Synthesis, characterisation and antimicrobial activity 1-aminopyrimidine- 2(1H)-thione and its Co(II), Ni(II), Pd(II) and Pt(II) complexes

Article abstract of DOI:10.3184/030823410X12743665489527

Metal complexes of 1-aminopyrimidine-2(1H)-thione were prepared from acetate salts of Co(II), Ni(II), Pd(II) and Pt(II) in methanol. Electronic spectral data and magnetic moment measurements suggest mononuclear square planar geometrical structures for the

Full text of DOI:10.3184/030823410X12743665489527

274 RESEARCH PAPER
MAY, 274–277
JOURNAL OF CHEMICAL RESEARCH 2010
Synthesis, characterisation and antimicrobial activity 1-aminopyrimidine-
2(1H)-thione and its Co(II), Ni(II), Pd(II) and Pt(II) complexes
Mehmet Gülcana and Mehmet Sönmezb*
aDepartment of Chemistry, Faculty of Science & Arts, YüzüncüYıl University, 65080, Van, Turkey
bDepartment of Chemistry, Faculty of Science & Arts, Gaziantep University, 27310, Gaziantep, Turkey
Metal complexes of 1-aminopyrimidine-2(1H)-thione were prepared from acetate salts of Co(II), Ni(II), Pd(II) and Pt(II)
in methanol. Electronic spectral data and magnetic moment measurements suggest mononuclear square planar
geometrical structures for the metal complexes. The ligand and all the metal complexes were evaluated for their
antimicrobial activity. The newly synthesised ligand and the Co(II) complex showed moderate activity against all
tested bacteria and yeast strains.
Keywords: 1-aminopyrimidine-2(1H)-thione, metal complexes, antimicrobial activity
Pyrimidine is the parent heterocycle of an important group of
compounds that occur in living systems.1 There has been
considerable attention in metal (II) complexes of polydentate
Schiff base ligands of N-aminopyrimidine type, due to their
structural richness, electrochemical properties as well as their
being a potential model for a number of important biological
systems.2 Heterocyclic thiones form the backbone of more
complicated organic ligands using other sites for attachment
to metals. Thioketo groups like 1,3-dithiole-2-thiones form
a vast and expanding field of research with technological
applications.3
In view of the biological significance and diverse coordinat-
ing behaviour of pyrimidines as well as the semiconducting
properties of some first row transition elements which have
been found to depend on the structure of the complex, we
prepared and studied some of these compounds.
proposed stoichiometry of the complexes. The molar conduc-
tivities of compounds 1–3 in DMF at 25 °C are in the range of
3.16–16.11 Ω−1 cm2 mol−1, indicating non-electrolytes.5
IR spectra of the ligand show characteristic bands at
3241 cm−1 ν(NH2), 3059 cm−1 ν(C–H pyrimidine ring), l648
cm−1 ν(C=O benzoyl), 1600 (C=Npyrimidine) 1104, 713 ν(C=S)
vibrations.6,7 IR spectra of the complexes were compared with
that of the free ligand to show changes during complexation.
The Co(II), Ni(II), Pd(II) and Pt(II) complexes of the ligand
3241 cm−1 for υ(NH) primer amine asymmetric-symmetric
stretching vibration bands vanished and the sec-amine peak
was observed at 3337–3423 cm−1. Also, the ν(C=S) vibration
at 1104, 713 cm−1 in the free ligand shifts to lower frequency at
1092, 698 cm−1 after complexation due to coordination with
sulfur atom of thione group to the metal ion.6–8 This situation
indicated coordination of sulfur and nitrogen to metal(II) ion.9
Thus, the metal–ligand bond formed over the NH2 group,
which lost one proton of ligand.10 The low frequency region
of the spectra revealed the presence of two new medium inten-
sity bands at 436 cm−1 and 566 cm−1 due to νM–S and νM–N
vibrations.10
We now describe the synthesis of novel metal (II) complexes
of bidentate ligand containing a ring of the mercapto pyri-
midine. Spectral and magnetic studies have been used to
characterise the structure of the complexes.
Electronic spectra were recorded in DMF. In the ligand, the
band at 363 nm is attributed to π–π* of the azomethine. Bands
at 316 and 268 nm are associated with phenyl and pyrimidine
π–π* transitions. In spectra of the complex, the π–π* of the
azomethine shifted to 370 nm, indicating that the azomethine
nitrogen is involved in coordination. UV-vis spectra of Ni(II)
complex shows three d–d bands at 562, 525 and 461 nm. These
bands can be assigned to 4T1g → 4A2g (F) and 3A2g → 3T1g (F),
respectively. Transitions are characteristic of square planar
configurations for Co(II) and Ni(II) complexes.11,12 The Co(II)
complex shows a magnetic moment of 2.01 B.M. which is in
good agreement with spin only value. This is further evidenced
by the electronic spectral data, which shows absorption in the
region 590 nm corresponding to 1A1g → 1B1g transitions which
also supports square planar geometry.12,13 Palladium(II) and
platinum(II) are a d8 system and three spin allowed singlet–
singlet d–d transitions are predicted.14 The ground state is
1A1g and exited states corresponding to the above transitions
are 1A2g, 1B1g and 1Eg in order of increasing energy. Three d–d
bands are observed in the region 488–585, 469–393 and
Results and discussion
1-Aminopyrimidine-2(1H)-thione (N-APTH) was prepared
according to the literature method by a two-step process.4 The
ligand and its complexes are very stable at room temperature
in the solid state. The ligand is soluble in common organic
solvents, but its metal complexes are generally only soluble
in DMF and DMSO. The elemental analytical data of the
complexes reveal a metal:ligand stoichiometry of 1:2 corre-
sponding to the square planar geometry of [M(N-APT)2]·nH2O
(Fig. 1). These analytical data are in good agreement with the
1
388–384 nm, respectively. These bands are attributed to A1g
→ 1A2g, 1A1g → 1B1g and to 1A1g → 1Eg transitions, respectively.
The electronic spectra of these complexes indicate the square
planar geometry and the values obtained correspond to those
reported earlier for the square planar complexes.15
1
DMSO-d6 was used as a solvent to measure the H NMR
spectra of Pd(II) and Pt(II) complexes. 1H NMR spectra of the
Pd(II) and Pt(II) complexes show a signal corresponding to the
primary amine at about 2.50 ppm. Sharp singlets at 8.92 ppm
and 8.73 ppm are due to C6(H)–pyrimidine proton; the phenyl
Fig. 1 Proposed structure of all the complexes.
* Correspondent. E-mail: vansonmez@hotmail.com

JOURNAL OF CHEMICAL RESEARCH 2010 275
multiplets successively were between δ 7.22–7.92 ppm and
7.11–7.93 ppm.13,14
Bacillus cereus ATCC 7064, Micrococcus luteus ATCC 9345
and Escherichia coli ATCC 4230 and for antifungal activity
against Candida albicans ATCC 14053, C. krusei ATCC 6258
and C. parapsilosis ATCC 22019 using broth microdilution
procedures.15,16 Ampicillin trihydrate for bacteria and flucon-
azole for yeast were used as the reference drugs. The results of
the antimicrobial activity of the ligand and its metal complexes
against all tested bacterial and fungal strains are shown in
Tables 1 and 2. All compounds inhibited the growth of bacteria
(Gram–negative and Gram-positive) with MIC values in the
range of 40–160 µg mL−1 as well as exhibited antifungal activ-
ity with MICs between 40 and 80 µg mL−1. The Co(II) complex
was found to possess an effective and selective antibacterial
activity against one Gram–negative bacterium (E. coli ATCC
4230) and other Gram-positive bacteria (S. aureus ATCC 6538,
S. aureus ATCC 25923 and M. luteus ATCC 9345) with MIC
values in range of 40 µg mL−1. On the other hand, other com-
pounds had moderate antibacterial activity against all Gram
positive and Gram–negative bacteria with MICs in the range
of 80 µg mL−1 except for the Ni(II) complex which was
160 µg mL−1. Moreover, our findings indicated that all pre-
pared compounds had similar antibacterial efficacy against
Gram-positive and Gram–negative bacteria. Table 2 sum-
marises the antifungal activities of the free ligand and the com-
plexes against three yeast strains (C. albicans ATCC 14053,
C. krusei ATCC 6258 and C. parapsilosis ATCC 22019).
According to antifungal studies, the ligand and Co(II) com-
plexes compounds displayed good anti-yeast efficacy against
The LC-API-ES mass spectrum of [59Co(NAPT)2]+, [58Ni
(N-APT)2]+, [108Pd(N-APT)2+2], [192Pt(N-APT)2+1] showed a
molecular ion peak M+ at m/z 691.0, 670.3, 670.3, 757.3 and
826.8, respectively that is equivalent to its molecular weight.
All the compounds are consistent with the molecular ion frag-
ment and support the proposed structure of the complexes.
The TGA data agree with the formula suggested from
elemental analyses. The thermal stabilities were investigated
using differential thermal and thermal gravitational analysis
(DTA/TGA) at a heating rate of 10 °C min−1 in N2 from 20 to
1000 °C. Mass losses correspond to H2O, Ph–CO– and the
other organic moieties in the first, second, third, fourth, and
fifth stages of decomposition. The Co(II), Pd(II) and Pt(II)
complexes suffered loss of H2O in the first stage, 37–130 °C,
and the ligands gradually decomposed from 220 to 580 °C.
The Co(II), Pt(II) and Pd(II) complexes contain 1, 1 and 2
moles of water of crystallisation per complex molecule, res-
pectively. The complexes had quite higher carbon residue with
CoO, NiO, Pd and Pt when they were heated to 1000 °C.13,14
The thermal stability of the complexes of N-PTH was found
to follow the order Pd(II) < Pt(II) ≈ Co(II) < Ni(II). The
thermogravimetric curve of the Co(II) complex is shown in
Fig. 2.
The ligand and its metal complexes [Co(II), Ni(II), Pd(II)
and Pt(II)] were screened for antibacterial activity against
Staphylococcus aureus ATCC 6538, S. aureus ATCC 25923,
tested fungal species (MICs, 40 µg mL−1). Also, other com-
plexes exhibited moderate antifungal activities (MICs,
80 µg mL−1).
The results of this investigation revealed that the ligand and
Co(II) complexes possess higher antimicrobial activity. It is
generally reported that the free ligand shows higher activity
than complexes.14,17,18 Additionally, when all the antimicrobial
MIC values are compared, the ligand and Co(II) complex
displayed the moderate antimicrobial efficacy with MIC values
Fig. 2 Thermogravimetric curves of the Pd(II) complex.
Table 1 MICsaof the ligand (N-APTH) and its metal complexes [Co(II), Ni(II), Pd(II), Pt(II)] against Gram–negative and Gram-positive
bacterial strains
Compounds
Bacillus cereus
ATCC 7064
Staphylococcus aureus
ATCC 6538
Staphylococcus aureus
ATCC 25923
Escherichia coli
ATCC 4230
Micrococcus luteus
ATCC 9345
N-APTH
80
80
160
80
80
5
80
40
160
80
80
5
80
40
160
80
80
10
80
40
160
80
80
20
40
40
160
80
80
10
1
2
3
4
Ampicillin
a The MICs values were determined as µg mL−1 active compounds in medium.

276 JOURNAL OF CHEMICAL RESEARCH 2010
Table 2 MICsa of the ligand (N-APTH) and its metal complexes [Co(II), Ni(II), Pd(II), Pt(II)] against fungal strains
Compounds
Candida albicans
ATCC 14053
Candida parapsilosis
ATCC 22019
Candida krusei
ATCC 6258
N-APTH
40
80
80
80
80
5
40
80
80
80
80
5
40
80
80
80
80
10
1
2
3
4
Fluconazole
a The MICs values were determined as µg mL−1 active compounds in medium.
ranging between 40 and 80 µg mL−1. Finally, the reason for the
good antimicrobial efficacy could be related to the inhibition
of several structural enzymes which play a key role in vital
metabolic pathways of the microorganisms.
(0.133 g) methanol was added dropwise with continuous stirring. The
mixture was stirred further for 1 h at 60 °C. The precipitated solid was
then filtered off, washed with diethyl ether, followed by cold methanol
and dried in a vacuum desiccator.
[Co(N-APT)2]·H2O (1): Yield was 305 mg (88%), m.p. 230 °C.
Anal. Calcd for C34H26CoN6O3S2 (689.67): C, 59.21; H, 3.80; N,
12.19; S, 9.30. Found: C, 59.35; H, 3.79; N, 12.21; S, 9.93%. Selected
IR data (KBr, ν cm−1): 3337 ν(NH), 3059 (C–Hpyrimidine), 1652 ν(C=O),
1594 (C=Npyrimidine) 1121, 740 ν(C=S) 510-520 (M–O), 430–440
(M–N). UV-Vis [λ (nm), ε (M−1cm−1)]: 224, 274, 290, 308, 332, 361,
379, 395, 413, 590. µeff, 2.01 BM, Λo (S cm2 mol−1) 16.11. API-ES:
m/z 691.0 [59Co(N-APT)2]+.
[Ni(N-APT)2] (2): Yield was 298 mg (88%), m.p. 241 °C. Anal.
Calcd for C34H24NiN6O2S2 (671): C, 60.82; H, 3.60; N, 12.52; S, 9.99.
Found: C, 60.51; H, 3.74; N, 12.50; S, 9.55%. Selected IR data,
ν (cm−1): 3343 ν(NH), 3059 (C–Hpyrimidine), 1652 ν(C=O), 1593
(C=Npyrimidine) 1116, 738 ν(C=S) 510-520 (M–O), 430–440 (M–N).
UV-Vis [λ (nm), ε (M−1cm−1)]: 253, 280, 313, 337, 375, 397, 411, 461,
525, 562. µeff, Dia, Λo (S cm2 mol−1) 3.16. API-ES: m/z 670.3 [58Ni
(N-APT)2]+.
Experimental
Elemental analyses (C, H, N, S) were performed by using a Leco
CHNS model 932 elemental analyser. The IR spectra were obtained
using KBr discs (4000–400) cm−1 on a Bio-Rad-Win-IR spectropho-
tometer. The electronic spectra in the 200–900 nm range were obtained
in DMF on a Unicam UV2-100 UV-Vis spectrophotometer. Magnetic
measurements were carried out by the Gouy method using
Hg[Co(SCN)4] as calibrant. Molar conductance of the ligand and their
transition metal complexes were determined in DMF at room tem-
1
perature by using a Jenway model 4070 Conductivity meter. The H
NMR, Pt and Pd complexes were recorded with a Bruker 300 MHz
Ultrashield TM NMR instrument. LC/MS-API-ES mass spectra
were recorded using an Agilent model 1100 MSD Mass Spectropho-
tometer. Thermal data were obtained by using Perkin-Elmer Diamond
Thermal Analysis. DTA/TGA measurements were made between
20 and 1000 °C in N2, 10 °C min−1.
[Pd(N-APT)2]·2H2O (3): Yield was 355 mg (84%), m.p. 251 °C.
Anal. Calcd for C34H28N6O4PdS2 (756.06) C, 54.08; H, 3.74; N, 11.13;
S, 8.49. Found: C, 54.59; H, 3.51; N, 10.79; S, 8.51%. Selected IR
data, ν (cm−1): 3421 ν(NH), 3059 (C–Hpyrimidine), 1665 ν(C=O), 1596
(C=Npyrimidine) 1144, 741 ν(C=S) 510-520 (M–O), 430–440 (M–N)..
UV-Vis [λ (nm), ε (M−1cm−1)]: 258, 273, 287, 297, 305, 323, 353, 376,
388, 469, 488. µeff, Dia, Λo (S cm2 mol−1) 6.12. API-ES: m/z 757.3
Synthesis of the ligand
1-Amino-5-benzoyl-4-phenylpyrimidine-2(1H)-thione was prepared
according to the literature method by a two-step process.4
An equimolar mixture of 1 and the corresponding thiosemicarba-
zone 2 was heated to 80 °C in dry toluene for 1 h After 12 h at tem-
perature, a yellow precipitate was separated out by filtration. Product
3 was recrystallised from n-butanol and dried in a vacuum dessicator.
The yield was 0.302 g (34%), m.p. 226 °C. (Scheme 1a). Compound
3 (1 g) was dissolved in 25 mL of concentrated hydrochloric acid and
200 mL of water was added to give a precipitate of 4 (Scheme 1b.) The
precipitated was filtered off, recrystallised from ethanol and dried in a
vacuum dessicator. The yield was 0.52 g (70%), m.p. 195 °C. Selected
IR data (KBr, ν cm−1): 3240 ν(NH2), 3059 (C–Hpyrimidine), 1648 ν(C=O),
1600 (C=Npyrimidine) 1104, 713 ν(C=S).
[
108Pd(N-APT)2+1].
[Pt(N-APT)2]H2O (4): Yield was 225 mg (49%), m.p. 216 °C. Anal.
Calcd for C34H26N6O3PtS2 (825,12 g/mol): C, 49.45; H, 3.17; N, 10.18;
S, 7.77. Found: C, 50.13; H, 3.15; N, 10.33; S, 8.17%. Selected IR
data, ν (cm−1): 3423 ν(NH), 3058 (C–Hpyrimidine), 1664 ν(C=O), 1597
(C=Npyrimidine) 1145, 742 ν(C=S) 510-520 (M–O), 430-440 (M–N).
UV-Vis [λ (nm), ε (M−1cm−1)]: 271, 285, 290, 294, 351, 373, 384, 393,
585. µeff, Dia, Λo (S cm2 mol−1) 14.4. API-ES: m/z 826.8 [192Pt
(N-APT)2+1].
Antibacterial assay
Newly synthesised compounds were screened for antibacterial
activity against four Gram-positive (S. aureus ATCC 6538, S. aureus
ATCC 25923, B. cereus ATCC 7064 and M. luteus ATCC 9345) and
one Gram–negative (E. coli ATCC 4230) bacteria as described by the
Synthesis of the complexes (1–4)
N-APTH 0.307 g (1.00 mmol) was dissolved in 25 mL of chloroform/
25 mL methanol, and a solution of (0.5 mmol) Co(AcO)2·4H2O
(0.125 g), Ni(AcO)2·4H2O (0.124 g) Pd(AcO)2 (0.112 g), and PtCl2
Scheme 1

JOURNAL OF CHEMICAL RESEARCH 2010 277
guidelines in NCCLS approved standard document M7-A4 using the
microdilution broth procedure.15 Ampicillin trihydrate was used as
the reference antibacterial agent. Solutions of the compounds and
reference drug were dissolved in DMSO at a concentration of
2560 µg mL−1. Two-fold dilution of compounds and reference drug
were prepared (1280, 640, 320, 160, 80, 40, 20, 10, 5 > µg mL−1).
Antibacterial activities of the newly synthesised compounds were
determined in the Mueller–Hinton broth (Difco) medium at pH 7.2
with an inoculum of (1–2) × 103 cells mL−1 by the spectrophotometric
method and an aliquot of 100 µL was added to each tube of serial dilu-
tion. The compounds-broth medium serial tube dilutions inoculated
with each bacterium were incubated on a rotary shaker at 37 °C for
18 h at 150 rpm. The minimum inhibitory concentrations (MICs)
of each compound were recorded as lowest concentration of each
compound in the tubes with no growth (i.e. no turbidity) of inoculated
bacteria.
cannot be described. However, the spectroscopic and magnetic
data enable us to predict possible structures. The antibacterial
activity results evidently show that all the complexes have
moderate activity against Gram-positive bacteria. They have
weak activity against Gram–negative bacteria, except the
ligand and Co(II) complex which has moderate activity against
E. coli.
The authors are grateful to Yuzuncu Yil University Research
Foundation (2009-FBE-D006) for their support in this research
and also Dr İsmet Berber at the Department of Biology, Sinop
University for the antimicrobial activity studies.
Received 1 April 2010; accepted 7 May 2010
Paper 1000046 doi: 10.3184/030823410X12743665489527
Published online: 8 June 2010
Antifungal assay
The antifungal activities of new synthesised chemical compounds
were tested against three yeast (C. albicans ATCC 14053, C. krusei
ATCC 6258 and C. parapsilosis ATCC 22019) strains according to the
guidelines in NCCLS approved standard document M27-A2 using
the microdilution broth procedure.16 Fluconazole was used as the ref-
erence antifungal agent. Solution of the test compounds and reference
drug were dissolved in DMSO at a concentration of 2560 µg mL−1.
The two-fold dilution of the compounds and reference drug were pre-
pared (1280, 640, 320, 160, 80, 40, 20, 10, 5 > µg mL−1). Antifungal
activities of the yeast strains were performed in RPMI 1640 Medium
(Sigma) which had been buffered to pH 7.0 with 0.165 M morpho-
linopropanesulfonic acid (Sigma), as outlined in document M27-A.
The stock yeast inoculum suspensions were adjusted to a concentra-
tion of (0.5–2.5) × 103 cells mL−1 by spectrophotometric method and
100 µL aliquot was added to each tube of dilution. The chemical com-
pound-broth medium serial tube dilutions inoculated with yeast were
incubated on a rotary shaker at 37 °C for 18 h at 150 rpm. The mini-
mum inhibitory concentrations (MICs) of each chemical compounds
were recorded as lowest concentration of each chemical compounds
in the tubes with no growth (i.e. no turbidity) of inoculated yeast.
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