Synthesis and characterization of mixed ligand complexes of lomefloxacin drug and glycine with transition metals. Antibacterial, antifungal and cytotoxicity studies

Article abstract of DOI:10.1016/j.molstruc.2011.05.018

Mixed ligand complexes derived from lomefloxacin (LFX, L¹) as primary ligand and glycine (L²) as secondary ligand have been prepared and characterized by conventional techniques including elemental analyses, XRD, infrared, electronic spectra, molar conductivity and thermal analyses. The elemental analyses data display the formation of 1:1:1 [M:L ¹:L²] complexes. The diffused reflectance and magnetic moment measurements reveal the presence of the complexes in an octahedral geometry. The infrared spectral data show that the chelation behavior of the ligands toward transition metal ions is through carbonyl O, and carboxylate O of LFX whereas the amino acid coordinate through the carboxylate oxygen and the amino nitrogen. The electronic spectral results display the existence of π-π (phenyl rings), n-π (NH₂ and CN) and confirm the mentioned structure. The molar conductivity reveals an electrolytic nature of all chelates. The thermogravimetric analysis data of the complexes displays the existence of hydrated and coordinated water molecules. The effect of LFX, glycine and their complexes on the inhibition of bacteria or fungi growth were evaluated. The prepared complexes were found to exhibit enhanced activity on bacteria or fungi growth compared to LFX and glycine ligands. LFX, [Mn(LFX)(Gly)(H₂O)₂]·Cl, [Co(LFX)(Gly)(H ₂O)₂]·Cl and [Zn(LFX)(Gly)(H₂O) ₂]·Cl were found to be very active against breast cancer cells with IC50 values 14, 11.2, 13 and 16.8, respectively, while glycine and other complexes had been shown to be inactive at lower concentration than 100 μg/ml.

Full text of DOI:10.1016/j.molstruc.2011.05.018

Journal of Molecular Structure 999 (2011) 29–38
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Synthesis and characterization of mixed ligand complexes of lomefloxacin drug
and glycine with transition metals. Antibacterial, antifungal and cytotoxicity studies
b
a
a
Gehad G. Mohamed a, , Hanan F. Abd El-Halim , Maher M.I. El-Dessouky , Walaa H. Mahmoud
⇑
a Chemistry Department, Faculty of Science, Cairo University, 12613 Giza, Egypt
b Pharmaceutical Chemistry Department, Faculty of Pharmacy, Misr International University, Cairo, Egypt
a r t i c l e i n f o
a b s t r a c t
Mixed ligand complexes derived from lomefloxacin (LFX, L1) as primary ligand and glycine (L2) as second-
ary ligand have been prepared and characterized by conventional techniques including elemental anal-
yses, XRD, infrared, electronic spectra, molar conductivity and thermal analyses. The elemental
analyses data display the formation of 1:1:1 [M:L1:L2] complexes. The diffused reflectance and magnetic
moment measurements reveal the presence of the complexes in an octahedral geometry. The infrared
spectral data show that the chelation behavior of the ligands toward transition metal ions is through car-
bonyl O, and carboxylate O of LFX whereas the amino acid coordinate through the carboxylate oxygen
Article history:
Received 9 March 2011
Received in revised form 9 May 2011
Accepted 11 May 2011
Available online 17 May 2011
Keywords:
Lomefloxacin
Glycine
Mixed ligand complexes
Biological activity
Anticancer activity
and the amino nitrogen. The electronic spectral results display the existence of
n–
p
–
p
⁄ (phenyl rings),
p
⁄ (NH2 and AC@N) and confirm the mentioned structure. The molar conductivity reveals an electro-
lytic nature of all chelates. The thermogravimetric analysis data of the complexes displays the existence
of hydrated and coordinated water molecules. The effect of LFX, glycine and their complexes on the inhi-
bition of bacteria or fungi growth were evaluated. The prepared complexes were found to exhibit
enhanced activity on bacteria or fungi growth compared to LFX and glycine ligands. LFX, [Mn(LFX)(Gly)
(H2O)2]ꢀCl, [Co(LFX)(Gly)(H2O)2]ꢀCl and [Zn(LFX)(Gly)(H2O)2]ꢀCl were found to be very active against
breast cancer cells with IC50 values 14, 11.2, 13 and 16.8, respectively, while glycine and other complexes
had been shown to be inactive at lower concentration than 100
lg/ml.
Ó 2011 Elsevier B.V. All rights reserved.
1. Introduction
mon. The literature contains few examples, such as a complex of
zinc whose structure was revealed by X-ray diffraction, where
two molecules of the ligand norfloxacin coordinate via the ketonic
and carboxylic oxygen atoms and two other molecules coordinate
by way of the terminal nitrogen of the piperazine [18,19]. Lome-
floxacin is a bactericidal fluoroquinolone agent with activity
against a wide range of gram-negative and gram-positive organ-
isms. Its chemical IUPAC name is 1-ethyl-6,8-difluoro-7-(3-meth-
ylpiperazin-1-yl)-4-oxoquinoline-3-carboxylic acid (Fig. 1). The
bactericidal action of lomefloxacin results from interference with
the activity of the bacterial enzymes DNA gyrase and topoisomer-
ase IV, which are needed for the transcription and replication of
bacterial DNA [1]. Modifications of LFX were made based on struc-
ture–activity relationships (SARs). It was discovered that a fluorine
atom at position 6 and a piperazine ring at position 7 greatly en-
hance the spectrum of activity. Recently, a relatively new approach
to the rational design of antitumor agents has been introduced
based on some new quinolone molecules that display a novel mode
of action [2,3].
Metal ion-mediated reactions involving nucleic acid constitu-
ents and amino acid side chains have been the subject of several
investigations [1–6]. These reactions provide an opportunity to
identify the nature of such interactions in vivo as they serve as
models for many metalloenzyme reactions. The fluoroquinolones
constitute an important class of synthetic antimicrobial agents,
which have been the objects of intensive study [7]. Numerous
studies regarding the interaction between various quinolones with
metallic cations have been reported in the literature [8–11]. These
studies have been primarily directed towards the identification of
functional groups directly linked to the metal and to establish
the structure formed by these coordination complexes. Other
investigations aim to show the effect of metal ions upon antibacte-
rial activity [12,13]. Still, other research groups have reported the
antibacterial properties of metal complexes with fluoroquinolones
[14–17]. The coordination of the fluoroquinolones with metallic
ions by way of the piperazine nitrogen atoms is much less com-
In order to gather more information, we thought it was impor-
tant to investigate the interaction of lomefloxacin and amino acid
(glycine) with the biologically important metal ions, Fe(III), Cr(III),
Mn(II), Zn(II), Cu(II), Ni(II) and Co(II). These complexes were
⇑
Corresponding author.
E-mail address: ggenidy@hotmail.com (G.G. Mohamed).
0022-2860/$ - see front matter Ó 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2011.05.018

30
G.G. Mohamed et al. / Journal of Molecular Structure 999 (2011) 29–38
plementation of RPMI-1640 medium prior to use. 0.025% (w/v)
Trypsin (Sigma Chemical Co., St. Louis, Mo, USA) was used for the
harvesting of cells. 1% (v/v) Acetic acid (Sigma Chemical Co., St.
Louis, Mo, USA) was used for dissolving the unbound SRB dye.
0.4% Sulphorhodamine-B (SRB) (Sigma Chemical Co., St. Louis,
Mo, USA) 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, USA) was prepared and stored. Fifty microliters
of the stock was added to 200 ll RPMI-1640 medium/well to yield
a final concentration 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).
Fig. 1. Structure of LFX drug.
prepared as models which might correspond to the complexes
formed with fluroquinolone drugs in vivo. The complexes were
characterized based on elemental analysis, conductivity data, infra-
red spectra, electronic spectra and magnetic susceptibility data and
their bonding modes assigned. LFX acts as a neutral bidentate li-
gand with OO coordination sites binding under the conditions em-
ployed whereas the amino acid (glycine) acts as bidentate ligand
coordinating through the carboxylate oxygen and the amino nitro-
gen. Octahedral geometry for metal chelates is proposed.
2.3. Measurements
Microanalyses of carbon, hydrogen and nitrogen were carried
out at the Microanalytical Center, Cairo University, Egypt, using
CHNS-932 (LECO) Vario Elemental Analyzer. The X-ray powder dif-
fraction analyses were carried out by using Philips Analytical X-ray
BV, diffractometer type PW 1840. Radiation was provided by cop-
per target (Cu anode 2000 W) high intensity X-ray tube operated at
4050 kV and 25 mA. Divergence and the receiving slits were 1 and
0.2, respectively. Analyses of the metals followed the dissolution of
the solid complex in concentrated HNO3, neutralizing the diluted
aqueous solutions with ammonia and titrating the metal solutions
with EDTA. Electronic and diffused reflectance spectra were re-
corded at room temperature on a Shimadzu 3101pc spectropho-
tometer as solutions in ethanol and solid complexes (BaSo4 disk),
respectively. 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. The molar magnetic sus-
ceptibility was measured on powdered samples using the
Faraday method. The diamagnetic corrections were made by
Pascal’s constant and Hg[Co(SCN)4] was used as a calibrant. pH
measurements were carried out using Jenway 3505 pH meter, UK
FT-IR spectra were recorded on a Perkin–Elmer 1650 spectrometer
(4000–400 cmꢂ1) in KBr pellets. The antibacterial and antifungal
activities were evaluated at the Microbiological laboratory, Micro-
analytical center, Cairo University, Egypt. The anticancer activity
was performed at the National Cancer Institute, Cancer Biology
Department, Pharmacology Department, and Cairo University,
Egypt. The optical density (O.D.) of each well was measured spec-
trophotometrically at 564 nm with an ELIZA microplate reader
2. Experimental
2.1. Materials
All chemicals and reagents used in this investigation were
laboratory pure (BDH, Aldrich or Sigma) including CrCl3ꢀ6H2O,
FeCl3ꢀ6H2O, CoCl2ꢀ6H2O, NiCl2ꢀ6H2O, CuCl2ꢀ2H2O, ZnCl2ꢀ2H2O,
UO2(NO3)2ꢀ2H2O, ThCl4, glycine, NH4OH, DMF, C2H5OH and double
distilled water.
2.2. Solutions
A fresh stock solution of 1 ꢁ 10ꢂ3 M LFX (0.351 g/l) was pre-
pared in the appropriate volume of absolute ethanol. 1 ꢁ 10ꢂ3
M
Stock solutions of the metal salts (Fe(III), 0.27 g/l; Co(II), 0.23 g/l;
Ni(II), 0.23 g/l; Cu(II), 0.17 g/l; Zn(II), 0.172 g/l; Cr(III), 0.26 g/l;
UO2(II), 0.50 g/l, Mn(II), 0.16 g/l and Th(IV), 0.37 g/l) were prepared
by dissolving the accurately weighed amounts of the metal salts in
the appropriate volume of de-ionized water. Acid mixture (0.04 M
phosphoric, acetic and boric acids) from which series of universal
buffer solution of different pH values (2–12) were prepared by
using 0.1 M sodium hydroxide solution for adjusting the desired
pH.
(Meter tech.
R
960, USA). Molar conductivities of 10ꢂ3 M solutions
Dimethylsulphoxide (DMSO) (was supplied from Sigma Chemi-
cal Co., St. Louis, Mo, and USA. It was used in cryopreservation of
cells. RPMI-1640 medium (Sigma Chemical Co., St. Louis, Mo, and
USA) is used. The medium was used for culturing and maintai-
nance 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 2 g sodium bicarbonate, completed to
1 l with distilled water and shacked carefully till complete dissolu-
tion. The medium was then sterilized by filtration in a Millipore
of the solid complexes in DMF were measured on the using Jenway
4010 conductivity meter. The thermal analyses (TG, DTG and DTA)
of the solid complexes were carried out from room temperature to
800 °C using a Shimadzu TG-50H thermal analyzer.
2.4. Preparation of mixed ligand complexes
The present mixed complexes were prepared by mixing equal
amounts (0.01 mol) of hot saturated ethanolic solution of the first
ligand (lomefloxacin) and second ligand (glycine) with the same
ratio of metal chloride or nitrate salts. The mixture was refluxed
for 3 h. The resulting complexes were filtered and washed several
times with hot ethanol until the filtrates become clear. The solid
complexes then dried in desiccator over anhydrous calcium chlo-
ride. The yield ranged from 74% to 91%.
bacterial filter (0.22 lm). The prepared medium was kept in a
refrigerator (4 °C) and checked at regular intervals for contamina-
tion. Before use the medium was warmed at 37 °C in a water bath
and the supplemented with penicillin/streptomycin and FBS.
Sodium bicarbonate (Sigma Chemical Co., St. Louis, Mo, USA)
was used for the preparation of RPMI-1640 medium. 0.05% isotonic
Trypan blue solution (Sigma Chemical Co., St. Louis, Mo, USA) 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, USA and were used for the sup-
MðIIÞ or MðIIIÞ or MðIVÞ þ L1 þ L2 ! ½ML1L2ꢃþ
M(II) = Mn(II), Co(II), Ni(II), Cu(II), Zn(II), M(III) = Cr(III), Fe(III),
M(IV) = Th(IV), L1 = lomefloxacin, L2 = glycine.

G.G. Mohamed et al. / Journal of Molecular Structure 999 (2011) 29–38
31
The dried complexes were subjected to elemental and spectro-
scopic analyses. The obtained complexes are soluble in ethanol,
DMF and DMSO. All melting points of the complexes were mea-
sured and found to be >200 °C.
ium the n ? p⁄ transition may be disappeared due to the proton-
ation of nitrogen atom.
It is obvious from the absorption spectra obtained that all the
ternary chelates have the same behavior. The band at 320 nm
may be assigned to n ? p⁄ transition within the C@O group or car-
boxylate group of free LFX and glycine ligands. This band is red
shifted to 321–326 nm in some chelates, while it disappeared in
all the remaining chelates revealing the involvement of the C@O
group of LFX ligand and carboxylate–O of amino acids in chelate
formation [22,23].
2.5. Biological activity
A filter paper disk (5 mm) was transferred into 250 ml flasks
containing 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 po-
sitive and gram negative) and two strains of fungi then, transferred
to a saturated disk with a tested solution in the center of Petri dish
(agar 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 un-
der the same condition described previously for each microorgan-
ism 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 [20]. All experiments were performed as triplicate and
data plotted were the mean value.
The n ? p⁄ transition within the LFX molecule is overlapped
with those of glycine molecule at k = 320–350 nm so renders it dif-
ficult to attribute the blue or red shift of these bands as a result of
the involvement of the N atom of LFX or amino group of glycine
during chelate formation (N ? M) [22,23].
3.2. Microanalysis
The elemental analyses data of the complexes (Table 1) show
the formation of the complexes in the ratio 1:1:1 for [ML1L2]. It
is found that the theoretical values are in agreement with the
found values.
Analytical and conductivity data of the complexes are presented
in Table 1. The analytical data correspond to a metal–lomefloxacin–
amino acid ratio of 1:1:1 and one mole of water per mole of metal
for Fe(III) and Ni(II) complexes, two moles of water per mole of me-
tal for Cu(II) complex and three moles of water for UO2(II) complex.
2.6. Anticancer activity
Potential cytotoxicity of the compounds was tested using the
method of Skehan et al. [21]. Cells were plated in 96-multiwell
plate (104 cells/well) for 24 h before treatment with the com-
pounds to allow attachment of cell to the wall of the plate. Differ-
ent concentrations of the compounds under investigation (0, 5,
3.3. Molar conductance measurements
From conductivity measurements, performed in dimethylform-
amide, it is concluded from the results given in Table 1 that the
Fe(III) and Cr(III) chelates have molar conductivity values of 178
12.5, 25, 50 and 100 lg/ml) were added to the cell monolayer trip-
licate wells were prepared for each individual dose. The monolayer
cells were incubated with the compounds for 48 h at 37 °C and in
5% CO2 atmosphere. 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 opti-
cal density (O.D.) of each well was measured spectrophotometri-
cally at 564 nm with an ELIZA microplate reader and the mean
background absorbance was automatically subtracted and mean
values of each drug concentration was calculated. The relation be-
tween surviving fraction and drug concentration is plotted to get
the survival curve of Breath tumor cell line for each compound.
and 152
X
ꢂ1 molꢂ1 cm2, respectively, indicating that they are 1:2
electrolytes. The molar conductivity values of Mn(II), Co(II), Ni(II),
Cu(II), Zn(II) and UO2(II) chelates under investigation (Table 1) are
found to be 108, 101, 126, 117, 124 and 139
X
ꢂ1 molꢂ1 cm2,
respectively. It is obvious from these data that these chelates are
ionic in nature and they are of the type 1:1 electrolytes. Th(IV)
complex has a molar conductance value of 289
X
ꢂ1 molꢂ1 cm2,
indicating its ionic nature and it is 1:3 electrolyte type.
3.4. IR spectral studies
The infrared spectra of various mixed ligand complexes synthe-
sized are compiled in (Table 2 and Supplementary Fig. 2). The
infrared spectra of these complexes in comparison with free LFX
drug and the respective free glycine amino acid show characteristic
band positions, shifts and intensities, which can be correlated to
bidentate LFX drug and bidentate amino acid chelation. The IR
spectra of the free LFX and glycine ligands and their metal com-
plexes were carried out in the range of 4000–400 cmꢂ1 and the
most effective bands are listed in Table 2. The strong band ob-
served at 1725 cmꢂ1 in the free LFX ligand is assigned to the car-
bonyl stretching vibration [24–26]. This band is found in the
spectra of the complexes at 1721–1739 cmꢂ1 (Table 2) or disap-
peared in some complexes indicating the participation of carbonyl
2.7. Calculation
The percentage of cell survival was calculated as follows:
Survival fraction ¼ O:D: ðtreated cellsÞ=O:D: ðcontrol cellsÞ:
The IC50 values are the concentrations of thymoquinone re-
quired to produce 50% inhibition of cell growth. The experiment
was repeated 3 times for each cell line.
3. Results and discussion
3.1. UV–visible spectra of metal chelates
oxygen atom in coordination (MAO) [25]. The m(OH), masym(COO)
UV–visible spectral data of the free LFX and glycine ligands and
their ternary chelates (1 ꢁ 10ꢂ3 M) solutions in aqueous universal
buffer of varying pH values ranged from 2 to 12 at k ranging from
200 to 600 nm using the same solvent as blank are studied. It is
obvious that free LFX ligand gives in the neutral and alkaline media
two maximum bands, the first at 325 nm and another shoulder
band at 295 nm. These bands may be attributed to n ? p⁄ and
and msym(COO) stretching vibrations are observed at 3367, 1590
and 1396 cmꢂ1, respectively, for LFX free ligand [27,28,25]. Coordi-
nation with metal ions via the carboxylate O atom indicated by
shift in position of
bands to 1530–1590 and 1396–1475 cmꢂ1
LFX–Gly–metal complexes (Table 2). The (OH) band is still broad
m
asym(COO) and
msym(COO) stretching vibration
,
respectively, for
m
in all complexes, which renders it difficult to attribute to the
p
?
p⁄ transitions inside the LFX molecule. But in the acidic med-
involvement of OH group in coordination. In the 3400 cmꢂ1 region,

32
G.G. Mohamed et al. / Journal of Molecular Structure 999 (2011) 29–38
Table 1
Analytical and physical data of LFX and its complexes with glycine.
Compound (molecular formula)
Color (%yield)
M.p.
(°C)
% Found (Calcd)
leff
(BM)
.
Km
X
ꢂ1 molꢂ1 cm2
C
H
N
M
[Cr(LFX)(Gly)(H2O)2]ꢀCl2 (C19H27N4O7F2Cl2Cr)
Dark green (91)
Light brown (88)
230
225
200
230
260
200
210
200
210
39.37
(39.03)
41.43
(41.39)
35.07
(35.05)
41.50
(41.02)
38.71
(38.58)
39.79
(39.76)
40.56
(40.56)
28.83
4.75
(4.62)
5.08
(4.90)
4.06
(4.98)
4.92
(4.86)
4.86
(4.57)
5.08
(5.06)
4.92
(4.80)
3.58
9.62 (9.59)
– (8.88)
3.55
152
108
178
101
126
117
124
289
139
[Mn(LFX)(Gly)(H2O)2]ꢀCl (C19 H27 N4O7F2Cl
Mn)
10.95
(10.17)
9.82 (9.62)
– (9.80)
– (9.62)
5.25
[Fe(LFX)(Gly)(H2O)2]Cl2ꢀH2O
Reddish brown
(85)
Violet (91)
5.82
(C17H29N4O8F2Cl2Fe)
[Co(LFX)(Gly)(H2O)2]ꢀCl (C19H27N4O5F2ClCo)
10.21
(10.08)
9.79 (9.48)
–
5.26
(10.61)
– (9.93)
[Ni(LFX)(Gly)(H2O)2]ClꢀH2O
(C19H29N4O8F2ClNi)
Light green (79)
Blue (80)
2.97
[Cu(LFX)(Gly)(H2O)2]Clꢀ2H2O
9.83 (9.76)
–
2.03
(C19H31N4O9F2ClCu)
(10.29)
–
(11.63)
–
(30.37)
–
[Zn(LFX)(Gly)(H2O)2]ꢀCl (C19H27N4O7F2ClZn)
White (85)
10.06 (9.96)
Diam.
Diam.
Diam.
[Th(LFX)(Gly)(H2O)2]ꢀCl3 (C19H27N4O7F2Cl3Th)
Pale yellow (76)
Yellow (74)
11.86
(11.75)
8.86 (8.67)
(28.51)
28.50
(3.38)
2.50
[UO2(LFX)(Gly)](NO3) (C19H23N5O10F2U)
(28.25)
(2.85)
(36.93)
Table 2
IR spectra (4000–400 cmꢂ1) of LFX, glycine and their ternary metal complexes.
LFX
Glycine [Cr(LFX) (Gly)
(H2O)2]Cl2ꢀ2H2O (H2O)2]Clꢀ2H2O (Gly)
(H2O)2]
[Mn(LFX) (Gly) [Fe(LFX)
[Co(LFX)
(Gly)
(H2O)2]
Clꢀ2H2O
[Ni(LFX)
(Gly)
(H2O)2]
ClꢀH2O
[Cu(LFX)
(Gly)
(H2O)2]
Clꢀ2H2O
[Zn(LFX)
(Gly)
(H2O)2]
Clꢀ2H2O
[Th(LFX)
(Gly)
(H2O)2]
Cl3ꢀ2H2O
[UO2(LFX) Assignment
(Gly)]
(NO3)
Cl2ꢀ2H2O
3367br
–
–
3053br
3155br
3376br
3037br
3299br
3128br
3376br
3156br
3337br
3263br
3350br
3128br
3415br
3131br
3363br
3153br
3428br
OH stretch
Asym. NH2
stretch
3400br 3376br
–
–
–
3084br 3053s
3048s
2900s
2103m
3037s
2819s
2140s
3045s
2927s
2453m
3012s
2960s
2118s
3059s
2941s
2467m
3042br
2868s
2044s
3131br
2897s
2453s
3153br
2897s
2453s
Asym.CH
stretch
Sym.CH
stretch
Combination
band
2896s
2900s
2097s
2103m
1725sh 1703s
1722sh
1622m
dis
1617sh
dis
1617m
dis
1614m
dis
1622m
1739sh
1614s
dis
1634m
dis
1633s
dis
1622m
C@O stretch
NH2
–
1613m
scissoring
COO asym.
COO sym.
NH2
1590s
1396s
–
1556m
1401m
1333m
1559s
1402s
1326m
1573sh
1404m
1309s
1530s
1397s
1324m
1574s
1406m
1386s
1574m
1402m
1324sh
1566s
1397s
1338s
1574m
1475m
1330s
1566s
1411s
1338s
1530s
1470s
1383s
twist + CH2
twist
808sh
1033sh 1049sh
1052sh
1049sh
1050sh
1050sh
1052sh
1049sh
1049sh
1049sh
CAN
stretch + CAC
vibration
NH2 bend
MAO
MAO in
coordinated
water
–
–
–
698sh
–
–
676s
574s
471s
676s
520s
499m
662s
544s
471s
658sh
544s
456s
659s
574s
485s
662s
559s
485s
658sh
544s
470s
662sh
559s
441s
660sh
558m
470s
–
–
411s
441s
441s
441s
456s
412s
426s
412s
427s
MAN
sh = sharp, m = medium, br = broad, s = small, w = weak.
one observes a broad absorption band due to the OH stretching of
the water molecule, since, according to the elemental analysis and
thermogravimetric studies, most of the complexes obtained con-
tain water of crystallization.
ward shift in
m
NH2 of free amino acids. At the isoelectric point, they
must show
m
NH2 in the region 3500–3300 cmꢂ1 [29]. In the pres-
ent complexes, the IR spectra show characteristic bands in the re-
gion 3428–3299 cmꢂ1, which are lower compared to those of free
As regards, chelation through amino acids, the IR spectra exhibit
mNH2. Hence, it can be concluded that the nitrogen of the amino
group is involved in coordination. The IR spectra show strong evi-
significant features in the
mNH2 and
m
COOꢂ regions. It is worth-
while to mention here that free amino acids exist as zwitterions
and the IR spectra of these cannot be compared entirely with those
of metal complexes as amino acids in metal complexes do not exist
as zwitterions. Free amino acids with NH3 functions in particular
dence in support of the involvement of carboxylate group in coor-
dination. In comparison with free amino acids, the
and
COOꢂ (sym) records different shifts, which confirm the mono-
denticity [30,31] of the carboxylate group. The values of band shift
asym(COO)–
sym(COO)) are all about 143–205 cmꢂ1, indicating
m
COOꢂ (asym)
m
show
m
NH3 in the range of 3130–3030 cmꢂ1. In the complexes,
D
m
(m
m
NH3 gets deprotonated and binds to metal through the neutral
that the carboxylate group in glycine is chelated in a uni-negatively
NH2 group. The transformation of NH3 to NH2 must result in an up-
manner to the metal ions.

G.G. Mohamed et al. / Journal of Molecular Structure 999 (2011) 29–38
33
Table 3
1H NMR spectral data of the lomefloxacin and its ternary chelates.
Compound
LFX
Chemical shift, (d) ppm
Assignment
13.5
8.93
7.89
3.57
3.55
3.39
1.46
1.44
(s, H, COOH)
(s, H, CH of carbon 2)
(d, H, aromatic CH of carbon 5)
(d, 4H, CH2 of carbon 50, 60)
(d, 2H, CH2 of carbon 20)
(d, H, CH of carbon 30)
(d, 3H, CH3 of carbon 1b)
(d, 3H, CH3 of carbon 3a0)
[Zn(LFX)(Gly)(H2O)2]ꢀCl
8.87
7.85
3.41
3.37
3.02
1.46
1.44
(d, H, CH of carbon 2)
(d, H, aromatic CH of carbon 5)
(d, 4H, CH2 of carbon 50, 60)
(d, 2H, CH2 of carbon 20)
(d, H, CH of carbon 30)
(d, 3H, CH3 of carbon 1b)
(d, 3H, CH3 of carbon 3a0)
O
_
COO
F
N
N
+
H2
N
CH2 CH3
F
CH3
Scheme 1. Zwitter-ion formation of LFX.
Thus, it may be concluded that amino acids act as monobasic
bidentates in these complexes coordinating through amino nitro-
gen and carboxylate oxygen [27–29]. Low intensity bands observed
the disappearance of this signal can be attributed to Zwitter-ion
formation shown in Scheme 1 [19,24].
in far-IR region in the range 580–400 cmꢂ1 are due to
m
(MAO) and
(MAN) stretching vibrations [30,31]. The metal–oxygen stretch-
ing frequencies could not be assigned unambiguously due to the
presence of three types of
(MAO) vibrations i.e., MACOOꢂ,
3.5. Magnetic moment measurements
m
The magnetic moment values are listed in Table 1. The magnetic
moment values are found to be 3.55, 5.25, 5.82, 5.26, 2.97 and
2.03 BM for Cr(III), Mn(II), Fe(III), Co(II), Ni(II) and Cu(II) complexes,
respectively, suggesting an octahedral geometry [23,32,33]. The
Zn(II), UO2(II) and Th(IV) complexes are diamagnetic. According
to the empirical formulae of these complexes, an octahedral geom-
etry was proposed.
m
MAH2O and MAC@O. However, the data are retained in Table 2
for clarity.
Therefore, from the IR spectral studies, it is concluded that LFX
behaves as a neutral bidentate ligand with OO coordination sites
and coordinated to the metal ions via the carbonyl oxygen and
protonated carboxylic oxygen [24–28]. Glycine behaves as a uni-
negative bidentate ligand with NO donor sites and coordinated to
the metal ions via the amino group N and deprotonated carboxylic
oxygen.
3.6. Diffused reflectance spectral studies
A comparison of the electronic spectra of the free LFX drug and
glycine ligands coordinated with those of the corresponding metal
complexes, some shifts were detected. This can be considered as
evidence for the complex formation. Additionally, the diffused
reflectance spectra of metal complexes show different bands at dif-
ferent wavelengths, each one is corresponding to certain transition
which suggests the geometry of the complexes. The diffused reflec-
tance spectra of the complexes are dominated by intense intra-
ligand charge transfer bands. The diffused reflectance spectrum of
Cr(III) complex exhibits three bands at 27,411, 25,569 and
3.4.1. 1H NMR spectral studies
Unfortunately, the insolubility of glycine in DMSO-d6 make it
difficult to carry out 1H NMR spectrum of glycine to further clarify
the way of binding of glycine ligand to the metal ions.
The proton NMR spectra of the LFX ligand and its diamagnetic
Zn(II) complex were recorded in DMSO-d6 solution using tetra-
methylsilane (TMS) as internal standard. The chemical shifts of
the different types of protons of the LFX ligand and its diamagnetic
Zn(II) complex are listed in Table 3 and represented graphically in
Supplementary Fig. 3.
4
13,532 cmꢂ1 which may be assigned to the A2g(F) ? 4T2g(F),
4
4A2g(F) ? 4T2g(F) and A2g(F) ? 4T2g(P) spin allowed d–d transi-
The comparative study of 1H NMR data of free LFX ligand and its
zinc complex reveals about the ligatational behavior of the ligand.
Upon comparison with the free LFX ligand, the signal observed at
13.5 ppm can be assigned to the carboxylate OH. This signal disap-
peared in the spectrum of the Zn(II) complex. Although the LFX li-
gand coordinated to the metal ions without proton displacement,
tions, respectively, suggesting an octahedral geometry [23,32,33].
The diffused reflectance spectrum of Mn(II) complex exhibits three
bands at 25,506, 19,085 and 16,542 cmꢂ1, which may be assigned to
4T1g ? 6A1g, 4T2g(G) ? 6A1g and 4T1g(D) ? 6A1g transitions, respec-
tively, which suggests an octahedral geometry [32,33]. From the
diffused reflectance spectrum, it is observed that, the Fe(III) chelate

34
G.G. Mohamed et al. / Journal of Molecular Structure 999 (2011) 29–38
Table 4
Thermoanalytical results (TG, DTG and DTA) of the ternary complexes.
Complex
TG range
(°C)
DTGmax (°C) n⁄ Estim. (Calcd)%
Assignment
Metallic
residue
DTA (°C)
Mass loss
Total mass
loss
[Fe(LFX)(Gly)(H2O)2]
Cl2ꢀH2O
50–220
66
1
1
3
5.40 (5.77)
ꢂLoss of H2O
212(+), 328(ꢂ),
514(ꢂ)
220–275
275–580
209
17.47
(17.14)
64.41
ꢂLoss of 2H2O and Cl2
1/2Fe2O3
282, 326,
508
87.28 (86.98) ꢂLoss of C19H24F2N4O3.5
ꢂLoss of H2O
(64.28)
[Ni(LFX)(Gly)(H2O)2]
ClꢀH2O
30–150
45
1
1
2
4.59 (3.13)
227(+), 492(ꢂ)
218(ꢂ), 512(ꢂ)
218(ꢂ), 526(ꢂ)
150–250
250–655
224
493
24.90
(25.50)
49.48
ꢂLoss of 2H2O, HCl and
C2H4NO2
78.99 (79.11) ꢂLoss of C17H20F2N3O2
NiO
(50.48)
[Cu(LFX)(Gly)(H2O)2]
Clꢀ2H2O
40–115
60
1
1
2
3.69 (3.11)
ꢂLoss of H2O.
115–255
255–695
199
408
22.90(21.87)
ꢂLoss of 2H2O, HCl and
CH2NO2
86.42 (86.36) ꢂLoss of C18H21F2N3O2
CuO
UO2
60.35
(60.85)
[UO2(LFX)(Gly)]ꢀ(NO3)
50–340
209
525
1
1
32.13
(33.04)
25.10
ꢂLoss of NO3 and C8H10F2O4
340–650
57.02 (57.60) ꢂLoss of C11H14N3O
(24.56)
n
⁄ = number of decomposition steps.
exhibits a band at 21,512 cmꢂ1, which may be assigned to the
6A1g ? T2g(G) transition in octahedral geometry of the complex
[23,32]. The 6A1g ? 5T1g transition appears to be split into two
bands at 12,845 and 15,758 cmꢂ1. The spectrum shows also a band
at 28,089 cmꢂ1 which may be attributed to ligand to metal charge
transfer. The diffused reflectance spectrum of the Co(II) complex
The [Fe(LFX)(Gly)(H2O)2]Cl2ꢀH2O complex gives a decomposi-
tion pattern as follows; the first stage is one step within the tem-
perature range of 50–220 °C, representing the loss of H2O
(hydrated) with a found mass loss of 5.40% (calcd. 5.77%). The sec-
ond step represents the loss of two coordinated water and Cl2 gases
with a mass loss of 17.47% (calcd. 17.14%). The subsequent step
represents the loss of the remaining part of the complex with mass
loss of 64.41% (calcd. 64.28%). At the end of the thermogram, the
metal oxide Fe2O3 was the residue 12.27% (calcd. 13.02%), which
is in good agreement with the calculated metal content obtained
and the results of elemental analyses (Table 4).
The [Ni(LFX)(Gly)(H2O)2]ClꢀH2O complex is thermally decom-
posed in four stages. The first stage corresponds to a mass loss of
4.59% (calcd. 3.13%) within the temperature range 30–150 °C rep-
resents the loss of one molecule of hydrated water. The second
stage corresponds to a mass loss of 24.90% (calcd. 25.50%) within
the temperature range 150–250 °C and represents the loss of two
coordinated water molecules, HCl and decomposition of organic
part of the complex. The third and fourth stages, 250–655 °C, with
a found mass loss of 49.48% (calcd. 50.48%) is reasonably ac-
counted for decomposition of the remaining organic part of the
complex leaving out NiO as a residue with a found mass loss of
21.01% (calcd. 20.89%).
gives three bands at 15,480, 12,723 and 14,492 cmꢂ1. The bands ob-
4
served are assigned to the transitions T1g(F) ? 4T2g(F)
(m1),
4
4T1g(F) ? 4A2g(F) (
m
2) and T1g(F) ? 4T1g(P) (
m
3), respectively, sug-
gesting an octahedral geometry around Co(II) ion [23,32,33]. The
region at 28,585 cmꢂ1 refers to the charge transfer band. The dif-
fused reflectance spectrum of the Ni(II) complex displays three
bands at
m
1: 13,390 cmꢂ1
:
3A2g(F) ? 3T2g(F),
m
2: 14,792 cmꢂ1
:
3A2g(F) ? 3T1g(F) and
m
3: 20,492 cmꢂ1
:
3A2g(F) ? 3T1g(P) [23,32].
The spectrum shows also a band at 27,024 cmꢂ1 which may be
attributed to ligand to metal charge transfer.
The reflectance spectrum of the Cu(II) chelate consists of bands
at 14,590 and 20,790 cmꢂ1 which can be attributed to the 2Eg and
2T2g transition normally observed for octahedral Cu(II) complex
[23,32]. An intense peak observed at 25,055 cmꢂ1 is due to ligand
to metal charge transfer transition [32].
3.7. Thermal analyses
The [Cu(LFX)(Gly)(H2O)2]Clꢀ2H2O complex is thermally decom-
posed in four stages. The first stage corresponds to a mass loss of
3.69% (calcd. 3.11%) within the temperature range 40–115 °C and
represents the loss of a molecule of hydrated water. The second
stage corresponds to a mass loss of 22.90% (calcd. 22.87%) within
the temperature range 115–255 °C and represents the loss of two
coordinated water molecules, HCl and decomposition of organic
part of the complex. The last two stage, 255–695 °C with a found
mass loss of 60.35% (calcd. 60.85%), is reasonably accounted for
the decomposition of the remaining organic part of the complex
leaving out CuO as a residue with a found mass loss of 13.58%
(calcd. 13.64%).
Thermogravimetric studies (TG) for the complexes were carried
out within a temperature range from room temperature up to
800 °C. TG results are in a good agreement with the suggested for-
mulae resulted from microanalyses data (Table 1). The determined
temperature ranges and percent losses in mass of the solid com-
plexes on heating are given in Table 4, which revealed the follow-
ing 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 3). In the sec-
ond estimated mass loss of 54.59% (calc. 54.94%), at 345–620 °C,
which may be attributed to the liberation of C7H9F2NO3 molecule
as gases.
[UO2ꢀ(LFX)(Gly)](NO3) chelate exhibits two steps of decomposi-
tion within the temperature range 50–650 °C. In the first step of
decomposition within the temperature range 50–340 °C in which

G.G. Mohamed et al. / Journal of Molecular Structure 999 (2011) 29–38
35
Table 5
Thermodynamic data of the thermal decomposition of the ternary complexes.
Complex
Decomp. temp. (°C)
E⁄ (kJ molꢂ1
)
A (sꢂ1
)
D
S⁄ J Kꢂ1 molꢂ1
)
D
H⁄ (kJ molꢂ1
)
D )
G⁄ (kJ molꢂ1
[Fe(LFX)(Gly)(H2O)2]Cl2ꢀH2O
50–220
220–275
275–580
63.88
163.5
197.6
56.51 ꢁ 106
14.23 ꢁ 107
13.65 ꢁ 108
ꢂ196.4
ꢂ116.9
ꢂ83.56
ꢂ59.08
ꢂ100.7
ꢂ116.7
ꢂ151.2
ꢂ140.4
ꢂ6.84
ꢂ94.42
ꢂ120.9
ꢂ92.74
ꢂ53.47
ꢂ124.3
71.19
77.98
206.2
55.78
141.3
132.1
[Ni(LFX)(Gly)(H2O)2]ClꢀH2O
[Cu(LFX)(Gly)(H2O)2]Clꢀ2H2O
[UO2(LFX)(Gly)]ꢀ(NO3)
30–150
150–250
250–655
55.04
64.08
96.27
1.63 ꢁ 109
2.34 ꢁ 107
7.76 ꢁ 106
76.82
98.42
260.2
40–115
115–255
255–695
24.22
35.14
103.2
4.14 ꢁ 109
1.90 ꢁ 105
4.22 ꢁ 1012
238.50
57.01
247.0
243.3
84.50
250.1
50–340
340–650
43.09
52.39
6.24 ꢁ 107
179.2
101.3
203.3
154.7
4.47 ꢁ 106
NO3 and C8H10F2O4 gases with an estimated mass loss of 32.13%
(calcd. 33.04%) occurs. The second step within the temperature
range 340–650 °C, involves liberation of C11H14N3O molecule with
an estimated mass loss of 25.10% (calcd. 24.56%).
– The high values of the energy of activation of the complexes
reveal the high stability of such chelates due to their covalent
bond character [36].
– The positive sign of
DG 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,
3.8. Kinetic data
D
G increases significantly for the subsequent decomposition
stages of a given complex. This is due to increasing the values
of T S significantly from one step to another which overrides
the values of H [36].
The kinetic and thermodynamic parameters of thermal degra-
dation process have been calculated using Coats–Redfern and
Horowitz–Metzger models [34,35]. Coats–Redfern relation [34] is
as follows:
D
D
The negative values of
ordered activated complex than the reactants or the reaction is
slow [36].
DS for all the complexes indicate more
ln½lnð1 ꢂ
a
Þ=T2ꢃ ¼ lnðAR=bEÞ ꢂ ðE=RTÞ
ð1Þ
a
represents the fraction of sample decomposed at time t, defined
The data listed in Table 5 show that the activation energy E⁄
change with the increase of atomic number in the 3rd series of d-
block elements, for the first decomposition step of their complexes.
The complexes of Fe(III) (d5) and Ni(II) (d8) present higher that of
Cu(II) (d9) complex. This means that these complexes are more sta-
ble at the beginning of the decomposition than those on the Cu(II)
complex [37]. The same trend is gained for these complexes at
the second steps of decomposition, except they become excited
before decomposition. These quantitative explanations of results
mean also that the thermal stability is mainly related to the ste-
reo-structure of the complexes and the electronic configuration of
the d-block elements. Therefore, pairing up energy P and energy
of splitting of metal orbitals in octahedral D0 in strong environment
are calculated. It is obvious that, those elements of Fe(III) (d5) (t2g5
eg0, D0 = ꢂ10/12 ꢂ P) and Ni(II) (d8) (t2g6 eg2, D0 = ꢂ6/12 ꢂ 2P) are
stable since they have high pairing up energy and even an electron
system. The Cu(II) (d9) (t2g6 eg3, D0 = 3/12) has less stability due to
the lower pairing effect. It can be concluded that, the relation be-
tween E⁄ vs. atomic number gives a quantitative interpretation to
the thermal stability of the complexes [37].
by:
a
= (wo ꢂ wt)/(wo ꢂ w1), where wo, wt and w are the weight
1
of the sample before the degradation, at temperature t and after to-
tal conversion, respectively. T is the derivative peak temperature. b
is the heating rate = dT/dt, E and A are the activation energy and the
Arrhenius pre-exponential factor, respectively.
A
plot of
ln[ꢂ(ln(1 ꢂ
a
))/T2] versus 1/T gives a straight line whose slope (E/
R) and the pre-exponential factor (A) can be determined from the
intercept.
The Horowitz–Metzger equation [35] is an illustrative of the
approximation methods. These authors derived the relation:
1ꢂn
log½ð1 ꢂ ð1 ꢂ
aÞ
Þ=ð1 ꢂ nÞꢃ ¼ Eꢄ
U
=2:303RT2s for n – 1
ð2Þ
when n = 1, the LHS of Eq. (2) would be log[ꢂlog(1 ꢂ
a
)]. For a first
order kinetic process the Horowitz–Metzger equation may be writ-
ten in the form (Eq. (3)):
log½logðwa=wcÞꢃ ¼ Eꢄ
U
=2:303RT2s ꢂ log 2:303
ð3Þ
where h = T ꢂ TS, w = w ꢂ w, w = mass loss at the completion of
c
a
a
the reaction; w = mass loss up to time t. The plot of log[log(w /
a
w )] versus h was drawn and found to be linear from the slope of
c
which E⁄ was calculated. The pre-exponential factor, A, was calcu-
3.9. X-ray powder diffraction
lated from the Eq. (4):
X-ray powder diffraction pattern in the 0° < 2h < 60° of the LFX
and glycine ligands and their metal complexes were carried out in
order to give an insight about the lattice dynamics of these com-
plexes. The X-ray powder diffraction obtained reflects a shadow
on the fact that each solid represents a definite compound of a def-
inite structure which is not contaminated with starting materials.
XRD analysis for ternary chelates shows that the coordination of
LFX alone or in the presence of glycine to the metal ions changes
the XRD pattern of the ligands. This means that the metal ions
are not fitted in the same phase of LFX and glycine. Therefore,
the non-similarity of XRD pattern between the metal ions and ter-
nary chelates suggests that these chelates have a different phase
Eꢄ=RT2s ¼ A=½/ expðꢂEꢄ=RTsÞꢃ
ð4Þ
A number of pyrolysis processes can be represented as a first or-
der 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 parame-
ters such as activation energy (E), preexponential factor (A), entro-
py of activation (
DS), enthalpy of activation (DH) and free energy of
activation ( G) of decomposition steps were calculated using
D
Coats–Redfern [34] and Horowitz–Metzger [35] methods and the
average values obtained are listed in Table 5. From the results,
the following remarks can be pointed out:

36
G.G. Mohamed et al. / Journal of Molecular Structure 999 (2011) 29–38
O
2HN
CH2
O
H2O
H2 N
CH2
OC
O
O
U
H2O
M
O
OC
O
O
O
CO
F
F
.(NO3)
CO
.
Clm .n H2O
N
N
N
N
+
+
H
2 N
F
H
2 N
CH2 CH3
CH2CH3
F
CH3
CH3
M = Cr(III), Mn(II), Fe(III),Co(II), Ni(II), Cu(II), Zn(II) and Th(IV) .
m =1-3, n =0-2
Fig. 4. Structures of metal complexes.
Table 6
Biological activity of ternary MALFXAgly complexes.
Sample
Inhibition zone diameter (mm/mg sample)
E. coli
Neisseria gonorrhoeae
Staphylococcus aureus
Bacillus subtilis
Control: DMSO
Glycine
LFX
0.0
10
43
40
42
44
45
40
40
46
43
49
0.0
9
0.0
0.0
44
43
40
46
48
44
40
42
45
50
0.0
10
[Cr(LFX)(Gly)(H2O)2]ꢀCl2
[Mn(LFX)(Gly)(H2O)2]ꢀCl
[Fe(LFX)(Gly)(H2O)2]Cl2ꢀH2O
[Co(LFX)(Gly)(H2O)2]ꢀCl
[Ni(LFX)(Gly)(H2O)2]ClꢀH2O
[Cu(LFX)(Gly)(H2O)2]Clꢀ2H2O
[Zn(LFX)(Gly)(H2O)2]ꢀCl
[Th(LFX)(Gly)(H2O)2]ꢀCl3
[UO2(LFX)(Gly)](NO3)ꢀ3H2O
45
45
47
47
43
42
44
44
50
44
41
46
45
41
42
47
47
51
Standard
Order of activity
Tetracycline 34
33
30
30
UO2(II) > Zn(II) = Th(IV) > Fe(III) >
Th(IV) > Ni(II) = LFX > Cr(III) > Co(II) > Cr(III) > Cu(II) > Mn(II) =
UO2(II) > Zn(II) > Co(II) >
Fe(III) > Th(IV) = LFX >
Mn(II) > Ni(II) = Cu(II) =
Cr(III) > tetracycline > glycine
UO2(II) > Fe(III) = Co(II) > Mn(II) = UO2(II) > Co(II) > Fe(III) >
Cr(III) > Zn(II) = Th(IV) > Ni(II) >
Cu(II) > tetracycline > glycine
Zn(II) > Mn(II) = Cu(II) >
tetracycline > glycine
Ni(II) > tetracycline > glycine
structures than the LFX and glycine ligands. In addition, on com-
paring the XRD spectra of the ternary chelates with the XRD spec-
tra of the free ligands, indicate the crystallinity of the ternary
chelates under study, except [Co(LFX)(Gly)(H2O)2]ꢀCl and
[UO2(LFX)(Gly)](NO3) chelates, they can be considered as amor-
phous structure.
5. Biological activity
5.1. Antimicrobial activity
Metal complexes may affect living systems. This has been
known for over a hundred years in respect of the curare-like activ-
ity in mammals of some metal ammines. The antibacterial activi-
ties of transition metal complexes have been extensively studied
following the discovery that chelating agents inhibit growth of
bacteria when complexed with many metals. To assess the biolog-
ical potential of the synthesized compounds, the LFX and glycine
ligands and their mixed metal complexes was tested against the
selected bacteria strains. The antimicrobial data were collected in
Table 6. The synthesized complexes were found to possess remark-
able bactericidal properties, it is however interesting that the bio-
logical activity gets enhanced on undergoing complexation with
the metal ions. Finally, to complete the evaluation of biological
activity of the synthesized complexes, some comparison with the
known standard antibiotic were performed and the data are col-
lected in Table 6 and shown in Fig. 5 and Supplementary Fig. 6.
The biological activity against the two gram positive (Staphylo-
coccus aureus and Bacillus subtilis) and gram negative bacteria
(Escherichia coli and Neisseria gonorrhoeae) of the ternary metal
4. Structural interpretation
From all of the above observations, the structure of these com-
plexes may be interpreted in accordance with ternary complexes of
LFX drug and glycine with a similar distribution of like coordinat-
ing sites [19,24,27,28]. The structural information from the previ-
ously reported complexes is in agreement with the data reported
in this paper based on the IR, molar conductivity, magnetic and
electronic spectra measurements. Consequently, the structures
proposed are based on octahedral geometry. The LFX drug always
coordinates via the carbonyl O and the protonated O atoms form-
ing a two binding chelating site and glycine behave as uninegative
bidentate ligand with NO donor sites and coordinated to the metal
ions via the amino group N and deprotonated carboxylic oxygen.
The proposed general structures are shown in Fig. 4.

G.G. Mohamed et al. / Journal of Molecular Structure 999 (2011) 29–38
37
60
50
40
30
20
10
0
Bacillus Staphylococcus Neisseria E.coli
Fig. 5. Biological activity of LFX, Gly and ternary complexes.
Table 7
Cytotoxicity effect of ternary complexes.
Complex
Surviving fraction (MCF7)
IC50 (lg/ml)
Concentration (
LFX
[Mn(LFX)(Gly)(H2O)2]ꢀCl
[Co(LFX)(Gly)(H2O)2]ꢀCl
[Ni(LFX)(Gly)(H2O)2]ClꢀH2O
[Cu(LFX)(Gly)(H2O)2]Clꢀ2H2O
[Zn(LFX)(Gly)(H2O)2]ꢀCl
l
g/ml)
0.0
5
12.5
25
50
1.00
1.00
1.00
1.00
1.00
1.00
0.64
0.99
0.59
0.99
0.99
0.65
0.53
0.95
0.51
0.99
0.99
0.61
0.27
0.99
0.19
0.94
0.99
0.30
0.19
0.78
0.21
0.86
0.90
0.24
14.0
11.2
13.0
–
–
16.8
C = 0
C = 5
C = 12.5
C = 25
C = 50
1.2
1
0.8
0.6
0.4
0.2
0
Mn(II)
Zn(II)
Ni(II)
Fig. 7. Anticancer activity of LFX and its ternary complexes.
Co(II)
Cu(II)
LFX
complexes is higher than that of the LFX drug and glycine ligands
and tetracycline standard. It is found that the activity increases
upon coordination. The increased activity of the metal chelates
can be explained on the basis of chelation theory [38]. 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 [39]. In some cases
increased lipophilicity leads to breakdown of the permeability bar-
rier of the cell [38,39].
(except difference in ions where both of ions have II valance state),
the inhibition zone diameter for B. subtilis, S. aureus, N. gonorrhoeae
and E. coli are different. The antimicrobial mechanism of zinc com-
plexes involves the capability of zinc ions to inhibit glycolysis of
microorganisms by oxidizing thiols groups in essential glycolytic
enzymes. It is therefore suggested that the potentiation of bacterial
killing activity of Zn complex may be due to facilitation of entry of
zinc ions into the inside of bacterial cells [40]. In addition, in biolog-
ical systems, only manganese ion is readily capable of replacing
Mg(II), but only in a limited set of circumstances. Mn(II) effectively
binds ATP and allows hydrolysis of the energy molecule by most
In Table 6, it is clear that although both of [Mn(LFX)(Gly)
(H2O)2]ꢀCl and [Zn(LFX)(Gly)(H2O)2]ꢀCl complexes are nearly similar

38
G.G. Mohamed et al. / Journal of Molecular Structure 999 (2011) 29–38
ATPases. Mn(II) can also replace Mg(II) as the activating ion for a
number of Mg(II)-dependent enzymes, although some enzyme
activity is usually lost [40]. Sometimes such enzyme metal prefer-
ences vary among closely related species: for example, the reverse
transcriptase enzyme of lentiviruses like HIV, SIV and FIV is typically
dependent on Mg(II), whereas the analogous enzyme for other retro-
viruses prefers Mn(II) [41]. Also according to the chelation theory
[38], the difference in activity between the two metal ions (Mn(II)
had d5 and Zn(II) had d10 configurations) can be attributed to the dif-
ference in probability of the d orbitals to overlap with the ligand
orbitals. Also it could be due to the difference in electronegativity,
size of the metal ion and the intermediate complex formation.
Appendix A. Supplementary material
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.molstruc.2011.05.018.
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Acknowledgments
The authors express their deep thanks to Prof. Dr. Maher M.I.
El-Dessouky, Professor of Inorganic Chemistry, Cairo University,
for revising the manuscript and his valuable comments.