Metal-based antibacterial agents: Synthesis, characterization, and in vitro biological evaluation of cefixime-derived Schiff bases and their complexes with Zn(II), Cu(II), Ni(II), and Co(II)

Article abstract of DOI:10.1080/00958972.2011.582867

The zinc(II), copper(II), nickel(II), and cobalt(II) complexes of Schiff bases, obtained by the condensation of cefixime with furyl-2-carboxaldehyde, thiophene-2-carboxaldehyde, salicylaldehyde, pyrrol-2-carboxaldehyde, and 3-hydroxynaphthalene-2-carboxal

Full text of DOI:10.1080/00958972.2011.582867

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Metal-based antibacterial agents:
synthesis, characterization, and
in vitro biological evaluation of
cefixime-derived Schiff bases and their
complexes with Zn(II), Cu(II), Ni(II), and
Co(II)
M. Arif a , M.M.R. Qurashi a & M.A. Shad a
a Department of Chemistry, Bahauddin Zakariya University, Multan
60800, Pakistan
Published online: 25 May 2011.
To cite this article: M. Arif , M.M.R. Qurashi & M.A. Shad (2011) Metal-based antibacterial agents:
synthesis, characterization, and in vitro biological evaluation of cefixime-derived Schiff bases
and their complexes with Zn(II), Cu(II), Ni(II), and Co(II), Journal of Coordination Chemistry, 64:11,
1914-1930, DOI: 10.1080/00958972.2011.582867
To link to this article: http://dx.doi.org/10.1080/00958972.2011.582867
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Journal of Coordination Chemistry
Vol. 64, No. 11, 10 June 2011, 1914–1930
Metal-based antibacterial agents: synthesis, characterization,
and in vitro biological evaluation of cefixime-derived Schiff
bases and their complexes with Zn(II), Cu(II), Ni(II), and Co(II)
M. ARIF*, M.M.R. QURASHI and M.A. SHAD
Department of Chemistry, Bahauddin Zakariya University, Multan 60800, Pakistan
(Received 20 April 2010; in final form 18 March 2011)
The zinc(II), copper(II), nickel(II), and cobalt(II) complexes of Schiff bases, obtained by the
condensation of cefixime with furyl-2-carboxaldehyde, thiophene-2-carboxaldehyde, salicylal-
dehyde, pyrrol-2-carboxaldehyde, and 3-hydroxynaphthalene-2-carboxaldehyde, were synthe-
sized and characterized by their elemental analyses, molar conductances, magnetic moments,
IR, and electronic spectral measurements. Analytical data and electrical conductivity
measurements indicated the formation of M : L (1 : 2) complexes, [M(L)2(H2O)2] or
[M(L)2(H2O)2]Cl2 [where M ¼ Zn(II), Cu(II), Ni(II), and Co(II)] in which ligands are bidentate
via azomethine-N and deprotonated-O of salicyl and naphthyl, furanyl-O, thienyl-S, and
deprotonated pyrrolyl-N. The magnetic moments and electronic spectral data suggest
octahedral complexes. The synthesized ligands, along with their metal complexes, were
screened for their antibacterial activity against different bacterial strains. The studies show the
metal complexes to be more active against one or more species as compared to the uncomplexed
ligands.
Keywords: Metal-based; Schiff bases; Cefixime; Antibacterial
1. Introduction
Cephalosporins are important in the treatment of bacterial infections, exhibiting broad
antibacterial activities with little toxicity and are generally well tolerated [1]. Structural
modifications of the cephem nucleus have produced a variety of antimicrobial agents
with improved spectra of activity and ꢀ-lactamase stability [2]. The antibiotic cefixime
belongs to the third generation cephalosporin. The third generation has somewhat
increased activity against Gram-negative microorganisms than the first and second
generation cephalosporins.
The metal chelates of different cephalosporins have been studied because of their
biological activity [3–5]. However, a survey of the literature reveals that metal chelates
with Schiff bases derived from cephalosporin have not been reported. In continuation
of earlier work [6, 7], we report a series of antibacterial Schiff bases derived by the
condensation of cefixime (a third generation cephalosporin) with different aldehydes
(L1–L5; figure 1) and their metal chelates (1–20; figures 2–4). The Schiff bases and their
*Corresponding author. Email: pdmarif@hotmail.com
Journal of Coordination Chemistry
ISSN 0095-8972 print/ISSN 1029-0389 online ß 2011 Taylor & Francis
DOI: 10.1080/00958972.2011.582867

Cefixime-derived Schiff bases
1915
Figure 1. Proposed structure of Schiff-base ligands.
metal chelates were screened for antibacterial activity against Escherichia coli,
Enterococcus faecalis, Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella
enteritidis, and Klebsiella pneumoniae. The Schiff bases showed increased antibacterial
activity against certain strains and their activities were enhanced on chelation.
2. Experimental
2.1. Materials and methods
All chemicals, analytical grade, were purchased from Aldrich & Sigma and used as
received. The solvents were redistilled by standard techniques before use. The metal
contents of the complexes were determined by atomic absorption spectroscopy after
decomposition with acid.
Elemental analyses were carried out on a Thermo Finnegan CHN MA 5200
elemental analyzer. FT-IR spectra were recorded with a Hitachi spectrometer using
KBr disks. Magnetic moments were determined with a Gouy balance using
Hg[Co(NCS)4] as the calibrant. Diamagnetic corrections were calculated from
Pascal’s constants [8]. Electronic absorption spectra of all the complexes were recorded
on a Shimadzu spectrophotometer. Conductance measurements were done in DMSO
1
(10ꢀ3 mol Lꢀ1) using an electroconductivity bridge. H and 13C NMR spectra were
recorded on a Bruker Spectrospin Avance DPX-400 spectrometer using TMS as
internal standard and DMSO(d6) as solvent. Electron impact mass spectra (EIMS) were
recorded on a JEOL MS Route instrument.

1916
M. Arif et al.
2.2. Preparation of Schiff bases (L1–L5)
A stirred solution of cefixime (4.53 g, 10 mmol) in methanol (30 mL) was mixed
with salicylaldehyde (1.3 g, 10 mmol) dissolved in methanol (25 mL). To this
KOH (0.1% in methanol) was added to adjust the pH of the solution at 7–8 and the
mixture was refluxed for ꢁ30 min. A clear colored solution was obtained. The
completion of reaction was monitored through TLC. After completion of the reaction,
a few drops of dilute acetic acid were added to adjust the pH to 7. The volume was
reduced to about one-third on a rotary evaporator and cooled to afford a solid product.
The solid residue was filtered, washed with ethanol, then with ether, and dried.
Crystallization from a mixture of ethanol–propanol (60 : 40) afforded the desired Schiff
bases. The same method was applied for the preparation of all other ligands by using
the corresponding aldehydes, working in the same conditions with their respective
molar ratio.
2.2.1. 8-(2-Carboxymethoxyimino-2-{2-[(2-hydroxy-benzylidene)-amino]-thiazol-4-yl}-
acetylamino)-7-oxo-4-vinyl-2-thia-bicyclo[4.2.0]oct-4-ene-5-carboxylic acid (L1). Yield
85%; m.p. 154–156ꢂC; (dark yellow), IR (KBr, cmꢀ1): 3435 (OH), 1610 (–HC ¼ N),
1
1766 (C ¼ O ꢀ-lactam), 1665 (C ¼ O amide), 1595 (COO), 1320, 1480 (C–N); H NMR
(DMSO-d6, ꢁ, ppm): 7.3–7.75 (m, 4H, –phenyl), 10.23 (s, 1H, –OH), 8.7 (s, 1H,
HC ¼ N), 11.0 (s, 1H, –COOH), 7.6 (s, 1H, thiozole), 9.1 (s, 1H, –NH–CO–), 6.1 (d, 1H,
J ¼ 7.2, ꢀ-lactam), 6.3 (d, 1H, J ¼ 7.4, ꢀ-lactam), 2.1 (s, 2H, six-membered thiozole
ring), 5.6 (t, 1H, vinyl), 4.47 (d, 2H, vinyl), 2.7 (s, 2H, –OCH2–COOH); 13C NMR
(DMSO-d6, ꢁ, ppm): 176.31 (C13–COOH), 170.45 (C15, five-membered thiazole ring),
168.39 (C11, –C ¼ N), 163.62 (C17, –CH ¼ N), 163.43 (C10, –HN–CO), 163.02
(C2, ꢀ–lactam), 161.50 (C7, –COOH), 157.82 (C19, –OH–ph), 142.61 (C5), 136.09
(C8, C ¼ CH2), 132.24, 130.46, 121.25, 118.45, 115.82 (C18, C20–C23 phenyl), 58.12 (C3,
ꢀ-lactam ring), 57.33 (C1, ꢀ-lactam); Anal. Calcd for C23H19N5O8S2 (557.56) (%): C,
49.55; H, 3.41; N, 12.57. Found (%): C, 49.88; H, 3.42; N, 12.54. Mass spectrum (ESI)
1
[M]þ ¼ 557.10. H NMR of Zn(II) complex (DMSO-d6, ꢁ, ppm): 4.67 (d, 2H, CH2),
7.48–7.87 (m, 4H, Ph), 8.32 (s, 1H, azomethine), 11.20 (s, 1H, COOH); 13C NMR
(DMSO-d6, ꢁ, ppm): 115.82, 118.45, 121.25, 130.46, 132.24, 157.82 (PhOH), 164.42
(–CH ¼ N), 176.34 (COOH).
2.2.2. 8-(2-Carboxymethoxyimino-2-{2-[(2-hydroxy-naphthalen-2-ylmethylene)-amino]
thiazol-4-yl}-acetylamino)-7-oxo-4-vinyl-2-thia-bicyclo[4.2.0]oct-4-ene-5-carboxylic acid
(L2). Yield 80%; m.p. 153–155ꢂC; (dark yellow); IR (KBr, cmꢀ1): 3445 (OH), 1610
(–HC¼N), 1770 (C¼O ꢀ-lactam), 1668 (C¼O amide), 1595 (COO), 1315, 1485 (C–N);
1H NMR (DMSO-d6, ꢁ, ppm): 7.35–7.81 (m, 6H, Naph), 8.11 (s, 1H, azomethine), 9.83
(s, 1H, OH), 11.10 (s, 1H, COOH), 7.5 (s, 1H, thiozole), 9.2 (s, 1H, –NH–CO–), 6.3 (d,
1H, J ¼ 7.2, ꢀ-lactam), 6.4 (d, 1H, J ¼ 7.8, ꢀ-lactam), 2.2 (s, 2H, six-membered thiozole
ring), 5.8 (t, 1H, vinyl group), 4.47 (d, 2H, vinyl), 2.9 (s, 2H, –OCH2–COOH);
13C NMR (DMSO-d6, ꢁ, ppm): 176.38 (C13–COOH), 170.42 (C15, five-membered
thiazole ring), 168.45 (C11, –C¼N), 163.65 (C17, –CH¼N), 163.21 (C10, –HN–CO),
163.02 (C2, ꢀ-lactam), 161.50 (C7, –COOH), 142.61 (C5), 136.09 (C8, C¼CH2), 111.4–
152.8 (nephthyl), 58.7 (C3, ꢀ-lactam ring), 57.01 (C1, ꢀ-lactam). Anal. Calcd for
C27H21N5O8S2 (607.61) (%): C, 53.38; H, 3.46; N, 11.53. Found (%): C, 53.82; H, 3.40;

Cefixime-derived Schiff bases
1917
N, 11.34. Mass spectrum (ESI) [M]þ ¼ 607.10. 1H NMR of Zn(II) complex (DMSO-d6,
ꢁ, ppm): 4.63 (d, 2H, CH2), 7.38–7.89 (m, 6H, Naph), 8.31 (s, 1H, azomethine), 11.23
(s, 1H, COOH). 13C NMR (DMSO-d6, ꢁ, ppm): 111.8–153.85 (NaphO), 164.21
(–CH ¼ N), 176.38 (COOH).
2.2.3. 8-(2-Carboxymethoxyimino-2-{2-[(furan-2-ylmethylene)-amino]-thiazol-4-yl}-
acetylamino)-7-oxo-4-vinyl-2-thia-bicyclo[4.2.0]oct-4-ene-5-carboxylic acid (L3). Yield
80%; m.p. 155–158ꢂC; (dark orange), IR (KBr, cmꢀ1): 3245 (OH), 1615 (–HC¼N),
1768 (C¼O ꢀ-lactam), 1667 (C¼O amide), 1590 (COOH), 1310, 1255 (C–O); 1H NMR
(DMSO-d6, ꢁ, ppm): 7.4 (d, 1H, J ¼ 1.81 Hz, furanyl C5–H), 6.35 (dd, 1H, J ¼ 3.62,
1.81 Hz, furanyl C4–H), 6.95 (d, 1H, J ¼ 3.62 Hz, furanyl C3–H), 7.5 (s, 1H, HC¼N), 7.3
(s, 1H, thiozole), 9.3 (s, 1H, –NH–CO–), 6.2 (d, 1H, J ¼ 7.1, ꢀ-lactam), 6.3 (d, 1H,
J ¼ 7.4, ꢀ-lactam), 11.15 (s, 1H, COOH), 2.2 (s, 2H, six-membered thiozole ring),
5.8 (t, 1H, vinyl group), 4.45 (d, 2H, vinyl), 2.9 (s, 2H, –OCH2–COOH); 13C NMR
(DMSO-d6, ꢁ, ppm): 170.31 (C13–COOH), 170.05 (C15, five-membered thiazole ring),
168.32 (C11, –C¼N), 163.71 (C17, –CH¼N), 163.42 (C10, –HN–CO), 163.05 (C2,
ꢀ-lactam), 161.25 (C7, –COOH), 143.7 (C19, furanyl), 141.56 (C22, furanyl), 141.91 (C5),
138.6 (C8, C¼CH2), 112.7 (C21, furanyl), 110.4 (C20, furanyl), 58.39 (C3, ꢀ-lactam ring),
57.71 (C1, ꢀ-lactam); Anal. Calcd for C21H17N5O8S2 (531.45) (%): C, 47.46; H, 3.20; N,
13.18. Found (%): C, 47.68; H, 3.40; N, 13.34. Mass spectrum (ESI) [M]þ ¼ 531.08.
1H NMR of Zn(II) complex (DMSO-d6, ꢁ, ppm): 4.67 (d, 2H, CH2), 6.38–7.45 (m, 3H,
furanyl), 7.73 (s, 1H, azomethine), 11.21 (s, 1H, COOH); 13C NMR (DMSO-d6, ꢁ,
ppm): 110.8–143.80 (furanyl), 164.20 (–CH¼N), 170.38 (COOH).
2.2.4. 8-(2-Carboxymethoxyimino-2-{2-[(thiophene-2-ylmethylene)-amino]-thiazol-4-yl}-
acetylamino)-7-oxo-4-vinyl-2-thia-bicyclo[4.2.0]oct-4-ene-5-carboxylic acid (L4). Yield
78%; m.p. 170–172ꢂC; (yellowish orange), IR (KBr, cmꢀ1): 3250 (OH), 1620 (–HC¼
1
N), 1765 (C¼O ꢀ-lactam), 1670 (C¼O amide), 1585 (COO), 755 (C–S); H NMR
(DMSO-d6, ꢁ, ppm): 7.11 (d, 1H, J ¼ 4.78 Hz, thienyl, C5–H), 7.0 (dd, 1H, J ¼ 4.78,
3.85 Hz, thienyl, C4–H), 7.21 (d, 1H, J ¼ 3.85 Hz, thienyl, C3–H), 7.55 (s, 1H, HC¼N),
7.7 (s, 1H, thiozole), 9.2 (s, 1H, –NH–CO–), 6.7 (d, 1H, J ¼ 7.3, ꢀ-lactam), 6.7 (d, 1H,
J ¼ 7.4, ꢀ-lactam), 11.10 (1H, –COOH), 2.5 (s, 2H, six-membered thiozole ring), 5.9
(t, 1H, vinyl group), 4.45 (d, 2H, vinyl), 4.47 (s, 2H, –OCH2–COOH); 13C NMR
(DMSO-d6, ꢁ, ppm): 170.21 (C13–COOH), 170.12 (C15, five-membered thiazole
ring), 168.37 (C11, –C¼N), 163.70 (C17, –CH¼N), 163.53 (C10, –HN–CO), 163.09
(C2– ꢀ-lactam), 161.28 (C7, –COOH), 144.6 (C19, thienyl), 141.95 (C5), 138.6
(C8, C¼CH2), 127.80 (C22, thienyl), 127.48 (C21, thienyl), 126.4 (C20, thienyl), 58.39
(C3, ꢀ-lactam ring), 57.71 (C1, ꢀ-lactam); Anal. Calcd for C21H17N5O7S3 (547.56)
(%): C, 46.07; H, 3.11; N, 12.80. Found (%): C, 47.65; H, 3.45; N, 12.34. Mass
1
spectrum (ESI) [M]þ ¼ 547.07. H NMR of Zn(II) complex (DMSO-d6, ꢁ, ppm): 4.57
(d, 2H, CH2), 7.23–7.45 (m, 3H, thienyl), 7.85 (s, 1H, azomethine), 11.20 (s, 1H,
COOH); 13C NMR (DMSO-d6, ꢁ, ppm): 126.8–127.80 (thienyl), 164.25 (–CH¼N),
170.58 (COOH).
2.2.5. 8-(2-Carboxymethoxyimino-2-{2-[(1H-pyrrol-2-ylmethylene)-amino]-thiazol-4-yl}-
acetylamino)-7-oxo-4-vinyl-2-thia-bicyclo[4.2.0]oct-4-ene-5-carboxylic acid (L5). Yield

1918
M. Arif et al.
78%; m.p. 170ꢂC; IR (KBr, cmꢀ1): 3310 (NH), 3250 (OH), 1610 (–HC¼N), 1765,
(C¼O ꢀ-lactam), 1660 (C¼O amide), 1590 (COO), 1H NMR (DMSO-d6, ꢁ, ppm): 6.43
(d, 1H, J ¼ 2.87 Hz pyrrolyl, C5–H), 6.2 (dd, 1H, J ¼ 3.95, 2.87 Hz, pyrrolyl, C4–H),
6.61 (d, 1H, J ¼ 3.95 Hz, pyrrolyl, C3–H), 9.7 (s, 1H, pyrrolyl, NH), 7.5 (s, 1H, HC¼N),
7.3 (s, 1H, thiozole), 9.2 (s, 1H, ꢀNH–CO–), 6.3 (d, 1H, J ¼ 7.4, ꢀ-lactam), 6.5 (d, 1H,
J ¼ 7.1, ꢀ-lactam), 11.10 (s, 1H, COOH), 2.3 (s, 2H, six-membered thiozole ring), 5.9
(t, 1H, vinyl), 4.47 (d, 2H, vinyl), 2.6 (s, 2H, ꢀOCH2–COOH); 13C NMR (DMSO-d6, ꢁ,
ppm): 170.60 (C13–COOH), 170.23 (C15, five-membered thiazole ring), 168.31 (C11,
–C¼N), 163.75 (C17, –CH¼N), 163.57 (C10, –HN–CO), 163.17 (C2, ꢀ-lactam), 161.22
(C7, –COOH), 141.95 (C5), 134.5 (C19, pyrrolyl), 128.75 (C8, C¼CH2), 118.70 (C22,
pyrrolyl), 108.4 (C21, pyrrolyl), 126.4 (C20, pyrrolyl), 59.2 (C3, ꢀ-lactam ring), 54.4 (C1,
ꢀ-lactam); Anal. Calcd for C21H18N6O7S2 (530.63) (%): C, 47.55; H, 3.40; N, 15.85.
Found (%): C, 47.60; H, 3.45; N, 15.54. Mass spectrum (ESI) [M]þ ¼ 530.08. 1H NMR
of Zn(II) complex (DMSO-d6, ꢁ, ppm): 4.50 (d, 2H, CH2), 6.23–6.65 (m, 3H, pyrrolyl),
7.90 (s, 1H, azomethine), 11.15 (s, 1H, COOH). 13C NMR (DMSO-d6, ꢁ, ppm): 108.8–
118.85 (pyrrolyl), 164.35 (–CH¼N), 170.60 (COOH).
2.3. Preparation of Schiff-base metal complexes (1–20)
The Schiff base (L1) (2.23 g, 2 mmol) dissolved in methanol (25 mL) was mixed with
CuCl2 ꢃ 2H2O (0.171 g, 1 mmol) dissolved in methanol (25 mL). The reaction mixture
was refluxed for 3–4 h. The volume was reduced to about one-third on a rotary
evaporator and then cooled to room temperature. On cooling a solid product
precipitated, was filtered off, washed with methanol, then with ether, and dried under
vacuum. Crystallization from hot methanol gave the desired metal complex. The same
method was used for the preparation of all other complexes by using their respective
hydrated metal(II) chlorides.
2.4. Antibacterial activity
All the synthesized ligands (L1–L5) and their corresponding metal(II) complexes (1–20)
were screened in vitro for their antibacterial activity against E. coli, E. faecalis,
S. aureus, P. aeruginosa, S. enteritidis, and K. pneumonia bacterial strains using
agar-well diffusion method, as described previously [9]. Two- to eight-hour-old
bacterial inoculums containing approximately 104–106 colony forming units
(CFU) mLꢀ1 were used in these assays. Wells were dug in the media with a sterile
metallic borer with centers at least 24 mm. Recommended concentration of the test
sample in DMSO was introduced in the respective wells. Other wells supplemented with
DMSO and reference antibacterial drug served as negative and positive controls,
respectively. The plates were incubated at 37ꢂC for 20 h. Activity was determined by
measuring the diameter of zones showing complete inhibition (mm). Growth inhibition
was compared with the standard drug [10]. In order to clarify any role of DMSO in the
biological screening, separate studies were carried out with DMSO alone, which showed
no activity against any bacterial strains.

Cefixime-derived Schiff bases
2.5. Minimum inhibitory concentration
1919
The minimum inhibitory concentrations (MIC)s of selected compounds, which showed
significant activity against selected bacterial strains, were determined using the disk
diffusion method [11] by preparing disks containing 10, 25, 50, and 100 mg mLꢀ1 and
applying the reported protocol. MIC was the lowest concentration of an antimicrobial
compound at which the inhibition of growth occurred.
3. Results and discussion
L1–L5 were prepared by refluxing the appropriate amount of cefixime with the
corresponding heteroaromatic (salicylaldehyde and 3-hydroxynaphthalene-2-carbox-
aldehyde) and heterocyclic (furyl-2-carboxaldehyde, thiophene-2-carboxaldehyde, and
pyrrole-2-carboxaldehyde) systems, respectively, in methanol. The structures of
synthesized Schiff-base ligands were established by IR, NMR, and microanalytical
data. The air and moisture stable metal complexes (1–20) of these ligands were prepared
by the stoichiometric reaction of the corresponding metal(II) chloride hydrate with the
ligand in a molar ratio M : L of 1 : 2. The synthesized colored complexes were
amorphous solids which decomposed without melting and were only soluble in DMSO.
Karl–Fischer titrations indicated the presence of water in all these complexes. Molar
conductance values (table 1) of the soluble complexes in DMSO (10ꢀ3 mol Lꢀ1 solution
at 25ꢂC) indicated that complexes with salicylaldehyde, 3-hydroxynaphthalene-
2-carboxaldehyde,
and
pyrrole-2-carboxaldehyde
have
low
values
(20–25 ꢀꢀ1 cmꢀ2 molꢀ1) indicating that they are non electrolytes, whereas complexes
with furyl-2-carboxaldehyde and thiophene-2-carboxaldehyde have high values
(120–125 ꢀꢀ1 cmꢀ2 molꢀ1) indicating that they are electrolytic [12]. Elemental analyses
of the Schiff bases (reported in experimental) and their complexes (table 2) are
compatible with the structures shown in figure 1 and with that of formulae of the
complexes, [M(L)2(H2O)2] where [M ¼ Zn(II), Cu(II), Ni(II), or Co(II) and L ¼ L1, L2,
or L5] and [M(L)2(H2O)2]Cl2 where [M ¼ Zn(II), Cu(II), Ni(II), or Co(II) and L ¼ L3
or L4]. The suggested structures of the ligands and their complexes are shown in
figures 1–4.
3.1. IR spectra
IR spectra of the ligands showed the absence of bands at 1735 and 3420 cmꢀ1 due to
ꢂ(C¼O) and ꢂ(NH2) stretching vibrations and instead, a new band appeared at
ꢁ1620 cmꢀ1 assigned [13] to azomethine ꢂ(HC¼N). This suggested that amino and
aldehyde moieties of the starting reagents have been converted into the corresponding
Schiff bases (figure 1). The bonding of the synthesized Schiff bases to metal ions was
investigated by comparing FT-IR spectra of the complexes with those of the free
ligands. Some important absorption bands and their assignments are given in table 3.
The spectra of these complexes exhibited a broad band around 3445–3540 cmꢀ1
,
assigned to water, ꢂ(OH), associated with the complexes. In addition to these modes,
coordinated water exhibited ꢁr(H2O) rocking at 850–890 cmꢀ1 and ꢁw(H2O) wagging at
540–550 cmꢀ1 [13]. The spectra of all the ligands contained a band at 1610–1620 cmꢀ1
,
ꢂ(C¼N), which shifted to higher values (1615–1645 cmꢀ1) in the complexes suggesting

1920
M. Arif et al.
that the ligands coordinate to the metal ion through azomethine [14]. The absence of
O–H and N–H stretching and bending vibrations, for salicyl-, naphthyl-, and pyrrolyl-,
from the spectra of the complexes indicate the deprotonation of O–H and/or N–H,
confirming formation of a bond to metal. A medium sharp band due to ꢂ(C–O) and
ꢂ(C–S) is found at 1140–1150 and 760–750 cmꢀ1, respectively, in the spectra of the
complexes which indicate the formation of a coordinate bond through these moieties
[15]. The absorption due to lactam (C¼O) and carboxylic groups did not change in
spectra of the complexes, indicating that these groups are not involved in coordination.
New absorption bands ꢂ(M–N), ꢂ(M–O), and ꢂ(M–S) appeared at 510–520, 420–430,
and 380–390 cmꢀ1, respectively, in the spectra of the complexes which indicate the
coordination of the ligands through nitrogen, oxygen, and sulfur [16].
3.2. 1H-NMR spectra
1H-NMR spectra of the Schiff bases (L1–L5) displayed the azomethine [17] proton
(–CH¼N) at ꢁ 7.5–8.7 as a singlet. Multiplets at 6.9–7.75 ppm due to phenyl protons
were also present with a hydroxyl proton as a singlet at ꢁ 10.23 and 10.85. Similarly in
1H-NMR spectra of L2 six protons in naphthalene moiety C3–8–H appear as a multiplet
at ꢁ 6.7–7.5 and the hydroxyl proton as a singlet at ꢁ 9.83 due to its attachment with
1
naphthalene. H-NMR spectra of L1–L5 doublets from CO–CH and N–CH on the
ꢀ-lactam ring and NH appear at 6.1–6.6 and 9.1–9.3 ppm, respectively [18]. In 1H NMR
spectrum of Schiff bases single peaks attributed to –CH2–COOH appear at 2.9 and
11.10 ppm, respectively. In all the ligands, a singlet appeared at ꢁ 2.3–2.6 due to 2H of
the six-membered thiazole ring while a singlet also appeared at ꢁ 7.5–7.7 due to 1H of
the five-membered thiazole.
3.3. 13C NMR spectra
The l3C NMR spectra of free ligands and their diamagnetic Zn(II) complexes were
recorded in CD l3C/DMSO-d6 and reported along with possible assignments in
the experimental section. Comparison of chemical shifts of the ligands with those of the
complexes shows that the signal due to phenolic proton (L1–L2) and pyrrolyl-NH were
absent in the complexes, suggesting coordination after deprotonation [19]. The
azomethine proton (ꢀCH¼N–) undergoes a significant shift, indicating coordination
of the azomethine nitrogen. More detailed information about the structure of the
ligands was provided by 13C NMR spectra. All the carbon atoms due to heteroatomic
and/or aromatic groups were found in their expected region [20, 21]. In the spectra of
diamagnetic Zn(II) chelates, these signals shifted downfield due to the increased
conjugation and coordination to the metal ions. The number of protons and carbons
calculated from the integration curves agreed with those obtained from the values of the
CHN analysis.
3.4. Magnetic and electronic absorption spectral studies
The Co(II) complexes exhibited well-resolved bands around 17,560–17,650 cmꢀ1 and
a strong high-energy band at 21,767–21,790 cmꢀ1 (table 1), which were assigned to

Cefixime-derived Schiff bases
1921
4
4
4
4T1g(F) ! T2g(F) and T1g(F) ! T1g(P), respectively, for a high-spin octahedral
geometry. The magnetic susceptibility measurements (4.7–4.9 BM) for the solid Co(II)
complexes are also indicative of three unpaired electrons per Co(II) ion consistent with
their octahedral environment [22]. The electronic absorption spectrum of the Cu(II)
complex showed a single low-intensity broad band at 15,256–15,320 cmꢀ1, typical for an
octahedral configuration. The magnetic moment (1.7–1.9 BM) suggested one unpaired
electron per Cu(II) consistent with their octahedral environment [23]. The spectrum of
the Ni(II) complex showed d–d bands at 12,978–13,020, 16,565–16,630, and 24,385–
3
24,440 cmꢀ1
,
assigned to the spin-allowed transitions 3A2g(F) ! T2g(F),
3A2g(F) ! T1g(F), and A2g(F) ! T1g(P), respectively, consistent with octahedral
configuration. The magnetic moment of 3.1–3.4 BM suggested two unpaired electrons
per Ni(II) also consistent with octahedral geometry. The spectrum of the Zn(II)
complex exhibited only a high-intensity band at 28,370–28,405 cmꢀ1, which was
assigned to a ligand-to-metal charge transfer [24, 25].
3
3
3
3.5. Thermogravimetric analysis
Thermogravimetric analyses (TGA) for the complexes were carried out from room
temperature to 700ꢂC. Coordinated waters are usually eliminated at higher tempera-
tures than those of hydration [26, 27], usually in the temperature range 100–350ꢂC. The
ligand together with the anions (Clꢀ) in the complexes may decompose in more than
two steps with the formation of intermediates [28, 29]; calculated and estimated mass
losses are comparable.
The TGA curve of Schiff-base metal complexes from L1, L2, and L5 have two stages
of mass loss, at ꢄ135–223ꢂC and at 223–595ꢂC. At 82–109ꢂC, the estimated mass loss of
5.47–5.67% may be due to the loss of two Cl atoms in complexes of L3 and L4. Weight
loss in the range 102–227ꢂC with estimated mass loss of 2.65–3.05% in all the complexes
indicates the loss of two coordinated waters. From 210ꢂC to 595ꢂC, a sharp decrease in
weight indicated the loss of one Schiff base from the complexes with estimated mass loss
of 42.85–46.35% for all the complexes, respectively. The data are given in table 4.
In general, the stages of thermal decomposition of the metal complexes may be
summarized by the following equations.
First decomposition step is represented as
80ꢀ110ꢂC
½MðLÞ2ð2H2OÞꢅCl2 ꢀ! ½MðLÞ2ð2H2OÞꢅ þ Cl2
102ꢀ227ꢂC
½MðLÞ2ð2H2OÞꢅ ꢀ! ½MðLÞ2ꢅ þ 2H2O,
Dehydration
where M ¼ Cu, Ni, Co, and Zn.
In the second step of decomposition, the loss of ligand occurs
227ꢀ595ꢂC
final decomp:
½MðLÞ2ꢅ
ꢀ!
ML þ L:
The molecular masses determined mass spectrometrically (table 1) also confirmed the
ML2 composition. Based upon experimental evidence thus obtained, the complexes
were characterized as six coordinates with the two positions occupied by water. The

1922
M. Arif et al.
Figure 2. Proposed structure of metal complexes of L1 and L2, where R ¼ H and phenyl; M ¼ Zn(II), Cu(II),
Ni(II), and Co(II).
Figure 3. Proposed structure of metal complexes of L3 and L4, where X ¼ O and S; M ¼ Zn(II), Cu(II),
Ni(II), and Co(II).
hydrated complexes have significant importance in the enzymatic systems, as the
substrates can bind to metal by substituting the coordinated water. The proposed
structures of the complexes under investigation, on the basis of above experimental
evidence, are shown in figures 2–4. Unsuccessful attempts to isolate crystals suitable for
X-ray analysis prevented further structure elucidation.

Cefixime-derived Schiff bases
1923
Figure 4. Proposed structure of metal complexes of L5, where M ¼ Zn(II), Cu(II), Ni(II), and Co(II).
Table 1. Physical and spectral data of the metal(II) complexes (1–20).
Metal chelates
Molar conductance (ꢀꢀ1 cmꢀ2 molꢀ1
)
m (BM)
ꢃmax (cmꢀ1 molꢀ1
)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
(Mþ: 1210 m/e)
20
24
22
20
25
20
21
24
120
124
122
125
123
124
121
125
20
Dia
1.8
3.2
4.7
Dia
1.7
3.4
4.9
Dia
1.9
3.1
4.9
Dia
1.8
3.3
4.8
Dia
1.7
3.2
4.7
–
(Mþ: 1211 m/e)
(Mþ: 1206 m/e)
(Mþ: 1206 m/e)
(Mþ: 1310 m/e)
(Mþ: 1311 m/e)
(Mþ: 1306 m/e)
(Mþ: 1306 m/e)
(Mþ: 1231 m/e)
(Mþ: 1232 m/e)
(Mþ: 1227 m/e)
(Mþ: 1227 m/e)
(Mþ: 1263 m/e)
(Mþ: 1264 m/e)
(Mþ: 1259 m/e)
(Mþ: 1259 m/e)
(Mþ: 1156 m/e)
(Mþ: 1157 m/e)
(Mþ: 1152 m/e)
(Mþ: 1152 m/e)
15,256
12,978; 16,570; 24,390
17,560; 21,780
–
15,320
13,020; 16,565; 24,385
17,620; 21,767
–
15,280
13,010; 16,630; 24,430
17,650; 21,780
–
15,275
12.980; 16,590; 24,440
17,590; 21,790
–
15,310
12,980; 16,610; 24,425
17,625; 21,785
23
22
25
3.6. Biological activity
All compounds were tested against E. coli, E. faecalis, S. aureus, P. aeruginosa,
S. enteritidis, and K. pneumonia bacterial strains (table 5) according to literature
protocol [10]. The ligands were active against one or more bacterial strains. Cobalt(II),
copper(II), nickel(II), and zinc(II) metal complexes of these synthesized ligands (L1–L5)

1924
M. Arif et al.

Cefixime-derived Schiff bases
1925

1926
M. Arif et al.
Table 3. Observed IR frequencies (cmꢀ1) and assignments.
Metal chelates
ꢂ(OH)
ꢂ(C¼N)
ꢂ(CO)lact
ꢂ(COO)
ꢂ(MN)
ꢂ(MO)
ꢂ(MS)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
3540
3500
3520
3510
3535
3445
3525
3505
3530
3505
3530
3520
3530
3495
3525
3515
3535
3500
3530
3510
1630
1625
1635
1625
1630
1630
1625
1635
1640
1630
1635
1640
1645
1640
1635
1640
1620
1615
1610
1620
1775
1770
1770
1775
1780
1770
1775
1780
1780
1775
1770
1770
1780
1770
1775
1780
1770
1770
1775
1775
1590
1595
1590
1595
1592
1591
1592
1595
1591
1593
1589
1590
1582
1580
1582
1584
1588
1587
1590
1585
510
512
520
511
514
519
516
520
513
512
518
510
517
515
516
520
515
513
518
513
419
420
425
430
430
427
426
428
420
426
430
430
421
423
426
420
430
427
423
421
–
–
–
–
–
–
–
–
–
–
–
–
390
380
385
390
–
–
–
–
Table 4. Thermal analyses (TGA and DTA) results of cef-binary chelates.
Mass loss %
Complexes
Temperature range (ꢂC)
Found (Calcd)
Assignment
1
2
3
4
5
6
7
8
9
155–220
220–590
150–215
215–592
150–210
210–585
157–220
220–595
150–223
223–584
156–210
210–590
150–225
225–590
157–210
210–593
82–109
109–227
227–559
82–109
109–225
225–558
80–110
110–225
225–590
83–110
110–220
220–593
2.81 (2.97)
45.65 (45.98)
2.85 (2.97)
45.58 (45.99)
2.87 (2.98)
46.03 (46.16)
2.86 (2.98)
46.05 (46.18)
2.65 (2.74)
46.11 (46.28)
2.67 (2.73)
46.15 (46.27)
2.71 (2.75)
46.35 (46.47)
2.67 (2.74)
46.35 (46.46)
5.57 (5.67)
2.67 (2.73)
42.95 (43.10)
5.47 (5.65)
2.65(2.74)
Loss of 2H2O
Loss of (L1) þ metallic residue
Loss of 2H2O
Loss of (L1) þ metallic residue
Loss of 2H2O
Loss of (L1) þ metallic residue
Loss of 2H2O
Loss of (L1) þ metallic residue
Loss of 2H2O
Loss of (L2) þ metallic residue
Loss of 2H2O
Loss of (L2) þ metallic residue
Loss of 2H2O
Loss of (L2) þ metallic residue
Loss of 2H2O
Loss of (L2) þ metallic residue
Loss of 2Cl2
Loss of 2H2O
Loss of (L3) þ metallic residue
10
11
12
Loss of 2Cl2
Loss of 2H2O
42.85 (43.09)
5.67 (5.70)
2.87(2.93)
43.15 (43.24)
5.67 (5.70)
2.85 (2.93)
43.17 (43.25)
Loss of (L3) þ metallic residue
Loss of 2Cl2
Loss of 2H2O
Loss of (L3) þ metallic residue
Loss of 2Cl2
Loss of 2H2O
Loss of (L3) þ metallic residue

Cefixime-derived Schiff bases
1927
13
14
15
16
83–110
110–227
227–595
75–105
105–225
225–587
70–102
102–217
217–590
77–105
105–210
210–593
135–220
220–574
138–223
223–587
135–219
219–585
137–211
211–590
5.47 (5.53)
2.75 (2.84)
43.25 (43.27)
5.51 (5.54)
2.76 (2.83)
43.08 (43.25)
5.52 (5.55)
2.81 (2.87)
43.33 (43.41)
5.48 (5.56)
2.79 (2.86)
43.15 (43.40)
3.02 (3.11)
45.75 (45.80)
3.02 (3.10)
45.68 (45.79)
3.05 (3.13)
45.85 (46.00)
3.05 (3.12)
45.78 (45.99)
Loss of 2Cl2
Loss of 2H2O
Loss of (L4) þ metallic residue
Loss of 2Cl2
Loss of 2H2O
Loss of (L4) þ metallic residue
Loss of 2Cl2
Loss of 2H2O
Loss of (L4) þ metallic residue
Loss of 2Cl2
Loss of 2H2O
Loss of (L4) þ metallic residue
17
18
19
20
Loss of 2H2O
Loss of (L5) þ metallic residue
Loss of 2H2O
Loss of (L5) þ metallic residue
Loss of 2H2O
Loss of (L5) þ metallic residue
Loss of 2H2O
Loss of (L5) þ metallic residue
Table 5. Antibacterial activity of cefixime Schiff base and their metal complexes (zone of inhibition in mm)
(400 mg mLꢀ1).
No.
Compounds
Cefixime
L1
L2
L3
(a)
(b)
(c)
(d)
(e)
(f)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
35
37
37
39
36
36
50
46
40
42
50
46
39
42
52
48
41
44
49
44
39
40
50
45
39
41
21
23
25
23
23
25
36
32
25
29
38
34
28
30
36
32
25
27
35
33
26
28
37
33
26
29
40
42
43
42
44
42
55
50
44
48
55
50
45
48
54
52
44
47
57
52
45
49
54
50
44
47
9
10
7
44
46
46
47
48
46
60
57
48
51
61
58
48
51
61
58
49
52
62
60
49
53
62
58
48
52
25
26
23
26
27
26
40
38
26
33
38
37
25
30
40
38
28
33
41
39
28
34
40
38
29
33
10
11
10
17
15
11
13
15
12
10
11
16
15
11
13
17
15
11
13
16
15
11
13
L4
L5
[Zn(L1)2(H2O)2]
[Cu(L1)2(H2O)2]
[Ni(L1)2(H2O)2]
[Co(L1)2(H2O)2]
[Zn(L2)2(H2O)2]
[Cu(L2)2(H2O)2]
[Ni(L2)2(H2O)2]
[Co(L2)2(H2O)2]
[Zn(L3)2(H2O)2]Cl2
[Cu(L3)2(H2O)2]Cl2
[Ni(L3)2(H2O)2]Cl2
[Co(L3)2(H2O)2]Cl2
[Zn(L4)2(H2O)2]Cl2
[Cu(L4)2(H2O)2]Cl2
[Ni(L4)2(H2O)2]Cl2
[Co(L4)2(H2O)2]Cl2
[Zn(L5)2(H2O)2]
[Cu(L5)2(H2O)2]
[Ni(L5)2(H2O)2]
[Co(L5)2(H2O)2]
(a) ¼ Escherichia coli, (b) ¼ Enterococcus faecalis, (c) ¼ Staphylococcus aureus, (d) ¼ Pseudomonas aeruginosa, (e) ¼
Salmonella enteritidis, (f) ¼ Klebsiella pneumoniae.

1928
M. Arif et al.
Table 6. MICs (mg mLꢀ1) of the cefixime Schiff-base ligands and their metal complexes (10, 25, 50,
100 mg mLꢀ1).
No.
Compounds
Cefixime
L1
L2
L3
(a)
(b)
(c)
(d)
(e)
(f)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
15
14
14
13
14.5
14.5
510
10.5
13.5
12
510
10.5
13
12
510
10
13.5
11.5
510
11.5
13
13.5
510
11
13
12.5
4100
4100
100
4100
4100
100
75
85
100
95
70
80
95
97
75
87
100
93
75
87
100
95
72
90
100
95
12.5
12.2
12.1
12.1
12
4100
4100
4100
4100
4100
4100
90
100
100
4100
100
510
510
510
510
510
510
510
510
510
510
510
510
510
510
510
510
510
510
510
510
510
510
510
510
510
510
50
48
55
48
47
48
20
25
48
35
24
25
50
40
20
25
44
35
21
25
44
36
20
25
46
35
L4
L5
12.2
[Zn(L1)2(H2O)2]
[Cu(L1)2(H2O)2]
[Ni(L1)2(H2O)2]
[Co(L1)2(H2O)2]
[Zn(L2)2(H2O)2]
[Cu(L2)2(H2O)2]
[Ni(L2)2(H2O)2]
[Co(L2)2(H2O)2]
[Zn(L3)2(H2O)2]Cl2
[Cu(L3)2(H2O)2]Cl2
[Ni(L3)2(H2O)2]Cl2
[Co(L3)2(H2O)2]Cl2
[Zn(L4)2(H2O)2]Cl2
[Cu(L4)2(H2O)2]Cl2
[Ni(L4)2(H2O)2]Cl2
[Co(L4)2(H2O)2]Cl2
[Zn(L5)2(H2O)2]
[Cu(L5)2(H2O)2]
[Ni(L5)2(H2O)2]
[Co(L5)2(H2O)2]
510
10.2
124
10.5
510
10.2
11.5
10.5
510
10
12
10.5
510
10
11.5
10.4
510
10.2
12
4100
4100
4100
95
100
4100
4100
90
100
4100
4100
95
100
4100
4100
10.6
(a) ¼ Escherichia coli, (b) ¼ Enterococcus faecalis, (c) ¼ Staphylococcus aureus, (d) ¼ Pseudomonas aeruginosa, (e) ¼
Salmonella enteritidis, (f) ¼ Klebsiella pneumoniae.
Figure 5. Average antibacterial activity.
were also screened against the same bacterial strains. The potency of the uncoordinated
ligands was enhanced on coordination with metal.
3.7. Minimum inhibitory concentration
The MIC was determined using the disk diffusion method [11]. MIC was the lowest
concentration of a substance at which the inhibition of growth occurred. The MIC of

Cefixime-derived Schiff bases
1929
Figure 6. Comparison of antibacterial activity.
these compounds varied from 10 to 100 mg mLꢀ1. The results (table 6) indicated that
these compounds are most active by inhibiting the growth of the tested organisms at
10 mg mLꢀ1. Some of the compounds showed good antibacterial activity against some
bacterial species (figures 5 and 6). This enhancement in the activity is rationalized on the
basis of the structures of (L1–L5) by possessing an additional azomethine (C¼N)
linkage important in elucidating the mechanism of transamination and resamination
reactions in biological system [30]. It has also been suggested that ligands with nitrogen
and oxygen donors might inhibit enzyme production, because the enzymes which
require these groups for their activity appear to be more susceptible to deactivation by
the metal ions upon chelation.
4. Conclusion
The synthesized cefixime-derived Schiff bases showed antibacterial properties with
metal complexes more active against all bacterial strains. These observations, in line
with other studies, suggest that the metal-based drugs possess potential as therapeutics.
Acknowledgments
Our sincere thanks are to the Higher Education Commission of Pakistan for providing
financial support. We are grateful to University of Manchester, U.K., for providing us
with the elemental analysis, NMR, and mass spectra. We are also thankful to HEJ
Research Institute of Karachi, University of Karachi, Pakistan, where in the
antibacterial assays were performed.

1930
M. Arif et al.
References
[1] N.X. Chin, J.W. Gu, W. Fang, H.C. Neu. Antimicrob. Agents Chemother., 35, 259 (1991).
[2] K.P. Fu, B.D. Foleno, S.C. Lafredo, J.M. Lococo, D.M. Isaacson. Antimicrob. Agents Chemother., 27,
301 (1993).
[3] J.R. Anacona, J. Estacio. Transition Met. Chem., 31, 227 (2006).
[4] J.R. Anacona, C.C. Gil. Transition Met. Chem., 30, 605 (2005).
[5] J.R. Anacona, P. Alvarez. Transition Met. Chem., 27, 856 (2002).
[6] M.S. Iqbal, I.H. Bukhari, M. Arif. Appl. Oraganomet. Chem., 19, 864 (2005).
[7] I.H. Bukhari, M. Arif, I. Akbar, A.H. Khan. Pak. J. Biol. Sci., 8, 614 (2005).
[8] A. Earnshaw. Introduction to Magnetochemistry, 3rd Edn, p. 6, Academic Press, New York (1968).
[9] Z.H. Chohan, M. Arif, M. Sarfraz. Appl. Organomet. Chem., 21, 294 (2007).
[10] J.L. McLaughlin, C.J. Chang, D.L. Smith. In Studies in Natural Products Chemistry, Bench–Top,
Bioassay for the Discovery of Bioactive Natural Products: An Update, Structure and Chemistry (Part-B),
Atta-ur-Rahman (Ed.), p. 283, Elsevier Science, Amsterdam (1991).
[11] Atta-ur-Rahman, M.I. Choudhary, W.J. Thomsen. Bioassay Techniques for Drug Development,
Harwood Academics, Netherlands (2001).
[12] W.J. Geary. Coord. Chem. Rev., 7, 81 (1971).
[13] K. Nakamoto. Infrared and Raman Spectra of Inorganic and Coordination Compounds, John Wiley,
New York (1978).
[14] G.H. Rist, J.S. Hydes, T. Vanngard. Proc. Natl. Acad. Sci., U.S.A., 67, 79 (1970).
[15] L.J. Bellamy. The Infrared Spectra of Complex Molecules, John Wiley, New York (1971).
[16] J.R. Ferrero. Low Frequency Vibrations of Inorganic and Coordination Compounds, John Wiley,
New York (1971).
[17] A.S. Burlov, E.N. Shepelenko, I.S. Vasil’chenko. Russ. J. Coord. Chem., 32, 879 (2006).
[18] J.R. Anacona, I. Rodriguez. J. Coord. Chem., 57, 1263 (2004).
[19] E. Canpolat, A. Yazici, M. Kaya. J. Coord. Chem., 60, 473 (2007).
[20] W.W. Simmons. The Sadtler Handbook of Proton NMR Spectra, Sadtler Research Laboratories Inc.,
Philadelphia (1978).
[21] Z.H. Chohan, C.T. Supuran. J. Enzyme Inhib. Med. Chem., 23, 240 (2008).
[22] Z.H. Chohan, H. Pervez, S. Kausar, C.T. Supuran. Synth. React. Inorg. Met.-Org. Chem., 32, 529 (2002).
[23] G.G. Mohameda, C.M. Sharaby. Spectrochim. Acta, Part A, 66, 949 (2007).
[24] W.E. Estes, D.P. Gavel, W.B. Hatfield, D.J. Hodgson. Inorg. Chem., 17, 1415 (1978).
[25] C.J. Balhausen. An Introduction to Ligand Field Spectra, McGraw Hill, New York (1962).
[26] G.G. Mohamed, Z.H. Abd El-Wahab. J. Therm. Anal. Calorim., 73, 347 (2003).
[27] Y.M. Essa, H.M. Abdel-Fattah, A.A. Soliman. J. Therm. Anal., 42, 1175 (1994).
[28] N.T. Abdel-Ghani, O. Esherif. Thermochim. Acta, 156, 69 (1989).
[29] M.A. Zayed, F.A. Nour El-Dien, G.G. Mohamed, N.E.A. El-Gamel. Spectrochim. Acta, Part A, 60,
2843 (2004).
[30] Z.H. Chohan, M. Arif, A. Rashid. J. Enzyme Inhib. Med. Chem., 6, 785 (2008).