Ligational behaviour of lomefloxacin drug towards Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Th(IV) and UO2(VI) ions: Synthesis, structural characterization and biological activity studies

Article abstract of DOI:10.1016/j.saa.2011.05.089

Nine new mononuclear Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Th(IV) and UO₂(VI) complexes of lomefloxacin drug were synthesized. The structures of these complexes were elucidated by elemental analyses, IR, XRD, UV-vis, ¹H NMR as well as conductivity and magnetic susceptibility measurements and thermal analyses. The dissociation constants of lomefloxacin and stability constants of its binary complexes have been determined spectrophotometrically in aqueous solution at 25 ± 1 °C and at 0.1 M KNO₃ ionic strength. The discussion of the outcome data of the prepared complexes indicate that the lomefloxacin ligand behaves as a neutral bidentate ligand through OO coordination sites and coordinated to the metal ions via the carbonyl oxygen and protonated carboxylic oxygen with 1:1 (metal:ligand) stoichiometry for all complexes. The molar conductance measurements proved that the complexes are electrolytes. The powder XRD study reflects the crystalline nature for the investigated ligand and its complexes except Mn(II), Zn(II) and UO₂(II). The geometrical structures of these complexes are found to be octahedral. The thermal behaviour of these chelates is studied where the hydrated complexes lose water molecules of hydration in the first steps followed by decomposition of the anions, coordinated water and ligand molecules in the subsequent steps. The activation thermodynamic parameters are calculated using Coats-Redfern and Horowitz-Metzger methods. A comparative study of the inhibition zones of the ligand and its metal complexes indicates that metal complexes exhibit higher antibacterial effect against one or more bacterial species than the free LFX ligand. The antifungal and anticancer activities were also tested. The antifungal effect of almost metal complexes is higher than the free ligand. LFX, [Co(LFX)(H ₂O)₄]·Cl₂ and [Zn(LFX)(H ₂O)₄]·Cl₂ were found to be very active with IC50 values 14, 11.2 and 43.1, respectively. While, other complexes had been found to be inactive at lower concentration than 100 μg/ml.

Full text of DOI:10.1016/j.saa.2011.05.089

Spectrochimica Acta Part A 82 (2011) 8–19
Contents lists available at ScienceDirect
Spectrochimica Acta Part A: Molecular and
Biomolecular Spectroscopy
journal homepage: www.elsevier.com/locate/saa
Ligational behaviour of lomefloxacin drug towards Cr(III), Mn(II), Fe(III), Co(II),
Ni(II), Cu(II), Zn(II), Th(IV) and UO (VI) ions: Synthesis, structural
2
characterization and biological activity studies
Hanan F. Abd El-Halim , Gehad G. Mohamed , Maher M.I. El-Dessouky , Walaa H. Mahmoudb
a
b,∗
a
a
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Misr International University, Cairo, Egypt
Chemistry Department, Faculty of Science, Cairo University, 12613, Giza, Egypt
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Nine new mononuclear Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Th(IV) and UO (VI) complexes of
2
Received 13 April 2011
Received in revised form 19 May 2011
Accepted 25 May 2011
lomefloxacin drug were synthesized. The structures of these complexes were elucidated by elemental
1
analyses, IR, XRD, UV–vis, H NMR as well as conductivity and magnetic susceptibility measurements
and thermal analyses. The dissociation constants of lomefloxacin and stability constants of its binary
◦
complexes have been determined spectrophotometrically in aqueous solution at 25 ± 1 C and at 0.1 M
Keywords:
KNO3 ionic strength. The discussion of the outcome data of the prepared complexes indicate that the
lomefloxacin ligand behaves as a neutral bidentate ligand through OO coordination sites and coordinated
to the metal ions via the carbonyl oxygen and protonated carboxylic oxygen with 1:1 (metal:ligand)
stoichiometry for all complexes. The molar conductance measurements proved that the complexes are
electrolytes. The powder XRD study reflects the crystalline nature for the investigated ligand and its
complexes except Mn(II), Zn(II) and UO2(II). The geometrical structures of these complexes are found to be
octahedral. The thermal behaviour of these chelates is studied where the hydrated complexes lose water
molecules of hydration in the first steps followed by decomposition of the anions, coordinated water and
ligand molecules in the subsequent steps. The activation thermodynamic parameters are calculated using
Coats–Redfern and Horowitz–Metzger methods. A comparative study of the inhibition zones of the ligand
and its metal complexes indicates that metal complexes exhibit higher antibacterial effect against one or
more bacterial species than the free LFX ligand. The antifungal and anticancer activities were also tested.
The antifungal effect of almost metal complexes is higher than the free ligand. LFX, [Co(LFX)(H2O)4]·Cl2
and [Zn(LFX)(H2O)4]·Cl2 were found to be very active with IC50 values 14, 11.2 and 43.1, respectively.
While, other complexes had been found to be inactive at lower concentration than 100 ␮g/ml.
Lomefloxacin
Metal complexes
Spectroscopy
Thermal analyses
Biological activity
Anticancer activity
©
2011 Elsevier B.V. All rights reserved.
1
. Introduction
duced based on some new quinolone molecules that display a novel
mode of action [2,3].
Lomefloxacin is a bactericidal fluoroquinolone agent with
The fluoroquinolones constitute an important class of synthetic
antimicrobial agents which have been the subject of intensive
study [4]. They possess a broad spectrum of activity against vari-
ous pathogenic microorganisms, and resistant to aminoglycosides,
penicillins, cephalosporins, tetracyclines and other antibiotics. This
class of compounds, when compared to existing bactericidal drugs,
shows improved pharmacokinetic properties and a broad spectrum
of activity against parasites, bacteria, and mycobacteria, includ-
ing resistant strains [5,6]. Metal coordination to biologically active
molecules can be used as a strategy to enhance their activity and
overcome resistance. Quinolones are particularly interesting due
to their ability to coordinate metal ions. Thus, numerous studies
regarding the interaction between quinolones with metallic cations
have been reported in the literature [2,7–9]. Some of these metal
complexes have been tested successfully for antibacterial activity
[10–15]. The effect of metal ions on the antibacterial activity of
activity against
a wide range of gram-negative and gram-
positive organisms. Its IUPAC name is 1-ethyl-6,8-difluoro-7-(3-
methylpiperazin-1-yl)-4-oxoquinoline-3-carboxylic acid (Fig. 1).
The bactericidal action of lomefloxacin resulted from interfer-
ence with the activity of the bacterial enzymes DNA gyrase and
topoisomerase IV, which are needed for the transcription and
replication of bacterial DNA [1]. Modifications of LFX were made
based on structure–activity relationships. It was discovered that
a fluorine atom at position 6 and a piperazine ring at position 7
greatly enhance the spectrum of activity. Recently, a relatively new
approach to the rational design of antitumor agents has been intro-
∗ Corresponding author. Tel.: +20 1523423103; fax: +20 235728843.
E-mail address: ggenidy@hotmail.com (G.G. Mohamed).
1
386-1425/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.saa.2011.05.089

H.F.A. El-Halim et al. / Spectrochimica Acta Part A 82 (2011) 8–19
9
appropriate volume of de-ionized water. Acid mixture (0.04 M
phosphoric, acetic and boric acids) from which series of univer-
sal buffer solutions of different pH values (2–12) were prepared by
using 0.1 N sodium hydroxide solution for adjusting the desired pH.
Dimethylsulphoxide (DMSO) (Sigma Chemical Co., St. Louis,
MO, and U.S.A.): It was used in cryopreservation of cells. RPMI-
1
640 medium (Sigma Chemical Co., St. Louis, MO, and U.S.A.). The
medium was used for culturing and maintenance of the human
tumor cell lines. The medium was supplied in a powder form. It
was prepared as follows: 10.4 g medium was weighed, mixed with
Fig. 1. Structural formula of lomefloxacin drug.
2
g sodium bicarbonate, completed to 1 L with distilled water and
shacked carefully till complete dissolution. The medium was then
norfloxacin has been previously reported. Fe(III) and Zn(II) com-
plexes were obtained and they showed increased activity over
norfloxacin against Gram negative E. coli and Bacillus dysenteriae
sterilized by filtration in a Millipore bacterial filter (0.22 ␮m). The
◦
prepared medium was kept in a refrigerator (4 C) and checked at
regular intervals for contamination. Before use, the medium was
◦
[
16]. Jain et al. [17] have reported a Co(II) complex with sparfloxacin
warmed at 37 C in a water bath and the supplemented with peni-
which is more potent against several pathogenic bacteria than
sparfloxacin. In a similar approach, Saha et al. [18] showed that the
Cu(II) complex and ciprofloxacin presents a significant enhance-
ment in antitubercular activity. Usually the fluoroquinolones act as
bidentate ligands binding to the metal ions through the carboxylate
and carbonyl oxygens. The metal ions can form a stable 6-member
chelate ring with a slightly distorted octahedral geometry as was
observed for Co(II), Ni(II), Zn(II), Cd(II), Mn(II) and Cu(II) complexes
cillin/streptomycin and FBS.
Sodium bicarbonate (Sigma Chemical Co., St. Louis, MO, U.S.A.)
was used for the preparation of RPMI-1640 medium. 0.05% isotonic
Trypan blue solution (Sigma Chemical Co., St. Louis, MO, U.S.A.)
was prepared in normal saline and was used for viability counting.
◦
10% Fetal Bovine Serum (FBS) (heat inactivated at 56 C for 30 min),
100 units/ml Penicillin and 2 mg/ml Streptomycin were supplied
from Sigma Chemical Co., St. Louis, MO, U.S.A. and were used for
the supplementation of RPMI-1640 medium prior to use. 0.025%
(w/v) Trypsin (Sigma Chemical Co., St. Louis, MO, U.S.A.) was used
for the harvesting of cells. 1% (v/v) Acetic acid (Sigma Chemical Co.,
St. Louis, MO, U.S.A.) was used for dissolving the unbound SRB dye.
0.4% Sulphorhodamine-B (SRB) (Sigma Chemical Co., St. Louis, MO,
U.S.A.) dissolved in 1% acetic acid was used as a protein dye. A stock
solution of trichloroacetic acid (TCA, 50%, Sigma Chemical Co., St.
Louis, MO, U.S.A.) was prepared and stored. 50 ␮l of the stock was
added to 200 ␮l RPMI-1640 medium/well to yield a final concen-
tration of 10% used for protein precipitation. 100% isopropanol and
70% ethanol were used. Tris base 10 mM (pH 10.5) was used for SRB
dye solubilization. 121.1 g of tris base was dissolved in 1000 ml of
distilled water and pH was adjusted by HCl acid (2 M).
[
13,19–21]. This site seems to be preferred for most metal ions.
Coordination of the fluoroquinolones with metal ions by way of
the piperazine nitrogen atoms is much less common [22].
As part of our ongoing study of metal complexes of fluoro-
quinolones [23,24], we report herein the coordination chemistry
and bioactivity of some transition metal complexes containing
oxygen–oxygen donor sites. The aim of the current work is to study
the chelating behaviour of LFX drug towards some transition met-
als. The structures of the metal complexes were characterized by
elemental analyses, IR, 1H NMR, UV–vis, XRD, conductivity and
magnetic susceptibility measurements at room temperature, ther-
mal analyses as well as some results of bioactivity tests are also
included.
2
. Experimental
2.3. Measurements
2
.1. Material and reagent
Microanalyses of carbon, hydrogen and nitrogen were carried
out at the Microanalytical Center, Cairo University, Egypt, using
CHNS-932 (LECO) Vario Elemental Analyzer. Analyses of the metal
content were followed by the dissolution of the solid complexes
All chemicals used were of the analytical reagent grade (AR),
and of highest purity available. They included lomefloxacine
drug, CuCl ·2H O, MnCl ·2H O, CrCl ·6H O and UO (NO ) ·2H O
in concentrated HNO , neutralizing the diluted aqueous solutions
2
2
2
2
3
2
2
3
2
2
3
(
Sigma), CoCl ·6H O and NiCl ·6H O (BDH), ThCl (Aldrich),
with ammonia and titrating the metal solutions with EDTA. pH
measurements were carried out using Jenway 3505 pH meter, U.K.
FT-IR spectra were recorded on a Perkin-Elmer 1650 spectrometer
2
2
2
2
4
ZnCl ·2H O (Ubichem) and FeCl ·6H O (Prolabo). Organic solvents
2
2
3
2
were spectroscopic pure from BDH included ethanol, diethyl ether
and dimethylformamide. Hydrogen peroxide and sodium chlo-
ride, sodium carbonate and sodium hydroxide (A.R.) were used.
Hydrochloric, phosphoric, acetic, boric and nitric acids (Merck)
were used.
−
1
(4000–400 cm ) in KBr pellets. Electronic spectra (measured in
ethanol) and diffused reflectance spectra (measured as BaSO disc)
4
were recorded at room temperature on a Shimadzu 3101pc spec-
trophotometer. 1H NMR spectra, as a solution in DMSO-d6, were
recorded on a 300 MHz Varian-Oxford Mercury at room tempera-
ture using TMS as an internal standard. Mass spectra were recorded
by the EI technique at 70 eV using MS-5988 GS–MS Hewlett-
Packard instrument at the Microanalytical Center, Cairo University.
The molar magnetic susceptibility was measured on powdered
samples using the Faraday method. The diamagnetic corrections
Human tumor cell lines (Brest cell) were obtained frozen in liq-
◦
uid nitrogen (−180 C) from the American Type Culture Collection.
The tumor cell lines were maintained in the National Cancer Insti-
tute, Cairo, Egypt, by serial sub-culturing.
2.2. Solutions
were made by Pascal’s constant and Hg[Co(SCN) ] was used as
a calibrant. Molar conductivities of 10 M solutions of the solid
4
A fresh stock solution of 1 × 10−3 M of LFX (0.351 g/L) was
−3
prepared by dissolving the accurately weighed amount in the
complexes in DMF were measured using Jenway 4010 conductiv-
ity meter. The thermogravimetric analyses (TG, DTG and DTA) of the
−
3
appropriate volume of absolute ethanol. 1 × 10 M Stock solu-
◦
tions of the metal salts (Fe(III), 0.27 g/L; Co(II), 0.23 g/L; Ni(II),
solid complexes were carried out from room temperature to 800 C
0
0
.23 g/L; Cu(II), 0.17 g/L; Zn(II), 0.172 g/L; Cr(III), 0.26 g/L; UO (II),
.50 g/L, Mn(II), 0.16 g/L and Th(IV), 0.37 g/L) were prepared by dis-
using a Shimadzu TG-50H thermal analyzer. The X-ray powder
diffraction analyses were carried out using Philips Analytical X-Ray
BV, diffractometer type PW 1840. Radiation was provided by cop-
2
solving the accurately weighed amounts of the metal salts in the

1
0
H.F.A. El-Halim et al. / Spectrochimica Acta Part A 82 (2011) 8–19
per target (Cu anode 2000 W) high intensity X-ray tube operated
at 40 kV and 25 mA. Divergence and the receiving slits were 1 and
was automatically subtracted and mean values of each drug con-
centration was calculated. The relation between surviving fraction
and drug concentration is plotted to get the survival curve of Breath
tumor cell line for each compound.
Calculation: The percentage of cell survival was calculated as
follows:
0.2, respectively. The antibacterial and antifungal activities were
evaluated at the Microbiological laboratory, Microanalytical cen-
ter, Cairo University, Egypt. The anticancer activity was performed
at the National Cancer Institute, Cancer Biology Department, Phar-
macology Department, Cairo University. The optical density (O.D.)
of each well was measured spectrophotometrically at 564 nm with
an ELIZA microplate reader (Meter tech. ꢀ 960, U.S.A.).
O.D. (treated cells)
O.D. (control cells)
survival fraction =
.
The IC50 values (the concentrations of thymoquinone required
to produce 50% inhibition of cell growth). The experiment was
repeated 3 times for each cell line.
2.4. Synthesis of metal complexes
Ethanolic or aqueous-ethanolic solution of lomefloxacin (0.4 g,
.03 mmol) and hydrated metal salts (0.274 g Cr(III), 0.167 g Mn(II),
.278 g Fe(III), 0.244 g Co(II), 0.244 g Ni(II), 0.176 g Cu(II), 0.176 g
1
0
3. Results and discussion
Zn(II), 0.385 g Th(IV) and 0.517 g UO (II), 1.0 mmol) were heated
3.1. Mass spectrum of LFX
2
under reflux for 2–3 h. The precipitates were filtered off, washed
with ethanol followed by diethyl ether and dried in vacuum desic-
The electron impact mass spectrum of LFX is recorded and inves-
tigated at 70 eV of electron energy. The mass spectrum of the
studied drug is characterized by moderate to high intensity molecu-
lar ion peaks at 70 eV. The abundance of the molecular ion depends
mainly on the structure (and therefore the potential energy sur-
face) of the molecular ion. The mass spectrum of LFX shows a
cator over anhydrous CaCl . The physical and analytical data of the
2
isolated complexes are listed in Suppl. Table 1. The complexes have
high melting points and insoluble in common organic solvents and
soluble in DMF or DMSO.
+
2.5. Spectrophotometric studies
well-defined parent peak at m/z = 351 (M ) with a relative inten-
sity = 29%. The parent ion and the fragments obtained by cleavage
in different positions in LFX molecule are shown in Scheme 1.
The absorption spectra of the LFX free ligand and its binary com-
plexes under study were scanned within the wavelength range
−
3
from 200 to 600 nm. The absorption spectra of 1 × 10 M solu-
tion of this ligand and its complexes were measured in a universal
buffer of different pH values ranged from 2 to 12. Two methods
were applied for the determination of pKa values of free ligand
namely half height and limiting absorbance methods [25].
3.2. Dissociation constants of LFX
Lomefloxacin drug is considered as quinoline derivatives which
derived from nalidixic acid. Nalidixic acid has a single protonation
constant (pKa = 6) in the pH range of 2–9 [2,28]. It is protonated in
a strong acid solution to form a naphthyridinium cation with a pKa
of −0.86 [29]. The drug exists in its undissociated form over the pH
range of 1.6–3.6. Fluoroquinolone analogues with the piperazinyl
group in the 7-position contain two relevant ionizable functional
groups. The protolytic equilibria of lomefloxacin are expressed
in Scheme 2. This molecule can exist in four possible forms: an
2.6. Biological activity
A filter paper disk (5 mm) was transferred into 250 ml flasks con-
taining 20 ml of working volume of tested solution (100 g/ml). All
◦
flasks were autoclaved for 20 min at 121 C. LB agar media surfaces
+
were inoculated with two investigated bacteria (gram positive and
gram negative) and two strains of fungi then, transferred to a sat-
urated disk with a tested solution in the center of Petri dish (agar
acidic cation H2Q , a neutral nonionized species HQ, an intermedi-
±
−
ate zwitter ion HQ and a basic anion Q , depending on the pH.
At low pH values, both the 7-piperazinyl group and 3-carboxyl
group are protonated, whereas at high pH values, neither is pro-
tonated. The carboxyl group is normally a stronger acid than the
ammonium group, the reason being that the neutral nonionic form
is spontaneously rearranged to the zwitter ion. Two macroscopic
dissociation constants can be determined for lomefloxacin. The
first (pKa1 = 5.57) applies to the 3-carboxyl proton and the second
(pKa2 = 11.50) to the 7-piperazinyl proton. The decrease in acidity
of the carboxylic group compared with benzoic acid (pKa = 4.2) is
explained by the intramolecular hydrogen bond to the keto oxygen
◦
plates). Finally, all these Petri dishes were incubated at 25 C for 48 h
where clear or inhibition zones were detected around each disk.
Control flask of the experiment was designed to perform under
the same condition described previously for each microorganism
but with dimethylformamide solution only and by subtracting
the diameter of inhibition zone resulting with dimethylformamide
from that obtained in each case, so antibacterial activity could be
calculated [26]. All experiments were performed as triplicate and
data plotted were the mean value.
[
2,30]. The pKa2, which is due to the presence of an ionizable proton
2.7. Anticancer activity
on the external piperazinyl nitrogen, was found at around 11.5.
Potential cytotoxicity of the compounds was tested using the
3.3. UV–vis spectra of metal chelates
method of Skehan et al. [27]. Cells were plated in 96-multiwell plate
104 cells/well) for 24 h before treatment with the compounds to
allow attachment of cell to the wall of the plate. Different concen-
trations of the compounds under investigation (0, 5, 12.5, 25, 50
and 100 ␮g/ml) were added to the cell monolayer triplicate wells
(
UV–visible spectral data of the free LFX ligand and its binary
−
3
chelates (1 × 10 M) solutions in aqueous universal buffer of vary-
ing pH values from 2 to 12 at ꢁ ranging from 200 to 600 nm using the
same solvent as blank are studied. In neutral and alkaline medium,
free LFX ligand gives two maximum bands, the first at 325 nm and
another shoulder band at 295 nm. These bands may be attributed
to n → ꢂ* and ꢂ → ꢂ* transitions inside the LFX molecule. While, in
acidic medium the n → ꢂ* transition may be disappear due to the
protonation of nitrogen atom.
were prepared for each individual dose. The monolayer cells were
◦
incubated with the compounds for 48 h at 37 C and in 5% CO atmo-
2
sphere. After 48 h, cells were fixed, washed and stained with SRB
stain. Excess stain was washed with acetic acid and attached stain
was recovered with tris-EDTA buffer. The optical density (O.D.) of
each well was measured spectrophotometrically at 564 nm with
an ELIZA microplate reader and the mean background absorbance
It is obvious that the absorption spectra of the binary com-
plexes have the same behaviour like the free LFX ligand. The band at

H.F.A. El-Halim et al. / Spectrochimica Acta Part A 82 (2011) 8–19
11
O
CH
C
COOH
CH2
CH2
N
CH2
(
m/z= 70, F.= 70, R.I= 41 % )
F
(
m/z= 56, F.= 56, R.I=75 % )
N
H
-
281
-172
F
-
295
(
m/z= 179, F.=179, R.I= 37 % )
O
O
N
O
COOH
COOH
F
F
-
100
CO
-
56
N
N
N
N
HN
F
CH CH
3
F
2
CH
CH2
H N
CH
CH2
(
m/z= 251, F.= 251, R.I= 70 %)
CH3
m/z= 351, F.= 351, R.I= 29 % ) CH3
(
(
m/z= 295, F. 295, R.I=100%)
-
88
O
F
N
N
H
N
F
(
m/z= 263, F.= 263, R.I= 4%)
Scheme 1. Mass fragmentation pattern of LFX.
O
+
CO OH
QH 2
F
N
N
+
2
H
N
CH CH 3
F
2
CH 3
±
QH
QH
O
_
O
CO
F
CO OH
F
O
N
N
+
N
N
H2
N
CH CH 3
F
2
HN
CH CH 3
F
2
CH 3
CH 3
_
O
N
CO
F
_
O
Q
N
H N
CH CH 3
F
2
CH 3
Scheme 2. Protolytic equilibria in lomefloxacin drug water solutions.

1
2
H.F.A. El-Halim et al. / Spectrochimica Acta Part A 82 (2011) 8–19
3
20 nm may be assigned to n → ꢂ* transition within the C O group
or carboxylate group of free LFX ligand. This band is red shifted to
21–326 nm in Cr(III), Th(IV) and UO (II) chelates, while it disap-
3
2
peared in all the remaining chelates revealing the involvement of
the C O group and carboxylate–O in chelate formation [28,31].
3.4. Calculation of the metal complexes formation constants
The stability constants are obtained spectrophotometrically
[
32,33] by measuring the absorbance of solutions of LFX ligand and
metal at fixed concentration but at distinct pH values ranging from
to 12. The degree of formation of the complex is obtained from
2
the relationship
Ax − AL
n˜ =
(1)
AML − AL
where Ax, AL and AML are the absorbances of the partially formed
complex at a specific pH, the free LFX ligand and the fully formed
complex, respectively. Then, the negative logarithm of the con-
centration of non-protonated ligand (pL) was obtained using Eq.
(
2):
2
H
1
+
H
+
1
+ B [H ] + B [H ] + · · ·
2
pL = log
(2)
TL − nTM
where B1H and B2H are the reciprocals of the acid dissociation
constants of the LFX ligand, i.e. [LH ]/[L][H] and [LH ]/[L][H] ,
2
1
2
respectively. TL and TM represent the stoichiometric concentra-
tion of the LFX ligand and metal. The stability constant (K) can be
calculated from Eq. (3).
n˜ + ( n˜ − 1) K(L) = 0
(3)
The calculated log K values for the Cr(III), Mn(II), Fe(III), Co(II),
Ni(II), Cu(II), Zn(II), Th(IV) and UO (II) complexes are given in Suppl.
2
Table 1. It is obvious that the complex-forming abilities of the tran-
sition metal ions are frequently characterized by stability orders.
The order of stability constants is found to be Cu (II) > Ni(II) > Co(II)
>
[
Mn(II) and Cr(III) in accordance with Irving and Williams order
34] for divalent metal ions of the 3d series. It is clear from Suppl.
Table 1 that the stability of Cu(II) complex is considerably larger
as compared to other metals of the 3rd series. Under the influence
9
of the ligand field, Cu(II)(3d ) will receive some extra stabilization
[
35] due to tetragonal distortion of octahedral symmetry in their
complexes. The Cu(II) complex will be further stabilized due to the
◦
Jahn–Teller effect [36]. The free energy of formation, ꢃG , accom-
panying the complexation reaction is found to be from −56.55 to
−
1
◦
−
57.63 kJ mol at 25 C.
From the previous data, it is apparent that the negative values of
ꢃG show that the driving tendency of the complexation reaction
◦
is from left to right and the reaction proceeds spontaneously.
3.5. Elemental analyses of the complexes
The results of elemental analyses (C, H, and N) with molecular
formula and the melting points are presented in Suppl. Table 1. The
results obtained are in good agreement with those calculated for
the suggested formula, and the melting point is sharp indicating
the purity of the prepared metal complexes.
3.6. Molar conductance measurements
The chelates are dissolved in DMF and the molar conductivities
−
3
◦
of their 10 M solutions at 25 ± 2 C are measured. It is con-
cluded from the results given in Suppl. Table 1 that the Fe(III)
and Cr(III) chelates have molar conductivity values of 290 and
−
1
−1
2
2
78 ꢄ mol cm , respectively, indicating that they are 1:3 elec-
trolytes. The molar conductivity values of Mn(II), Co(II), Ni(II),

H.F.A. El-Halim et al. / Spectrochimica Acta Part A 82 (2011) 8–19
13
Scheme 3. Zwitter-ion formation of LFX.
3.8. 1H NMR spectral studies
Cu(II), Zn(II) and UO (II) chelates under investigation (Suppl. Table
2
− −1
1
2
1
) are found to be 165, 159, 136, 115, 176 and 146 ꢄ mol cm ,
Comparative study between the 1H NMR data of LFX ligand and
its zinc complex gives an idea about the ligatational behaviour of
the ligand. The doublets at 7.89 and 7.87 ppm was assigned to the
5-H of LFX and Zn-LFX complex, respectively [23,24,37,38,41]. The
respectively. It is obvious from these data that these chelates are
ionic in nature and they are of the type 1:2 electrolytes. Th(IV)
complex has a molar conductance value of 314 ꢄ mol cm ,
−
1
−1
2
indicating that it is 1:4 electrolyte.
bands at 8.93 and 8.91 ppm (s, H, CH of carbon 2) and 3.39 and
ꢀ
3
.27 ppm (d, H, CH of carbon 3 ) are assigned to the CH proton in
3
.7. Infrared spectra and mode of bonding
the LFX ligand and Zn-LFX, respectively. While, the bands observed
at 3.39 and 3.40 ppm (d, 4H, CH2 of carbon 5 , 6 ) and 3.55 and
.37 ppm (d, 2H, CH2 of carbon 2 ) are assigned to the CH2 pro-
tons in the LFX ligand and Zn-LFX complex, respectively. The bands
observed at 1.46 and 1.48 ppm (d, 3H, CH of carbon 1b) for LFX and
Zn-LFX, respectively. In addition, bands observed at 1.44 ppm (d,
H, CH of carbon 3a’) is found in both LFX and Zn-LFX. These bands
are assigned to the CH proton in the LFX ligand and its Zn(II) com-
plex. Upon comparison with the free LFX ligand, the signal observed
at 13.5 ppm can be assigned to the carboxylate OH. This signal dis-
appeared in the spectra of the complexes. Although the LFX ligand
coordinated to the metal ions without proton displacement, the dis-
appearance of this signal can be attributed to Zwitter-ion formation
shown in Scheme 3 [41].
ꢀ
ꢀ
In the absence of a powerful technique, such as X-ray crystal-
ꢀ
3
lography, IR spectra has proven to be the most suitable technique
to give enough information to elucidate the way of bonding of LFX
to the metal ions. The IR spectra of the free LFX ligand and its metal
complexes were carried out in the range of 4000–400 cm and
the most effective bands are listed in Table 1. The strong band
observed at 1725 cm
carbonyl stretching vibration [37,38]. This band is found in the spec-
tra of the complexes at 1721–1739 cm (Table 1) or disappeared
in some complexes indicating the participation of carbonyl oxy-
gen atom in coordination (M–O) [38]. The ꢅ(OH), ꢅasym(COO) and
3
−
1
3
3
−1
in the free LFX ligand is assigned to the
−1
ꢅ
1
sym(COO) stretching vibrations are observed at 3367, 1590 and
−1
396 cm , respectively, for LFX free ligand [23,24,38]. The ꢅ(OH)
band is still broad in all complexes, which renders it difficult to
attribute to the involvement of OH group in coordination, since,
according to the elemental analysis and thermogravimetric stud-
ies, most of the complexes obtained contain water of crystallization
and coordination. Coordination with metal ions via the carboxylate
3
.9. Electronic spectra and magnetic moments studies
A comparison of the electronic spectrum of the free LFX lig-
and with those of the corresponding metal complexes show some
shifts that can be considered as evidence for the complex forma-
tion. Additionally the solid reflectance spectra of metal complexes
show different bands at different wavelengths each one is cor-
responding to certain transition which suggests the geometry of
the complexes. The magnetic moment values are listed in Suppl.
Table 1. The diffused reflectance spectra of the complexes are dom-
inated by intense intra-ligand charge transfer bands. The diffused
O
atom is indicated by shift in position of
ꢅasym(COO)
and ꢅsym(COO) stretching vibration bands to 1528–1580 and
−
1
1
1
(
370–1420 cm , respectively, in the complexes (Table 1). The ꢃꢅ
−
150–160 cm ) indicates the presence of monodentate carboxy-
late group [39].
The bands observed at 900–945 and 810–855 cm−1 can be
assigned to coordinated water molecules [40].
New bands are found in the spectra of the complexes in the
reflectance spectrum of Cr(III) complex exhibits three bands at
−1
regions 530–552 and 400–500 cm
which can be assigned to
−1
2
7,855, 25,563, 13,441 cm which may be assigned to the tran-
ꢅ(M–O) stretching vibrations of carbonyl oxygen and coordinated
water attached to metal ions, respectively. It is noticed from the
spectra of the parent LFX ligand and its metal complexes that
some bands show significant wavenumber shifts in all complexes,
although these groups did not participate in the bonding to metal
ions. These bands are the ꢅ(C C), ꢅ(C N), ꢅ(C–N), ꢅ(C–F), ꢅ(CH
stretch in CH3 and in CH2 groups) and the benzene and pyri-
dine rings stretching vibrations. These bands are either shifted to
sitions A2g(F) → T2g(F), 4A2g(F) → T (F) and 4A2g(F) → T2g(P)
4
4
4
4
2g
spin allowed d-d transitions, respectively. The magnetic moment
value is found to be 3.65 B.M which suggest an octahedral geome-
try [31,42,43]. The diffused reflectance spectrum of Mn(II) complex
−1
exhibit three bands at 25,189, 19,757, 16,570 cm , which may be
assigned to 4T1g → A1g, T2g(G) → A and T1g(D) → A tran-
6
4
6
4
6
1g
1g
sitions, respectively, which suggests an octahedral geometry. The
assignment of an octahedral geometry to the Mn(II) complex is fur-
ther supported by its magnetic moment of 5.37 B.M [42,43]. From
the diffused reflectance spectrum, it is observed that, the Fe(III)
−1
−1
lower (9–60 cm ) or higher (6–25 cm ) frequencies. This shift is
attributed to the change in the environment around these atoms as
the results of coordination of LFX ligand to metal ions.
−1
chelate exhibits a band at 21,522 cm , which may be assigned
Therefore, it is concluded from the IR spectra that LFX behaves as
neutral bidentate ligand coordinated to the metal ions via the car-
bonyl oxygen and protonated carboxylate oxygen in accordance
with the previously published data on similar types of flouro-
quinolone drugs [23,24,37,38].
6
to the A1g → T2g(G) transition in octahedral geometry [31,42].
6
5
The A1g → T g transition appears to be split into two bands at
1
−1
1
5,562 and 13,175 cm . The Fe(III) complex is found to have mag-
netic moment value of 5.06 B.M., indicating octahedral geometry
involving sp d hybridization in Fe(III) ion [42,43]. The spectrum
3
2

1
4
H.F.A. El-Halim et al. / Spectrochimica Acta Part A 82 (2011) 8–19
shows also a band at 24,530 cm−1 which may be attributed to lig-
and to metal charge transfer. The diffused reflectance spectrum
of the Co(II) complex gives three bands at 14,492, 15,099 and
−
1
2
2,031 cm . The bands observed are assigned to the transitions
4
T1g(F) → 4T2g(F) (ꢆ ), T1g(F) → A (F) (ꢆ ) and T1g(F) → T1g(P)
4
4
4
4
1
2g
2
(
ꢆ ), respectively, suggesting an octahedral geometry around Co(II)
3
−1
ion [31,42–44]. The region at 28,585 cm
refers to the charge
transfer band. The magnetic moment value is found to be 5.32 B.M.
which is an indicative of octahedral geometry [42]. The Ni(II) com-
plex reported herein is high spin with a room temperature magnetic
moment value of 3.04 B.M. indicating that the Ni(II) complex
is octahedral [31,43]. The diffused reflectance spectrum displays
−
1
3
3
−1
:
three bands at ꢆ : 13,201 cm : A (F) → T (F), ꢆ : 14,804 cm
1
2g
2g
2
3
3
3
−1
3
A2g(F) → T (F) and ꢆ : 20,243 cm
:
A
(F) → T (P) [31,42].
1g
3
2g
1g
−
1
The spectrum shows also a band at 25,315 cm
attributed to ligand to metal charge transfer.
which may be
The diffused reflectance spectrum of the Cu(II) chelate has two
−1
broad bands at 15,670 and 20,124 cm which can be assigned to
2
2
2
2
Eg → T and B1g → A transitions characteristic of octahedral
2
g
1g
geometry [31,40–42]. The magnetic moment of this complex is 1.94
B.M. which fall within the range normally observed for octahedral
Cu(II) complexes [31,42]. A moderately intense peak observed in
the range of 24,764 cm is due to ligand to metal charge transfer
transition [31,42].
−
1
The Zn(II), UO (II) and Th(IV) complexes are diamagnetic.
2
According to the empirical formulae, an octahedral geometry was
proposed for these chelates.
3.10. Thermal analyses
Thermogravimetric studies (TG) for the complexes were car-
ried out within the temperature range from room temperature up
◦
to 800 C. TG results are in good agreement with the suggested
formulae resulted from microanalyses data (Suppl. Table 1). The
determined temperature ranges and percent mass losses of the
solid complexes on heating are given in Table 2, which revealed
the following findings:
The TG curve of LFX drug exhibits a first estimated mass loss
◦
of 45.02% (calcd. 44.98%) at 200–345 C, which may be attributed
to the liberation of C10H10N2 molecule as gases (Table 2). The sec-
◦
ond estimated mass loss of 54.59% (calcd. 54.94%), at 345–620 C,
may be attributed to the liberation of C7H F NO molecule as
9
2
3
gases.
The [Fe(LFX)(H O) ]Cl ·H O complex gives a decomposition
2
4
3
2
pattern as follows; the first stage is one step within the temper-
◦
ature range of 30–120 C, representing the loss of H O (hydrated)
2
and Cl2 gases with a found mass loss of 14.11% (calcd. 14.70%). The
subsequent steps represent the loss of three coordinated water,
HCl and LFX drug with a mass loss of 71.75% (calcd. 72.00%). At
the end of the thermogram, the metal oxide Fe O3 was the residue
2
1
2.33% (calcd. 13.30%), which is in good agreement with the calcu-
lated metal content obtained and the results of elemental analyses
Table 2).
(
The [Ni(LFX)(H O) ]Cl ·H O complex is thermally decomposed
2
4
2
2
in four stages. The first stage corresponds to a mass loss of 2.67%
◦
(
calcd. 3.15%) within the temperature range 30–130 C and rep-
resents the loss of one molecule of hydrated water. The second
stage corresponds to a mass loss of 12.68% (calcd. 12.90%) within
◦
the temperature range 130–250 C and represents the loss of four
coordinated water molecules. The third and fourth stages, 250–350
◦
and 350–700 C, with a found mass loss of 12.45% (calcd. 12.43%)
and 59.74% (calcd. 58.69%), respectively, are reasonably accounted
for the loss of Cl and decomposition of the organic part of the com-
2
plex leaving out NiO as a residue with a found mass loss of 11.88%
(
calcd. 13.13%).

H.F.A. El-Halim et al. / Spectrochimica Acta Part A 82 (2011) 8–19
15
Table 3
Thermodynamic data of the thermal decomposition of metal complexes of LFX.
◦
−1
−1
−1
−1
−1
ꢃG* (kJ mol )
Complex
LFX
Decomp. Temp. ( C)
E* (kJ mol
)
A (s
)
ꢃS* (kJ mol
)
ꢃH* (kJmol
)
3
6
6
7
6
4
1
1
200–345
17.408
52.289
2.29
27.35
14.62
24.33
48.62
78.19
59.67
4.59
15.70
20.15
52.29
13.07
64.63
5.57 × 10
7.49 × 10
1.25 × 10
1.07 × 10
2.57 × 10
6.35 × 10
1.09 × 10
3.54 × 10
−58.70
−60.81
14.82
47.80
1.73
25.81
12.43
23.33
46.37
74.34
54.93
3.66
14.13
17.27
47.63
11.03
61.03
77.65
137.05
15.41
42.96
66.52
27.79
74.84
116.86
149.19
26.77
45.54
91.02
128.75
62.54
105.81
3
45–620
30–120
20–270
70–650
30–130
30–250
50–350
50–700
30–95
[
Fe(LFX)(H2O)4]Cl3·H2O
Ni(LFX)(H2O)4]Cl2·H2O
−203.92
−92.44
1
2
−205.28
−37.31
[
0
1
1
2
3
−105.37
−91.71
5
2.9 × 10
−165.43
−207.24
−166.34
−213.23
−144.79
−209.51
−103.38
4
7
6
5
6
6
[
[
Cu(LFX)(H2O)4]Cl2·2H2O
UO2 (LFX) (H2O)2]·(NO3)2
8.21 × 10
1.92 × 10
8.54 × 10
1.46 × 10
4.61 × 10
3.16 × 10
95–221
2
3
21–310
10–523
200–385
85–686
3
The [Cu(LFX)(H O) ]Cl ·2H O complex is thermally decom-
when n = 1, the LHS of Eq. (5) would be log[−log(1 − ˛)]. For a first
order kinetic process the Horowitz–Metzger equation may be writ-
ten in the form (Eq. (6)):
2
4
2
2
posed in four stages. The first stage corresponds to a mass loss of
◦
5
.68% (calcd. 6.06%) within the temperature range 30–95 C and
represents the loss of two molecules of hydrated water. The sec-
ond and third stages correspond to a mass loss of 12.16% (calcd.
ꢂ
ꢃ
ꢄꢅ
∗
w˛
wꢈ
E ꢇ
log log
=
− log 2.303
(6)
2.303RT2
1
2.13%) and 11.59% (11.96%) within the temperature range 95–220
s
◦
and 220–310 C and represent the loss of two coordinated water
and Cl gases, respectively. The last stage, 310–525 C with a found
where ꢇ = T − TS, wꢈ = w˛ − w, w˛ = mass loss at the completion of
the reaction; w = mass loss up to time t. The plot of log[log(w˛/wꢈ )]
versus ꢇ was drawn and found to be linear from the slope of which
E* was calculated. The pre-exponential factor, A, was calculated
from Eq. (7):
◦
2
mass loss of 56.15% (calcd. 56.47%), is reasonably accounted for
the decomposition of the organic part of the complex leaving
out CuO as a residue with a found mass loss of 14.42% (calcd.
1
3.38%).
UO (LFX)(H O) ](NO ) chelate exhibits two steps of decom-
∗
E
A
[
2
2
2
3 2
=
(7)
◦
RTs2
∗
position within the temperature range 200–690 C. In the first
step of decomposition within the temperature range 200–385 C in
ϕ exp(−E /RTs)
◦
A number of pyrolysis processes can be represented as a first
order reaction. The degradation of a series LFX complexes was sug-
gested to be first order, therefore we assume n = 1 for the remainder
of the present text. The other thermodynamic parameters such as
activation energy (E), preexponential factor (A), entropy of activa-
tion (ꢃS), enthalpy of activation (ꢃH) and free energy of activation
which two coordinated water molecules, 2NO3 and C7H11F2N O2
2
gases with an estimated mass loss of 42.05% (calcd. 41.97%) occurs.
◦
The second step within the temperature range 385–690 C, involves
liberation of C10H NO molecule with an estimated mass loss of
8
1
0.86% (calcd. 10.78%).
(
[
ꢃG) of decomposition steps were calculated using Coats–Redfern
45] and Horowitz–Metzger [46] methods and the average val-
3
.11. Kinetic data
ues obtained are listed in Table 3. From the results, the following
remarks can be pointed out:
The kinetic and thermodynamic parameters of thermal degra-
dation process have been calculated using Coats–Redfern [45] and
Horowitz–Metzger methods [46]. Coats–Redfern relation [45] is as
follows:
-
-
The high values of the energy of activation of the complexes reveal
the high stability of such chelates due to their covalent bond
character [47].
The positive sign of ꢃG for the investigated complexes reveals
that the free energy of the final residue is higher than that of
the initial compound, and all the decomposition steps are non-
spontaneous processes. Also, the values of the activation, ꢃG
increases significantly for the subsequent decomposition stages
of a given complex. This is due to increasing the values of TꢃS
significantly from one step to another which overrides the values
of ꢃH [47].
ꢀ
ꢁ
ꢀ
ꢁ
ln −ln(1 − ˛)
AR
ˇE
E
= ln
−
(4)
2
T
RT
where ˛ represents the fraction of sample decomposed at time t,
defined by: ˛ = (wo − wt)/(wo − w∞), wo, wt and w∞ are the weight
of the sample before the degradation, at temperature t and after
total conversion, respectively. T is the derivative peak tempera-
ture. ˇ is the heating rate = dT/dt, E and A are the activation energy
and the Arrhenius pre-exponential factor, respectively. A plot of
-
The negative values of ꢃS for all the complexes indicate more
ordered activated complex than the reactants or the reaction is
slow [47].
2
ln[−(ln(1 − ˛))/T ] versus 1/T gives a straight line whose slope (E/R)
and the pre-exponential factor (A) can be determined from the
intercept.
3
.12. X-ray powder diffraction of complexes
The Horowitz–Metzger equation [44] is an illustrative of the
approximation methods. These authors derived the relation:
◦
◦
X-ray powder diffraction pattern in the 0 < 2ꢇ < 60 of the LFX
ligand and its metal complexes were carried out in order to give
an insight about the lattice dynamics of these compounds. The X-
ray powder diffraction obtained reflects a shadow on the fact that
each solid represents a definite compound of a definite structure
1−n
(
1 − (1 − ˛)
Eꢇ
log
=
,
for n =/ 1
(5)
2.303RT2
1
− n
s

1
6
H.F.A. El-Halim et al. / Spectrochimica Acta Part A 82 (2011) 8–19
H O
2
OH2
H O
2
OH2
OH2
O=U=O
H O
2
M
O
O
.(NO3)2
O
N
O
.
Cl .nH O
m 2
F
F
-
-
O
O
N
N
N
+
N
+
H
2
F
H
2
N
F
CH
3
CH
3
CH
3
CH
3
M = Cr(III), Mn(II), Fe(III), Co(II), Ni(II),
Cu(II), Zn(II) and Th(IV)
m = 2-4, n = 0-2
Fig. 2. Structures of metal complexes.
which is not contaminated with starting materials. Such facts sug-
gest that the LFX ligand and its Cr(III), Fe(III), Co(II), Ni(II), Cu(II) and
biological potential of the synthesized compounds, the LFX ligand
and its metal complexes was tested against the selected bacte-
ria and fungi. The in vitro antibacterial and antifungal activity
tests were performed using the disc diffusion method. Tetracycline
and amphotricine were used as positive control for bacteria and
fungus, respectively. The growth of inhibition zones after incuba-
tion is shown in Table 4. The synthesized compounds were found
to possess remarkable bactericidal and fungicidal properties. It is
however interesting that the biological activity gets enhanced on
undergoing complexation with the metal ions.
Th(IV) complexes are crystalline while Mn(II), Zn(II) and UO (II)
2
complexes are amorphous.
3.13. Structural interpretation
From all of the above observations, the structure of these
complexes may be interpreted in accordance with complexes of
LFX drug with a similar distribution of like coordinating sites
[
14,15,23,24]. The structural information from the previously
From structure point of view of the prepared compounds with
their effects on microbial tested, it is clear that formation of the
chelate derivatives in 1:1 molar ratio (M:L) sometimes increase the
biological activity as appeared from the results. So the enhanced
activities of the metal complexes compared to the free ligand may
be attributed to the increase in the number of oxygen group around
the central metal atom arising from chelation in 1:1 molar ratio
(M:L) and hence, the central metal atom was not only the respon-
sible for biological activity because some metal complexes can
enhance the activity and others can reduced this activity with
respect to the parent ligand. Finally, to complete the evaluation
of biological activity of the synthesized compounds, some compar-
ison with the known standard antibiotics were performed and the
data are summarized in Table 4 and shown in Fig. 3). Using Staphy-
reported complexes is in agreement with the data reported in
this paper based on the pK, IR, molar conductance, magnetic and
electronic spectra measurements. Consequently, the structures
proposed are based on octahedral complexes. The LFX drug always
coordinates via the carbonyl O and the protonated O atoms forming
a two binding chelating sites. The proposed general structures are
shown in Fig. 2.
3
3
.14. Biological activity
.14.1.1. Antimicrobial activity
The question about the involvement of metal ligand com-
plexes in medical treatment are of special interest. To assess the
Table 4
Biological activity of binary LFX-metal complexes.
Sample
Inhibition zone diameter (mm/mg sample)
E. coli
Staphylococcus aureus
Aspergillus flavus
Candida albicans
Control: DMSO
LFX
0.0
43
36
43
40
40
40
42
42
40
37
0.0
44
38
48
46
44
40
43
47
37
42
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
11
12
11
13
20
21
12
12
12
12
[
[
[
[
[
[
[
[
[
Cr(LFX)(H2O)4]·Cl3
Mn(LFX)(H2O)4]·Cl2
Fe(LFX)(H2O)4]Cl3·H2O
Co(LFX)(H2O)4]·Cl2
Ni(LFX)(H2O)4]Cl2·H2O
Cu(LFX)(H2O)4]Cl2·2H2O
Zn(LFX)(H2O)4]·Cl2
Th(LFX)(H2O)4]·Cl4
UO2 (LFX) (H2O)2]·(NO3)2
Standard
Tetracycline
Amphotericin B
33
–
31
–
–
16
–
19

H.F.A. El-Halim et al. / Spectrochimica Acta Part A 82 (2011) 8–19
17
(a) E. coli
50
40
30
20
10
0
(
b) Staphylococcus aureus
5
4
4
3
3
2
2
1
1
0
5
0
5
0
5
0
5
0
5
0
(
c) Candida albicans
3
2
1
0
0
0
0
Fig. 3. Biological activity of LFX and its metal complexes.
+
−
lococcus aureus (G ) and Escherichia coli bacteria (G ), it is noticed
that the biological activity of Fe(III), Mn(II) and Zn(II) complexes
are higher than that of the LFX drug and tetracycline standard. In
complexes are found to be higher than that of the free LFX lig-
and but lower than amphotricine standard except Co(II) and Ni(II)
complexes.
addition, the biological activity of Ni(II), Cu(II), Cr(III), UO (II) and
The LFX drug presented here and its transition metal complexes
gave better results against the growth of bacteria and fungi. It is
found that the activity increases upon co-ordination. The increased
activity of the metal chelates can be explained on the basis of
2
Th(IV) complexes are lower than that of the free LFX ligand. For
Co(II) complex, its biological activity is the same like that of LFX.
Using Candida albicans fungus, the biological activity of the metal
Table 5
Antibreastic cancer activity of LFX and its binary complexes.
Complex
Surviving fraction (MCF7)
IC50 (␮g/ml)
Concentration (␮g/ml)
0.0
5
12.5
25
50
LFX
1.00
1.00
1.00
1.00
1.00
1.00
0.64
0.99
0.64
0.99
0.89
0.99
0.53
0.99
0.47
1.03
0.89
0.89
0.27
0.95
0.28
1.05
0.90
0.75
0.19
0.89
0.22
0.95
0.59
0.40
14.0
–
11.2
–
–
43.1
[
[
[
[
[
Mn(LFX)(H2O)4]·Cl2
Co(LFX)(H2O)4]·Cl2
Ni(LFX)(H2O)4]Cl2·H2O
Cu(LFX)(H2O)4]Cl2·2H2O
Zn(LFX)(H2O)4]·Cl2

1
8
H.F.A. El-Halim et al. / Spectrochimica Acta Part A 82 (2011) 8–19
1
.2
1
C = 0
C = 5
C = 12.5
C = 25
C = 50
0
0
0
0
.8
.6
.4
.2
0
LFX
Mn(II)
Co(II)
Ni(II)
Cu(II)
Zn(II)
Fig. 4. The anticancer activity of LFX and its binary complexes.
chelation theory [48]. The orbital of each metal ion is made so as
to overlap with the ligand orbital. Increased activity enhances the
lipophilicity of complexes due to delocalization of pi-electrons in
the chelate ring [46]. In some cases increased lipophilicity leads to
breakdown of the permeability barrier of the cell [44,48,49].
gal activity tests were performed using the disc diffusion method.
Also the anticancer activity against breast cancer cell line (MCF7)
was also studied. The complexes show a remarkable biological and
anticancer activity.
Appendix A. Supplementary data
3.14.1.2. Cytotoxic activity
The LFX drug and its metal complexes were tested for their
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.saa.2011.05.089.
activity against breast cancer cell line (MCF7) by using 100 ␮g/ml
concentration. From these result summarized in Table 5), it
is clear that LFX, [Mn(LFX)(H O) ]·Cl , [Co(LFX)(H O) ]·Cl
2
4
2
2
4
2,
[
[
Ni(LFX)(H O) ]Cl ·H O,
[Cu(LFX)(H O) ]Cl ·2H O
and
References
2
4
2
2
2
4
2
2
Zn(LFX)(H O) ]·Cl were found to be very active against breast
2
4
2
[
[
[
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