrument; ESIMS spectra were recorded
on a VG AUTOSPEC mass spectrometer. Digital conductivity meter of model DI-909 hav-
ing a dip-type cell was calibrated with KCl solution. Electronic spectra of metal complexes
in DMSO were recorded on a Shimadzu UV-Vis 1601 spectrophotometer. Magnetic suscep-
tibilities of the complexes were determined on a Gouy balance model 7550 using Hg[Co
(NCS)4] as standard. Diamagnetic corrections of the complexes were computed using Pas-
cal’s constants. Thermogram of complexes were carried out on a Mettler Toledo Star system
in the temperature range of 0–1000 °C. Melting points of the ligands and decomposition
temperature of complexes were determined on a Polmon instrument (model No. MP-96). IR
spectra of the compounds were recorded using KBr pellets (4000–400 cmꢀ1) on a Perkin-
Elmer Infrared model 337. The C, H, N compositions of the compounds were determined
by using microanalytical techniques on a Perkin Elmer 240C (USA) elemental analyzer.
EPR spectra of the copper complexes were recorded on an EPR Varian-E-112 at RT. The
percentage composition of metal ions in solid metal complexes was determined by EDTA
titration. All chemicals used were analytical reagent grade. Water, methanol, acetone, petro-
leum ether, and chloroform were purified by standard procedures [16].
2.2. General procedure for the synthesis of isoxazole Schiff bases
3,4-Dimethyl-5-amino-isoxazole (1.0 mM) was dissolved in hot methanol to which salicyl-
aldehyde/5-hydroxy salicylaldehyde/5-bromo salicylaldehyde/5-chloro salicylaldehyde/3-
methoxy salicylaldehyde and 5-nitro salicylaldehyde (1.0 mM) was added and the mixture
was refluxed for 3 h under nitrogen. The dark yellow product formed was filtered and

276
V.K. Chityala et al.
washed with petroleum ether and recrystallized from methanol. Purity of the compounds
was checked by TLC showing a single spot in petroleum ether and ethyl acetate (6:4)
mixture. Yield: 80–85%.
2.3. Microwave-assisted synthesis of isoxazole Schiff bases
Microwave assisted condensation of 3,4-dimethyl-5-amino-isoxazole (1.0 mM) and
salicylaldehyde/5-hydroxy salicylaldehyde/5-bromo salicylaldehyde/5-chloro salicylalde-
hyde/3-methoxy salicylaldehyde, and 5-nitro salicylaldehyde (1.0 mM) was carried out in
1 mL of methanol in a domestic oven (LG, 1300 W, 28 L capacity). The reaction mix-
ture was subjected to microwave irradiation at 320 W for the period of time specified in
table 1. Microwave-assisted synthesis brought down the reaction time from 3 h to 3 min
and improved the yield from 80–85 to 90–95% in comparison with the conventional
method. The purity of the compounds was checked by TLC showing a single spot in
petroleum ether and ethyl acetate (6 : 4) mixture.
2.4. Synthesis of Cu(II) metal complexes
In preparation of metal complexes, the metal-to-ligand ratio was maintained at 1 : 2. Hot
methanol solution of ligand (1.0 mM) and hot methanol solution of copper acetate
monohydrate [Cu(CH3COOH)2·H2O (0.5 mM)] were mixed with constant stirring. The
mixture was refluxed for 2–3 h at 70–80 °C on a water bath. On cooling, metal complexes
precipitated. The products were filtered, washed with cold methanol, and dried under
vacuum over P4O10.
2.5. X-ray crystallographic procedures
Dark green single crystals of [Cu(DMIIMP)2] were grown by slow evaporation of methanol
and chloroform mixture for three days at room temperature. A crystal of the complex was
mounted on a glass fiber and used for data collection. Crystal data were collected at 298 K
using a Bruker SMART APEX CCD single crystal diffractometer equipped with a graphite
monochromator and Mo Kα fine-focus sealed tube (λ = 0.71073Å) operated at 2.0 kW, with
increasing ω (width of 0.3o/frame) at a scan speed of 5 s/frame. Data integration and reduc-
tion were processed with SAINTPLUS software [17] and an empirical absorption correction
was applied to the collected reflections with SADABS [18]. The crystal structure of the
compound was solved by direct methods and refined on F2 by full-matrix least-squares
Table 1. Comparison of conventional and microwave assisted syntheses of the compounds.
Conventional
Microwave at 320 W
Time (s) Yield (%)
60 94
S.No.
Ligand
M.P (°C)
Time (h)
Yield (%)
1
2
3
4
5
6
DMIIMP
128
162
147
281
110
232
3
4
2
2
3
2
75
75
85
76
80
78
DMIIMBD
DMIIMBP
DMIIMCP
DMIIMMP
DMIIMNP
90
40
45
95
30
92
95
94
93
96

Studies on Cu(II) complexes
277
using SHELXTL-97 [19]. All nonhydrogen atoms were refined anisotropically and hydro-
gens on carbons were added from calculation.
2.6. Cell culture
The human cervical carcinoma cell lines (HeLa) were cultured as a monolayer with
Roswell Park Memorial Institute medium (RPMI-1640), supplemented with 10% (v/v) fetal
bovine serum (FBS), 2 mM L-glutamine, 4.5 g Lꢀ1 glucose, 1 ꢁ nonessential amino acids,
and 1 ꢁ antibiotics consisting of penicillin/streptomycin, gentamycin, amphotericin B, and
nystatin at 37 °C, in a humidified atmosphere of 5% CO2, in a CO2 incubator.
2.6.1. Cytotoxicity assay (MTT assay). The MTT assay was used to assess cytotoxicity
[20]. HeLa were obtained from the National Center for Cell Science (NCCS), Pune, India.
Copper complexes (1–6) were dissolved in DMSO, diluted in culture medium, and used to
treat the cancer cell, with the complex at 2–10 μg mLꢀ1, for 72 h. DMSO diluted in the
culture medium was used as the solvent control. A miniaturized viability assay using
3-[4,5-dimethyl thiazole-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) was carried out
according to the method described by Mosmann [21]. HeLa cells growing exponentially
were added to 96-well plates (Orange Scientific) at a density of 3 ꢁ 103 per well after
counting on a Bright Line Haemocytometer (Sigma Ltd.). Compounds (1–100 μM) were
then added to the wells, ensuring an equal volume of 200 μL across the plates. Cell
number/proliferation was measured at 72 h using a standard-based assay (MTT assay)
without modification. MTT (Hi Media Ltd.) was added to each well to yield a working
concentration of 0.4 mg mLꢀ1 and the plates were returned to the incubator for an
additional 2 h. Then the medium was aspirated, 200 μL of DMSO (Sigma Ltd.) was added
to each well and the plates were agitated gently for 5 min before measuring the optical
density at 600 nm using a Thermo Scientific Multi Skan EX Elisa reader. The IC50 value
was determined as concentration of the complex that is required to reduce the absorbance
to half that of the control.
3. Results and discussion
3.1. Characterization of metal complexes
All the complexes are stable at room temperature and nonhygroscopic. On heating, they
decompose at high temperatures. The complexes are insoluble in water but are soluble in
DMSO.
3.1.1. Elemental analysis. The analytical data of the ligands, complexes, and the
composition assigned to the complexes are presented in table 2. From the data, it is clear
that the experimental values shown for each of the complexes are in agreement with the
theoretical values calculated for 1 : 2 ratios.
3.1.2. IR spectra. In order to study binding of the Schiff bases to copper, IR spectra of
the free ligands are compared with spectra of corresponding complexes. The important
absorption frequencies of all complexes with their ligands and their assignments are given
in table 3.

278
V.K. Chityala et al.

Studies on Cu(II) complexes
279
Table 3. IR absorption frequencies (cmꢀ1) of Schiff bases and complexes.
Compound
v (OH)
v (CH=N)
v (C–O)
v (M–O)
v (M–N)
Other bands
DMIIMP
[Cu(DMIIMP)2]
DMIIMBD
3427w, br
–
3416w
3325m
3365 br
3446w, br
1598s
1611s
1572s
1164m
1179w
1171s
–
580m
–
–
453m
–
–
–
–
[Cu(DMIIMBD)2]
DMIIMBP
1586m
1641s
1194m
1182s
521w
–
421w
–
–
779s
v(C–Br)
[Cu(DMIIMBP)2]
DMIIMCP
–
1647s
1605s
1174s
1183s
542m
–
455m
456w
3453w
778(s)
v(C–Cl)
[Cu(DMIIMCP)2]
DMIMNP
[Cu(DMIIMNP)2]
DMIIMMP
–
1607s
1602m
1604s
1597s
1610s
1176s
1293
1311m
1255s
1249s
545w
–
523m
–
3447w, br
–
–
–
–
–
3444w, br
–
417m
–
454w
[Cu(DMIIMMP)2]
525w
In Schiff bases, azomethine stretches appear as split bands with two maxima at
1646–1602 and 1598–1561 cmꢀ1. These bands shift to higher frequency by 10–35 cmꢀ1 in
complexes, indicating nitrogen of azomethine is coordinated [22–25]. A broad band at
3447 to 3416 cmꢀ1 due to phenolic OH disappears in their complexes, indicating coordina-
tion through phenolic hydroxyl [26]. For DMIIMBD, two medium intensity bands at 3416
and 3325 cmꢀ1 are due to stretch of the phenolic OH and the second OH para with respect
to the phenolic OH. A medium intensity band at 1293 to 1164 cmꢀ1 due to phenolic
υC–O shifted to higher or lower frequency by 8–23 cmꢀ1 in the complexes, suggesting
participation of the oxygen of the hydroxyl in bonding [27, 28]. Shifts are due to coordina-
tion of ligand to copper by the azomethine nitrogen and phenolic oxygen. This is also
supported by υM–O and υM–N vibrations in the far infrared region (523–580 and
417–456 cmꢀ1), respectively [29–32].
3.1.3. Thermal analysis. The thermogram of Cu-DMIIMP is given in (Supplementary
material with heating rate of 10 °C minꢀ1 under nitrogen, from ambient temperature to
1000 °C. Thermal decomposition of [Cu(DMIIMP)2] can be divided into four stages
113–283, 284–368, 369–453, and 454–708 °C, respectively. The mass loss of 34.51,
10.34, 11.25, and 7.70% against calculated values of 39.64, 11.87, 12.92, and 8.84% show
partial decomposition of the ligand. There is no clear plateau observed in the DT curve of
the complex, i.e. the intermediate is unstable, continuing to lose mass. The final residue
estimated as copper with 0.26 ligand is obtained at 708 °C and has mass loss of 23.45%
against the calculated value of 26.73%.
3.1.4. Magnetic susceptibility and electronic spectra. Electronic spectra and magnetic
moment of the metal complexes are listed in table 4. Magnetic moment values of Cu(II)
complexes are 1.84–1.98 B.M. The Cu(II) complexes show a single broad band at 15,455 to
2
2
16,920 cmꢀ1 due to B1g → Eg, suggesting square planar geometry. Square planar Cu(II)
complexes are expected to give three bands. However, these bands usually overlap, giving
only one broad absorption. The electronic spectra and magnetic moment data coupled with
the analytical and conductance data suggest square planar geometry for the Cu(II)
complexes.

280
V.K. Chityala et al.
Table 4. Electronic spectral data and magnetic susceptibilities.
Complex
Frequency in cmꢀ1 (nm)
e = 102 Mꢀ1 cmꢀ1
μeff (BM)
[Cu(DMIIMP)2]
[Cu(DMIIMBD)2]
[Cu(DMIIMBP)2]
[Cu(DMIIMCP)2]
[Cu(DMIIMMP)2]
[Cu(DMIIMNP)2]
16,920 (591)
15,455 (647)
16,233 (616)
16,891 (592)
15,954 (627)
16,273 (614)
0.045
0.051
0.059
0.061
0.072
0.049
1.87
1.84
1.98
1.92
1.89
1.96
3.1.5. ESR Spectra. ESR spectra of the Cu(II) complexes were recorded as polycrystal-
line samples on X band at 9.3 GHz under magnetic field strength 3400G. The complexes
show one intense isotopic absorption in the high field region due to tumbling of the
molecules in solution. The EPR parameters of viz. g‖, g\, Δg, and G are presented in table 5.
Values of g‖ and g\ are 2.149–2.159 and 2.039–2.043, respectively; g‖ > g\ > 2.0023 (ge)
2
suggest the unpaired electron is in the dx2ꢀy2 orbital giving B1g as the ground state,
consistent with square planar geometry. The g‖ values for all Cu(II) complexes are less than
2.3, in agreement with covalent metal ligand bond. The g values are related to axial symme-
try parameter G by the Hathway expression, i.e. G = (g‖ –2.0023)/(g –2.0023). According to
the data, the G values for the Cu(II) complexes are less than four, indicating the ligands are
strong field and the metal ligand bonding in these complexes is covalent [33, 34].
3.1.6. Structural elucidation of [Cu(DMIIMP)2] by single crystal analysis. Single
crystal X-ray diffraction reveals that [Cu(DMIIMP)2] consists of [C24H22CuN4O4] and crys-
tallizes in centrosymmetric orthorhombic Pbca space group with Cu(II) on a special position.
The X-ray crystal structure of [Cu(DMIIMP)2] shows half of the complex in its asymmetric
unit and eight molecules in the unit cell; relevant parameters are tabulated in table 6. An
ORTEP representation is shown in figure 2 with the atom numbering scheme; atoms shown
with (A) are generated through symmetry relation and the relevant symmetry codes are (A)
#1 ꢀx + 1,ꢀy,ꢀz + 1. Selected bond lengths and angles are given in table 7. Copper lies on a
crystallographic twofold rotational axis and is coordinated to two Schiff bases. The crystal
structure consists of discrete molecular species in which Cu(II) is square planar, ligated
through deprotonated phenolate oxygen O1 and the azomethine nitrogen N1. The observed
bond distances from metal center to donor sites are Cu(1)–O(1) = 1.8743(19) Å and Cu(1)–N
(1) = 1.984(2) Å, in agreement with reported values [35]. The O–Cu–O, N–Cu–N angles are
180.00 and 179.99, O–Cu–N angles are 90.92–89.08 [O(1)–Cu(1)–N(1) = 90.92° and O(1)
#1–Cu(1)–N(1) = 89.08°] which are ideal values for square planar geometry. The unit cell
parameters of the complex are a = 10.0321(19) Å, b = 9.8785(18) Å, c = 22.786(4) Å, and
α = β = γ = 90°.
Table 5. ESR data of copper complexes.
Complex
Temperature (K)
g‖
g\
Δg
G
[Cu(DMIIMP)2]
[Cu(DMIIMBD)2]
[Cu(DMIIMBP)2]
[Cu(DMIICP)2]
[Cu(DMIIMMP)2]
[Cu(DMIIMNP)2]
300
300
300
300
300
300
2.1594
2.1539
2.1498
2.1510
2.1497
2.1526
2.0431
2.0402
2.0423
2.0391
2.0411
2.0426
0.1162
0.1137
0.1075
0.1119
0.1086
0.1099
3.6928
3.8279
3.5416
3.8624
3.6437
3.5807

Studies on Cu(II) complexes
281
Table 6. Crystal data and structure refinement details for [Cu(DMIIMP)2].
Empirical formula
Formula weight
Temperature
C24H22CuN4O4
494.00
298(2) K
Wavelength
Crystal system
Space group
0.71073 Å
Orthorhombic
Pbca
Unit cell dimensions
a = 10.0321(19) Å
b = 9.8785(18) Å
c = 22.786(4) Å
α = 90.00
β = 90.00
γ = 90.00
Volume
Z
Density (calculated)
Absorption coefficient
F(0 0 0)
Crystal size
Theta range for data collection
Index ranges
Reflections collected
Independent reflections
Completeness to theta = 26.02°
Absorption correction
Max. and min. transmission
Refinement method
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I > 2σ(I)]
R indices (all data)
Largest diff. peak and hole (eÅꢀ3
2258.2(7) Å3
4
1.453 Mg mꢀ3
1.006 mmꢀ1
1020
0.42 ꢁ 0.32 ꢁ 0.16 mm3
1.79–26.02°
ꢀ12<=h<=11, ꢀ12<=k<=12, ꢀ27<=l<=27
19,924
2213 [R(int) = 0.0545]
99.1%
Semi-empirical from equivalents
0.8556 and 0.6774
Full-matrix least-squares on F2
2213/0/153
1.077
R1 = 0.0481, wR2 = 0.1141
R1 = 0.0643, wR2 = 0.1224
0.332 and ꢀ0.386
)
Figure 2. Thermal ellipsoidal plot of [Cu(DMIIMP)2] with atom labeling scheme. Displacement ellipsoids are
drawn at 30% probability level except for the H atoms, which are shown as circles of arbitrary radius. Atoms
shown with (A) are generated through symmetry relation and the relevant symmetry codes are (A) #1 ꢀx + 1,ꢀ
y,ꢀz + 1.

282
V.K. Chityala et al.
Table 7. Selected bond lengths [Å] and angles [°] for [Cu(DMIIMP)2].
C(7)–N(1)
C(8)–O(2)
C(8)–C(10)
C(8)–N(1)
C(9)–N(2)
C(9)–C(11)
C(10)–C(12)
Cu(1)–O(1)
1.299(4)
1.340(3)
1.341(4)
1.397(3)
1.289(5)
1.491(5)
1.482(4)
1.8743(19)
1.8743(19)
1.984(2)
1.984(2)
1.409(3)
Cu(1)–O(1)#1
Cu(1)–N(1)#1
Cu(1)–N(1)
N(2)–O(2)
O(1)–Cu(1)–O(1)#1
O(1)–Cu(1)–N(1)#1
O(1)#1–Cu(1)–N(1)#1
O(1)–Cu(1)–N(1)
O(1)#1–Cu(1)–N(1)
N(1)#1–Cu(1)–N(1)
180.0
89.08(9)
90.92(9)
90.92(9)
89.08(9)
179.998(1)
Symmetry transformations used to generate equivalent atoms: #1 ꢀx + 1,ꢀy,ꢀz + 1.
3.1.7. Antimicrobial activity. DMIIMP, DMIIMBD, DMIIMBP, DMIIMCP, DMIIMMP,
and DMIIMNP and their binary complexes with Cu(II) have been screened for antimicro-
bial activity against bacteria (Escherichia coli and Pseudomonas aeruginosa) and fungi
(Aspergillus niger and Rhizopus oryzae) by paper disc method. The susceptibility of the
ligands and their metal complexes were determined by measuring the size of inhibition
diameter. The concentration for these samples was maintained as 1 mg mlꢀ1 in DMSO.
The results thus obtained (table 8) are explained on the basis of Overtone’s concept and
Chelation theory [36, 37]. The mode of action of the compounds may involve formation
of a hydrogen bond through the azomethine group with the active centers of cell
constituents, resulting in interference with normal cell process [38].
The variation in the activity of different complexes against different organisms depend
either on the impermeability of the cells of the microbes or difference in ribosome of
microbial cells. A comparison of the biological activity of the synthesized compounds with
some known antibiotics (Gentamycin) is presented in table 8. [Cu(DMIICP)2], [Cu
Table 8. Antimicrobial activities of the Schiff bases and metal complexes.
Complex
E. coli
P. aeruginosa
R. oryzae
A. niger
DMIIMP
[Cu(DMIIMP)2]
DMIIMBD
[Cu(DMIIMBD)2]
DMIIMBP
[Cu(DMIIMBP)2]
DMIIMCP
++
++
++
+++
++
+++
+
+
++
++
+++
++
+++
++
+++
+
+
++
+
++
++
++
+
+
++
+
++
++
++
+
[Cu(DMIIMCP)2]
DMIIMMP
+++
+
++
+
++
+
[Cu(DMIIMMP)2]
DMIMNP
++
+
++
+
++
+
++
+
[Cu(DMIIMNP)2]
Gentamycin (Standard)
+
++
+
++
+
ꢀ
+
ꢀ
Highly active = +++ (inhibition zone > 15 mm); Moderatively active = ++ (inhibition zone > 10 mm); Slightly
active = + (inhibition zone > 5 mm); Inactive = ꢀ (inhibition zone < 5 mm).

Studies on Cu(II) complexes
283

284
V.K. Chityala et al.
(DMIIMBD)2], and [Cu(DMIIMBP)2] show good activity against bacteria and fungi. The
Schiff bases show moderate activity and all Cu(II) complexes show appreciable activity,
suggesting increase in activity upon complexation. On comparison with earlier reported sim-
ilar N,O donor Schiff base Cu(II) complexes, activity enhances upon complexation [39, 40].
3.1.8. Cytotoxic activity. The cytotoxic activity of copper complexes was examined on
cultured HeLa for 72 h to medium containing the respective complexes at 2–10 μg mlꢀ1
using MTT assay and results are given in table 9. The cytotoxic activity determined
according to dose values of the exposure of the complex required to reduce survival of the
cell is given in figure 3. Toxicities of 10 μg mlꢀ1 of [Cu(DMIIMP)2], [Cu(DMIIMBD)2],
[Cu(DMIIMBP)2], [Cu(DMIIMCP)2], [Cu(DMIIMMP)2], and [Cu(DMIIMNP)2] are 50.22,
53.65, 54.51, 63.52, 45.93, and 47.47%, respectively. [Cu(DMIIMCP)2] is a good
antitumor agent on HeLa cell lines. The IC50 values are given in table 10. The IC50 values
100
80
Control
2 µg/ml
4 µg/ml
60
6 µg/ml
8 µg/ml
40
10 µg/ml
12 µg/ml
14 µg/ml
20
0
Concentration of the copper complexes
Figure 3. Percentage of cell viability vs. different concentrations for HeLa cells exposed to the copper
complexes after 72 h incubation.
Table 10. IC50 range of Cu(II) complexes for HeLa cells.
Complex
IC50 (μg mlꢀ1
)
[Cu(DMIIMP)2]
[Cu(DMIIMBD)2]
[Cu(DMIIMBP)2]
[Cu(DMIIMCP)2]
[Cu(DMIIMMP)2]
[Cu(DMIIMNP)2]
10 0.04
10 0.7
6
6
0.08
0.9
10 0.8
12 0.6

Studies on Cu(II) complexes
285
of [Cu(DMIIMP)2], [Cu(DMIIMBD)2], [Cu(DMIIMMP)2], and [Cu(DMIIMMNP)2] are
higher for the 72 h treatment groups, in the range of 10 0.04–12 0.61 μg mlꢀ1, whereas
[Cu(DMIIMBP)2] and [Cu(DMIIMCP)2] are 6 0.90 μg mlꢀ1
.
4. Conclusions
Complexes of Cu(II) with N,O donor Schiff bases DMIIMP, DMIIMBD, DMIIMBP,
DMIIMCP, DMIIMMP, and DMIIMNP have been synthesized and characterized by analyt-
ical, conductance, IR, electronic, ESR spectral data, magnetic moments, and single crystal
X-ray crystallographic data. The metal ligand stoichiometries in these complexes are 1 : 2.
The Schiff-based ligands are mononegative, bidentate, coordinating through nitrogen of
azomethine and phenolic oxygen. Based on analytical data, all these complexes are square
planar. The ligands and metal complexes were screened against bacteria and fungi as size
of inhibition diameter. The Schiff bases show moderate activity and all Cu(II) complexes
show appreciable activity. [Cu(DMIICP)2], [Cu(DMIIMBD)2], and [Cu(DMIIMBP)2]
exhibit more potent antibacterial activity than the antibiotic. The cytotoxicity of all the
Cu(II) complexes was studied and [Cu(DMIIMCP)2] at 10 μg mlꢀ1 concentration shows
63.52% toxicity, suggesting a good antitumor agent on HeLA.
Supplementary material
Crystallographic details of [Cu(DMIIMP)2] in the form of CIF file is available with the
CCDC, number 851,651. This data can be obtained free of charge from the Cambridge
Crystallographic Data Center, 12 Union Road, Cambridge CB21EZ, UK; Fax: (+44)
1223-336-033 or E-mail: deposit@ccdc.cam.ac.uk.
Acknowledgments
The authors are grateful to the Head, Department of the Chemistry for providing the
necessary facilities. The authors are thankful to the Director, CFRD, Osmania University,
Hyderabad and the Director, IICT, Hyderabad for providing spectral and analytical data.
The authors are also thankful to UGC, New Delhi for providing financial assistance.
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