Spectral, analytical, thermal, and antimicrobial studies of novel sodium 2-[4(2-hydroxy-3-izopropylaminopropoxy)phenyl]acetamide (atenolol) dithiocarbamate and its divalent transition metal complexes

Article abstract of DOI:10.1134/s1070328408020061

Atenolol dithiocarbamate (ADTC) and its complexes with Cu(II), Co(II), Ni(II), Zn(II), and Cd(II) have been synthesized. These newly synthesized products have been characterized by elemental analyses (C, H, N, and S), thermal (thermogravimetry (TG) and di

Full text of DOI:10.1134/s1070328408020061

ISSN 1070-3284, Russian Journal of Coordination Chemistry, 2008, Vol. 34, No. 2, pp. 106–114. © Pleiades Publishing, Ltd., 2008.
Spectral, Analytical, Thermal, and Antimicrobial Studies
of Novel Sodium 2-[4(2-Hydroxy-3-
Izopropylaminopropoxy)Phenyl]Acetamide (Atenolol)
Dithiocarbamate and its Divalent Transition Metal Complexes1
A. Gölcü and P. Yavuz
Department of Chemistry, Faculty of Science and Arts, Kahramanmaras Sütcu Imam University,
Kahramanmaras 46100, Turkey
E-mail: ag518@ksu.edu.tr
Received November 9, 2006
Abstract—Atenolol dithiocarbamate (ADTC) and its complexes with Cu(II), Co(II), Ni(II), Zn(II), and Cd(II)
have been synthesized. These newly synthesized products have been characterized by elemental analyses (C,
H, N, and S), thermal (thermogravimetry (TG) and differential thermal analyses (DTA)) as well as by spectral
(UV, IR, and NMR (1H)) studies. The stability constants (β) of metal complexes ofADTC have been determined
by UV-Vis data in solutions in DMSO. The antimicrobial activities of the metal complexes have been screened
in vitro against ten bacteria.
DOI: 10.1134/S1070328408020061
1
INTRODUCTION
tor blocking drugs in use are aryloxypropanolamines.
Atenolol is an aminoalcohol and induces a chiral cen-
ter. β-Blockers are exceptionally toxic and most of
them have a narrow therapeutic range: the differences
between the lowest therapeutic and the highest tolera-
ble doses are small [13]. Many methods have been
described for the quantitative determination and analy-
sis of β-blockers including non-aqueous titrimetric
[14], colorimetric [15], spectrophotometric [16], fluori-
metric [17], and chromatographic [18, 19]. Besides,
atenolol have been determined via dithiocarbamate
metal complexes in pharmaceutical and biological flu-
ids in our laboratory. The chemical structure of atenolol
is given below:
Dithiocarbamates are a large family of compounds
that have been widely investigated because they are of
great interest in different fields. Many studies have been
carried out in order to gain information on the com-
plexes formed by dithiocarbamate and metal ions,
which are used as fungicides and pesticides [1]. Their
range of applications covers several uses in chemical
industries, biology, and biochemistry. For example,
some of the dialkyl-substituted dithiocarbamate salts
have also shown interesting biological effects, which
include antialkylation [2, 3] or anti-HIV properties
[4, 5]. They are also used as effective antidotes for cad-
mium intoxication [6, 7]. The ability of dithiocarbam-
ate to bind to metal has been known for many years. It
forms a chelate with virtually all transition elements
[8]. The bidentate anion is also known to bridge two
transition metal centers [9]. Water-soluble dialky-
ldithiocarbamate complexes have been tested in various
medical applications [10]. In our previous study, we
reported the spectrophotometric determination of anti-
hypertensive drug propranolol via dithiocarbamate
metal complexes [11].
NH2
CH3
O
H3C
NH
O
HO
In a previous publication, we reported the synthesis
and characterization of the Cu(II) and Co(II) complexes
of atenolol [20]. The binuclear Cu(II) and mononuclear
Co(II) complexes of atenolol have not any biological
activity, while metal complexes with atenolol dithiocar-
bamate (ADTC) have high biological activity. In other
previous study [21], we synthesized and characterized
new propranolol-dithiocarbamate and its metal com-
plexes too. However, we showed that in this study the
stability constant values of ADTC metal complexes are
Atenolol belongs to the category of β-blockers and,
more specifically, it is a hydrophillic β1-receptor block-
ing agent. This β1-andrenoceptor blocking drug is of
therapeutic value in the treatment of various cardiovas-
cular disorders, such as angina pectoris, cardiac arrhyt-
mia, and hypertension [12]. Most of the β-andrenocep-
1
The text was submitted by the authors in English.
106

SPECTRAL, ANALYTICAL, THERMAL, AND ANTIMICROBIAL STUDIES
Table 1. Some analytical and synthetical data for the dithiocarbamate complexes
107
Contents (found/(calcd)), %
Formula
weight
Compound
Color Yield, % M.p., °C
C
H
N
S
M
[C30H42N4O6S4Cu] · H2O (I)
746.5
Brown
55
161
53.4
(53.5)
5.7
7.5
17.2
8.5
(5.9) (7.2) (17.2) (8.2)
Na[C19H27N2O7S2Co] · 5H2O (II)
Na[C17H29N2O5S2Ni] · H2O (III)
Na[C19H27N2O7S2Zn] · H2O (IV)
Na[C15H21N4O9S2Cd] · 2H2O (V)
631.1
505.0
565.4
636.0
Green
Green
White
Yellow
50
53
65
50
291
175
291
156
35.7
5.9
4.6
14.14
9.3
(35.6) (4.1) (5.5) (14.15) (9.5)
35.7
6.1
5.5
12.7
11.6
(35.6) (5.4) (6.0) (12.1) (11.1)
56.0 5.1 4.9 11.3 11.5
(55.9) (5.3) (4.5) (11.5) (11.9)
28.3 3.3 8.8 10.6 17.6
(28.7) (3.9) (8.5) (10.1) (18.1)
higher than the propranolol-dithiocarbamate metal decomposed in HNO3 : H2O2 (1 : 1) and then dissolved
complexes.
in 1.5 N HNO3. The amounts of Cu, Co, Ni, Zn, and Cd
were determined [22, 23]. UV spectra were recorded in
DMSO solution at room temperature on a Shimadzu
UV–160 A spectrophotometer. The metal contents of the
complexes were determined with the aid of an Ati Uni-
cam 929 Model AA spectrometer in solutions prepared
by decomposing the compounds in aqua regia and then
subsequently digesting them in concentrated
In the present work, the synhesis and chemical charac-
terization as well as the biological effects of novel transi-
tion metal complexes (Cu(II), Co(II), Ni(II), Zn(II), and
Cd(II)) containing dithiocarbamate, are reported. Differ-
ent complexes, such as [C30H42N4O6S4Cu] · H2O (I),
Na[C19H27N2O7S2Co] · 5H2O (II), Na[C17H29N2O5S2Ni] ·
H2O (III), (Na[C19H27N2O7S2Zn] · H2O (IV) and HNO3/H2O2 (1 : 1). Molar conductances of all com-
Na[C15H21N4O9S2Cd] · 2H2O (V), are characterized by plexes were determined in DMSO (~10–3 M) at room
temperature using a Jenway Model 4070 conductivity
meter. Magnetic measurements were carried out by the
Gouy method using Hg[Co(SCN)4] as a calibrant. Ace-
tate and nitrate ions (in cobalt, zinc, and cadmium dithio-
carbamate complexes) were determined gravimetrically
as silveracetate and ammonia, respectively [24].
elemental analyses, thermal and differential thermal anal-
yses as well as by spectral studies.
EXPERIMENTAL
Atenolol was kindly received from Sanofi Dogu Drug
Co. (Istanbul, Turkey) and used without further purifica-
tion. All other chemicals were of analytical reagent
grade: CuCl2 · 2H2O (Merck), Co(CH3COO)2 · 4H2O
(Merck), NiCl2 · 6H2O (Merck), Cd(NO3)2 · 4H2O
(Merck), and Zn(CH3COO)2 · 2H2O (Merck). Carbon
disulfide (CS2) and NaOH were purchased from Aldrich.
Infrared spectra were recorded on a Shimadzu 8300
FT-IR spectrophotometer using KBr discs in the range
4000–400 cm–1. 1H NMR spectra were taken on a Bruker
Avance DPX–400 NMR instrument. Tetramethylsilan
(TMS) was used as a internal standard and deuterated
dimethylsulfoxide served as solvent. The thermogravi-
metric analyses were made by means of a Perkin Elmer
Pyris Diamond DTA/TG Thermal System electrobalance
converted to a thermobalance by addition of a small fur-
nace and a sample holder. The temperature was mea-
sured by using a chromal–alumal thermocouple attached
to a suar MF–550 digital multimeter, and the heating rate
was adjusted to be 10 K/min. The elemental analysis (C,
H, N, and S) was performed at the TUBITAK Instrumen-
talAnalysis Laboratory (Besevler/Ankara, Turkey) using
a Carlo Erba 1106 elemental analyzer. The ratios of the
metal present in all complexes were determined by
Sodium hydroxide (0.200 g, 0.005 mol) dissolved in
100 ml of H2O was mixed with a diethyl ether solution
(100 ml) containing atenolol (1.331 g, 0.005 mol) and CS2
(0.38 g, 0.005 mol) was added dropwise to this solution in
a water–ice bath at about 0°C. The resulting solution was
stirred for 60 min at 0°C and then transferred into a sepa-
ratory funnel. The aqueous phase was separated and evap-
orated in a water bath at 95°C. Obtained solid sodium
atenolol dithiocarbamate (NaADTC) was washed with
diethyl ether for several times and dried in air.
Metal chloride/acetate/nitrate (0.0025 mol) dissolved
in distilled H2O: methanol (1 : 10, v : v) (50 ml) was
added with stirring a solution of NaADTC (1.82 g,
0.005 mol) in H2O/methanol (1 : 10, v : v) (50 ml). The
metal complexes precipitated immediately as polycrys-
talline solids and were filtered by suction, washed with
H2O, and diethyl ether and dried in air. The yield was
0.90−1.20 g (50–65%). The melting points of the com-
plexes are between 156–291°C. The relevant synthetic
and analytical data for all the complexes are given in
Table 1.
Synthesis of the atenolol dithiocarbamate copper(II)
atomic absorption spectroscopy. The complexes were and other metal complexes is shown below:
RUSSIAN JOURNAL OF COORDINATION CHEMISTRY Vol. 34 No. 2 2008

108
GÖLCÜ, YAVUZ
NH2
CH3
1. CS2, OH–
2. Cu2+
O
O
H3C
NH
O
HO
NH2
CH3
O
H3C
N
Cu
N
HO
S
S
S
S
· H2O
OH
O
CH3
CH3
O
H2N
NH2
CH3
1. CS2, OH–
2. M2+
O
H3C
NH
O
HO
NH2
CH3
O
H3C
N
O
HO
S
S
Na
· nH2O
M
X
X
M : Ni, X = MeO, n = 1
M : Cd, X = NO–3, n = 2
M : Zn, X = AcO−, n = 1
M : Co, X = AcO–, n = 5
The growth inhibitory activity of the chemical mat- the agar-disc diffusion method as will be described
ter was tested against ten bacteria (Bacillus megaterium below. The bacteria were first incubated at 37 0.1°C for
DSM 32, Bacillus brevis NRS, Yersinia enterocolitica 24 h in nutrient broth (Difco), and the yeasts were incu-
CMC 120, Micrococcus luteus LA 2971, Pseudomonas bated in sabouraud dextrose broth (Difco) at 25 0.1°C
aeruginosa ATCC 27853, Enterococcus faecalis ATTC for 24 h. The cultures of the bacteria and yeast were
15753, Kluyveromyces marxianus CBS 6556, Candida injected into the Petri dishes (9 cm) an amount of
tropicalis DSM 4959, Candida albicansATCC 1023 and 0.1 ml. Then, mueller hinton agar and sabouraud dex-
Kluvyeromyces fragilis A 230). These microorganisms trose agar (sterilized in a flask and cooled to 45–50°C)
were provided from the Microbiology Laboratory Cul- were homogenously distributed onto the sterilized Petri
ture Collection (Department of Biology, Kahramanma- dishes in an amount of 15 ml. Subsequently, the steril-
ras Sütcü Imam University, Turkey). Antimicrobial ized blank paper discs 6 mm in diameter were saturated
activities of the chemical matter were determined using with 1200 µg of chemical matters per disc. The discs
RUSSIAN JOURNAL OF COORDINATION CHEMISTRY Vol. 34 No. 2 2008

SPECTRAL, ANALYTICAL, THERMAL, AND ANTIMICROBIAL STUDIES
109
Table 2. Molar conductance, electronic spectral data and
were placed onto the agar plates, which had previously
been inoculated with the above organisms. In addition,
blank paper discs treated with ampicillin, streptomycin,
and nystatin antibiotics were used as positive controls.
Afterwards the plates combined with the discs were left
at 4°C for 2 h, the plates injected with yeast were incu-
bated at 25 0.1°C for 24 h, and those injected with
bacteria were incubated at 37 0.1°C for 24 h. After
24 h, inhibition zones appearing around the discs were
measured and recorded in mm. The initial number of
microorganisms in the suspension was determined for
the total yeasts and bacterial count during 24 h at 37°C
for bacteria and 48 h 25°C for yeasts [21].
magnetic moments of all complexes in DMSO
Λ,
Compound
λmax
µeff, µB*
Ohm–1 cm2 mol–1
I
613, 450, 296 1.90
590, 381, 275 4.16
II
III
11.6
16.3
634, 441,
360, 274
Diamagnetic
IV
V
70.1
90.1
440, 361, 267 Diamagnetic
Job’s method [25, 26] was used to determine (in
DMSO) the stoichiometric ratios for the reactions
between the NaADTC and metal ions. The solutions
were prepared by mixing solutions of both components
with equal molar concentrations (1.0 × 10–4 M) in ratios
varying from 1 : 0 to 9 : 1. The complexes were pre-
pared by mixing in methanol of adequate stoichiomet-
ric amounts of NaADTC and the corresponding salts.
364, 275
Diamagnetic
* Magnetic moment data for per metal.
where A is the absorbance of the solution at a chosen
wavelength after addition of a given amount of the cat-
ion at the concentration [M], A0 is the absorbance of the
free ligand at a given wavelength before the addition of
the cation, and ALIM is the absorbance at a given wave-
length in the presence of such an excess of cation that
the ligand is fully complexed.
Let us consider a complex MmLl (where L is ligand
and M is the metal ion) formed according to the equa-
tion:
mM + lL = MmLl,
with stability constant
βml = [MmLl]/([M]m[L]l).
(1)
RESULTS AND DISCUSSION
The analytical data of the dithiocarbamate metal
complexes consist of 1 : 1 or 1 : 2 ligand to metal ratio
and support the sructures given in schemes. The values
equivalent conductances of complexes I–V were found
to be in the 11.6–90.1 Ohm–1 cm2 mol–1 range. From
these data we can say that these complexes have the cat-
ionic nature and conduct electricity in solution [22, 23]
(Table 2). The mononuclear [C34H40N2O4S4Cu] · H2O
complex was found to be nonelectrolyte in DMSO [22].
The electronic absorption spectral data of the new
dithiocarbamate metal complexes are listed in Table 2,
and tentative assignments of the important characteris-
tic bonds have been made with the help of an earlier
publication [22, 23, 27].
The electronic spectra of these newly synthesized
dithiocarbamate metal complexes exhibit some bonds.
The most intense bonds (296–274 nm) are assigned to
the intramolecular charge transfer of the ligand (π–π*
and n–π* in the N–C=S group) [28, 29]. The intense
bonds at 450, 381, 360, 361, and 363 nm in the spectra
of the Cu(II), Co(II), Ni(II), Zn(II), and Cd(II) dithio-
carbamate complexes, respectively, are ascribed to
charge transfer processes, probably, from ligand to
metal, mainly associated with the N–C=S and S–C=S
groups. The absorption at higher wave lengths in
Cu(II), Co(II), and Ni(II), dithiocarbamate complexes
are due to d–d transitions [30–32].
(2)
The principle of the method is as follows: the absor-
bance (A) is measured for a series of solutions contain-
ing the ligand and cation, so such that the sum of the
total concentration of ligand and cation is constant
cL + cM = c = constant.
(3)
The position of the absorbance maximum (Amax) is
then related to the ratio m/l as shown below. It is conve-
nient to use the following dimensionless quantity
(which is analogous to the molar fraction but not
strictly)
X = cM/cM + cL.
It has been shown [24, 26] that
m/l = Xmax/1 – Xmax
(4)
,
(5)
where Xmax corresponds to the Amax (absorbance maxi-
mum) at an appropriate wavelength (chosen so that the
changes in absorbance are as large as possible). For the
1 : 1 complex Xmax = 1/2 according to Eq. (4). In this
case
M + L = ML,
and stability constant Ks = [ML]/([M][L]) can be found
[26] from the equation:
The most significant FT-IR bands assignments are
listed in Table 3. These vibrational spectra were ana-
lyzed on the basis of general references [33] and by
(A – A0)/ALIM – A = Ks[M],
RUSSIAN JOURNAL OF COORDINATION CHEMISTRY Vol. 34 No. 2 2008

110
GÖLCÜ, YAVUZ
Table 3. Infrared spectral data of the complexes (cm–1)
salts. Canonical forms a, b and hybrid form c in ADTC
are shown below:
Com-
–
–
–
R
R
S
S
R
1
S
S
ν(OH) ν(NH2) ν(CN) ν(C–S) ν(M–S) ν(M–N)
1
+
1
S
S
pound
..
..
N
N
N
C
–
R
2
R
R
2
2
I
3375.2 1658.7 1510.2 1242.1 575
491
a
b
c
OH
II
3421.5 1659.7 1510.2 1251.7 526.8 453
3325.0 1657.7 1510.2 1236.3 518.5 455
O
CH
3
H2C
R1:
, R2:
HC
III
IV
V
CH
3
O
3342.4 1624.5 1510.2 1244.0 596
3386.7 1616.5 1510.2 1242.1 520
418.5
NH2
A strong band at 1241.1, 1236.3, 1242.2, 1244.0,
and 1261.7 cm–1 observed in the spectra of the Cu(II),
Ni(II), Cd(II), Zn(II), and Co(II) dithiocarbamate com-
plexes, respectively, is assigned to the v(C=N) vibra-
tion of the –R–N=CS2 group.
430
comparison with other related compounds [34]. The
free ligand atenolol shows an IR spectrum with two
bands (3355 and 3174 cm–1), due to the aliphatic OH
and the secondary NH vibrations, respectively, engaged
in inter- or intramolecular H-bonds. In the carbamate
derivative (ADTC), the nitrogen atom of the secondary
NH group interacts with the CS2 moleculeand hydrogen
atom of this group is leaving from the molecule. In the
IR spectra of ADTC and its complexes, the bands due
to the stretching of the secondary NH-vibrations disap-
peared. In the spectrum of atenolol, the characteristic
band at 1644 cm–1 can be due to the amide ν(NH2)
vibrations. In the complexes, this band does not shift to
higher or lower regions and this situtation confirms that
the nitrogen atom of the amide group did not coordinate
to the metal ions or carbamate group. The ν(CN) band
in the spectra of the ADTC is observed at around
1250 cm–1 [35]. This low value indicates a great contri-
bution of the canonical forms (a) and (b) for the reso-
The spectral region of 1000–900 cm–1 is characteris-
tic for disulfuric chelation. The νassym(CS2) vibration
was observed at a higher frequency in the spectra of the
sodium salts of dithiocarbamates (ca. 978 cm–1) [36]
than that in the spectra of the complexes studied here:
904, 914.1, 900.7, 943.1, and 947 cm–1 for Cu(II),
Ni(II), Cd(II), Zn(II), and Co(II) dithiocarbamate com-
plexes, respectively [37]. The shifts observed in the
νas(CS2) and νas(CN) in the spectra of the compounds
studied here, when compared with the spectra of the
ADTC ligand, are consistent with the increased impor-
tance of the canonical form (c) in all metal complexes.
The spectra of the complexes also show the expected
medium band in the 500−400 cm–1 range assigned to
the M–S stretching vibration indicating the gem-disul-
fur ligand.
The magnetic moment of the complexes (Table 2)
were measured at room temperature. On the basis of the
magnetic and spectral evidence the copper (II) complex
nance hybrid form (c) in the dithiocarbamate sodium has mononuclear structure in which the Cu2+ cation has
1
Table 4. H NMR data (δ, ppm) for the dithiocarbamate complexes
δ, ppm
Compound
–CH3
–NCH
–CH2
–OCH3
–NH2
–OH
Na[C17H29N2O5S2Ni] · H2O (III)
Na[C19H27N2O7S2Zn] · H2O (IV)
Na[C15H21N4O9S2Cd] · 2H2O (V)
1–1.6
1–1.6
1–5
3.85
3.78
3.60
2.65
2.75
3–4
3.6
4–5
5.6
5.2
3–4
3–4
4
3.5–4.5
55.5
RUSSIAN JOURNAL OF COORDINATION CHEMISTRY Vol. 34 No. 2 2008

SPECTRAL, ANALYTICAL, THERMAL, AND ANTIMICROBIAL STUDIES
111
an approximately tetrahedral environment [27]. The groups in the complex. In the third step, the DTA curves
reveal several simultaneous processes with a large
endothermic effect due to the combustion of the inter-
mediate formed. The final product formed at 806.81°C
consists of CdO. The Na[C19H27N2O7S2Zn] · H2O com-
plex decomposes in two steps. The first step between
164–176°C corresponds to dehydration. After dehydra-
tion, it melts at 291°C. Degradation of the organic part
of the ligand takes place in the second decomposition
step in the range 244–450°C. The final decomposition
product was identified as ZnO from the IR spectra and
mass loss calculations.
Na[C19H28NO5S2Co] · H2O complex has an effective
magnetic moment per cobalt atom of 4.16 µB at room
temperature, and this complex is tetrahedral around the
Co2+ ion [35]. The Ni(II) complex has a diamagnetic
character and square-planar geometry around the Ni(II)
centre [38]. In addition, the zinc (II) and cadmium(II)
complexes are diamagnetic with tetrahedral geometry
and are mononuclear.
1
The H chemical shifts of the Ni(II), Cd(II), and
Zn(II) dithiocarbamate complexes are listed in Table 4.
1
The H NMR spectra of the atenolol ligand contained
All complex formation was studied at the same con-
centration of NaADTC (1 × 10–4 mol/l) and in a wide
range of metal ions (Cu+2, Co+2, Ni+2, Zn+2, and Cd+2)
concentrations (7 × 10–7 – 6 × 10–3 mol/l). A low and un-
changed concentration of the lectroneutral organic ligand
allowed us to exclude from consideration the theoretical-
ly possible formation of the biligand or monoligand com-
absorptions due to the protons of ADTC. The Ni(II),
Cd(II), and Zn(II) dithiocarbamate complexes show a
sharp singlet at 1.0–1.60 ppm due to methyl protons
thus suggesting the magnetical equivalence of these
protons. The –CH protons, in the complexes appear as
a triplet at 3.60–3.85 ppm and a sharp singlet at
2.65−4.0 ppm due to –CH2 protons, respectively. While the
free ligand atenolol has a sharp singlet at 4.00–4.28 ppm
due to the –NH protons, this peak disappear in the three
dithiocarbamate complex spectra [38–40].
plexes (according to the equilibrium 2L + M+2 = ML22+
or L + M = ML), whose detection, under our experimen-
tal conditions, requires the complex formation constant to
be higher than 107–109 mol/l. Information on the stoichi-
ometry of the metal–ligand complexes of compound
NaADTC was obtained from the continuous variation
method [24–26]. Job’s plot for the M+2 complex is pre-
sented on figure a and b. It was found from Job’s plots for
Na[C19H28NO5S2Co] · H2O, [C17H26NO5S2Ni]Cl · H2O,
Na[C21H26NO6S2Zn], and Na[C17H22N3O9S2Cd] · H2O
complexes that Xmax = 1/2 for these complexes, hence, the
stoichiometry of the metal–ligand complexes of
NaADTC was found to be 1 : 1 at used concentration of
the ligand (1 × 10–4 mol/l) (figure b). The plot reached a
maximum at a fraction of 0.3 indicating the formation of
3 : 7 for ADTC–Cu(II) complex. In this situtation, the
[C34H40N2O4S4Cu] · H2O complex is more likely 1 : 2
(figure a) [22, 23, 27–29]. The elemental analyses were
satisfactory and show that the complexes have a ligand to
metal ratio for 2 : 1 or 1 : 1 too. The calculated values of
stability constants for all the complexes are listed bellow:
The synthesized complexes were placed into dried
Schlenk tube against a dry N2 flow at atmospheric pres-
sure [41]. The complexes were then heated to the
desired temperature under static N2. The thermal data
on the complexes are given in Table 5.
The TG data of the complex C30H42N4O6S4Cu · H2O,
show the formation of the anhydrous complex by
175°C, which indicates the loss of water of hydration,
and this high-temperature dehydration confirms the
loss of coordinated water. The second step at 235°C is
endothermal and relates to the decomposition of the
DTC ligand. The subsequent decomposition step com-
pleted at 359°C produces CuO as the final solid prod-
ucts. The thermal dehydration of Na[C19H27N2O7S2Co] ·
5H2O complex occurs in three steps, giving endother-
mal effects at 70, 158, and 198°C, respectively. One
molecule of crystallization water is removed in the first
step of dehydration. The second step, in the tempera-
ture range 158–228°C, corresponds to the loss of 4 mol-
ecules of water. The third step, between 220–334°C,
involves the endothermal loss of two H3C–COO
groups. The following steps involve the endothermal
decomposition of the intermediate formed to give
metallic Co as the final solid product. The
Na[C17H29N2O5S2Ni] · H2O complex decomposes in
two steps. The first step involves endothermal decom-
position at 137°C, corresponding to loss of the crystal-
lization water, as indicated by the TG mass loss. The
second step at 290°C is endothermal and reveals the
loss of two –O–CH3 groups ligand. The subsequent
logKs
Compound
[C34H40N2O4S4Cu] · H2O
Na[C19H28NO5S2Co] · H2O
Na[C17H26NO5S2Ni] · H2O
Na[C21H26NO6S2Zn]
5.16 0.01
2.99 0.04
4.01 0.02
3.02 0.01
4.13 0.02
Na[C17H22N3O9S2Cd] · H2O
The bacteria Bacillus megaterium DSM 32, Bacillus
decomposition step completed at 600°C produces NiO brevis NRS, Yersinia enterecolitica CMC 120, Micro-
as the final product. The Na[C15H21N4O9S2Cd] · 2H2O
complex exhibits three distinct decomposition steps.
The first step in the temperature range 168–180°C cor-
responds to the loss of water molecules. The second
coccus luteus La 2971, Pseudomonas aeruginosa
ATCC 27853, Enterococcus feacalis ATTC 15753 and
Kluyveromyces marxianusADH1 and the yeast cultures
Candida tropicalis FMC 23, Candida albicans ATCC
step at 290°C corresponds to the loss of the nitrate 10231 and Kluyveromyces fragilis NRRL 2415 were
RUSSIAN JOURNAL OF COORDINATION CHEMISTRY Vol. 34 No. 2 2008

112
GÖLCÜ, YAVUZ
Table 5. Thermal degradation of the dithiocarbamate complexes
Loss of coordinated water
(found/calcd), %
Loss of ligands mass
(found/calcd), %
Compound
T, °C
T, °C
Final product
I
2.50 (2.41)
14.59 (14.26)
3.37 (3.56)
3.46 (3.18)
5.94 (5.66)
175
88.98 (89.35)
89.54 (90.65)
85.00 (85.15)
86.04 (85.67)
79.02 (79.87)
359–967
CuO
Co
II
70.74–228.72
137.53
334.68–962
III
IV
V
290.83–600
NiO
ZnO
CdO
164.93–176.83
168.79–180.71
244.85–450.00
290.36–806.81
used in this study as test microorganisims [27]. The bated at 30 0.1°C for 24 h by inoculation into Nutrient
Broth (Difco), and the yeasts studied were incubated in
Malt extract Broth (Difco) for 72 h. An inoculum con-
tannimg 105 bacterial cells or 104 yeast cells/ml was
spread on Mueller-Minton Agar plates (1 ml inocu-
lum/plate). The discs injected with solutions were
placed on the inoculated agar by pressing slightly, and
incubated at 30°C (18–24 h) for bacteria, and at 25°C
(72 h) for yeasts. On each plate a appropriate reference
antibiotic disc was applied depending on the test micro-
organisms. The data reported in Table 6 are the average
data of five experiments.
compounds were dissolved in DMSO to a final concen-
tration of 30 µg/ml. Empty sterilized antibiotic discs
having a diameter of 6 mm (Schleicher and Schull no:
2668, Germany) were each impregnated with 10 l of
solution. All the bacteria mentioned above were incu-
Absorbance
0.8
(a)
0.6
Table 6 shows antimicrobial activities of the com-
plexes. Besides, the inhibition zones formed by stan-
dard antibiotic discs are indicated in Table 7. As can
clearly be seen from Table 6, all complexes, except the
Cu(II) complex, show strong antimicrobial activities
against all tested microorganisms. In classifying the
antimicrobial activity as Gram(+) or Gram(–), it is gen-
erally expected that a much greater number would be
active against Gram(+) than Gram(–) bacteria [42].
However, in this study, the complexes were active
against both Gram(+) and Gram(–) bacteria. The
ADTC cobalt complex has formed the highest antimi-
crobial effect against all tested microorganisms, while
the ADTC cadmium complex has formed the smallest
antimicrobial effect against all tested microorganisms.
When the results obtained were compared to those of
standard antibiotics, the bacterium Micrococcus luteus
from all the tested bacteria is the most influenced bac-
terium against the ADTC cobalt complex, having a
diameter zone of 26 mm. This complex has a stronger
antimicrobial effect than those of the standard antibiot-
ics P10, AMP20, and VA30 aginst Pseudomonas aerug-
inosa. Against the bacterium Enterococcus feacalis, the
ADTC cobalt, nickel and zinc complexes have higher
activities than those of P10, AMP20, CTX30, and
VA30. In addition, the ADTC cadmium complex is
equivalent to the standard antibiotic P10 against Bacil-
0.4
0.1
0.3
0.5
0.7
NaADTC to Cu(II) ratio
(b)
0.8
0.6
0.4
0.1
0.5
1.0
NaADTC to metal ratio
Continuous variation plots for the stoichiometry of the reac-
tion of ADTC–copper(II) (a) and ADTC and metals (b).
RUSSIAN JOURNAL OF COORDINATION CHEMISTRY Vol. 34 No. 2 2008

SPECTRAL, ANALYTICAL, THERMAL, AND ANTIMICROBIAL STUDIES
113
Table 6. Antimicrobial activity data for the dithiocarbamate
lus brevis and it has higher antibacterial activity than
P10 against Pseudomonas too. All complexes, except
the ADTC copper(II), have high antimicrobial activity
against the yeast cultures used in this study as com-
pared to the standard antifungal antibiotics Ketacano-
zole and Clotrimaole. Notably, the ADTC cobalt com-
plex shows a higher antiyeast activity than the other
complexes. The ADTC cobalt complex has stronger
antiyeast activity than those of KET20 and CLT10
against Candida tropicalis and Kluyveromyces fragilis,
while they are equivalent to the standard antibiotics
KET20 and CLT10. C. albicans is succeptible to the
ADTC nickel complex, as compared two standard anti-
yeast antibiotics [43].
The complexes differ significantly in their activity
against tested microorganisms. These diffrences can be
attributed to the fact that the cell wall in Gram(+) bac-
teria consists of a single layer, whereas the Gram(–) cell
wall is a multilayered structure and the yeast cell wall
is a quite complex.
complexes
Diameter of inhibition zones, mm*
Microorganisms
II
III
IV
V
VI**
B. megaterium
B. brevis
12
19
19
26
25
25
21
20
28
24
9
16
10
12
8
14
11
12
10
9
8
4
8
5
5
4
3
3
3
2
2
12
6
Y. enterecolitica
M. luteus
8
P. aeruginosa
E. feacalis
10
6
21
16
6
24
12
12
13
11
K. marxianus
C. tropicalis
C. albicans
K. fragilis
9
ACKNOWLEDGMENTS
This work was supported by a grant from the Kahr-
amanmaras Sütcu Imam University Scientific Research
Project Foundation (Grant no: 2004/2–7) (Turkey). The
authors are grateful to Prof. Dr. Selahattin Serin (Uni-
versity of Cukurova, Faculty of Science and Arts,
Department of Chemistry, Adana, Turkey), Assoc. Prof.
Dr. Mehmet Tumer and Chem. Mustafa Dolaz (Univer-
sity of Kahramanmaras Sütcu Imam, Faculty of Sci-
ence and Arts, Department of Chemistry, Kahraman-
maras, Turkey) for their useful suggestions and Chem.
GokturkAvsar (University of Cukurova, Faculty of Sci-
7
28
6
6
9
Notes: * Antimicrobial activity of complex I is absent for all micro-
organisms.
** VI – NaADTC.
Table 7. Antimicrobial activities of some standard antibiotics
Diameter of inhibition zones, mm
Microorganism
P10
AMP20
CEF30
VN30
KET20
CLT10
B. megaterium
B. brevis
38
12
28
22
8
24
16
44
28
10
10
30
32
40
43
30
34
54
13
18
34
18
32
22
32
10
14
16
19
Y. enterecolitica
M. luteus
P. aeruginosa
E. feacalis
12
25
32
K. marxianus
C. tropicalis
C. albicans
K. fragilis
21
26
16
15
20
18
P10 – Penicillin G (10 Units); AMP20 – Ampicillin 10 µg; CEF30 – Cefotaxime 30 µg; VN30 – Vancomycin 30 µg; KET20 – Ketaconazole
20 µg; CLT10 – Clotrimazole 10 µg.
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GÖLCÜ, YAVUZ
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