Sulfanilamide copper(II) chelates with 2-[(2-Hydroxyphenyl-imino)methyl] phenolom and 1-[(2-Hydroxyphenylimino)-methyl]naphthalen-2-ol

Article abstract of DOI:10.1134/S1070363210070224

2-[(2-Hydroxyphenylimino)methyl]phenol (H₂L¹) and 1-[(2-hydroxyphenylimino)methyl]naphthalen- 2-ol (H₂L²) reacted with copper(II) acetate hydrate and sulfanilamide (Sf¹), sulfathiazole (Sf²), sulfaethidole (Sf³), sulfadiazine (Sf⁴), and sulfadimidine (Sf⁵) in ethanol to give mixed-ligand copper chelates with the composition Cu(Sf^1-5)(L ^1-2) . nH₂O (n = 1, 2). All these complexes are monomeric. Salicylaldehyde imines (H₂L¹ and H₂L ²) behave as doubly deprotonated tridentate O,N,O ligands, whereas sulfanilamides (Sf^1-5) are unidentate ligands. Thermolysis of the synthesized complexes includes dehydration at 70-90°C, followed by complete thermal decomposition (290-380°C). The complexes [Cu(Sf¹)(L ¹)] . 2H₂O and [Cu(Sf³)(L¹)] . H₂O at a concentration of 10^-4 M inhibited growth and reproduction of 100% of human myeloid leukemia cells (HL-60). The inhibitory effect was 90 and 75%, respectively, at a concentration of 10^-5 M, whereas no antitumor activity was observed at a concentration of 10^-6 M. Pleiades Publishing, Ltd., 2010.

Full text of DOI:10.1134/S1070363210070224

ISSN 1070-3632, Russian Journal of General Chemistry, 2010, Vol. 80, No. 7, pp. 1351–1354. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © A.P. Gulya, V.I. Tsapkov, D. Poirier, K. Aruksandei, E. Pakhontsu, 2010, published in Zhurnal Obshchei Khimii, 2010, Vol. 80,
No. 7, pp. 1185–1188.
Sulfanilamide Copper(II) Chelates
with 2-[(2-Hydroxyphenyl-imino)methyl]phenolom
and 1-[(2-Hydroxyphenylimino)-methyl]naphthalen-2-ol
A. P. Gulyaa, V. I. Tsapkova, D. Poirierb, K. Aruksandeic, and E. Pakhontsud
a Moldavian State University, ul. Mateevicha 60, Kishinev, 2009 Moldova
e-mail: dociu1946@yahoo.com
b Université Laval, 2325, rue de l’Université, Québec, G1V 4G2 Canada
c Alexandru Ioan Cuza University of Iaşi, Bulevardul Carol I, Nr. 11, Iasi, 700506 Romania
d Universitatea de Medicina si Farmacie “Carol Davila,” Strada Dionisie Lupu 37, Bucuresti, Romania
Received April 28, 2009
Abstract—2-[(2-Hydroxyphenylimino)methyl]phenol (H2L1) and 1-[(2-hydroxyphenylimino)methyl]naphtha-
len-2-ol (H2L2) reacted with copper(II) acetate hydrate and sulfanilamide (Sf1), sulfathiazole (Sf2), sulfaethidole
(Sf3), sulfadiazine (Sf4), and sulfadimidine (Sf5) in ethanol to give mixed-ligand copper chelates with the
composition Cu(Sf1–5)(L1–2)·nH2O (n = 1, 2). All these complexes are monomeric. Salicylaldehyde imines
(H2L1 and H2L2) behave as doubly deprotonated tridentate O,N,O ligands, whereas sulfanilamides (Sf1–5) are
unidentate ligands. Thermolysis of the synthesized complexes includes dehydration at 70–90°C, followed by
complete thermal decomposition (290–380°C). The complexes [Cu(Sf1)(L1)]·2H2O and [Cu(Sf3)(L1)]·H2O at a
concentration of 10–4 M inhibited growth and reproduction of 100% of human myeloid leukemia cells (HL-60).
The inhibitory effect was 90 and 75%, respectively, at a concentration of 10–5 M, whereas no antitumor activity
was observed at a concentration of 10–6 M.
DOI: 10.1134/S1070363210070224
Transition metal salts with Schiff bases derived
from 2-aminophenol give rise to biologically active
coordination compounds with various compositions
and structures [1–3]. The structure and physico-
chemical and biological properties of these compounds
are determined by the nature of the central metal ion
and its inner-sphere ligand environment [4, 5]. Taking
the above stated into account, accumulation of experi-
mental data on the synthesis and properties of new coor-
dination compounds of biometals with such ligands is
important from both theoretical and practical viewpoints.
The goal of the present work was to synthesize mixed-
ligand copper chelates containing 2-[(2-hydroxyphenyl-
imino)methyl]phenol (H2L1) and 1-[(2-hydroxyphenyl-
imino)methyl]naphthalen-2-ol (H2L2) ligands together
with sulfanilamide ligands, namely sulfanilamide (Sf1),
sulfathiazole (Sf2), sulfaethidole (Sf3), sulfadiazine
(Sf4), and sulfadimidine (Sf5), and study their structure
and physicochemical properties.
OH
N
OH
O
N
H2L1
H2L2
S
NHR
H2N
=
=
HO
HO
O
Sf1−5
N
CH3
N
N
S
S
(Sf2),
(Sf4),
R = H (Sf1),
C2H5 (Sf3),
(Sf5).
CH3
N
N
N
N
1351

1352
GULYA et al.
By reaction of a hot (50–55°C) ethanol suspension
for all complexes displayed an endothermic effect at
70–95°C. Judging by the relatively low temperature,
this effect corresponds to their dehydration. The next
peak on the DTA curve is observed in the temperature
range from 290 to 360°C and is exothermic. It reflects
oxidative decomposition of the coordinated sul-
fanilamide (Sf1–5) and salicylaldehyde imine ligands
(H2L1 and N2L2). The temperature of complete decom-
position (Tdec) depends on the nature of the inner-sphere
ligands: it increases upon replacement of naphtha-
lenylidene fragment in the Schiff base ligand by
salicylidene. For complexes with the same Schiff base
ligand, the temperature of complete decomposition
decreases in the sulfanilamide series Sf5 ≥ Sf4 > Sf3 ≥
Sf2 > Sf1.
of copper(II) acetate hydrate with salicylaldehyde
imines H2L1 and H2L2 and sulfanilamides Sf1–5 at a
molar ratio of 1:1:1 we obtained finely crystalline
substances I–X. On the basis of their elemental
analyses (Table 1), the products were assigned the
composition Cu(Sf1–5)(L1–2)·nH2O (I, VI, Sf1; II, VII,
Sf2; III, VIII, Sf3; IV, IX, Sf4; V, X, Sf5; I–V, H2L1;
VI–X, H2L2; II, III, V, VII, VIII, X, n = 1; I, IV, VI,
IX, n = 2). Coordination compounds I–X are insoluble
in diethyl ether, poorly soluble in water and alcohols,
and readily soluble in N,N-dimethylformamide (DMF),
dimethyl sulfoxide (DMSO), and acetonitrile. Their
yields and physical constants are given in Table 1.
Microscopic study of compounds I–X showed that
they are homogeneous powders. Their purity and struc-
ture were determined by elemental and thermal gravi-
metric analysis, magnetochemistry, and IR spec-
troscopy. Determination of molar electric conductivity
æ of complexes I–X in DMF (Table 1) revealed that
they are nonelectrolytes. Magnetochemical parameters
of coordination compounds I–X corresponded to a spin
value for one unpaired electrone (Table 1) and in-
dicated their monomeric structure.
Using the Horowitz–Metzger method [6] supple-
mented by Topor [7], we estimated the kinetic param-
eters for dehydration of coordination compounds I–X.
The results are presented in Table 2. Judging by the
energies of activation Ea and preexponential factors Z,
the process is analogous to previously reported
reactions [8, 9].
The mode of ligand coordination to the central
copper ion was determined by analysis of the IR
spectra of complexes I–X and initial Schiff bases H2L1
and H2L2 and sulfanilamides Sf1–5, as well as of
previously described [1–5] coordination compounds of
The results of thermal gravimetric analysis of
complexes I–X are collected in Table 2. Thermolysis
of compounds I–X includes two steps. The DTA curves
Table 1. Yields, effective magnetic moments, molar electric conductivities, and elemental analyses of sulfanilamide-
containing copper(II) chelates with 2-[(2-hydroxyphenylimino)methyl]phenol and 1-[(2-hydroxyphenylimino)methyl]
naphthalen-2-ol
Found, %
N
Calculated, %
S
Comp. Yield,
μef,a
B. M.
æ,a
Formula
no.
%
Ω–1 cm2 mol–1
Cu
S
6.39
Cu
6.63
N
68
75
80
65
72
85
67
70
78
82
1.80
1.82
1.89
1.76
1.77
1.88
1.84
1.82
1.76
1.78
3
2
3
4
2
2
3
3
3
2
12.96
11.40
10.85
11.17
11.01
11.77
10.46
10.03
10.20
10.07
8.92
C19H21CuN3O6S
C22H20CuN4O5S2
C23H23CuN5O5S2
C23H23CuN5O6S
C25H25CuN5O5S
C23H23CuN3O6S
C26H22CuN4O5S2
C27H25CuN5O5S2
C27H25CuN5O6S
C29H27CuN5O5S
8.70
13.25
11.68
11.09
11.41
11.21
12.01
10.70
10.21
10.47
10.31
I
9.97
11.45
10.91
5.47
11.68
11.09
5.70
10.22
12.13
12.48
12.26
7.88
II
11.88
12.32
11.97
7.60
III
IV
5.33
5.60
V
5.80
6.00
VI
9.08
10.61
10.06
5.02
10.70
10.21
5.24
9.36
VII
VIII
IX
10.91
11.34
11.09
11.16
11.46
11.27
4.94
5.15
X
a
At 293 K.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 80 No. 7 2010

SULFANILAMIDE COPPER(II) CHELATES
1353
Table 2. Thermal gravimetric analysis of sulfanilamide-containing copper(II) chelates with 2-[(2-hydroxyphenylimino)-
methyl]phenol and 1-[(2-hydroxyphenylimino)methyl]naphthalen-2-ol
Complete
decomposition
temperature, °C
Weight loss
Kinetic parameters
Comp.
no.
Dehydration
temperature, °C
found, %
7.3
calculated, %
lost fragment
2H2O
H2O
Ea, kJ mol–1
34.2
log Z
75
80
85
70
95
80
75
80
75
85
7.5
3.3
3.1
6.4
3.2
6.8
3.0
2.9
5.9
2.9
4.0
4.7
3.9
3.8
4.5
2.8
3.6
4.3
4.2
4.2
320
350
360
360
380
290
320
330
350
350
I
3.5
43.5
II
3.0
H2O
31.4
III
IV
V
6.5
2H2O
H3O
31.0
3.5
41.2
7.0
2H2O
H2O
27.3
VI
VII
VIII
IX
X
2.7
31.2
3.0
H2O
38.7
6.2
2H2O
H2O
36.5
3.1
36.9
transition metals with structurally related Schiff bases.
We found that aldehyde imines H2L1 and N2L2 act as
doubly deprotonated tridentate O,N,O-ligands which
are coordinated to the copper ion through phenolic
oxygen atoms and nitrogen atom of the C=N group
with formation of five- and six-membered chelate
rings. The IR spectra of the complexes lack ν(OH)
bands typical of initial Schiff bases H2L1 and H2L2
(3530–3520 cm–1). In addition, the ν(C=N) band is
displaced by 25–20 cm–1 toward higher frequencies,
indicating coordination of the nitrogen atom in the
ligand to the metal atom. All complexes displayed in
the IR spectra a series of new absorption bands which
were assigned to ν(Cu–N) (525–505, 430–405 cm–1)
and ν(Cu–O) vibrations (490–460 cm–1). Participation
of the other functional groups in H2L1 and H2L2 in
coordination with the central metal ion may be ruled
out, for the corresponding characteristic absorption
bands appear in the same regions as in the spectra of
the free Schiff bases. The IR data also indicated that
sulfanilamide is coordinated through the nitrogen atom
in the amino group and that coordination of sulfathia-
zole, sulfaethidole, sulfadiazine, and sulfadimidine
involves nitrogen atom in the heteroring (thiazole, thia-
diazole, or pyrimidine). This follows from splitting and
low-frequency shift (by 25–15 cm–1) of the ν(NH2) and
ν(NH) absorption bands in the IR spectra of complexes
I and VI. In the spectra of coordination compounds II–
V and VII–X we observed splitting and low-frequency
shift (by 15–20 cm–1) of the ν(C=N) band.
Thus, the data of elemental analyses and physico-
chemical studies allowed us to assign structures A and
B to coordination compounds I–X.
Sf1_5
O
O
Cu
Sf1_5
O
Cu
O
n H2O
n H2O
N
N
A
B
Sf 1 = 4-aminobenzenesulfonamide, Sf2 = 4-amino-N-(1,3-thiazol-2-yl)benzenesulfonamide, Sf3 = 4-amino-N-(1,3,4-thiadiazol-
2-yl)benzenesulfonamide, Sf 4 = 4-amino-N-(pyrimidin-2-yl)benzenesulfonamide, Sf 5 = 4-amino-N-(4,6-dimethylpyrimidin-
2-yl)benzenesulfonamide; n = 1, 2.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 80 No. 7 2010

1354
GULYA et al.
As shown in [10–12], many coordination com-
imino)methyl]phenol (H2L1) or 1-[(2-hydroxyphenyl-
imino)methyl]naphthalen-2-ol (H2L2), copper(II) acetate
hydrate, and 4-aminobenzenesulfonamide, 2-(4-amino-
phenylsulfonylamino)-1,3-thiazole, 2-(4-aminophenyl-
sulfonylamino-5-ethyl-1,3,4-thiadiazole, 2-(4-amino-
phenylsulfonylamino)pyrimidine, or 2-(4-aminophe-
nylsulfonylamino)-4,6-dimethylpyrimidine, taken at a
molar ratio of 1:1:1. The yields of compounds I–X
and their elemental analyses and some physico-
chemical parameters are given in Tables 1 and 2.
pounds of 3d elements with O,N,O- and O,N,S-ligands
selectively inhibit growth of malignant tumor cells
(human myeloid leukemia HL-60). We examined the
activity of complexes I and III against HL-60 cells in
vitro. Compounds I and III at a concentration of 10–4 M)
inhibited growth and reproduction of 100% of HL-60
cells. The inhibitory effect of I and III activity at a
concentration of 10–5 M was estimated at 90 and 75%,
respectively, whereas no antitumor activity was
observed at a concentration of 10–6 M.
ACKNOWLEDGMENTS
EXPERIMENTAL
The author thank Dr. J. Roy (Centre hospitalier
universitaire de Quebec) for her help in studying
antitumor activity of the synthesized complexes.
The resistance of solutions of complexes I–X in
DMF (20°C, c = 0.001 M) was measured with the aid
of an R-38 rheochord bridge. The IR spectra were
recorded on a Specord M-80 spectrometer from
samples preliminarily dried in a drying box at 105°C
until constant weight and dispersed in mineral oil. The
effective magnetic moments of compounds I–X were
determined by the Gouy method. The molar magnetic
susceptibilities were calculated with correction for
diamagnetism from the theoretical magnetic suscep-
tibilities of organic compounds. Thermal gravimetric
analysis of complexes I–X was performed on a Paulik–
Paulik–Erdey instrument in the temperature range from
20 to 1000°C in air using a corundum crucible and
Al2O3 as reference.
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 80 No. 7 2010