Preparation, spectroscopic and thermal characterization of new metal complexes of verlipride drug. in vitro biological activity studies

Article abstract of DOI:10.1016/j.saa.2012.01.021

Metal complexes of the general formula [M(VER)₂Cl ₂(H₂O)₂]·yH₂O and [Cr(VER)₂Cl₂(H₂O)₂]Cl·H ₂O (where VER = verlipride, M = Mn(II) (y = 2), Co(II) (y = 2), Ni(II) (y = 2), Cu(II) (y = 1) and Zn(II) (y = 0)) are prepared and characterized based on elemental analyses, IR, ¹H NMR, magnetic moment, molar conductance, and thermal analyses (TG and DTA) techniques. From the elemental analyses data, the complexes are formed in 1:2 [Metal]:[VER] ratio. The molar conductance data reveal that all the metal chelates are non-electrolytes except Cr(III) complex, it is 1:1 electrolyte. IR spectra show that VER is coordinated to the metal ions in a neutral monodentate manner with O donor site of the carbonyl O atom. On the basis of spectral studies and magnetic moment measurements an octahedral geometry has been assigned for the complexes. The thermal behavior of these chelates is studied using thermogravimetric analysis technique. The results obtained show that the complexes lose hydrated water, HCl and coordinated water molecules followed immediately by decomposition of the ligand molecules in the successive unseparate steps. The VER drug, in comparison to its metal complexes is also screened for its biological activity against Gram positive bacterial (Staphylococcus aureus) and Gram negative bacteria (Escherichia coli) and fungi (Candida albicans and Aspergillus flavus) in vitro. The activity data show that most of the metal complexes have antibacterial activity like or higher than that of the parent VER drug against one or more species.

Full text of DOI:10.1016/j.saa.2012.01.021

Spectrochimica Acta Part A 91 (2012) 11–17
Contents lists available at SciVerse ScienceDirect
Spectrochimica Acta Part A: Molecular and
Biomolecular Spectroscopy
journal homepage: www.elsevier.com/locate/saa
Preparation, spectroscopic and thermal characterization of new metal complexes
of verlipride drug. In vitro biological activity studies
M.H. Solimana,∗, Gehad G. Mohamedb
a Chemistry Department, Faculty of Science, Helwan University, Helwan, Egypt
b Chemistry Department, Faculty of Science, Cairo University, 12613 Giza, Egypt
a r t i c l e i n f o
a b s t r a c t
Article history:
Metal complexes of the general formula [M(VER)2Cl2(H2O)2]·yH2O and [Cr(VER)2Cl2(H2O)2]Cl·H2O
(where VER = verlipride, M = Mn(II) (y = 2), Co(II) (y = 2), Ni(II) (y = 2), Cu(II) (y = 1) and Zn(II) (y = 0)) are
prepared and characterized based on elemental analyses, IR, 1H NMR, magnetic moment, molar conduc-
tance, and thermal analyses (TG and DTA) techniques. From the elemental analyses data, the complexes
are formed in 1:2 [Metal]:[VER] ratio. The molar conductance data reveal that all the metal chelates are
non-electrolytes except Cr(III) complex, it is 1:1 electrolyte. IR spectra show that VER is coordinated to
the metal ions in a neutral monodentate manner with O donor site of the carbonyl O atom. On the basis
of spectral studies and magnetic moment measurements an octahedral geometry has been assigned for
the complexes. The thermal behavior of these chelates is studied using thermogravimetric analysis tech-
nique. The results obtained show that the complexes lose hydrated water, HCl and coordinated water
molecules followed immediately by decomposition of the ligand molecules in the successive unsepa-
rate steps. The VER drug, in comparison to its metal complexes is also screened for its biological activity
against Gram positive bacterial (Staphylococcus aureus) and Gram negative bacteria (Escherichia coli) and
fungi (Candida albicans and Aspergillus flavus) in vitro. The activity data show that most of the metal
complexes have antibacterial activity like or higher than that of the parent VER drug against one or more
species.
Received 25 August 2011
Received in revised form
31 December 2011
Accepted 16 January 2012
Keywords:
Verlipride
Metal complexes
IR
Molar conductance
Magnetic moment
1H NMR
Thermal analyses
Biological activity
Published by Elsevier B.V.
1. Introduction
2. Experimental
Verlipride (VER) (Fig. 1) is an anti-psychotic drug, used in treat-
ment of cardiovascular and psychological symptoms associated
with the menopause [1–3]. It is N-[(1-allyl-2-pyrrolidinyl)methyl]-
5-sulfamoyl-2-veretramide [4]. In literature, gas chromatography
with mass spectrometry or flame ionization detector was used [5].
The international conference on harmonization (ICH) guidelines
recommended that stress testing should be carried out to eluci-
date the inherent stability characteristics of the active substance.
Acidic, alkaline and oxidative stability are required [6,7]. However,
in this work, metal chelates of Mn(II), Cr(III), Co(II), Ni(II), Cu(II) and
Zn(II) transition metals with VER drug molecule are prepared. The
solid chelates are characterized using different physico-chemical
methods like elemental analyses (C, H, N, and metal content), IR,
1H NMR, magnetic moment, and thermogravimetric analysis (TG).
Biological activities of the complexes are studied in vitro.
2.1. Materials and reagents
All chemicals used were of the analytical reagent grade
(AR) and of the highest purity available. They included VER
(UniPharma), CuCl2·2H2O (Prolabo), CoCl2·6H2O and NiCl2·6H2O
(BDH), ZnCl2·2H2O (Ubichem), CrCl3·6H2O (Sigma), and MnCl2
(Prolabo). Zinc oxide, disodium salt of ethylenediaminetetraacetic
acid, EDTA were from Analar, ammonia solution (33%, v/v), and
ammonium chloride from El-Nasr Pharm. Chem. Co., Egypt. Organic
solvents used included absolute ethyl alcohol, diethylether, and
dimethylformamide (DMF). These solvents were spectroscopic
pure from BDH. Hydrogen peroxide, hydrochloric, and nitric acids
(MERCK) were used. The test organisms were kindly supplied from
the microbiological resource center, Ain Shams University, Faculty
of Agricultural, Egypt (CAIM, Cairo Mircen), and from Bacterio-
logical Department of National Organization for Drug Control and
Research (NODACR), ATCC, American type culture collection. Bacte-
rial test organisms were inoculated on nutrient agar slants for 24 h
at 37 ◦C. Yeast and Fungi organisms were inoculated on Sabouraud’s
dextrose-agar slants and incubated at 28 ◦C for 48 h.
∗
Corresponding author.
E-mail address: drmadihahasan@yahoo.com (M.H. Soliman).
1386-1425/$ – see front matter. Published by Elsevier B.V.
doi:10.1016/j.saa.2012.01.021

12
M.H. Soliman, G.G. Mohamed / Spectrochimica Acta Part A 91 (2012) 11–17
2.4.2. Sabouraud’s dextrose agar medium (pH 5.6)
It consists of peptone (10 g), dextrose (20 g), agar (15 g), and
distilled water (100 mL).
O
O
O
N
N
S
N
H
H
3. Results and discussion
2
OMe
The formation of metal complexes with drug compounds has
long been recognized. However, the binary complexes of the cited
drug with metal ions have not been studied yet, although they
may be an area of interest. This is because these complexes
may affect the bioavailability of this drug as certain metal ions
were present in relatively appreciable concentration in biological
fluids [8].
OMe
Fig. 1. Structural formula of VER drug.
2.2. Instruments
The molar conductance of the solid complexes in DMF was
measured using Sybron–Barnstead conductometer (Meter-PM.6,
E = 3406). Elemental microanalyses of the separated solid chelates
for C, H, N, and S were performed at the Microanalytical Center,
Cairo University. Infrared spectra were recorded on a Perkin-
Elmer FT-IR type 1650 spectrophotometer in wave number region
4000–400 cm−1. The spectra were recorded as KBr pellets. The
1H NMR spectra were recorded using 300 MHz Varian-Oxford
Mercury. The molar magnetic susceptibility was measured on
powdered samples using the Faraday method. The diamagnetic cor-
rections were made by Pascal’s constant and Hg[Co(SCN)4] was
used as a calibrant. The thermogravimetric (TG and DTG) analy-
3.1. Mass spectrum of VER
The electron impact mass spectrum of VER is recorded and
investigated at 70 eV of electron energy. The mass spectrum of
the studied drug (Supplementary Fig. 1) is characterized by mod-
erate to high relative intensity molecular ion peaks at 70 eV. The
abundance of the molecular ion depends mainly on the structure
(and therefore the potential energy surface) of the molecular ion.
The mass spectrum of VER shows a well-defined parent peak at
m/z = 383.5 (M+) with a relative intensity = 5%. The parent ion and
the fragments obtained by cleavage in different positions in VER
molecule are shown in Scheme 1.
sis was carried out in dynamic nitrogen atmosphere (20 mL min−1
)
with a heating rate of 10 ◦C min−1 using Shimadzu TG-60H thermal
analyzers.
3.2. Composition and structures of metal complexes
The aim of this work is to prepare the solid complexes of the
drug under investigation and carrying out complete characteriza-
tion using different physicochemical techniques. Many attempts
were done to prepare crystal(s) suitable for X-ray analysis in order
to confirm the structures but all are failed. Therefore, IR spectra
have proven to be the most suitable technique to give enough
information’s to elucidate the nature of bonding of the ligand to
the metal ion. The present works deals specifically the coordina-
tion properties of VER drug (Fig. 1) concerning its interactions with
Cr(III), Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) ions. The bioefficacy of
these complexes has also been examined against the growth of bac-
teria and pathogenic fungi in vitro to evaluate their anti-microbial
potential and in order to throw more light on the effect of chelation
on the drug activity.
2.3. Synthesis of metal complexes
The metal complexes were prepared by the addition of hot solu-
tion (60 ◦C) of the appropriate metal chloride salts (0.278, 0.168,
0.277, 0.248, 0.225, and 0.217 g of Cr(III), Mn(II), Co(II), Ni(II), Cu(II)
and Zn(II), respectively, 1 mmol) in an ethanol–water mixture (1:1,
25 mL) to the hot solution (60 ◦C) of VER (0.4 g, 2 mmol) in the
same solvent (25 mL). The resulting mixture was stirred under
reflux for 1 h whereupon the complexes precipitated. They were
collected by filtration, washed with a 1:1 ethanol:water mixture
and diethylether.
2.4. Biological activity
The isolated solid complexes of Cr(III), Mn(II), Co(II), Ni(II), Cu(II)
and Zn(II) ions with the VER ligand are subjected to elemental anal-
yses (C, H, N, S, Cl and metal content), IR, 1H NMR, magnetic moment
studies, molar conductance, and thermal analysis (TG), to identify
their tentative formulae in a trial to elucidate their molecular struc-
tures. The results of elemental analyses listed in Table 1 suggest that
the complexes are formed in 1:2 [Metal]:[VER] ratio and they pro-
posed to have the general formulae [MCl2(VER)2(H2O)2]·yH2O and
[CrCl2(VER)2(H2O)2]Cl·H2O (where M = Mn(II) (y = 2), Co(II) (y = 2),
Ni(II) (y = 2), Cu(II) (y = 1) and Zn(II) (y = 0)).
The antimicrobial activities were carried out by disc diffusion
technique as described in British pharmacopoeia (2003). Nutrient
agar was melted at 45 ◦C and inoculated by the cell suspension
(1 mL/100 mL) bacteria or yeast. The flask was shaken well and
poured into a petri-dish (15 cm in diameter). Filter paper discs
(6 mm) Whatman No. 2 were thoroughly moistened by antibiotics
(50 ␮g), the treated discs were aseptically transferred and placed
upon the surface of the inoculated plates with tested organisms
and kept in a refrigerator for 1 h to permit diffusion of antimicro-
bial substances. The plates were incubated at 37 ◦C for 24 h in case
of bacteria and at 28 ◦C for 48 h in case of yeast. The zones of inhi-
bition were measured in mm the mean values of inhibitions were
calculated from triple reading in each test [7].
3.3. Molar conductivity measurements
The following media were used in studying the antimicrobial
properties of VER drug and its complexes. The weights are given in
gram per 1-L medium.
Table 1 summarizes the molar conductance values of the com-
plexes (10−3 M) in DMF solvent at 25 ◦C. It is concluded from
the results that, the divalent metal chelates are found to have
molar conductance values of 15.40–24.50 ꢀ−1 mol−1 cm2 indicat-
ing that all the divalent metal chelates are non-electrolytes. The
Cr(III) complex is found to have a molar conductance value of
68 ꢀ−1 mol−1 cm2 indicating its electrolytic nature and of the type
1:1 electrolyte.
2.4.1. Nutrient agar medium (pH 7.4)
It consists of beef extract (1.0 g), yeast extract (2.0 g), peptone
(5.0 g), sodium chloride (5.0 g), agar (15.0 g), and distilled water
(100 mL).

M.H. Soliman, G.G. Mohamed / Spectrochimica Acta Part A 91 (2012) 11–17
13
Scheme 1. Mass fragmentation pattern of VER drug.
3.4. IR spectral studies
(2) The NH2 and NH stretching vibrations are found in VER drug
at 3325–3249 and 3050 cm−1, respectively. For VER–metal
complexes, the bands at 3350–3075 and 3050–2918 cm−1, are
assigned to NH2 and NH stretching vibrations, respectively.
However, the shift in the NH2 and NH stretching vibrations can
be attributed to the keto–enol form or hydrogen bonding for-
mation with the adjacent SO2 group (in case of NH2 group) or
The IR data of the spectra of VER drug and its complexes are
listed in Table 2. In order to determine the coordination sites that
may be involved in chelation, the IR spectra of the complexes are
compared with the free VER drug. It is found that:
C
O group (in case of NH group).
(3) The ꢁ(C O) stretching vibrations are observed at 1638 cm−1
for VER drug. The participation of the carbonyl O atom in the
complex formation is evidenced from the shift in position of
this band to1651–1641 cm−1 for VER–metal complexes.
(1) The ꢁasym(SO2) and ꢁsym(SO2) stretching vibrations are
observed at 1336 and 1078 cm−1 for VER drug and at 1411–1291
and 1242–1106 cm−1 for VER–metal complexes, respectively.
The shift of these bands to higher or lower wave numbers may
be attributed to the involvement of the SO2 in hydrogen bond-
ing with the adjacent NH2 atom.
(4) In the 3550–3450, 950–880 and 850–820 cm−1 regions, one
observes absorption bands due to the OH stretching of the water

14
M.H. Soliman, G.G. Mohamed / Spectrochimica Acta Part A 91 (2012) 11–17
molecules. Since, according to the elemental analysis and ther-
mogravimetric studies, most of the complexes obtained contain
water of coordination and crystallization.
(5) New bands are found in the spectra of the complexes in the
region 523–459 cm−1, which is assigned to ꢁ(M–O) stretching
vibration [9–13].
Therefore, from the IR spectra, it is concluded that VER behaves
as a neutral monodentate ligand coordinated to the metal ions via
the carbonyl O atom.
3.5. Magnetic susceptibility studies
The magnetic moment values of Cr(III) and Mn(II) complexes are
found to be 4.95 and 4.82 B.M., respectively, which indicate their
presence in octahedral structure [14].
The Ni(II) and Co(II) complexes reported herein are found to
have a room temperature magnetic moment values of 3.66 and
5.28 B.M.; which are in the normal range observed for octahe-
dral Ni(II) (ꢂeff = 2.9–3.3 B.M.) [9,14] and Co(II) (ꢂeff = 4.3–5.2 B.M.)
[14–16] complexes, respectively.
The magnetic moment value of 2.15 B.M. falls within the range
normally observed for octahedral Cu(II) complexes [8,14]. The
Zn(II) complex is diamagnetic and according to the empirical for-
mula, an octahedral geometry is proposed.
3.6. 1H NMR spectra
The 1HNMR spectra of VER drug and its Zn(II) complex are
recorded in d6-dimethylsulfoxide (DMSO-d6) solvent using tetram-
ethylsilane (TMS) as internal standard. The chemical shifts of the
different types of protons of the VER drug and its diamagnetic Zn(II)
complex are listed in Supplementary Table 1. It is found that:
(1) The NH2 signal, appeared in the spectrum of VER drug at
2.19 ppm (Supplementary Table 1), the spectrum of its Zn(II)
complex gives band at 2.115 ppm.
(2) The signal observed at 8.440 ppm for VER drug, is assigned to
NH proton. This signal is found at 8.451 ppm for Zn(II) complex.
This small shift can be attributed to change in the skeleton of
VER drug as the results of metal chelation.
(3) The spectrum of Zn(II) complex shows a broad band at
4.045 ppm which can be attributed to the presence of coordi-
nated water molecules.
Therefore, it is clear from these results that the data obtained
from the elemental analyses, IR, and 1H NMR spectral measure-
ments are in agreement with each other.
3.7. Thermal analyses (TG and DTG) of VER drug
The TG curve of VER drug (Supplementary Fig. 2a) refers to two
stages of mass losses at temperature ranges from 200 to 920 ◦C
(Table 3). The first estimated mass loss of 51.10% (calcd. = 53.26%)
within the temperature range from 200 to 400 ◦C, may be attributed
to the liberation of C7H10NSO4 molecule as gases. In the 2nd stage
within the temperature range from 500 to 920 ◦C, VER losses the
remaining part with an estimated loss of 49.45% (calcd. = 46.74%)
which may be attributed to the liberation of C10H15N2O molecule
with a complete decomposition as CO, CO2, NO, NO2, etc. gases.
Supplementary Fig. 2b–g and Table 3 show the TG and DTG
results of thermal decomposition of VER chelates.
The thermogram of [CrCl2(VER)2(H2O)2]Cl·H2O chelate
(Supplementary Fig. 2b) shows five decomposition steps within
the temperature range from 25 to 900 ◦C. The first step of

M.H. Soliman, G.G. Mohamed / Spectrochimica Acta Part A 91 (2012) 11–17
15
Table 2
IR spectra (4000-400 cm−1) of VER and its binary metal complexes.
Compound
ꢁ(C O)
ꢁ(SO2) (asym)
ꢁ(SO2) (sym)
ꢁ(NH2)
ꢁ(NH)
ꢁ(M–O)
VER
1638 sh
1645 sh
1644 sh
1641 sh
1645 sh
1651 sh
1631 sh
1336 sh
1292 sh
1292 sh
1291 sh
1328 sh
1328 sh
1399 sh
1078 sh
1145 sh
1154 sh
1154 sh
1106 sh
1106 sh
1295 sh
3325 s, 3249 sh
3425 s, 3327 sh
3410 s, 3322 sh
3345 s, 3290 sh
3450 s, 3344 sh
3450 s, 3344 sh
3333 s, 3075 sh
3076 sh
3045 sh
2918 sh
2923 sh
3050 sh
3050 sh
2997 sh
–
[Cr(VER)2Cl2(H2O)2]Cl·H2O
[Mn(VER)2Cl2(H2O)2]·2H2O
[Co(VER)2Cl2(H2O)2]·2H2O
[Ni(VER)2Cl2(H2O)2]·2H2O
[Cu(VER)2Cl2(H2O)2]
[Zn(VER)2Cl2(H2O)2]
523 m
523 m
523 m
478 m
478 m
523 m
Sh = sharp, m = medium, br = broad, s = small, and w = weak.
decompositions within the temperature range 25–120 ◦C corre-
sponds to the loss of H2O and 3HCl with a mass loss of 12.30%
(calcd. = 13.00%). The subsequent steps (120–900 ◦C) correspond
to the removal of the organic part of the drug leaving metal oxide
and carbon as a residue. The overall weight loss amounts to 57.90%
(calcd. = 58.48%).
The TG curve of the [MnCl2(VER)(H2O)2]·2H2O chelate is shown
in Supplementary Fig. 2c and listed in Table 3. It decomposes in six
steps in the temperature range from 35 to 800 ◦C. The first two steps
can be attributed to the loss of 2H2O and HCl with mass loss of 7.98%
(calcd. = 7.53%). The subsequent steps (150–800 ◦C) correspond to
the removal of coordinated water, HCl and the residue of the drug
molecules with mass loss of 58.81% (calcd. = 59.03%), leaving MnO
and 21C as residues.
The TG curve of the [CoCl2(VER)2(H2O)2]·2H2O chelate exhibits
four decomposition steps (Supplementary Fig. 2d). The first step
within the temperature range 30–100 ◦C in which the complex
losses two hydrated water molecules with an estimated mass
loss = 3.45% (calcd. = 3.72%) (Table 3). The three subsequent steps
correspond to the removal of two coordinated water molecules,
2HCl and remaining part of the drug (estimated mass loss = 60.28%,
calcd. = 60.49%). The total mass losses of the decomposition steps
are found to be 63.73% (calcd. = 62.45%), leaving CoO and carbon as
residues.
TG curve of the [NiCl2(VER)2(H2O)2]·2H2O (Supplementary Fig.
2e) chelate shows six stages of decomposition within the temper-
ature range from 30 to 650 ◦C. The first stage corresponds to the
loss of two hydrated water molecules and HCl. While, the subse-
quent steps involve the loss of coordinated water molecules, HCl
and the remaining organic part of VER drug molecules leaving NiO
and carbon residues. The overall weight losses amount to 66.20%
(calcd. = 66.18%).
The TG curve of the [CuCl2(VER)2(H2O)2] chelate exhibits three
decomposition steps (Supplementary Fig. 2f). The first step within
the temperature range (100–220 ◦C) in which the complex losses
two coordinated water and HCl molecules with an estimated
mass loss of 7.38% (calcd. = 7.74%) (Table 3). The subsequent steps
(220–800 ◦C) correspond to the removal of HCl and the organic part
of the drug leaving CuO residue. The overall weight loss amounts
to 90.14% (calcd. = 91.51%).
The TG curve of the [ZnCl2(VER)2(H2O)2] (Supplementary Fig.
2g) chelate shows seven stages of decomposition within the tem-
perature range from 35 to 650 ◦C. The first stage corresponds to the
loss of 2HCl. While, the subsequent steps involve the loss of two
coordinated water and the organic part of VER drug molecules. The
overall weight losses amount to 71.15% (calcd. = 72.28%). ZnO and
carbon are the residues of decomposition.
3.8. Calculation of activation thermodynamic parameters
The thermodynamic activation parameters of decomposition
processes of complexes namely activation energy (E*), enthalpy
(ꢄH*), entropy (DS*), and Gibbs free energy change of the
decomposition (DG*) are evaluated graphically by employing the
Coats–Redfern relation [17].
ꢀ
ꢁ
ꢀ
ꢂ
ꢀ
ꢂ
ln(1 − ˛)
AR
bE
E
ln
−
= ln
−
(1)
T2
RT
Table 3
Thermoanalytical results (TG, DTG and DTA) of VER and its metal complexes.
Complex
TG range (◦C)
DTGmax (◦C)
n*
Mass loss
Total mass loss Assignment
Metallic residue
Estim (Calcd) (%)
VER
200–400
400–950
25–120
268
780
56
1
1
1
4
52.10 (53.26)
48.45 (46.74)
12.30 (13.00)
45.60 (45.48)
100.5 (100.0)
57.90 (58.48)
Loss of C7H10NO4S
–
Loss of C10H15N2O
Loss of H2O and 3HCl
Loss of 2H2O and
C13H47N6O8.5S2
[Cr(VER)2Cl2(H2O)2]Cl·H2O
1/2Cr2O3 + 21C
120–900
176, 236, 411, 550
Phase transition
Loss of 2H2O and HCl
Loss of 2H2O, HCl and
C13H48N6O9S2
Loss of 2H2O
Loss of 2H2O, 2HCl and
C13H48N6O9S2
Loss of 2H2O and HCl
Loss of 2H2O, HCl and
C13H48N6O9S2
Loss of 2H2O and HCl
Loss of HCl and
[Mn(VER)2Cl2(H2O)2]·2H2O 35–150
74, 144
236, 364, 629, 717
2
4
7.98 (7.53)
58.81 (59.03)
66.79 (66.56)
63.73 (62.45)
66.20 (66.18)
90.14 (91.51)
MnO + 21C
CoO + 21C
NiO + 21C
CuO
150–800
[Co(VER)2Cl2(H2O)2]·2H2O
[Ni(VER)2Cl2(H2O)2]·2H2O
[Cu(VER)2Cl2(H2O)2]
30–100
50–600
51
1
3
3.45 (3.72)
60.28 (58.73)
190, 340, 522
30–130
130–650
51, 95
192, 294, 404, 553
2
4
7.90 (7.45)
58.30 (58.73)
100–220
220–430
430–800
150
303
620
1
1
1
7.38 (7.74)
40.51 (40.84)
42.25 (42.93)
C14H24N3O5S
Loss of C20H24N3O4S
Loss of 2HCl
Loss of 2H2O and
C19H48N6O9S2
[Zn(VER)2Cl2(H2O)2]
35–100
100–650
57
1
6
7.94 (7.78)
63.21 (64.50)
71.15 (72.28)
ZnO + 15C
169, 231, 300, 354, 441,
623

16
M.H. Soliman, G.G. Mohamed / Spectrochimica Acta Part A 91 (2012) 11–17
OMe
OMe
MeO
MeO
H
NH2
H
NH2
N
N
N
S
N
S
O
O
O
O
O
O
Cl
Cl
Cl.H2O
.yH2O
Cr
OH2
N
H2O
O
M
OH2
H2O
Cl
Cl
O
O
O
O
O
N
S
S
N
H
N
H
H2N
H2N
OMe
OMe
OMe
OMe
M = Mn(II) (y = 2), Co(II) (y = 4), Ni(II) (y = 4),
Cu(II) (y = 1) and Zn(II) (y = 0).
Fig. 2. Structural formulae of metal complexes.
where ˛ represents the fraction of sample decomposed at time t,
3.10. Biological activity
defined by: ˛ = (wo − wt)/(wo − w ), where 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 temper-
ature, ˇ is the heating rate = dT/dt, E and A are the activation energy
and the Arrhenius pre-exponential factor, respectively.
In testing the antibacterial activity of VER drug and its metal
complexes, more than one test organism are used to increase the
chance of detecting antibiotic principles in tested materials. The
sensitivity of a microorganism to antibiotics and other antimicro-
bial agents is determined by the assay plates which are incubated
at 37 ◦C for 2 days for bacteria. All the tested compounds show
a remarkable biological activity against different types of Gram-
positive (G+) bacteria, Gram-negative (G−) bacteria and fungi. The
data are listed in Table 4. The data show that VER drug under inves-
tigation and its metal complexes have the capacity of inhibiting the
metabolic growth of the investigated bacteria and fungi to differ-
ent extent. The size of the inhibition zone depends upon the culture
medium, incubation conditions, rate of diffusion, and the concen-
tration of the antibacterial agent. The activities of all the tested
complexes may be explained on the basis of chelation theory;
chelation reduces the polarity of the metal atom mainly because
of partial sharing of its positive charge with the donor groups and
possible p electron delocalization within the whole chelate ring.
Also, chelation increases the lipophilic nature of the central atom
which subsequently favors its permeation through the lipid layer
of the cell membrane [18].
A plot of the left-hand side of Eq. (1) against 1/T gives a slope
from which E* was calculated and A (Arrhenius factor) was deter-
mined from the intercept. The entropy of activation (ꢄS*), enthalpy
of activation (ꢄH*), and the free energy change of activation (ꢄG*)
are calculated using the following equations:
ꢃ
ꢀ
ꢂꢁ
Ah
kT
ꢄS∗ = 2.303 log
R
(2)
ꢄH∗ = E ∗ −RT
(3)
(4)
ꢄG∗ = ꢄH ∗ −TꢄS∗
The data are summarized in Supplementary Table 2. The acti-
vation energies of decomposition were found to be in the range
10.3–169.6 kJ mol−1. The entropy of activation is found to be of
negative values in all the complexes which indicate that the decom-
position reactions proceed spontaneously.
3.9. Structural interpretation
On comparing the biological activity of the VER drug and its
metal complexes, the following results are obtained:
The structures of the complexes of VER drug with metals are
confirmed by the elemental analyses, 1H NMR, IR, molar conduc-
tance, magnetic and thermal analyses data. The structures of the
complexes are given as shown below in Fig. 2.
(1) Biological activity against Gram-positive bacteria follow the
order:
[ZnCl2(VER)2(H2O)2] > [NiCl2(VER)2(H2O)2]·2H2O >
[CoCl2(VER)2(H2O)2]·2H2O > [CuCl2(VER)2(H2O)2] > [MnCl2
Table 4
Biological activity of VER and its binary metal complexes.
Sample
Inhibition zone diameter (mm/mg sample)
Esherichia coli (G−
)
Staphylococcus aureus (G+)
Aspergillus flavus (Fungus)
Candida albicans (Fungus)
Control: DMSO
VER
0.0
12
11
12
20
15
14
15
33
–
0.0
11
12
12
18
22
15
23
31
–
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
–
0.0
0.0
0.0
0.0
14
22
14
12
–
[Cr(VER)2Cl2(H2O)2]Cl·H2O
[Mn(VER)2Cl2(H2O)2]·2H2O
[Co(VER)2Cl2(H2O)2]·2H2O
[Ni(VER)2Cl2(H2O)2]·2H2O
[Cu(VER)2Cl2(H2O)2]
[Zn(VER)2Cl2(H2O)2]
Tetracycline antibacterial agent
Amphotericin B antifungal agent
16
19

M.H. Soliman, G.G. Mohamed / Spectrochimica Acta Part A 91 (2012) 11–17
17
(VER)2(H2O)2]·2H2O = [CrCl2(VER)2(H2O)2]Cl·H2O > VER drug.
It is obvious that the biological activity of the metal complexes
are more than the parent VER drug which means that the
complexes can have the same action like the parent drug. The
biological activity of the VER drug and its complexes are lower
than tetracycline standard.
calculated using Coats–Redfern equation. The metal chelates of VER
possess reasonable antimicrobial potential.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.saa.2012.01.021.
(2) Biological activity against Gram-negative bacteria follow the
order:
[CoCl2(VER)2(H2O)2]·2H2O > [ZnCl2(VER)2(H2O)2] =
[NiCl2(VER)2(H2O)2]·2H2O > [CuCl2(VER)2(H2O)2] > VER =
[MnCl2(VER)2(H2O)2]·2H2O > [CrCl2(VER)2(H2O)2]Cl·H2O. The
biological activity of the VER drug and its complexes are lower
than tetracycline standard.
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4. Conclusion
In conclusion, we have described the synthesis and spectro-
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