Synthesis, characterization, and antimicrobial activity of copper(II) complexes with N,N′-propanediyl-bis-benzenesulfonamide and N,N′-ethanediyl-bis-2-methylbenzenesulfonamide

Article abstract of DOI:10.1007/s00044-012-0171-2

Copper(II) complexes of new aryldisulfonamides (L ₁ = N,N′-bis[(2-methylphenyl)sulfonyl]ethylenediamine) and L ₂ = N,N′-propanediyl-bis-benzenesulfonamide with 1,10-phenanthroline have been synthesized and characterized by using elemental analyses, FT-IR, LCMS, conductivity, and magnetic susceptibility techniques. The structures of [Cu(phen)₂]L₁ (1) and [CuL₂(phen)₂] (2) compounds have been determined. Complex (1) has also been characterized by single crystal X-ray diffraction. The complex (1) crystallizes in the triclinic system, space group P1, with cell constants a = 12.9353(8) ?, b = 13.8543(9) ?, c = 14.4513(10) ?, α = 103.593(5), β = 113.713(5), γ = 106.104(5), and Z = 1. The antibacterial activities of synthesized compounds were studied against Gram-positive bacteria: Staphylococcus aureus, Bacillus subtilis, and B. cereus and Gram-negative bacteria: Escherichia coli, Pseudomonas aeruginosa, and Yersinia enterocolitica by microdilution (as MICs in μg/mL) and disk diffusion (as diameter zone in mm) method. The biological activity screening showed that (1) has more activity than (2) against the tested bacteria.

Full text of DOI:10.1007/s00044-012-0171-2

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res (2013) 22:2051–2060
DOI 10.1007/s00044-012-0171-2
ORIGINAL RESEARCH
Synthesis, characterization, and antimicrobial activity
of copper(II) complexes with N,N0-propanediyl-bis-
benzenesulfonamide and N,N0-ethanediyl-bis-2-
methylbenzenesulfonamide
¨
˙
•
•
•
Saliha Alyar Neslihan Ozbek Nazan Ocak Iskeleli
Nurcan Karacan
Received: 6 February 2012 / Accepted: 28 June 2012 / Published online: 14 September 2012
Ó Springer Science+Business Media, LLC 2012
Abstract Copper(II) complexes of new aryldisulfonamides
(L1 = N,N0-bis[(2-methylphenyl)sulfonyl]ethylenediamine)
and L2 = N,N0-propanediyl-bis-benzenesulfonamide with
1,10-phenanthroline have been synthesized and characterized
by using elemental analyses, FT-IR, LCMS, conductivity, and
magnetic susceptibility techniques. The structures of
[Cu(phen)2]L1 (1) and [CuL2(phen)2] (2) compounds have
been determined. Complex (1) has also been characterized by
single crystal X-ray diffraction. The complex (1) crystallizes
in the triclinic system, space group P1, with cell constants
Keywords Sulfonamide Cu(II) complexes ꢀ
Antimicrobial activity ꢀ Disk diffusion method ꢀ
MICs
Introduction
The importance of sulfonamide was realized (Domagk,
1935) whensulfonylamide, akey analog of sulfonamide, was
reported (Mandell et al., 1996) to be the first antibacterial
drug. Sulfonamides were the first effective chemotherapeu-
tic agents used systematically for the prevention and the cure
of bacterial infections in humans and other animal systems
(Bult, 1983; Nogrady, 1988). Many thousands of molecules
containing the sulfanilamide structure have been created
since its discovery, yielding improved formulations with
greater effectiveness and less toxicity. Sulfa drugs are still
widely used for conditions such as acne and urinary tract
infections, and are receiving renewed interest for the treat-
ment of infections caused by bacteria resistant to other
antibiotics. Also, a number of other activities, some of which
have been recently observed, include endotelin antagonism,
anti-inflammatory activity, tubular transport inhibition,
insulin release, carbonic anhydrase, and saluretic action,
among others (Wolff, 1996).
˚
˚
˚
a = 12.9353(8) A, b = 13.8543(9) A, c = 14.4513(10) A,
a = 103.593(5)°, b = 113.713(5)°, c = 106.104(5)°, and
Z = 1. The antibacterial activities of synthesized compounds
were studied against Gram-positive bacteria: Staphylococcus
aureus, Bacillus subtilis, and B. cereus and Gram-negative
bacteria: Escherichia coli, Pseudomonas aeruginosa, and
Yersinia enterocolitica by microdilution (as MICs in lg/mL)
and disk diffusion (as diameter zone in mm) method. The
biological activity screening showed that (1) has more activity
than (2) against the tested bacteria.
S. Alyar (&)
Department of Chemistry, Science and Art Faculty,
Karatekin University, 18100 C¸ ankırı, Turkey
e-mail: saliha@karatekin.edu.tr
To find better compounds, some metal sulfonamides
have attracted much attention due to the fact that com-
plexes showed more activity than both free ligands and the
corresponding metallic salts. In particular, Ag-sulfadiazine
has proved to be an effective topical antimicrobial agent of
significance in burn therapy, and better than the free ligand
or AgNO3 (Reynolds, 1996). Moreover, several Cu(II),
Ce(III), Bi(III), Cd(II), and Hg(II) sulfonamide complexes
have shown antibacterial activity (Bult, 1983; Casanova
et al., 1994; Chohan et al., 2005). In particular, a series of
¨
N. Ozbek
Department of Primary Education, Faculty of Education,
Ahi Evran University, 40100 Kırs¸ehir, Turkey
˙
N. O. Iskeleli
Department of Science Education, Ondokuz Mayıs University,
55200 Samsun, Turkey
N. Karacan
Department of Chemistry, Science and Art Faculty,
Gazi University, 06500 Ankara, Turkey
123

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Med Chem Res (2013) 22:2051–2060
X-ray structure determination
copper complexes with heterocyclic sulfonamides was
studied and a plausible explanation in terms of their
activities was presented (Kremer et al., 2006).
The crystal structure of the title molecule was mounted on
the goniometer of an STOE IPDS 2 diffractometer with
In our previous studies, aliphatic/aromatic bis sulfona-
mides were synthesized and tested for antimicrobial activity
(Alyar and Karacan, 2009; Ozbek et al., 2007a, b; Alyar
et al., 2007). Also, we have reported conformational analysis
and the vibrational spectroscopic investigation of methane-
sulfonic acid hydrazide (Ienco et al., 1999), methanesulfonic
acid 1-methylhydrazide (Ozbek et al., 2009a, b), and some
methanesulfonyl hydrazone derivatives (Dodoff et al., 1999;
Ozbek et al., 2009a, b; Alyar et al., 2008). In this study,
copper(II) complexes of N,N0-ethanediyl-bis-2-methylben-
zenesulfonamide and N,N0-propanediyl-bis-benzenesulfo-
namide were synthesized, characterized by elemental
analyses, FT-IR, LC–MS spectrometric methods, magnetic
susceptibility, conductivity measurements, and the X-ray
crystallography method for complex (1). These ligands were
obtained and characterized as previously reported (Alyar
et al., 2011). The antibacterial activities of synthesized
compounds were studied against Gram-positive bacteria:
Staphylococcus aureus, Bacillus subtilis, and B. cereus and
Gram-negative bacteria: Escherichia coli, Pseudomonas
aeruginosa, and Yersinia enterocolitica by the microdilution
method (as MICs) and disk diffusion method.
graphite
monochromatized
˚
Mo
Ka
radiation
(k = 0.71073 A). Data collection, reduction, and correc-
tions for absorption and decomposition were achieved
using X-AREA, X-RED software (Stoe and Cie, 2002).
The structure was solved by SHELXS-97 and refined with
SHELXL-97 (Sheldrick, 1997a, b). The positions of the H
atoms bonded to C atoms were calculated (C–H distance
˚
0.96 A) and refined using a riding model. The H atom
displacement parameters were restricted to be 1.2 Ueq of
the parent atom.
The complex (1) crystallizes in the triclinic system,
˚
space group P1, with cell constants a = 12.9353(8) A,
˚
˚
b = 13.8543(9) A, c = 14.4513(10) A, a = 103.593(5)°,
b = 113.713(5)°, c = 106.104(5)°, and Z = 1. Details of
the X-ray data collection, structure solution, and structure
refinements are given in Table 1. Selected bond distances
and angles are listed in Table 2. The molecular structure
with the atom-numbering scheme is shown in Fig. 1.
Synthesis of the complexes
Synthesis of [Cu(phen)2]L1 complex
0.5 mmol of L1 was added to a solution of 0.5 mmol of
Cu(II) acetate in 40 mL of acetonitrile. The mixture was
stirred for 3–4 h. Then, 1 mmol of 1,10-phenanthroline
was added. The compound precipitated slowly to a blue-
green solid when the mixture was warmed. The product
was filtered off, dried, and recrystallized from CH2CI2/n-
hexane. Single crystals were obtained after 1 month from
the resulting slow evaporation. Data for complex (yield
70 %). mp 338–340 °C APCI-MS (100 eV) m/z: 775.12
(M?, 12 %; M?1, 5.6 %); Anal. Calcd. for
C40H34N6O4S2Cu: C, 56.99; H, 3.58; N, 10.61; S, 10.61.
Found: C, 59.75; H, 4.18; N, 12.61; S, 6.19.
Experimental
Physical measurements
The elemental analyses (C, H, N, and S) were performed on
a LECO CHNS 9320 type elemental analyzer. The IR
spectra (4,000–400/cm) were recorded on a Mattson 1000
FT-IR Spectrophotometer with samples prepared as KBr
pellets. LC/MS-APCl was recorded on an AGILENT 1100
Spectrometer. The melting points were measured using an
Opti Melt apparatus. TLC was conducted on 0.25-mm
silica gel plates (60F 254, Merck). The molar magnetic
susceptibilities were measured on powdered samples using
Gouy method. The molar conductance measurements were
carried out using a Siemens WPA CM 35 conductometer.
All solvents purchased from Merck and reagents were
obtained from Aldrich Chem. Co. (ACS grade) and used as
received. The experiments were carried out in a dynamic
nitrogen atmosphere (20 mL/min) with a heating rate of
10 °C/min in the temperature range 30–400 °C using
platinum crucibles. The microdilution broth method was
used to determine the antibacterial activity of compounds
against the bacteria: E. coli ATCC 35218, P. aeruginosa
ATCC 27853, and Y. enterocolitica 0:3, S. aureus
ATCC 25923, B. subtilis ATCC 6633, and B. cereus
RSKK 709.
Synthesis of [CuL2(phen)2] complex
0.5 mmol of L2 was added to a solution of 0.5 mmol of
Cu(II) acetate in 40 mL of acetonitrile. The mixture was
stirred for 3–4 h. Then, 1 mmol of 1,10-phenanthroline
was added. The resulting solution was heated at 50 °C for
15 min. The compound precipitated quickly to a blue solid
after stirring the mixture at room temperature. The product
was filtered off, dried, and recrystallized from CH2CI2/n-
hexane. Slow evaporation of this filtrate produces prismatic
blue crystals. Data for complex (yield 70 %). mp
352–354 °C APCI-MS (100 eV) m/z: 790.41 (M?, 12 %;
M?1, 4.6 %); Anal. Calcd. for C39H32N6O4S2Cu: C, 65.62;
123

Med Chem Res (2013) 22:2051–2060
2053
˚
Table 1 Summary of crystal parameters, data collection, and
refinement for the complex (1)
Table 2 Some selected bond lengths (A) and bond angles for com-
plex (1)
˚
The bond lengths (A)
Color/shape
Blue/prism
40H34N6O4S2Cu
Chemical formula
Formula weight
Crystal system
Space group
C
Cu(1)–N(3)
1.9881
1.994
2.107
2.150
1.329
1.359
1.334
1.361
1.323
1.358
1.329
1.359
1.431
1.431
1.779
1.425
1.426
1.589
1.772
1.456
0.77
789.38
Triclinic
P1
Cu(1)–N(2)
Cu(1)–N(1)
Cu(1)–N(4)
˚
a = 12.9353(8) A
Unit cell dimensions
N(3)–C(22)
˚
b = 13.8543(9) A
N(3)–C(23)
˚
c = 14.4513(10) A
a = 103.593(5)°
b = 113.713(5)°
c = 106.104(5)°
N(2)–C(10)
N(2)–C(11)
N(4)–C(13)
N(4)–C(24)
3
˚
Volume
2093.8(2) A
N(1)–C(1)
Formula Z
2
N(1)–C(12)
Density (calculated)
Extinction coeff.
Absorption coefficient
1.252 M/gm3
0.0012(5)
0.666/mm
0.6945, 0.7735
816
S(2)–O(2)
S(2)–O(2)
S(2)–C(27)
T
min, Tmax
F000
min, hmax
min, kmax
min, lmax
S(4)–O(3)
S(4)–O(4)
h
-16, 16
S(4)–N(5)
k
-18, 17
S(4)–C(34)
l
-18, 18
N(6)–C(26)
R(int)
0.0304
N(6)–H(56)
Diffractometer/meas. meth
Unique reflections measured
Observed reflections
Data/parameters
Goodness of fit on F2
R indices [I [ 2r(I)]
Weighting scheme
STOE IPDS 2/x-scan
9,648
C(26)–C(25)
1.408
The bond angles (°)
N(3)–Cu(1)–N(1)
N(3)–Cu(1)–N(2)
N(3)–Cu(1)–N(4)
N(2)–Cu(1)–N(4)
N(2)–Cu(1)–N(1)
C(22)–N(3)–Cu(1)
C(23)–N(3)–Cu(1)
C(10)–N(2)–Cu(1)
C(11)–N(2)–Cu(1)
C(13)–N(4)–Cu(1)
C(24)–N(4)–Cu(1)
C(1)–N(1)–Cu(1)
C(12)–N(1)–Cu(1)
O(2)–S(2)–O(1)
O(2)–S2–N6
8,018
93.55
171.11
80.50
9,648/543
1.06
R1 = 0.045, wR2 = 0.115
w = 1/[r (F20) ? (0.0522P)2]
94.14
80.82
where P = (F2o ? 2Fc2)/3
126.28
115.04
126.98
114.42
132.36
110.04
131.0
H, 4.80; N, 11.95; S, 11.95. Found: C, 65.50; H, 4.76; N,
11.78; S, 7.95.
Procedure for antibacterial activity
110.92
118.92
107.59
107.62
107.05
106.66
117.30
106.91
108.06
109.33
107.25
108.69
107.65
Disk diffusion method (in vitro)
E. coli ATCC 35218, P. aeruginosa ATCC 27853, and Y.
enterocolitica 0:3, S. aureus ATCC 25923, B. subtilis
ATCC 6633, and B. cereus RSKK 709 cultures were
obtained from the Department of Biology at Gazi Univer-
sity and the Refik Saydam Hygiene Center Culture Col-
lection. Bacterial strains were cultured overnight at 37 °C
in a nutrient broth. These stock cultures were stored in the
dark at 4 °C during the survey. The compounds were
screened in vitro for their antibacterial activity against
three Gram-negative (E. coli, P. aeruginosa, and Y. en-
terocolitica) and three Gram-positive species (S. aureus,
O(2)–S(2)–C(27)
O(1)–S(2)–N(6)
O(1)–S(2)–C(27)
O(3)–S(4)–O(4)
O(3)–S(4)–N(5)
O(3)–S(4)–C(34)
O(4)–S(4)–N(5)
O(4)–S(4)–C(34)
N(6)–S(2)–C(27)
N(5)–S(4)–C(34)
123

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Med Chem Res (2013) 22:2051–2060
prepared at 400 lg/mL concentration were added to the
first wells. Then, 100 lL from the serial dilutions was
transferred into 14 consecutive wells. The contents of the
wells were mixed and the microplates were incubated at
37 °C for 24 h. The compounds were tested against each
microorganism twice. The MIC values were determined
from visual examinations as the lowest concentration of the
extracts in the wells with no bacterial growth (Koneman
et al., 1997; Gu¨ndu¨zalp Balaban et al., 2011).
Table 2 continued
C(25)–C(26)–N(6)
116.5
108.2
108.2
107.3
108.3
108.3
108.3
C(25)–C(26)–H(26B)
N(6)–C(26)–H(26A)
H(26A)–C(26)–H(26B)
N(5)–C(25)–H(25A)
C(26)–C(25)–H(25B)
N(5)–C(25)–H(25B)
B. subtilis, and B. cereus) of bacterial strains by the agar-
well diffusion method (Rahman et al., 2001; Chohan,
2004). The synthesized compounds were dissolved in
dimethylsulfoxide (10 %) to a final concentration of 4 mg/
mL and sterilized by filtration by 0.45 lm Millipore filters.
Two to eight hours old bacterial inocula containing
approximately 104–106 colony forming units (CFU/mL)
were spread on the surface of the nutrient agar using the
help of a sterile cotton swab. The paper disks impregnated
with the test compounds and complexes (70 lg) were
placed on the solidified medium. The plates were incubated
immediately at 37 °C for 24 h. The activity was deter-
mined by measuring the diameter of zones showing com-
plete inhibition (mm). Ciprofloxacin (5 lg/disk), ampicillin
(10 lg/disk), and penicillin (10 U) were chosen as a stan-
dard for the antibacterial activity measurements (positive
control). To clarify any participating role of DMSO in the
biological screening, separate studies were carried out with
the solutions alone of DMSO and they showed no activity
against any bacterial strains. Percentage of inhibition by
comparing distance of the compounds to the positive
control using (ciprofloxacin) the equation below (Mulaudzi
et al., 2011):
Results and discussion
Structure of the complexes
An ORTEP diagram of (1) is presented in Fig. 1. In
[Cu(phen)2]2? cationic complex, the copper atom is located
on a twofold axis and is tetracoordinated by the four
nitrogen atoms of two bidentate 1,10-phenanthroline mol-
˚
ecules. The equatorial Cu–N distances of 1.990 and 2.11 A
are similar to those determined for related copper com-
˚
plexes involving sulfonamides, for example, 1.992(2) A in
square planar bis[4-methyl-N-(2-pyridin-2-ylethyl) ben-
zenesulfonamide]copper(II) (Duran et al., 1997). The
angles between the nitrogen atoms and the copper atom is
N3–Cu1–N1 = (93.55)°, N2–Cu1–N4 = (94.14)°, N3–
Cu1–N4 = (80.50)°, N2–Cu1°N1 = (80.82)°. Unusually,
the sulfonamidate anions are not coordinated to copper(II).
The sulfonamide derivative (L1) does not interact with the
metal ion and behaves as a counter-ion in complex (1). A
lot number of Cu(II) complexes of related N-substituted
sulfonamides have been reported (Ferrer et al., 1989;
Casanova et al., 1996; Gutierrez et al., 2000, 2001; Alzuet
et al., 2001; Casanova et al., 2000). Important information
about the deprotonated sulfonamide group conformation
has been obtained.
ꢀ
ꢁ
diameter of the sample
%inhibition ¼
ꢁ 100:
diameter of the positive control
Figure 2 shows the molecular structure of (2). As seen in
Fig. 2, the copper atom is located on a twofold axis and is
hexacoordinated by the two amide nitrogen atoms of the
dianionic ligand and by four nitrogen atoms of Cu(II) can
be approximated as a distorted octahedron.
Microdilution assays
All tests were performed in a nutrient broth supplemented
with DMSO to a final concentration of 10 % (v/v) to
enhance their solubility. Test strains were suspended in the
nutrient broth by adjusting to the 0.5 McFarland standards.
The compounds to be tested were dissolved in DMSO to
give the highest concentration (400 lg/mL), and serial
dilutions thereafter in sterile 10-mL test tubes containing
nutrient broth to achieve sample concentrations in the
range of 40–400 lg/mL. The minimum inhibitory con-
centration (MIC) values of compounds were determined
using a modification of the microwell dilution assay
method. A total of 96-well plates were prepared by dis-
pensing 95 lL of nutrient broth and 5 lL of the inoculums
into each well. 100 lL from test compounds initially
IR spectra
IR spectra support the structure of the complexes by the
determination of the coordination modes. The changes in
the characteristic vibrations of the ligands were compared
with complexes. The t(NH) band in the free ligands is
observed around 3,198 and 3,288/cm strongly, but it dis-
appears by the chelation through the amide nitrogen in the
complexes. This observation indicates deprotonation of the
amide group. The asymmetric and symmetric –SO2 group
stretching vibrations in the ligands were observed at
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Med Chem Res (2013) 22:2051–2060
2055
Fig. 1 The molecular structure
of [Cu(phen)2]L1 with the atom-
numbering scheme;
displacement ellipsoids are
drawn at the 50 % probability
level
1,336–1,329 and 1,169–1,167/cm for L1 and L2, respec-
tively. In complex (1), the ta (SO2) and ts (SO2) did not
show significant shifts with respect to those of ligands, in
spite of deprotonation of the amide group. However, in the
spectra of complex (2), the ta (SO2) and ts (SO2) shifted to
lower frequencies by the chelation through the amide
nitrogen in the complex (Kremer et al., 2006; Macias et al.,
2003). In the IR spectra of complex (1), the vibration of the
imine nitrogen bond (C=N) of the stretching band of the
phenanthroline rings shifts from 1,644 to 1,585/cm by
complexation, which causes a great need for the oscillation
of the bonds in the ring. And as the electron clouds of
the C–N bonds flow to the phenantroline rings, making
the electron density around the C–N bonds decrease, the
stretching vibration of the C–N bond in Cu(II) complexes
shifts to low field. And also, the C–H out-of-plane bending
vibrations of the phenantroline ring were shifted in the
range 855–715/cm as compared with the coordination
compound in the range 865–725/cm included in between
ligand and rare earth ion (Yongliang et al., 2006). The
changes in the characteristic vibrations of the L2 were
compared with complex (2). The phenantroline rings with
two nitrogen atoms in the sulfonamide chelate copper(II)
ion, this does not make sense. In the IR spectra of the
compound, the vibration of the imine nitrogen bond (C=N)
of the stretching band of the phenanthroline rings shifts
from 1,644 to 1,588/cm by complexation. Also, the spectra
of the complex (2) shows two of the C–H out-of plane
bending vibration bands at 869 and 720/cm due to the
coordinated phenanthroline molecule (Sanchez-Piso et al.,
2002). The main vibration frequencies of the compounds
are listed in Table 3.
Mass spectra
Main fragmentation steps for complexes are exhibited in
Figs. 3, 4. As seen in Fig. 3, mass spectra of the complex
?
(1) gives the molecular ion [Cu(phen)2]L1 peak at m/z
(intensity%) = 790.41 (12 %). The spectra also exhibit
two peaks for the [Cu(phen)2]? fragment m/z = 423.96
(50 %) and for the [L1]? fragment m/z = 368.47 (14 %).
The removal of one (phen) group (C12H8N2Cu) gives peak
at m/z = 243.0 (8.0 %) and the residual group (C12H8N2)
gives peak at m/z = 181.0 (100 %). The mass spectra of
the complex (2) show (in Fig. 4) the molecular ion
[CuL2(phen)2]? peak at m/z = 775.12 (12 %). The spectra
also show three peaks for the [CuL2(phen)]? fragment at
m/z = 596.0 (14 %), for the [L2]? fragment at m/
z = 354.44 (22 %) and for the (C12H8N2) fragment at m/
z = 181.0 (100 %).
Table 3 Major IR absorption bands (/cm) of sulfonamide derivatives
and their Cu(II)complexes
Assignment
L1
L2
(1)
(2)
Fig. 2 The molecular structure
of [CuL2(phen)2]
t (NH)
3,198(s)
3,063(w)
1,336(s)
2,973(w)
1,169(s)
1,452(m)
3,288
3,060
1,329
–
–
–
tar (C–H)
tas (SO2)
tas (CH3)
ts (SO2)
d (NH)
3,030
1,336
2,973
1,169
–
3,050
1,328
–
1,167
1,451
1,167
–
123

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Med Chem Res (2013) 22:2051–2060
+
N
N
+
+
CH3
H3C
CH3
SO2NH(CH2)2NHSO2
H3C
N
N
SO2N(CH2)2NSO2
Cu
N
N
N
N
Cu
N
N
Cu
N
N
C12H8N2Cu
m/z=243.0 (4%)
CH3
H3C
C24H16N4Cu
SO2N(CH2)2NSO2
m/z=423.96 (50%)
C40H34N6O4S2Cu
m/z=790.41 (12%)
Cu
CH3
H3C
N
N
SO2N(CH2)2NSO2
N
N
N
Cu
N
+
+
CH3
H3C
SO2NH(CH2)2NHSO2
N
N
C16H20N2O4S2
C12H8N2
m/z=181.0 (33%)
m/z=368.47 (14%)
Fig. 3 The main fragmentation route of [Cu(phen)2]L1
+
Fig. 4 The main fragmentation
route of [CuL2(phen)2]
+
SO2
N
SO2
N
N
N
N
N
N
(CH2)3 Cu
N
N
(CH2)3 Cu
N
N
O2S
N
O2S
C39H32N6O4S2Cu
m/z=775.12 (12%)
C27H24N6O4S2Cu
m/z=596.0 (14%)
SO2
N
(CH2)3Cu
N
N
N
N
Cu
N
N
O2S
N
+
+
SO2NH(CH2)3NHSO2
N
N
C15H18N2O4S2
C12H8N2
m/z=181.0 (100%)
m/z=354.44 (22%)
123

Med Chem Res (2013) 22:2051–2060
2057
Molar conductivity
agar-disk diffusion method (Tables 4, 5). The antibacterial
activity results evidently show that the sulfonamide com-
pounds possessed a broad spectrum of activity against the
tested bacteria at the concentrations of 60–320 l/mL. All
compounds showed poor activity against B. subtilis, and L2
exhibited the lowest inhibitory activity with an MIC of
320 lg/mL. It is observed that the copper(II) complexes
are better antibacterial agents than Schiff bases. Chelation
reduces the polarity of the metal ion because of the partial
sharing of its positive charge with the donor groups and a
possible p-electron delocalization system. Meanwhile, the
increment of the lipophilic character of the complexes may
be responsible for their potent biological activities. The
lipids and polysaccharides are main fragments of the cell
walls and membranes, which are responsible for the metal
interactions. The permeation of complexes through the
lipid layer of the cell membranes blocks some cellular
enzymes, which play a vital role in various metabolic
systems of these microorganisms like Tweed’s chelation
The complexes appear to be air stable, soluble in DMSO,
and slightly soluble in acetonitrile. The molar conductivi-
ties (Km) of 10-3 M solutions of the complexes were
measured in DMSO at 25 °C. The experimental conduc-
tivity value falls in the range of a 1:1 electrolyte (Geary,
1971). Anionic ligand (L1)2- is bonded out of the coordi-
nation sphere as counter-ion. Complex (2) is non-con-
ducting and the measured molar conductance ranged from
2.0 to 3.6 S cm2/mol, indicating its neutrality.
Magnetic properties
The magnetic moment of the octahedral complexes (as
BM) was measured at room temperature. The magnetic
moment of the complex (1) (2.06 BM) is close to the spin
value 1 for one unpaired electron and within the general
range for Cu(II) complexes. Complex (2) has paramagnetic
characters and the effective magnetic moment value is
1.91 BM.
˘
theory (Keskioglu et al., 2008; Venkatachalam and Ra-
mesh, 2005; Mohamed et al., 2005). If ligands are com-
pared with each other, L1 has more activity than L2 against
the tested bacteria. The results obtained revealed that the
antibacterial activity decreased as the length of the carbon
chain increased (Alyar and Karacan, 2009; Ozdemir et al.,
2009; Ozdemir and Olgun, 2008). As seen in Tables 4, 5,
complex (1) shows higher antibacterial activity than com-
plex (2). The sulfonamide ligand in complex (1) increased
the activity against bacteria for the acts as a counter-ion. In
Antibacterial bioassay
Ligands and their Cu(II) complexes were screened in vitro
for their antibacterial activity against three Gram-positive
species (S. aureus, B. subtilis, and B. cereus) and three
Gram-negative species (E. coli, P. aeruginosa, and Y. en-
terocolitica) of bacterial strains by the microdilution and
Table 4 Antimicrobial activity
Compounds MIC (lg/mL)
of sulfonamide derivatives and
their Cu(II) complexes with
microdilution method
E. coli P. aeruginosa
ATCC35218 ATCC27853
Y. B. cereus
enterocolitica RSKK709
0:3
B. subtilis
ATCC6633
S. aureus
ATCC25923
L1
L2
(1)
(2)
80
100
60
120
180
100
140
80
80
60
80
100
280
80
240
320
120
160
80
100
60
80
240
80
Table 5 Result of the
antimicrobial test of
sulfonamide derivatives and
Cu(II) complexes disk potency
70 lg
Compounds Diameter inhibition zone (mm, 70 lg/disk)
E. coli P. aeruginosa Y.
ATCC35218 ATCC27853
B. cereus
B. subtilis
enterocolitica RSKK709 ATCC6633 ATCC25923
S. aureus
0:3
L1
L2
(1)
(2)
23
20
25
22
24
18
26
20
–
18
17
19
18
–
16
17
22
20
26
8
22
18
26
23
–
18
17
20
18
29
8
Ciprofloxacin 36
Penicillin
17
11
–
–
–
\10: weak, [10: moderate,
[16: significant
Ampicillin
–
–
13
–
14
123

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Med Chem Res (2013) 22:2051–2060
Fig. 5 Comparison of
antibacterial activities
Fig. 6 Percentage of inhibition
of the compounds
Acknowledgments The authors wish to thank TUBITAK for the
financial support (No: TBAG 104 T 390) and Gazi University Sci-
entific Research Projects (No: 05/2008-05). We would also like to
thank TUBITAK for the allocation of time for the NMR, Mass
Spectra, and Elemental Analyses.
addition, the inhibition zones formed by standard antibi-
otics (ciprofloxacin, penicillin, and ampicillin) against all
bacteria are reported in Table 5, Figs. 5, 6. The results
were compared with those of the standard drugs. All
compounds showed significant activity than penicillin and
ampicillin for all Gram-negative and Gram-positive bac-
terial strains.
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