Synthesis, characterization, and antitumor activity of some metal complexes with schiff bases derived from 9-fluorenone as a polycyclic aromatic compound

Article abstract of DOI:10.1080/10426500802080444

New bidendate Schiff base ligands HL1 [(9H-fluorene-9-ylidene)- thiosemicarbazide], HL2 [(9H-fluorene-9-ylidene)semicarbazide] and L3 [N1,N2-di(9H-fluorene-9-ylidene)ethan-1,2-diamine] derived from the condensation of thiosemicarbazide, semicarbazide, and ethylenediamine with 9-fluorenone as polycyclic aromatic compound (PAC). Ag(I), Cu(II), VO(IV), La(III), and Zn(II) of the ligands HL1, HL2, and L3 have been prepared and characterized by conductance and magnetic measurements, and electronic, infrared, and 1H NMR spectral data. Tetrahedral structures are suggested for Ag (I) with HL1, HL2, and L3, whereas Cu(II)-HL1 and VO(IV)-HL2 have octahedral and square-planar structures, respectively. The Erlich antitumor activity in vivo (E. A. A.) have been studied and showed that the free ligands L3, HL2, and its VO(IV)-HL2 complex are the most active in the inhibition of cell viability, whereas the ligands HL1, La(III) -L3, and Cu(II)-HL1 are the least active ones.

Full text of DOI:10.1080/10426500802080444

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Phosphorus, Sulfur, and Silicon
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Synthesis, Characterization,
and Antitumor Activity of
Some Metal Complexes with
Schiff Bases Derived from 9-
Fluorenone as a Polycyclic
Aromatic Compound
a
a
Nabil S. Youssef , Eman A. El Zahany , Manal M.
b
b
Anwar & Sohair A. Hassan
a
Inorganic Chemistry Department, National
Research Centre , Dokki , Giza , Egypt
b
Medicinal Chemistry Department, National
Research Centre , Dokki , Giza , Egypt
Published online: 19 Dec 2008.
To cite this article: Nabil S. Youssef , Eman A. El Zahany , Manal M. Anwar & Sohair
A. Hassan (2008) Synthesis, Characterization, and Antitumor Activity of Some Metal
Complexes with Schiff Bases Derived from 9-Fluorenone as a Polycyclic Aromatic
Compound, Phosphorus, Sulfur, and Silicon and the Related Elements, 184:1, 103-125,
DOI: 10.1080/10426500802080444
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Phosphorus, Sulfur, and Silicon, 184:103–125, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802080444
Synthesis, Characterization, and Antitumor Activity of
Some Metal Complexes with Schiff Bases Derived from
9-Fluorenone as a Polycyclic Aromatic Compound
1
1
2
Nabil S. Youssef, Eman A. El Zahany, Manal M. Anwar,
2
and Sohair A. Hassan
Inorganic Chemistry Department, National Research Centre,
1
Dokki, Giza, Egypt
2
Medicinal Chemistry Department, National Research Centre,
Dokki, Giza, Egypt
New
bidendate
Schiff
base
ligands
HL1
[(9H-fluorene-9-ylidene)-
2
3
1
2
thiosemicarbazide], HL [(9H-fluorene-9-ylidene)semicarbazide] and L [N ,N -
di(9H-fluorene-9-ylidene)ethan-1,2-diamine] derived from the condensation of
thiosemicarbazide, semicarbazide, and ethylenediamine with 9-fluorenone as
polycyclic aromatic compound (PAC). Ag(I), Cu(II), VO(IV), La(III), and Zn(II)
of the ligands HL , HL , and L have been prepared and characterized by
conductance and magnetic measurements, and electronic, infrared, and H NMR
spectral data. Tetrahedral structures are suggested for Ag (I) with HL , HL ,
and L , whereas Cu(II)-HL and VO(IV)-HL have octahedral and square-planar
structures, respectively. The Erlich antitumor activity in vivo (E. A. A.) have been
studied and showed that the free ligands L , HL , and its VO(IV)-HL complex
are the most active in the inhibition of cell viability, whereas the ligands HL ,
1
2
3
1
1
2
3
1
2
3
2
2
1
3
1
La(III) -L , and Cu(II)-HL are the least active ones.
Keywords Antitumor activity; 9-fluorenone; polycyclic aromatic compound; semicar-
bazide; thiosemicarbazide
INTRODUCTION
Thiosemicarbazones and their metal complexes have been the subject
of extensive investigations, not only because of their potential phar-
macological properties,1−5 but also their wide variation in their mul-
tifunctional coordination modes of bonding and stereochemistry. How-
ever, semicarbazones are also reported to possess versatile structural
2
6,7
features, and antifungal and antibacterial properties. The biological
Received 14 January 2008; accepted 14 February 2008.
Address correspondence to Nabil S. Youssef, Inorganic Chemistry Department,
National Research Centre, Dokki, Giza, Egypt. E-mail: nabilyoussef@hotmail.com
103

104
N. S. Youssef et al.
N
NH
C
X
NH2
1
2
FIGURE 1 Structure of ligands of HL (X=S), HL (X=O).
activity of these compounds may come from their interaction with po-
8
−10
tential donors of biological heterocyclic in vivo.
Recently, the inter-
est in the studies of semicarbazones is due to their unusual coordination
modes when bound to metals, high pharmacological potentiality, and
good chelating property.
The use of PACS and their derivatives as anticancer agents has been
1
1,12
explored.
These studies mainly focused on the synthesis of the poly-
cyclic ring systems and the examination of their metabolic activation
within target cells. In addition, the structure–activity relationship of
PACs as anticancer agents were studied, because the anticancer agents
revealed two common structural features: They have a planar ring sys-
1
3
tem and a basic-side chain group.
The coordination chemistry of transition metals, particularly that
of vanadium, has received considerable attention. Vanadium biological
importance includes potent cytotoxic activity against human cancer
1
4
cells.
In the present study, we describe the synthesis and characterization
1
2
3
of HL , HL , and L ligands (Figures 1 and 2) and their metal complexes
with Ag(I), Cu(II), VO(IV), La (III), and Zn(II) ions, together with the
examination of their antitumor activity.
EXPERIMENTAL
Chemicals
All chemicals used were of highest available purity. They included
9-fluorenone, semicarbazide hydrogen chloride, thiosemicarbazide,

Antitumor Activity of Some Metal Complexes
105
H C CH2
2
N
N
FIGURE 2 Structure of ligand L3.
lanthanum chloride LaCl3.7H2O, zinc chloride ZnCl2 and silver nitrate
AgNO3 (Merck), copper acetate Cu(Ac)2 (Aldrich), vanadyl sulphate
VOSO4.H2O (BDH), and ethylenediamine (Rasayan). Organic solvents
used, including absolute ethyl alcohol, methyl alcohol, diethyl ether,
and dimethyl sulfoxide (DMSO), were purchased from Merck or Sigma.
Measurements
All melting points were determined on electrothermal melting point ap-
paratus and were uncorrected. All the analytical and spectral data were
carried out at the Microanalytical Center, Cairo University. The in-
frared spectra were carried out using BRUKER VECTOR2 (Germany).
1
The H NMR spectra were measured with Gemini 200 MHz and Var-
ian mercury VX-300 MHz spectrometers in DMSO-d6, and chemical
shifts were recorded in δ ppm relative to TMS. The mass spectra were
run at 70 ev with HP Model MS. 5988A and/or GCMS. Cap 1000 EX
SHIMADZU spectrometer using Electron Impaction Technique. The
electronic spectra of the ligands and their complexes were obtained
in Nujol mulls and in saturated DMF or DMSO solutions using a
Shimadzu UV-240 UV-visible recording spectrophotometer. Molar con-
◦
ductivities in DMF at 25 C were measured 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 pharmacology unit, National
Cancer Institute of Cairo University.
Preparation of ligand HL1
To a warm solution containing 9-fluorenone (1.8 g, 0.01 mol), a warm
solution of thiosemicarbazide (0.91 g, 0.01 mol) was added in 30 mL
ethyl alcohol, then 5 drops of glacial acetic acid. The resulting solution
◦
was refluxed at 50–60 C for 15 h, where a yellowish white precipitate

106
N. S. Youssef et al.
was formed. The precipitate was then filtered, washed with ethyl alco-
1
hol and diethyl ether, and finally dried in vacuum. The ligand HL was
previously prepared15 by a different method using fluorenone to replace
diazafluorenone in 4,5 diazafluorenone thiosemicarbazone. Structure of
1
ligand HL is shown in Figure 1.
1
Preparation of HL complexes
1
1
Ag-HL . A complex Ag-HL was synthesized by the direct reaction of
1
silver nitrate with the ligand HL . A solution of silver nitrate (0.16 g,
0
.001 mol) in 5 mL water was added dropwise to a hot solution of ligand
1
HL (0.253 g, 0.001 mol) in 20 mL ethyl alcohol/chloroform mixture
◦
(1:1). The resulting solution was refluxed for 24 h at 50 C, and the
solution turned dirty green. The solution was then allowed to evaporate
slowly. The formed precipitate was filtered, washed with ethyl alcohol
and diethyl ether, and finally dried in vacuum.
1
Cu(II)-HL . This complex was obtained when a hot solution of cop-
1
per acetate (0.182 g, 0.001 mol) was added to a hot solution of HL
(
0.253 g, 0.001 mol) in 20 mL of ethyl alcohol/chloroform mixture (1:1)
with stirring. A deep brown precipitate was immediately formed. The
stirring was continued for 2 h at 50 C, after which the precipitate was
◦
filtered, washed with ethyl alcohol and diethyl ether, and finally dried
in vacuum.
Preparation of ligand HL2
To an aqueous solution containing 9-fluorenone (1.44 g, 0.008 mol)
in 30 mL ethyl alcohol solution (50%) containing anhydrous sodium
◦
acetate (1.31 g, 0.016 mol) at 35–40 C, the semicarbazide hydrochlo-
ride (0.89 g, 0.008 mol) in 10 mL ethyl alcohol (50%) was added. The
resulting solution was then refluxed for 6 h, and a yellow precipitate
was formed. The precipitate was filtered, washed, with ethyl alcohol
and diethyl ether, and finally dried in vacuum. The synthesis of the hy-
2
16
drochloride salt of HL was reported, but the condition of the reaction
2
is not similar. Structure of ligand HL is shown in Figure 1.
2
Preparation of HL complexes
2
Ag(I)-ligand HL . This complex was prepared when a hot solution
of silver nitrate (0.16 g, 0.001 mol) was added to a hot solution of lig-
2
and HL (0.237 g, 0.001 mol) in 20 mL ethyl alcohol/chloroform (1:1)
mixture with continuous stirring, which resulted in a brown precip-
itate immediately. The stirring was continued with reflux for 1 h at
◦
4
0 C. A dark green precipitate was formed after slow evaporation of the

Antitumor Activity of Some Metal Complexes
107
resulting solution. The produced precipitate was filtered, washed with
ethyl alcohol and diethyl ether, and finally dried in vacuum.
2
2
) VO-ligand HL . This complex was prepared by adding solution
of VOSO4 . H2O (0.181 g, 0.001 mol) in 5 mL water to a hot solution
2
of ligand HL (0.237 g, 0.001 mol) in 20 mL ethyl alcohol-chloroform
mixture (1:1 by volume). The stirring was continued for 1 h, and a green
precipitate was formed. The resulting precipitate was filtered, washed
with ethyl alcohol and diethyl ether, and finally dried in vacuum.
Preparation of ligand L3
To an aqueous solution containing 9-F (3.6 g, 0.02 mol) in 15 mL ethyl
◦
alcohol) at 35 C, ethylendiamine (0.6 g, 0.01 mol) was added followed
by 5 drops of glacial acetic acid. The resulting solution was refluxed
◦
at 50 C for 15 h, and a yellowish white precipitate was formed. The
precipitate was washed, with ethyl alcohol and diethyl ether, and dried
3
in vacuum. Structure of ligand L is shown in Figure 2.
3
Preparation of L complexes
3
◦
La(III)-ligand L . To a warm suspension (∼ 40 C) of the Schiff base
3
ligand L (0.384 g, 0.001 mol) in 50 mL methyl alcohol, a hot solution
of LaCl3.7H2O (0.371 g, 0.001 mol) in 20 mL ethyl alcohol was added.
◦
The resulting mixture was refluxed at 40 C for 6 h, and the produced
◦
solution was allowed to evaporate slowly at 60 C when yellow crystals
were obtained. The crystals formed were filtered, washed, with ethyl
alcohol and diethyl ether, and finally dried in vacuum.
3
Zn (II)-L . This complex was formed when a warm solution of ZnCl2
(
0.136 g, 0.001 mol) in 10 mL ethyl alcohol was added to a hot sus-
3
pension of the Schiff base ligand L (0.38 g, 0.001 mol). The resulting
◦
solution was refluxed at 60 C for 10 h. Upon allowing this solution to
◦
evaporate slowly at 60 C, yellow crystals were formed. The crystals
were filtered, washed with ethyl alcohol and diethyl ether, and finally
dried in vacuum.
3
Ag(I)-L . Upon adding a warm solution of AgNO3 (0.169 g, 0.001 mol)
3
in 5 mL H2O to a hot suspension of the Schiff base ligand L (0.38 g,
◦
0
.001 mol) with stirring at 50 C, a yellowish green precipitate was
formed immediately. The precipitate was then filtered, washed with
ethyl alcohol and diethyl ether, and finally dried in vacuum.
Antitumor activity of the (E. A. A.)
5
A set of sterile test tubes was used, where 2.5 × 10 tumor cells
per mL were suspended in phosphate buffer saline. Then, 25, 50, and

108
N. S. Youssef et al.
1
2
3
1
1
00 µg/mL from each of the ligands HL , HL and L , Cu(II)-HL ,
3
2
La(III)-L , and VO(IV)-HL complexes were added to the suspension
and kept at 37 C for 2 h. Trypan blue dye exclusion test was then
carried out to calculate the percentage of nonviable cells.
◦
1
7
RESULTS AND DISCUSSION
1
2
3
The elemental analyses of the ligands HL , HL , and L and their
complexes were listed in Table I.
Mass Spectra
1
2
3
The mass spectra of the ligands used, HL , HL , L , exhibit the molec-
ular ion peaks at m/e 253, 237, and 384, respectively (Figure 3), which
confirms the proposed formulas. Their proposed pathway fragmenta-
tion patterns are described in Schemes 1–3.
IR Spectra
The significant IR bands of the ligands and their metal complexes are
1
2
given in Table II. Both ligands HL and HL can exhibit tautomerism,
since they contain NH C S and NH C O functional groups, respec-
−
1
tively. However, the absence of the ν (S-H) band at 2570 cm in the case
1
−1
of ligand HL and a band at higher than 3500 cm from the spectrum
of ligand HL (representative of hydroxyl form of the enolic structure)
2
indicates the thionic and ketonic nature of these ligands, respectively,
1
8,19
−1
in the solid state.
Moreover, the bands around 1597 cm , 1057
−1
−1
1
cm , and 850 cm in the ligand HL spectra are assigned, respec-
tively, to ν C N, ν N N and ν C S groups. These bands are shifted or
weakened upon complexation with silver and copper ions, indicating
the participation of both of S and imine N in complexation. Also, the
−1
new band appeared around 1708 cm due to a new C=N group in the
case of Cu-ligand. HL complex shows the coordination via the S atom
1
with the displacement of one hydrogen atom upon thioenolization. In
−
1
1
addition, the band observed at 1296 cm in case of Ag-HL complex
2
0
may be due to a coordinated nitrate group.
The infrared spectra of ligand HL exhibit two bands around 1708,
575 cm are assigned respectively, to νC O and νC N of the semi-
2
−1
1
carbazone ligand. These bands are shifted and weakened upon com-
plexation in the case of vanadyl and silver complexes. This indicates
that coordination takes place through the nitrogen and oxygen of the
C N and C O groups, respectively. The coordination of the azomethine

109

110
N. S. Youssef et al.
FIGURE 3 (Continued on next page)

Antitumor Activity of Some Metal Complexes
111
1
2
3
FIGURE 3 Mass spectra of HL (a), HL (b), L (c).
nitrogen atom is also supported by the shift of the band assigned to
−
2
1
−1
2
the N-N stretching from 1068 cm to 1129 cm in Ag(I)-HL and
−1
21
1
172 cm in the case of the VO-HL complex.
The two bands that appeared at 1381 and 812 cm show that
the nitrate group acts as a monodonate coordinating agent in Ag(I)-
−1
2
18
HL complex. Also, the appearance of the two new bands at 1119
and 615 cm indicates unidentate behavior of the sulphate group,
whereas the new band shown around 998 is due to ν V=O stretching in
case of HL -VO complex.
The infrared spectra of ligand L shows two bands at 1642 and
601 cm . These bands can be attributed to the two azomethine
−1
22
2
23
3
−1
1
1
8
groups, R−C N indicating the formation of the Schiff base products.
−1
−1
The band at 1641 cm is shifted to higher wavenumber (1713 cm )
in both the La and Zn complexes, while the other band is observed
at nearly the same position in the IR spectra of the ligand, indicating

112
N. S. Youssef et al.
+
-SH
m/e 113
C H
N
NH2
N
N
H
NH2
3
2
N
S
H
_
H NCSNH2
m/e 253
m/e 222
2
m/e 90
-NH2
m/e 151
+
-
CH2
N
N
H
S
m/e 166
m/e 236
CSNH2
-NH
-
-NH2
-C
NH2
-
N
N
NH2
m/e 194
m/e 178
Fragmentation of HL1
SCHEME 1
involvement of only one azomethine nitrogen in chelation. However,
these bands are shifted towards lower frequency in the spectra of the
−1
Ag complex (1630 and 1594 cm ), which suggests the coordination
through both azomethine groups. Also, the appearance of two charac-
−
1
teristic bands at 827 and 1341 cm indicates the participation of the
2
4
nitrate group in the complex formation as ionic fashion. The presence
of new broad band in the 3376–3463 cm region may be due to ν OH
of water in the ligands HL , HL , and L complexes.
−1
1
2
3

Antitumor Activity of Some Metal Complexes
113
+
-
CN
N
-OH
N
N
NH2
NH2
+2H
N
N
H
NH2
H
O
m/e 237.2
m/e 221
m/e 195
-
N H
2
2
m/e 166
Fragmentation of HL2
SCHEME 2
1H NMR spectra
1
1
2
The H NMR spectra of the ligands HL and HL and their diamag-
netic complexes in DMSO solutions with assignments are collected in
Table III, and shown in Figures 4–6.
1
The H NMR spectra of the free ligands shows beside the aromatic
proton signals appearing at 7.33–8.08 and 7.32–8.31 ppm exchangeable
signals at 10.85 and 10.08 ppm assigned to the imino proton and 8.45–
1
8
.75 and 6.97 ppm assigned to amino protons in case of the ligands HL
2
and HL , respectively. These later signals disappeared in presence of
D2O. The high frequency singlets at 10.85 ppm and at 10.08 ppm in case
of HL and HL ligands are assigned to hydrazinic (N(2)-H) protons,
1
2
1
2
indicating that in solution the ligands HL and HL exist in thionic
2
5
and ketonic forms, respectively.3
Unfortunately, the ligand L is insufficiently soluble in DMSO to
1
acquire a H NMR spectrum.
The signals due to the hydrazinic protons are either shielded or
1
2
deshielded in the case of HL -Ag and HL -Ag complexes, confirming
non-deprotonation and S-coordination or O-coordination in these com-
plexes, respectively.26

114
N. S. Youssef et al.
N
N
C
H
C
H
2
2
m/e 384
+
N
+
CH2
m/e 192
CH N
-
2
+H
m/e 165
Fragmentation of L3
SCHEME 3
Electronic Spectra
The significant electronic absorption bands of the ligands and their
metal complexes are listed in Table IV. The free semicarbazone,
thiosemicarbazone, and ethylenediamine ligands have bands in the
range 240–285 nm, 260–295 nm, and 265–290 nm in case of the lig-
1
2
3
ands HL , HL , and L , respectively. These bands are assigned to
∗
π → π transition, while the bands around 355, 320, and 300 nm
1
2
3
∗
in case of the ligands HL , HL , and L are assigned to n→ π ,
2
7−29
respectively.
These bands were shifted on complexation, and the
1
new bands around 430 nm in the case of Ag-HL and 425 nm in
the case of Cu(II)-HL , and 330 nm in Ag-HL and VO-(IV) may
be considered as M-L charge transfer bands.3 In addition the two bands
1
1
0
1
appearing at 460 nm and 590 nm in the case of the Cu(II)-HL complex

115

116
N. S. Youssef et al.
TABLE III 1H NMR Spectral Data of the Ligand (HL ), (HL ) and
1
2
Their Diamagnetic Ag (I) Complexes Recorded in DMSO-d Solution
6
Ligands and their Complexes
Ar-H
CS-NH2
CS-NH
CO-NH2
CO-NH
1
Ligand HL
HL - Ag(I)
7.33–8.08
7.39–7.91
7.32–8.31
7.32–8.30
8.75, 8.45
9.00, 9.39
10.85
11.60
1
2
Ligand HL
6.97
6.94
10.08
10.50
2
HL - Ag(I)
may be assigned to d-d transition, suggesting the six-coordinated Oh
geometry of the copper(II) complex.31 The expected d-d transition in the
case of VO-(IV) can not be detected even with concentrated solutions. It
3
2−35
may be lost in the low energy tail of the charge transfer transition.
Molar Conductance Data
The metal complexes discussed herein were dissolved in DMF, and the
−3
molar conductivities of 10 M of their solutions at room temperature
were measured to establish the charge of the metal complexes. The
conductance data in Table II indicate that all the metal complexes ex-
cept Ag-L3 have conductivity values in the range characteristic for the
3
6
non-electrolytic nature, suggesting that these complexes are neutral.
−1
Ag-L3 complex has molar conductance value of 85 ꢁ , which indicates
that the nitrate group is uncoordinated, and which may also be sup-
−1
ported by the presence of two bands observed at 827 and 1341 cm ,
indicating the participation of the ionic nitrate group in complex
formation.
Magnetic Susceptibility Measurements
1
2
The µ eff values of Cu-HL and VO-HL are 1.87 and 1.66 BM, re-
spectively. These results of the magnetic susceptibility measurements
at room temperature showed that these complexes were paramag-
netic and copper (II) and oxovanadium (IV) have single electron in the
d-orbital, suggesting octahedral and square pyramidal geometries for
3
7
the Cu(II) and VO(IV) complexes, respectively.
1
2
3
3
3
The complexes: Ag-HL , Ag-HL , La-L , Ag-L , and Zn-L are dia-
magnetic, and according to the elemental analyses data of these com-
plexes, we suggest the tetrahedral geometry for the silver and zinc
3
complexes, whereas La-L has an octahedral geometry.

Antitumor Activity of Some Metal Complexes
117
FIGURE 4 1HNMR spectra of HL ligand in DMSO (a) and in D
1
O (b).
2

118
N. S. Youssef et al.
FIGURE 5 1HNMR spectra of HL ligand in DMSO (a) and in D
2
O (b).
2
Suggested Structural Formulas of the Complexes
From the spectral data and the elemental analyses, the structural of the
prepared complexes may be formulated as shown in the Figures 7–9.

Antitumor Activity of Some Metal Complexes
119
FIGURE 6 1HNMR Spectra of Ag-HL (a) and Ag-HL (b) complexes.
1
2

120
N. S. Youssef et al.
H O
2
N
NH
Ag
C
O NO
2
S
NH2
NH2
N
C
N
S
H O
Cu
OH2
2
.
2H O
2
S
N
C
N
H N
2
1
FIGURE 7 Suggested structures of HL complexes M L=1:2 and1:1.
Biological Evaluation
1
2
3
1
Antitumor activity of ligands HL , HL , L and Cu (II)-HL , VO(IV)-
2
3
HL , La(III)-L complexes are listed in Table V.
The synthesis of polycyclic aromatic systems by various methodolo-
gies has been published extensively, and the carcinogenic properties

Antitumor Activity of Some Metal Complexes
121
H
N
C
NH2
N
.
H O
2
O
Ag
H O
2
O-NO2
NH2
C
HN
O
N
OH
2
V
O
.
2H O
2
2
FIGURE 8 Suggested structures of HL complexes M;L=1;1.
of such compounds have been explained by advancing a number of
different mechanisms.12 The antitumor activity of such compounds is
suggested to depend on intercalation with or covalent binding to DNA,
whereas many other sites of interaction such as the cell membrane
have also been identified.
The results of antitumor activity using (E. A. A.) for ligands and their
1
3
complexes showed no antitumor activity of ligand HL , La (III)- L , and
1
3
Cu(II)-HL complexes for all concentrations, whereas ligand L shows
more activity than ligand HL at 25 and 50 µg/mL concentrations. This
2

122
N. S. Youssef et al.
H
C
2
2
H C
N
N
Cl
Zn
4
H O
2
Cl
N
N
2
H C
C
H
2
H2
C
H C
2
N
N
Cl
Cl
Cl La
H O
2
N
N
CH2
C
H
2
FIGURE 9 (Continued on next page)

Antitumor Activity of Some Metal Complexes
123
H2C
CH2
N
N
Ag
NO .5H O
3
2
N
N
H2C
CH2
3
FIGURE 9 Suggested structures of the L complexes M L=1:2.
TABLE IV Electronic Absorption Spectral Bands of the Ligands and
Their Complexes
Electronic absorption bands (λmax nm)
Ligand and
their complexes
Intra ligand and CT bands
d-d bands
µeff (B.M)
HL1
240, 285, 355
260, 290, 330, 430
260, 295, 370, 425
230, 250, 260, 295, 320
240, 255, 300, 330
235, 245, 260, 300, 330
265, 290, 300
270, 285, 295, 310, 325, 390
265, 285, 295, 310, 330, 390
255, 275, 295
1
[
[
Ag(HL )(H2O)NO3]
diamagnetic
1.87
1
Cu(L )2(H2O)2]2H2O
460, 590
2
HL
2
[
[
L
Ag(HL )(H2O)NO3]H2O
diamagnetic
1.66
2
VO(HL )(H2O)SO4]2H2O
3
3
[
[
La(L )2(H2O)Cl3]
Zn(L )2Cl2].4H2O
Diamagnetic
Diamagnetic
diamagnetic
3
3
Ag(L )2NO3.5H2O
may be attributed to the aromatic ring stacking between nucleobases,
which is considered to be a major driving force that leads to binding
to DNA, and the extent of binding is expected to depend on the size
and electron density of the interacting aromatic rings, as well as on

124
N. S. Youssef et al.
1
TABLE V Antitumor Activity of Ligands HL ,
2
3
HL , and L and Their Metal Complexes
Cu(II), VO(IV), and La(III) Using (E. A. A.)
%
Inhibition of cell viability µg/mL
Compound
HL1
25
50
100
0%
0%
30%
50%
40%
0%
0%
0%
50%
70%
60%
0%
0%
0%
90%
90%
90%
0%
1
Cu (II)-HL
2
HL
2
VO (IV)-HL
3
L
3
La (III)-L
the combined effect of hydrophobic and hydrophilic interactions.38 On
2
the other hand, VO(IV)-HL complex exhibited the maximum antitu-
mor activity at all concentrations. It should be noted that the chelation
could facilitate the ability of a complex to cross a cell membrane and can
be explained by Tweedy’s chelation theory. Chelation considerably re-
duces the polarity of the metal ion, mainly because of partial sharing of
its positive charge with the donor groups and possible electron delocal-
ization over the whole chelate ring. Such chelation could also enhance
the lipophilic character of the central metal atom, which subsequently
favors its permeation through the lipid layer of the cell membrane.3
9
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