Synthesis, spectral, characterization, and anticancer activity of some binary and mixed ligand complexes of 4-methyl-2-pentanone thiosemicarbazone and some amino acids

Article abstract of DOI:10.1080/10426500903241739

The Schiff base ligand 4-methyl-2-pentanone thiosemicarbazone (MPTSC) (HL) has been synthesized by the interaction of 4-methyl-2-pentanone (MP) and thiosemicarbazone (TSC). The Ni(II), Cu(II), and Fe(III) binary complexes of this ligand have been prepared. The ternary complexes of VO(IV) and Mn(II) ions with HL and glutamine (Glu) as a secondary ligand, in addition to VO(IV), Mn(II), and La(III) with HL and glycine (Gly) as a secondary ligand, have also been synthesized. The binary and ternary complexes have been characterized based on elemental analysis, IR, UV-VIS, molar conductance, mass spectra, magnetic moment, and ESR measurements. The magnetic moment, UV, and ESR studies suggest that Ni(II) and Cu(II) complexes are square planar, whereas Fe(III), Mn(II), and La(III) complexes have octahedral geometry, but VO(IV) ternary complexes have square pyramidal geometry. The analytical data indicate that the metal-to-ligand ratio in binary complexes is 1:1, except HL-Cu(II) chloride complex where the metal-to-ligand to secondary ligand ratio in ternary complexes is 1:1:1. The anticancer studies showed that the anticancer activity is in the decreasing order: ternary complexes > binary complexes > free ligand (HL). Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500903241739

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Phosphorus, Sulfur, and Silicon and the
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Synthesis, Spectral, Characterization,
and Anticancer Activity of Some Binary
and Mixed Ligand Complexes of 4-
Methyl-2-Pentanone Thiosemicarbazone
and Some Amino Acids
Nabil S. Youssef a , Eman A. El Zahany a & Mamdouh M. Ali b
a Inorganic Chemistry Department , National Research Centre ,
Dokki , Giza , Egypt
b Biochemistry Department , Division of Genetic Engineering and
Biotechnology, National Research Centre , Dokki , Giza , Egypt
Published online: 05 Nov 2010.
To cite this article: Nabil S. Youssef , Eman A. El Zahany & Mamdouh M. Ali (2010) Synthesis,
Spectral, Characterization, and Anticancer Activity of Some Binary and Mixed Ligand Complexes of 4-
Methyl-2-Pentanone Thiosemicarbazone and Some Amino Acids, Phosphorus, Sulfur, and Silicon and
the Related Elements, 185:11, 2171-2181, DOI: 10.1080/10426500903241739
To link to this article: http://dx.doi.org/10.1080/10426500903241739
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Phosphorus, Sulfur, and Silicon, 185:2171–2181, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500903241739
SYNTHESIS, SPECTRAL, CHARACTERIZATION, AND
ANTICANCER ACTIVITY OF SOME BINARY AND MIXED
LIGAND COMPLEXES OF 4-METHYL-2-PENTANONE
THIOSEMICARBAZONE AND SOME AMINO ACIDS
Nabil S. Youssef,1 Eman A. El Zahany,1 and Mamdouh M. Ali2
1Inorganic Chemistry Department, National Research Centre, Dokki, Giza, Egypt
2Biochemistry Department, Division of Genetic Engineering and Biotechnology,
National Research Centre, Dokki, Giza, Egypt
The Schiff base ligand 4-methyl-2-pentanone thiosemicarbazone (MPTSC) (HL) has been
synthesized by the interaction of 4-methyl-2-pentanone (MP) and thiosemicarbazone (TSC).
The Ni(II), Cu(II), and Fe(III) binary complexes of this ligand have been prepared. The
ternary complexes of VO(IV) and Mn(II) ions with HL and glutamine (Glu) as a secondary
ligand, in addition to VO(IV), Mn(II), and La(III) with HL and glycine (Gly) as a secondary
ligand, have also been synthesized. The binary and ternary complexes have been character-
ized based on elemental analysis, IR, UV-VIS, molar conductance, mass spectra, magnetic
moment, and ESR measurements. The magnetic moment, UV, and ESR studies suggest
that Ni(II) and Cu(II) complexes are square planar, whereas Fe(III), Mn(II), and La(III)
complexes have octahedral geometry, but VO(IV) ternary complexes have square pyramidal
geometry. The analytical data indicate that the metal-to-ligand ratio in binary complexes is
1:1, except HL-Cu(II) chloride complex where the metal-to-ligand to secondary ligand ratio
in ternary complexes is 1:1:1. The anticancer studies showed that the anticancer activity is
in the decreasing order: ternary complexes > binary complexes > free ligand (HL).
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental
file.
Keywords Amino acids; mixed ligands; thiosemicarbazone
INTRODUCTION
In recent decades, considerable studies have been carried out on the interaction
between various metal ions and ligands that takes place in biochemical processes.1 The bio-
logical importance of mixed ligand complexes is that they are sometimes more effective than
the free ligands.2 Also, amino acids and their compounds with different metal ions play
an important role in biology, pharmacy, and industry. Moreover, coordination chemists
have been interested for many years in the donor properties of amino acids as models
for metal–protein interaction, and recent studies have also emphasized the reactivity of
Received 23 April 2009; accepted 4 August 2009.
Address correspondence to Nabil S. Youssef, Inorganic Chemistry Department, National Research Centre,
Dokki, Giza, Egypt. E-mail: nabilyoussef@hotmail.com
2171

2172
N. S. YOUSSEF ET AL.
coordinated amino acid in the hope of finding simple and easily interpretable models for
the reactivity of some biological systems that contain metals. Furthermore, a great deal of
attention has been paid recently to the close relationships between metals, or their com-
plexes, and carcinogenesis, and some metal complexes are used in anticancer therapy. In
cancer chemotherapy, amino acids assume a remarkable importance,3 and when discussing
the possibility of introducing an amino acid into an anticancer drug, it is very important to
know whether the amino acid forms metal complexes, and in particular, any special metal
complexes. Furthermore, thiosemicarbazones and their complexes4–6 have received consid-
erable attention because of their potential therapeutic activities against bacterial and viral
infections,7,8 tuberculosis, 9 and leprosy.10 In addition, particular attention has been given to
their antitumor activity, which seems to be due to inhibition of DNA synthesis caused by a
modification in the reductive conversion of ribonucleotides to deoxyribonucleotides.11 The
interaction of metal complexes with DNA is an area of intense interest to both inorganic
chemists and biochemists.12 On the other hand, the importance of metal compounds in
medicine dates back to the 16th century with reports on the therapeutic use of metals or
metal-containing compounds in the treatment of cancer. Metal ions are electron-deficient,
whereas most biological molecules (proteins and DNA) are electron rich; consequently,
there is a general tendency for metal ions to bind to and interact with many important bio-
logical molecules. Metal ions also have a high affinity for many small molecules, e.g., O2,
that are crucial to life. These considerations alone have fueled much of the past and current
interest in developing novel means to use metals or metal-containing agents to modulate
biological systems.13
Moreover, the coordination chemistry of vanadium is of great current interest because
of the discovery of its presence in abiotic as well as biotic systems. Another important im-
petus to the coordination chemistry of vanadium in the context of medical applications
has arisen from ability of vanadium complexes to promote the insulin mimetic activity
pathophysiological state of diabetes mellitus in humans.14 Nickel species in various coordi-
nation environments are also of interest to inorganic biochemists. For instance, some nickel
complexes of thiosemicarbazone derivatives are observed to exhibit antitumor activity.15
Also, Cu(II), La(III), and Mn(II) complexes have found possible medical uses in the
treatment of many diseases including cancer.16–18
The first row transition metal ions occupy an important position due to the involvement
of these elements in various biological systems.18 Furthermore, some lanthanum complexes
possibly represent a new class of potential antitumor agent.17
RESULTS AND DISCUSSION
The structure of the ligand is shown in Figure 1. The quantities used are shown in
Table I. The elemental and physical data of the ligand HL and its complexes (Table II)
3
NH2
H
N
2
H3C
N
1
S
H9C4
(HL)
Figure 1 Structure of the ligand.

METHYL-2-PENTANONE THIOSEMICARBAZONE
2173
Table I Amounts of the reactants used in the formation of the metal complexes
Metal
chloride or
acetate in
ethanol
(10–20 mL)
Ligand HL in Glu or Gly in
ethanol (15
mL)
ethanol (10
mL)
Sodium
hydroxide
Mass
Mass
Mass
Mass
No.
Complex
Metal salt
(g) Mmol (g) Mmol (g) Mmol (g) Mmol
1
2
3
[Ni(HL)Cl2].H2O
[Cu(HL)2]Cl2.4H2O
[Cu(HL)(OH2)2]
NiCl2.6H2O 0.247 2.0 0.346 2.0
CuCl2.2H2O 0.340 2.0 0.692 4.0
Cu(Ac)2
0.364 2.0 0.346 2.0
(CH3COO)2·H2O
4
5
6
7
8
9
[Fe(HL)Cl2·H2O]
FeCl26H2O
0.540 2.0 0.346 2.0
[VO(Glu)(L)].5H2O
[Mn(Glu)(L)].H2O
[VO(Gly)(HL)].4H2O
[Mn(Gly)(HL)]Cl.2H2O
[La(Gly)(HL)Cl2].H2O
VOSO4. H2O 0.360 2.0 0.346 2.0 0.292 2.0
MnCl2.2H2O 0.322 2.0 0.346 2.0 0.292 2.0
VOSO4. H2O 0.360 2.0 0.346 2.0 0.150 2.0
MnCl2.2H2O 0.322 2.0 0.346 2.0 0.150 2.0
LaCl3.7H2O 0.500 2.0 0.346 2.0 0.150 2.0
0.16
0.16
0.16
0.16
0.16
4.0
4.0
4.0
4.0
4.0
show that the stoichiometry of the complexes obtained is 1:1, 1:2 (metal:ligand), and 1:1:1
(ligand:metal:AA).
Mass Spectra of Ligand HL and Its Complexes
The mass spectra of the free ligand HL and its binary and ternary complexes 1–9
exhibit the molecular ion peaks at m/e 173, 322, 554, 409, 354, 475, 391, 385, 408,
and 476, respectively, which confirm their proposed formulae. Their proposed pathway
fragmentation patterns are provided as supplemental files (Figures S1 and S2, respectively,
Supplemental Materials, available online).
IR Spectra
The main bands of the HL ligand and its complexes are summarized in Table S1
(Supplemental Materials). The spectrum of the free ligand HL shows bands at 1607, 1597,
and 853 cm−1, characteristic of δ NH2, υ C N, and υ C S groups, respectively. Also, the
absence of the υ S H band, suspected at about 2570 cm−1, indicates the thionic nature of
the ligand. The appearance of the δ NH at 3160 cm−1 gives further support for the existence
of the ligand in the thione form.
Moreover, the δ NH2 band of the ligand (1607 cm−1) remains at the same position,
1600–1610 cm−1, in all binary and ternary complexes, indicating that the NH2 group does
not participate in coordination in these complexes.19
The band of the azomethine group of the ligand at 1597 cm−1 shifts to higher or
lower frequencies20 in all binary and ternary complexes (1570–1647 cm−1). This band
appears as a broad one centered at 1612 cm−1 in the iron complex, suggesting coordination
of the azomethine nitrogen to the metal atom.20 Furthermore, the υ C S vibration in the
free ligand is either shifted or absent in all binary and ternary complexes, indicating the
involvement of a sulfur atom in coordination.21

2174

METHYL-2-PENTANONE THIOSEMICARBAZONE
2175
Coordination of the azomethine N to the metal ion is also suggested by occurrence of
the N–N band at higher wave numbers in all the studied complexes.22 These results indicate
the coordination of the thiosemicarbzone ligand to all metal ions in binary and ternary
complexes through the N azomethine and sulfur atoms as bidentate chelating agents.
On the other hand, it was found that many complexes of the metal–amino acid ligands
act as bidentate chelating agents that coordinate through the amino and carboxyl groups.23
A few cases are known in which the two carboxyl oxygens are bound to the metal in a
bidentate mode, leaving the amino group free, and this behavior takes place in the presence
of a bulky organic group bound to the metal.24
Also, the spectra of complex 3 showed the appearance of two characteristic bands
at 1525 and 1367 cm−1, attributed to asym(OCO) and sym(OCO), respectively, having the
separation value ꢂ(OCO) 158 cm−1, suggesting the ionic nature of the acetate.25
Combination and overt+one bands in the 2042–2110 cm−1 region of Glu and Gly amino
acids, characteristic of NH3 groups, are absent in the spectra of all ternary complexes,
except complex 5 where this band remains at the same position (2042 cm−1), indicating
coordination of the NH2 group in these complexes.26 Furthermore, the C O amide band
of the free Glu at 1686 cm−1 is unchanged in complexes 5 and 6, excluding participation of
the amide C O group in complexation. In addition, there are differences in the positions of
asym(OCO) and sym(OCO) stretching vibrations of the free amino acids and the complexes
consistent with the coordination of the carboxyl groups.
The ꢂυ(OCO) values for all the complexes except complex 5 are greater than the
ꢂυ(OCO) values found for the free amino acids. Such increase in the value of ꢂυ(OCO)
is indicative of monodentate coordination of the amino acid via the carboxyl group.25 In
the case of complex 5, the ꢂυ(OCO) becomes smaller as compared to that in the free Glu
acid, showing the bidentate chelation of the carboxylate group in this complex.25
1H NMR Spectra
The 1H NMR spectra of the free ligand HL in chloroform solution with assignments
are reported in the Experimental section. The hydrazinic proton (-N2H) of the free ligand
(HL) appears as a single broad peak at δ 8.56 ppm. The free thiosemicarbazone ligand
showed a singlet at δ 6.45 ppm assigned to the amino (N3H2) protons. Unfortunately, the
diamagnetic binary nickel complex 1 is insufficiently soluble in chloroform or in DMSO
to acquire a 1H NMR spectrum.
Magnetic, Electronic, and ESR Spectral Studies
The electronic spectra of the free ligand HL show three bands, 275, 290, and 310
nm, assigned to π→ π∗ and n→ π∗ in the free ligand,15 whereas the bands in the range
210–320 nm in the spectra of the amino acids can be assigned to n→ π∗ and π→ π∗
intraligand transitions associated to amino acids.27 The electronic spectra of HL and its
complexes and magnetic moment are shown in Table S2 and Figure S3 (Supplemental
Materials).
Structures of the Binary Complexes
The room temperature magnetic susceptibility data of the HL-Ni (II) complex shows
1
1
that this complex is diamagnetic and of low-spin with 1A1g→ A2g, 1A1g→ Eg transitions,

2176
N. S. YOUSSEF ET AL.
NH2
H
N
H3C
NH2
H
N
S
N
H3C
H9C4
H9C4
Cu
Cl2.4H2O
N
S
.H2O
H9C4
Ni
N
S
H3C
Cl
Cl
N
H
NH2
2
1
NH2
SH
NH2
SH
N
H3C
N
H3C
N
N
.(CH3COO)2.H2O
H9C4
H9C4
Fe
Cl
H2O
Cl
Cu
OH2
H2O
Cl
3
4
Figure 2 Structure of binary complexes 1–4.
respectively.23 This complex is of square-planar geometry because it is diamagnetic and
there is no band seen below 1000 nm.28
The two Cu complexes have a magnetic moment value of 1.80 and 1.88 BM, respec-
tively, corresponding to the presence of one unpaired electron.29
The spectrum of the binary copper complex 2 (Figure 2) shows bands at 705 and
2
2
560 nm, which are assigned to the 2B1g → A1g and 2B1g → Eg transitions, respectively,
while the absorption band pointed at 370 nm is assignable to charge transfer transition.30
The spectrum of copper complex 3 (Figure 2) shows a band at 420 nm assignable to the
charge transfer.31
The X-band ESR spectra of the polycrystalline samples of the copper complexes are
recorded at room temperature (298 K). The ESR spectra of these complexes are of axial
shape with g11 › g › 2.0023, characteristic for complexes with 2β1(d x -y2) ground state in
2
⊥
agreement with the square planar environment of the copper. Both complexes exhibit g11
‹ 2.3, suggesting covalent character of the copper ligand bonding in these complexes. The
axial symmetry parameter G = (g11–2)/(g –2), which measures the exchange interaction
⊥
between copper centers in the polycrystalline solid sample of the complex, have also been
calculated. According to Hathaway and Billing,32 if the value of G is above 4, then the
exchange interaction is negligible; if, however, the value of G is less than 4, it indicates
considerable exchange interaction in the solid complexes. In the complexes reported here,
the G value is greater than 4, indicating that interaction is negligible.
Also, the electronic spectra of the iron complex 4 shows charge transfer at 360 nm
between the ligand and the metal. In general, the electronic spectra of Fe(III) complexes
consist of forbidden transitions, and hence weak bands are often marked charge transfer
bands.33–35 The magnetic moment of this iron (III) complex is 5.82 BM, and it is expected

METHYL-2-PENTANONE THIOSEMICARBAZONE
2177
NH2
NH2
N
N
H3C
H3C
O
V
N
S
N
S
H9C4
H9C4
.H2O
Mn
.5H2O
O
O
H2N
O
C
C
H2NCOCH2H2C
C
H2
H
O
H2N H
CH2CH2CONH2
5
6
NH2
H
NH2
H
N
N
H3C
H9C4
H3C
O
V
S
N
N
S
H9C4
H2O
H2N
OH2
O
Mn
.4H2O
H2N
Cl. 2H2O
O
C
H2
C
O
H2
O
7
8
NH2
H
N
H3C
N
S
H9C4
Cl
La
Cl
.H2O
O
H2N
C
H2
O
9
Figure 3 Structure of ternary complexes 5–9.
that the Fe(III) complex is a high-spin octahedral arrangement (t2g3eg2), where the literature
magnetic moment values is around 5.92 BM.
Structures of the Ternary Complexes
The electronic spectra of vanadium complexes 5 and 7 (Figure 3) show broad bands
2
at 860 and 840 nm, for the two complexes, respectively, which may be assigned to B2
2
2
→ E transition, while the other band due to 2B2 → B1 transition disappeared due to the
broadness of the first band.36 Also, the magnetic moments of these complexes are 1.58
and 1.62 BM, respectively, which confirms that vanadium ions are in the V(IV) state with
square-pyramidal geometry.37 However, the electronic spectra of Mn complexes 6 and 8
show broad bands at 430 and 360 nm, respectively, with their tail to the UV region. These
bands, attributable to the spin forbidden d–d transition, are responsible for the color of the

2178
N. S. YOUSSEF ET AL.
compound.38 The magnetic moments of the two Mn(II) complexes are 5.85 and 5.90 nm,
respectively, corresponding to high-spin configuration due to five unpaired electrons39 in
ground state 6S (6A1), in which orbital contribution to the magnetic moment is quenched.
The diamagnetic of lanthanum complex 9 has octahedral geometry.
Molar Conductance Data
The metal complexes discussed in this article were dissolved in DMF, and the molar
conductivities of 10−3 M of their solutions at room temperature were measured to establish
the charge of the metal complexes. The conductance data (Table S2) indicate that all binary
and ternary complexes, except complexes 2, 3, and 8, have conductivity values in the range
characteristic for the non-electrolytic nature, suggesting that these complexes are neutral,40
whereas copper and manganese complexes have molar conductance of 69.10, 87.42, and
52.9 ꢁ−1 cm2 mol−1, respectively, which indicates that the chloride ion and acetate groups
are uncoordinated.
The molar conductance of complex 2 in DMF is 69.1 Ω−1cm2 mol−1. Abnormally
low conductance value is usually attributed to ion-pair formation resulting from coulombic
interactions or to the formation of an intra- or intermolecular hydrogen bond between the
counter ion and the imino groups.41,42
Biological Activity
As shown in Table S3 (Supplemental Materials), compounds HL (free ligand) and
complexes 1, 5, 6, 7, and 9 inhibited in dose-dependent manner Ehrlich ascites carcinoma
(EAC) cells, being observed only for the maximum dose of 25 µg/mL.
The results showed that all six compounds studied have anticancer activity, and
the GI50 values for these compounds were 21.25, 20.5, 26.25, 17.5, 17.5, and 18 µM,
respectively, where the free ligand has minimum antitumor activity that increases in case of
the binary complex 1 at 25 µg/mL concentration. This may be attributed to the lipophilic
character of the central metal atom explained by Tweedy’s chelation theory.43
Also, the ternary complexes 5, 6, 7, and 9 showed greater antitumor activity than the
free ligand and the binary complex 1 at all concentrations when free amino acids (Glu and
Gly) were introduced as secondary ligands.
It should be noted that mixed ligand complexes have a key role in biological chem-
istry44 because the mixed chelation occurs commonly in biological fluids, as millions of
potential ligands are likely to compete for metal ions in vivo.40 These create specific struc-
tures44–46 and have been implicated in the storage and transport of active substances through
membranes. On the other hand, the complex 5 has more antitumor activity than complex 7,
while the complex 6 showed greater antitumor activity than complex 9 at all concentrations
except at 20 µg/mL. This may be explained on the basis that the antiproliferative activity
on tumor cells increases with the increase of the alkyl chain greater than 3 carbon atoms.
Moreover, it was found that antiproliferative activity of the amide group in Glu is greater
than the antiproliferative activity of COOH in free Gly acid.47
We can conclude that the two ternary vanadyl complexes 5 and 7 have maximum
antitumor activity, which may be due to the fact that vanadyl (IV) is capable of undergoing
spontaneous oxidation to vanadate (V) in vivo.48 Also, studies on antitumor activities of

METHYL-2-PENTANONE THIOSEMICARBAZONE
2179
vanadium compounds have been reviewed extensively.49 Vanadium compounds seem to ex-
ert their antitumor effects mainly through inhibition of cellular protein tyrosine phosphates
(PTPs) and/or activation of protein tyrosine kinases (PTKs). Both effects activate signal
transduction pathways, leading either to apoptosis and/or to activation of tumor suppressor
genes.
CONCLUSION
Metal complexes were prepared by the reaction of HL and metal salts in 1:1, 1:2,
or 1:1:1 molar ratios, and their structures were proposed from analytical and spectral data.
The biological results suggest that the tested compounds could be used as an alternative
to synthetic chemotherapeutic agents. The anticancer activity is in the decreasing order:
ternary complexes > binary complexes > the ligand.
EXPERIMENTAL
Materials
All the chemicals used were of A.R. grade. They include 4-methyl-2-pentanone
[(CH3)2CH.CH2COCH3], glycine H2NCH2COOH, vanadyl sulfate VOSO4·H2O, ferric
chloride FeCl3.6H2O (BDH), manganese chloride MnCl2.2H2O (Prolabo), thiosemi-
carbazide NH2CSNHNH2, lanthanum chloride LaCl3.7H2O, copper acetate (Aldrich),
nickel chloride NiCl2.6H2O, copper chloride CuCl2.2H2O (Merck), and glutamine
HOOC CH(NH2) CH2 CH2CONH2 (LOBA chemi). The organic solvents used,
including absolute ethyl alcohol, methyl alcohol, diethyl ether, and dimethyl sulfoxide
(DMSO), were purchased from Merck or Sigma.
Measurements
All the analytical and spectral data were carried out at Central Services Laboratory
in the National Research Center, Dokki, Giza, Egypt. The electronic spectra of the ligands
and their complexes were carried out using T80+UV/VI spectrometer PG instruments
LTD 190–1000. The IR spectra of the ligands and their complexes were measured using
1
a Nexus 670. The H NMR spectra were recorded in chloroform using a JNM-EX270
FT NMR system. The mass spectra were measured with a Jeol JMS-AX500. Molar con-
ductivities in DMF at 25◦C were recorded using a model CM-1K-TOA company (Japan)
conductivity meter. Magnetic moments at 25◦C were determined using the Gouy method
with Hg[Co(SCN)4] as calibrant. Antitumor activity was performed in the National Cancer
Institute of Cairo University. The solid ESR spectra of the complexes were recorded with
an ELEXSYS E5OO Bruker spectrometer in 3-mm Pyrex tubes at 298 K. Diphenylpicryl
hydrazine (DPPH) was used as a g-marker for the calibration of the spectra.
Synthesis of the Ligand
A warm solution of 4-methyl-2-pentanone thiosemicarbazone (MPTSC) (10 g,
0.1 mol) in ethyl alcohol (10 mL) was added to a warm solution of thiosemicarbazide
(9.1 g, 0.1 mol) in ethyl alcohol (50 mL), and then 5 drops of concentrated H2SO4 acid
were added. The mixture was then refluxed at 50◦C for about 20 h, and was evaporated to

2180
N. S. YOUSSEF ET AL.
concentrate the solution where a white precipitate was formed. The precipitate was filtered,
washed with ethyl alcohol, then with diethyl ether, and dried under vacuum over anhydrous
CaCl2.
1H NMR: δ 8.56 ppm (N2H), δ 6.45 ppm (N3H2), δ 0.86 ppm (CN1-CH3) and δ 4.78,
2.11, 0.92 ppm (CH, CH2, 2CH3; C-C4H9).
Syntheses of the Metal Complexes
The metal complexes of the ligand HL were prepared by mixing a hot ethanolic solu-
tion of the NiCl2.6H2O, CuCl2.2H2O, Cu(Ac)2, FeCl2.6H2O, VOSO4·H2O, MnCl2.2H2O,
and LaCl3.7H2O with the required amount of a hot ethanolic solution of the ligand to form
1:1 or 1:2 M/L (metal/ligand) complexes, or in the presence of glycine (Gly) or glutamine
(Glu) as a secondary ligand, as shown in Table I. The reaction mixture was then refluxed
for a time depending on the transition metal salt used. Some complexes (5, 6, 7, 8, and 9)
did not separate upon standing, but only when an aqueous NaOH solution was added under
stirring at 40–50◦C. The precipitates formed were filtered, washed with ethanol, then with
diethyl ether, and dried in a vacuum desiccator over anhydrous CaCl2.
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