Synthesis, crystal structures, and cytotoxicity studies of two cobalt(III) and zinc(II) complexes derived from 2-ethoxy-6-[(3-methylaminopropylimino) methyl]phenol

Article abstract of DOI:10.1080/15533174.2011.555851

A new cobalt(III) complex, [CoL₂]·ClO₄ (1), and a new zinc(II) complex, [Zn(HL)₂(NCS)]·NCS (2) (HL = 2-ethoxy-6-[(3- methylaminopropylimino)methyl]phenol), have been synthesized and characterized by elemental analysis, IR

Full text of DOI:10.1080/15533174.2011.555851

Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry, 41:229–233, 2011
Copyright © Taylor & Francis Group, LLC
ISSN: 1553-3174 print / 1553-3182 online
DOI: 10.1080/15533174.2011.555851
Synthesis, Crystal Structures, and Cytotoxicity Studies of
Two Cobalt(III) and Zinc(II) Complexes Derived from
2-Ethoxy-6-[(3-methylaminopropylimino)methyl]phenol
Guo-Biao Cao
Department of Chemistry, Ankang University, Ankang Shanxi, P. R. China
analyses were performed on a Vario-EL-III analyzer. The IR
spectra were recorded on a Perkin Elmer 2000 spectrophotome-
A new cobalt(III) complex, [CoL2]·ClO4 (1), and a new
zinc(II) complex, [Zn(HL)2(NCS)]·NCS (2) (HL = 2-ethoxy-6-[(3-
methylaminopropylimino)methyl]phenol), have been synthesized
and characterized by elemental analysis, IR spectra, and single
crystal X-ray diffraction. In (1), the Co atom, lying on the inver-
sion center, is six-coordinate in an octahedral coordination, with
two phenolate O, two imine N, and two amine N atoms from two
Schiff base ligands. In (2), the Zn atom is five-coordinate in a
trigonal-bipyramidal coordination, with two imine N atoms from
two Schiff base ligands and one thiocyanate N atom defining the
basal plane, and with two phenolate O atoms from two Schiff base
ligands occupying the axial positions. The cytotoxic activities of
both complexes were evaluated.
ter with KBr pellets in the region 4000–400 cm−1
.
Synthesis of HL
3-Ethoxysalicylaldehyde (1.0 mmol, 166.2 mg) and N-
methylpropane-1,3-diamine (1.0 mmol, 88.2 mg) were mixed
in 50 mL methanol solution and then stirred and refluxed for
30 min. The solvent was removed by distillation to give orange
product. The product was washed with methanol and dried in
air. Yield: 93%. Anal. calcd. for C13H20N2O2: C, 66.1; H, 8.5;
N, 11.8. Found: C, 65.7; H, 8.6; N, 12.1%.
Keywords cobalt, crystal structure, cytotoxicity, Schiff base, synthe-
Synthesis of [CoL2]·ClO4 (1)
sis, zinc
A methanol solution (10 mL) of cobalt(II) perchlorate hex-
ahydrate (0.1 mmol, 36.6 mg) was added to the methanol so-
lution (10 mL) of HL (0.1 mmol, 23.6 mg), and refluxed for 1
h. The resulting clear brown solution was allowed to evaporate
slowly in air at room temperature for a week, affording red crys-
tals which were collected by filtration, washed with methanol,
and dried in air. Yield: 73% (based on HL). Anal. calcd. for
C26H38ClCoN4O8: C, 49.6; H, 6.1; N, 8.9. Found: C, 49.1; H,
6.3; N, 8.7%.
INTRODUCTION
Schiff bases are kinds of versatile ligands in coordi-
nation chemistry due to their easy synthesis and wide
applications.[1−4] The biological properties of Schiff bases
and their metal complexes have been widely investigated.[5−7]
Recent research indicates that the Schiff base complexes
have potent antitumor activities.[8,9] In this paper, a new
cobalt(III) complex, [CoL2]·ClO4 (1), and a new zinc(II)
complex, [Zn(HL)2(NCS)]·NCS (2) (HL = 2-ethoxy-6-[(3-
methylaminopropylimino)methyl]phenol), were synthesized
and structurally characterized. The cytotoxic activities of the
complexes were investigated.
Synthesis of [Zn(HL)2(NCS)]·NCS (2)
A methanol solution (10 mL) of zinc(II) acetate dihydrate
(0.1 mmol, 22.0 mg) was added to the methanol solution (10
mL) of HL (0.1 mmol, 23.6 mg) and ammonium thiocyanate (0.1
mmol, 7.6 mg), and refluxed for 1 h. The resulting clear colorless
solution was allowed to evaporate slowly in air at room temper-
ature for a few days, affording colorless crystals which were
collected by filtration, washed with methanol and dried in air.
Yield: 61% (based on HL). Anal. calcd. for C28H40N6O4S2Zn:
C, 51.4; H, 6.2; N, 12.8. Found: C, 51.7; H, 6.1; N, 12.5%.
EXPERIMENTAL
Materials and Measurements
All chemicals were available commercially as AR grade and
were used without further purification. C, H, and N elemental
Received 9 July 2010; accepted 6 October 2010.
Address correspondence to Guo-Biao Cao, Department of Chem-
istry, Ankang University, Ankang Shanxi 725000, P. R. China. E-mail:
guobiao cao@126.com
Cytotoxicity Assay
The cytotoxicity assay was carried out according to the liter-
ature method.[10] Two human leukemia cell lines, promyelocytic
229

230
G.-B. CAO
TABLE 1
Crystal data for the complexes
HL-60 and lymphoblastic NALM-6, were used as targets. Car-
boplatin was used as a reference. Cells were cultured in an
RPMI 1640 medium supplemented with 10% fetal calf serum
in a 5% CO2/95% air atmosphere. Exponentially growing cells
were seeded at 3 × 105 per well of 24-well plate (Nunc), and
cells were then exposed to the tested compounds for 48 h. Stock
solutions were freshly prepared in DMSO, and then dilutions
from 10−3 to 10−7 M in complete culture medium were made.
The number of viable cells was counted in a Buˆrker hemo-
cytometer using the trypan-blue exclusion assay. The values of
IC50 (the concentration of test compounds required to reduce
the cell survival fraction to 50% of the control) were calculated
from dose-response curves and used as a measure of cellular
sensitivity to a given treatment. All data are expressed as mean
standard deviation.
Complex
(1)
(2)
Formula
FW
C26H38ClCoN4O8 C28H40N6O4S8Zn
628.98
block/red
654.15
Crystal shape/colour
Crystal size /mm3
Crystal system
Space group
block/colorless
0.20×0.18×0.17 0.23×0.20×0.20
Orthorhombic
Pbcn
Monoclinic
P21/c
˚
a /A
17.759(2)
8.537(1)
19.238(2)
90
2916.7(6)
4
0.71073
298(2)
0.734
9.851(2)
27.252(3)
12.737(2)
105.534(3)
3294.5(9)
4
˚
b /A
˚
c /A
β /o
V /A
3
˚
Z
Crystal Structure Determination
˚
λ (MoKα) /A
T /K
0.71073
298(2)
The suitable single crystals of the complexes were mounted
on glass fibers for data collection performed on a Bruker
SMART 1000 CCD area diffractometer equipped with a
µ (MoKα) /cm−1
Tmin
0.913
0.817
0.838
0.867
0.885
˚
graphite-monochromatic Mo Kα radiation (λ = 0.71073 A)
Tmax
at 298 K. The unit cell dimensions were obtained with the
least-squares refinements and the structures were solved by di-
rect methods using SHELXTL-97 program.[11] The final refine-
ment was performed by full-matrix least-squares methods with
anisotropic thermal parameters for the non-hydrogen atoms on
F2. H atoms were placed in calculated positions and constrained
to ride on their parent atoms. Multi-scan absorption correction
was applied by using the SADABS program.[12] The N2-C13
group in (1) is disordered over two distinct sites, with occupan-
cies of 0.410(3) and 0.590(3), respectively. The crystallographic
data and experimental details for structural analysis of the com-
plexes are summarized in Table 1. Selected bond lengths and
angles are given in Table 2. Hydrogen bonds are listed in Table 3.
Crystallographic data for the complex has been deposited with
the Cambridge Crystallographic Data Centre (CCDC 738696
for (1) and 738697 for (2)).
Reflections/parameters 2813/212
7121/374
1.012
Goodness of fit on F2 1.081
R1, wR2 [I ≥ 2σ(I)]a 0.0567, 0.1590
0.0440, 0.0846
0.0923, 0.0997
ꢀ
R1, wR2 (all data)a
0.0808, 0.1798
ꢀ
ꢀ
aR1
w(Fo2)2]1/2
=
||Fo| − |Fc||/ |Fo|, wR2
=
[
w(Fo2-Fc2)2/
ꢀ
.
TABLE 2
◦
˚
Selected bond lengths (A) and bond angles ( ) for the
complexes
(1)
Co1-O1
Co1-N2
1.895(3)
2.001(4)
Co1-N1
1.929(3)
O1-Co1-O1A 180
O1-Co1-N1A
N1-Co1-N1A 180
O1-Co1-N2A
N1-Co1-N2A
89.85(14)
RESULTS AND DISCUSSION
O1-Co1-N1
O1-Co1-N2
N1-Co1-N2
90.15(14)
88.66(17)
87.46(17)
The red crystals of (1) and the colorless crystals of (2) are
stable in air at room temperature, soluble in most polar organic
solvents, such as MeOH, EtOH and MeCN, but insoluble in
water and non-polar organic solvents such as Et2O.
91.34(17)
92.54(17)
N2-Co1-N2A 180
(2)
IR Spectra of the Complexes
Zn1-O1
Zn1-N1
Zn1-N5
N5-Zn1-O3
O3-Zn1-O1
O3-Zn1-N3
N5-Zn1-N1
O1-Zn1-N1
2.0654(18) Zn1-O3
2.0619(18)
2.068(2)
Both complexes show two bands above 3000 cm−1 at 3317
and 3233 cm−1, what can be attributed to the νNH frequency.
The strong and sharp bands at 1613 cm−1 for (1) and 1615 cm−1
for (2) are assigned to the –C=N– stretching vibrations.[13] The
strong absorption band at 1093 cm−1 in (1) is assigned to the
perchlorate anion. The occurrence of the strong peaks at 2064
cm−1 and 2077 cm−1 in (2) are ascribed to the stretching vibra-
tions of the coordinate and dissociative thiocyanate groups.[14]
2.078(2)
2.018(3)
Zn1-N3
89.19(8)
178.06(7)
88.88(8)
116.33(10)
87.91(7)
N5-Zn1-O1
N5-Zn1-N3
O1-Zn1-N3
O3-Zn1-N1
N3-Zn1-N1
91.41(8)
114.29(9)
92.55(8)
90.17(8)
129.34(9)

TWO COBALT(III) AND ZINC(II) COMPLEXES
231
TABLE 3◦
the greatest deviation of the bond angles from those expected
for an ideal octahedral geometry is found for N1-Co1-N2 with
87.5(2)◦ and N1-Co1-N2A with 92.5(2)◦. The conformation of
the six-membered ring containing the Co, azomethine N (N1),
amine N (N2) and three C atoms (C10, C11 and C12) is a twisted
chair. The perchlorate anion in the complex is disordered about
an inversion center.
In the crystal structure, molecules are linked through inter-
molecular hydrogen bonds of types N–H· · ·O, forming chains
running along the c axis as shown by Figure 2.
˚
Hydrogen-bond geometry (A, ) for the complexes
D–H· · ·A
D–H H· · ·A
D· · ·A
D–H· · ·A
(1)
N2–H2· · ·O3
0.91
2.48
3.302(11)
150
(2)
N4–H4B· · ·N6i
N4–H4A· · ·O2
N4–H4A· · ·O1
N2–H2B· · ·O4
N2–H2B· · ·O3
N2–H2A· · ·S2ii
0.90
0.90
0.90
0.90
0.90
0.90
2.01
2.31
1.91
2.31
1.88
2.46
2.852(4)
2.831(3)
2.792(3)
2.793(3)
2.770(3)
3.286(3)
156
117
165
113
170
152
Structure Description of (2)
Complex (2) is a thiocyanate salt of a mononuclear zinc(II)
complex cation (Figure 3). All the bond lengths and angles
are comparable to those observed in the similar Schiff base
zinc(II) complex.[17] The coordination of the Zn atom may be
regarded as midway between trigonal–bipyramidal and square–
pyramidal as described by the τ parameter, an index of the
degree of trigonality.[18] The τ value calculated for the complex
is 0.813. Thus, the coordination of the Zn atom in the complex
is close to distorted trigonal-bipyramidal. The basal plane of
the trigonal–bipyramid is furnished by two imine N atoms from
two Schiff base ligands and one thiocyanate N atom, and the
axial positions are occupied by two phenolate O atoms from
two Schiff base ligands. The amine N atoms are protonated, and
not coordinate to the metal atom.
Symmetry codes: (i) 1 − x, −1/2 + y, 3/2 − z; (ii) x, −1 + y, z.
The typical bridging acetate vibrations are at 1571 and 1450
cm−1, respectively.[15]
Structure Description of (1)
Complex (1) is a perchlorate salt of a centrosymmetric
mononuclear cobalt(III) complex cation (Figure 1). All the bond
lengths and angles are comparable to those observed in the sim-
ilar Schiff base cobalt(III) complex.[16] The CoIII atom, lying
on an inversion center, is six-coordinate in an octahedral coor-
dination, with two phenolate O, two imine N, and two amine N
atoms from two Schiff base ligands. The coordination around
the Co atom displays somewhat distortion. The bond lengths
In the crystal structure, molecules are linked through inter-
molecular hydrogen bonds of types N–H· · ·N and N–H· · ·S,
forming chains running along the b axis as shown by Figure 4.
˚
around the Co atom are range from 1.895(3) to 2.001(4) A, and,
FIG. 1. The molecule of (1), showing the atom-numbering scheme. Displace-
ment ellipsoids are drawn at the 30% probability level. H atoms have been omit-
ted for clarity. Atoms labeled with the suffix A or unlabeled are at the symmetry
position –x, 1 – y, 1 – z.
FIG. 2. The molecular packing of (1), viewed along the b axis. Intermolecular
hydrogen bonds are shown as dashed lines.

232
G.-B. CAO
TABLE 4
Cytotoxic activities (IC50, µM)
Compound
HL-60
NALM-6
HL
(1)
(2)
>1000
113.0 23.6
>1000
>1000
127.3 21.9
783.5 63.3
1.3 0.5
Carboplatin
5.4 1.1
FIG. 3. The molecule of (2), showing the atom-numbering scheme. Displace-
ment ellipsoids are drawn at the 30% probability level. H atoms have been
omitted for clarity.
CONCLUSIONS
In this paper, a new cobalt(III) complex (1) and a new zinc(II)
complex (2) have been synthesized and structurally character-
ized. The cytotoxicity studies indicate that complex (1) has
stronger activities than those of (2). Both complexes show much
less activity than the carboplatin.
Cytotoxic Activity
The cytotoxic activities of the complexes were evaluated
on two human leukemia cell lines HL-60 and NALM-6. The
cytotoxic activity is expressed as the concentration required
reducing the cell survival fraction to 50% after 48 h of exposure
to the compounds (IC50). The results are summarized in Table 4.
It can be seen that the Schiff base HL has no cytotoxic activity
against both cell lines. Complex (1) has stronger activities than
those of (2). However, both complexes have much less activities
than the carboplatin which was used as a reference.
REFERENCES
1. Biswas, M.; Pilet, G.; Tercero, J.; El Fallah, M.S.; Mitra, S. Synthesis,
crystal structure, and magnetic properties of a new tetranuclear Cu(II) Schiff
base compound. Inorg. Chim. Acta 2009, 362, 2915–2920.
2. Zhang, C.-X.; Cui, C.X.; Lu, M.; Yu, L.; Zhan, Y.-X. In situ synthesis,
characterization and crystal structure of a novel cobalt(III) complex with
tridentate Schiff bases. Synth. React. Inorg. Met.-Org. Nano-Met. Chem.
2009, 39, 136–138.
3. Sheikhsoaie, I.; Rezaeffard, A.; Monadi, N.; Kaafi, S. A novel tridentate
Schiff base dioxo-molybdenum(VI) complex: Synthesis, crystal structure
and catalytic performance in green oxidation of sulfides by urea hydrogen
peroxide. Polyhedron 2009, 28, 733–738.
4. Yaftian, M.R.; Rayati, S.; Safarbali, R.; Torabi, N.; Khavasi, H.R. A new
tetradentate N2O2-type Schiff base ligand. Synthesis, extractive proper-
ties towards transition metal ions and X-ray crystal structure of its nickel
complex. Trans. Met. Chem. 2007, 32, 374–378.
5. Badwaik, V.B.; Deshmukh, R.D.; Aswar, A.S. Synthesis, structural, and
biological studies of some bivalent metal ion complexes with the tridentate
Schiff base ligand. Russ. J. Coord. Chem. 2009, 35, 247–252.
6. Abu-Hussen, A.A.A.; Linert, W. Synthesis, spectroscopic and biological
activity of new mononuclear transition metal complexes of macrocyclic
Schiff bases derived from 1,1’-diacetylferrocin. Synth. React. Inorg. Met.-
Org. Nano-Met. Chem. 2009, 39, 13–23.
7. Kumari, B.S.; Rijulal, G.; Mohanan, K. Microwave assisted synthesis, spec-
troscopic, thermal and biological studies of some lanthanide(III) chloride
complexes with a heterocyclic Schiff base. Synth. React. Inorg. Met.-Org.
Nano-Met. Chem. 2009, 39, 24–30.
8. Thomas, J.; Parameswaran, G. Antitumour and thermogravimetric stud-
ies of transition metal complexes of the Schiff base, anthracene-9-
carboxaldehyde thiosemicarbazone. Asian J. Chem. 2002, 14, 1370–
1382.
9. Nath, M.; Yadav, R.; Gielen, M.; Dalil, H.; deVos, D.; Eng, G. Syn-
thesis, characteristic spectral studies and in vitro antimicrobial and
antitumour activities of organotin(IV) complexes of Schiff bases de-
rived from amino-acids. Appl. Organomet. Chem. 1997, 11, 727–
736.
10. Budzisz, E.; Malꢀecka, M.; Lorenz, I.-P.; Mayer, P.; Kwiecien˜, R.A.;
Paneth, P.; Krajewska, U.; Ro´zalski, M. Synthesis, cytotoxic effect, and
structure-activity relationship of Pd(II) complexes with coumarin deriva-
tives. Inorg. Chem. 2006, 45, 9688–9695.
FIG. 4. The molecular packing of (2), viewed along the a axis. Intermolecular
hydrogen bonds are shown as dashed lines.
11. Sheldrick, G.M. SHELXTL-97, Program for X-ray Crystal Structure Solu-
tion; University of Go¨ttingen, Germany 1997.

TWO COBALT(III) AND ZINC(II) COMPLEXES
233
12. Sheldrick, G.M. SADABS, Siemens Area Detector Absorption (and Other)
Correction, University of Go¨ttingen: Germany 1997.
13. Chattopadhyay, S.; Ray, M.S.; Drew, M.G.B.; Figuerola, A.; Diaz, C.;
Ghosh, A. Facile synthesis of Cu(II) complexes of monocondensed N,N,N
donor Schiff base ligands: Crystal structure, spectroscopic and magnetic
properties. Polyhedron 2006, 25, 2241–2253.
nolate and carboxylate bridges. Correlations between 13C NMR chemi-
cal shifts and carboxylate binding modes. Inorg. Chem. 2002, 41, 6426–
6431.
16. Yuan, C.-L. trans-Bis2,4-dichloro-6-[(3-cyclohexylaminopropylimino)-
methyl]phenolatocobalt(III) perchlorate. Acta Crystallogr. 2005, E61,
m2112–m2114.
14. Bose, D.; Mostafa, G.; Walsh, R.D.B.; Zaworotko, M.; Ghosh, 17. Zhang, Q.-W.; Wang, G.-X. 2-[3-(Dimethylammonio)propyliminomethyl]
B.K. Synthesis, structure and properties of
a
trinuclear com-
-6-methoxyphenolatodiisothiocyanatozinc(II) chloroform solvate. Acta
Crystallogr. 2007, E63, m652–m653.
18. Addison, A.W.; Rao, T.N.; Reedijk, J.; van Rijn, J.; Verschoor, G.C. Tau-
descriptor for 5-coordination. J. Chem. Soc., Dalton Trans. 1984, 1349–
1356.
pound [Cu2Cd(tren)2(NCS)6]: Example of dynamic molecular ion,
[Cd(NCS)6−n(SCN)n]4− (n = 0-6). Polyhedron 2006, 25, 1477–1482.
15. Ye, B.-H.; Li, X.-Y.; Williams, I.D.; Chen, X.-M. Synthesis and struc-
tural characterization of di- and tetranuclear zinc complexes with phe-

Copyright of Synthesis & Reactivity in Inorganic, Metal-Organic, & Nano-Metal Chemistry is the property of
Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv
without the copyright holder's express written permission. However, users may print, download, or email
articles for individual use.