Transition metal complexes of α-aminophosphonates part II: Synthesis, spectroscopic characterization, and in?vitro anticancer activity of copper(II) complexes of α-aminophosphonates

Article abstract of DOI:10.1080/10426507.2019.1700258

A one pot procedure was used to synthesize two new derivatives of α-aminophosphonates. Novel copper(II) complexes of α-aminophosphonates were synthesized by coordinating different copper salts with the newly synthesized α-aminophosphonates. Their structur

Full text of DOI:10.1080/10426507.2019.1700258

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: https://www.tandfonline.com/loi/gpss20
Transition metal complexes of α-
aminophosphonates part II: Synthesis,
spectroscopic characterization, and in vitro
anticancer activity of copper(II) complexes of α-
aminophosphonates
Mariam Ahmed Azzam, Hanaa Abdel Latif El-Boraey & Ibrahim El Tantawy El-
Sayed
To cite this article: Mariam Ahmed Azzam, Hanaa Abdel Latif El-Boraey & Ibrahim El Tantawy
El-Sayed (2019): Transition metal complexes of α-aminophosphonates part II: Synthesis,
spectroscopic characterization, and inꢀvitro anticancer activity of copper(II) complexes of
α-aminophosphonates, Phosphorus, Sulfur, and Silicon and the Related Elements, DOI:
10.1080/10426507.2019.1700258
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PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
https://doi.org/10.1080/10426507.2019.1700258
Transition metal complexes of a-aminophosphonates part II: Synthesis,
spectroscopic characterization, and in vitro anticancer activity of copper(II)
complexes of a-aminophosphonates
a
b
b
Mariam Ahmed Azzam
, Hanaa Abdel Latif El-Boraey , and Ibrahim El Tantawy El-Sayed
a
b
Applied Organic Chemistry Department, National Research Centre, Giza, Egypt; Chemistry Department, Faculty of Science, El-Menoufia
University, Shebin El Koom, Egypt
ABSTRACT
ARTICLE HISTORY
A one pot procedure was used to synthesize two new derivatives of a-aminophosphonates. Novel
copper(II) complexes of a-aminophosphonates were synthesized by coordinating different copper
salts with the newly synthesized a-aminophosphonates. Their structures were characterized by dif-
Received 16 January 2019
Accepted 14 November 2019
2
KEYWORDS
ferent spectral and analytical techniques. Evaluation of the metal-free ligands HL1, HL , and their
a-Aminophosphonates;
copper(II) complexes;
spectroscopic characteriza-
tion; anticancer activity
Cu(II) complexes against human colon carcinoma HT-29 cell lines was performed, using cisplatin
1
as a reference drug. The results indicated that the complexes of the ligand HL exhibited
2
enhanced anticancer activity, while ligand HL complexes showed decreased anticancer activity.
GRAPHICAL ABSTRACT
Introduction
With this regard, synthesis of aminophosphonic acid deriva-
tives has been a focus of appreciable attention. Our specific
interest in the area of metal phosphonate chemistry has been
directed toward the interaction of transition metal ions with
a-aminophosphonate ligands. The incorporation of the metal
ions into organic ligands can drastically change their thera-
peutic effects, and pharmacological properties. “Metals can
play an important role in modifying the pharmacological prop-
erties of known drugs after coordination to a metal. Chelation
causes drastic changes in the biological properties of ligands, as
There is currently considerable interest in developing novel
metal-based complexes in order to improve efficiency and
[
1]
reduce the severe side effects of the antitumor drugs. It is
generally considered that the antitumor properties of com-
plexes are affected by the nature of the compounds (ligands)
bonded to the metal ions. Aminophosphonic acids I and their
derivatives II, which are analogs of naturally occurring amino
acids III (Figure 1) have been shown to possess a wide range
[
2–4]
of applications and varied biological activities.
Previous studies suggested that diphenyl ester of a-amino- well as metal moieties, and in many cases, it causes the syner-
phosphonates and its complexes act as inhibitors of serine pro- gistic effect of both metal ions and ligand. For example, the
[
5,6]
teases which play an important role in cancer cell invasion.
complexation of nonsteroidal anti-inflammatory drugs with
CONTACT Mariam Ahmed Azzam
mariam_ahmed_987@yahoo.com
Applied Organic Chemistry Department, National Research Centre, Dokki, Giza, Egypt.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/gpss.
Supplemental data for this article can be accessed https://doi.org/10.1080/10426507.2019.1700258.
ß 2019 Taylor & Francis Group, LLC

2
M. A. AZZAM ET AL.
[
19–25]
copper overcomes some of the gastrointestinal side effects of temperature for 5–18 h under identical conditions.
The
[
7]
these drugs. Because of the range of coordination geometries, solid formed was filtered and recrystallized from methanol
1
2
metal complexes provide more stereochemical variability than to produce the novel compounds (HL ) and (HL ), respect-
is possible in organic molecules, and often introduce new ele- ively, in 45–57% yields as depicted in Scheme 1.
1
The chemical structures of a-aminophosphonates 4 (HL )
ments of chirality, which may be important for biological mol-
ecule recognition and interaction. The metal complexes can
also be extremely positively-charged; since many biological
structures, such as several types of phospholipids, DNA and
RNA, and some regions of proteins are negatively charged; for
electrostatic reasons the positive charge of metal complexes
2
1
and 6 (HL ) were confirmed by IR, H NMR and MS. The
IR spectra of the latter products showed overlapped broad
absorption bands of the t(OH) and t(NH) groups in the
ꢀ
1
ꢀ1
region 3414–3431 cm . Bands at 1187–1084 cm
are
1
2
attributed to the P ¼ O group of (HL ) and (HL ); in add-
ꢀ
1
[
8]
ition, the P–O–C groups appeared at 995 and 997 cm
,
could aid the binding with intracellular targets”.
ꢀ
1
1
whereas the P-CH group appeared at 752, 754 cm
.
H
The interaction of transition metal ions with a-amino-
phosphonate ligands, having a carbocyclic ring bearing
donor group, is limited. As a part of our ongoing project on
synthetic and biological applications of a-aminophospho-
nate, this stimulated us to explore the influence of inter-
action of metal ions with a-aminophosphonates on their
biological activity.
2
NMR of 6 (HL ) showed an exchangeable singlet signal at
.64 and 10.8 ppm attributable to the NH and OH protons,
respectively. The exchangeable signal of the CH-aliphatic
9
1
2
proton for HL and HL appeared at 5.25–5.89 ppm.
Moreover, electron impact (EI) mass spectrometry con-
1
firmed the probable formulae of the ligands HL and
2
[20,21]
1
ꢁ
HL .
The melting point of HL is about 140–145 C
The most widely studied transition metal ion in this
respect is copper. Copper(II) complexes have been proven
2
ꢁ
and that of HL is about 225–230 C.
[
9–14]
[15–17]
to act as anticancer,
antimicrobial,
and antiviral
[
18]
agents.
This study describes the synthesis, and spectro-
Synthesis and characterization of the metal complexes
scopic and in vitro anticancer activity of certain novel
copper(II) complexes with a-aminophosphonate ligands.
Cu(II) complexes 5a-c and 7a-d were afforded by the reac-
1
2
tion of HL and HL with different copper(II) salts (chloride,
nitrate, perchlorate or bromide) in 1: 1 (M: L) molar ratio
(Scheme 2).
Results and discussion
Postulated structures of the newly synthesized Cu(II)
complexes 5a-c and 7a-d were in full agreement with the
Synthesis and characterization of ligands
Aryl aldehydes 1 or 5 with aniline 2 and triphenylphosphite elemental analyses data (Table 1), which showed 1 M: 1 L
in the presence of lithium perchlorate (10 mol %), as a molar ratio for these complexes except for complex 5a,
3
Lewis acid catalyst, were dissolved in CH Cl2 at room which displayed 2 M: 1 L molar ratio composition and com-
2
plexes 5 b and 7 b, which showed 1 M: 2 L molar ratio com-
position. The novel Cu(II) complexes are powder-like
paramagnetic compounds, colored green to dark-brown, and
are stable in the solid state under normal laboratory condi-
tions. Owing to the partial solubility of the complexes in
common organic or mixed solvents, we failed to obtain sin-
Figure 1. a-Aminophosphonic acids I and their analogs II as structural mimics
of a-amino acids III.
gle crystals suitable for X-ray diffraction studies. However,
they are soluble in DMF and DMSO. According to the
1
2
Scheme 1. Synthesis of a-aminophosphonate ligands 4 (HL ) and 6 (HL ).

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
3
Scheme 2. Synthesis of copper(II) a-aminophosphonate complexes 5a-c, 7a-d.
ꢀ
1
molar conductance values (Table 1), all complexes have (1226–1211 cm ) in the complexes, suggesting the partici-
[
23]
non-electrolytic nature except complexes 5 b and 7c, which pation of the OH group in chelation.
The IR spectrum of
are 1:1 electrolytes and complex 7 b, which is 1:2 complex 5a showed significant variation in the position of
[
22,23]
ꢀ1
electrolyte.
t(P ¼ O) absorption (1162 cm ) than that observed for the
ꢀ
1
free ligands (1187 cm ) suggesting that (P ¼ O) group is
[
24]
involved in the metal coordination,
while all other IR
FT-IR spectra
spectra of the complexes showed no shifts in the position of
The FT-IR spectra of the complexes showed broad bands in t(P ¼ O) as it is not coordinated. “The small variation in the
ꢀ
1
the range of 3414–3230 cm assigned to t(OH) group and position of the t(P ¼ O) absorptions displayed in the above
solvent molecules associated with the complexes. The lower region is arising from their sensitivity to the hydrogen
ꢀ
1
shift between 1627 and 1530 cm corresponding to t(NH) bonding which may change the polarity of the phosphoryl
ꢀ
1
by up to 20 cm in the metal complexes indicated the con- oxygen atom and brings about the appearance of these
[
20]
tribution of the aminophosphonate nitrogen atom in the bands at higher or lower frequencies.”
The IR spectra of
[
4]
coordination.
Also, t(C-O) of the free ligands at complexes 5 b and 7 b showed very strong bands at
ꢀ
1
ꢀ1
ꢀ1
1
315–1273 cm
was shifted to lower frequencies 1384 cm
and 837 cm
indicating the presence of ionic

4
M. A. AZZAM ET AL.
[
25]
nitrate groups,
which was confirmed by molar conduct-
ance measurements (Table 2). Also, IR spectrum of complex
ꢀ
1
7
c exhibits an intense band at 1114 cm along with a weak
ꢀ
1
band at 631 cm , which have been assigned to ꢀ(Cl-O) of
[
26]
ꢀ1
uncoordinated perchlorate anion.
Peaks at 535–530 cm
may be assigned to t(M–O) and t(M–N) vibrations.
1
2
Accordingly, the ligands HL and HL acted as mono-basic
2
or neutral bidentate ligands in all complexes. However, HL
acted as neutral tridentate ligand in case of the complex 5a.
Mass spectra
The structure of the complexes was also supported by the (EI)
2
1
mass spectra. The mass spectrum of [Cu(L )Cl(H O)] ꢂ =2
2
EtOH (7a) (Figure 2) provides good evidence for its molecular
formula by observing molecular ion peak at m/z ¼ 620 amu,
which coincides with its formula weight (calculated M ¼ 620).
One of the most common mechanisms of ion formation
observed in the full-scan positive ion mass spectrum for com-
plex 7a is the formation of sodium and potassium adducts
þ
þ
[
M þ Na] at m/z ¼ 643.57 amu, [(M þ K)-2H] at m/
z ¼ 657.87 amu, respectively. The mass spectrum of this com-
plex also shows important fragment ions at m/z ¼ 586.63
þ
þ
[
4
(M þ K)-C H þ4H] , 555.65 [(M þ Na)–C H NH þ 4H] ,
6
5
6
5
þ
79.28[M–(C H NHO þH O) þH] .
6
5
2
2
Electronic, EPR spectra and magnetic measurements
Magnetic moment per metal ion of Cu(II) complexes 5a-c
and 7a-d at room temperature lies in the range 1.75–2.4
B.M. (Table 1) corresponding to one unpaired electron and
excludes antiferromagnetic interaction. Electronic spectra of
the ligands display three absorption bands at 38461, 28985,
ꢀ
1
1
ꢀ1
ꢃ
2
2417 cm for HL and at 37174, 28571, 21052 cm for
2
ꢃ
HL . These bands may be assigned to p!p , n!p and
charge transfer transitions, respectively. All complexes dis-
play two main electronic spectral bands. The moderately
ꢀ
1
intense peak at 21505–22727 cm
is assigned to MLCT
transition, whereas the broad band at 16129–20833 (Table
2
2
1
) can be assigned to the combination of B ! E and
1g
g
2
2
B ! A
transitions[ in
a
distorted square-planar
These values may be due to
square-planar toward tetrahe-
1g
1g,
27,28]
copper(II) environment.
the
distortion
of
[
29]
dral geometry.
The powder EPR spectrum of copper(II) complex 5 b
(Figure 3) displayed anisotropic spectrum with g-values,
g ¼ 2.23 and g? ¼ 2.03. The trend g >g?> 2.0023 sug-
=
=
==
2
x -
gests that the unpaired electron is most likely present in d
2
orbital of Cu(II) ion which is characteristic of a square
y
planar geometry. Moreover, splitting seen in the perpendicu-
lar region of the spectrum corresponds to the interaction of
electrons with nuclear spin of nitrogen, which gives an evi-
dence[20]for the coordination of phosphonate nitrogen
atom.
Furthermore, the exchange coupling interaction
between two copper centers is explained by Hathaway
[
30]
expression,
7.68) is > 4.0 and therefore, the local tetragonal axes are
aligned parallel or only slightly misaligned and there is no
G ¼g 22.0023 / g?22.0023. The value of G
==
(

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
5
Table 2. Thermal data of the investigated copper(II) complexes.
ꢁ
Temperature range/( C)
Mass loss %
Compound
Leaving species
DTG
TG
Calc.
(F)
1
[
Cu
2
(L )Cl
4
(H
2
O)].5H
2
O (5a)
59
72,290
31,558
25–100
100–225
255–574
at 575
33–128
130–799
at 800
29–133
134–207
207–799
at 800
27–104
191–799
at 800
25–116
116–199
200–799
at 800
26–118
118–259
259–688
at 688
4.46
6.7
(4.44)
(6.2 )
ꢀ2H
2
O
ꢀ3H2O
1
4
60.34
28.5
4.46
74.09
21.45
3.5
(61.09)
(28.27)
(4.24)
(74.62)
(21.14)
(3.7)
Decomp.
1
ꢄ (CuOþ =2Cu
2 2 7
P 0 )
1
[
[
Cu(L )
2
].NO
3
.EtOH (5b)
75
EtOH
1
67,455,570
Decomp.
ꢄCu(PO
3 2
)
1
1
1
Cu(L )Br(H
2
O)]2H
2
O. =2EtOH (5c)
68
- =2EtOH
1
59
5.5
(6)
ꢀ2H
2
O
Decomp.
4
51,584
73.32
17.68
3.7
(72.91)
(17.39)
(4.2)
1
1
ꢄ =2(CuOþ =2Cu
2 2 7
P 0 )
2
1
1
[
[
Cu(L )Cl(H
2
O)]. =2EtOH (7a)
55
- =2EtOH
2
3
70,448,533
68
13,170
11,470,523
72.03
24.27
3.85
10.37
67.25
18.53
4.64
4.64
71.32
19.4
(71.82)
(23.98)
(3.98)
(10.66)
(66.81)
(18.55)
(3.73)
(4.35)
(72.76)
(19.16)
Decomp.
1
ꢄ =2Cu
2 2 7
P 0
2
Cu(L )
2
] .2NO
3
.EtOH (7b)
- EtOH
ꢀ2NO
Decomp.
1
3
ꢄCu(PO
3 2
)
O
O
2
[
Cu (L ) Br
2
].4H
2
O (7d)
46
10,311
27,563
ꢀ2H
2
2
4
ꢀ2H
2
Decomp.
1
2 2 7
ꢄ =2(Cu P 0 )
exchange interaction between copper centers in the polycrys- water of crystallization in two successive stages (complex
talline compound.
7d) (Table 2).
The solid state EPR spectrum of complex 7a shows
The TG curves of the complexes 5 b and 7 b (Figure 4)
rhombic spectral features with three g-values (g1¼ 1.92, g2¼ showed that they display lower thermal stability
[
31]
ꢁ
ꢁ
2
.03, g3¼ 2.23), respectively.
The g3 value is less than 2.3, (116–130 C) than that of the complexes 5a, 5c, 7a, and 7d
which is in agreement with the covalent character of M ꢀ L (130–259 C); this may be attributed to the steric effect
resulting from the presence of two ligand molecules in com-
bonds. For rhombic spectrum, G ¼ (g ꢀ2.0023)/(g
=
=
?
plexes 5 b and 7 b compared to one ligand molecule in com-
plexes 5a, 5c, 7a, and 7d. The final end products are
ꢀ
2.0023);g?¼ (g1 þ g2)/2); G ¼ 8.4) suggesting that there is
no exchange coupling interactions in the complex. The
1
supposed to be a mixture of (CuO þ =2 Cu P 0 ) for com-
rhombic spectral parameter R ¼ (g -g )/(g -g ) may be sig-
2 2 7
2
1
3
2
[
33,34]
plexes 5a and 5c,
Cu P 0 for complexes 7a and 7d,
2 2 7
nificant, if R > 1, a predominant d 2 ground state is present.
z
[
35]
2
2
and Cu(PO ) for complexes 5 b and 7 b.
ratio of the metal residue was in agreement with the sug-
gested formulae.
The percentage
If R < 1, a predominant d
ground state exists. Here
ground state is assigned to
3 2
x -y
2
2
x -y
R ¼ 0.55 < 1. Therefore d
this complex.
Anticancer activity
Thermal properties (TG/DTG)
In vitro anticancer activity of all copper(II) complexes and
The thermogravimetric studies have been made in the tem-
perature range RT–800 C. The nature of proposed chemical
1
2
ꢁ
the corresponding free ligands HL and HL was evaluated
against human colon carcinoma (HT-29) cell line using
MTT colorimetric assay. The percentage of the in vitro cell
change with temperature and the percentage of final product
obtained are given in Table 2. The results obtained from
thermogravimetric analysis were in agreement with the the-
oretical formulae proposed from the elemental analyses.
The TG curves of the complexes 7a, 5c and 7d showed
[
36]
inhibition at 10 mM concentration was measured
using
cisplatin, as the reference drug, and a colorimetric method.
The results shown in Figure 5 indicated that no specific
1
anticancer effects of the free ligand HL were noted, but
ꢁ
weight loss from RT-133 C corresponding to loss of solvent
meanwhile, its copper(II) complexes 5a-c demonstrated mild
of crystallization. The desolvation or dehydration process for
these complexes is characterized by two successive stages
suggesting that the solvent has a different nature of inter-
2
activity. Ligand HL exhibited moderate anticancer activity
higher than its complexes 7a-d.
[
32]
action in the crystal.
The TG curves of these complexes
show weight loss of (Calc./Found %); (4.46/4.44, 6.7/6.2) Experimental
corresponding to loss of two molecules of water of crystal-
lization followed by three molecules in the second stage
Materials and physical measurements
(
complex 5a); weight loss of (3.5/3.7, 5.5/6.0) due to the All chemicals and solvents were of analytical grade and were
1
removal of =2 EtOH molecule followed by loss of two water used as received without further purification. The metal salts
molecules in the second stage (complex 5c); and weight loss CuCl ꢂ 2 H O (BDH), CuBr (BDH) and Cu(ClO ) ꢂ 6 H O
2
2
2
4 2
2
of (4.64/3.73, 4.64/3.95) due to loss of two molecules of were used as supplied. Elemental microanalyses (C, H, N)

6
M. A. AZZAM ET AL.
2
1
Figure 2. Mass spectra of [Cu(L )Cl(H
2
O)] ꢂ =2 EtOH (7a).
recorded in DMSO-d on a Varian Gemini 300 NMR spec-
6
trometer at 400 MHz. The electron impact mass spectra (EI)
for the ligands and its metal complexes were run on
Shimadzu-QP 2010 plus mass spectrometer, Microanalytical
Laboratory, Faculty of Science, Cairo University, Egypt. The
molar conductivity has been measured at room temperature
ꢀ
3
with approximately 10
M in DMSO solution using a
CON6000 conductometer, Cyberscan, Eutech instruments.
Magnetic susceptibility of metal complexes was measured
using the modified Gouy method at room temperature on
Magnetic
susceptibility
Johnson
Matthey
balance.
Diamagnetic corrections were made using Pascal’s constant.
The thermal analysis (TG/DTG) was carried out by using a
Shimadzu DAT/TG-50 thermal analyzer with a heating rate
ꢁ
of 10 C/min under N atmosphere with a flowing rate of
2
2
ꢁ
0 mL/min in the temperature range RT-800 C using plat-
1
Figure 3. Solid state X-band EPR spectra of [Cu(L )
2
]NO
3
ꢂ EtOH (5 b) and
2
inum crucibles. Melting points were measured with The
MPS21 device. Biological tests were measured at Okayama
University, Japan. The Supplemental Materials contains sam-
ple IR, UV-vis and TG/DTG spectra (Figures S1–S15).
1
[
2
Cu(L )Cl(H O)] ꢂ =2 EtOH (7a) at RT.
were performed at the Micro Analytical unit, Cairo
University, Giza, Egypt. Copper(II) content in the complexes
was determined via complexometric method, while halide
ions were determined by Mohr’s method. IR spectra have
been recorded on NeneyeusNicolidite–640MSA FT-IR,
Synthesis of ligands
Thermo Electronic CO. using KBr pellets. The electronic (1 mmol, 0.11 mL) of salicylaldehyde (1) or (1 mmol,
spectra have been measured in nujol mull using 4802 UV- 172 mg) of 2-hydroxynaphthaldehyde (5) was stirred with
1
Vis spectrophotometer. The
H NMR spectrum was (1.1 mmol, 0.1 mL) of aniline (2) and (1 mmol, 0.26 mL) of

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
7
1
ꢂ EtOH (7 b). ꢃweight of sample (mg).
Figure 4. TG/DTG curves of the complexes [Cu(L )
2
]NO
3
2 2 2 3
ꢂ EtOH (5 b) and [Cu(L ) ] NO
triphenylphosphite (3) in the presence of (10 mol %, 11 mg) (d, J ¼ 12.0 Hz,1H, CH-aliphatic, exchangeable), 6.47–7.44
þ
of lithium perchlorate as a Lewis acid, in 15 mL of CH Cl2 (m, 19 H, Ar-H). MS (70 eV, EI): m/z ¼ 431 (M , 58%), 432
2
at room temperature for 5–18 h (the reaction progress was (M þ 1, 58%).
[
37–40]
followed by TLC).
The resulting precipitate was fil-
tered off, recrystallized from methanol and dried to give the
1
2
newly synthesized ligands HL and HL , respectively.
Diphenyl(2-hydroxynaphthalen-1-
yl)(phenylamino)methylphosphonate HL (6)
2
Diphenyl(2-
ꢁ
Yellow solid, yield (57%), mp. 225–230 C. IR (KBr)
hydroxyphenyl)(phenylamino)methylphosphonate
ꢀ1
ꢀ
(cm ) ¼ 3431 (O-H) þ (N-H), 1084 (P ¼ O), 997 (P-O-
1
HL (4)
1
C), 754 (P-CH). H NMR (DMSO-d , 400 MHz): d ¼ 5.89
6
ꢁ
White solid, yield (45.5%), mp. 140–145 C, IR (KBr): (br.s, 1 H, CH-aliphatic, exchangeable), 6.97–8.48 (m, 21 H,
ꢀ
1
ꢀ
(cm ) ¼ 3414 (OH), 3235 (NH), 1187 (P ¼ O), 995 (P-O- Ar-H), 9.64 (br.s, 1 H, NH), 10.8 (br.s, 1 H, OH). MS (70 eV,
1
C), 752 (P-CH). H NMR (DMSO-d , 400 MHz): d ¼ 5.25 EI): m/z ¼ 482 (M þ 1, 76%).
6

8
M. A. AZZAM ET AL.
of Methyl vs. Phenyl Group on Uranium Sorption. Chem. Eng.
J. 2018, 352, 1022–1034. DOI: 10.1016/j.cej.2018.06.003.
[
3] Boshta, N. M.; Elgamal, E. A.; El-Sayed, I. E. Bioactive Amide
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M.; Zani, F.; Tu ꢀs ek-Bo ꢀz i ꢁc , L. Palladium(II) Complexes of
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Figure 5. Inhibition rate (%) was calculated at 10 lM concentration using MTT
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2
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Synthesis of the complexes 5a-c and 7a-d
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To a solution of the ligand HL or HL (1 mmol) in ethanol
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(
rate or bromide (1 mmol) in ethanol was added slowly with
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cipitated from petroleum ether-acetonitrile mixture, filtered
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chlorides 5a, 7a, nitrates 5 b, 7 b, perchlorate 7c and bro-
mides 5c, 7d, respectively.
[
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[
Conclusions
In conclusion, we report a new series of copper(II) com-
plexes containing novel a-aminophosphonate ligands. Based
on the analytical, spectral and thermal data, the structure
and geometry of the complexes were proposed. The evalu-
ation of their anticancer activity against HT-29 cell lines
proved that the synthesized copper(II) complexes 5a-c
exhibited higher anticancer activity than the free ligand
[
10] Wehbe, M.; Lo, C.; Leung, A. W. Y.; Dragowska, W. H.; Ryan,
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2
HL1, while complexes 7a-d of ligand HL showed lower
[
[
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Acknowledgments
The authors would like to thank Professor Masaharu Seno research
team, Division of Biochemistry, Graduate School of Natural Science
and Technology, Okayama University, Japan, for their help with the
in vitro anticancer activity.
[
ORCID
Mariam Ahmed Azzam
http://orcid.org/0000-0002-0622-6575
1021/jm061174f.
[
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ica.2010.08.009.
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