INTRODUCTION:
Many thiosemicarbazones possess a wide spectrum of medicinal and
biological properties1-14. Their activity has frequently been
thought to be due to their ability to chelate trace metals. Leibermeister15
showed that Cu2+ enhance the antitubercular activity of p-acetamidobenzaldehyde
thiosemicarbazone. Similar Petering et al. 16 showed that the
active intermediate in the antitumour activity of 3-ethoxy-2-oxobutyraldehyde bis(thiosemicarbazone)
(H2KTS) was the chelate Cu(KTS). These findings have continuously
led to an increased interest in the chemistry of metal chelates of
thiosemicarbazones.
Comparatively less is known about transition metal coordination
complexes of thiosemicarbazones having a pyrazolone ring. Herein present
studies, two new thiosemicarbazones i.e.,
4[N-(2’,4'-dichlorobenzalidene) amino]antipyrine thiosemicarbazone (DCBAAPTS)
and 4[N-(2',4'-dinitrobenzalidene)amino] antipyrine thiosemicarbazone
(DNBAAPTS) have been synthesized and their coordination behaviour towards Co2+
, Ni2+ and Cu2+ are reported.
EXPERIMENTAL:
MX2·nH2O (M = Co2+ , Ni2+
or Cu2+; X = Cl, Br, NO3 or CH3COO–)
were obtained from SD Fine Chemicals Ltd. (Mumbai, India) and were used as
received. M(NCS)2 was prepared by mixing metal chloride (in ethanol)
and ethanolic solution of potassium thiocyanate in 1:2 molar ratio. The
precipitated KCl was filtered off and the filtrate having respective metal thiocyanate
was used immediately for complex formation. The ligands DCBAAPTS and DNBAAPTS
were synthesized in the laboratory by reported method17.
Fig.1:4[N-(2’,4'-dichlorobenzalidene)amino]antipyrine
thiosemicarbazone (DCBAAPTS)
[m.f. C19H18N6SCl2,
m.s. 433]
Fig.2:4[N-(2',4'-Dinitrobenzalidene)amino]antipyrine
thiosemicarbazone (DNBAAPTS)
[m.f. C19H18N8O4S,
m.s. 454]
Synthesis of the complexes:
A general method has been used for the preparation of all the
complexes. A hot ethanolic solution of the corresponding cobalt(II), nickel(II)
or copper (II) salt was mixed with a hot ethanolic solution of the ligand (in
1:1 molar ratio). The reaction mixture was refluxed on water bath for ca.
2 hrs. On cooling in ice cold water, the coloured complexes precipitated out in
each case. They were filtered, washed with ethanol and recrystallized and dried
over P4O10 under vacuum.
Physical measurements and analytical estimations:
The cobalt(II) ,nickel(II) and copper (II) in their metal
complexes were estimated complexometrically with EDTA using murexide and
erichrome black-T as indicators respectively after decomposing the complexes
with conc. H2SO4 and H2O218.
The percentage of sulfur was estimated gravimetrically as BaSO4. The
nitrogen content was determined by the Kjeldahl method.
The molecular weight of the complexes was determined in the
laboratory cryoscopically in freezing nitrobenzene using a Beckmann thermometer
of ±0.01 ºC accuracy. The conductivity measurements were carried out at room
temperature in nitrobenzene, using a conductivity bridge and dip type cell
operated at 220 volts A.C. mains. The magnetic measurements on powder form of
the complexes were carried out at room temperature on Evan’s balance using
anhydrous copper(II) sulfate as calibrant. The infrared spectra of the
complexes were recorded on a Perkin-Elmer infrared spectrophotometer model
Spectrum 1000 in CsI pellets in the range of 4000-200 cm-1. Diffused
reflectance spectra of the solid compounds were recorded on a Beckmann DK-2A
spectrophotometer at C.D.R.I. Lucknow, India. Thermogravimetric studies of the
complexes were carried out on Santon Red Craft Thermobalance Model TG-750 in
static air with open sample holder and a small boat, the heating rate was 6
ºC/min.
RESULTS AND DISCUSSION:
The reaction of Co2+ , Ni2+ and Cu2+
with DCBAAPTS and DNBAAPTS yielded the MX2(L) (H2O); [M =
Co2+ or Ni2+; X = C1, Br, NO3, NCS or CH3COO];
L = DCBAAPTS or DNBAAPTS]. The analytical data of these complexes showed that
the solids are stable and can be stored for months without any significant
change in their formulae. These complexes are generally soluble in common
organic solvents. The molar conductance values of the complexes in nitrobenzene
reveal that all the halo, nitrato, isothiocyanato and acetato complexes are
essentially non-electrolytes19. The cryoscopic molecular weights and
conductivity data are presented in Table 1. The molecular weight results are in
broad agreement with the conductance data suggesting monomeric formulations.
Magnetic susceptibility:
The magnetic measurements of the cobalt(II) complexes (4.8-5.4 BM)
(Table 1) show that all are paramagnetic and have three unpaired electrons
indicating a high-spin octahedral configuration. The paramagnetism observed for
the present series of Ni2+ complexes ranges from 2.6-3.2 BM
(Table-1), which is consistent with the octahedral stereochemistry of these
complexes.The observed magnetic moments of all the Cu(II) complexes (Table1)
are in the 1.83-1.90 B.M. range. The observed magnetic moments of the complexes
are consistent with the presence of a single unpaired electron20,21
Infrared spectra:
A study and comparison of infrared spectra of both
thiosemicarbazone ligands (DCBAAPTS and DNBAAPTS) and their Co2+ ,Ni2+
and Cu2+complexes (Tables 2 and 3) imply that these ligands behave
as neutral tridentate and the metals are coordinated through N and N of two
azomethine groups and of S of thio-keto group.
Biological properties:
A number of workers42-49 were interested in
investigating the biological and medicinal properties of transition metal
complexes of thiosemicarbazones. Thomas and Parmeswaran studied the antitumour
activities of Mn2+, Co2+, Ni2+ and Cu2+
chelates of anthracene-9-carboxaldehyde thiosemicarbazone. Murthy and
Dharmaraja46 reported the cytotoxic activity of phenylglyoxal bis(thiosemicarbazone)
against Ehrlich ascites carcinona cells. These compounds were also
screened for antimicrobial activity on B. subtilis and E. coli.
They inhibited the bacterial growth considerably. In the present studies, the
antibacterial activities of the cobalt(II) complexes and standard drugs
(ampicillin and teracycline) were screened by agar-cup method in DMF solvent at
a concentration of 50 µg/ml; the results were checked against gram positive
bacteria B. subtilis and S. aureus and gram negative bacteria E.
coli and S. typhi (Table 7). The diameters of zone of inhibition (in
mm) of the standard drug ampicillin against gram positive bacteria B.
subtilis and S. aureus and gram negative bacteria E. coli and
S. typhi were found to be 24, 22, 17 and 16, respectively, while tetracycline
gave 18, 17, 21 and 22, respectively. Under identical conditions, Table 7 shows
that all the cobalt(II)-thiosemicarbazone complexes have moderate antibacterial
activities against these bacteria. Both thiosemicarbazones and their cobalt(II)
complexes were screened for their antifungal activities against two fungi (A.
niger and C. albicans). The results (Table-10) showed that almost
all complexes showed nearly the same extent of activity, but they are less
active compared to salicylic acid. It is interesting to note that due to
presence of furan ring and comparatively faster diffusion of DCBAAPTS complexes
showed increased antifungal activity than that of DNBAAPTS complexes. These
compounds were found to be efficient antifungal agents.
Fig. 3. Proposed structure of M(L)·H2O·X2
M = Co2+ , Ni2+ or Cu2+ X =
Cl, Br, NO3, NCS or CH3COO; L = DCBAAPTS or DNBAAPTS
CONCLUSION:
The type of complexes isolated during the present study
demonstrate that interactions of Co2+ and Ni2+ salts with
thiosemicarbazones lead to complexes with 1:1 stoichiometries. Co(II) complexes
of both the thiosemicarbazones showed moderate antibacterial activities against
E. coli and S. typhi. The compounds have antifungal activity
against A. niger and C. albicans. DCBAAPTS complexes showed
lesser antifungal activity than that of DNBAAPTS complexes. The overall
experimental evidence shows that these metal ions display a coordination number
six and presumably have a distorted octahedral environment around the metal ion
as shown in Figures 1 and 2.
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C=N-SH) in these ligands has
been ruled out for no bands around 2700-2500 cm-1, which is
characteristic of thiol groups displayed in the infrared absorption27,28.
In the far infrared spectral region, some new bands with medium to weak
intensity in region 450-335 cm-1 were assigned to n (M-N) and n (M-S). Thus the infrared
spectral suggested the tridentate nature of the thiosemiearbazones and pointed
out the N, N, S sites as possible donor atoms. In these complexes, the presence
of coordinated water was suggested by the very broad absorption centered around
3400 cm-1 in their infrared spectra. Bands at ~ 930 and 770 cm-1
may be attributed to rocking and wagging modes of the coordinated water29,30.