Synthesis, characterization, molecular modeling and antimicrobial activity of 2-(2-(ethylcarbamothioyl)hydrazinyl)-2-oxo-N-phenylacetamide copper complexes

Article abstract of DOI:10.1016/j.saa.2009.11.007

Six Cu(II) complexes of 2-(2-(ethylcarbamothioyl)hydrazinyl)-2-oxo-N-phenylacetamide (H₃APET) have been prepared and characterized by elemental analyses, spectral (IR, UV-vis, ¹H NMR and ESR) as well as magnetic and thermal measurements. The data revealed that the ligand acts as ON bidentate, ONS tridentate or ONNS tetradentate forming structure in which each copper atom is a tetrahedral or tetragonal environment. The bond length, bond angle, HOMO, LUMO, dipole moment and charges on the atoms have been calculated to confirm the geometry of the ligand and the investigated complexes. Kinetic parameters were determined for each thermal degradation stage of the Cu(II) complexes using Coats-Redfern and Horowitz-Metzger methods. Moreover, the ligand and its complexes were screened against bacteria Staphylococcus aureus, Escherichia coli, Candida and fungi, Albicans and Aspergillus flavus using the inhibitory zone diameter.

Full text of DOI:10.1016/j.saa.2009.11.007

Spectrochimica Acta Part A 75 (2010) 533–542
Contents lists available at ScienceDirect
Spectrochimica Acta Part A: Molecular and
Biomolecular Spectroscopy
journal homepage: www.elsevier.com/locate/saa
Synthesis, characterization, molecular modeling and antimicrobial activity of
2-(2-(ethylcarbamothioyl)hydrazinyl)-2-oxo-N-phenylacetamide copper
complexes
Ola A. El-Gammal∗
Department of Chemistry, Faculty of Science, Mansoura University, Mansoura, P.O. Box 70, Mansoura, Egypt
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 28 July 2009
Received in revised form 31 October 2009
Accepted 3 November 2009
Six Cu(II) complexes of 2-(2-(ethylcarbamothioyl)hydrazinyl)-2-oxo-N-phenylacetamide (H3APET) have
been prepared and characterized by elemental analyses, spectral (IR, UV–vis, 1H NMR and ESR) as well
as magnetic and thermal measurements. The data revealed that the ligand acts as ON bidentate, ONS tri-
dentate or ONNS tetradentate forming structure in which each copper atom is a tetrahedral or tetragonal
environment. The bond length, bond angle, HOMO, LUMO, dipole moment and charges on the atoms have
been calculated to confirm the geometry of the ligand and the investigated complexes. Kinetic parame-
ters were determined for each thermal degradation stage of the Cu(II) complexes using Coats–Redfern
and Horowitz–Metzger methods. Moreover, the ligand and its complexes were screened against bac-
teria Staphylococcus aureus, Escherichia coli, Candida and fungi, Albicans and Aspergillus flavus using the
inhibitory zone diameter.
Keywords:
Copper complexes
Spectroscopy
Molecular modeling
Antimicrobial
© 2009 Elsevier B.V. All rights reserved.
1. Introduction
(H3APET) towards different salts of Cu(II) and screened against
some microbial organisms.
Thiosemicarbazides constitute an important class of NS donors.
Due to their remarkable properties, variable donor properties,
structural diversity and biological applications, they have been
the subject of numerous coordination chemical studies [1–9].
Thiosemicarbazide complexes have anticancer and antimicrobial
activity owing to their ability to diffuse through the semiperme-
able membrane of the cell lines. The enhanced effect may be due to
the increase of lipophilicity of the complexes compared to the lig-
and [5,10–12]. Thiosemicarbazides have been used for extraction
and determination of some metal ions in biological and pharmaco-
logical samples [13,14].
Thiosemicarbazide complexes, in particular Cu(II) complexes,
seem to present an implemental biological activities [15–17]. Ben-
zil bis(4-methyl-3-thiosemicarbazide) copper(II) complexes have
been investigated as anticancer chemotherapeutic agents [5,18]
and as superoxide dismutase like radical scavengers [19] and used
as delivery agents for radioactive copper in the development of new
copper based radiopharmaceutical agents [20–24].
2. Experimental
2.1. Instrumentation and materials
All the chemicals were purchased from Aldrich and Fluka and
used without further purification. Elemental analyses (C, H, N)
were performed with a Perkin-Elmer 2400 series II analyzer. Molar
conductance values (10−3 mol/l) of the complexes in DMF were
measured using a Tacussel conductivity bridge model CD6NG.
IR spectra (4000–400 cm−1) for KBr discs were recorded on a
Mattson 5000 FTIR spectrophotometer. Electronic spectra were
recorded on a Unicam UV–Vis spectrophotometer UV2. Magnetic
susceptibilities were measured with a Sherwood scientific mag-
netic susceptibility balance at 298 K. 1H NMR measurements in
d6-DMSO at room temperature were carried out on a Varian Gemini
WM-200 MHz spectrometer at the Microanalytical Unit, Cairo Uni-
versity. Thermogravimetric measurements (TGA, DTA, 20–1000 ◦C)
were recorded on a DTG-50 Shimadzu thermogravimetric analyzer
at a heating rate of 10 ◦C/min and nitrogen flow rate of 20 ml/min.
ESR spectra were obtained on a Bruker EMX spectrometer working
in the X-band (9.78 GHz) with 100 kHz modulation frequency. The
microwave power and modulation amplitudes were set at 1 mW
and 4 G, respectively. The low field signal was obtained after four
scans with 10 fold increase in the receiver again. A powder spec-
trum was obtained in a 2 mm quartz capillary at room temperature.
Recently in our laboratory, numerous complexes of thiosemi-
carbazide and its derivatives have been reported [25–27]. This
paper extended the investigation of the chelating properties of
2-(2-(ethylcarbamothioyl)hydrazinyl)-2-oxo-N-phenylacetamide
∗
Tel.: +20 2 0193443558.
E-mail address: olaelgammal@yahoo.com.
1386-1425/$ – see front matter © 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.saa.2009.11.007

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O.A. El-Gammal / Spectrochimica Acta Part A 75 (2010) 533–542
2.2. Synthesis of H3APET
3.1. Molecular modeling
H3APET was synthesized as reported earlier [2] by heating
under reflux for 4 h an ethanol solution of 2-hydrazino-2-oxo-N-
phynylacetamide with ethylisothiocyanate. The white precipitate
was filtered off, washed with ethanol and recrystallized from hot
ethanol and finally dried in a vacuum desiccator over anhydrous
CaCl2 (m.p., 265–66 ◦C).
The molecular structure along with atom numbering of H3APTS
and its Cu(II) complexes are shown in structures (I–VII). Analysis
of the data in Tables 1S–15S (Supplementary Materials) calculated
for the bond lengths and angles for the bond, one can conclude the
following remarks:
1. The bond angles of the thiosemicarbazide moiety are altered
somewhat upon coordination; the largest change affects
S17–C15–N14 and S17–C15–N16 angles which are reduced
from 121.2◦ on ligand to 112.2◦ on complexes as a conse-
quence of bonding. All bond angles in complexes are quite near
to a tetrahedral geometry predicting sp3 hybridization except
[Cu(H2APET)Br]·2H2O, which have a square planar geometry
with dsp2 hybridization.
2.3. Synthesis of Cu(II) complexes
Ethanolic or aqueous-ethanolic solution of H3APET (0.266 g,
1.0 mmol) and hydrated copper salts (bromide, nitrate, acetate, per-
chlorate and sulfate) (1.0 mmol) was heated under reflux for 2–3 h.
The precipitates were filtered off, washed with ethanol followed
by diethyl ether and dried in a vacuum desiccator over anhydrous
CaCl2. The nitrate salt yielded mono- and binuclear complexes
according to the preparation conditions. The physical and analytical
data of the isolated complexes are listed in Table 1. The com-
plexes have high melting points and insoluble in common organic
solvents; partially soluble in DMF or DMSO and found to be non-
electrolytes. The color of the complexes is similar indicating that the
thiosemicarbazide moiety plays an important role in determining
the color rather than the particular coordinated anion occupying
the fourth position.
2. All the active groups taking part in coordination have
bonds longer than that already exist in the ligand (like
C
S, N–H, and C O). Short bond lengths are observed in
[Cu2(HAPET)(NO3)2(H2O)2] [31].
3. Coordination is significantly shorten the N14–H27 and N7–H9
(N–H)Ph and (N4HEt) bond lengths of the ligand probably due to
loss of intramolecular hydrogen bonds.
4. There is
a large variation in N12–N14 bond lengths on
complexation. It becomes slightly longer as the coordina-
tion takes place via N atoms of –C N–C N– group that is
formed on deprotonation of C–OH and thiol C–SH groups in
[Cu2(HAPET)(NO3)2(H2O)2].
2.4. Antimicrobial activity
The in vitro antimicrobial activity of the reported complexes was
evaluated against Escherichia coli as gram negative, Staphylococ-
cus aureus as gram positive bacterial cultures, Candida albicans and
Aspergillus flavus as fungal cultures using Gentamycin and Diflu-
can as standard controls. The hole plate diffusion method [28]
was adopted for the activity measurements. The bacterial strains
were grown in nutrient agar slants and fungal strains were grown
in Sabouraud dextrose agar slants (Dox’s medium). A suspension
of the studied compounds (0.2 ml of each (10 ␮g/ml) was incu-
bated at 36 ◦C for 36 and 76 h for the bacterial and fungal cultures,
respectively. After inoculation, the diameter (in mm) of the clear
inhibition zone surrounding the sample is taken as a measure of
the inhibition power against the particular organisms. The experi-
ments were repeated three times and the values recorded are the
mean average.
3.2. IR and 1H NMR spectra
The most important IR bands of H3APET (Structure I) and its
complexes with probable assignments are given in Table 2. The
ligand has multi coordination sites which gave variable coordi-
nation modes. A comparison of the spectrum of H3APET and its
complexes revealed that the ligand coordinates in the thione and
thiol forms. H3APET showed bands at 3313, 3285, 3165, 3102,
1722 and 1675 cm−1 assigned to ꢀ(NH)Ph, ꢀ(N4H), ꢀ(N1H), ꢀ(N2H),
ꢀ(C O)1 and ꢀ(C O)2, respectively. The medium intensity band
at 950 cm−1 is referred to ꢀ(N–N) [32] in addition to a band at
798 cm−1 attributed to ꢀ(C S) vibration. The doublets at 2900
and 2970 cm−1 are attributed to the symmetric and asymmet-
ric stretching vibrations of ethyl group. The broad weak bands at
1800–1960 cm−1 and 2300–2400 cm−1 can be taken as an evidence
for intramolecular hydrogen bonding (N–H· · ·O) [33].
2.5. Molecular modeling
The 1H NMR spectrum of H3APET, in d6-DMSO, showed signals
at 8.02 (d), 9.33 (s) and 10.70 and 10.72 ppm (d) due to N2H, N1H,
N4HEt and NHPh protons, respectively. Also, the multiple signals at
7.12–7.89 ppm are assigned to the protons of phenyl ring.
An attempt to gain a better insight on the molecular structure of
the ligand and its complexes, geometric optimization and confor-
mational analysis has been performed using MM+ [29] forcefield as
implemented in hyperchem 7 [30].
In [Cu(H2APET)Br]·2H2O (Structure II), H3APET behaves as a
mononegative tridentate coordinating via the C–O1, (N2H) and
(C S) centers. This is confirmed by: (i) the disappearance of
ꢀ(C O)1 and ꢀ(N1H) with simultaneous appearance of new bands
at 1124 and 1585 cm−1 assigned to ꢀ(C–O) and ꢀ(C N)*, resulting
3. Results and discussion
The data of elemental analysis together with some physical
properties of the complexes are summarized in Table 1.
Table 1
Physical properties and elemental analyses of H3APET and its complexes.
Compound, formula
Color
Yield (%)
m.p. (◦C)
Found (Calcd.) (%)
C
H
N
Cu
H3APET
White
Dull green
Brown
Olive green
Pale green
Grey
85
92
90
85
80
70
85
265–266
>300
>300
>300
>300
49.48 (49.61)
30.5 (29.7)
5.30 (5.29)
4.53 (3.85)
4.60 (4.16)
4.13 (4.08)
3.02 (2.92)
3.69 (4.10)
4.85 (3.40)
20.92 (21.03)
–
–
–
14.87 (15.29)
17.12 (17.43)
–
–
[Cu(H2APET)Br]·2H2O, C11H17N4O4SbrCu
[Cu(HAPET)(OAc)], C13H16N4O4SCu
[Cu(HAPET)(H2O)], C11H14N4O3SCu
[Cu2(HAPET)(NO3)2(H2O)2], C11H16N6O10SCu2
[Cu(H2APET)(NO3)(H2O)], C11H15N5O6Scu
[Cu(H2APET)(ClO4)(H2O)], C11H15N4O3SClO4Cu
15.00 (14.26)
16.20 (16.37)
15.10 (15.19)
24.00 (23.04)
15.50 (16.20)
14.90 (14.29)
40.21 (40.26)
38.52 (38.24)
24.23 (23.96)
33.81 (34.21)
29.42 (29.74)
>300
>300
Yellowish green

O.A. El-Gammal / Spectrochimica Acta Part A 75 (2010) 533–542
535
Table 2
IR absorption spectral bands of H3APET and its copper complexes.
Compound
ꢀ(N4H)
ꢀ(N1H)
ꢀ(N2H)
ꢀ(C O)1
ꢀ(C O)2
ꢀ(C N*)
ꢀ(C S)
ꢀ(C–O)
ꢀ(M–O)
H3APET
3285s
3165m
3102m
3100w
3100w
–
1722s
1675s
1658w
1676m
1659w
1679w
1676s
1679m
–
798s
757m
–
–
–
–
–
[Cu(H2APET)Br]·2H2O
[Cu(H2APET)(OAc)]
[Cu(HAPET)(H2O)]
[Cu2(HAPET)(NO3)2(H2O)2]
[Cu(H2APET)(NO3)(H2O)]
[Cu(H2APET)(ClO4)(H2O)]
3280m
3290w
3245w
3270w
3280m
3284m
–
–
–
–
–
–
–
–
–
–
–
–
1585s
1553b
1600s
1590b
1635s
1604m
1124m
1180s
1238s
1207s
1087s
1123s
500s
505s
503s
491s
505s
506s
–
3101w
3073m
792m
794s
s: strong; m: medium; b: broad; and w: weak.
from enolization, (ii) the weakness of (N2H) band and (iii) the shift
of ꢀ(C S) to lower wavenumber. The (C O)2 band is affected due to
its interaction with another copper atom. Steric factors prevent the
coordination of the two carbonyls to a single metal ion, therefore,
the ligand may bridged the two metal centers through (C O)2. The
appearance of new bands at 500 and 414 cm−1 assignable to ꢀ(M–O)
and ꢀ(M–N) vibrations.
nitrogen [34], (iv) the new bands at 505 and 420 cm−1 assignable to
ꢀ(M–O) and ꢀ(M–N), respectively and (v) the broad band appeared
at 1553 cm−1 which may be considered as an overlap of ꢀ(C N)*
with ꢀas(OCO) and 1447 cm−1 assignable to ꢀs(OCO) affording wave
number separation value (ꢁ = 106 cm−1) characteristic of bidentate
acetate anion [35].
The ligand acts as
a mononegative bidentate coordinat-
ing through (C–O)1 and (N2H) in the thione-enol form in
[Cu(H2APET)(OAc)] (Structure III). This mode of complexation is
confirmed by: (i) the disappearance of the bands due to (C O)1
and (N1H) vibrations with simultaneous appearance of new bands
at 1180 and 1553 cm−1 assigned to ꢀ(C–O) and ꢀ(C N)*, respec-
tively, (ii) the weakness of the band due (N2H) vibration, (iii) the
increase of the frequency of ꢀ(N–N) is due to the increase in the
bond strength confirming the coordination via the azomethine

536
O.A. El-Gammal / Spectrochimica Acta Part A 75 (2010) 533–542
In [Cu(H2APET)(H2O)(NO3)] and [Cu2(HAPET)(NO3)2(H2O)2]
(Structures IV and V), H3APET behaves as NO mononegative
bidentate and ONNS binegative tetradentate, respectively. In the
first complex, the coordination takes place through (C–O)1 and
(N2H) groups. This is due to the disappearance of ꢀ(C O)1 and
ꢀ(N1H) with the appearance of new bands at 1635 and 1087 cm−1
assignable to ꢀ(C N*) and ꢀ(C–O)1, respectively and the shift of
ꢀ(N2H) to lower wavenumber. The spectrum of the second com-
plex showed that, the ligand coordinates in thiol-enol form via
(C–O)1, (C O)2, (C N*) and (C–S) groups. This is revealed by the
disappearance of ꢀ(C O)1, ꢀ(N1H), ꢀ(C S) and ꢀ(N2H) with the
appearance of bands at 1590, 1207, and 636 cm−1 attributed to
ꢀ(C N*–N C), ꢀ(C–O) and ꢀ(C–S) vibrations, respectively. More-
over, the spectra of the two complexes exhibit two bands at
1462 and 1349 cm−1 for the former and 1482 and 1351 cm−1
for the later assignable to ꢀ5(NO3) and ꢀ1(NO3) with difference
(ꢂꢀ < 150 cm−1) supporting the unidentate nature of the nitrate
group [36].
The spectrum of [Cu(H2APET)(ClO4)(H2O)] (Structure VI)
showed that H3APET acts as NO donor via (C–O)1 and (C N)*.
The bands at 1085, 649 and 922 cm−1 due to ꢀ3(ClO4), ꢀ4(ClO4)
and ꢀ1(ClO4) suggest the weak coordinated perchlorate ion
[34]. Finally, the ligand showed a binegative tridentate behav-
ior in [Cu(HAPET)(H2O)] (Structure VII) coordinating via (C–O)2,
(C N*) and (C–S). This is supported by the disappearance
of bands due to (C O)2, (N1H), (N2H) and (C S) vibrations
suggesting enolization of (C O)2 and thioenolization of (C S)
with appearance of new bands at 1600, 1238 and 632 cm−1
assignable to ꢀ(C N)*, ꢀ(C–O)1 and ꢀ(C–S) vibrations, respec-
tively. The IR spectra of the complexes exhibit broad band
around 3400 cm−1, assignable to the stretching modes of water
molecules.

O.A. El-Gammal / Spectrochimica Acta Part A 75 (2010) 533–542
537
3.3. Electronic spectra and magnetic moments
(II) centers in the solid state is negligible, whereas when it is less
than 4, a considerable exchange interaction is indicated in the solid
complex. The calculated G values for the copper complexes except
[Cu(H2APET)Br]·2H2O are less than 4 suggesting copper–copper
exchange interactions. A forbidden magnetic dipolar transition for
[Cu(H2APET)Br]·2H2O and [Cu2(HAPET)(NO3)2(H2O)2] is observed
at half-field (ca. 1600 G, g ≈ 4.0) but the intensity is very weak. The
present ESR spectra are similar to the ESR spectra of the reported
binuclear Cu(II) complexes [43]. The appearance of the half-field
signal confirms that the complex, [Cu2(HAPET)(NO3)2(H2O)2] has
a binuclear unit that there exist a magnetic interaction between
the two Cu(II) ions and in accordance with the subnormal effective
magnetic moment.
The ESR spectra of [Cu(H2APET)Br]·2H2O and [Cu2(HAPET)-
(NO3)2(H2O)2] exhibit broad single line, nearly isotropic signal
centered at g = 2.07 and 2.09, respectively, (Fig. 1) is attributable
to dipolar broadening and enhanced spin lattice relaxation
[44]. This line broadening is probably due to insufficient spin-
exchange narrowing toward the coalescence of four copper
hyperfine lines to a single line. Note that, the same kind of
powder ESR line shapes; have also been observed for many
tetrahedral or square planar binuclear Cu(II) complexes with
The magnetic moments and the electronic absorption bands
of H3APET and its Cu(II) complexes, in Nujol mull, are listed
in Table 3. The electronic spectra of the complexes are domi-
nated by intense intra-ligand charge transfer bands. The electronic
spectrum of the ligand showed ␲ → ␲* and n → ␲* bands
in the range 25380–28735 cm−1. Large change is observed in
the spectra of its complexes with
a
new n → ␲* band at
25577–27322 cm−1. The charge transfer band assigned to S → Cu
transition [37,38] in [Cu(H2APET)Br]·2H2O, [Cu(H2APET)(OAc)],
[Cu2(HAPET) (NO3)2(H2O)2] and [Cu(HAPET)(H2O)] is shifted to
higher energies (23041–26315 cm−1) possibly due to the coordi-
nation via S atom. The spectrum of [Cu(HAPET)Br]·2H2O, exhibits
a band at 21459 cm−1 assigned to Br → Cu(II) [39,40] transition
supporting the coordination via terminal bromo ligand to Cu(II)
atom. The d–d bands (16611–14045 cm−1) appear as broad or weak
shoulders in the tail of CT bands are consistent with four coordinate
species.
The ꢃeff values of the mononuclear Cu(II) complexes are normal
within the range reported for one unpaired electron in a tetrahedral
or square-planer geometry. However, it is impossible to differ-
entiate between these two geometries on the basis of electronic
spectra. Hence, may be distinguished on the basis of EPR spectra.
On the other hand, the subnormal value (1.43 BM) of the binu-
clear complex, [Cu2(HAPET)(NO3)2(H2O)2], reveals a strong Cu–Cu
interaction.
a
considerably strong intranuclear spin-exchange interaction
[45].
An index of the increase of the tetrahedral distortion in the coor-
dination sphere of copper is the decrease of A with the increase
||
of g [46]. To quantify the degree of distortion of the Cu(II) com-
plexes, the f-factor g /A was calculated which is considered as
||
|| ||
3.4. Electron spin resonance
an empirical index of tetrahedral distortion [47]. Its value ranges
between 105 and 135 for square planar complexes, depending on
the nature of the coordinated atoms. In the presence of a distorted
tetrahedral structure, the values can be much larger [46]. In case of
[Cu(H2APET)(OAc)] and [Cu(H2APET)(H2O)] the values are 136 and
156, respectively, demonstrating the presence of significant dihe-
dral angle distortion in the xy-plane and indicating a tetrahedral
distortion from square planar geometry and the results are con-
sistent with distorted tetragonal geometry around the copper site.
Molecular orbital coefficients, ˛2 (a measure of the covalency of
the in-plane ␴-bonding between a copper 3d orbital and the ligand
orbitals) and ˇ2 (covalent in-plane ␲-bonding), were calculated by
using the following equations [47–49]:
To obtain further information about the stereochemistry and
the site of the metal ligand bonding and to determine the magnetic
interaction in the metal complexes, ESR spectra of the complexes
were recorded in the solid state. The spin Hamiltonian parameters
of the complexes were calculated and summarized in Table 4.
The room temperature solid state ESR spectra of the copper
complexes exhibit an axially symmetric g-tensor parameters with
g > g >2.0023 indicating that the copper site has a d
state characteristic of square planar or octahedral stereochemistry
ground-
2
2
||
⊥
x
−y
[41]. In axial symmetry, the g-values are related by the expres-
sion, G = (g − 2)/(g⊥ − 2) = 4. According to Hathaway [42], as value
||
of G is greater than 4, the exchange interaction between copper

538
O.A. El-Gammal / Spectrochimica Acta Part A 75 (2010) 533–542
Table 3
Magnetic moments and electronic spectral data of Cu(II) complexes.
Complex
ꢃeff (BM)
d–d transition (cm−1
)
Charge transfer bands (cm−1
)
[Cu(H2APET)Br]·2H2O
[Cu(H2APET)(OAc)]
[Cu(HAPET)(H2O)]
[Cu2(HAPET)(NO3)2(H2O)2]
[Cu(H2APET)(NO3)(H2O)]
[Cu(H2APET)(ClO4)(H2O)]
1.70
2.00
1.76
1.43
2.00
2.04
14045
16611
15720
16555
16340
15975
25770, 21460
20570, 24155
26315, 20492
23695, 20745
20745, 25168
20900, 23041
Table 4
ESR data of the some Cu(II) complexes at room temperature.
2
Complex
g
||
g
⊥
A
|| × 10−4 cm−1
G
g /A
˛
ˇ2
||
||
[Cu(H2APET)Br]·2H2O
[Cu2(HAPET)(NO3)2(H2O)2]
[Cu(H2APET)(OAc)]
2.30
2.34
2.25
2.19
2.07
2.09
2.10
2.06
–
–
165
140
4.287
3.70
2.20
3.10
–
–
136
156
–
–
0.78
0.64
–
–
0.79
0.70
[Cu(HAPET)(H2O)]
ꢀ
ꢁ
The values of ˛2 and ˇ2 for the complexes indicate that the in-
plane ␴-bonding and in-plane ␲-bonding are appreciably covalent,
and are consistent with very strong in-plane ␴-bonding in these
complexes. For the copper (II) complexes, the high values of ˇ2
compared to ˛2 indicate that the in-plane ␲-bonding is less cova-
lent than the in-plane ␴-bonding. These data are well consistent
with other reported values [48–51].
A
3
7
||
2
˛
=
=
+ (g|| − 2.0023) + (g⊥ − 2.0023) + 0.04
(1)
(2)
0.036
(g|| − 2.0023)E
ˇ2
−8ꢄ˛2
where ꢄ = −828 cm−1 for the free copper ion and E is the electronic
transition energy. The covalency of the in-plane ␴-bonding, ˛2 = 1
indicates complete ionic character, whereas ˛2 = 0.5 denotes 100%
covalent bonding, with the assumption of negligibly small values
of the overlap integral. The ˇ2 parameter gives an indication of the
covalency of the in-plane ␲-bonding. The smaller the ˇ2 the larger
is the covalency of the bonding.
3.5. Thermogravimetric studies
The stages of decomposition, temperature range, decomposi-
tion product as well as the weight loss percentages of H3APET and
its Cu(II) complexes are given in Table 16S. A glance at Table 16S
Fig. 1. ESR spectra of (a) [Cu(H2APET)Br]·2H2O, (b) [Cu2(HAPET)(NO3)2(H2O)2] (c) [Cu(H2APET)(OAc)] and (d) [Cu(HAPET)(H2O)] at room temperature.

O.A. El-Gammal / Spectrochimica Acta Part A 75 (2010) 533–542
539
Table 5
Kinetic parameters evaluated by Coats–Redfern equation.
Compound
H3APET
Stage
Temp. range (K)
Ea (kJ/mol)
A (s−1
)
ꢂH (kJ/mol)
ꢂS (kJ/mol K)
ꢂG (kJ/mol)
1st
2nd
504–540
564–588
567.21
431.08
2.86 × 1055
562.92
426.28
0.8121
0.4660
143.03
157.35
2.67 × 1037
1st
2nd
3rd
352–376
532–569
602–635
242.97
381.87
328.42
2.25 × 1033
4.70 × 1034
7.05 × 1025
239.95
377.31
323.30
0.3919
0.4138
0.2439
97.83
150.22
173.13
[Cu(H2APET)Br·2H2O
1st
2nd
513–555
560–634
192.04
115.84
4.97 × 1016
187.66
110.95
0.0699
−0.0968
150.72
168.06
[Cu(H2APET)(OAc)]
1.07 × 108
[Cu(H2APET)(H2O)]
[Cu2(HAPET)(NO3)2(H2O)2]
1st
1st
580–625
587–693
79.79
92.86
1.44 × 105
1.71 × 105
75.32
87.71
−0.1511
−0.1510
156.59
181.12
1st
2nd
530–567
567–627
443.57
144.24
1.28 × 1040
438.97
139.25
0.5177
−0.0492
152.40
168.74
[Cu(H2APET)(NO3)(H2O)]
[Cu(H2APET)(ClO4)(H2O)]
3.37 × 1010
1st
381–435
524–606
606–650
652–831
64.00
161.97
565.99
312.23
1.89 × 106
3.00 × 1012
2.46 × 1046
7.60 × 1018
60.67
157.19
560.88
305.78
−0.1272
−0.0115
0.6370
111.52
163.81
169.02
221.51
2nd
3rd
4th
0.1085
indicates that thermal stability of H3APET increases on complex
formation. Also, [Cu(H2APET)Br]·2H2O complex has the lowest sta-
bility which may be attributed to low electronegative nature of
the bromide ion. On the other hand, [Cu(H2APET)(ClO4)(H2O)]
complex shows the greatest stability may be ascribed to greater
heat resistance character of ClO4 linkage compared with those
of other inner sphere inorganic ligands [52–54]. The TG data
of [Cu(H2APET)Br]·2H2O shows the first stage at 44–113 ◦C with
weight loss of 8.1 (Calcd. 8.2%) corresponding to the loss of the
two lattice water molecules. The second step with weight loss
of 38.5 (Calcd. 38.8%) at 259–296 ◦C is attributed to the elimina-
tion of C6H6N + Br. The third step at 270–483 ◦C with weight loss
of 16.8 (Calcd. 16.4%) is referring to the removal of CO + C2H7N.
The residual part is CuCON2S (Found 34.8, Calcd. 34.1%). The
[Cu(H2APET)(NO3)(H2O)] showed a thermal stability till 230 ◦C
where the first decomposition stage in the range 530–567 with
weight loss of 49.8 (Calcd. 49.2%) was observed and attributed to
the removal of C6H7N, NO3, H2O, CO fragments. The next decompo-
sition step with weight loss of 21.0 (Calcd. 21.6%) is corresponding
to elimination of C2H6N, CS at 295–354 ◦C. A plateau is obtained at
355–800 ◦C which referring to the formation of CuCON2. In case of
[Cu(H2APET)(ClO4)(H2O)], four degradation steps were observed,
the first with weight loss of 3.4 (Calcd. 3.5%) corresponds to the
removal of coordinated water at 108–162 ◦C. The second step at
251–333 ◦C represents the loss of C6H6N, CO. The ClO4 may be elim-
inated in the third decomposition step at 334–377 ◦C with weight
loss of 22.3 (Calcd. 22.4%). This is followed by the removal of CO,
CS species with weight loss of 16.0 (Calcd. 16.2%) at 378–558 ◦C. A
plateau is obtained (558–800 ◦C) which referring to the formation
of CuCON2. It is clear that, the high residual part of the studied com-
plexes reflects a higher thermal stability owing to the existence of
five membered rings.
3.6. Kinetic data
The kinetic and thermodynamic parameters of thermal degra-
dation process have been calculated using Coats–Redfern and
Horowitz–Metzger models [55,56]. Coats–Redfern relation is as fol-
lows:
ꢂ
ꢃ
ꢀ
ꢁ
ln(1 − ˛)
AR
ˇE
E
ln
−
= ln
−
(3)
T2
RT
where ˛ represents the fraction of sample decomposed at time
t, defined by: ˛ = (wo − wt)/(wo − w ), wo, wt and w are the
∞
∞
weight of the sample before the degradation, at temperature t and
after total conversion, respectively. T is the derivative peak tem-
perature. ˇ is the heating rate = dT/dt, E and A are the activation
energy and the Arrhenius pre-exponential factor, respectively. A
plot of ln[−(ln(1 − ˛))/T2] versus 1/T gives a straight line whose
slope (E/R) and the pre-exponential factor (A) can be determined
from the intercept.
Table 6
Kinetic parameters evaluated by Horowitz–Metzger equation.
Compound
H3APET
Stage
Mid temp. (K)
Ea (kJ/mol)
A (s−1
)
ꢂH (kJ/mol)
ꢂS (kJ/mol K)
ꢂG (kJ/mol)
1st
2nd
517
577
563.34
438.83
2.86 × 1056
559.04
434.04
0.6863
0.4799
204.22
157.11
1.41 × 1038
1st
2nd
3rd
362.6
548.8
615.7
244.18
387.84
330.62
5.59 × 1033
2.30 × 1035
1.96 × 1026
241.17
383.29
325.49
0.3995
0.4263
0.2524
96.29
149.31
170.10
[Cu(H2APET)Br]·2H2O
1st
2nd
527.9
589.8
191.08
122.54
1.09 × 1017
186.62
117.64
0.0765
−0.0839
146.22
167.18
[Cu(H2APET)(OAc)]
5.03 × 108
[Cu(H2APET)(H2O)]
[Cu2(HAPET)(NO3)2(H2O)2]
1st
1st
538
619.4
79.08
94.51
2.61 × 105
4.61 × 105
74.60
89.36
−0.1461
−0.1426
153.22
181.12
1st
2nd
553.5
599.8
446.09
154.13
3.68 × 1040
441.15
149.14
0.5265
−0.0333
150.06
169.12
[Cu(H2APET)(NO3)(H2O)]
[Cu(H2APET)(ClO4)(H2O)]
2.27 × 1011
1st
403
575
615
776
71.26
165.42
571.49
319.61
1.80 × 107
1.07 × 1013
1.05 × 1047
3.48 × 1019
67.93
160.64
566.38
313.16
−0.1080
−0.0009
0.6492
111.31
161.18
167.08
219.08
2nd
3rd
4th
0.1210

540
O.A. El-Gammal / Spectrochimica Acta Part A 75 (2010) 533–542
The Horowitz–Metzger relation used to evaluate the degrada-
Thermodynamic parameters such as activation energy (E), pre-
tion kinetics is:
exponential factor (A), entropy of activation (ꢂS), enthalpy of
activation (ꢂH) and free energy of activation (ꢂG) of decom-
position steps were calculated using Coats–Redfern [55] and
Horowitz–Metzger [56] methods (Tables 5 and 6). In both meth-
ods, the lift side of Eqs. (3) and (4) are plotted against 1000/T and
ꢅ, respectively (Fig. 2). From the results, the following remarks can
be pointed out:
Eꢅ
RTs2
ln[− ln(1 − ˛)] =
(4)
where ꢅ = T − Ts, Ts is the DTG peak temperature, T is the temper-
ature corresponding to weight loss wt. A straight line should be
observed between ln[−ln(1 − ␣)] and ꢅ with a slope of E/RTs2. A
number of pyrolysis processes can be represented as a first order
reaction. Particularly, the degradation of a series of H3APET com-
plexes was suggested to be first order, therefore we assume n = 1
for the remainder of the present text. The other thermodynamic
parameters of activation can be calculated by Eyring equation [57]:
- The high values of the energy of activation, E of the complexes
reveals the high stability of such chelates due to their covalent
bond character [58].
- The positive sign of ꢂG for the investigated complexes reveals
that the free energy of the final residue is higher than that of
the initial compound, and all the decomposition steps are non-
spontaneous processes. Also, the values of the activation, ꢂG
increases significantly for the subsequent decomposition stages
of a given complex. This is due to increasing the values of TꢂS
ꢂH = E − RT
hA
(5)
(6)
(7)
ꢂS = R ln
kBT
ꢂG = ꢂH − TꢂS
Fig. 2. Coats–Redfern plots [a, b and c] and Horowitz–Metzger plots [d, e and f] of the first peak for (i) [Cu(H2APET)Br]·2H2O, (ii) [Cu(H2APET)(NO3)(H2O)] and (iii)
[Cu(H2APET)(ClO4((H2O)].

O.A. El-Gammal / Spectrochimica Acta Part A 75 (2010) 533–542
541
Table 7
Antimicrobial activities in terms of inhibition zone diameter (mm) of H3APET and its Cu(II) complexes.
Compound
Inhibition zone diameter (mm/mg sample)
E. coli (G+)
S. aures (G−
)
A. flavus (Fungus)
C. albicans (Fungus)
H3APET (1)
3.0
14.0
13.0
12.0
14.0
10.0
14.0
20.0
–
3.0
17.0
13.0
13.0
15.0
11.0
14.0
25.9
–
–
13.0
–
–
–
–
–
–
16.0
–
12.0
14.0
–
14.0
–
–
–
14.0
[Cu(H2APET)Br]]·2H2O (2)
[Cu(H2APET)(OAc)] (3)
[Cu(H2APET)(H2O)] (4)
[Cu2(HAPET)(NO3)2(H2O)2](5)
[Cu(H2APET)(NO3)(H2O)] (6)
[Cu(H2APET)(ClO4)(H2O)] (7)
Gentamycin
Diflucan
significantly from one step to another which overrides the values
of ꢂH [59].
Acknowledgement
- The negative values of ꢂS for [Cu(H2APTS)ClO4·H2O],
[Cu(H2APTS)(OAc)] and [Cu2(HAPTS)(NO3)2(H2O)2] indicate
more ordered activated complex than the reactants or the
reaction is slow [60].
The author wishes to express many thanks for the Microana-
lytical Unit of Cairo University for carrying out the antimicrobial
activity.
Appendix A. Supplementary data
3.7. Antimicrobial activity
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.saa.2009.11.007.
The biological activity of H3APET and its Cu(II) complexes
against two bacterial cultures viz., E. coli and S. aures and two fun-
gal cultures viz., C. albicans and A. flavus is summarized in Table 7. A
glance at the table indicates that the complexes exhibit moderate
inhibitory activity against bacteria E. coli and S. aures more than the
uncomplexed thiosemicarbazide following the order (i) against
S. aures; [Cu(H2APET)Br]·2H2O > [Cu2(HAPET)(NO3)2(H2O)2]
> [Cu(H2APTS)ClO4·H2O] > [Cu(H2APET)(OAc)] > [Cu(HAPET)(H2O)]
> [Cu(H2APET)(NO3)(H2O)] and (ii)the activity against E. coli is
in the order; [Cu(H2APET)Br]·2H2O > [Cu(H2APTS)ClO4·H2O]
> [Cu2(HAPET)(NO3)2(H2O)2] > [Cu(H2APET)(OAc)] > [Cu(HAPET)-
(H2O)] > [Cu(H2APET)(NO3)(H2O)], respectively. The inhibition
action of the complexes can be attributed to their inhibition of
the replication of DNA by interacting with enzyme prosthetic
group [61]. Though the complexes are found to ineffective against
the fungal culture A. flavus except [Cu(H2APET)Br]·2H2O complex
which shows potential inhibition activity. On the other hand,
the complexes, [Cu(H2APET)Br]·2H2O, [Cu(H2APET)(OAc)] and
[Cu2(HAPET)(NO3)2(H2O)2] are found to have better growth
inhibition activity against C. albicans.
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