Novel metal-based antimicrobial agents of copper(II) complexes: Synthesis, spectral characterization and DNA interaction study

Article abstract of DOI:10.1134/S0036023610070120

Few novel mixed ligand copper(II) complexes of the type [Cu(L)(Cl)2(H2O)], [Cu(L)₂]Cl₂, [Cu(L)L¹] and [Cu(L)(phen)H ₂O]Cl₂ (where L is the ligand obtained from the condensation of N-(2-aminoethyl)-1,3

Full text of DOI:10.1134/S0036023610070120

ISSN 0036ꢀ0236, Russian Journal of Inorganic Chemistry, 2010, Vol. 55, No. 7, pp. 1064–1074. © Pleiades Publishing, Ltd., 2010.
COORDINATION COMPOUNDS
Novel Metalꢀbased Antimicrobial Agents of Copper(II) Complexes:
Synthesis, Spectral Characterization and DNA Interaction Study1
N. Raman and J. Joseph
Research Department of Chemistry, VHNSN College, Virudhunagarꢀ626 001, India
eꢀmail: drn_raman@yahoo.co.in
Received July 29, 2008
Abstract—Few novel mixed ligand copper(II) complexes of the type [Cu(L)(Cl)2(H2O)], [Cu(L)2]Cl2,
[Cu(L)L1] and [Cu(L)(phen)H2O]Cl2 (where L is the ligand obtained from the condensation of
N
ꢀ(2ꢀamiꢀ
ꢀchlorobenzaldehyde (Lb)/benzaldehyde
pꢀhydroxybenzaldehyde (Le)/furfuraldehyde (Lf)/pyrroleꢀ2ꢀcarboxaldeꢀ
noethyl)ꢀ1,3ꢀpropanediamine with
(Lc)/ ꢀmethoxybenzaldehyde (Ld)/
mꢀnitrobenzaldehyde (La)/o
p
hyde (Lg); L1 is another ligand obtained from the condensation of anthranilic acid with salicyaldehyde; phen
= 1,10ꢀphenanthroline) have been synthesized and characterized by the spectral and analytical techniques.
From these data, it is found that the ligands adopt distorted octahedral geometry on metalation with Cu(II)
ion. The XRD data indicate that the complexes are polycrystalline with nanosized grains. The SEM images
of [Cu(La)phen(H2O)]Cl2 and [Cu(Lf)2]Cl2 complexes show that they have leaf and cauliflower like morꢀ
phology. The in vitro biological screening effects of the investigated compounds have been tested against the
bacteria such as Escherichia coli, Klebsiella pneumoniae, Salmonella typhi, Pseudomonas aeruginosa and Staꢀ
phylococcus aureus and fungi such as Aspergillus niger, Rhizopus stolonifer, Aspergillus flavus, Rhizoctonia bataꢀ
icola and Candida albicans by the well diffusion method. A comparative study of MIC values of the Schiff base
ligands and their complexes indicates that the complexes exhibit higher antimicrobial activity than the free
ligands. An electrochemical study of the copper complexes containing electron withdrawing substituted
ligands reveals that they prefer to bind to DNA in Cu(II) rather than Cu(I) oxidation state.
DOI: 10.1134/S0036023610070120
1
INTRODUCTION
Cu(II) complexes. Furthermore, taking into considerꢀ
ation the use of copper complexes in the treatment of
some diseases, mentioned above, we have tested the
antimicrobial activity of the synthesized ligands and
complexes using bacteria such as Escherichia coli,
Klebsiella pneumoniae, Salmonella typhi, Pseudomonas
aeruginosa and Staphylococcus aureus and fungi such
as Aspergillus niger, Rhizopus stolonifer, Aspergillus flaꢀ
vus, Rhizoctonia bataicola and Candida albicans.
With their versatile structures, redox behavior, and
physicochemical properties, transition metal comꢀ
plexes are often useful as chemical nucleases [1–5].
The interaction of these complexes with DNA has
gained much attention due to their possible applicaꢀ
tions as new therapeutic agents. The manipulation of
the ligands greatly facilitates the interaction between
the complexes and DNA [6–17].
The discovery and development of antibiotics are
among the most powerful and successful achievements
of modern science and technology for the control of
infectious diseases. Metal based drugs represent a
novel group of antimicrobial agents with potential
applications for the control of bacterial and fungal
infections. This inspires synthetic chemists to search
for new metal complexes for bioactive compounds and
copper in particular has attracted the researchers.
Probably the most widely studied cation in this respect
is Cu(II), since a host of lowꢀmolecularꢀweight copper
complexes have been proven beneficial against several
diseases such as tuberculosis, rheumatoid, gastric
ulcers and cancers [18, 19].
EXPERIMENTAL
Materials and methods. All reagents were of Merck
products and used as supplied. Micro analytical data
and FAB Mass spectra of the compounds were
recorded at the Sophisticated Analytical Instrument
Facility, Central Drug Research Institute (SAIF,
CDRI), Lucknow. The FAB mass spectrum of the
complex was recorded on a JEOL SX 102/DAꢀ6000
mass spectrometer/data system using argon/xenon
(6 kV, 10 mA) as the FAB gas. The accelerating voltage
was 10 kV and the spectra were recorded at room temꢀ
perature using
mꢀnitrobenzyl alcohol (NBA) as the
matrix. The IR spectra of the samples were recorded
on a Shimadzu FTIRꢀ8400S spectrophotometer in
4000–200 cm–1 range using pellet with KBr. The UVꢀ
Vis. spectra were recorded on a Shimadzu UVꢀ1601
Hence, this work presents the synthesis and charꢀ
acterization of few novel mixed ligands and their
1
The article is published in the original.
1064

NOVEL METALꢀBASED ANTIMICROBIAL AGENTS
1065
spectrophotometer. Magnetic susceptibility measureꢀ H, 5.64; N, 9.42. Found: Cu, 14.29; C, 51.22; H, 5.68;
ments of the complexes were carried out by Gouy balꢀ N, 9.46%; μeff (BM), 2.06; Λm(mhocm2 mol–1), 18;
ance using copper sulphate as the calibrant. The values Data of [Cu(Ld)Cl2(H2O)]: Yield: 40%; Elemental
were corrected for diamagnetism by applying Pascal’s analysis: Anal. Calc. for CuC20H29N3O3Cl2]: Cu,
constants. The molar conductance of the complexes 12.87; C, 48.63; H, 5.91; N, 8.51. Found: Cu, 12.90;
was measured using a Systronic conductivity bridge. C, 48.70; H, 5.95; N, 8.55%; μeff(BM), 1.94;
The Xꢀband EPR spectra of the complex was recorded Λm(mhocm2 mol–1), 29; Data of [Cu(Le)Cl2(H2O)]
:
at 300 and 77 K at IIT, Mumbai using TCNE (tetracyꢀ Yield: 65%; Elemental analysis: Anal. Calc. for
anoethylene) as the gꢀmarker. SEM images were CuC19H25N3O3Cl2: Cu, 13.30; C, 68.09; H, 5.26; N,
recorded in a Hitachi SEM analyzer. XRD was 8.79. Found: Cu, 13.35; C, 68.14; H, 5.31; N, 8.83;
recorded on a Rigaku Dmax Xꢀray difrractometer with μeff(BM), 2.02; Λm(mhocm2 mol–1), 24; Data of
CuKa radiation (
Synthesis of Schiff base ligands. The Schiff base was
synthesized by mixing an ethanolic solution of
λ
= 1.5404 Å).
[Cu(Lf)Cl2(H2O)]: Yield: 56%; Elemental analysis:
Anal. Calc. for CuC15H21N3O3Cl2: Cu, 14.92; C, 42.31;
H, 4.97; N, 9.87. Found: Cu, 14.95; C, 42.34; H, 5.05;
N, 9.91%; μeff(BM), 1.94; Λm(mhocm2 mol–1), 26; Data
of [Cu(Lg)Cl2(H2O)]: Yield: 60%; Elemental analysis:
Anal. Calc. for CuC15H23N5OCl2: Cu, 14.99; C, 42.51;
H, 5.46; N, 16.53. Found: Cu, 15.03; C, 42.54; H, 5.50;
N, 16.56%; μeff(BM) 1.98; Λm(mhocm2 mol–1) = 22.
m
ꢀnitrobenzaldehyde(La)/
benzaldehydes(Lc)/ ꢀmethoxy benzaldehyde(Ld)/
hydroxybenzaldehyde(Le)/ furfuraldehyde (Lf)/ pyrꢀ
roleꢀ2ꢀcarboxaldehyde(Lg) (10 mM) with ꢀ(2ꢀamiꢀ
oꢀchlorobenzaldehyde(Lb)/
p
pꢀ
N
noethyl)ꢀ1,3ꢀpropanediamine (5 mM) followed by
reflux for 3 h and the resulting solution was then
Molar ratio 1 : 2. Data of [Cu(La)2]Cl2
analysis: Anal. Calc.
obtained solid was filtered, washed with ethanol and CuC38H42N10O8Cl2: Cu, 7.04; C, 50.53; H, 4.68; N,
:
Yield: 60%;
allowed to stand at room temperature for 8 h. The Elemental
for
dried in vacuo.
15.50. Found: Cu, 7.09; C, 50.56; H, 4.72; N, 15.55%;
μeff(BM), 1.89; Λm(mhocm2 mol–1), 117; Data of
[Cu(Lb)2]Cl2: Yield: 45%; Elemental analysis: Anal.
Calc. for CuC38H42N6Cl6: Cu, 7.39; C, 53.13; H, 4.92;
N, 9.78. Found: Cu, 7.44; C, 53.16; H, 4.96; N,
9.83%; μeff(BM), 1.86; Λm(mhocm2 mol–1), 84; Data
of [Cu(Lc)2]Cl2: Yield: 30%; Elemental analysis: Anal.
Calc. for CuC38H42N6Cl2: Cu, 8.81; C, 63.28; H, 6.42;
N, 11.65. Found: Cu, 8.85; C, 63.35; H, 6.46; N,
11.70%; μeff(BM), 1.88; Λm(mhocm2 mol–1), 89; Data of
[Cu(Ld)2]Cl2: Yield: 35%; Elemental analysis: Anal.
Calc. for CuC40H54N6O4Cl2: Cu, 7.78; C, 58.78; H,
7.78; N, 10.28. Found: Cu, 7.82; C, 58.83; H, 6.70; N,
10.33%; μeff(BM), 1.90; Λm(mhocm2 mol–1), 95; Data
of [Cu(Le)2]Cl2: Yield: 50%; Elemental analysis: Anal.
Calc. for CuC38H46N6O4Cl2: Cu, 8.09; C, 58.13; H,
3.33; N, 10.70. Found: Cu, 8.13; C, 58.16; H, 3.36; N,
10.75%; μeff(BM), 2.02; Λm(mhocm2 mol–1), 98; Data
of [Cu(Lf)2]Cl2: Yield: 30%; Elemental analysis: Anal.
Calc. for CuC30H38N6O4Cl2: Cu, 9.33; C, 65.91; H,
7.00; N, 15.37. Found: Cu, 9.36; C, 65.95; H, 7.04; N,
15.41%; μeff(BM), 1.96; Λm(mhocm2 mol–1), 140; Data
of [Cu(Lg)2]Cl2: Yield: 56%; Elemental analysis: Anal.
Calc. for CuC30H42N10Cl2: Cu, 9.38; C, 53.21; H, 6.25;
N, 20.67. Found: Cu, 9.42; C, 53.25; H, 6.30; N,
Data of La: Yield: 56%; Elemental analysis: Anal.
Calc. for C19H21N5O4: C, 59.52; H, 5.51; N, 18.26.
Found: C, 59.55; H, 5.54; N, 18.30%; Data of Lb:
Yield: 62%; Elemental analysis: Anal. Calc. for
C19H21N3Cl2: C, 62.99; H, 5.83; N, 11.59. Found: C,
63.02; H, 5.85; N, 11.63%; Data of Lc: Yield: 42%;
Elemental analysis: Anal. Calc. for C19H23N3: C,
77.78; H, 7.89; N, 14.32. Found: C, 77.81 H, 7.92; N,
14.35%; Data of Ld: Yield: 36%; Elemental analysis:
Anal. Calc. for C20H27N3O2: C, 70.36; H, 7.96; N,
12.30. Found: C, 70.40; H, 8.01; N, 12.35%. Data of
Le: Yield: 75%; Elemental analysis: Anal. Calc. for
C19H23N3O2: C, 70.13; H, 7.12; N, 12.91. Found: C,
70.17; H, 7.16; N, 12.95%; Data of Lf: Yield: 60%; Eleꢀ
mental analysis: Anal. Calc. for C15H19N3O2: C, 65.92;
H, 7.00; N, 15.37. Found: C, 65.95; H, 7.05; N,
15.40%; Data of Lg: Yield: 48%; Elemental analysis:
Anal. Calc. for C15H21N5: C, 66.40; H, 7.79; N, 25.81.
Found: C, 66.45; H, 7.83; N, 25.85%.
Molar ratio 1:1/ Molar ratio 1 : 2. A hot ethanolic
solution of Schiff base and CuCl2 · 2H2O (1 : 1/2 : 1
molar ratio) was refluxed for 4 h. Then the solution
was reduced to oneꢀthird on a water bath. The solid
complex precipitated was filtered and washed with
20.71%; μeff(BM), 1.86; Λm(mhocm2 mol–1), 135
.
ethanol and dried in vacuo
.
Synthesis of Schiff base L1. The Schiff base L1 was
prepared using the reported method [20].
Molar ratio 1 : 1. Data of [Cu(La)Cl2(H2O)]: Yield:
49%; Elemental analysis: Anal. Calc. for
CuC19H23N5O5Cl2: Cu, 11.85; C, 42.58; H, 4.32; N,
13.06. Found: Cu, 11.88; C, 42.62; H, 4.35; N,
13.10%; μeff(BM), 1.86; Λm(mhocm2 mol–1), 25; Data
of [Cu(Lb)Cl2(H2O)]: Yield: 58%; Elemental analysis:
Anal. Calc. for CuC19H23N3Cl4O: Cu, 12.35; C, 44.33;
H, 4.50; N, 8.16. Found: Cu, 12.38; C, 44.36; H, 4.54;
N, 8.20%; μeff(BM), 1.98; Λm(mhocm2 mol–1), 14; Data
of [Cu(Lc)Cl2(H2O)]: Yield: 35%; Elemental analysis:
Mixed ligand complexes of phenanthroline. A hot
ethanolic solution of Schiff base and 1, 10ꢀphenanꢀ
throline in ethanol was added to an ethanolic solution
of CuCl2 2H2O (1 : 1 : 1 molar ratio) and the mixture
⋅
was stirred for 1 h. The solid product so formed was
separated by filtration and washed with ethanol and
dried in vacuo
.
Data of [Cu(La)phen(H2O)]Cl2: Yield: 45%; Eleꢀ
Anal. Calc. for CuC19H25N3OCl2: Cu, 14.25; C, 51.18; mental analysis: Anal Calc. for CuC31H30N7O5: Cu,
RUSSIAN JOURNAL OF INORGANIC CHEMISTRY Vol. 55 No. 7 2010

1066
RAMAN, JOSEPH
8.87; C, 52.00; H, 21.80; N, 13.69. Found: Cu, 8.92; 9.79%; μeff(BM)
C, 52.05; H, 21.85; N, 13.74%; μeff(BM), 2.02; of [Cu(Lg)L1]: Yield: 56%; Elemental analysis: Anal.
Λm(mhocm2 mol–1),
108; Data of Calc. for CuC29H30N6O3: Cu, 11.06; C, 60.67; H,
[Cu(Lb)phen(H2O)]Cl2: Yield: 52%; Elemental analꢀ 5.26; N, 11.64. Found: Cu, 11.11; C, 60.72; H, 5.32;
,
1.88; Λm(mhocm2 mol–1), 18; Data
ysis: Anal. Calc. for CuC31H31N5OCl2: Cu, 10.18; C, N, 11.68%; μeff(BM), 2.00; Λm(mhocm2 mol–1), 20
.
In vitro antimicrobial activity. In vitro antimicroꢀ
bial assay was performed by well diffusion method.
The complexes and ligands were tested against bacteꢀ
ria such as Escherichia coli, Klebsiella pneumoniae,
Salmonella typhi, Pseudomonas aeruginosa and Staꢀ
phylococcus aureus by the well diffusion method using
nutrient agar as the medium and fungi such as
Aspergillus niger, Rhizopus stolonifer, Aspergillus flavus,
Rhizoctonia bataicola and Candida albicans, cultured
on potato dextrose agar as medium. In a typical proceꢀ
dure, a well was made on the agar medium inoculated
with the microorganisms. The well was filled with the
test solution using a micropipette and the plate was
59.65; H, 5.00; N, 11.23. Found: Cu, 10.21; C, 59.69; H,
5.04; N, 11.27%; μeff(BM), 1.90; Λm(mhocm2 mol–1),
145. Data of [Cu(Lc)phen(H2O)]Cl2: Yield: 56%;
Elemental analysis: Anal. Calc. for CuC31H33N5O
Cu, 10.15; C, 59.47; H, 5.31; N, 11.19. Found: Cu,
10.19; C, 59.55; H, 5.35; N, 11.22%; μeff(BM)
:
,
1.96; Λm(mhocm2 mol–1), 110; Data of
[Cu(Ld)phen(H2O)]Cl2: Yield: 30%; Elemental analyꢀ
sis: Anal. Calc. for CuC32H37N5O3: Cu, 9.42; C, 57.02;
H, 5.53; N, 10.39. Found: Cu, 9.47; C, 57.06; H, 5.58;
N, 10.55%; μeff(BM), 2.00; Λm(mhocm2 mol–1), 136;
Data of [Cu(Le)phen(H2O)]Cl2: Yield: 43%; Elemental
analysis: Anal. Calc. for CuC31H33N5O3: Cu, 9,66; C,
56.58; H, 5.05; N, 10.64. Found: Cu, 9.70; C, 56.62;
H, 5.10; N, 10.70%; μeff(BM), 1.92; Λm(mhocm2 mol–1),
126; Data of [Cu(Lf)phen(H2O)]Cl2: Yield: 45%;
incubated at 30 C for 72 h. During this period, the test
°
solution diffused and the growth of the inoculated
microorganisms was affected. The inhibition zone
developed on the plate was measured. The MIC of the
complexes was determined by serial dilution techꢀ
nique [21].
DNA binding experiments. CTꢀDNA was purꢀ
chased from Bangalore Genei (India). DNA solution
in 5 mM TrisꢀHCl/50 mM NaCl (pH 7.2) buffer
medium gave a ratio of UVꢀ absorbance at 260–
280 nm of ca. 1.8–1.9 indicating that the DNA was
sufficiently free from protein concentration. The
DNA concentration per nucleotide was determined by
absorption spectroscopy using the molar absorption
coefficient (6600 M–1 cm–1) at 260 nm [22]. TrisꢀHCl
buffer solution was prepared using deionized, soniꢀ
cated triply distilled water.
Cyclic voltammetry study was performed on a Bioꢀ
AnalyticalꢀSystem CVꢀ50W electrochemical analyzer
with three electrode system of a glassy carbon (GC)
electrode as the working electrode, a platinum wire as
auxiliary electrode and Ag/AgCl as the reference elecꢀ
trode. Solutions were deoxygenated by purging with
N2 prior to measurements. The freshly polished GC
Elemental analysis: Anal. Calc. for CuC27H29N5O3
:
Cu, 10.47; C, 53.50; H, 4.82; N, 11.55. Found: Cu,
10.51; C, 53.55; H, 4.87; N, 11.61%; μeff(BM),
1.88; Λm(mhocm2 mol–1), 112; Data of
[Cu(Lg)phen(H2O)]Cl2: Yields: 60%; Elemental analyꢀ
sis: Anal. Calc. for CuC27H31N7O: Cu, 10.52; C, 53.69;
H, 5.17; N, 16.23. Found: Cu, 10.55; C, 53.74; H, 5.22;
N, 16.26%; μeff(BM), 1.92; Λm(mhocm2 mol–1), 108
.
Mixed ligand complexes of L1. A hot ethanolic
solution of Schiff base and L1 was added to an ethanꢀ
olic solution of CuCl2 2H2O (1 : 1 : 1 molar ratio) and
⋅
the mixture was refluxed for 1 h and the resulting soluꢀ
tion was then allowed to stand at room temperature for
3 h. The solid product so formed was separated by filꢀ
tration and washed with ethanol and dried in vacuo
.
Data of [Cu(La)L1]: Yield: 30%; Elemental analyꢀ
sis: Anal. Calc. for CuC33H30N6O7: Cu, 9.23; C, 57.60;
H, 4.68; N, 12.21. Found: Cu, 9.27; C, 57.65; H, 4.72;
N, 12.25%; μeff(BM),
1.93; Λm(mhocm2 mol–1), 12;
Data of [Cu(Lb)L1]: Yield: 75%; Elemental analysis:
Anal. Calc. for CuC33H30N4O3Cl2: Cu, 9.56; C, 59.60;
H, 4.54; N, 8.42. Found: Cu, 9.60; C, 9.65; H, 4.60;
electrode was modified by transferring a droplet of
of 5.75
2 L
μ
10–3 M of DNA solution on to the surface,
N, 8.47%; μeff(BM),
1.90; Λm(mhocm2 mol–1), 05;
×
Data of [Cu(Lc)L1]: Yield: 52%; Elemental analysis:
Anal. Calc. for CuC33H32N4O3: Cu, 10.66; C, 66.49;
H, 5.41; N, 9.40. Found: Cu, 10.70; C, 66.52; H, 5.43;
followed by air drying. Then the electrode was rinsed
with distilled water. Thus, a DNAꢀmodified GC elecꢀ
trode was obtained and both, the peak currents and the
peak potentials, were reproducible to better than 10%
under experimental conditions [23].
N, 9.44%; μeff(BM),
2.04; Λm(mhocm2 mol–1), 20;
Data of [Cu(Ld)L1]: Yield: 50%; Elemental analysis:
Anal. Calc. for CuC34H36N4O5: Cu, 9.86; C, 63.39; H,
5.63; N, 8.70. Found: Cu, 9.91; C, 63.44; H, 5.69; N,
8.75%; μeff(BM), 1.98; Λm(mhocm2 mol–1), 10; Data
of [Cu(Le)L1]: Yield: 44%; Elemental analysis: Anal.
RESULTS AND DISCUSSION
The ligands and their complexes are found to be
Calc. for CuC33H32N4O5: Cu, 10.11; C, 63.10; H, stable in air. The ligands are soluble in common
5.13; N, 8.92. Found: Cu, 10.15; C, 63.15; H, 5.17; N, organic solvents but their complexes are soluble in
8.95%; μeff(BM), 1.90; Λm(mhocm2 mol–1), 12; Data acetonitrile, DMF and DMSO. The elemental analyꢀ
of [Cu(Lf)L1]: Yield: 42%; Elemental analysis: Anal. sis results for the metal complexes agree well with the
Calc. for CuC29H27N4O5: Cu, 11.05; C, 60.57; H, calculated values. The observed low molar conducꢀ
4.73; N, 9.74. Found: Cu, 11.09; C, 60.61; H, 4.80; N, tance values of the complexes [Cu(L)(Cl)2(H2O)] and
RUSSIAN JOURNAL OF INORGANIC CHEMISTRY Vol. 55 No. 7 2010

NOVEL METALꢀBASED ANTIMICROBIAL AGENTS
1067
[
Cu(L)(L1)] in acetonitrile of 10–3 M solution at room 1595 and 1400 cm–1 in the Schiff base corresponding
temperature are consistent with their nonꢀelectrolytic to the asymmetric and symmetric stretching vibration
nature due to the absence of counter (chloride) ions in bands of the ionic carboxyl group
(COO–) in the
the structure of the complexes. However, [Cu(L)2]Cl2 complexes are shifted to lower frequencies 1585 and
and [Cu(L)(phen)(H2O)]Cl2 complexes show higher 1390 cm–1 respectively. The
(OH) band originally
ν
ν
molar conductance values indicating 1 : 2 electrolytic found in the Schiff base disappeared on complexation
nature of the complexes due to two counter (chloride) indicating deprotonation of the phenolic hydroxyl
ions in the structure of the complexes [24].
group and coordination of phenolic oxygen to the
metal. This is further supported by the shift in the
stretching frequency of the phenolic
ν
1530 cm–1 to the higher side by 10–20 cm–1. In the
low frequency region, the bands observed in the region
(C–O) at
Mass Spectra
The FAB mass spectra of the Schiff base ligands
and their copper complexes are used to compare their
stoichiometric composition. The Schiff base ligand
Lf) shows a molecular ion peak at 271
copper complex [Cu(Lf)2]Cl2, exhibits at 677
ther, one of the fragment ions exhibits a peak at
607 suggesting the presence of two chloride ions.
These two chloride ions are present outside the coorꢀ
dination sphere which is indicated by the test with silꢀ
ver nitrate. These data confirm the stoichiometry of
the copper chelates as [Cu(Lf)2]Cl2. This is also supꢀ
ported by the FAB mass spectra of the other comꢀ
plexes. Similarly, FAB mass spectra confirm the stoꢀ
ichiometry of the other type of copper chelates. The
elemental analysis values are also in good agreement
with the values calculated for molecular formulae
assigned to these complexes.
of 525–535 cm–1 are attributed to
ν
(Cu–N), in the
(Cu–O) phenolic, and in
the region of 415–420 cm–1 to
(Cu–O) carboxyl
groups. The sharp bands in the range 750–780 and
1525–1535 cm–1 are due to aromatic
(C–H) and
region of 465–480 cm–1 to
ν
ν
(
m
/
z
whereas its
m/z. Furꢀ
ν
ν
(C=C), respectively. A band in the region 310–
m/z
280 cm–1 is also present due to M–Cl bond.
Electronic Absorption Spectra
The electronic absorption spectra of Schiff base
ligands and their copper complexes were recorded at
300 K using ethanol and acetonitrile solvents respecꢀ
tively. The absorptions in the ultraviolet region are
attributed to transitions within the ligand orbital and
those in the visible region are probably due to allowed
metalꢀtoꢀligand charger transfer transitions (MLCT).
The selected electronic absorption bands are discussed
here. The Schiff base shows two absorptions, 29560
and 32680 cm–1, which are intraꢀligand charger transfer
transitions. The UVꢀVis., spectrum of the copper comꢀ
IR Spectra
The IR spectra taken in the region 4000–200 cm–1
provide some information regarding the mode of coorꢀ
dination in the complexes and were analyzed by a
careful comparison with that of the free ligands. The
selected IR absorption bands are discussed here. The
plex displays a broad band in the 12260–15460 cm–1
2
region, which is assigned to E2g
2T2g transition,
attributed to an octahedral geometry around the cenꢀ
tral metal ion. The broadness of the band can be taken
as an indication of Jahn–Teller distortion from the
regular symmetry.
ligands show characteristic band for
ν
(N–H) at
3320 cm–1. In all the complexes, the
ν(N–H) bands
were shifted by 122–140 cm–1 to lower frequencies,
due to coordination of the NH groups. The formation
of the Schiff bases is confirmed by the presence of a
band specific for (C=N) and the subsequent disapꢀ
ν
EPR Spectra
pearance of bands due to aldehydic and amino groups.
IR spectra of the Schiff bases exhibit a band in 1625–
The EPR spectra of metal chelates provide inforꢀ
1400 cm–1 region attributable to the
ν
(C=N) groups. mation about hyperfme and super hyperfme structures
On chelation, due to possible drift of the lone pair which are of importance in studying the metal ion
density towards the metal, the azomethine (C=N) environment in the complexes i.e., the geometry,
ν
bond is expected to absorb at lower frequency in the nature of the coordinating sites of the Schiff base and
complex. The bands were also shifted by 19–48 cm–1 the metal and the degree of covalency of the metalꢀ
to lower frequencies, due to participation of the ligand bonds. The EPR spectrum of the [Cu(Lg)2]Cl2
azomethine groups in coordination. The coordination was recorded in CH3CN at 300 and 77 K. The specꢀ
of nitrogen to the metal atom is supported by the trum of the above copper complex at 300 K shows one
appearance of a new band in the region 430–478 cm–1 intense absorption band in the highꢀfield region,
assignable to
ν
(Cu–N) vibration. The IR spectra which is isotropic due to the tumbling motion of the
exhibit a broad band in the region 3400–3000 cm–1
,
molecules. However, this complex in the frozen soluꢀ
suggesting the presence of coordinated water moleꢀ tion shows four wellꢀresolved peaks with low intensiꢀ
cules. The weak bands around 850 and 710 cm–1 are ties in the low field region. No band corresponding to
assigned as (OH) rocking and wagging vibrations the ms = 2 transition was observed in the spectra, rulꢀ
ν
respectively. The two absorption bands occurring near ing out any Cu–Cu interaction.
RUSSIAN JOURNAL OF INORGANIC CHEMISTRY Vol. 55 No. 7 2010

1068
RAMAN, JOSEPH
2
2
The observed
that there is interaction in the outꢀplane
whereas inꢀplane ꢀbonding is completely ionic. This
is also confirmed by orbital reduction factors (K|| and
) which are calculated from the following equaꢀ
β
(1.05) and
γ
(0.17) values indicate
π
ꢀbonding,
π
HC
N
OH
K
H
N
⊥
tions:
R
N CH
K2|| = (g – 2.0023)(E/8
λ
),
(4)
(5)
N
||
C OH
H
R C
K2 = (g – 2.0023)(E/8
λ
),
O
⊥
⊥
(L1)
(L)
where
λ
Eqs. (4) and (5) is 17538 and 16578 cm–1 respectively.
= –828 cm–1 for the free metal ion and E of
Fig. 1. Structure of the Schiff base ligands.
In the case of pure
σ
ꢀbonding K = K , whereas K <
||
⊥
||
K
implies considerable inꢀplane
π
ꢀbonding while for
ꢀbonding K > K . For the present comꢀ
plex, the observed order||is K ⊥(0.92) > K (0.39) implyꢀ
⊥
outꢀplane
π
The observed g|| and
respectively. The gꢀvalues of the above copper complex
are consistent with tetragonally elongated octahedral
geometry (g|| > g > 2.0) and the unpaired electron
occupies predominantly in the dx
axial spectra, the gꢀvalues are related with exchange
coupling constant (G) by the expression
g values are 2.24 and 2.05
⊥
||
⊥
ing a greater contribution from outꢀplane ꢀbonding
π
than from inꢀplane ꢀbonding in metal ligand
ꢀbonding.
Based on the above spectral and analytical data, the
π
⊥
π
orbital [25]. In
2 – y2
proposed structures of the Schiff base ligands and their
copper complexes are shown in Fig. 1 and Fig. 2
respectively.
g|| – 2.0023
g – 2.0023
G = ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ.
⊥
XRD Study
According to Hathaway [26, 27], if the G is larger
than four, exchange interaction is negligible because
the local tetragonal axis is misaligned. For the present
copper complex, the G value is 4.8, which suggests
that the local tetragonal axis is aligned parallel or
slightly misaligned and consistent with dx 2 ground
The XRD pattern of [Cu(La)phen(H2O)]Cl2 comꢀ
plex (Fig. 3) shows well defined crystalline peaks indiꢀ
cating that the sample is crystalline in nature. It has
specific 'd' values which can be used for its characterꢀ
ization. The crystallite size of the complex dXRD could
be estimated from XRD patterns using the Scherre’s
formula (1)
2 –
y
state.
EPR and optical spectra have been used to deterꢀ
mine the covalent bonding parameters for the Cu(II)
ion in various environments. Since there has been
wide interest in the nature of bonding parameters in
the system, we adopted the simplified molecular
orbital theory [25] to calculate the bonding coeffiꢀ
dXRD = 0.9
is the wavelength,
maxima and is the diffraction angle. The XRD shows
λ/β(cos
θ),
(6)
where
λ
β
is the full width at half
θ
that the above complex has the average crystallite size
of 53 nm, confirming the nanocrystalline nature of the
complex.
cients such as inꢀplane
ꢀbonding (
2). The inꢀplane
is related to and according to the following
π
ꢀbonding (
β
2) and inꢀplane
σ
α
σ
ꢀbonding parameter,
2
The surface morphology of [Cu(La)phen(H2O)]Cl2
and [Cu(Lf)2]Cl2 complexes are shown in Figs. 4a and
4b. From the SEM images of the complexes, it is
inferred that the [Cu(La)phen(H2O)]Cl2 has leaf like
morphology, while [Cu(Lf)2]Cl2 has cauliflower like
morphology. The particle size of the above complexes
was in the diameter range of few microns. However,
particles with sizes less than 100 nm were also observed
which groups to form agglomerates of larger size. The
smaller grain sizes found from XRD data suggest that
these complexes are polycrystalline with nanosized
grains.
α
g
g
||
⊥
equation:
2
α = (A||/0.036) + (g|| – 2.0023)
(1)
+3/7(g – 2.0023) + 0.04.
⊥
If the
2 value is 0.5, it indicates a complete covaꢀ
α
2
lent bonding, while the value of
α
= 1.0 suggests a
2
α
complete ionic bonding. The observed value of
(0.85) indicates that the complex has some covalent
character. The inꢀplane ꢀbonding (
2) and outꢀplane
ꢀbonding (
2) parameters are calculated from the folꢀ
lowing equations:
π
β
π
γ
2 = (g
−
2.0032)(E/–8λα2),
2.0032)(E/–2λα2),
(2)
Antimicrobial Activity
β
||
In view of the biological importance of copper(II)
complexes, in the present study, the antibacterial and
γ
2 = (g
−
(3)
⊥
where
λ
Eqs. (2) and (3) is 17538 and 16578 cm–1 respectively. tested against the bacteria such as E. coli, K. pneumoꢀ
= –828 cm–1 for the free metal ion and E of antifungal activities of the copper(II) complexes were
RUSSIAN JOURNAL OF INORGANIC CHEMISTRY Vol. 55 No. 7 2010

NOVEL METALꢀBASED ANTIMICROBIAL AGENTS
1069
R
R
CH
N
CH
N
R
H2O
M
CH
Cl
Cl
HN
N
N
NH
Cl2
M
N
NH
N
CH
CH
R
CH
R
Molar ratio (M : L)
1 : 1 complexes
R
1 : 2 complexes
R
R
H2O
CH
CH
CH
N
O
N
N
N
N
M
M
Cl2
O
C
NH
N
NH
N
O
CH
R
CH
R
[M(L)(L1)]
[M(L)(phen)(H2O)]Cl2
Where
M = Cu(II);
R =
;
Y
X
X = –NO2 (La); –Cl (Lb); –H (Lc); –OCH3 (Ld); –OH (Le)
Y = O (Lf), NH (Lg);
Fig. 2. Structure of the copper(II) complexes.
niae, S. typhi, P. aeruginosa and S. aureus and fungi charge with the donor groups and possibly the
πꢀelecꢀ
such as A. niger, R. stolonifer, A. flavus, R. bataicola
tron delocalization within the whole chelate ring sysꢀ
tem thus formed during coordination. This process of
chelation thus increases the lipophilic nature of the
copper ion, which in turn favors its permeation
through the lipid layer of the membrane. This in turn
is responsible for increasing the hydrophobic characꢀ
ter and liposolubility of the molecule in crossing cell
membrane of the microorganism, and hence enhances
the biological utilization ratio and activity of the testꢀ
ing drug/compound. The enhanced activity of the
complexes may also be explained on the basis of their
solubility, fineness of the particles, size of the metal ion
and C. albicans by the well diffusion method. The minꢀ
imum inhibitory concentration (MIC) values of the
compounds are summarized in Tables 1 and 2. A comꢀ
parative study of the ligands and their copper comꢀ
plexes (MIC values) indicates that complexes exhibit
higher antifungal activity than the free ligands. From
the MIC values (Table 1), it was found that the
[Cu(Lg)(phen)H2O]Cl2 was more potent among the
other investigated complexes and the standard (nystaꢀ
tin) against Candida albicans
.
Chelation reduces the polarity of the copper ion
mainly because of the partial sharing of its positive and the presence of bulkier organic moieties.
RUSSIAN JOURNAL OF INORGANIC CHEMISTRY Vol. 55 No. 7 2010

1070
RAMAN, JOSEPH
Counts
3000
2000
1000
0
1 μm
(а)
20
30
40
Position
50 60
° θ
70
80
2
Fig. 3. Xꢀray diffraction of [Cu(L )phen(H O)]Cl comꢀ
a
2
2
plex.
Molar Ratio 1 : 1 Complexes
Rosenberg’s studies demonstrate that the biologiꢀ
cal activities of metal complexes depend upon the
charge, the nature of the counter anion, the geometriꢀ
cal configuration, and the oxidation state of the cenꢀ
tral metal ion [28]. It is observed from the results
(Tables 1 and 2), the higher inhibition of microbial
growth is not only due to chelation, heterocyclic moiꢀ
ety, coordinated chloride ions but also due to the presꢀ
ence of azomethine group. 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 interferences with the
normal cell process [29–31].
1 μm
(b)
Fig. 4. SEM images of [Cu(L )phen(H O)]Cl (a) and
a
2
2
[Cu(L ) ]Cl complex (b).
f 2
2
per complex into cell membrane in the presence of
methoxy group.
Effect of Chloride Ion
Copper(II)
complexes
of
the
type
Effect of Heterocyclic Moiety
[
Cu(L)(Cl)2(H2O)] possess broad spectrum of antibacꢀ
terial and antifungal activity in vitro and the greater
growth inhibition which may be due to presence of
chloride ion in the coordination sphere. From the
observation, the order of activity of the synthesized
complexes both in bacteria and fungi depends on the
nature of the substituents present in the phenyl ring
and decreases in the following order:
The compounds containing phenyl moiety is
replaced by heterocyclic rings such as pyrrole and furan
to find out the inhibitory effect due to the presence of
heterocyclic moiety. It is observed the heterocyclic moiꢀ
ety enhances the biochemical properties such as antiꢀ
bacterial and antifungal activities of the Schiff base
ligands and their complexes (Tables 1 and 2).
[Cu(La)(Cl)2(H2O)] > [Cu(Lb)(Cl)2(H2O)]
> [Cu(Lc)(Cl)2(H2O)] > [Cu(Ld)(Cl)2(H2O)]
Effect of Substituents
> [Cu(Le)(Cl)2(H2O)].
Further, inhibitory action gets enhanced with the
introduction of electronꢀwithdrawing substituent in
the phenyl ring. The complexes, however, with elecꢀ
tronꢀreleasing substituents such as methoxy and
hydroxyl groups, are lesser active compared to unsubꢀ
stituted phenyl ring. It is interesting to note that methꢀ
oxy group of copper complexes showed increased
activity than that of hydroxyl group of copper comꢀ
plexes due to the comparatively faster diffusion of copꢀ
Based on the facts, the inhibitory activity of synꢀ
thesized complexes (1 : 1 molar ratio) for both in bacꢀ
teria and fungi is as follows:
[Cu(Lg)(Cl)2(H2O)] > [Cu(Lf)(Cl)2(H2O)]
> [Cu(La)(Cl)2(H2O)] > [Cu(Lb)(Cl)2(H2O)]
> [Cu(Lc)(Cl)2(H2O)] > [Cu(Ld)(Cl)2(H2O)]
> [Cu(Le)(Cl)2(H2O)].
RUSSIAN JOURNAL OF INORGANIC CHEMISTRY Vol. 55 No. 7 2010

NOVEL METALꢀBASED ANTIMICROBIAL AGENTS
1071
Table 1. Minimum inhibitory of concentration of the synthesized compounds against the growth of fungi (
µ
g/mL)
S. No
Compound
A. niger
R. stolinifer
A. flavus
R. bataicola C. albicans
1
2
3
4
5
6
7
8
9
La
Lb
Lc
Ld
Le
Lf
58
62
66
70
75
55
48
25
16
25
15
29
18
33
24
35
28
22
13
18
11
28
12
32
15
35
18
39
20
44
24
26
08
22
06
10
64
68
74
76
80
60
52
30
23
31
23
34
28
37
34
40
37
26
20
21
15
32
16
36
19
41
23
45
26
48
28
30
15
27
10
16
76
82
85
88
90
74
65
34
28
35
28
38
32
42
36
44
40
30
25
26
19
35
22
39
23
44
27
50
32
55
34
38
16
32
12
8
80
85
88
90
94
76
69
24
22
26
24
30
30
34
32
39
35
19
18
16
14
26
24
30
25
33
30
37
35
41
38
29
19
21
14
12
64
68
76
85
92
58
50
28
25
28
26
32
33
38
35
42
38
23
22
19
16
28
19
31
18
36
25
42
28
46
30
40
14
25
09
14
Lg
[Cu(La)(Cl)2 H2O]
[Cu(La)L1]
10 [Cu(Lb)(Cl)2 H2O]
11 [Cu(Lb)L1]
12 [Cu(Lc)(Cl)2 H2O]
13 [Cu(Lc)L1]
14 [Cu(Ld)(Cl)2 H2O]
15 [Cu(Ld)L1]
16 [Cu(Le)(Cl)2 H2O]
17 [Cu(Le)L1]
18 [Cu(Lf)(Cl)2 H2O]
19 [Cu(Lf)L1]
20 [Cu(Lg)(Cl)2 H2O]
21 [Cu(Lg)L1]
22 [Cu(La)2]Cl2
23 [Cu(La)(phen)H2O]Cl2
24 [Cu(Lb)2]Cl2
25 [Cu(Lb)(phen)H2O]Cl2
26 [Cu(Lc)2]Cl2
27 [Cu(Lc)(phen)H2O]Cl2
28 [Cu(Ld)2]Cl2
29 [Cu(Ld)(phen)H2O]Cl2
30 [Cu(Le)2]Cl2
31 [Cu(Le)(phen)H2O]Cl2
32 [Cu(Lf)2]Cl2
33 [Cu(Lf)(phen) H2O]Cl2
34 [Cu(Lg)2 Cl2
35 [Cu(Lg)(phen)H2O]Cl2
36 Nystatin
Molar Ratio 1 : 2 Complexes
linkage which imports in elucidating the mechanism
of transamination and resamination reactions in bioꢀ
logical system [32, 33], Based on this, the inhibitory
activity of synthesized complexes both in bacteria and
fungi is as follows:
The complexes (molar ratio 1 : 1 complexes) conꢀ
taining a chloride ion attached directly to the copper
ion also showed antimicrobial activity, but the replaceꢀ
ment of chloride by one more same ligand moiety (i.e
.
L in 1 : 2 molar ratio) enhances the antimicrobial
activity. This enhancement in the activity is rationalꢀ
ized on the basis of the structures of 1 : 2 (Cu : L) comꢀ
plexes by possessing an additional azomethine (C=N)
[Cu(Lg)2]Cl2 > [Cu(Lf)2]Cl2 > [Cu(La)2]Cl2
> [Cu(Lb)2]Cl2 > [Cu(Lc)2]Cl2 > [Cu(Ld)2]Cl2
> [Cu(Le)2]Cl2
.
RUSSIAN JOURNAL OF INORGANIC CHEMISTRY Vol. 55 No. 7 2010

1072
RAMAN, JOSEPH
Table 2. Minimum inhibitory of concentration of the synthesized compounds against growth of bacteria (
µ
g/mL)
S. No
Compound
E. coli
K. pneumonia
S. typhi
P. aeruginosa
S. aureus
1
2
3
4
5
6
7
8
9
La
Lb
Lc
Ld
Le
Lf
52
56
60
66
72
46
42
24
18
28
20
32
24
34
26
38
28
18
15
16
12
24
16
28
20
32
24
36
26
38
30
20
13
15
14
04
54
56
60
64
68
50
46
26
22
30
24
32
26
35
28
40
32
22
19
19
16
26
24
30
27
34
32
39
35
42
38
24
20
18
20
08
58
62
66
68
72
54
50
28
25
32
28
35
32
38
36
42
40
25
22
22
19
31
22
34
25
38
28
44
34
46
36
28
21
26
18
10
60
64
66
70
75
56
48
22
24
25
28
28
30
32
34
39
38
20
18
18
15
25
20
29
24
35
30
40
35
44
40
22
15
18
13
06
63
68
72
75
78
58
52
32
30
34
32
38
36
40
40
44
42
28
28
24
23
28
28
32
32
36
36
38
38
40
42
25
24
24
16
12
Lg
[Cu(La)(Cl)2 H2O]
[Cu(La)L1]
10 [Cu(Lb)(Cl)2 H2O]
11 [Cu(Lb)L1]
12 [Cu(Lc)(Cl)2 H2O]
13 [Cu(Lc)L1]
14 [Cu(Ld)(Cl)2 H2O]
15 [Cu(Ld)L1]
16 [Cu(Le)(Cl)2 H2O]
17 [Cu(Le)L1]
18 [Cu(Lf)(Cl)2 H2O]
19 [Cu(Lf)L1]
20 [Cu(Lg)(Cl)2 H2O]
21 [Cu(Lg)L1]
22 [Cu(La)2]Cl2
23 [Cu(La)(phen)H2O]Cl2
24 [Cu(Lb)2]Cl2
25 [Cu(Lb)(phen)H2O]Cl2
26 [Cu(Lc)2]Cl2
27 [Cu(Lc)(phen)H2O]Cl2
28 [Cu(Ld)2]Cl2
29 [Cu(Ld)(phen)H2O]Cl2
30 [Cu(Le)2]Cl2
31 [Cu(Le)(phen)H2O]Cl2
32 [Cu(Lf)2]Cl2
33 [Cu(Lf)(phen) H2O]Cl2
34 [Cu(Lg)2]Cl2
35 [Cu(Lg)(phen)H2O]Cl2
36 Streptomycin
MixedꢀLigand Complexes of L1
The replacement of chloride ion from 1 : 1 molar
zoic acidꢀSchiff bases show antimicrobial activity
against microorganisms. The activity of these subꢀ
stances may be due to carboxyl group. The ligand conꢀ
taining phenolic and carboxylic moieties shows better
inhibition against bacteria and fungi. The alteration in
ratio of complexes by another ligand moiety (L1
)
enhances the antimicrobial activity due to the presꢀ
ence of phenolic and carboxylic moieties. The results
of antimicrobial screening indicate that oꢀaminobenꢀ the activity of different molecules against different
RUSSIAN JOURNAL OF INORGANIC CHEMISTRY Vol. 55 No. 7 2010

NOVEL METALꢀBASED ANTIMICROBIAL AGENTS
1073
organisms depends either on the impermeability of the
cells of the microbes or differences in ribosomes of
microbial cells [34].
2μA
Further, increase of inhibition of microbial growth
is due to uncoordinated hetero atoms present in the
copper complexes of type [Cu(L)(L1)]. In the comꢀ
plexes, the ligands have some uncoordinated donor
atoms which enhance the activity of the complexes by
bonding with trace elements present in microorganꢀ
isms may combine with the uncoordinated site and
may inhibit the growth of fungi.
It has also been suggested [35, 36] that the ligands
with nitrogen and oxygen donor systems might inhibit
enzyme production, since the enzymes which require
these groups for their activity appear to be especially
more susceptible to deactivation by the metal ions
upon chelation.
+0.2
–0.4
E(V)Ag/AgCl
Fig. 5. Cyclic voltammogram of [Cu(L )phen(H O)]Cl
a
2
2
complex in the presence (dotted line) and absence of DNA
(dark line).
decrease in
Δ
Ep of 12 mV. The ipc/ipa values also
decrease in the presence of DNA. The decrease of the
anodic and cathodic peak currents of the complex in
the presence of DNA is due to decrease in the apparꢀ
ent diffusion coefficient of the Cu(II) complex upon
complexation with the DNA macromolecules. These
results show that [Cu(La)phen(H2O)]Cl2 stabilizes the
duplex (GC pairs) by intercalating way. The peak
potential and current of the Cu(II) complex were
changed in the presence of DNA. According to equaꢀ
tion,
MixedꢀLigand Complexes of Phenanthroline
1,10ꢀphenanthroline (phen) and substituted derivꢀ
atives, both in the metalꢀfree state and as ligands coorꢀ
dinated to transition metals, disturb the functioning of
a wide variety of biological systems [37]. From the
view of biological relevance, we have chosen this type
of metalꢀphen mixed ligand complexes (1 : 1 : 1 molar
ratio, M : L : phen) to study the antimicrobial activity.
From the observation, the order of activity of the synꢀ
thesized compounds in both bacteria and fungi is as
follows:
0
0
'
'
Eb – Ef = 0.059log(k+/k2+),
0
0
'
'
where Eb and Ef are the formal potentials of the
[Cu(Lg)(phen)]Cl2 > [Cu(Lf)(phen)]Cl2
> [Cu(La)(phen)]Cl2 > [Cu(Lb)(phen)]Cl2
> [Cu(Lc)(phen)]Cl2 > [Cu(Ld)(phen)]Cl2
Cu(II)/Cu(I) couple in the binding and free forms,
respectively. The ratio of the binding constants
(
k+/k2+) is found to be less than unity (Table 3) which
> [Cu(Le)(phen)]Cl2
.
indicates that the Cu(II) is displaying higher DNA
binding affinity than Cu(I) form. Similarly, the increꢀ
mental addition of DNA to the complex, the redox
couple causes a significant shift in E1/2 of 5–40 mV and
The compounds (molar ratio 1 : 1 complexes) conꢀ
taining a chloride ion attached directly to the central
atom also showed inhibitory activity, but the replaceꢀ
ment of chloride ion by another ligand moiety (phen)
enhances the inhibition of microbial growth.
a decrease in Ep of 5–20 mV. The ipc/ipa values also
Δ
decrease in the presence of DNA. The decrease of the
anodic and cathodic peak currents of the complex in
the presence of DNA is due to decrease in the apparꢀ
ent diffusion coefficient of the Cu(II) complexes upon
complexation with the DNA macromolecules. Moreꢀ
over, the ratio of the binding constants (k+/k2+) is
found to be less than unity (Table 3) which indicates
that the Cu(II) is displaying higher DNA binding
affinity than Cu(I) form.
Interaction of Copper Complex with DNA
by Cyclic Voltammetry Study
Cyclic voltammetric technique is extremely useful
in probing the nature and mode of DNA binding of
metal complexes. A typical cyclic voltammogram of
[Cu(La)phen(H2O)]Cl2 in the absence and in presence
of varying amount of [DNA] is shown in Fig. 5.
In the absence of DNA, the cathodic peak appears
CONCLUSIONS
at –0.107 V for Cu(II)
Cu(I) couple (Epa =
Ep = 0.174 V and E1/2
0.194 V. This redox couple ratio of ipc/ipa is approxiꢀ
In this work, few mixed ligand copper complexes
have been designed and synthesized in 1 : 1 and 1 : 2
molar ratios and they are characterized by analytical
and spectral methods. A preliminary study involving
the interaction of the synthesized copper complexes
with DNA has also been carried out using cyclic voltaꢀ
mmetry. From the results, it is found that the syntheꢀ
sized complexes stabilize the duplex (GC pairs) by
⎯
0.281V, Epc = –0.107 V,
Δ
=
⎯
mately unity. This indicates that the reaction of the
complex on the glassy carbon electrode surface is
quasiꢀreversible redox process. During the incremenꢀ
tal addition of DNA to the complex, the redox couple
causes a significant shift in E1/2 of 17 mV and a
RUSSIAN JOURNAL OF INORGANIC CHEMISTRY Vol. 55 No. 7 2010

1074
RAMAN, JOSEPH
Table 3. Electrochemical behaviour of copper complexes containing electron withdrawing substituted ligands on interacꢀ
tion with CTꢀDNA
E1/2 (V)
Δ
Ep (V)
SI.
No
Complexes
K+/K2+
Ipc/Ipa
Free
bound
Free
bound
1
2
3
4
5
6
7
8
[Cu(La)(Cl)2 H2O]
[Cu(La)L1]
–0.180
–0.189
–0.203
–0.188
–0.212
–0.194
–0.197
–0.203
–0.162
–0.191
–0.206
–0.196
–0.207
–0.236
–0.188
–0.175
0.108
0.117
0.121
0.135
0.118
0.174
0.130
0.178
0.123
0.129
0.131
0.144
0.122
0.162
0.137
0.192
0.76
0.87
0.87
0.74
0.95
0.80
0.91
0.83
0.84
0.91
0.86
0.76
0.64
0.78
0.67
0.68
[Cu(Lb)(Cl)2 H2O]
[Cu(Lb)L1]
[Cu(La)2]Cl2
[Cu(La)(phen)H2O]Cl2
[Cu(Lb)2]Cl2
[Cu(Lb)(phen)H2O]Cl2
14. X. Wang , H. Chao, H. Li, et al., J. Inorg. Biochem. 98
423 (2004).
15. A. M. Thomas, M. Nethaji, A. R. Chakravarty, J. Inorg.
,
intercalating way. The antibacterial and antifungal
activities of the ligands and their copper(II) complexes
have been done. It is found that these compounds are
not only good candidates as antibacterial and antifunꢀ
gal agents, but also a promising addition of new class
of compounds as the metalꢀbased drugs. Further studꢀ
ies are required to explore these complexes as drugs.
Biochem. 98, 1087 (2004).
16. T. Hirohama, Y. Kuranuki, E. Ebina, et al., J. Inorg.
Biochem. 99, 1205 (2005).
17. H. Zhang, C. S. Liu, X. H. Bu, M. Yang, J. Inorg. Bioꢀ
chem. 99, 1119 (2005).
18. J. R. J. Sorenson, J. Med. Chem. 19, 135 (1976).
ACKNOWLEDGMENTS
19. D. H. Brown, A. J. Lewis, W. E. Smith, J. W. Teape,
J. Med. Chem. 23, 729 (1980).
The authors express their sincere thanks to the
Managing Board, Principal and Head of the Departꢀ
ment of Chemistry, VHNSN College, Virudhunagar
for their constant encouragement and providing
research facilities. NR thanks the University Grants
Commission (UGC), New Delhi and JJ thanks the
Tamilnadu Government for financial assistance.
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