Accepted Manuscript

Transition Metal Complexes of Neocryptolepine Analogues Part I: Synthesis,

Spectroscopic Characterization, and In Vitro Anticancer Activity of Copper(II)
Complexes

Sanaa Moustafa Emam, Ibrahim El Tantawy El Sayed, Nagla Nassar

PII: S1386-1425(14)00537-X
DOI: http://dx.doi.org/10.1016/j.saa.2014.03.114
Reference: SAA 11947

To appear in: Spectrochimica Acta Part A: Molecular and Biomo-

lecular Spectroscopy

Received Date: 21 December 2013

Revised Date: 9 March 2014
Accepted Date: 29 March 2014

Please cite this article as: S.M. Emam, I.E.T. Sayed, N. Nassar, Transition Metal Complexes of Neocryptolepine
Analogues Part I: Synthesis, Spectroscopic Characterization, and In Vitro Anticancer Activity of Copper(II)
Complexes, Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy (2014), doi: http://dx.doi.org/
10.1016/j.saa.2014.03.114

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
 Transition Metal Complexes of Neocryptolepine Analogues Part I: Synthesis,
Spectroscopic Characterization, and In Vitro Anticancer Activity of
Copper(II) Complexes
Sanaa Moustafa Emam, Ibrahim El Tantawy El Sayed*, Nagla Nassar
El-Menoufia University, Faculty of Science, Chemistry Department, Shebin El koom, Egypt
(This paper is dedicated to the spirit of Professor Ahmed Donia, who died on April 24, 2013)

Abstract:

New generation of copper(II) complexes with aminoalkylaminoneocryptolepine as

bidentate ligands has been synthesized and It is characterized by elemental analyses, magnetic
moment, spectra (IR, UV-Vis, 1H NMR and ESR) and thermal studies. The IR data suggest the
coordination modes for ligands which behave as a bidentate with copper(II) ion. Based on the
elemental analysis, magnetic studies, electronic and ESR data, binuclear square planar
geometry was proposed for complexes 7a, 7b, square pyramidal for 9a, 9b and octahedral for
8a, 8b, 10a, 10b. The molar conductance in DMF solution indicates that all complexes are
electrolyte except 7a and 7b. The ESR spectra of solid copper(II) complexes in powder form
showed an axial symmetry with 2B1g as a ground state and hyperfine structure. The thermal
stability and degradation of the ligands and their metal complexes were studied employing
DTA and TG methods. The metal-free ligands and their copper(II) complexes were
tested for their in vitro anticancer activity against human colon carcinoma (HT-29). The results
showed that the synthesized copper(II) complexes exhibited higher anticancer activity than
their free ligands. Of all the studied copper(II) complexes, the bromo-substituted
complex 9b exhibited high anticancer activity at low micromolar inhibitory
concentrations (IC50 = 0.58 µM), compared to the other complexes and the free
ligands.

Keywords: Neocryptolepine, Copper(II) complexes, Synthesis, Spectroscopic characterization,

Anticancer activity

Introduction:

In recent years, there has been a rapid expansion in research and development of novel
metal-based anticancer drugs to improve clinical effectiveness, reduce general toxicity and
broaden the spectrum of activity [1]. Cisplatin is regarded as one of the most effective

1
anticancer drugs, even if severe toxicities and drug resistance phenomena limit its clinical use
[2]. Among extensive researches aiming to characterize other anticancer-active inorganic
complexes with improved pharmacological properties compared to cisplatin are the ones
focusing on the use of biologically active complexes formed by essential ions such as copper
[3]. Copper has a long history of medicinal application but its potential anticancer activity has
been explored only in the last decades [4,5]. In this context, complexes with biologically active
ligands are particularly attractive, as they combine qualities of classic non-targeted coordination
compounds and organic ligands with selectivity for cellular targets [1-11]. The inclusion of
biologically active ligands into organometallic complexes offers much scope for the design of
novel drugs with enhanced, targeted activity. Studies on such complexes are expected to
indicate that new mechanisms of action are possible through combining the bioactivity of the
ligand with the properties inherent to the metal, leading to the possibility of overcoming current
drug resistance pathways. As an extension to our previous work on neocryptolepine-based
therapy [12], we were interested in studying the effect of incorporation of metal ions into
biologically active ligand with natural origin such as neocryptolepine (5-methyl-5H-indolo[2,3-
b]quinoline), Figure 1.
Insert Figure 1 and its caption here
The pharmacological importance of neocryptolepine is demonstrated by the fact that it is a
natural product alkaloid isolated from the roots of Cryptolepis sanguinolenta, an African plant
used in traditional medicine [13]. The medicinal applicability of neocryptolepine as
antimalarial, antischistosomal and anticancer active compounds has been confirmed [12-18].
However, metal complexes with neocryptolepine containing ligand have never been reported in
the literature. With the aim of improving the biological activity and reducing the cyctotoxcity of
the neocryptolepine core herein we report on the synthesis and in vitro anticancer activity of the
first generation of copper(II) complexes with aminoalkylamino substituted neocryptolepine
ligand.
Experimental
Materials and physical measurements
All chemicals and solvents were of analytical grade and were used as received without
further purification. The metal salts CuCl2.2H2O (BDH), CuBr2 (BDH), Cu(OAc)2.H2O
(Sigma) and Cu(ClO4)2.6 H2O were used as supplied.
Elemental microanalyses (C,H,N) were performed at the Micro Analytical unit, Cairo
University Giza, Egypt. Copper(II) content in the complexes was determined via
complexmetric method, while halide ions were determined by Mohr's method [19a,b]. IR

2
spectra have been recorded on Neneyeus Nicolidite–640MSAFT-IR, Thermo Electronic CO.
using KBr pellets. The electronic spectra have been measured in nujol mull using 4802 UV-Vis
spectrophotometer. The 1H NMR spectrum was recorded in DMSO-d6 on a Varian Gemini 200
NMR spectrometer at 300 MHz. The electron paramagnetic resonance (EPR) spectra were
recorded on a Varian E-109c spectrometer equipped with a field modulation unit at 100 kHz.
Measurements were effected in the X-band on a microcrystalline powder at room temperature;
the microwave power was around 10 mW. The molar conductivity has been measured at room
temperature with approximately 10-3 M in DMF 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 [20]. The Thermal
analysis (TG/DTA)were carried out by using a Shimadzu DAT/TG-50 thermal analyzer with a
heating rate of 10oC/min under N2 atmosphere with a flowing rate of 20 mL/min in the
temperature range 20-900oC using platinum crucibles. Melting points were measured by
using Stuart melting point apparatus.
Synthesis of ligands L1 and L2 :
The starting material 11-chloro-6H-indolo[2,3-b]quinoline 5, was prepared as described
previously [18]. The L1/L2 ligands were synthesized by refluxing a hot ethanolic solution of 5
(0.5g/1.8mmol) with excess of 1,2-diaminoethane and 1,3-diaminopropane, respectively for 3-5
h at 80 0C. The progress of reaction was monitored by TLC. The reaction mixture was poured
into cold water, the product was extracted with chloroform dried over anhydrous Na2SO4,
evaporate the organic layer to give yellow precipitate, the formed precipitate was collected by
filtration, washed and dried in vacuum over anhydrous CaCl2.
N-(2-Aminoethyl)-5-methyl-5H-indolo[2,3-b]quinolin-11-amine (L1): Yield (90%); yellow
solid; m.p: 100 °C. FT-IR (KBr, cm-1): 3392, 3352 υ(NH2); 1613, 1549, 1240, 1161, 742
δ(NH2); 3247, 3160 υ(NH)sec; 1H NMR (DMSO-d6, δ ppm): 2.88 (br. s, 2H, -NH-CH2-CH2-
NH2), 3.78 (br. s, 2H, NH2), 3.87 (br. m, 2H, -NH-CH2-CH2-NH2), 4.16 (s, 3H, N-CH3), 5.37
(br. s, 1H, NH ), 6.88 (br. s, 1H, NH), 7.08 (d, 1H, Ar-H), 7.27-7.50 (m, 3H, Ar-H); 7.80-7.99
(m, 3H, Ar-H); 8.49 (d, 1H, Ar-H).
N-(3-Aminopropyl)-5-methyl-5H-indolo[2,3-b]quinolin-11-amine (L2). Yield 95%; yellow
solid; m.p: 95−98 °C. FT-IR (KBr, cm-1): 3322, 3260 υ(NH2); 1604, 1551, 1249, 1120, 738
δ(NH2); 3195, 3150 υ(NH)sec; 1H NMR (DMSO-d6, δ ppm): 1.74 (br. m, 2H, -NH-CH2-CH2-
CH2-NH2), 2.61 (br. s, 2H, -NH-CH2-CH2-CH2-NH2), 2.98 (br. s, 2H, NH2), 3.61 (br. s, 2H, -
NH-CH2-CH2-CH2-NH2), 4,14 (s, 3H, N-CH3), 6.85 (br. s, 1H, NH) 7.09 (t, 1H, Ar-H), 7.27 (t,

3
1H, Ar-H), 7.39 (t, 1H, Ar-H), 7.50 (d, 1H, Ar-H ), 7.81 (t, 1H, Ar-H), 7.93 (t, 1H, Ar-H), 8.49
(br. m., 1H, Ar-H ).
General method for the preparation of copper(II) complexes, 7a-10a, 7b- 10b:
All copper(II) complexes were prepared by adding a hot ethanolic solution of the
appropriate copper(II) salts (1.0 mmol) to a stirred absolute ethanolic solution of ligands (1.0
mmol) L1/L2. The reaction mixture was further stirred for 4-6 h, the precipitated complexes
were filtered off, washed several times with ethanol and finally dried under vacuum over
anhydrous calcium chloride.
Anticancer activity:

The inhibition of cell growth by copper(II) complexes 7a,7b; 8a, 8b; 9a, 9b; 10a,
10b and the corresponding uncoordinated ligands L1 and L2 was evaluated using a 3-(4,5-
dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cleavage assay with
colorectal adenocarcinoma (HT-29) cells [21]. The cells were seeded at 1×10 4 cells/well
in 96-well plates in RPMI medium supplemented with 10% FBS. After 20 h of
culture, copper(II) complexes 7a,7b; 8a, 8b; 9a, 9b; 10a, 10b and the corresponding
uncoordinated ligands L1 and L2 M at 10 µM concentration were added in triplicate, and
the cells were further cultured for 72 h. The cells were then exposed to 5 mg/mL MTT
in PBS at a final concentration of 1 mg/mL in culture for 5 h. Formazan crystals
formed during the incubation period were dissolved overnight at 37 ◦C by adding 10%
SDS containing 20 mM HCl. The absorbance was measured at 570 nm.
Results and discussion
Neocryptolepines with amino-substitution in position 11th were prepared from methyl
1H-indole-3-carboxylate, 1 and N-methylaniline 2 (Scheme 1). The intermediate methyl 2-(N-
methylphenylamino)-1H-indole-3-methylcarboxylate 3, obtained via chlorination with N-
chlorosuccinimide in the presence of 1,4-dimethylpiperazine, followed by addition of N-
methylaniline as trichloroacetate, was cyclized in boiling diphenyl ether to 5,6-dihydro-11H-
indolo[2,3-b]quinolin-11-one 4, which was dehydroxy chlorinated with POCl3 to afford the key
structure 11-chloroneocryptolepine 5, which was aminated via SNAr reaction in ethanol with the
appropriate amines at high temperature, yielding target ligands 6 (L1 and L2). This method is
used for synthesis of neocryptolepines with substitutions on B rings (11-substitution) as
depicted in Scheme 1.
Insert Scheme 1 and its caption here

4
All spectroscopic data are consistent with the proposed structures for all compounds
(cf. experimental section).
Insert Scheme 2 and its caption here

The reaction of L1 and L2 ligands with CuX2 salts (X= OAc, Cl, Br and ClO4) in the
(1:1) molar ratio led to the formation of copper(II) complexes 7a-10a and 7b-10b, Scheme 2.
The analytical Table (1); spectral data, Tables (2), (3) and (5) and thermal studies Table (4) are
consistent with the formulation in Scheme 2. All copper(II) complexes derived from L1 and L2
ligands are separated with (1M:1L) molar ratio whereas, the binuclear metal complexes 7a and
7b are formed through the reaction containing 1 mole of ligand (L1 or L2 ) and 1 mole of
copper(II) acetate. All the metal complexes are stable, nonhydroscopic, partially soluble in most
organic solvents such as absolute ethanol, methanol, acetone, acetonitrile, chloroform,
dichloromethane, and benzene. They are completely soluble in DMSO and DMF. The molar
conductivity measurements for all metal complexes in (1x10-3 M) DMF solution at 25° C are
found within the range of conducting feature except complexes 7a and 7b. The molar
conductance values, 73.1, 86, 61.2 and 62.5 Ω-1cm2mol-1 for complexes
[Cu(L1)Cl(H2O)3].Cl.3H2O.0.5EtOH, [Cu(L1)Br(H2O)2].Br.3.25H2O,
[Cu(L2)Cl(H2O)3].Cl.6H2O, and [Cu(L2)Br(H2O)2].Br.3H2O.0.5EtOH are found of the type 1:1
electrolytes [22-24]. Also, the molar conductance values for complexes
1 2
[Cu(L )(H2O)4](ClO4)2.2.75H2O and [Cu(L )(H2O)4](ClO4)2.7.5H2O.0.5EtOH are found to be
100 and 95 Ω-1 cm2 mol-1 indicating the 2:1 electrolytic nature of these complexes [22-24,25].
However, the low conductance value for [Cu2(L2)(OAc)4].3H2O (15.5 Ω-1cm2mol-1) indicates
its non-electrolytic nature. The low molar conductivity of non-electrolyte of this complex is due
to partial displacement of the anion by DMF molecules [22].

Insert Table 1 and its caption here

Infrared spectral data of L1, L2 ligands and their Cu(II) complexes
The important IR spectral bands with their assignment of L1, L2 and their metal
complexes taken in the region 4000-400 cm-1 are given in Table (2). These spectra proved some
information regarding the mode of coordination in copper(II) complexes and are compared
carefully with that of the free ligands, possessed several donor sites as quinolone and indole
nitrogens, NH2 group and secondary NH which have a great tendency to interact with copper(II)
ion.
L1 and L2 ligands have characteristic bands at around (3392, 3358), 1613 and (3322,

5
3260), 1604 cm-1 which are associated to the asymmetric, symmetric NH2 stretching vibrations
and in plane –NH2 deformation vibrations, respectively [26-28]. These bands are splitted and
lost their intensities for both L1 and L2 complexes. Also, they display a bathochromic shift by
36-117 cm-1 for L1 complexes and they are shifted to different frequencies for L2 complexes.
Besides, the red (1582-1608) and the blue (1610-1619) cm-1 shifting of the in plane –NH2
vibrations for L1 and L2 complexes is due to the participation of the NH2 group in coordination.
On the other hand, the bands observed at around 1549, 1240, 1161, 745 and 1551, 1249, 1120,
738 cm-1 are assigned to the amino scissoring [27,29], twisting, wagging and rocking modes for
L1 and L2 ligands, respectively [28b,29]. The result, as Table (2) shows, is that these amino
vibrational bands are strongly affected by complexation. Also, the ligands were characterized
by the relevant peaks assignable to the secondary N-H stretching vibration in the range 3150-
3247 cm-1 [30,31]. Upon complexation of L1 and L2 ligands to the copper(II) ion, the stretching
vibration of this group is red and blue shifted for L1 and L2 complexes, respectively. All other
bands characterized to quinoline and indole nitrogens remain unchanged in copper(II)
complexes when compared with the free ligands, indicating that the ring nitrogens are not
involved in the coordination. The above results proved that the side-chain nitrogens on the
indoloquinoline core are involved in the coordination with the copper(II) ion.
The IR spectra of the acetate complexes 7a and 7b exhibit two new bands at 1563-1597
and 1300-1339 cm-1, attributed to asymmetric and symmetric stretching vibrations of acetate
ion, respectively. The coordination mode of acetate group has been proved from the difference
value (∆υ) between υasym(COO- ) and υsym (COO-). This value is around 264 and 258 cm-1 in
copper(II) complexes 7a and 7b, respectively, indicating that the acetate ions are coordinated to
the metal ion in the monodentate fashion [32]. In addition, the acetate complexes display
medium bands at 1563-1566 and 1403-1409 cm-1 corresponding to bridged bidentate acetate ion
[33].
In copper(II) complexes 10a and 10b the presence of perchlorate ion is confirmed by
the appearance of strong absorption bands in the region 1080-1089 and 930-934 cm-1 pointed to
the asymmetric and symmetric stretching of ClO-4 ion, respectively, in addition to a relatively
medium band in the range of 624-627 cm-1 due to bending mode for ClO-4 ion [34]. This
indicates that the symmetry of perchlorate ion is maintained in complexes 10a and 10b.
Therefore, these data are in agreement with the molar conductance values, Table (1), indicates
that the perchlorate ions were found outside the coordination sphere of these complexes. The
medium to strong absorption bands of the copper(II) complexes at 3210-3580 cm-1 were found
to be ascribed to the overlap between the different NH2 vibrations, lattice/coordinated water

6
molecules or ethanol. Moreover, the spectra of all complexes except 7a and 7b display an
additional band at 915-969 cm-1 assigned to coordinated water molecules [24,25]. The
appearance of weak bands at 432-486 and 500-595 cm-1 regions in all metal complexes may be
assigned to υ(M-N) [33b] and υ(M-O) vibrations, respectively [33a,35a].
Insert Table 2 and its caption here
Electronic spectra and magnetic moments:
Electronic spectral data of L1, L2, their copper(II) complexes and the room temperature
magnetic moment values (µeff BM.) per metal ion are recorded in Table (3). The electronic
spectra of L1 and L2 ligands displayed five electronic bands at 250, 285, 315, 345, 380 nm and
255, 283, 310, 340, 385 nm, respectively. The first and the second electronic bands correspond
to π-π* transitions of the benzenoid system and heterocyclic rings of the compounds [36,37]
which remain nearly unchanged in the spectra of their metal complexes. The third and the
fourth bands correspond to n-π* due to the lone pairs of electrons on the nitrogen atom [36] and
indole ring. The fifth band can be ascribed to the transition within the whole molecule,
essentially an intramolecular charge transfer interaction. The CT bands seem to be originated
from the aryl moiety. Copper(II) complexes (d9 system) have different structures due to their
various coordination numbers. Six coordinated Cu(II) complexes possesses distorted octahedral
structure. Also, four coordinated copper(II) complexes possess distorted tetrahedral or square
planar geometry, whereas, five coordinated copper(II) complexes have distorted square
pyramidal or triagonal bipyramidal geometry. The observed tetragonal distortion is due to
splitting of the eg and t2g levels of the 2D free ion term into B1g, A1g, B2g and Eg levels,
respectively. The energy level sequence that depends on the amount of distortion is attributed to
the ligand field and Jahn-Teller effect [37]. The electronic spectra of copper(II) complexes 7a
and 7b display broad bands at 730, 620, 533 and 720, 610, 520 nm assigned to 2B1g→2A1g(υ1),
2
B1g→2B2g(υ2) and 2B1g→2Eg (υ3) transitions, respectively indicating the square-planar structure
[38]. A moderately intense band observed at 400-430 nm is attributed to O→Cu charge transfer
[39]. Also, the electronic spectra of Cu(II) complexes 8a, 8b, 10a and 10b exhibit three bands
at 840-860, 600-760 and 480-530 nm corresponding to 2B1g→2A1g(υ1), 2B1g→2B2g(υ2) and
2
B1g→2Eg (υ3), respectively. The spectra are typical of copper(II) complexes with an elongated
tetragonal geometry [40]. This is due to the splitting of 2Eg and 2T2g states of the octahedral
Cu(II) (d9) under the effect of the tetragonal distortion. The copper(II) complexes 9a and 9b
show three absorption bands with variable intensities at 823-872, 640-711 and 514-580 nm,
2
assigned to B1g→2A1g(υ1), 2
B1g→2Eg(υ2) and 2
B1g→2B2g(υ3) transitions, respectively,
indicating the five-coordinated Cu(II) in square-pyramidal geometry [35,41]. In all copper(II)

7
complexes, a moderately intense peak observed at 345-480 nm is assigned to ligand-metal
charge transfer transition [42,43]. The measured magnetic moment values for Cu(II) complexes
except 7a and 7b are 1.98-2.2 BM. The value of magnetic moments is higher than the normal
value (1.73 BM.) of the copper(II) complexes. This may be due to the spin-orbital coupling
[36]. Complexes 7a and 7b show low magnetic moment of 1.4 and 1.3 BM. per copper ion,
respectively. The subnormal magnetic moment indicates that the copper centers are
antiferromagnetically coupled.
Insert Table 3 and its caption here
Thermal studies:
DTA, (TG and DTG) curves and the data characterized the thermal decomposition
behaviors of L1, L2 ligands and their copper(II) complexes 7a-10a, 7b-10b are presented in
Table (4). Thermal degradation of ligands L1, L2 and their copper(II) complexes were studied
within the temperature range of 20-900°C. DTA curves of L1 and L2 ligands depict two broad
endothermic peaks and one asymmetric peak at Tmax=76, 122°C and Tmax =80 °C, respectively.
The TG weight losses (12.25 %) and (15.08 %) in these temperature ranges confirm the loss of
2.25 and 3.0 moles of hydrated water. The lower temperature of dehydration Tmax=76 and 80
°C, as well as the weak nature of DTA peak indicating that, the water molecules do not
participate in the lattice forces [44,46]. The dehydration process is followed by several
endothermic/exothermic peaks located at Tmax = 269, 440, 588, and 148, 403, 428, 497, 675 °C
assigned to decomposition of L1 and L2 ligands, respectively, Table (4). The TG curves of
ligands ended with 1.0 C as a final product which is stable up to 800-900 °C. The observed
differences in the thermal stability of L1 and L2 ligands may be related to the presence of the
lattice water molecules that keep the structure of L1 ligand less flexible due to the inner and
inter hydrogen bonding [45].
DTA and TG data of copper(II) complexes established that the complexes lose their
solvent of crystallization in the temperature range 20-308°C. The desolvation/dehydration
process has been characterized by endothermic behavior. The lower onset temperature of
desolvation and/or dehydration process (20-26°C) together with its extended range of
temperature pointed to the fact that the solvent of crystallizations are distributed in the crystal
voids with a physical bonding [35a,46-48]. The desolvation peak is followed by successive
endothermicl⁄exothermic peaks assignable to decomposition process. The thermal
decomposition of all complexes ended with the formation of copper metal [44,48], copper metal
mixed with some of carbon [49a,50a] or a mixture of copper(II) oxide and carbon [49b].

8
 The thermal decomposition of acetate complexes 7a and 7b takes place mainly in three
successive stages in the temperature range 26-129, 129-223, 223-600 and 20-170, 170-255,
255-450°C, respectively. The first decomposition stage corresponds to the loss 0.75 mole of
EtOH+0.75 mole of hydrated H2O and 2.5 moles of hydrated H2O with mass losses of 6.85 %
and 6.24 % for complexes 7a and 7b, respectively. The desolvation process is characterized by
two successive endothermic DTA peaks at Tmax (53,113°C) and (54,142°C) for complexes 7a
and 7b, respectively. The dehydration or desolvation process started at low temperature with
weak and broad nature of endothermic peaks suggesting that the solvent has a different
crystalline nature [51] as well as the uncoordinated nature of the solvent molecules [48,52-54].
The second stage accompanied by the removal of 2.0 moles of coordinated acetate and (3.0
moles of coordinated acetate+0.5 mole of lattice water) for complexes 7a and 7b, respectively.
The DTA curves represented the second stage depicting three/two weak-medium endothermic
peaks at Tmax (148, 182, 216) and (205,229°C) for complexes 7a and 7b, respectively. These
peaks may be ascribed to the rupture of the coordinate and covalent bonds formed between
metal ions and acetate ions [55a], confirming the coordination of acetate [55b]. The third stage
assigned to mass loss of 1.46 and 0.46 mole of coordinated acetate associated with ligand
decomposition, as indicative from TG mass loss for complexes 7a and 7b, respectively. The
third decomposition stage is associated by one strong exothermic DTA peak at Tmax (281°C)
and two distinct exothermic DTA peaks at Tmax (297, 368°C) for complex 7a and 7b,
respectively. The observed higher percentages of the residue in 7a and 7b than the calculated
ones for 2CuO may be due to contamination of the oxide with some of carbon or the formation
of other compounds during thermal reaction [49b]. The contamination of the oxide with some
of carbon expected to result from the anion breakdown process [50b,c].
The thermal decomposition of halogen complexes 8a, 9a, 8b and 9b proceeds mainly
in three stages within temperature range 20-900 °C, Table (4). The first step within temperature
range 20-308°C corresponds to loss of TG mass loss of 0.5EtOH, 2.75 H2O in complexes 8a
and 9b, complete dehydration in complex 9a and partially dehydration for complex 8b, (loss of
4.75 moles of H2O molecules). This stage is characterized by endothermic peaks, Table (4). In
the second decomposition stage within the temperature range 224-404, 308-452, 210-433 and
284-431°C, lattice and/or coordinated water molecules together with the partial decomposition
of chlorine or bromine gas were eliminated for 8a, 9a, 8b and 9b chelates, respectively. This
stage is associated with endothermic reaction, Table (4). In the third decomposition stage the
elimination of 0.25 mole Cl2 gas along with one mole of L1; 0.95 mole of L1; 0.5 mole of Cl2
gas along with 0.85 mole of L2 and 0.6 mole of Br2 gas together 0.84 mole of L2 are

9
 characterized by mass losses of 55.42%; 45.26 %; 49.06% and 54.97% for complexes 8a, 9a,
8b and 9b, respectively. The decomposition of L1 and L2 ligands as gases appeared in the DTA
graph as broad exothermic peaks at Tmax (719, 810, 719 and 760°C) for these complexes. The
thermal decomposition of halogen complexes ended with copper [44] or copper mixed with
some of carbon as a final product [49a,50a]. This is attributed to the reducing properties of
halide ions towards the copper(II) ions, in addition to the reducing properties of the ligands
[44].
Complex 10b is behaving in a manner different from complexes 7a-9a and 7b-9b
because during further heating, this complex undergoes delegation reaction in one stage
accompanied with the loss of lattice/coordinated water molecules and ionic perchlorate at low
temperature but some of the other Cu(II) complexes undergo delegation reaction in more than
one stage at higher temperature. This is evident from their plateaus observed in TG curves. The
degradation of complex 10b comprises three stages in the temperature range 20-218, 218-229
and 229-400°C. The first one starts with release of 0.5 mole of ethanol and 2.5 moles of
hydrated water molecules with a weight loss of 8.54%, whereas, the second decomposition
stage within the temperature range 218-229°C corresponds to the loss of five moles of lattice
water together with 1.5 moles of ionic perchlorate with a weight loss of 30.02%. Finally, the
third decomposition stage exhibits a weight loss of 53.47 % attributed to elimination of four
moles of coordinated water, half mole of ionic perchlorate along with one mole of L2 ligand.
The TG data, Table (4) indicated that complex 10b starts its decomposition at 218°C to give
copper metal as an ultimate pyrolysis product [50,55a]. The mass loss of the final residue of
copper(II) complexes 8a, 9a and 8b, 9b has confirmed the chemical formulae agrees with the
Cu% which is determined by complexmetric titration. The above discussion and Table (4)
showed that all copper(II) complexes of L2 ligand are thermally more stable than those of L1.
This may be due to the difference in the size of the chelate ring formed between ligand and
copper(II) ion.
Insert Table 4 and its caption here
Electron spins resonance (ESR) spectral studies
The ESR spectral data for copper(II) complexes are listed in Table (5). The ESR
spectra of powdered complexes are measured at room temperature and are all axial symmetry
with g // › g ⊥ › 2.0023, Table (5). Also, the observed data pointed to the fact that the unpaired

electron lies predominantly in the dx2-y2 orbital [37], resulting in a 2B1g ground state [24,56]. In
these complexes the g ⊥ > 2.03 where all the principal axes aligned parallel indicating the

10
 tetragonal distorted structure for Cu(II) complexes. The geometric parameter G, which is a
measure of the exchange interaction between Cu(II) ions has been calculated using this relation
G = g // − 2.0023 g ⊥ − 2.0023 . In this case the axial symmetry parameter G, lies in the

range 4.10-4.35 for all complexes except complexes 7a and 7b, indicating to the absence of the
exchange interaction, while, the G values for complexes 7a and 7b are found to be 3.71 and
3.24, respectively, indicating the existence of some exchange interactions between Cu(II)
centers. In addition, the g // values < 2.3 indicating a considerable covalence character in

copper-ligand bonding in the bonding between copper(II) ion and the ligand [35a,57]. The
complexes showed hyperfine spectral lines at the lower field, in addition to an intense
unresolved peak in the higher field region as in complex 8b. The high field parts of the spectra
are slightly splitted in most of copper(II) complexes. The complexes showed hyperfine splitting
and their g // , g ⊥ , A// , A⊥ values have been estimated in Table (5). In case of complex 9a, no

detectable hyperfine structure was observed in the solid state, indicating the presence of one
species. The spectrum of this complex is anisotropic with g // =2.22 and g ⊥ =2.056

components. The g // region does not exhibit hyperfine coupling. This may be attributed to

dipolar interactions between the copper(II) ions in the unit cell [58]. The ESR
parameters g // , g ⊥ , A// , A⊥ and the energies of d-d transitions were used to calculate the

bonding parameters α2, β2 and γ2 which may measure the covalence of the in-plane σ bonds, in-
plane π bonds and out-of-plane π bonds, respectively [35a]. The values of the bonding
parameters α2, β2 , γ2 and the orbital reduction factors were calculated using the equations
reported elsewhere [59]. The observed α 2 values (0.60-0.72) for complexes 7a-9a and 7b-9b,
indicate that these complexes have some covalent character for σ-bond between Cu(II) ion and
ligands. Meanwhile, the α 2 values are found to be 0.58 and 0.50 for complexes 10a and 10b,
indicating complete covalent bonding between copper(II) ion and the ligands [24]. According to
Hathaway [59], the K // and K ⊥ values for the complexes under investigation are in agreement

with the relation K // < K ⊥ which indicates the presence of significant in-plane π bonding. This is

further supported by the bonding parameters α2 and β2 which are less than one, indicating
significant in-plane σ-bonding and in-plane π-bonding. Moreover, γ2 values of all complexes
except (8a, 7b and 8b) are found to be less than 1.0 indicating the covalent character of the
bonds whereas, γ2 values for complexes 8a, 7b and 8b are found to be greater than 1.0 indicate
to some ionic character for out-of-plane π bonding. The empirical factor ƒ = g // A// , can be

considered as diagnostic of the stereochemistry. The range reported for square planar

11
 complexes may vary from 105 to 135 cm, for small to extreme distortion and 150 to 250 cm for
tetragonal distorted complexes. The calculated ƒ values for complexes 7a and 7b are in 134.7-
138.1 cm indicating the distorted square planar structure. Meanwhile, the large ƒ values 161.0-
214.15 cm, indicate the moderate distortion from planarity.
Anticancer Activity:
All copper(II) complexes 7a,7b; 8a,8b; 9a,9b; and 10a,10b and the corresponding
uncoordinated ligands L 1 and L2 were examined in vitro for their anticancer activity against
human colon carcinoma (HT-29) cell line. Screening for anticancer activity included
measurement of % of the in vitro cell inhibition by using MTT colorimetric assay at 10 µM
concentration [21]. The results shown in Table (6) indicated that these complexes exhibited
much higher anticancer activity when compared to the corresponding ligands which indicate
that the coordination of the chelate ligand around the copper(II) enhances the anticancer
activity.
Insert Table 6 and its caption here

Furthermore, this result confirmed that the participation of the chloro, bromo, acetate
and perchlorate substituent groups in the complex anticancer activities has slight effect. IC50
values were estimated for the most active complexes 7b, 8a and 9b at around 8.77 µM for 7b,
2.21 µM for 8a and 0.58 µM for 9b where complex 9b showed the best anticancer activity as
depicted in Figure 2.
Insert Figure 2 and its caption here
Conclusion
In summary, new copper(II) complexes coordinated with
aminoalkylaminoneocryptolepine ligands have been synthesized. The analytical and the spectral
data supported the structure and the geometry of complexes. The evaluation of anticancer
activity against human colon carcinoma (HT-29) cell line proved that both ligands and their
copper(II) complexes are promising anticancer active agents. Of all the studied copper(II)
complexes, compound 9b exhibited higher anticancer activity with an IC50 of 0.58 µM. The
results also proved that the complexes are more biologically active than that of their ligands.
Further variation in transition metal type to obtain more biologically active complexes is
currently underway in our laboratory.

Acknowledgements

12
 The authors would like to thank Professor Masaharu Seno research team, Division of
Biochemistry, Graduate School of Natural Science and Technology, Okayama University for
their help with the in vitro anticancer activity.

References and Notes

[1] (a) W. Liu, R. Gust ''Metal N-heterocyclic Carbene Complexes as Potential

Antitumor Metallo Drugs'' Chem. Soc. Rev. 42 (2013) 755-773; (b) S.R. Pattan,
S. B. Pawar, S. S. Vetal, U. D. Gharate, S. B. Bhawar ''The Scope of Metal
Complexes in Drug Design'' Indian drugs 49 (2012) 5-12; (c) P.C.A.
Bruijnincx, P.J. Sadler ''New Trends for Metal Complexes with Anticancer
Activity'' Curr. Opin. Chem. Biol. 12 (2008) 197–206; (d) T.W. Hambley
''Metal-Based Therapeutics'' Science 318 (2007) 1392-1393. (e) C. Orvig, M. J.
Abrams ''Medicinal inorganic chemistry'' Chem. Rev. 99 (1999) 2201–2203.
[2] P.J. Sadler ''Inorganic Chemistry and Drug Design'' Advanced Inorganic Chemistry 36
(1991) 1-48.
[3] R. Mukherjee, In Comprehensive Coordination Chemistry II-From Biology to
Nanotechnology; McCleverty J. A, Meyer T. J, Eds.; Elsevier Ltd.: Oxford (UK), 6
(2004) 747-910.
[4] S. Tardito, O. Bussolati, M. Maffini, M. Tegoni, M. Giannetto, V. Dall'Asta, R. Franchi-
Gazzola, M. Lanfranchi, M.A. Pellinghelli, C. Mucchino, G. Mori, L. Marchio,
''Thioamido Coordination in a Thioxo-1,2,4-Triazole Copper(II) Complex Enhances
Nonapoptotic Programmed Cell Death Associated with Copper Accumulation and
Oxidative Stress in Human Cancer Cells'' J. Med. Chem. 50 (2007) 1916-1924.
[5] B.S. Creaven, B. Duff, D.A. Egan, K. Kavanagh, G. Rosair, V.R. Thangella,
M. Walsh ''Anticancer and Antifungal Activity of Copper(II) Complexes of
Quinolin-2(1H)-one-derived Schiff Bases'' Inorg. Chim. Acta 363 (2010)
4048–4058 and references cited therein.
[6] W.H. Ang. P.J. Dyson ''Classical and Non-Classical Ruthenium-Based Anticancer
Drugs: Towards Targeted Chemotherapy'' Eur. J. Inorg. Chem. 20 (2006) 4003–4018.
[7] P. Heffeter, U. Jungwirth, M. Jakupec, C. Hartinger, M. Galanski, L. Elbling, M.
Micksche, B. Keppler, W. Berger ''Resistance Against Novel Anticancer Metal
Compounds: Differences and Similarities'' Drug Resist. Updates 11 (2008) 1-16.
[8] M. Frezza, S.S. Hindo, D. Tomco, M.M. Allard, Q.C. Cui, M.J. Heeg, D. Chen,

13
 Q.P.Dou, C.N. Verani '' Comparative Activities of Nickel(II) and Zinc(II) Complexes of
Asymmetric [NN'O] Ligands as 26S Proteasome Inhibitors'' Inorg. Chem.48 (2009)
5928–5937.
[9] G.E. Atilla-Gokcumen, D.S. Williams, H. Bregman, N. Pagano, E. Meggers
''Organometallic Compounds with Biological Activity: A Very Selective and Highly
Potent Cellular Inhibitor for Glycogen Synthase Kinase 3'' Chem. Biochem. 7 (2006)
1443–1450.
[10] E. Meggers ''Targeting proteins with metal complexes'' Chem. Commun. 9 (2009)1001–
1010.
[11] L.K. Filak, S. Göschl, P. Heffeter, S.K. Ghannadzadeh, A.E. Egger, M.A. Jakupec, B.K.
Keppler, W. Berger, V.B. Arion ''Metal-Arene Complexes with Indolo[3,2-c]-Quinolines:
Effects of Ruthenium vs Osmium and Modifications of the Lactam Unit on
Intermolecular Interactions, Anticancer Activity, Cell Cycle, and Cellular Accumulation''
Organometallics 32 (2013) 903-914.
[12] W.-J. Lu, K.J. Wicht, L. Wang, K. Imai, Z.-W. Mei, M. Kaiser, I. El-Sayed, T.J. Egan T.
Inokuchi “Synthesis and Antimalarial Testing of Neocryptolepine Analogues: Addition
of Ester Function in SAR Study of 2,11-disubstituted Indolo[2,3-b]Quinolones” Eur. J.
Med. Chem. 64 (2013) 498-511.
[13] Z.-W. Mei, L. Wang, W.-J. Lu, W. Peng, T. Maeda, C.-Q.P. M.Kaiser, I. El-Sayed, T.
Inokuchi ''Synthesis and In Vitro Antimalarial Testing of Neocryptolepines: SAR Study
for Improved Activity by Introduction and Modifications of Side Chains at C2 and C11
on Indolo[2,3-b]quinolines'' J. Med. Chem. 56 (2013) 1431–1442.
[14] N. Wang, K. Wicht, L. Wang, W.-J. Lu, R. Misumi, M.-q. Wang, A.A. Aelkgoha, M.
Kaiser, I. El-Sayed, T.J. Egan, T. Inokuchi ''Synthesis and in Vitro Testing of
Antimalarial Activity of Non-natural-type Neocryptolepines: SAR Study of 2,11- and
9,11-Disubstituted 6-Methylindolo[2,3-b]Quinolones'' Chem. Pharm. Bulletin, 61 (2013)
1-9.
[15] W. Peng, M. Świtalsk, Z.-W. Mei, Y.Edazawa, L. Wang, I. El-Sayed, J. Wietrzyk, T.
Inokuchi ''Synthesis and in Vitro Antiproliferative Activity of New 11-
Aminoalkylamino-Substituted Chromeno[2,3-b]indoles'' Eur. J. Med. Chem. 58 (2012)
441-451.
[16] L. Wang, M. S´witalska, Z.-W. Mei, W.-J. Lu, Y. Takahara, X.-W. Feng, I. El-Sayed, J.
Wietrzyk, T.Inokuchi ''Synthesis and in Vitro Antiproliferative Activity of New11-

14
 Aminoalkylamino-substituted 5H- and 6H-Indolo[2,3-b]Quinolines; Structure–Activity
Relationships of Neocryptolepines and 6-methyl Congeners'' Bioorg. Med. Chem. 20
(2012) 4820–4829.
[17] I. El-Sayed, F. Ramzy, S. William, M. El-Bahanasawy, M.M. Abdel-Staar
''Neocryptolepine Analogues Containing N-Substituted Side-Chains at C-11: Synthesis
and Antischistosomicidal Activity'' Med. Chem. Res. 21 (2012) 4219-4229.
[18] I. El-Sayed, P.V. der Veken, L. Dhooghe, S. Hostyn, G.V. Baelen, G. Lemière, B.U.W.
Maes, P. Cos, L. Maes, J. Joossens, A. Haemers, L. Pieters, K. Augustyns "Synthesis and
Antiplasmodial Activity of Aminoalkyl- aminosubstituted Neocryptolepine Derivatives"
J. Med. Chem. 52 (2009) 2979–2988.
[19] (a) J. Bassett, R.C. Denney, G.H. Jeffery, J. Mendham, Vogel’s Textbook of Quantitative
Inorganic Analysis Including Elementary Instrumental Analysis, 4th edition, Longman
Group, London, 1978, pp. 316–322. (b) Note: The halide content in the complexes was
indirectly determined by Mohr's method after the decomposition of the samples in
concentrated nitric acid by boiling, followed by addition of distilled H2O to give
aqueous solution of metal salt.
[20] J. Lewis, R.G. Wilkins, Modern Coordination Chemistry, Interscience, New York, 1960,
p. 403.
[21] T. Mosmann ''Tim Rapid Colorimetric Assay for Cellular Growth and Survival:
Application to Proliferation and Cytotoxicity Assays'' Immunol. Methods 65 (1983)
55–63.
[22] W.J. Geary ''The use of Conductivity Measurements in Organic Solvents for the
Characterization of Coordination Compounds'' Coord. Chem. Rev. 7 (1971) 81-122.
[23] H.F. Abd-El-halim, M.M. Omar, G.G. Mohamed ''Synthesis, Structural, Thermal Studies
and Biological Activity of a Tridentate Schiff Base Ligand and their Transition Metal
Complexes'' Spectrochim. Acta A 78 (2011) 36-44.
[24] S.M. Emam, S.A. AbouEl-Enein, F.A. El-Saied, S.Y. Alshater ''Synthesis and
Characterization of some Bi, Tri and Tetravalent Transition Metal Complexes of N-
(Furan-2-yl-methylene)-2-(p-tolylamino)acetohydrazide HL1 and N-(Thiophen-2-yl-
methylene)-2-(p-tolylamino)acetohydrazide HL2'' Spectrochim. Acta A 92 (2012) 96-
104 and references cited therein.
[25] (a) S.M. Emam, F.A. El-Saied, S.A. AbouEl-Enein, H.A. El-shater ''Cobalt(II),
Nickel(II), Copper(II), Zinc(II) and Hafnium(IV) Complexes of N′-(Furan-3-

15
 ylmethylene)-2-(4-methoxyphenylamino)acetohydrazide'' Spectrochim. Acta A 72
(2009) 291-297; (b) H.F. Abd.El-Halim, F.A. NourEl-Dien, G.G. Mohamed, N.A.
Mohamed ''Synthesis, Spectroscopic, Thermal Characterization, and Antimicrobial
Activity of Miconazole Drug and its Metal Complexes'' J. Therm. Anal. Calorim. 109
(2012) 883-892.
[26] P. Karthikeyan, S.A. Aswar, P.N. Muskawar, P.R. Bhagat, S.S. Kumar ''Development
and efficient 1-glycyl-3-methyl imidazolium chloride–copper(II) complex catalyzed
highly enantioselective synthesis of 3,4-dihydropyrimidin-2(1H)-ones'' J. Organomet.
Chem. 723 (2013) 154-162.
[27] J.M. Ramos, O. Veysiane, J. Felcman, C.A. Tèllezs ''FT-IR vibrational spectrum and
DFT: B3LYP/6-31G and B3LYP/6-311G structure and Vibrational Analysis of
Glycinate–guanidoacetate Nickel(II) Complex: [Ni(Gly)(Gaa)]'' Spectrochim. Acta A 72
(2009) 182-189.
[28] (a) V. Arjunan, A. Raj, R. Santhanam, M.K. Marchewka, S. Mohan 'Structural,
Vibrational, Electronic Investigations and Quantum Chemical Studies of 2-Amino-4-
methoxybenzothiazole'' Spectrochim. Acta A 102 (2013) 327-340; (b) M.M.A. Jinnah,
V. Sasirekha, V. Ramakrishnan ''Vibrational Spectral Studies of l-Citrullinium
Perchlorate'' Spectrochim. Acta A 62 (2005) 840-844.
[29] W.M.I. Hassn, M.A. Badawy, G.G. Mohamed, H. Moustafa, S. Elramly ''Synthesis,
Spectroscopic, Thermal and DFT Calculations of 2-(3-Amino-2-hydrazono-4-
oxothiazolidin-5-yl) acetic acid Binuclear Metal Complexes'' Spectrochim. Acta A 111
(2013) 169-177.
[30] (a) H.R. Lobo, B.S. Singh, D.V. Pinjar, A.B. Pandit, G.S. Shankarling ''Ultrasound-
Assisted Intensification of Bio-catalyzed Synthesis of Mono-N-alkyl aromatic Amines''
Biochem. Eng. J. 70 (2013) 29-34; (b) M. Salavati-Niasari, A. Amiri '' Synthesis
and Characterization of Bis(macrocyclic)nickel(II) Complexes Containing
Aromatic Nitrogen–Nitrogen Linkers Produced by Template Condensation''
Transition Met. Chem. 31 (2006) 157-162.
[31] (a) K. Karemi, M.H. Kharat, C. Rizzoli, J. Lipkowski ''Synthesis and Structural Studies
of Cyclopalladated Complexes of Secondary Benzylamines'' J. Organomet. Chem.728
(2013) 16-22; (b) M. Lòpez-Deber, A. ldrey, G. Castro-Justo, M.D.C. Fernảndez-
Fernảndez, V. García-Gonzảlez, R. Bastida, A. Macías, P. Pẻrez-Lourido, L. Valencia
''Cd(II) complexes with Pendantarmed Oxa- and Azamacrocyclic Ligands''

16
 Polyhedron 54 (2013) 54-59.
[32] K. Nakamoto, P.J. Mcarthy ''Spectroscopy and Structure of Metal Chelate Compounds''
John Wiley and Sons Inc. New York, 1968.
[33] (a) I. Alan, A. Kriza, M. Badea, N. Stanica, R. Olar ''Synthesis and Characterization of
Co(II), Ni(II), Zn(II) and Cd(II) Complexes with 5-Bromo-N,N'-bis-(salicylidene)-o-
tolidine'' J. Therm. Anal. Calorim. 111 (2013) 483-490; (b) M. Salavati-Niasari, S.
Abdolmohammadi ''Synthesis, Characterization and Catalytic Oxidation of
Ethylbenzene over “Neat” and Host (Nanocavity of Zeolite-Y)/guest(tetraza
tetraone Macrocyclic Copper(II) Complexes) Nanocomposite Materials
(HGNM)'' J. Porous Mater 16 (2009) 19-26.
[34] (a) S. D.Ross ''Forbidden Transitions in the Infra-red Spectra of some Tetrahedral
Anions-I. Perchlorates'' Spectrochim. Acta A 18 (1962) 225-228; (b) A. Kriza, M.L.
Dianu, C. Andronescu, A.E. Rogozea, A.M. Musuc ''Synthesis, Spectral and Thermal
Studies of New Copper(II) Complexes with 1,2-Di(imino-2-aminomethylpyridil)ethane''
J. Therm. Anal. Calorim. 100 (2010) 929-935.
[35] (a) H.A. El-Boraaey, S.M. Emam, D.A. Tolan, A.M. El-Nahas ''Structural Studies and
Anticancer Activity of a Novel (N6O4) Macrocyclic Ligand and its Cu(II) Complexes''
Spectrochim. Acta A 78 (2011) 360-370 and references cited therein; (b) M.
Salavati-Niasari, M. Shaterian ''Host (Nanocavity of zeolite-Y)/guest (Mn(II),
Co(II), Ni(II) and Cu(II) Complexes of Pentadendate Schiff Base Ligand)
Nanocomposite Materials (HGNM): Application in the Heterogeneous
Oxidation of Cyclohexene. J. Porous Mater 15(2008) 581-588.
[36] A.A.A. Emara, B.A. El-Sayed, E.A. E.Ahmed ''Syntheses, Spectroscopic
Characterization and Thermal Behavior on Novel Binuclear Transition Metal
Complexes of Hydrazones derived from 4,6-Diacetylresorcinol and Oxalyldihydrazine''
Spectrochim. Acta A 69 (2008) 757-769.
[37] A.A. El-Bindary, A.Z. El-Sonbati ''Synthesis and Properties of Complexes of Copper(II),
Nickel(II), Cobalt(II) and Uranyl Ions with 3-(p-Tolylsulphonamido)rhodanine'' Polish
J. Chem. 74 (2000) 615-620.
[38] a) M. Tabanowska, E. Bidzińska, A. Para, M. Kurdziel ''EPR Investigation of Cu(II)-
Complexes with Nitrogen derivatives of Dialdehyde Starch'' Carbohydrate Polymers 87
(2012) 2605-2613; (b) A.B.P. Lever ‘Inorganic electronic spectroscopy’ 2nd edn.
Elsevier, Amsterdam 1984; (c) F.M.A. Altalbawy, G.G. Mohamed, M.A. Sayed, M.I.A.

17
 Mohamed ''Synthesis, Characterization, and Biological Activity of some Transition
Metal Complexes with Schiff Base Ligands derived from 4-Amino-5-phenyl-4H-1,2,4-
triazole-3-thiol and Salicaldehyde'' Monatsh Chem. 143 (2012) 79-89.
[39] A.S. El-Tabl, S.A. El-Enein ''Reactivity of the New Potentially Binucleating
Ligand, 2-(Acetichydrazido-N-methylidene-α-naphthol)-benzothiazol, towards
Manganese(II), Nickel(II), Cobalt(II), Copper(II) and Zinc(II) Salts'' J. Coord.
Chem. 57 (2004) 281-294.
[40] (a) V.P. Singh, A. Katiyar, S. Singh ''Synthesis, Characterization of some Transition
Metal(II) Complexes of Acetone-p-aminoacetophenone salicyloylhydrazone and their
Antimicrobial Activity'' Biometals 21 (2008) 491-501; (b) S. AboEl-Enein, F.A. El-
Saied, S. M. Emam, M.A. Ell-Salamony ''First Raw Transition Metal Complexes of
Salicylidene and 2- Hydroxy-1-naphthylidene-N-cyanoacetohydrazone'' Spectrochim. Acta
A 71 (2008) 421-429; (c) A.K. Sharma, S. Chandra ''Spectroscopic and Mycological
Studies of Co(II), Ni(II) and Cu(II) Complexes with 4-Aminoantipyrine derivative''
Spectrochim. Acta A 81 (2011) 424-430.
[41] M.G. Quintero-Tèllez, M.D.J.R. Hoz, S. Bernès, R. Zamorano-Ulloa, D. Ramírez-
Rosales, J.L. Alcántara-Flores, Y. Reyes-Ortega '' Synthesis, Structural, Electronic and
Magnetic Studies of [Cu(II)(saleanN3H3)]'' J. Mol. Struct. 1034 (2013) 183-188.
[42] G.G. Mohamed, N.A. Ibrahim, H.A. E.Attia ''Synthesis and anti-fungicidal activity of
some Transition Metal Complexes with Benzimidazole Dithiocarbamate Ligand''
Spectrochim. Acta A 72 (2009) 610-615.
[43] F.A. Cotton, G. Wilkinson, C.A. Murillo, M. Bochman, ''Advanced Inorganic Chemistry''
sixth ed., Wiley, New York, 1999.
[44] A.M. Donia, H.A. El-Boraey, M.F. El-Samalehy ''Thermal Investigation of Iron(III) and
Manganese(II,III) Complexes of Dianils derived from 6-Formylkhellin, Synthesis,
Characterization'' J. Therm. Anal. Calorim. 73 (2003) 987-1000 and references cited
therein.
[45] Y. Baran, I. Kaya, M. Turkyilmaz ''Synthesis, Spectroscopic and Thermal Properties of
Pt(II) Complexes of some Polydentate Ligands'' J. Therm. Anal. Calorim. 107 (2012)
869-875.
[46] A.M. Donia, H.A. El-Boraey ''Preparation of Highly Insulating Dimeric and Polymeric
Metal Complexes with Higher Thermal Stability in the Solid State'' J. Anal. Appl. Pyrol.
63 (2002) 69-84.

18
 [47] H.A. El-Boraey, R.M. Abdel-Raham, E.M. Atia, K.H. Hilmy ''Spectroscopic, Thermal
and Toxicity Studies of some 2-Amino-3-cyano-1,5-diphenylpyrrole Containing Schiff
Bases Copper(II) Complexes'' Cent. Eur. J. Chem. 8 (2010) 820-833.
[48] S.A. Abou El-Enein ''Polymeric and Sandwich Schiff’s Bases Complexes derived from
4,4′-Methylenedianiline'' J. Therm. Anal. Calorim. 91 (2008) 929-936.
[49] (a)H.A. El-Boraey 'Structural and Thermal Studies of some Aroylhydrazone Schiff
Bases-Transition Metal Complexes'' J. Therm. Anal. Calorim. 81 (2005) 339-346.
(b) A.H. Osman ''Synthesis and characterization of cobalt(II) and nickel(II) complexes
of some Schiff bases derived from 3-hydrazino-6-methyl[1,2,4] triazin-5(4H)one''
Transition Met. Chem. 31 (2006) 35-41.
[50] (a)H.A. El-Boraey, A.M. Donia, M.F. El-Samalehy ''Preparation Charaterization and
Thermal Investigation of Polymeric and Monomeric Binuclear Complexes of
Dianils derived from 6-Formylkhellin with Cobalt(II), Nickel(II) and
Copper(II), J. Anal. Appl. Pyrol. 73 (2005) 204- 211.
(b) M.A. Mohamed, A.K. Galwey, S.A. Halawy '' Kinetic and Thermodynamic
Studies of the Non-isothermal Decompositions of Nickel Malonate Dihydrate
and Nickel Hydrogen Malonate Dihydrate'' Thermochim. Acta 323 (1998) 27-
36. (c) M. Lalia-Kantouri, L. Tzavellas, D. Paschalidis ''Novel lanthanide
Complexes with Di-2-Pyridyl Ketone-p-Chloro-Benzoylhydrazone. Thermal
Investigation by Simultaneous TG/DTG-DTA and IR Spectroscopy'' J. Therm.
Anal. Calorim. 91 (2008) 937-942.
[51] F. Yuhua, B. Caifeng, A. Xiaokang, G. Feng, X. Yaosen, H. Xuetao, X. Yan ''Synthesis
and Thermal Decomposition Kinetics of Er(III) Complex with Unsymmetrical Schiff-
Base ligand'' J. Coord. Chem. 59 (2006) 1575-1581.
[52] C.K. Modi, M.N. Patel ''Synthetic, Spectroscopic and Thermal Aspects of some
Heterochelates'' J. Therm. Anal. Calorim. 94 (2008) 247-255.
[53] R. Olar, M. Badea, D. Marinescu 'Thermal Study of some New Ni(II) and Cu(II)
Complexes with Ligands derived from N,N-Dimethylbiguanide as Potential
Antimicrobials'' J. Therm. Anal. Calorim. 99 (2010) 893-898.
[54] M. Gaber, A.F. Rehab, D.F. Badr-Eldeen 'Spectral and Thermal Studies of New Co(II)
and Ni(II) Hexaaza and Octaaza Macrocyclic Complexes'' J. Therm. Anal. Calorim. 91
(2008) 957-962.
[55] (a) D. Haffar, T. Douadi, S. Chafaa, M.A. Khan, G. Bouet ''Synthesis, Characterization

19
 and Electrochemical Study of 4,4'-Bis(Salicylideneimino)diphenylethane and its
Complexes with Cobalt(II), Copper(II) and Cadmium(II)'' Transition Met. Chem. 29
(2004) 245-250; (b) M.S. Masoud, E.A. Khalil, A.M. Ramadan ''Thermal
Properties of some CoII, NiII and CuII Complexes of New Substituted
Pyrimidine Compounds'' J. Anal. Appl. Pyrol. 78 (2007) 14-23.
[56] T. Rosu, M. Negoiu, S. Pasculescu, E. Pahontu, D. Poirier, A. Gulea '' Metal-based
Biologically Active Agents: Synthesis, Characterization, Antibacterial and Antileukemia
Activity Evaluation of Cu(II), V(IV) and Ni(II) Complexes with Antipyrine-derived
Compounds'' Eur. J. Med. Chem. 45 (2010) 774-781.
[57] D. Kivelson, R. Neiman ''ESR Studies on the Bonding in Copper Complexes'' J..
Chem. Phys. 35 (1961) 149-155.
[58] A.P.S. Fontes, W. Guerra, F.C. Machado, M.V. deAlmeida, W.A. Alves, A.M.D. Ferreira,
A. Padauan-Filho ''New Copper(II) Complexes Containing 2-Fuoric hydrazide and 5-
Nitro-2-furoic hydrazide Ligands: Synthesis, Thermal, Magnetic and Spectroscopic
Characterization'' Transition Met. Chem. 29 (2004) 382-387.
[59] B.J. Hathaway, G. Wilkinson, R.D. Gillary, J.A. McClenerty (Eds.), ''Comprensive
Coordination Chemistry II'' Vol.5. Pergamom, Oxford, 1987.

20
 10 9
1 11
D 8
2
A B C
3 7
N N
4 5 6
Me

Figure 1. Structure of neocryptolepine.

Figure 2. Dose-survival curves for complexes 7b, 8a and 9b.

120
Relative cell number (%)

100

80
7b
60
9b
40 8a

20

0
0.0001 0.001 0.01 0.1 1 10

Log concentration (µM)

21
 Scheme1: Synthesis of the amino neocryptolepine analogues containing N-substituted side-chains at C-
11. Reagents and conditions: (i) a. N-chlorosuccinimide, 1,4-dimethylpiperazine, CH2Cl2, 0 °C, 2-16 h.
b. trichloroacetic acid, N-methylaniline 2, room temperature, 2 h. (ii) diphenyl ether, reflux, 3 h. (iii)
POCl3, toluene, reflux, 6-12 h. (iv) appropriate amine, Ethanol, 80 °C, 3-5 h.

22
 Compound no. n m q Compound no. n m q

7a 2 0.75 0.75 9a 1 3.25 -

7b 3 3 - 9b 2 3 0.5
8a 1 3 0.5 10a 1 2.75 -
8b 2 6 - 10b 2 7.5 0.5

Scheme 2: Synthesis of copper(II) complexes of L1 and L2 ligands

23
Table 1: Analytical and physical data of L1, L2 ligands and their copper(II) complexes

Empirical Formula Elemental analysis Found (calcd.) % a

M.P. Λ
No Compound Colour Yield%
( o C)
Formula weight C H N M X

C18 H 22.5 N4O2.25 65.70 6.03 15.60 - -

L1.2.25 H2O Brown 90 100 -

330.91 (65.33) (6.85) (16.93) - -

7a [Cu2(L1)(OAc)4].0.75H2O. 0.75EtOH Green C27.5H36N4O9.5Cu2 30 115 47.19 5.22 9.01 18.4 - Insoluble
701.62 (47.10) (5.17) (8.00) (18.1)
8a [Cu(L1)Cl(H2O)3].Cl.3H2O.0.5EtOH Green C19H33N4 O6.5CuCl2 60 601 41.00 6.09 10. 7 11.10 12.75 73.1
556.001 (41.04) (5.98) (10.1) (11.42) (12.77)
1
9a [Cu(L )Br(H2O)2].Br.3.25H2O Green C18H28.5 N4O5.25CuBr2 90.5 140 35.5 4.41 9.02 10.50 26.50 86.0
608.45 (35.53) (4.72) (9.21) (10.44) (26.30)
1
10a [Cu(L )(H2O)4](ClO4)2. 2.75H2O Beige C18H31.5N4 O14.75CuCl2 45 230 32.14 43.88 7.73 9.60 - 100
674.474 (32.05) (4.67) (8.31) (9.41)
C18 H 25.5 N4O2.75
L2. 3 H2O Yellow 95 95 63.89 6.16 14.01 - - -
358.45 (63.67) (7.31) (15.63)

7b [Cu2(L2)(OAc)4].3H2O Green C27H38N4 O11Cu2 44 145 44.85 5.08 8.11 17.6 - 15.3
721.63 (44.94) (5.30) (7.76) (17.0)
8b [Cu(L2)Cl(H2O)3].Cl.6H2O Green C19H38N4O9CuCl2 54 165 37.99 5.32 9.21 10.50 11.80 61.2
601.41 (37.97) (6.37) (9.32) (10.57) (11.81)
2
9b [Cu(L )Br(H2O)2].Br.3H2O.0.5EtOH Beige C19H31N4 O5.5Cu Br2 67 162 37.76 5.15 8.69 10.0 25.30 62.5
641.01 (37.48) (5.19) (8.74) (9.91) (24.96)
2
10b [Cu(L )(H2O)4](ClO4)2.7.5H2O. 0.5EtOH Green C20H46 N4O20CuCl2 41 265 30.37 3.86 6.97 8.21 - 95.0
797.12 (30.15) (5.82) (7.03) (7.97)
a
: Ω-1 cm 2 mol -1, X: anion (Cl, Br, ClO4, OAc)
Table 2: IR Spectral bands (cm-1) and their assignments for L1, L2 and their copper(II) complexes

Compound υ(O-H)a υas,υs (NH 2) υsec (NH ) δ(NH 2)b δscis (NH2 ) δr(NH2 )d δt(NH2 ) δw (NH2 ) υ(M-N) υ(M-O) υ(Anion)

L1.2.25 H2O 3581w 3392s 3247w 1613 v.s 1549v.s 742 s 1240 m 1161 w - - -
3473w 3358s 3160w

7a 3480w 3347s 3214w 1608 w 1563(br.s)c 745 s 1254 m 1157 w 474 w 600w (1564,1300)e
3400w 3268w 3154w (1403)e

8a 3439(w) 3306br 3200w 1582 s 1540w 746 s 1253 m 1146 w 456w 520w -
3360(w) 3241w 3147w 1234 w
932*

9a 3477w 3311-3300m 3189m 1593 w 1540w 747 s 1253 m 1142 m 480m 514w -
3406w 3270w 1104 w
951*

10a 3541sh 3404s 3237m 1582 sh 1521w 752 s 1262 m 1141 w 445w 500w (1089s,934,
3505s 3350w 3178w 1511m 622m)f
969* 3322w

L2 .3 H2O 3579sh 3322s 3195w 1604v.s 1551v.s 738 s 1249 w 1120 m - - -

3434w 3260w 3150w 1214 w
3373sh

7b 3560sh 3411s 3200w 1617 m 1566 (br.s)c 753 w 1257m 1140 w 432 w 564 w (1597,1339 )e
3466s 719 w 1219m 1116 w (1409)e
8b 3454sh 3368sh 3180w 1615 s 1581sh 750 s 1255 m 1181 w 439 m 595 w -
3407sh 3320w 3114w 1502w 1150 w
9430* 3210w
9b 3430w 3350s, 3171m 1610 s 1560sh 731 s 1243 m 1186 w 479 w 548 w -
951* 3277w 1132 m
3215w
10b 3362sh 3295w 3200w 1619 s 1589sh 747 s 1264 m 1154 m 486 w 527w (1080s,930
3500s 3261w 3180w 1508m 624m)f
3408s
915*
Abbreviations: br. broad ; m.medium ; s.strong ; v.very ; sh.shoulder; a :overlapping bands with (OH)of EtOH; b overlapped with pyridine and indole
rings; c :overlapping with (COO - ); d overlapping with bands with wagging of secondary(NH); e :acetate anions f :perchlorate anions * :coordinated
water
Table 3: Electronic spectra and magnetic moment values for copper(II) complexes:

No Compound Electronic spectral Assignments μeff per metal

bands (nm) (BM.)
L1.2.25H2O 380, 345 (s.splitted) n-π* -
315(s), 285 (s),250(s) π-π*
2
7a [Cu2(L1)(OAc)4].0.75H 2O.0.75EtOH 730(br) B1g→2A1g 1.40
2
620(sh) B1g→2B2g
2
533(sh) B1g→2E g
430(s) O → Cu
345(m) LM charge transfer
285(s) Intraligand transition
2
8a [Cu(L1)Cl(H2O)3].Cl.3H2O.0.5EtOH 840(br) B1g→2A1g 2.1
2
670(sh) B1g→2B2g
2
520(sh) B1g→2E g
440(s) LM charge transfer
285(s) Intraligand transition
2
9a [Cu(L1)Br(H2O)2].Br.3.25H 2O 872(br) B1g→2A1g 1.8
2
640(sh) B1g→2E g
2
580(sh) B1g→2B2g
440(m) LM charge transfer
2
10a [Cu(L1)(H2O)4](ClO 4)2.2.75H2O 760(br) B1g→2B2g 2.2
2
510(sh) B1g→2E g
420(sh) LM charge transfer
347(s), 275(s) Intraligand transition
L2.3H2O 385, 340 (s.splitted) n-π* -
310(s), 283(s),255(s) π-π*
2
7b [Cu2(L2)(OAc)4].3H2O 720 (br) B1g→2A1g 1.30
2
610(sh) B1g→2B2g
2
520(sh) B1g→2E g
400(s) O → Cu
360(m) LM charge transfer
250(s) Intraligand transition
2
8b [Cu(L2)Cl(H2O)3].Cl.6H2O 860(br) B1g→2A1g 2.09
2
660(sh) B1g→2B2g
2
530(sh) B1g→2E g
440(s) LM charge transfer
340(m), 285(s) Intraligand transition
2
9b [Cu(L2)Br(H2O)2].Br.3H2O.0.5EtOH 823(br) B1g→2A1g 1.90
2
711(sh) B1g→2E g
2
514(sh) B1g→2B2g
420(w.sh) LM charge transfer
340(s), 280, 240 Intraligand transition
2
10b [Cu(L2)(H2O)4](ClO 4)2.7.5H2O.0.5 EtOH 750(br) B1g→2A1g 2.2
2
538(sh) B1g→2B2g
2
480(m) B1g→2E g
425(sh) LM charge transfer
350(s), 280(s) Intraligand transition
br: broad, m: medium, s: strong, sh: shoulder
Table 4: Thermal analysis of Cu(II) complexes of L 1 and L 2 ligands :

No Compound DTA DTA TG Mass Loss % Assignment Ts (0C )

range Peak range Found Calcd.
(°C) (°C) (°C)
L1.2.25 H2O 21-115w 76(+) 21-196 12.30 12.25 Loss of 2.25 moles of hydrated water a 196
115-142w 122(+)
196-386br 269(+) 196-400 46.70 47.20 Loss of C10H8N2 (= 0.54 mole of L1)c
415-496 440(+) 400-500 10.66 10.9 Loss of two moles of NH3 and one of H2 (= 0.12 mole of L1)c

528-656 588(-) 500-750 26.56 26.02 Loss of 7C and one mole of H2 (= 0.30 mole of L1)c

750 3.80 3.63 1.0 C (=0.04 mole of L1)f

7a [Cu2(L1)(OAc)4].0.75H2O. 26-80w 53(+) 26-129 6.79 6.85 Loss of 0.75 mole of ethanol molecule and 0.75 mole of 129
0.75EtOH 88-127m 113(+) hydrated water a
129-167w 148(+) 129-223 16.82 16.83 Loss of two moles of coordinated acetate c
167-207s 182(+)
207-223w 216(+)
239-364vs 281(-) 223-600 26.90 26.76 Loss of C4H6O 2 (=1.46 moles of coordinated acetate) and 4NH3,
364-600br 470(+) C2H2, 0.5C (=0.35 mole of L1)c
600 49.51 49.56 2CuO and ligand residue (0.65 mole of L1) f
8a [Cu(L1)Cl(H2O)3].Cl.3H2O. 20-122br 70(+) 20-224 13.00 13.05 Loss of 0.5 mole of ethanol molecule and 2.75 moles of 224
0.5EtOH 143-162s 152(+) hydrated water a
162-191 Sh.
280-346br 324(+) 224-404 19.80 20.11 Loss of 0.25 mole of lattice water, 3 moles of coordinated water
346-404br 365(+) and 0.75 mole of chlorine gas c
365-434w 404 (+) 404-900 55.45 55.42 Loss of 0.25 mole of chlorine gas and 2NH3, N2, 2C6H6 , 6C (=
446-521s 484(+) one mole of L1)c
601-787br 719(-)
810-845w 826(+)
845-900w 858(+)
900 11.12 11.42 Cuf

a
: Dehydration, b: Desolvation, c: Decomposition, f: Final residue, w: weak, s: strong, m: medium, br: broad, sh.: shoulder, v.s: very strong, (+):
endothermic peak, (-): exothermic peak

-1-
Table 4: Continued

No Compound DTA DTA TG Mass Loss % Assignment Ts (0C )

range Peak range Found Clacd.
(°C) (°C) (°C)
9a [Cu(L1)Br(H2O)2].Br.3.25H2O 26-90w 49(+) 26-308 9.53 9.62 Loss of 3.25 moles of hydrated watera 308
90-184 Sh.
184-235w 213(+)
235-308 Sh.
308-388 Sh. 308-452 32.50 32.22 Loss of two moles of coordinated water and one mole of
388-452w 448(+) bromine gasc
452-692s 527(+) 452-900 45.05 45.26 Loss of 2NH3, N2, 2C6H6, 4.75C (=0.95 L1)c
692-753w 700(+)
783-831br 810(-)
900 12.99 12.9 Cu and 1.25C (=0.05L1)f

L2.3 H2O 21-111 80 (+) 21-111 15.34 15.08 Loss of 3.0 moles of hydrated water a 111
129-164 148(+) 111-174 10.22 10.07 Loss of two moles of NH3 gas and one mole of H2 gas (=0.12
mole of L2)c
339-417 403(+) 174-417 47.10 47.20 Loss of C11H9N2 (=0.56 mole of L2)c
417-471 428(+), 417-715 23.43 23.46 Loss of 1.5 moles of H2 gas and 6.75 moles of C (=0.28 mole of
471-542 497(+) L2)c
650-715 675(-)
715 3.94 4.19 1.25C (=0.05mole of L2) f

7b [Cu2(L2)(OAc)4].3H2O 20-90br 54 (+) 20-170 6.40 6.24 Loss of 2.5 moles of hydrated water a 170
100-170w 142(+)
172-217s 205(+) 170-255 25.74 25.80 Loss of 0.5 mole of lattice water and 3 moles of coordinated
217-255w 229(+) acetate c
255-324s 297(-) 255-450 27.51 27.62 Loss of 0.46 mole of coordinated acetate and 4NH3, C6H6,
324-477 368(-) C2H2 (=0.57mole of L2)c
434-600br 477(+)
450 40.41 40.34 2CuO + ligand residue (=0.43mole of L2)f

a
: Dehydration, b: Desolvation, c: Decomposition, f: Final residue, w: weak, s: strong, m: medium, br: broad, sh.: shoulder, v.s: very strong, (+):
endothermic peak, (-): exothermic peak

-2-
Table 4 : Continued

No Compound DTA DTA TG range Mass Loss % Assignment Ts

range (°C) Peak (°C) Foun Clacd. (0 C )
(°C) d
8b [Cu(L2)Cl(H2O)3].Cl.6H2O 21-110br 62(+) 21-210 14.29 14.23 Loss of 4.75 moles of hydrated water a 210
141-171s 156(+)
171-210 Sh.(+)
252-355s 325(+) 210-433 18.68 18.65 Loss of 1.25 moles of lattice water, 3 moles of coordinated
355-433br 377(+) water and 0.5 mole of chlorine gas c
433-523br 487(+) 433-800 48.97 49.06 Loss of 0.5 mole of chlorine gas and 2NH3, N2, H2 C6H6, 3.25C
601-787br 719(-) (=0.85 mole of L2)c
800 18.14 18.06 Cu+3.75C(=0.15 mole of L2) f

9b [Cu(L2)Br(H2O)2].Br.3H2O. 21-101br 65(+) 21-284 11.34 11.32 Loss of 0.5 mole of ethanol molecule and 2.75 moles of 284
0.5EtOH 127-151w 141(+) hydrated water a, b
151-184br 164(+)
200-284 Sh.
284-319w 304(+) 284-431 16.15 16.31 Loss of 0.25 mole of lattice water , two moles of coordinated
319-404br 389(+) water and 0.4 mole of bromine gasc
404-431br 416(+)
453-491w 477(+) 431-850 55.12 54.97 Loss of 0.6 mole of bromine gas and 2NH3, N2, H2, 2C6H6, 3C
491-526br 509(+) (=0.84 mole of L2)c
557622w 586(+)
683-795br 760(-)
850 17.03 17.4 Cu+4 C (=0.16 mole of L2) f
10b [Cu(L2)(H2O)4](ClO4)2.7.5H2O. - - 20-218 8.53 8.54 Loss of half mole of ethanol and 2.5 moles of hydrated water a,b 218
0.5EtOH
218-229 30.10 30.02 Loss of five moles of lattice water and 1.5 moles of ionic
perchlorate c
229-400 53.54 53.47 Loss of four moles of coordinated water, half mole of ionic
perchlorate and one mole of L2)c
400 7.86 7.97 Cuf

a
: Dehydration, b: Desolvation, c: Decomposition, f: Final residue, w: weak, s: strong, m: medium, br: broad, sh.: shoulder, v.s: very strong, (+):
endothermic peak, (-): exothermic peak

-3-
Table 5: ESR spectral parameters of copper(II) complexes of L1 and L2 ligands:

Parameter 7a 8a 9a 10a 7b 8b 9b 10b

g// 2.191 2.233 2.220 2.204 2.212 2.244 2.210 2.093

g⊥ 2.053 2.058 2.056 2.051 2.068 2.062 2.050 2.031

a
gav 2.099 2.116 2.111 2.102 2.116 2.123 2.103 2.047

G 3.710 4.150 4.100 4.140 3.240 4.300 4.350 4.200

b
A// 162.0 104.27 - 114.35 160.1 104.79 136.0 129.99

b
A⊥ 31.60 19.280 32.24 39.9 40.60 - 48.00 -

c
Aav 75.30 47.130 - 64.76 80.43 - 78.00 -

*ƒ 134.7 214.15 - 192.70 138.1 214.14 163.0 161.0

α2 0.700 0.600 - 0.580 0.720 0.604 0.650 0.510

β2 0.650 0.896 - 0.691 0.718 0.920 0.680 0.460

γ2 0.820 1.115 - 0.994 1.060 1.140 0.850 0.530

K// 0.670 0.720 - 0.633 0.719 0.741 0.660 0.480

K⊥ 0.760 0.804 - 0.759 0.874 0.825 0.750 0.520

d
Kav 0.730 0.776 - 0.717 0.822 0.798 0.720 0.510
e
Δ2 16129 14925 - 13157 16393 15151 14065 16667
e
Δ3 18762 19231 - 19607 19231 18868 19455 20833

a b
gav=2g⊥+g///3, A values in 10-4 cm-1, c
Aav=2A⊥+A///3
d
Kav=2K⊥+K///3, e
d-d transition in cm-1, * ƒ (in cm) = g///A//
Table 6: The percentages of cell inhibition induced by ligands and their corresponding
copper(II) complexes in the human colon carcinoma cell line.

Compound % of cell inhibition after 72 h Compound % of cell inhibition after 72 h

L1 80 L2 83.7
7a 81 7b 95.4
8a 90.4 8b 89.1
9a 87.30 9b 92
10a 88.6 10b 90.1

*Inhibition rate (%) was calculated at 0.01 mM concentration using MTT assay, DMSO was
used as solvent which is widely used in cell-culture studies.
Transition Metal Complexes of Neocryptolepine Analogues Part I: Synthesis,
Spectroscopic Characterization, and In Vitro Anticancer Activity of
Copper(II) Complexes
S. M. Emam, I. El-T. El Sayed, N. M. Nassar
Highlights

► New series of copper(II) complexes bearing aminoalkylaminoneocryptolepine ligands were

synthesized.

► Spectroscopic characterization of ligands and complexes.

► The ligands and complexes showed potent anticancer activity against HT-29.

► The complexation led to a remarkable increase in anticancer activity.