X-ray structure and multinuclear NMR studies of platinum(II) complexes with 5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one

Article abstract of DOI:10.1016/j.poly.2006.09.010

New dichloride platinum(II) complexes with 5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one (HmtpO) have been synthesized and characterized by thermal analysis, infrared and ¹H, ¹³C, ¹⁵N, ¹⁹⁵Pt NMR spectroscopy. X-ray crystal structures of cis-PtCl₂(NH₃)(HmtpO) (1) and cis-PtCl₂(HmtpO)₂ · 4H₂O (2b) were determined to R = 0.0332 and R = 0.0802, respectively. In both complexes the Pt(II) ions have a square-planar geometry with two adjacent corners being occupied by two nitrogens of HmtpO molecules for 2b or NH₃ and HmtpO molecules for 1, whereas the remaining adjacent corners are occupied by two chloride anions. Spectroscopic data confirm the square planar geometry with N(3) bonded HmtpO, S-bonded dimethylsulfoxide and two trans chloride anions for trans-PtCl₂(dmso) · 4H₂O (3).

Full text of DOI:10.1016/j.poly.2006.09.010

Polyhedron 26 (2007) 803–810
www.elsevier.com/locate/poly
X-ray structure and multinuclear NMR studies of platinum(II)
complexes with 5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one
a,
a
b,c
Iwona Łakomska *, Andrzej Wojtczak , Jerzy Sitkowski
,
b
a
Lech Kozerski , Edward Szłyk
a
Department of Chemistry, Nicholas Copernicus University, Gagarina 7, 87-100 Torun´, Poland
b
National Institute of Public Health, Chełmska 30/34, 00-725 Warsaw, Poland
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
c
Received 25 May 2006; accepted 7 September 2006
Available online 26 September 2006
Abstract
New dichloride platinum(II) complexes with 5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one (HmtpO) have been synthesized and
characterized by thermal analysis, infrared and 1H, 13C, 15N, 195Pt NMR spectroscopy. X-ray crystal structures of cis-PtCl2(NH3)-
(HmtpO) (1) and cis-PtCl2(HmtpO)2 Á 4H2O (2b) were determined to R = 0.0332 and R = 0.0802, respectively. In both complexes the
Pt(II) ions have a square-planar geometry with two adjacent corners being occupied by two nitrogens of HmtpO molecules for 2b or
NH3 and HmtpO molecules for 1, whereas the remaining adjacent corners are occupied by two chloride anions. Spectroscopic data con-
firm the square planar geometry with N(3) bonded HmtpO, S-bonded dimethylsulfoxide and two trans chloride anions for
trans-PtCl2(dmso) Á 4H2O (3).
ꢀ 2006 Elsevier Ltd. All rights reserved.
Keywords: Platinum complex; 1,2,4-Triazolo[1,5-a]pyrimidine derivative; Dimethylsulfoxide; Multinuclear NMR; X-ray structure
1. Introduction
Triazolopyrimidine derivatives revealed structures simi-
lar to purine, differing from it by the presence of a pyrim-
idine nitrogen atom in a bridgehead position, and the lack
of the acidic H-proton in the five-membered ring [8,9].
Triazolopyrimidine derivatives display a great versatility
in their interaction with metal ions, because they can bind
metal ions through different sites. Reported studies of tria-
zolopyrimidine complexes display an appreciable variabil-
ity in their molecular structure. There are examples of
mono-, di- and multinuclear structures, which exhibited
the central ion and inorganic anions influence on the com-
plex’s geometry [10–15]. Nevertheless, when triazolopyrim-
idines act monodentately to the platinum(II) ion, the
preferred binding position appears to be N(3) [12,14].
Mononuclear platinum(II) species such as: cis-PtCl2-
(HmtpO)2 Á 2H2O [13], cis-[Pt(HmtpO)2(NH3)2](NO3)2 Á
2H2O [10] and trans-PtCl2(dmso)(dmtp) [14] revealed
N(3) coordinated heterocycles. Polymeric compounds are
usually obtained due to N(1) and N(3) coordination [16],
Cisplatin is one of the most commonly used anticancer
drugs in the treatment of testicular, ovarian, bladder and
head and neck cancer [1,2]. Despite the great success of
treating certain kinds of cancer there are several side-
effects, and both intrinsic and acquired resistance limit
the organotropic profile of the drug [3].
There is a continuing interest in development of new
platinum complexes, which are less toxic and have a
broader activity spectrum. Variation in the nature of the
amine can have a significant effect on the activity and tox-
icity of these complexes. Several platinum complexes with
N-heterocyclic ligands, such as imidazole, thiazole, pyri-
dine and purine derivatives, have been reported [4–7].
*
Corresponding author. Fax: +48 56 654 2477.
E-mail address: dziubek@umk.pl (I. Łakomska).
0277-5387/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.poly.2006.09.010

804
I. Łakomska et al. / Polyhedron 26 (2007) 803–810
whereas dimers with eight-member rings are formed for
the N(3), N(4) bridging mode [10]. The exceptions were
complexes with 4,5,6,7-tetrahydro-5,7-dioxo-1,2,4-triaz-
olo[1,5-a]pyrimidine (H2tpO2), where the bidentate ligands
were linked through the exocyclic oxygen O(7) and endocy-
clic nitrogen N(1) [17].
It was recently demonstrated that the coordination com-
pounds with 1,2,4-triazolo[1,5-a]pyrimidine revealed biolog-
ical activity [13,18–21]. Some transition metal complexes
with triazolopyrimidines significantly inhibited in vitro cell
growth of the epimastigote [19] and Gram(+) and Gram(À)
bacteria. The antitumor activity studies (in vitro) of cis plat-
inum(II) compounds with the triazolopyrimidine ligands,
5-methyl-1,2,4-triazolo[1,5-a]pyrimidin- 7(4H)-one (HmtpO)
[13], 5,7-diterbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp)
[20] and 5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine (dptp)
[20], indicate a moderate antiproliferative activity against
the cells of rectal, breast and bladder cancer.
Following this research line, we have tried to synthesize
new platinum(II) compounds, which will reveal activity
similar to cisplatin, but have an additional functional
group, where they could be linked to carrier substances.
Therefore, for our studies we have chosen 5-methyl-1,2,4-
triazolo[1,5-a]pyrimidin-7(4H)-one, with a structure similar
to the purine ring existing in DNA, as a ligand for
platinum(II). In this paper, we present the results on the
synthesis and molecular structure characterization of
the novel compounds: cis-PtCl2(HmtpO)(NH3) (1),
cis-PtCl2(HmtpO)2 Á H2O (2a) and trans-PtCl2(HmtpO)
(dmso) Á 4H2O (3).
solvent was dmso-d6, the concentrations of the saturated
solutions were ca. 0.01–0.05 M and the temperature was
298 K. The reference standard was TMS for 1H and
13C, CH3NO2 (external) for 15N and K2PtCl6 (external)
for 195Pt.
The 13C CPMAS spectra were performed with a Bruker
AMX 300 MHz spectrometer using a Bruker MAS-
VTN500SB BL4 probe head and 4 mm zirconia rotors, at
296 K.
2.3. Preparation of the platinum(II) complexes
Cis-PtCl2(dmso)2 [22] and K[PtCl3(NH3)] [23] were pre-
pared from K2PtCl4 by the known method.
Cis-PtCl2(NH3)(HmtpO) (1): To
a
solution of
K[PtCl3(NH3)] (0.050 g, 0.13 mmol) in 10 cm3 of water, a
solution of HmtpO (0.0210 g, 0.13 mmol) in 5 cm3 of 1 M
HCl was added. Reaction mixture was stirred at room tem-
perature for 12 h. The yellow precipitate was filtered,
washed with water, acetone, diethyl ether and dried in vac-
uum. Yield 0.0270 g (48%). Anal. Calc. for C6H9Cl2N5OPt:
Pt, 45.0; C, 16.6; N, 16.2; H, 2.1. Found: Pt, 44.6; C, 16.7;
N, 16.0; H, 1.8%.
Cis-PtCl2(HmtpO)2 Á H2O (2a):
A
suspension of
K2PtCl4 (0.100 g; 0.26 mmol) in 5 cm3 of water was treated
with HmtpO (0.0798 g; 0.53 mmol) in 8 cm3 of 1 M HCl
and the reaction mixture stirred at room temperature for
48 h. The yellow precipitate was filtered, washed with
water, acetone, diethyl ether and dried in vacuum. Yield
0.0456 g (30%). Anal. Calc. for C12H14Cl2N8O3Pt: Pt,
33.4; C, 24.7; N, 19.2; H, 2.4. Found: Pt, 33.0; C, 24.3;
N, 19.1; H, 2.6%. The thermal analysis confirmed detach-
ment of water molecule (95–140 ꢁC, weight calc. 3.35%,
exp. 3.65%). Further decomposition proceeds in several
endothermal stages and leads to metallic platinum above
885 ꢁC. By slow crystallization of 2a from a mixture of
HCl and water (1:3 v/v), single crystals of 2b suitable for
X-ray structure analysis were obtained.
2. Experimental
2.1. Materials
Dipotassium tetrachloroplatinum(II), 5-methyl-s-tria-
zolo[1,5-a]pyrimidine-7-ol (98%), potassium hexafluoro-
phosphate (98%), tetraethylammonium chloride hydrate
and tetraphenylphosphonium chloride (98%) were pur-
chased from Aldrich, whereas the inorganic salts and
organic solvents of analytical grade were from POCh
Gliwice (Poland).
Trans-PtCl2(dmso) Á 4H2O (3): A solution of HmtpO
(0.036 g; 0.23 mmol) in 5 cm3 of 1 M HCl was dropped
to a solution of cis-PtCl2(dmso)2 (0.100 g, 0.23 mmol)
in 10 cm3 water–ethanol mixture. The reaction mixture
was stirred at room temperature for 24 h. The filtrate
was left for crystallization and after 3 days a yellow pre-
cipitate was filtered off, washed with ethanol, acetone,
diethyl ether and dried in vacuum. Yield 0.0443 g
(34%). Anal. Calc. for C8H20Cl2N4O6SPt: Pt, 34.4; C,
17.0; N, 9.9; H, 3.6. Found: Pt, 34.1; C, 17.1; N, 9.4;
H, 3.9%. The content of solvated water molecules in 3
has been confirmed by thermogravimetric analyses. The
first endothermic step in the range 83–272 ꢁC corre-
sponds to the mass loss in the TG curves which can
be correlated with detachment of 4 water molecules
and dimethylsulfoxide (calc. 26.38%, exp. 26.87%). The
next endothermic processes (275–820 ꢁC) can be related
to decomposition of 3 leaving platinum as a final
product.
2.2. Instrumentation
The content of C, H, N was determined by elemental
semi-microanalysis, Pt spectrophotometrically as H2PtCl6
on a Specord M40 Carl Zeiss Jena (k = 400 nm). Thermo-
gravimetric analyses were performed with a SDT-2960 TA
Instrument (samples – 5 mg, heating range 25–1000 ꢁC,
heating rate 3.5 deg/min, N2 atmosphere). IR spectra were
measured with a Perkin–Elmer Spectrum-2000 FT-IR
spectrometer, using KBr (400–4000 cmÀ1) and polyethyl-
1
1
ene discs (100–400 cmÀ1). The H{13C} HSQC, H{13C}
HMBC and 1H{15N} HMQC spectra were performed
with a Varian INOVA-500 NMR spectrometer equipped
with an inverse Nalorac Z-gradient shielded probe. The

I. Łakomska et al. / Polyhedron 26 (2007) 803–810
805
˚
2.4. X-ray structure determination
radiation (k = 0.71073 A) and the x–2h method. The
shape-based numerical absorption correction was applied
with minimum and maximum transmissions of 0.04914
and 0.39687 for 1 and 0.17132 and 0.55792 for 2b. The
structure was solved by Patterson methods and refined with
the full-matrix least-squares method on F2 with the use of
the SHELX-97 program package [24]. The data collection
and refinement processes are summarized in Table 1. The
Pale yellow crystals of cis-PtCl2(NH3)(HmtpO) (1) and
cis-PtCl2(HmtpO)2 Á 4H2O (2b) were obtained by slow
evaporation from a mixture of HCl and water. Complex
1 crystallized in monoclinic space group P21/c, whereas
complex 2b crystallized in the triclinic P1 space group.
The X-ray data for 1 and 2b were collected at 293(2) K with
ꢀ
˚
an Oxford Sapphire CCD diffractometer, using Mo Ka
residual peaks tabulated for 2b are positioned 1.16 A from
˚
Cl(1) and 0.86 A from Pt(1), respectively, therefore not
indicating any missing atoms. The fractional coordinates
of 1, 2b and selected bond lengths and angles are presented
in Table 4.
Table 1
Crystal data and structure refinement for 1 and 2b
Identification code
cis-PtCl2(NH3)-
(HmtpO) (1)
cis-PtCl2(HmtpO)2 Æ
4H2O (2b)
2.5. Cytotoxic activity
Empirical formula
Formula weight
Temperature (K)
C6H9Cl2N5OPt
435.15
293(2)
0.71073
monoclinic
P2(1)/c
C12H20Cl2N8O6Pt
638.4
293(2)
0.71073
triclinic
The antiproliferative activity in vitro against HCV29T
(bladder cancer) and T47D (breast cancer) cell lines were
performed by using the SRB test as described [20].
˚
Wavelength (A)
Crystal system
Space group
Unit cell dimensions
ꢀ
P1
3. Results and discussion
˚
a (A)
9.718(2)
11.417(2)
11.138(2)
7.121(1)
10.681(1)
14.817(2)
75.08(1)
76.33(1)
71.64(1)
1018.6(2)
2
˚
b (A)
˚
3.1. NMR spectroscopy
c (A)
a (ꢁ)
b (ꢁ)
c (ꢁ)
Volume (A )
Z
1
We have measured H, 13C and 15N NMR spectra for
114.27(3)
1, 2a in solution but not for 3 due to the low solubility of
this complex in dmso-d6 and another solvents. The 1H
NMR chemical shifts of the studied complexes are listed
in Table 2. The spectra exhibit a singlet at 2.41 (1), 2.40
(2a) and 2.31 ppm (3) for the methyl group and singlets
from H(2), H(6) (5.99–8.61 ppm) and H(4) (13.55–
13.66 ppm) (Table 2). All signals from H(2), H(6) and
H(4) are shifted towards lower fields due to coordination
of the triazolopyrimidine ligand. This effect being more
expressed for H(2) (0.27–0.44 ppm) and H(4) (0.36–
0.44 ppm) than H(6) (0.17–0.26 ppm) (Table 2), suggests
slightly stronger deshielding of H(2) and H(4). Therefore
the monodentate coordination of HmtpO via N(3) can be
proposed, because in the case of the bridging mode
(N(3), N(4)), the coordination shifts were bigger (ca.
0.88 ppm) [25]. Additionally, the 1H NMR spectrum of
1 exhibited a broad signal for the NH3 protons (d =
4.06 ppm), which confirms its coordination [26–29].
3
˚
1126.5(4)
4
2.560
Calculated density
(Mg/m3)
Absorption coefficient
(mmÀ1
2.081
12.911
7.198
)
F(000)
804
616
Crystal size (mm)
Theta range for
data collection (ꢁ)
Index ranges
0.40 · 0.18 · 0.10
2.68–31.17
0.38 · 0.28 · 0.23
2.73–31.18
À12 6 h 6 13,
À16 6 k 6 16,
À15 6 l 6 14
10821/3403
[0.0524]
À10 6 h 6 9,
À15 6 k 6 15,
À21 6 l 6 18
10043/5940
[0.1559]
Reflections collected/
unique [Rint
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I > 2r(I)]
]
3403/0/138
1.095
5940/0/264
1.089
R1 = 0.0332,
wR2 = 0.0796
R1 = 0.0388,
wR2 = 0.0829
3.299 and À2.074
R1 = 0.0802,
wR2 = 0.2228
R1 = 0.0863,
wR2 = 0.2284
5.759 and À4.496
R indices (all data)
Largest difference peak
and hole (e A
Coordination sites of the heterocyclic ring were deter-
À3
˚
1
mined by H{15N} HMQC spectra of the complexes. In
)
Table 2
1H and 13C NMR chemical shifts (d) of the ligand HmtpO and its platinum(II) complexes
Compound
H(6)
H(2)
H(4)
C(2)
C(3a)
150.5
C(5)
C(6)
98.0
C(7)
HmtpO (in dmso-d6)
5.82
8.17
13.19
151.7
151.5
155.8
(1) cis-PtCl2(NH3)(HmtpO)
6.02 (+0.20) 8.44 (+0.27) 13.66 (+0.47) 150.6 (À1.1) 149.8 (À0.7) 153.1 (+1.6)
99.8 (+1.8) 154.5 (À1.3)
(2a) cis-PtCl2(HmtpO)2 Æ H2O 5.99 (+0.17) 8.61 (+0.44) 13.64 (+0.45) 149.9 (À1.8) 149.5 (À1.0) 152.7 (+1.5) 100.2 (+2.2) 154.4 (À1.4)
b
(3) trans-PtCl2(dmso)
(HmtpO) Æ 4H2O
HmtpO (in the solid state)
a
6.08 (+0.26) 8.55 (+0.38) 13.55 (+0.36) 148.3a (À1.9)
153.4a(+0.7) 101.7a (+6.5) 155.9a (À1.9)
b
150.2
152.7
95.2
157.8
Data from 13C CPMAS NMR.
The signal was not observed in the spectrum.
b

806
I. Łakomska et al. / Polyhedron 26 (2007) 803–810
the 15N NMR spectra four resonances at: À112.7, À257.3,
À251.3, À157.8 for 1 and: À112.1, À257.8, À253.5,
À157.9 ppm for 2a were detected (Fig. 1, Table 3). In com-
parison to the free ligand spectrum, the shielding effect of
N(1), N(3) and N(8) in the complexes is evident, while the
0.7–6.5 ppm towards the low field (Table 2) which can be
explained by the deshielding effect of the metal due to coor-
dination via N(3).
A spectrum for complex 3 was measured in the solid
phase and data are listed in Table 2. It should be noted that
this is the first report of a 13C CPMAS spectrum of HmtpO
and one of its platinum(II) complexes. The spectrum pre-
sents a similar pattern of coordination shifts as observed
in solution (Table 2), which indicates HmptO coordination
via N(3). However, the coordination shift of the C(6) signal
is larger (maximum 6.5 ppm).
biggest coordination shift was observed for N(3) (Dcoord
=
91–92 ppm) (Table 3). The strong shielding effect of N(3) is
an unambiguous result of N(3) coordination in solution.
13C NMR spectra of 1 and 2a were recorded, while for 3
no peaks were detectable, due to the low solubility of the
latter complex. The signals were assigned by a heterocorre-
lation 1H–13C technique and data are listed in Table 2. The
coordination effect has an impact on C(2) and C(3a) signals
which are shielded by 0.7–1.9 ppm in relation to free
HmtpO, while C(5) and C(6) resonances are detected
195Pt NMR spectra of 1 and 2a were measured in
dmso-d6 and data are listed in Table 3. The signals of the
cis-dichloro complexes were observed at À2089 (2a) and
À2116 (1). These values are at lower field than those
1
Fig. 1. H{15N} NMR spectra of (a) HmptO; (b) cis-[PtCl2(HmtpO)2] Æ H2O (1).

I. Łakomska et al. / Polyhedron 26 (2007) 803–810
807
Table 3
15N NMR and 195Pt chemical shifts (d) of the platinum(II) complexes in dmso-d6
Compound
N(1)
N(3)
N(4)
N(8)
Pta
HmtpO
(1) cis-PtCl2(HmtpO)(NH3)
(2a) cis-PtCl2(HmtpO)2 Æ H2O
À110.8
À165.7
À252.7
À155.3
À112.7 (À1.9)
À112.1 (À1.3)
À257.3 (À91.6)
À257.8 (À92.1)
À251.3 (+1.4)
À253.5 (+0.8)
À157.8 (À2.5)
À157.9 (À2.6)
À2116 (À492)
À2089 (À465)
a
The 195Pt NMR values in parentheses exhibit the chemical shift related to K2PtCl4 (d = À1624 ppm).
reported in the literature for complexes containing amines.
This chemical shift range was also observed for other
PtN2Cl2 chromophore systems [30–32]. In case of Pt(II)
complexes containing amines the chemical shifts of 195Pt
were noted at: À2188 ppm (Me2NH), À2224 ppm (i-PrNH2),
À2104 ppm (NH3), À2184 ppm (1-adamantanamine),
À2235 ppm (cyclobutyloamine) (in dmf-d7) [33], whereas
for cis-pyridine derivatives the chemical shifts were
between À1998–À2021 ppm (in CDCl3) [34]. However,
the resonances for the complexes with triazolopyrimidine
derivatives are observed at lower field than those reported
in the literature for complexes containing aromatic amines.
The low field shift of 195Pt signals can be related to a smal-
ler r electron donation effect in triazolopyrimidine ligands
than in aliphatic amines complexes. This phenomenon can
cause a reduction of electron density on the Pt(II) nuclei,
resulting in its deshielding and larger 195Pt signal coordina-
tion shift.
In the spectrum of 3, two new intensive absorption
bands were detected at 1135 and 1024 cmÀ1, which can
be assigned to qCH3 rocking vibrations and mSO stretching
vibration, respectively [22,35]. Similar bands were noted
in the spectra of trans- and cis-PtCl2(thiazole)(dmso) where
S-bonded dmso was postulated (1150 and 1140 cmÀ1
,
respectively) [29,36]. Recently, we have found a mSO band
in the spectra of trans-PtCl2(dmso)L complexes
(L = 1,2,4-triazolo[1,5-a]pyrimidine or its 5,7-disubstituted
derivatives), at similar frequencies (1142–1147 cmÀ1) [14].
From group theory calculations, for a C2v coordination
sphere geometry (PtCl2N2) two of each stretching vibra-
tions of Pt–Cl and Pt–N should of A1 and B1 type, all
active in IR spectra. Far-IR spectra of complexes 1–3 exhi-
bit one broad band of medium intensity, which can be
assigned to Pt–Cl vibrations (A1) (332–342 cmÀ1). In the
spectra of 1 and 2a the second band appeared as a shoul-
der, due to coincidence with the ligand normal oscillations.
However, the frequencies of the m(Pt–Cl) bands in the spec-
tra of the studied complexes were in the range characteris-
tic for the cis geometry. In the case of platinum(II)
complexes with HmtpO one broad band was reported at
330 cmÀ1 [13]. Similar complexes with 1-(2-aminophe-
nyl)isoquinoline derivatives exhibit the band in the range
328–335 cmÀ1 [7], whereas those with substituted benzimid-
azole derivatives between 337 and 312 cmÀ1, which is con-
sistent with the values reported in this work [37].
3.2. IR spectra
Absorption bands of m(C@O) stretching vibrations at
1724 (1), 1709 (2a), 1714 cmÀ1 (3) upon coordination were
shifted towards higher frequencies (max. 23 cmÀ1). In addi-
tion, the two most characteristic bands of pyrimidine and
imidazole ring skeleton vibrations after coordination
appeared at higher frequencies by 18–30 cmÀ1 and 11–
19 cmÀ1, respectively. A similar effect has been already
found for other complexes with N(3) coordinated triazolo-
pyrimidine derivatives [13,14,20].
3.3. Crystal structure of cis-PtCl2(NH3)(HmtpO) (1)
The crystal structure of 1 is formed by cis-PtCl2(NH3)-
(HmtpO) units. The atom numbering scheme of 1 is shown
in Fig. 2.
Table 4
˚
Selected bond lengths (A) and angles (ꢁ) for cis-PtCl2(NH3)(HmtpO) (1)
The coordination sphere of 1 is formed by the ammine
and HmtpO ligand bonded in cis positions and two chloro
ligands. The rms deviation of the atoms from the best
and cis-PtCl2(HmtpO)2 Æ 4H2O (2b)
Bond/angle
1
2b Ligand I
2b Ligand II
Pt(1)–N(3)
Pt(1)–N(21)
Pt(1)–Cl(1)
Pt(1)–Cl(2)
C(2)–N(3)
N(3)–C(3A)
2.022(4)
2.029(5)
2.2667(15)
2.2971(16)
1.355(7)
1.323(6)
2.059(8)
2.052(9)
˚
PtN2Cl2 plane is 0.05 A. The HmtpO ligand is coordinated
˚
via the N(3) atom, the Pt–N distance being 2.022(4) A. The
2.276(3)
2.290(3)
1.355(14)
1.293(13)
˚
ammonia N(21) atom forms a 2.029(5) A bond to plati-
1.350(13)
1.286(12)
num(II). The chloro ligands form Pt–Cl(1) and Pt–Cl(2)
˚
bonds of 2.267(2) and 2.297(2) A, respectively, as expected
N(3)–Pt(1)–N(21)
N(3)–Pt(1)–Cl(1)
N(21)–Pt(1)–Cl(1)
N(3)–Pt(1)–Cl(2)
N(21)–Pt(1)–Cl(2)
Cl(1)–Pt(1)–Cl(2)
C(3A)–N(3)–Pt(1)
C(2)–N(3)–Pt(1)
91.7(2)
92.2(3)
178.9(2)
for such bonds. The slight elongation of Pt–Cl2 might
result from the trans influence of the ammine ligand and
the steric effect of the HmtpO ligand being stronger than
that of the ammine ligand. That conclusion is supported
by the observed value of the N(3)–Pt(1)–Cl(2) angle
89.6(1)ꢁ, slightly larger than that of 87.3(2)ꢁ found for
N(21)–Pt(1)–Cl(1).
176.13(13)
87.30(16)
89.57(14)
177.49(16)
91.60(7)
87.6(2)
87.8(3)
179.3(2)
92.30(14)
124.3(8)
126.8(8)
129.7(3)
125.6(3)
127.7(7)
124.9(7)

808
I. Łakomska et al. / Polyhedron 26 (2007) 803–810
Fig. 2. Molecular structure of compound 1 as determined from X-ray
diffraction data.
Fig. 3. Molecular structure of compound 2b as determined from X-ray
diffraction data.
The HmtpO ligand is planar, the rms deviation of the
˚
atoms from the best plane is 0.0127 A. However, there is
times the average value for the other HmtpO ligand. Also,
authors commented that the poor quality data did not
allowed any discussion of the ligand geometry [13]. There-
fore, we decided to re-determine the structure of 2b
because of its biological significance and compare it with
the structure of 1. The crystal of 2b was taken out from
the solution and immediately mounted on the diffractom-
eter for a fast experiment with the CCD detector. The
reported structure contains four independent water mole-
cules, two of which reveal slightly larger atomic displace-
ment parameters than the other two. That might indicate
the ability of the crystal to partially dehydrate and also a
possible change of the lattice symmetry. However, the
analysis of the experiment does not reveal the possible
choice of the monoclinic cell corresponding to the dihy-
drated complex [13]. Furthermore, the quality of the
new triclinic form of the hydrated cis-[PtCl2(HmtpO)2] Á
4H2O structure (2b) reported here is much better than
that of the monoclinic form determined by the other
authors [13]. Partial dehydration would be consistent with
the difficulties of getting high quality diffraction data, we
tried several crystals (with relatively high Rint), as
reported by the other group [13].
a slight bend of the ring system along the N(8)–C(3a) bond,
the angle between the triazole ring and pyrimidine ring
planes being 1.1(4)ꢁ. The HmtpO ring system is almost per-
pendicular to the PtN2Cl2 plane, the dihedral angle being
88.97ꢁ.
The intermolecular interactions in the crystal lattice
include a network of hydrogen bonds formed by all donor
N–H groups of the ligands. The ammine ligand N(21)
forms H-bonds to Cl(2) [Àx + 1,y + 1/2,Àz + 3/2], O(71)
[x + 1,y,z] and Cl(1) [x,Ày + 1/2,z + 1/2] atoms (NÁ Á ÁCl/
˚
O distances of 3.430, 3.103 and 3.244 A, respectively).
˚
N(1)–H participates in the 2.904 A contact with N(4)
[x,Ày + 1/2,z + 1/2]. The C(2)–H and C(6)–H groups
form almost linear interactions to chloride ions,
C(2)Á Á ÁCl(2) [1 À x,Ày,2 À z] and C(6)–H(6A)Á Á ÁCl(2)
˚
[Àx,0.5 + y,1.5 À z] being 3.579(6) and 3.551(6) A, respec-
tively. The corresponding H(2A)Á Á ÁCl(2) and H(6A)Á Á Á
˚
Cl(2) distances are 2.67 and 2.64 A, while the C(2)–
H(2A)Á Á ÁCl(2) and C(6)–H(6A)Á Á ÁCl(2) angles are 165.9ꢁ
and 167.5ꢁ, respectively. Such C–HÁ Á ÁCl interactions have
been reported for other complexes of 1,2,4-triazolo-
[1,5-a]pyrimidines [14] and indicate the significant polariza-
tion of these C–H bonds.
Similar to the lower quality complex structure, the
coordination sphere is formed by two cis chloride ions
and two HmtpO ligands bonded to the Pt atom via
N(3) atoms [13]. The Pt(1)–Cl(1) and Pt(1)–Cl(2) dis-
3.4. Crystal structure of cis-PtCl2(HmtpO)2 Á 4H2O (2b)
˚
Cis-PtCl2(HmtpO)2 Á 4H2O molecules form the crystal
structure of 2b. The atom numbering scheme is shown in
Fig. 3.
tances observed in 2b are 2.276(3) and 2.290(3) A, respec-
tively and are similar to the analogous distances in
complex 1. The Pt(1)–N(3) and Pt(1)–N(13) distances
˚
The structure of the new form of cis-[PtCl2(HmtpO)2] Á
are 2.059(8) and 2.052(9) A, respectively and are slightly
ꢀ
4H2O (2b) was solved in the triclinic P1 space group. A
longer than those found in 1. The HmtpO ligands are
oriented in the same way with respect to the chloride
ligands (Fig. 3). Such a position results from the pair
of H-bonds formed by the N(4)–H groups to water
O(63).
similar X-ray structure of [PtCl2(HmtpO)2] dihydrate
was solved in the monoclinic P21/c space group with poor
diffraction data [13]. However, the authors reported prob-
lems with the refinement of the second HmtpO ligand and
explained the poor data quality by crystal dehydration
during the experiment. Analysis of that paper revealed
that one of the HmtpO ligands had a significant disorder,
which resulted in its isotropic refinement and large values
of the reported atomic displacement parameters, being 5
The HmtpO ligands are planar, the rms deviation of the
˚
atoms from the best plane is 0.013 and 0.019 A for
the N(1)–N(8) and N(11)–N(18) ligands, respectively. The
dihedral angle between the best planes of these two ligands
is 70.3(2)ꢁ. The corresponding value reported for the

I. Łakomska et al. / Polyhedron 26 (2007) 803–810
809
Table 5
3.5. Cytotoxic activity
Structural differences between mononuclear Pt(II) complexes with
triazolopyrimidines
Many transition metals complexes with triazolopyrim-
idines show significant antitumor activity [13,20]. We
have observed high activity of similar platinum(II) com-
plexes with analogs of HmtpO (e.g 5,7-diphenyl-1,2,4-
triazolo[1,5-a]pyrimidine (dptp) and 5,7-diterbutyl-1,2,4-
triazolo[1,5-a]pyrimidine (dbtp) [20]). The in vitro anti-
proliferative activity of the studied platinum compounds
1, 2a was determined against two human cell lines: T47D
(breast cancer) and HCV29T (bladder cancer). However,
the obtained results indicate that studied platinum
complexes are not cytotoxic in the concentration range
0.1–100 lg/ml.
˚
Compounds
Bond distances (A)
Pt–N(3) Pt–Cl
Angles (ꢁ)
Ref.
L–Pt–N(3) Pt–N(3)
–C(3A)
cis-PtCl2
(HmtpO)2 Æ
2H2O
2.00(2)
1.98(2)
2.278 (6) 91.7(4)
2.274(8)
129(1)
130(2)
[13]
89.7(7)
178.5(6)
177.3(4)
cis-[Pt(NH3)2
(HmtpO)2]
(NO3)2 Æ 2H2O
2.018(8)
2.012(8)
88.0(3)
90.9(3)
90.6(3)
90.7(3)
176.6(3)
176.3(3)
127.0(6) [25]
129.5(7)
a
4. Conclusion
trans-PtCl2
(dmtp)
(dmso)
a
2.048(5) 2.295(2)
2.303(2)
87.63(15)
89.2(2)
176.9(2)
[14]
The molecular structure and antiproliferative activity
in vitro of mononuclear platinum(II) complexes with
HmtpO were studied. The observed coordination mode
via N(3) may be regarded as representative for triazolopy-
rimidines and analogous to N(9) complexation in purine.
The crystal structures of 1, 2b indicate that the Pt(II) ion
has a square planar geometry with N(3) bonded HmtpO,
N-bonded second ligand (NH3 (1) and HmtpO (2b)) and
two cis chloride anions.
The results of the human cancer cell lines treatment with
the new platinum(II) complexes confirm lower cytotoxicity
of these compounds than cisplatinum in the concentration
range 0.1–100 lg/ml.
Data unavailable.
monoclinic form [13] was 79.8ꢁ, and has been strongly
affected by the reported HmtpO ring disorder. The dihedral
angles formed between the coordination PtN2Cl2 plane and
HmtpO ring systems are 82.0(2) and 73.4(2)ꢁ for N(1)–N(8)
and N(11)–N(18) ligands, respectively. The bend of the
HmtpO ring system along the N(8)–C(3a) bond is similar
to that detected in 1. The dihedral angle between the tria-
zole ring and pyrimidine ring planes are 1.2(8) and
2.2(6)ꢁ for N(1)–N(8) and N(11)–N(18) ring systems.
The intermolecular interactions include the network of
H-bonds formed by N(1)–H(1A)Á Á ÁO(64) [Àx À 1,Ày,
Àz + 1], N(4)–H(4A)Á Á ÁO(63) and N(14)–H(14A)Á Á ÁO(63),
the corresponding NÁ Á ÁO distances being 3.025(2),
5. Supplementary material
CCDC 276404 and 276405 contain the supplementary
crystallographic data for 1 and 2b. These data can be
obtained free of charge via http://www.ccdc.cam.ac.uk/
conts/retrieving.html, or from the Cambridge Crystallo-
graphic Data Centre, 12 Union Road, Cambridge CB2
1EZ, UK; fax: (+44) 1223-336-033; or e-mail: deposit@
ccdc.cam.ac.uk.
˚
2.788(2) and 2.854(2) A. The water molecules also interact
with other waters and chloride ions, although lack of
hydrogen atoms in the model does not allow a discussion
of the details of those interactions. One C–HÁ Á ÁCl interac-
tion was found, that is analogous to those described for 1.
That is C(12)–H(12A)Á Á ÁCl(1) [Àx,Ày,1 À z] with a CÁ Á ÁCl
Acknowledgment
˚
distance of 3.693(11) A and C–HÁ Á ÁCl angle of 173.2ꢁ. The
series of stacking interactions between the ring systems
of the neighboring molecules complete the packing
interactions.
Financial support from Polish Committee for Scientific
Research (KBN) Grant No 4 T09A 11623 is gratefully
acknowledged.
Table 5 presents the main structural differences between
known mononuclear Pt(II) complexes with triazolopyrimi-
dines. Careful interpretation has shown that the Pt–N and
Pt–Cl distances are not significantly different, but the Pt–N
bond seems slightly longer when it is in a trans position to
the chloro ligands. These results indicate that the trans
influence of the chloro and triazolopyrimidine ligands is
very similar and it might be greater for chloro ligands.
However, more X-ray data are needed to determine with
a bigger probability that the trans impact of the chloro
ligands is larger than the influence of the heterocyclic
ligands.
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