Synthesis, characterization and electronic spectra of cefadroxil complexes of d-block elements.

Article abstract of DOI:10.1016/j.saa.2003.11.019

Cefadroxil (CD) is an essential pharmaceutical drug used in curing many diseases. Due to its popular use in many pharmaceutical forms, attention is paid in this research to the synthesis and stereochemistry of new iron, cobalt, nickel, copper, and zinc co

Full text of DOI:10.1016/j.saa.2003.11.019

Spectrochimica Acta Part A 60 (2004) 2215–2224
Synthesis, characterization and electronic spectra of cefadroxil
complexes of d-block elements
M.A. Zayed∗, S.M. Abdallah
Chemistry Department, Faculty of Science, Cairo University, Giza, A.R., Egypt
Received 10 March 2003; accepted 25 November 2003
Abstract
Cefadroxil (CD) is an essential pharmaceutical drug used in curing many diseases. Due to its popular use in many pharmaceutical forms,
attention is paid in this research to the synthesis and stereochemistry of new iron, cobalt, nickel, copper, and zinc complexes of this drug both
in solution and the solid states. The spectra of these complexes in solution and the study of their stoichiometry refer to the formation of 1:1
and 1:2 ratios of metal (M) to ligand (L). The calculated stability constants (Kf ) of these complexes (1.5 × 107 to 5 × 1013) and the change
in free energy of formation (ꢀGf = 2.5–12.5 kcal mol−1 degree−1) are indicative of their high stability. The stereo chemical structure of the
solid complexes was studied on the basis of their analytical, spectroscopic, magnetic, and thermal data. Infrared spectra proved the presence
of M–N and M–O bonds. Magnetic susceptibility and solid reflectance spectral measurements were used to infer the structure. The prepared
complexes were found to have the general formulae [ML(OH)x(H2O)y](H2O)z—M: Fe(II), x = 0, y = 2, z = 1; M: Fe(III) and Co(III),
x = 1, y = 2, z = 1; M: Co(II) and Zn(II), x = 0, y = 1, z = 0; M: Ni(II) and Cu(II), x = 1, y = 0, z = 1; L: CD. Octahedral and tetrahedral
structures were proposed for these complexes depending upon the magnetic and reflectance data and were confirmed by detailed mass and
thermal analyses comparative studies.
© 2003 Elsevier B.V. All rights reserved.
Keywords: Synthesis; Cefadroxil complexes; Spectroscopic; Thermal analyses
1. Introduction
[5]. Several spectrophotometric methods were applied for
the determination of CD through interaction with Ni(II) and
Fe(III) [6,7]. HPLC [8] and reversed phase [9] chromato-
graphic techniques were used for the assay of CD in bulk
pharmaceuticals.
The main thrust of this study is to synthesize CD transition
metal-complexes and to determine their stability constants,
and the coordination behavior of CD toward these transition
metal ions. The data obtained by spectroscopic, magnetic,
and thermal techniques were correlated and used to elucidate
the structural formulae of the prepared complexes.
Cefadroxil (CD) is a semi-synthetic cephalosporin, in-
troduced into clinical practice and recommended for oral
use. CD has an inhibitor activity similar to cefalexin and
cefradine against 602 clinical isolates of different kinds
of bacteria [1]. CD was observed while present in the
gastro-intestinal tract, and its concentration in the plasma
and urine was more sustained than cefalexin [2]. The ion-
ization constants of CD were determined potentiometrically
and from UV spectrometry [2]. The structure of CD (Fig. 1)
and cefalexin were characterized by thermal and spectral
analyses [3]. Two spectrophotometric methods have been
suggested for the determination of CD using Cu(II) in a
sulfuric acid medium and were applied for its successful
analysis in different preparations [4]. The stability con-
stants (Kf) of some transition metal-complexes of CD were
determined spectrophotometrically and potentiometrically
2. Experimental
2.1. Materials and methods
All chemicals used in this study were of the analyti-
cal grade. They include CD (from Sigma), FeSO4·6H2O
and Fe2(SO4)3 (from Merck), Co(NO3)2·6H2O and
Na3[Co(NO2)6] (from BDH), NiSO4·7H2O, CuCl2 and
∗
Corresponding author.
E-mail address: mazayed429@hotmail.com (M.A. Zayed).
1386-1425/$ – see front matter © 2003 Elsevier B.V. All rights reserved.
doi:10.1016/j.saa.2003.11.019

2216
M.A. Zayed, S.M. Abdallah / Spectrochimica Acta Part A 60 (2004) 2215–2224
nitrogen atmosphere (20 ml min−1) with a heating rate of
10 ◦C min−1 (25–1000 ◦C). The mass spectra were recorded
by the EI technique at 70 eV on a model MS-5988 GC-MS
Hewlett–Packard instrument at the Microanalytical Center
of Cairo University. Metal (M) contents of the complexes
were determined by titration against standard EDTA after
complete digestion in aqua regia in a Kjeldahl flask several
times and adjusting the pH of the solution to a suitable one.
2.3. Procedures
Fig. 1. Structural formula of the cefadroxil (CD) ligand (L).
The reaction of various metal ions such as Fe(II), Fe(III),
Co(II), Co(III), Ni(II), Cu(II), and Zn(II) ions with CD was
studied under different experimental factors. The effect of
pH on the formation of different complexes was studied
by mixing of 1 ml of a 10−3 M solution of CD in a 5 ml
measuring flask followed by the addition of a series of uni-
versal buffers of pH = 1.91–12.4, then measuring spec-
trophotometrically in the λ range 330–390 nm. The effect of
n-bromosuccinamide (NBS) as oxidizing agent and the ef-
fect of temperature and pH (Table 1) on complex formation
between CD and several d-block element ions were studied.
The stoichiometry of the complexes was determined by ap-
plying the molar ratio method (mrm) [11], the continuous
variation (cvm) [12], and the slope ratio method (srm) [13].
The data obtained were used in the calculation of stability
constants of the complexes.
ZnSO4·7H2O (from Aldrich). The organic solvents used
were acetone (97% purity), diethethyl ether (97% purity),
ethanol (99% purity), methanol (98% purity), and n-pentane
(99% purity) (all from BDH) and were used without further
purification. The 10−3 M solutions of CD and the transition
metal cations Fe(II), Fe(III), Co(II), Co(III), Ni(II), Cu(II),
and Zn(II) were prepared by dissolving appropriate masses
in twice distilled water.
2.2. Instruments and apparatus
The reflectance spectra of the solid complexes were mea-
sured using a PC model 3101 Shimadzu spectrophotometer
and BaSO4 as a background. The UV and visible spectra
were measured using Shimadzu UV-Vis 240 recording or
manual spectronic 601 Milton Roy spectrophotometers, at
a suitable temperature using 1 cm matched silica cells and
a Haake model NB22 ultrathermostat. The FT-IR spectra
of the solid compounds and complexes were measured us-
ing a Perkin-Elmer 1430 recording spectrophotometer at
a range of 400–4000 cm−1. The meters used for pH ad-
justments were a Radiometer pH-meter model 28, digital
pH/mV-Messgerate model 87 or a pH/mV-ion analyzer
model 701A. Molar magnetic susceptibilities were measured
at ambient temperature on powdered samples using the
Faraday method [10]. Diamagnetic corrections were made
by Pascal’s constant. Hg[Co(SCN)4] was used for calibra-
tion purposes. The thermal analyses (TG, DTG, DTA, and
derivative DTA (derDTA)) were carried out using TGA-50H
and DTA-50H Shimadzu thermal analyzers, under dynamic
2.4. Synthesis and analysis of the solid complexes
The metal-complexes were prepared by addition of a so-
lution of appropriate weight of metal salt (1.0 mmol; Fe(II),
0.260 g; Fe(III), 0.4 g; Co(II), 0.291 g; Co(III), 0.403 g;
Ni(II), 0.281 g; Cu(II), 0.1345 g; and Zn(II), 0.287 g) in
25 ml (1:1) ethanol–water to a 25 ml solution of CD
(0.0351 g, 10 mmol) in the same solvent. The resulting
mixture was adjusted to a suitable pH, stirred, and refluxed
for 1 h, whereupon the complexes formed and precipi-
tated. They were removed by filtration using a Hearsh
funnel of suitable pores, washed with n-pentane, acetone
and then with diethyl ether. The elemental analyses (C, H,
and N) were made at the Microanalytical Center of Cairo
Table 1
The optimum conditions for the formation of d-block elements–CD complexes in solution
Complex
λmax (nm)
pH
[Mn+
(ml)a
]
[CD]
(ml)
[NBS]
(ml)
NaNO2 ionic
strength (M)
C16H24Fe(II)N3O8S (molecular mass = 472)
325, 345
340, 355
320, 355
325, 345
320, 350
270, 310
320, 340
7.71
8.80
9.81
9.81
9.81
8.80
9.80
0.8
0.7
0.6
0.6
0.7
0.6
0.5
0.7
0.8
0.6
0.8
0.7
0.8
0.7
1.0
1.0
1.0
0.8
0.8
0.8
1.0
0.06
0.05
0.04
0.04
0.08
0.05
0.07
C16
C16
C16
H
H
H
23Fe(III)N3O9S (molecular mass = 489)
18Co(II)N3O6S (molecular mass = 438)
23Co(III)N3O9S (molecular mass = 490)
C16H19Ni(II)N3O6S (molecular mass = 439)
C16H19Cu(II)N3O6S (molecular mass = 444)
C16H25Zn(II)N3O6S (molecular mass = 454)
MXn: FeSO4·6H2O, Fe2 (SO4)3, Co(NO3)2·6H2O, Na3[(NO2)6], NiSO4·7H2O, CuCl2, and ZnSO4·7H2O. [Mnn+] = 10−3 M, [CD] = 10−3 M,
a
n-bromosuccinamide [NBS] = 10−3 M, and L·H2O = CD = C16H18N3O6S.

M.A. Zayed, S.M. Abdallah / Spectrochimica Acta Part A 60 (2004) 2215–2224
2217
University. Mass spectra, IR, reflectance spectra, and ther-
mal analyses were carried out at the Central Laboratory of
our Chemistry Department at Cairo University.
the formation of complexes in solution are given in Table 1.
Table 2 shows the calculated apparent stability constant of
d-block elements–CD complexes obtained using the mrm
method under selected optimum conditions. From the data
obtained (Table 2), it is clear that the Kf values ranged from
2.45 × 107 to 1.44 × 1012 for the Fe(II)–CD complex (1:1
to 1:2 ratios) at λ = 330 nm; 1.69 × 106 to 6.23 × 1013
for the Fe(III)–CD complex at λ = 325 nm; 7.5 × 106 to
1.56 × 1012 for the Co(II)–CD complex at λ = 380 nm;
6 × 106 to 1.56 × 1012 for the Co(III)–CD complex at λ =
375 nm; 1.7×107 to 1.56×1012 for the Ni(II)–CD complex
at λ = 370 nm; 3.26×106 to 1.56×1012 for the Cu(II)–CD
complex at λ = 370 nm; and 1.79 × 107 to 4.58 × 1011 for
the Zn(II)–CD complex at λ = 330 nm. Generally, the high
values of log Kf (=6–13) indicate that these complexes are
stable and this stability is confirmed by the high values of
the calculated activation thermodynamic parameter ꢀG =
8.5–18.5 kcal mol−1 degree−1 (Table 2).
3. Results and discussion
The reaction in solution between cefadroxil as ligand (L)
and transition metal cations may proceed by the following
general Eq. (1):
MXn + nHL → MLn + nHX
(1)
where n = 2 or 3; M: Fe(II), Fe(III), Co(II), Co(III), Ni(II),
Cu(II), and Zn(II); X: corresponding anion of metal salts.
Several methods such as molar ratio and slope ratio meth-
ods were used to study the possible formed complex ra-
tio between CD and d-block elements in solution. Most of
these ions formed complexes with stoichiometric ratios M:L
of 1:1 and 1:2. Most attention was applied to the detailed
study of d-block transition metal cations commonly present
in the aqueous phase in biological systems such as the human
body, together with CD as a very important and commonly
used drug. The optimum conditions selected for studying
3.1. IR spectra and mode of bonding
The separated, purified, and crystallized solid complexes
(of 1:1, M:L ratio) were analyzed for C, H, N, and M contents
Table 2
The stoichiometry and the apparent formation constant (Kf ) (conditional) and free energy change (ꢀG, kcal mol degree−1) obtained using the molar ratio
method (mrm)
a
Complex
λmax (nm)
Ratio
A
Am
A/Am
1 − A/Am
Kf
ꢀG
(kcal mol degree−1
)
[Fe(II)L(H2O)]·2H2O
325
390
1:1
1:2
1:1
1:2
1.80
2.38
0.48
2.16
1.84
2.42
0.56
2.20
0.97
0.98
0.85
0.98
0.03
5.02
0.15
0.02
1.79 × 107
9.95
16.92
2.13 × 1012
6.29 × 105
2.13 × 1012
6.29 × 105
16.92
[Fe(III)L(OH)(H2O)2]·H2O
[Co(II)L·H2O]
330
380
1:1
1:2
1:1
1:2
1.76
2.40
0.72
2.20
1.84
2.42
0.80
2.28
0.95
0.99
0.90
0.96
0.05
0.01
0.10
0.04
6.33 × 106
17.1 × 1012
1.5 × 106
9.33
18.17
8.48
2.60 × 1011
15.67
290
350
1:1
1:2
1:1
1:2
1.80
2.44
0.72
2.48
1.96
2.50
0.80
2.54
0.96
0.97
0.90
0.97
0.04
0.03
0.10
0.03
10.0 × 106
6.23 × 1011
1.50 × 106
6.23 × 1011
9.61
16.17
8.48
16.19
[Co(III)L(OH)(H2O)2]·H2O
[Ni(II)L(OH)]·H2O
325
380
1:1
1:2
1:1
1:2
1.80
2.40
0.76
2.36
1.88
2.44
0.80
2.40
0.95
0.98
0.95
0.98
0.05
0.02
0015
0.02
6.233 × 106
2.12 × 1012
6.33 × 106
2.12 × 1012
1.79 × 107
2.12 × 1012
6.33 × 106
2.12 × 1012
9.34
16.91
9.34
16.91
325
385
1:1
1:2
1:1
1:2
1.92
2.40
0.80
2.40
1.96
2.44
0.84
2.44
0.97
0.98
0.95
0.98
0.03
0.02
0.05
0.02
9.95
16.91
9.34
16.91
[Cu(II)L(OH)]·H2O
325
380
1:1
1:2
1:1
1:2
2.00
2.63
4.80
1.96
2.04
2.40
5.20
2.00
0.93
0.98
0.92
0.98
0.17
0.02
0.08
0.02
4.78 × 105
2.13 × 1012
4.78 × 105
2.12 × 1012
7.79
16.91
17.40
16.91
[Zn(II)L(H2O)]
330
380
1:1
1:2
1:1
1:2
1.04
2.40
0.40
1.88
1.04
2.40
0.40
1.88
0.94
0.98
0.98
0.96
0.06
0.02
0.17
0.04
4.78 × 105
2.13 × 1012
4.78 × 105
2.12 × 1012
16.91
9.11
8.04
15.67
a
A is absorbance at any wave length and Am is the absorbance at λmax
.

2218
M.A. Zayed, S.M. Abdallah / Spectrochimica Acta Part A 60 (2004) 2215–2224
Table 3
Analytical and physical data of cefadroxil (CD) d-block metal-complexes
Complexa
Color
(yield, %)
Melting
point (◦C)
Found (calcd., %)
Found molecular
ion (m/z) (calcd.)
µeff
(BM)
C
H
N
M
[Fe(II)L(H2O)]·2H2O
[Fe(III)L(OH)(H2O)2]·H2O
[Co(II)LH2O]
[Co(III)L(OH)(H2O)2]·H2O
[Ni(II)L(OH)]·H2O
[Cu(II)L(OH)]H2O
[Zn(II)L(H2O)]
White (62)
White (65)
Rose (60)
Brown (70)
Brown (65)
White (68)
White (70)
>300
>300
>300
>300
>300
>300
>300
41.50 (41.38)
39.18 (38.90)
43.73 (43.61)
39.10 (39.00)
43.63 (43.51)
43.14 (43.00)
42.10 (42.00)
4.86 (4.66)
4.89 (4.80)
3.64 (3.61)
4.88 (4.60)
3.63 (3.49)
3.59 (3.52)
3.94 (3.90)
8.87 (8.76)
8.57 (8.48)
9.56 (9.18)
8.58 (8.50)
9.54 (9.50)
9.43 (9.38)
9.21 (9.11)
11.83 (10.90)
11.42 (11.31)
12.98 (12.50)
11.60 (11.56)
13.40 (13.10)
14.26 (14.20)
14.25 (14.20)
473 (472)
490 (489)
439 (438)
491 (490)
438 (439)
445 (444)
456 (454)
2.42
5.01
1.69
4.17
3.34
1.44
Diamb
a
The general of the above complexes [ML(OH)x(H2O)y](H2O)z— M: Fe(II), x = 0, y = 2, z = 1; M: Fe(III), Co(III), x = 1, y = 2, z = 1; M:
Co(II), Zn(II), x = 0, y = 1, z = 0; M: Ni(II), Cu(II), x = 1, y = 0, z = 1; and L = CD = C16H18N3O6S.
b
Diam.: diamagnetic.
gions 3200–3000 and 3000–2800 cm−1 due to the ν(NH)
and ν(CONH) groups, respectively [11–13]. These bands
remain unchanged on complex formation. Also, the amide
group in all the complexes is not affected and thus remains
unchanged, strongly indicating non-involvement in chelate
ring formation. The presence of bands at 687–593 cm−1
(M–N) and 450–470 cm−1 (M–O) confirms the bonding of
nitrogen and oxygen atoms of ligand groups to the metal
cation [11]. The IR spectra of the solid complexes exhib-
ited a broad band at 3500–3400 cm−1, which is attributed
to ν(OH) of water molecules of crystallization, while the
band observed at approximately 850–780 cm−1 is assigned
to coordinated water and OH groups [10].
and the data obtained are shown in Table 3. From the el-
emental analyses results the formation of these solid com-
plexes may proceed by the general Eq. (2):
MXn + H2L · H2O + xOH− + yH2O
→ [ML(OH)x(H2O)y](H2O)z + nX− + nH+
(2)
where MXn is the metal salt, x the number of coordinated
OH, y the number of coordinated water, z the water of crys-
tallization or of hydration, and H2L·H2O is the enol-form
of mono-hydrated cefadroxil.
In order to clarify the mode of bonding and the metal
ion effect on the ligand, the IR spectra of the free ligand
and metal chelates were studied (Table 4 and Fig. 2) and
assigned on the basis of the careful comparison of their
spectra with that of the free ligand (CD). The IR spectra
of CD reveal a band at 1354 cm−1 due to ν(C–N) of the
␤-lactam and thiazole ring nitrogen. This band is absent
in all complexes, indicating participation of the ␤-lactam
and thiazole ring nitrogen atom in the bonding. The band
of ν(CO) group of the ␤-lactam ring at 1759 cm−1 is ab-
sent in all complexes. This means that the ␤-lactam ring
carboxylic group is involved in the complex formation.
The bands νsym(COO) are shifted to higher frequencies
(about 30–50 cm−1). This indicates that the carboxylic
group is involved in the coordination to the metal ion. In
addition, the ligand exhibits bands in the wave number re-
3.2. Solid reflectance spectra and magnetic susceptibility
measurements
The obtained magnetic moment of the Fe(II)–CD complex
(µeff = 2.42 BM) is within the range of values correspond-
ing to a tetrahedral arrangement. The magnetic moment of
the Fe(III)–CD complex has been found to be 5.01 BM; well
within the range of values corresponding to high-spin oc-
tahedral complexes of Fe(III) ions. The reflectance spectra
(Fig. 3a) of this complex have transitions confirming an oc-
tahedral configuration [10]. The magnetic moment of the
complex Co(II)–CD (µeff = 1.69 BM) indicates a tetrahe-
dral complex, whereas the observed Co(III)–CD magnetic
Table 4
Selected IR data and band assignment for cefadroxil (CD) and its complexes at 4000–200 cm−1
=
Complex
ν(C–N)
ν(C O)
νasym(COO)
νsym(COO)
ν(M–O)
ν(M–O)
N (M–N)
␤-lactam
␤-lactam
(coordinated H2O)
␤-lactam
Cefadroxil
1354 s
disap.
disap.
disap.
disap.
disap.
disap.
disap.
1759 s
Disap.
Disap.
Disap.
disap.
disap.
disap.
disap.
1564 s
1559 s
1600 s
1606 s
1601 s
1588 s
1603 s
1600 s
1234 s
1261 s
1266 s
1268 s
1268 s
1236 s
1234 s
1230 s
–
–
–
[Fe(II)L(H2O)]·2H2O
[Fe(III)L(OH)(H2O)2]·H2O
[Co(II)L·H2O]
878 s, 750 s
837 s, 750 s
835 s, 750 s
840 s, 750 s
842 s, 750 s
839 s, 750 s
830 s, 740 s
463 s
455 s
458 s
456 s
468 s
454 s
458 s
620 s
621 s
633 s
624 s
593 s
634 s
636 s
[Co(III)L(OH)(H2O)2]·H2O
[Ni(II)L(OH)]·H2O
[Cu(II)L(OH)]·H2O
[Zn(II)L(H2O)]
s: strong band; disap.: band disappear.

M.A. Zayed, S.M. Abdallah / Spectrochimica Acta Part A 60 (2004) 2215–2224
2219
4Eg(G) transition [13]. The Racah interelectronic repulsion
parameter for the cobalt complex may be calculated using
the following equations [18]:
10 Dq = 2ν1 − ν3 + 15B
(3)
(4)
B = [−(2ν1 − ν3) (−ν1 + ν32 + ν1ν3)−1/2
]
1
30
The Racah parameter is of the order 0.6 of the free ion value,
suggesting considerable overlapping in the metal–ligand
bond [13].
The magnetic moment of the Ni(II)–(CD) complex has
been found to be 3.34 BM which is within the range of val-
ues corresponding to distorted octahedral and/or tetrahedral
geometry. The solid reflectance spectra of the Ni(II) com-
plex (Fig. 3c) are consistent with this proposal. The appear-
3
ance of three bands at ν1 = (5860–11,070 cm−1), A2g
→
3T2g; ν2 = (11,240–18,870 cm−1), A2g → T1g(F); and
3
3
ν3 = (21,830–27,470 cm−1), A2g → T1g(P) are support-
ive and consistent with this proposal. The 10 Dq value lies
in the range of 5860–11,070 cm−1 confirming the proposed
distortion and the partial presence of tetrahedral configura-
tion as a result of this distortion [13].
3
3
The solid reflectance spectra of the copper complex
(Fig. 3d) give bands in the range 21,650 cm−1, consistent
with a tetrahedral or square-planar environment [4]. The
magnetic data have the value of µeff = 1.44 BM, which is
indicative of antiferromagntic spin–spin interaction through
molecular association. Hence, the Cu(II)–CD complex ap-
pears to be in a square-planar geometry with a dx2 − dy2
ground state [14]. The zinc complex is diamagnetic and is
likely to be tetrahedral.
The measured magnetic moments at various temperatures
of a series of complexes of CD which are tetrahedral, dis-
torted octahedral, and square-planar impose to steric require-
ments on the proposed formulae of these complexes [10] as
given by Fig. 4.
Fig. 2. IR spectra of: (a) cefadroxil (CD); and (b) its com-
plexes: [Fe(II)L(H2O)]·2H2O, (c) [Fe(III)L(OH)(H2O)2]·H2O, (d)
[Co(II)L·H2O], (e) [Co(III)L(OH)(H2O)2]·H2O, (f) [Ni(II)L(OH)]·H2O,
(g) [Cu(II)L(OH)]·H2O, and (h) [Zn(II)L(H2O)].
3.3. Thermal analyses and mass spectra
The thermal analyses data (TGA, DTG, DTA, and dif-
ferential (dr) DTA, Fig. 5), temperature ranges, TGA peak
temperatures in ◦C, and mass loss % (found and calcu-
lated), together with fragmentation assignments are given
in Table 5. These data may be summarized as follows.
moment (µeff = 4.17 BM) is consistent with a high-spin
octahedral structure for this complex [13,14]. The solid re-
flectance spectra (Fig. 3b) show two bands of medium in-
tensity at 21,053 and 12,165 cm−1, which may be due to
partial reduction of Co(III) in its complex [10]. These bands
3.3.1. Thermal analyses and comparison with mass
spectra of Fe(II)–CD complex
4
4
are assigned to the transitions T1g(F) → T1g(P) (ν3) and
4T2g(F) → T2g(F) (ν1) of the tetrahedral cobalt(III) com-
The TG thermal analysis of the Fe(II)–CD complex
(Fig. 5a) of the general formula FeL(H2O)·2H2O (L = CD),
gives a three stages decomposition pattern, which is sup-
ported by DTA data. The first mass loss of 3.47% occurs
within the temperature range 32–141 ◦C is correlated with
the loss of H2O molecule (calcd. loss = 3.8%). This is
immediately followed by another mass loss at 141–326 ◦C
of 16.73% (calcd. loss = 16.06%) which is due to the loss
of the second water molecule (coordinated) together with
4
plex. The transition 4T1g → T1g (ν2) may also be assigned
4
to a two-electron process, which is normally weak. The ra-
tio ν3/ν2 = 1.70, which is lower than that expected for
octahedral cobalt(II) complexes (1.95–2.48) [10]. This in-
dicates a certain distortion from a true octahedral geometry
due to the presence of a mixed ligand field (CD and OH or
H2O) in the moiety of the complex. The weak band observed
at 7230 cm−1 is assigned to the spin-forbidden T1g(F) →
4

2220
M.A. Zayed, S.M. Abdallah / Spectrochimica Acta Part A 60 (2004) 2215–2224
Fig. 3. Reflectance spectra of cefadroxil (CD) complexes: (a) [Fe(III)L(OH)(H2O)2]·H2O, (b) [Co(III)L(OH)(H2O)2]·H2O, (c) [Ni(II)L(OH)]·H2O, and
(d) [Cu(II)L(OH)]·H2O.
a fragment of CD; CH3NHCO. The loss of another part
of CD equal to 17.59% at 327–604 ◦C may be assigned as
the loss of CH2CHCH2NHCO (calcd. loss = 17.97%). The
final mass loss of 5.85% may due to the loss of CH3NH2
(6.55%) leaving Fe3O4·2H2O (molecular mass = 268) as
residue compound (Fig. 6). The mass losses given by TG
appear in the DTA as exothermic peaks in the tempera-
ture range 200–800 ◦C. This may be explained by several
chemical reactions between the fragments obtained. Some
of these peaks are centered at 47 ◦C, which may refer to
the loss of water of hydration (E = 68.5 J g−1). The second
one at 295 ◦C is due to the loss of H2O (coordinated) and
CH3NHCO molecules (E = 260 J g−1) and the fourth one,
which occurs at 663 ◦C (E = 1.16 kJ g−1), may be due to
the formation of the final stable oxide residue [14].
The mass spectra of CD is shown in Fig. 5a and the
mass spectra of the Fe(II)–CD complex (Fig. 5b) show a
molecular ion of m/z = 473 of 2.68% abundance, followed
by a molecular ion of m/z = 295 (abundance, 7.2%), of the
complex containing a remainder part of the ligand (Lrem.) of
the formula [Fe(Lrem.)(H2O)]. Finally, a residual molecule
of the stable oxide Fe3O4·2H2O (molecular mass = 268) of
m/z = 267 (abundance, 3.62%).
3.3.2. Thermal analyses and comparison with mass
spectra of Fe(III)–CD complex
The TGA of the Fe(III)–CD complex of the general
formula [FeL(OH)(H2O)2]·H2O is shown in Fig. 5b. The
Fig. 4. General structural formula of cefadroxil transition metal
chelates—M: Fe(II), x = 0, y = 1, z = 2; M: Fe(III) and Co(III), x = 1,
y = 2, z = 1; M: Co(II) and Zn(II), x = 0, y = 1, z = 0; M: Ni(II) and
Cu(II), x = 1, y = 0, z = 1.

M.A. Zayed, S.M. Abdallah / Spectrochimica Acta Part A 60 (2004) 2215–2224
2221
Fig. 5. Thermal analyses (TG, DTG, and DTA) of cefadroxil (CD) complexes: (a) [Fe(II)L(H2O)]·2H2O, (b) [Fe(III)L(OH)(H2O)2]·H2O, (c) [Co(II)L·H2O],
(d) [Co(III)L(OH)(H2O)2]·H2O, (e) [Ni(II)L(OH)]·H2O, (f) [Cu(II)L(OH)]·H2O, and (g) [Zn(II)L(H2O)].
calculated and found mass losses are reasonably assigned
in Table 5. The DTA curves of the Fe(III)–CD complex
show broad exothermic peaks in the temperature range
40–480 ◦C. These peaks refer to the exothermic mass losses
of the given complex during the heating process and chem-
ical recombination of the fragments to give stable and/or
volatile molecules. It starts with a small peak at 44.5 ◦C due
to the loss of one water molecule (E = 92.5 J g−1) followed
by a distinct peak at 278 ◦C of E = 1.86 kJ g−1. This is due
to the ligand fragmentation and the loss of another water
molecule. The third exothermic peak centered at 456 ◦C
has E = −144 J g−1 and a further one at 483 ◦C has E =
−167 J g−1 and corresponds to the exothermic loss of other
chemically combined fragments of the CD ligand. The mass
spectra of the Fe(III)–CD (molecular mass = 474) complex
(Fig. 7c) appeared as a molecular ion of m/z = 474 (abun-
dance, 4.26%) followed by a molecular ion of the formula
FeLrem·2H2O (molecular mass = 455) after loss of one
molecule of water, appeared as a molecular ion of m/z =
458 (abundance, 9.57%) other molecular ions are also de-
tected; at m/e = 408 (abundance, 4.27%) and at m/z = 381
(abundance, 6.31%). The residue of a complex is found to
have a formula of Fe3O4·2H2O of molecular mass = 268
and corresponding to m/z = 267 (abundance, 3.11%).
3.3.3. Thermal analyses and comparison with mass
spectra of Co(II)–CD complex
The TG curves of the Co(II)–CD complex (Fig. 5c) of the
general formula [CoL(H2O)] exhibit mass losses reasonably
assigned as given in Table 5. The DTA curves of Co(II)–CD
complex show a very small sharp exothermic peak at 50 ◦C
which may be due to the loss of CH3NH2 (E = 254.5 J g−1).
This is followed by another sharp peak at 260.3 ◦C due to the
loss of water, phenol, and another part of the decomposed
CD ligand (E = 403.5 J g−1). There is a steep lowering
of the heat capacity finally followed by sharp endothermic
peaks at 362 ◦C (E = 1.84 J g−1), at 471 ◦C (E = 34 J g−1
)
and 898 ◦C (E = −14.4 kJ g−1), respectively. These peaks
may be due to the complete decomposition of CD as frag-
ments chemically recombine leaving Co3O4 as residue. The
mass spectra of the Co(II)–CD complex (Fig. 7d) show the
molecular at m/z = 440 (abundance, 15.07%), followed by
a loss of ligand parts leaving the cobalt complex containing
a remainder part of ligand of the form CoLrem. of molecular

Table 5
Thermal decomposition of cefadroxil (CD) d-block metal-complexes
Complex
TG temperature
range (◦C)
TG peak
temperature (◦C)
Mass loss (%)
Calcd.
Residue (%)
Found
Calcd. (found)
Residue form
[Fe(II)L(H2O)]·2H2O
32–141, 141–326,
327–604,
606–866
80.83, 251.56,
398.61, 716.37
3.8, 16.06, 17.97,
3.47, 16.73, 17.39,
55.6 (56.8), Fe3O4·2H2O,
molecular mass = 268
Loss of H2O (hydration), loss of
CH3NHCO and H2O (coordinated),
loss of CH2CH(CH2)–NHCO
molecule, loss of CH3NH2
ꢀ
ꢀ
(molecular mass = 473)
6.55;
44.38
5.85;
43.17
[Fe(III)L(OH)(H2O)2]·H2O
(molecular mass = 490)
32–133, 135–754
73.52, 323.32,
613.48
3.67, 43.26;
46.93
4.26, 43.70;
47.96
54.0 (53.7), Fe3O4·2H2O,
molecular mass = 268
Loss of H2O (hydration), loss of
CH2CH(CH3)NHCONH2 + H2O
(coordinated) and C6H5OH and
HNCH2CH2CHSH
ꢀ
ꢀ
[Co(II)L.H2O] (molecular
mass = 439)
27–148, 142–381,
384–640
70.06, 295.73,
455.72
7.06, 38.49, 33.25;
78.80
6.34, 38.90, 32.99;
78.23
22.0 (21.0), CoO2,
molecular mass = 91
Loss of CH3NH2, H2O (coordinated),
CH2CONH2 and C6H4OH, loss of
C2H4, CO, CH2CH2CH2N and CH2S
molecules
ꢀ
ꢀ
[Co(III)L(OH)(H2O)2]·H2O
(molecular mass = 491)
22–130, 122–419,
423–789
60.34, 259.09,
534.14
6.31, 27.98, 18.73;
53.02
6.97, 27.98, 12.72;
47.67
47.0 (48.0), Co3O4,
molecular mass = 238
Loss of CH3 NH2, loss of C6H4 OH
and CONH2 molecules, loss of H2O
(coordinated), and CH2CH2CH2NH2
and CH3CH2CH3 molecules
ꢀ
ꢀ
[Ni(II)L(OH)]·H2O
26–184, 186–429,
430–625
84.92, 333.07,
493.07
7.72, 30.22, 24.27;
62.21
7.92, 30.46, 24.06;
62.44
37.79 (37.3), Ni2O3,
molecular mass = 164
Loss of CH4 and H2O (hydration),
loss of C6H4OH and CH2NH2, loss of
NH2CH2CHNH2CH2S molecules
Loss of CH3NH2, loss of C6H4OH,
loss of H2O (coordinated), CO, C2H4,
N2, SO2 and C3H3 molecules
Loss of CH3NH2, loss of CH2CoNH2,
H2O (coordinated), C6H4OH and
CH2CH2CH2N Co2 and
ꢀ
ꢀ
(molecular mass = 440)
[Cu(II)L(OH)]·H2O
57–189, 189–425,
427–697
117.57, 284.110,
540.42
6.90, 20.89, 22.92;
6.13, 19.85, 23.70;
50.0 (50.3), Cu2O·CuO,
molecular mass = 223
ꢀ
ꢀ
(molecular mass = 455)
50.71
49.56
[Zn(II)L(H2O)] (molecular
mass = 446)
43–189, 189–759
81.63, 470.23
6.95, 51.56;
6.82, 51.82;
43.0 (42.0), Zn2O4,
molecular mass = 199.5
ꢀ
ꢀ
58.51
58.64
CH2CH2CH2SH molecules

M.A. Zayed, S.M. Abdallah / Spectrochimica Acta Part A 60 (2004) 2215–2224
2223
This means that mass spectra confirm the thermal analyses
previously explained.
3.3.4. Thermal analyses and comparison with mass
spectra of Co(III)–CD complex
The Co(III)–CD complex of the general formula
[Co(OH)(H2O)2]·H2O thermally decomposed in several
stages (Fig. 5d) and assigned as given in Table 5. The DTA
of the Co(III)–CD complex includes four exothermic peaks
at 52 ◦C (E = 11.3 J g−1), 250.5 ◦C (E = 300.4 J g−1),
445 ◦C (E = 3.8 kJ g−1), and 782.5 ◦C (E = 208 J g−1), re-
spectively. The first two peaks may be due to an exothermic
loss of H2O + CH3NH2; the third one may be due to the
loss of other water molecules, phenol, and other fragments
of CD ligand. The fourth one may be due to the chemical
combination of some CD fragments leaving a stable resid-
ual oxide (Co3O4) of molecular mass = 241. The mass
spectra of the Co(III)–CD complex (Fig. 8a) show a main
complex molecular ion of m/z = 440 (abundance, 15%),
followed by a molecular ion of the formula CoLrem·H2O,
that containing a remainder part of ligand, of m/z = 323
(abundance, 17.5%), leaving a stable cobalt oxide residue
(Co3O4) of the molecular ion of m/z = 238 (abundance,
25.1%) as given by its mass spectra (Fig. 8a).
Fig. 6. Mass and thermal fragmentation scheme of [Fe(II)L(H2O)]·2H2O
complex.
3.3.5. Thermal analyses and comparison with mass
spectra of Ni(II)–CD complex
mass = 239 that corresponds to a molecular ion of m/z =
238 (abundance, 19%). The residual molecule of CoO2 has
a molecular mass of 89 and m/z = 89 (abundance, 34.93%)
that may recombine to give the final stable oxide Co3O4.
The TG curves of Ni(II)–CD complex (Fig. 5e) of the
general formula NiL(H2O) show that it decomposed in three
steps, that reasonable explained in Table 5. The DTA of
Ni(II)–CD complex shows broad exothermic peaks at 199 ◦C
(E = 210.4 J g−1) and at 434 ◦C (E = −275.35 J g−1).
These peaks may be due to the loss of a water molecule
and the exothermic loss of some CD volatile fragments. The
Fig. 7. Mass spectra of cefadroxil (CD) complexes of: (a) cefadroxil
(CD), (b) [Fe(II)L(H2O)]·2H2O, (c) [Fe(III)L(OH)(H2O)2]·H2O, and (d)
[Co(II)L·H2O].
Fig. 8. Mass spectra of: (a) [Co(III)L(OH)(H2O)2]·H2O, (b)
[Ni(II)L(OH)]·H2O, (c) [Cu(II)L(OH)]·H2O, and (d) [Zn(II)L(H2O)].

2224
M.A. Zayed, S.M. Abdallah / Spectrochimica Acta Part A 60 (2004) 2215–2224
mass spectra of the Ni(II)–CD complex (Fig. 8b) of molec-
ular mass = 440 show a molecular ion of m/z = 440
(abundance, 5.31%), followed by a molecule of the formula
NiLrem·H2O containing the remainder part of the ligand of
molecular mass = 283 which appears as a molecular ion of
m/z = 283 (abundance, 6.37%). The residual nickel oxide
NiO of molecular mass = 74, appears as a molecular ion of
m/z = 75 (abundance, 34.16%).
455 (abundance, 4.28%), followed by the appearance of the
ion of the formula ZnLrem·H2O (molecular mass = 415) of
m/z = 415 (abundance, 13.3%) after the loss of CH3NH2
and the residual complex of the molecular ion of m/z =
199.5 (abundance, 43.68%).
4. Conclusion
This study of the reactions between essential transition
d-block elements and cefadroxil drug in aqueous media
indicates the high stability of the formed metal-complexes.
Therefore, it is clear from this study that this drug has seri-
ous biological effects on the human body. This encourages,
the synthesis and careful investigation of the nature of bond-
ing between this drug and the transition metal cations of im-
portant biological role, using physico-chemical methods of
analyses. It is clear from the above discussion that the ther-
mal fragmentation and the spectra of the above complexes
confirm and illustrate the proposed general and structural
formulae of the above complexes obtained by elemental
analyses, UV-Vis, IR, MS, TA, and reflectance spectra.
3.3.6. Thermal analyses and comparison with mass
spectra of Cu(II)–CD complex
The TG thermogram of the Cu(II)–CD complex (Fig. 5f)
of the general formula CuL(H2O) is thermally decomposed
in several stages and can be reasonably accounted by the
losses given in Table 5. The DTA and derivative DTA
curves for the Cu(II)–CD complex show a low intensity first
exothermic peak at 66 ◦C (E = 108.8 J g−1), which may
be due to the loss of a CH3NH2 molecule from the entity
of the complex. There are also sharp exothermic peaks at
486 ◦C (E = 1.5 kJ g−1) and at 580 ◦C (E = 1.05 kJ g−1
)
which may be due to the vigorous fragmentation of the
CD ligand on heating and chemical recombination of the
fragments leading to the above mentioned gases. The mass
spectra of this complex (Fig. 8c) includes a molecular ion
of m/z = 446 (abundance, 4.6%), followed by a molecule
of the formula, Cu(II)Lrem. of molecular mass = 321 ap-
peared at m/z = 322 (abundance, 4.8%). It decomposed to
give stable residual mixture of copper oxides (Cu2O·CuO)
of molecular mass = 222 that appeared at m/z = 223
(abundance, 7.38%).
References
[1] E. R Buck, E.K. Price, Antimicrob. Agents Chemother. 11 (1977)
324.
[2] M. Pfeiffer, Antimicrob. Agents Chemother. 11 (1977) 331.
[3] L.J. Delarbre, L. Maury, J. Rambaud, B. Pauvert, M.B. Simeonde,
Farmac. Ed. Sci. 43 (1988) 1961.
[4] S.S. Badawy, F.M. Abdel Gawad, M.M. Ibrahim, Anal. Lett. 26
(1993) 487.
[5] F.M. Abdel-Gawad, S.S. Badawy, M.M. Ibrahim, Egypt J. Chem. 37
(1994) 103.
3.3.7. Thermal analyses and comparison with mass
spectra of Zn(II)–CD complex
The TG thermogram of the Zn(II)–CD complex (Fig. 5g)
of the general formula ZnL(H2O), gives two stages of ther-
mal decomposition that explained by losses in Table 5. The
DTA curves of this complex contain three main exothermic
[6] M.E. Pascussi, Bull. Chem. Farm. 119 (1980) 52.
[7] P.S. Chilukuri, R. Rao, S.D. Prasad, Mikrochim. Acta 126 (1997)
167.
[8] W.P. Gluth, F. Soergel, S. Plank, V.M. Geldmacher, Proc. Int. Congr.
Chempther. 13 (7) (1983) 118.
[9] C. Hendrix, C. Wijen, E. Roets, J. Hoognartens, J. Chromatogr. 628
(1993) 49.
[10] G.G. Mohamed, E.A.E. Nadia, F.A. Nour El-Dien, Synth. React.
Inorg. Met.–Org. Chem. 31 (2001) 347.
[11] A.S. Amin, Anal. Lett. 27 (1994) 95.
[12] A.S. Amin, Analusis 23 (1995) 415.
[13] S. Pal, G. Mukherjee, Poddarsn, J. Indian Chem. Soc. 69 (1992) 461.
[14] D.R. Lide, CRC Hand Book of Chemistry and Physics, 73rd ed.,
Wiley, 1992–1993.
peaks. The first one occurs at 373.4 ◦C (E = 4.1 kJ g−1
)
which may be due to the loss of a CH3NH2 molecule from
the moiety of the complex as the first loss given by TG.
The second one occurs at 580 ◦C (E = −252.9 J g−1), and
the third one occurs at 598.9 ◦C (E = 212 J g−1), assignable
to the complete decomposition of the CD ligand, leaving
ZnO as residue. The mass spectra of this complex (Fig. 8d)
(molecular mass = 456) show a molecular ion of m/z =