In vitro cytotoxic-active platinum(II) complexes derived from carboplatin and involving purine derivatives

Article abstract of DOI:10.1002/ejic.201000322

Six platinum(II) complexes of the general formula [Pt(cbdc)-(HL _n)₂] (1-6; cbdc = cyclobutane-1,1-dicarboxylate and HL₁-HL₆ = benzyl-substituted 6-benzylamino-2-chloro-9- isopropylpurine derivatives) have been synthesized by the reaction of [Pt(cbdc)(dmso)₂] with the corresponding HL_n compound. The prepared complexes were characterized by elemental analysis and FTIR, Raman and NMR (¹H, ¹³C, ¹⁵N and 195Pt) spectroscopy. Based on the results of these techniques, it can be concluded that the central PtII atom of the complexes 1-6 is coordinated to two oxygen atoms originating from the cyclobutane-1,1-dicarboxylate group and to two nitrogen atoms from two HL_n molecules, that is, having a PtN₂O₂ donor set. Detailed multinuclear and two-dimensional NMR studies indicated the N-7 atom to be the coordination site of the purine derivatives. The coordination mode was proven by a single-crystal X-ray analysis of the [Pt(cbdc)(dmso)- (HL₇)]·H₂O (7_a.H₂O) intermediate [HL₇ = 2-chloro-6-(2-methoxybenzyl)amino-9- isopropylpurine]. The geometry is slightly distorted square-planar and the central Pt^II atom is coordinated to one bidentate cyclobutane-1,1-dicarboxylate dianion, one dmso molecule through the sulfur atom and one HL7 molecule through the N-7 atom of the purine ring, that is, with a PtNO₂S donor set. The complexes 1-6 were tested for their in vitro cytotoxicity against K-562 (chronic myelogenous leukaemia) and MCF7 (breast adenocarcinoma) human cancer cell lines. Values of IC₅₀ (drug concentrations lethal for 50% of the tumour cells) ranged from 4.5 to 14.1 μm for the K-562 cells and from 4.3 to 21.0 μm for the MCF7 cells. The in vitro cytotoxicities were in several cases comparable or even higher than those of therapeutically used platinumbased anticancer drugs, that is, cisplatin, carboplatin and oxaliplatin.

Full text of DOI:10.1002/ejic.201000322

FULL PAPER
DOI: 10.1002/ejic.201000322
In Vitro Cytotoxic-Active Platinum(II) Complexes Derived from Carboplatin
and Involving Purine Derivatives
[a]
[a]
[a]
[a]
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ˇ
ˇ
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Lukás Dvorák, Igor Popa, Pavel Starha, and Zdenek Trávnícek*
Keywords: Platinum / Nucleobases / Cytotoxicity / Antitumor agents
Six platinum(II) complexes of the general formula [Pt(cbdc)-
(HL7)]·H2O (7a·H2O) intermediate [HL7 = 2-chloro-6-(2-
(HLn)2] (1–6; cbdc = cyclobutane-1,1-dicarboxylate and HL1–
methoxybenzyl)amino-9-isopropylpurine]. The geometry is
slightly distorted square-planar and the central PtII atom is
HL6
=
benzyl-substituted 6-benzylamino-2-chloro-9-iso-
propylpurine derivatives) have been synthesized by the reac- coordinated to one bidentate cyclobutane-1,1-dicarboxylate
tion of [Pt(cbdc)(dmso)2] with the corresponding HLn com-
pound. The prepared complexes were characterized by ele-
mental analysis and FTIR, Raman and NMR (1H, 13C, 15N and
dianion, one dmso molecule through the sulfur atom and one
HL7 molecule through the N-7 atom of the purine ring, that
is, with a PtNO2S donor set. The complexes 1–6 were tested
195Pt) spectroscopy. Based on the results of these techniques, it for their in vitro cytotoxicity against K-562 (chronic myeloge-
can be concluded that the central PtII atom of the complexes nous leukaemia) and MCF7 (breast adenocarcinoma) human
1–6 is coordinated to two oxygen atoms originating from the
cyclobutane-1,1-dicarboxylate group and to two nitrogen
atoms from two HLn molecules, that is, having a PtN2O2 do-
nor set. Detailed multinuclear and two-dimensional NMR
studies indicated the N-7 atom to be the coordination site of
the purine derivatives. The coordination mode was proven
by a single-crystal X-ray analysis of the [Pt(cbdc)(dmso)-
cancer cell lines. Values of IC50 (drug concentrations lethal
for 50% of the tumour cells) ranged from 4.5 to 14.1 µ for
the K-562 cells and from 4.3 to 21.0 µ for the MCF7 cells.
The in vitro cytotoxicities were in several cases comparable
or even higher than those of therapeutically used platinum-
based anticancer drugs, that is, cisplatin, carboplatin and
oxaliplatin.
M
M
The derivatives of 6-benzylamino-2-chloro-9-iso-
propylpurine (HLn) used for the preparation of the plati-
num(II) complexes 1–6 were chemically derived from a 6-
benzylaminopurine (N6-benzyladenine, bap) skeleton. The
latter represents one of the groups of plant growth regula-
tors called cytokinins.[4] 6-Benzylamino-2-chloro-9-iso-
propylpurine itself is an inactive precursor of cyclin-de-
pendent kinase (CDK) inhibitors such as 6-benzylamino-2-
(3-hydroxypropylamino)-9-isopropylpurine (bohemine) or
6-benzylamino-2-(2-hydroxymethyl-1-propylamino)-9-iso-
propylpurine (roscovitine, ros).[5] These types of organic
compounds have formerly been used in the synthesis of
metallocomplexes, including platinum(II) and platinum(IV)
complexes. Compounds cis-[PtCl2(HL)2], trans-[PtCl2-
(HL)2], [Pt(ox)(HL)2], [PtCl3(H+HL)], cis-[PtCl2(H+HL)2]-
Cl2 and [PtCl5(H+HL)] have been reported and their in vi-
tro cytotoxic activity on selected human cancer cell lines
have also been discussed (HL = variously substituted bap;
H+HL = protonated form of bap derivatives; see ref.[6] and
references cited therein). The best results were obtained for
cis-[PtCl2(ros)2], the IC50 (concentration of the tested com-
pound lethal for 50% of cells) values of which were equal
to 1 µ for the K-562 (chronic myelogenous leukaemia), G-
361 (malignant melanoma) and HOS (osteogenic sarcoma)
human cancer cell lines and to 2 µ for the MCF7 (human
breast adenocarcinoma) cells. The in vitro cytotoxicity of
this complex exceeds that of cisplatin, the IC50 values of
Introduction
One of the best known platinum-based complexes used
in the treatment of cancer is cis-diamminedichloridoplatin-
um(II) complex (cisplatin).[1] Since 1978 it has been used in
chemotherapy against testicular, ovarian, oesophageal,
lung, head, neck and other human malignancies.[2] How-
ever, the therapy itself is accompanied by several unwanted
side-effects (e.g., nephrotoxicity and ototoxicity) and drug
resistance. These limitations led to the preparation of new
platinum(II) complexes, that is, diamminecyclobutane-1,1-
dicarboxylatoplatinum(II) (carboplatin), (1R,2R)-diamino-
cyclohexaneoxalatoplatinum(II) (oxaliplatin) and diam-
mineglycolatoplatinum(II) (nedaplatin), which have also
been approved as platinum-based anticancer drugs. In the
case of carboplatin and nedaplatin, the carrier N-donor li-
gands (NH3) are identical to those in cisplatin. However,
the replacement of the chlorido-leaving ligands in cisplatin
by the cyclobutane-1,1-dicarboxylate (carboplatin) or
glycolate (nedaplatin) dianion led to the suppression of un-
wanted side-effects such as nephrotoxicity.[3]
[a] Department of Inorganic Chemistry, Faculty of Science,
Palacký University
Trˇ. 17. listopadu 12, 77146 Olomouc, Czech Republic
Fax: +420-585-634-357
E-mail: zdenek.travnicek@upol.cz
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejic.201000322.
Eur. J. Inorg. Chem. 2010, 3441–3448
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3441

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L. Dvorˇák, I. Popa, P. Starha, Z. Trávnícˇek
FULL PAPER
which were determined to be 3, 3, 5 and 11 µ, respectively, formation), were synthesized from 2,6-dichloropurine, as
for the above cell lines. With the exception of the above- shown in Scheme 1.[10]
mentioned compounds with 6-benzylaminopurine deriva-
A series of light-grey platinum(II) complexes 1–6 of the
tives, complexes of the type [Pt(1,4dach)(L)2]X involving general formula [Pt(cbdc)(HLn)2], formally derived from
different types of nucleobase or their derivatives (L = ade- carboplatin, were prepared by a general procedure with
nine, hypoxanthine, 9-methylguanine, cytosine and 1-meth- [Pt(cbdc)(dmso)2] as a key intermediate, which was allowed
ylcytosine) and 1,4-diaminocyclohexane (1,4dach) can be to react with 2 molequiv of the 6-benzylamino-2-chloro-9-
regarded as platinum(II) complexes with similar types of N- isopropylpurine derivatives (HL1–HL6) to give the final
2–
–
donor ligand; X = SO4 or Cl2 ).[7]
products of general formula [Pt(cbdc)(HLn)2] (summarized
A total number of 308 platinum(II) complexes involving in Scheme 1; dmso = dimethyl sulfoxide).[11] The reactions
the [PtN2(cbdc)] motif have been reported to date (Sci- were performed in distilled water/isopropyl alcohol (1:1,
Finder Scholar, 2004 edition). Moreover, 28 X-ray struc- v/v) at 90 °C. The substitution of the two dmso molecules
tures of platinum(II) square-planar complexes have been proceeded in two steps, as reported for the reactions of
deposited at the Crystallographic Structural Database [Pt(cbdc)(dmso)2] with 1,2-diaminocyclohexane (dach),
(CSD ver. 5.31, November 2009 update),[8] but only two of aminocyclohexane (ach) and n-propylamine (pa).[11] In the
them, namely [Pt(cbdc)(2-mp)2] and [Pt(cbdc)(hmi)2]·H2O,
have two unidentate N-donor heterocyclic ligands (2-meth-
ylpyridine, 2-mp; hexamethyleneimine, hmi) coordinated to
the PtII atom.[9] In relation to this, the complexes 1–6 repre-
sent the first ever prepared carboplatin-based complexes
with two substituted purine molecules coordinated to the
metal centre.
In this work we report the preparation and characteriza-
tion of the platinum(II) complexes [Pt(cbdc)(HLn)2] 1–6
bearing N-donor carrier ligands derived from 6-ben-
zylamino-2-chloro-9-isopropylpurine (HLn) and the cyclo-
butane-1,1-dicarboxylate dianion (cbdc) as the leaving bi-
dentate O-donor group. The complexes prepared were
screened in an acetoxymethyl (AM) assay for their in vitro
cytotoxicity against K-562 and MCF7 human cancer cell
lines.
Results and Discussion
Figure 1. Molecular structure of [Pt(cbdc)(dmso)(HL7)]·H2O
(7a·H2O) with non-hydrogen atoms drawn as thermal ellipsoids at
the 50% probability level. Hydrogen atoms have been omitted for
Synthesis
The 6-benzylamino-2-chloro-9-isopropylpurine deriva-
tives (HLn), depicted in Scheme S1 (see the Supporting In- clarity.
Scheme 1. Mechanism for the synthesis of 6-benzylamino-2-chloro-9-isopropylpurine derivatives (HLn) and the [Pt(cbdc)(HLn)2] com-
plexes 1–6 via the [Pt(cbdc)(dmso)(HLn)] intermediates (shown in grey). R = 5-bromo-2-fluoro (HL1; complex 1), 3,4-dichloro (HL2; 2),
3-bromo (HL3; 3), 2-trifluoromethyl (HL4; 4), 3-trifluoromethyl (HL5; 5) and 4-trifluoromethyl (HL4; 6) derivatives of 6-benzylamino-2-
chloro-9-isopropylpurine.
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Eur. J. Inorg. Chem. 2010, 3441–3448

Cytotoxic-Active Platinum(II) Complexes from Carboplatin
cases of the complexes 1–6, the syntheses proceeded by a pounds (HLn) were also found in the spectra of the com-
two-step reaction mechanism, the first stage involving the plexes 1–6. However, most of these signals were shifted as
substitution of one dmso molecule in the starting a consequence of the coordination of HLn to the PtII atom
[Pt(cbdc)(dmso)2] complex by one HLn molecule to form and the formation of the final products 1–6. The highest
[Pt(cbdc)(dmso)(HLn)]. It is supposed that intermediates of coordination shifts (∆δ = δcomplexes – δligand) were found for
this type are quite stable, probably due to the relative kinetic the 8-H and 6-H signals in the 1H NMR spectra; these were
inertness of the latter complex and the intra- and intermo- shifted significantly more than for the other proton signals.
lecular non-covalent interactions (e.g., hydrogen bonds) Significant coordination shifts were also observed in the 13
C
present both in the solid state and solution, which makes NMR spectra for the C-5 and C-8 atoms of the purine moi-
the substitution of the second dmso molecule quite difficult eties of HLn: the C-5 signals are shifted upfield and the C-
and the whole process longer. The described mechanism 8 signals downfield by more than 3.0 ppm. These findings
was proven by determining the molecular (Figure 1) and indirectly support the conclusion that the organic molecules
crystal structures of [Pt(cbdc)(dmso)(HL7)]·H2O (7a·H2O). HLn are coordinated to the PtII atom through their N-7
Subsequently, the second dmso ligand was substituted by atoms.
another HLn molecule to form the final product
[Pt(cbdc)(HLn)2] (see Scheme 1).
1H–15N gs-HMBC experiments were performed on 2–6
(unfortunately, signals from the nitrogen atoms in the struc-
ture of 1 were not detected) to confirm the above conclu-
sion. Table 1 summarizes the chemical and coordination
shifts obtained, the values of which correlate well for the
individual nitrogen atoms for all the complexes. The largest
values of ∆δ were found for the N-7 atom of the purine ring
with values of around –110 ppm (Table 1). The coordina-
tion shifts for the N-1, N-3, N-6 and N-9 atoms are much
smaller. These NMR results clearly prove that 6-benz-
ylamino-2-chloro-9-isopropylpurine derivatives (HLn) are
coordinated to the metal centre of the prepared plati-
num(II) complexes through the N-7 atom.
FTIR and Raman Spectroscopy
Most of the bands observed in the FTIR spectra of 1–6
between 640 and 900 cm–1 could be assigned to the purine
skeletal vibrations of the coordinated HLn molecules.[12]
The very strong bands detected in the 1609–1621 cm–1 re-
gion belong to ν(C=N)ar vibrations. The weak-to-medium
bands observed between 3050 and 3142 cm–1 may be attrib-
uted to ν(C–H)ar vibrations, whereas the maxima of the
ν(C–H)ar vibrations were detected in the 2873–2983 cm–1
region. The ν(C–Cl)al vibration is characterized by a band
of medium or strong intensity with the maximum between
1163 and 1171 cm–1. Three bands with maxima at around
1480, 1530 and 1580 cm–1 can be assigned to ν(C=C)ar vi-
brations. The νas(C=O) vibration can be attributed to the
band observed at 1679–1680 cm–1, which is the typical re-
gion for this vibration and it has previously been assigned
to the carboxy groups of the cbdc dianion.[11,13] The bands
observed for 1–6 in the 150–600 cm–1 region, with maxima
at 540–545 and 554–563 cm–1, could be assigned to the
ν(Pt–N) and ν(Pt–O) stretching vibrations, respectively.[14]
The presence of these two vibrations in the far-FTIR spec-
tra indirectly confirmed the coordination of both types of
organic ligands, that is, HL1–HL6 and cbdc, to the central
PtII atom.
Table 1. Results of the 1H–15N gs-HMBC experiments given as
chemical shifts with the coordination shifts (∆δ = δcomplexes – δligand
)
given in parentheses.
δ [ppm]
N1
N3
N6
N7
N9
1[a]
2
3
4
5
–
–
–
–
–
232.7 (5.7) 225.3 (1.2) 96.3 (8.4)
232.4 (7.1)
230.8 (6.3)
231.8 (4.0) 223.9 (–0.3) 97.3 (5.4)
232.4 (4.4) 225.0 (–0.5) 96.5 (5.3)
129.3 (–109.4) 185.2 (7.1)
129.1 (–107.7) 184.9 (8.8)
128.0 (–109.3) 184.1 (7.2)
129.0 (–111.6) 185.3 (6.2)
129.0 (–112.0) 185.4 (6.4)
n.o.[b]
n.o.[b]
97.4 (7.7)
92.4 (5.9)
6
[a] Signals from the N-1, N-3, N-6, N-7 and N-9 atoms of 1 were
not detected. [b] The N-3 signal was not observed for 3, HL3 or 4.
Signals characterizing the cyclobutane-1,1-dicarboxylate
dianion were detected in both the 1H and 13C NMR spectra
of 1–6 (see the Exp. Sect.) and these signals were refined by
1H–13C gs-HMQC and gs-HMBC 2D NMR experiments.
The most characteristic signal of the coordinated cbdc di-
anion, which belongs to the C-22 and C-23 atoms of the
two carboxy groups, was found at around 177.5 ppm.
The 195Pt NMR spectra of 1–6 exhibit signals between
–1631 and –1620 ppm. Note that the 195Pt NMR chemical
shifts of platinum(II) complexes with the formula
[Pt(cbdc)(L)], in which L symbolizes two monodentate or
one bidentate N-donor ligand, namely amine, cyclopen-
tylamine (cpa), 1,2-ethylenediamine (en), 1,2-diaminopro-
pane (meen), N,N-dimethylethylenediamine (Me2en) and
1,2-diaminocyclohexane (dach), range from –1968 to
As can be seen from the data given in the Exp. Sect., only
some of the above characteristic vibrations were detected in
the Raman spectra of 2, 3, 5 and 6 (1 and 4 were burnt
under the laser beam). Nevertheless, it can be noted that
the positions of the band maxima assignable to these vi-
brations for both the HLn and cbdc ligands correlate well
in the FTIR and Raman spectra of the particular complexes
1–6. The bands with maxima at 3063–3140 and 2870–
2987 cm–1 can be assigned to ν(C–H)ar and ν(C–H)al vi-
brations, respectively.[15] The very strong skeletal vibration
of the purine ring was detected in the range of 1338–
1340 cm–1.[16]
NMR Spectroscopy
All the signals of the free HLn molecules detected in the –1647 ppm.[17] Thus, it can be said that the shifts for 1–6
1H and 13C NMR spectra of the appropriate starting com- approach the upper limit of 195Pt NMR chemical shifts of
Eur. J. Inorg. Chem. 2010, 3441–3448
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L. Dvorˇák, I. Popa, P. Starha, Z. Trávnícˇek
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the cited complexes. Moreover, these values are also similar sion angles C(6)–N(6)–C(9)–C(10), C(5)–C(6)–N(6)–C(9)
to those obtained for oxalatoplatinum(II) complexes (ca. and N(6)–C(9)–C(10)–C(15) are equal to 165.1(4), 176.6(4)
–1690 ppm) involving 6-benzylamino-2-chloro-9-isopro- and –120.6(5)°, respectively. The dihedral angle formed by
pylpurine-based N-donor ligands.[6b]
the benzene and purine rings is 53.62(13)°. Moreover, the
dihedral angle between the purine ring and the basal plane
formed by the atoms of the PtNO2S donor set was deter-
mined to be 87.34(8)°. The cyclobutane-1,1-dicarboxylate
dianion is coordinated to the metal centre through its O(1)
and O(3) atoms. The Pt–O bond lengths determined for
7a·H2O (Table 3) correlate well with those of the cyclobu-
tane-1,1-dicarboxylatoplatinum(II) complexes deposited in
the CSD,[8] which range from 1.977 to 2.065 Å (mean of
2.016 Å). The dihedral angle, typical of platinum(II) com-
plexes coordinated to the cbdc dianion, formed by the basal
plane (PtNO2S donor set) and the cyclobutane ring, is
equal to 79.5(2)°. The dimethyl sulfoxide molecule is coor-
dinated to the PtII atom through its S(1) atom.
Single-Crystal X-ray Analysis of [Pt(cbdc)(dmso)
(HL7)]·H2O (7a·H2O)
Attempts to prepare single crystals of platinum(II) com-
plexes 1–6 suitable for single-crystal X-ray analysis were un-
successful. Nevertheless, very important findings about the
compositions and coordination modes of these complexes
were obtained by analysis of the [Pt(cbdc)(dmso)(HL7)]·
H2O (7a·H2O) intermediate, the molecular (Figure 1) and
crystal (Figure 2) structures of which were determined by
this important method (Table 2). Selected bond lengths and
angles are presented in Table 3 and non-bonding contacts
are given as a footnote in Figure 2.
Table 3. Selected bond lengths and angles for 7a·H2O.
Bond lengths [Å]
Bond angles [°]
Table 2. Crystal data and structure refinement details for
[Pt(cbdc)(dmso)(HL7)]·H2O (7a·H2O).
Pt(1)–O(1)
Pt(1)–O(3)
Pt(1)–N(7)
Pt(1)–S(1)
N(1)–C(2)
N(1)–C(6)
C(2)–N(3)
N(3)–C(4)
C(4)–C(5)
C(4)–N(9)
C(5)–C(6)
C(5)–N(7)
N(7)–C(8)
C(8)–N(9)
O(1)–C(22) 1.302(6)
O(3)–C(23) 1.308(6)
C(22)–O(2) 1.218(6)
C(22)–C(24) 1.520(7)
C(23)–O(4) 1.216(6)
C(23)–C(24) 1.525(7)
2.018(3)
O(1)–Pt(1)–O(3)
O(1)–Pt(1)–N(7)
O(1)–Pt(1)–S(1)
O(3)–Pt(1)–N(7)
O(3)–Pt(1)–S(1)
N(7)–Pt(1)–S(1)
Pt(1)–N(7)–C(5)
Pt(1)–N(7)–C(8)
Pt(1)–O(1)–C(22)
Pt(1)–O(3)–C(23)
Pt(1)–S(1)–C(20)
Pt(1)–S(1)–C(21)
Pt(1)–S(1)–O(6)
C(5)–N(7)–C(8)
N(7)–C(5)–C(4)
N(7)–C(5)–C(6)
N(7)–C(8)–C(9)
O(1)–C(22)–O(2)
89.89(13)
88.56(15)
178.00(11)
178.45(15)
88.94(10)
92.60(12)
128.0(3)
125.3(3)
119.9(3)
119.8(3)
107.2(2)
108.7(2)
118.7(2)
106.6(4)
108.3(4)
134.3(4)
111.4(4)
121.3(5)
2.004(3)
2.011(4)
2.1819(12)
1.331(6)
1.346(6)
1.312(6)
1.353(6)
1.367(6)
1.372(6)
1.407(6)
1.380(6)
1.313(6)
1.350(6)
Molecular formula
Formula weight
Temperature [K]
Wavelength [Å]
Crystal system
Space group
Unit cell dimensions
a [Å]
C24H32ClN5O7PtS
765.15
120(2)
0.71073
orthorhombic
Pbca
13.8086(3)
14.4052(3)
b [Å]
c [Å]
α [°]
28.3693(5)
90
β [°]
90
90
5643.1(2)
8, 1.801
5.193
0.40ϫ0.35ϫ0.30
3024
γ [°]
V [Å3]
Z, Dcalcd. [gcm–3]
Absorption coefficient [mm–1]
Crystal size [mm]
F (000)
O(1)–C(22)–C(24) 117.2(4)
O(3)–C(23)–O(4) 121.1(5)
O(3)–C(23)–C(24) 117.7(4)
θ range for data collection [°]
Index ranges (h, k, l)
2.83ՅθՅ25.00
–16ՅhՅ16
–17ՅkՅ12
–32ՅlՅ33
44469/4960 (0.0393)
0.3049/0.2305
4960/0/363
1.256
S(1)–C(20)
S(1)–C(21)
S(1)–O(6)
1.763(6)
1.745(6)
1.455(4)
Reflections collected/unique (Rint
Max./min. transmission
Data/restraints/parameters
Goodness-of-fit on F2
)
A network of intra- and intermolecular hydrogen bonds
and non-covalent contacts stabilize the crystal structure of
7a·H2O (Figure 2). As a consequence of the intramolecular
N(6)–H(6)···O(5) hydrogen bond [d(D–H) = 0.8800 Å,
d(H···A) = 2.435(4) Å, d(D···A) = 2.815(5) Å and Ͻ(DHA)
= 106.5(3)°], the methoxy group is orientated towards the
Final R indices [IϾ2σ(I)]
R indices (all data)
R1 = 0.0285, wR2 = 0.0616
R1 = 0.0334, wR2 = 0.0639
0.822/–1.789
Largest peak/hole [eÅ–3]
The [Pt(cbdc)(dmso)(HL7)]·H2O (7a·H2O) complex has imidazole ring. The water molecule is involved in hydrogen
a distorted square-planar arrangement with a PtNO2S do- bonds of the O–H···O type with the O(2) and O(4) atoms of
nor set and it contains one water molecule of crystallization two different 7a molecules to form the following hydrogen
(Figure 1). The donor atoms originate from 2-chloro-6-(2- bonds: O(7)–H(7W)···O(4)i [d(D–H) = 0.89(7) Å, d(H···A)
methoxybenzyl)amino-9-isopropylpurine (HL7), the biden- = 1.93(7) Å, d(D···A) = 2.767(6) Å and Ͻ(DHA) = 157(6)°]
tate-coordinated cyclobutane-1,1-dicarboxylate dianion and O(7)–H(7V)···O(4)ii [d(D–H) = 0.81(7) Å, d(H···A) =
and the S-coordinated dmso molecule. The coordination 2.00(7) Å, d(D···A) = 2.806(6) Å and Ͻ(DHA) = 168(6)°]
site of HL7 is the N(7) atom of the purine moiety.
[Figure 2; symmetry codes: (i) 1 – x, y + 0.5, 0.5 – z; (ii) x
The HL7 molecule consists of three aromatic systems, + 0.5, y, 0.5 – z]. Finally, C–H···O, C–H···Cl, C···Cl and
benzene (A), pyrimidine (B) and imidazole (C), with the Cl···O non-covalent contacts were detected in the crystal
biggest deviations from planarity being 0.003(5) Å for structure of the complex 7a·H2O and their parameters are
C(13), 0.018(4) Å for N(1) and 0.012(4) Å for C(5). The tor- given in Table S1 of the Supporting Information.
3444
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© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Inorg. Chem. 2010, 3441–3448

Cytotoxic-Active Platinum(II) Complexes from Carboplatin
Figure 2. Part of the crystal structure of [Pt(cbdc)(dmso)(HL7)]·H2O (7a·H2O) showing N–H···O and O–H···O hydrogen bonds (dashed
light-grey lines) and C–H···O non-covalent contacts (dashed dark-grey lines). Hydrogen atoms not involved in hydrogen bonds have been
omitted for clarity. Symmetry codes: (iii) 0.5 – x, y – 0.5, z; (iv) x, y – 1, z; (v) 0.5 – x, y + 0.5, z; (vi) x – 0.5, y – 1, 0.5 – z; (vii) 1 – x,
y – 0.5, 0.5 – z; (viii) x – 0.5, y, 0.5 – z.
In Vitro Cytotoxic Activity
tin have been prepared by a synthetic strategy with
[Pt(cbdc)(dmso)2] as a key intermediate. The products ob-
tained were fully characterized. Based on the results of vari-
ous physicochemical techniques it can be concluded that
the central PtII atom is tetracoordinated to two unidentate
N-donor carrier ligands derived from 6-benzylamino-2-
chloro-9-isopropylpurine (HL1–HL6) and the bidentate O-
donor cyclobutane-1,1-dicarboxylate dianion (cbdc). Multi-
nuclear and two-dimensional NMR studies proved the N-7
atom to be the coordination site of the HLn ligands, which
was also confirmed by single-crystal X-ray analysis of the
[Pt(cbdc)(dmso)(HL7)]·H2O (7a·H2O) intermediate. IC50
values for the in vitro cytotoxicity of the prepared plati-
num(II) complexes showed that several of the prepared
complexes can be considered to have comparable or even
higher in vitro cytotoxicity than the platinum-based anti-
cancer drugs, that is, cisplatin, carboplatin and oxaliplatin.
The prepared complexes 1–6 were tested for their in vitro
cytotoxic activity by performing a calcein AM assay on the
chronic myelogenous leukaemia (K-562) and breast adeno-
carcinoma (MCF7) human cancer cell lines (Table 4).
Table 4. IC50 values (µ) of the in vitro cytotoxicity of the com-
plexes 1–6 and platinum-based anticancer drugs against K-562
(chronic myelogenous leukaemia) and MCF7 (breast adenocarci-
noma) human cancer cell lines; the cells were exposed to the com-
pounds for 72 h; experiments were repeated three-times.
Complex
IC50 [µ]
Ref.
K-562
MCF7
1
9.5Ϯ2.5
4.8Ϯ0.6
4.5Ϯ1.0
7.0Ϯ1.3
14.1Ϯ3.3
7.5Ϯ1.9
4.7
9.0Ϯ2.3
4.3Ϯ0.2
5.0Ϯ0.3
7.9Ϯ2.3
21.0Ϯ1.4
19.2Ϯ8.6
10.9
this work
this work
this work
this work
this work
2
3
4
5
6
this work
[18a]
Cisplatin
Carboplatin
Oxaliplatin
[18b,18c]
[18a]
60.0
8.8
250.0
18.2
Experimental Section
Materials: The chemicals and solvents were purchased from com-
mercial sources, namely Sigma–Aldrich, Acros Organics, Lachema
and Fluka, and they were used as received.
The results reveal very promising cytotoxic activities with
IC50 values in the range of 4.5–14.1 and 4.3–21.0 µ for the
K-562 and MCF7 cell lines, respectively. In the case of the
K-562 cells, complexes 2 and 3 have an in vitro cytotoxicity
comparable to that of cisplatin. Moreover, these com-
pounds, together with 4 and 6, exceed the activity of oxali-
platin and all the tested substances are significantly more
effective than carboplatin. As for the MCF7 human cancer
cells, 1–6 are again more cytotoxic than carboplatin. The in
vitro cytotoxic activities of the complexes 1–4 were evalu-
ated as even higher than those of commercially used plati-
num-based drugs cisplatin and oxaliplatin.
The 6-benzylamino-2-chloro-9-isopropylpurine derivatives (HLn;
see Scheme S1 in the Supporting Information) were synthesized
from 2,6-dichloropurine according to previously reported pro-
cedures for the preparation of the 2,6,9-trisubstituted purine deriv-
atives.[10] The synthetic strategy is given in Scheme 1. The molecules
of HL1–HL6 were characterized by elemental analysis, melting-
point determination and FTIR, Raman and NMR (1H, 13C and
15N) spectroscopy. The results can be found in the Supporting In-
formation. Yields ranged from 76–88%.
Methods: Chemical analysis (C, H, N) was performed with a Flash
EA1112 Elementar Analyzer (ThermoFinnigan). The purities of
the prepared organic compounds HL1–HL7 were determined with
a Beckman HPLC. Melting points were determined with a Büchi
B-540 melting-point apparatus with a temperature gradient of
2 °Cmin–1. The FTIR spectra were obtained with KBr pellets (400–
4000 cm–1) and by using the Nujol technique (150–600 cm–1) with
a Nexus 670 FT–IR device (ThermoNicolet). Raman spectroscopy
Conclusions
The seven novel [Pt(cbdc)(HLn)2] (1–6) and
[Pt(cbdc)(dmso)(HL7)]·H2O (7a·H2O) cyclobutane-1,1-di-
carboxylatoplatinum(II) complexes derived from carbopla- was performed on the complexes 2, 3, 5 and 6 (1 and 4 burned
Eur. J. Inorg. Chem. 2010, 3441–3448
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjic.org
3445

ˇ
L. Dvorˇák, I. Popa, P. Starha, Z. Trávnícˇek
FULL PAPER
under the laser beam) in the 150–3750 cm–1 region with a FT–Ra-
man Nicolet NXR 9650 spectrometer with a liquid-nitrogen-cooled
NXE Genie germanium detector.
11), 128.5 (C-14), 116.7 (C-5), 56.8 (C-24), 49.8 (C-17), 44.1 (C-9),
31.4 (C-25, C-27), 22.1 (C-18, C-19), 15.8 (C-26) ppm. 15N NMR
([D7]DMF): δ = 232.7 (N-1), 225.3 (N-3), 185.2 (N-9), 129.3 (N-7),
96.3 (N-6) ppm. 195Pt NMR: δ = –1622 ppm. C36H34Cl6N10O4Pt
(1078.51): calcd. C 40.09, H 3.18, N 12.99; found C 39.89, H 3.11,
N 13.20.
1
1
1H, 13C and 195Pt NMR spectra as well as H–1H gs-COSY, H–
13C gs-HMQC and 1H–13C gs-HMBC ([D7]DMF solutions) data
were collected with a Bruker Avance 300 spectrometer for HLn and
1–6 {[Pt(cbdc)(dmso)2] is insufficiently soluble in the used solvent}.
1H–15N gs-HMBC experiments were performed on complexes 2–6
(at natural abundance) using the same device. Spectra were cal-
ibrated against SiMe4 (for 1H and 13C) and K2PtCl4 (D2O; for
195Pt, –1628 ppm) and against the residual signals of the solvent
(for 15N, 104.7 ppm). The multiplicities in the proton spectra are
defined as: s = singlet, d = doublet, t = triplet, quint = quintet,
sept = septet, dd = doublet of doublets and m = multiplet.
[Pt(cbdc)(HL ) ] (3): IR (Nujol): ν = 554 (vs, PtO), 540 (vs,
˜
3 2
PtN) cm–1. IR (KBr): ν = 3138 (w), 3092 (w), 3054 (w, CH ), 2978
˜
ar
(m), 2936 (m), 2878 (w, CHal), 1679 (s, CO), 1620 (vs, CN), 1584
(vs), 1524 (m), 1477 (s, CC), 1166 (m, CCl) cm–1. Raman: ν = 3140
˜
(w), 3063 (m, CHar), 2983 (s), 2942 (s), 2870 (w, CHal), 1679 (w,
CO), 1583 (s), 1537 (w), 1484 (m, CC), 1166 (m, CCl), 540 (w,
1
PtN) cm–1. H NMR ([D7]DMF): δ = 9.42 (t, J = 6.6 Hz, 1 H, 6-
H), 9.31 (s, 1 H, 8-H), 7.65 (t, J = 1.7 Hz, 1 H, 11-H), 7.58 (dd, J
= 7.9, 1.3 Hz, 1 H, 15-H), 7.47 (dd, J = 7.9, 2.0 Hz, 1 H, 13-H),
7.28 (t, J = 7.9 Hz, 1 H, 14-H), 4.94 (d, J = 6.4 Hz, 2 H, 9-H), 4.85
(sept, J = 6.8 Hz, 1 H, 17-H), 2.89 (m, 2 H, 25-Ha, 27-Ha), 1.79
(m, 1 H, 26-Ha), 1.69 (m, 2 H, 25-Hb, 27-Hb), 1.62 (d, J = 6.7 Hz,
6 H, 18-H, 19-H), 1.48 (m, 1 H, 26-Hb) ppm. 13C NMR ([D7]-
DMF): δ = 177.5 (C-22, C-23), 155.2 (C-6), 153.9 (C-2), 150.0 (C-
4), 144.3 (C-8), 142.5 (C-10), 131.1 (C-13), 130.9 (C-14), 130.6 (C-
15), 127.2 (C-11), 122.5 (C-12), 116.6 (C-5), 56.8 (C-24), 49.8 (C-
17), 44.6 (C-9), 31.4 (C-25, C-27), 22.1 (C-18, C-19), 15.8 (C-
26) ppm. 195Pt NMR: δ = –1621 ppm. C36H36Br2Cl2N10O4Pt
(1098.53): calcd. C 39.36, H 3.30, N 12.75; found C 39.76, H 3.11,
N 13.04.
Synthesis of [Pt(cbdc)(dmso)2]: The silver(I) salt of cyclobutane-1,1-
dicarboxylic acid (Ag2cbdc) and cis-[PtCl2(dmso)2] were synthe-
sized according to previously reported methods with cyclobutane-
1,1-dicarboxylic acid (cbdca) and PtCl2 used as starting com-
pounds.[17a,19] The prepared cis-[PtCl2(dmso)2] was dissolved in dis-
tilled water and an equimolar amount of Ag2cbdc was added to
the solution.[11] The mixture was stirred in darkness at room tem-
perature for 24 h. The solvent was evaporated and white crystals of
[Pt(cbdc)(dmso) ] formed (Scheme 1). Yield 88%. IR (Nujol): ν =
˜
2
567 (s, PtO) cm–1. IR (KBr): ν = 1663 (CO) cm–1. C H O PtS
˜
10 18
6
2
(493.46): calcd. C 24.34, H 3.68; found C 24.42, H 3.96. M.p. 200–
202 °C.
[Pt(cbdc)(HL ) ] (4): IR (Nujol): ν = 562 (vs, PtO), 540 (vs,
˜
4 2
Synthesis of [Pt(cbdc)(HLn)2] 1–6: [Pt(cbdc)(dmso)2] (0.2 mmol)
was dissolved in distilled water (15 mL) and the appropriate 6-
benzylamino-2-chloro-9-isopropylpurine derivative (HLn; 0.4 mmol)
suspended in isopropyl alcohol (20 mL) was added (Scheme 1).[11]
The mixture was stirred at 90 °C and a light-grey precipitate
formed in 2 days. The product was removed by filtration, washed
with cold distilled water and dried in the desiccator over silica gel.
PtN) cm–1. IR (KBr): ν = 3095 (w), 3050 (w, CH ), 2982 (m), 2939
˜
ar
(w), 2883 (w, CHal), 1679 (m, CO), 1621 (vs, CN), 1583 (s), 1536
1
(w), 1482 (m, CC), 1163 (s, CCl) cm–1. H NMR ([D7]DMF): δ =
9.44 (t, J = 6.4 Hz, 1 H, 6-H), 9.42 (s, 1 H, 8-H), 7.74 (m, 3 H, 13-
H, C14-H, 15-H), 7.48 (m, 1 H, 12-H), 5.64 (d, J = 6.0 Hz, 2 H,
9-H), 4.88 (sept, J = 7.0 Hz, 1 H, 17-H), 2.90 (m, 2 H, 25-Ha, 27-
Ha), 1.80 (m, 1 H, 26-Ha), 1.66 (d, J = 6.8 Hz, 6 H, 18-H, 19-H),
1.61 (m, 2 H, 25-Hb, 27-Hb), 1.43 (m, 1 H, 26-Hb) ppm. 13C NMR
([D7]DMF): δ = 177.7 (C-22, C-23), 155.2 (C-6), 154.1 (C-2), 150.1
(C-4), 143.7 (C-8), 138.1 (C-10), 133.1 (C-14), 128.2 (C-15), 127.7
(C-13), 127.4, 123.8 (C-16), 126.7 (C-12), 116.6 (C-5), 56.9 (C-24),
49.9 (C-17), 41.4 (C-9), 31.5 (C-25, C-27), 22.1 (C-18, C-19), 15.8
(C-26) ppm. 195Pt NMR: δ = –1631 ppm. C38H36Cl2F6N10O4Pt
(1076.73): calcd. C 42.39, H 3.37, N 13.01; found C 42.33, H 3.28,
N 13.19.
[Pt(cbdc)(HL ) ] (1): IR (Nujol): ν = 563 (vs, PtO), 541 (vs,
˜
1 2
PtN) cm–1. IR (KBr): ν = 3142 (w), 3095 (w), 3053 (w, CH ), 2980
˜
ar
(m), 2933 (w), 2873 (w, CHal), 1679 (m, CO), 1621 (vs, CN), 1583
(s), 1540 (m), 1484 (s, CC), 1171 (m, CCl) cm–1. 1H NMR ([D7]-
DMF): δ = 9.38 (t, J = 6.4 Hz, 1 H, 6-H), 9.08 (s, 1 H, 8-H), 7.59
(s, 1 H, 15-H), 7.49 (d, J = 8.4 Hz, 1 H, 13-H), 7.32 (d, J = 7.7 Hz,
1 H, 12-H), 4.96 (d, J = 6.0 Hz, 2 H, 9-H), 4.87 (sept, J = 6.7 Hz,
1 H, 17-H), 2.86 (m, 2 H, 25-Ha, 27-Ha), 1.80 (m, 1 H, 26-Ha),
1.67 (m, 2 H, 25-Hb, 27-Hb), 1.63 (d, J = 6.8 Hz, 6 H, 18-H, 19-
H), 1.48 (m, 1 H, 26-Hb) ppm. 13C NMR ([D7]DMF): δ = 177.4
(C-22, C-23), 155.3 (C-6), 153.7 (C-2), 150.1 (C-4), 144.0 (C-8),
141.9 (C-10), 132.3 (C-11), 130.8 (C-14), 130.6 (C-12), 129.7 (C-
13), 128.8 (C-15), 116.5 (C-5), 56.8 (C-24), 49.9 (C-17), 44.3 (C-9),
31.4 (C-25, C-27), 22.1 (C-18, C-19), 15.9 (C-26) ppm. 195Pt NMR:
δ = –1626 ppm. C36H34Br2Cl2F2N10O4Pt (1134.51): calcd. C 38.11,
H 3.02, N 12.35; found C 37.74, H 2.82, N 12.57.
[Pt(cbdc)(HL ) ] (5): IR (Nujol): ν = 560 (m, PtO), 542 (s,
˜
5 2
PtN) cm–1. IR (KBr): ν = 3093 (w), 3050 (w, CH ), 2982 (w), 2941
˜
ar
(w), 2884 (w, CHal), 1680 (m, CO), 1609 (vs, CN), 1583 (s), 1537
(w), 1484 (m, CC), 1166 (s, CCl) cm–1. Raman: ν = 3072 (s, CH ),
˜
ar
2987 (vs), 2946 (vs, CHal), 1609 (w, CN), 1579 (s), 1538 (m), 1480
1
(m, CC), 1170 (w, CCl) cm–1. H NMR ([D7]DMF): δ = 9.48 (t, J
= 6.2 Hz, 1 H, 6-H), 9.31 (s, 1 H, 8-H), 7.88 (d, J = 7.9 Hz, 1 H,
15-H), 7.84 (s, 1 H, 11-H), 7.65 (d, J = 7.9 Hz, 1 H, 13-H), 7.55 (t,
J = 7.9 Hz, 1 H, 14-H), 5.03 (d, J = 6.2 Hz, 2 H, 9-H), 4.83 (sept,
J = 6.8 Hz, 1 H, 17-H), 2.89 (t, J = 8.0 Hz, 4 H, 25-H, 27-H), 1.78
(quint, J = 8.0 Hz, 2 H, 26-H), 1.61 (d, J = 6.8 Hz, 6 H, 18-H, 19-
H) ppm. 13C NMR ([D7]DMF): δ = 177.6 (C-22, C-23), 155.1 (C-
6), 154.0 (C-2), 150.0 (C-4), 144.8 (C-8), 141.2 (C-10), 132.3 (C-
15), 130.8, 130.4, 130.0, 129.6 (C-12), 130.1 (C-14), 130.7, 127.1,
123.5, 119.9 (C-16), 125.1, 125.0 (C-11), 124.5, 126.4 (C-13), 116.6
(C-5), 56.8 (C-24), 49.8 (C-17), 44.8 (C-9), 31.4 (C-25, C-27), 22.1
(C-18, C-19), 15.8 (C-26) ppm. 195Pt NMR: δ = –1620 ppm.
C38H36Cl2F6N10O4Pt (1076.73): calcd. C 42.39, H 3.37, N 13.01;
found C 42.01, H 3.34, N 13.26.
[Pt(cbdc)(HL ) ] (2): IR (Nujol): ν = 563 (v, PtO) cm–1. IR (KBr):
˜
2 2
ν = 2980 (w, CH ), 1633 (vs, CN), 1586 (m, CC), 1169 (m,
˜
al
CCl) cm–1. Raman: ν = 3123 (w), 3064 (m, CH ), 2982 (s), 2942
˜
ar
(vs), 2873 (w, CHal), 1587 (s), 1535 (w), 1483 (m, CC), 1164 (m,
CCl), 565 (w, PtO) cm–1. 1H NMR ([D7]DMF): δ = 9.44 (t, J =
6.4 Hz, 1 H, 6-H), 9.32 (s, 1 H, 8-H), 7.68 (d, J = 1.8 Hz, 1 H, 11-
H), 7.58 (dd, J = 8.4, 1.8 Hz, 1 H, 14-H), 7.53 (d, J = 8.4 Hz, 1 H,
15-H), 4.96 (d, J = 6.2 Hz, 2 H, 9-H), 4.84 (sept, J = 6.8 Hz, 1 H,
17-H), 2.90 (m, 2 H, 25-Ha, 27-Ha), 1.80 (quint, J = 7.7 Hz, 1 H,
26-Ha), 1.67 (m, 2 H, 25-Hb, 27-Hb), 1.62 (d, J = 6.8 Hz, 6 H, 18-
H, 19-H), 1.47 (m, 1 H, 26-Hb) ppm. 13C NMR ([D7]DMF): δ =
177.6 (C-22, C-23), 155.2 (C-6), 153.9 (C-2), 150.3 (C-4), 143.9 (C- [Pt(cbdc)(HL ) ] (6): IR (Nujol): ν = 560 (m, PtO), 545 (m,
˜
6 2
8), 140.9 (C-10), 132.1 (C-12), 131.1 (C-15), 130.6 (C-13), 130.0 (C-
PtN) cm–1. IR (KBr): ν = 3142 (w), 3097 (w), 3055 (w, CH ), 2983
˜
ar
3446
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© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Inorg. Chem. 2010, 3441–3448

Cytotoxic-Active Platinum(II) Complexes from Carboplatin
(w), 2939 (w), 2883 (w, CHal), 1679 (m, CO), 1618 (vs, CN), 1585 repeated three times and the IC50 values are given in Table 4 to-
(s), 1530 (w), 1483 (m, CC), 1167 (m, CCl) cm–1. Raman: ν = 3072 gether with their standard deviations.
˜
(s, CHar), 2984 (s), 2945 (vs), 2876 (w, CHal), 1679 (w, CO), 1618
Supporting Information (see also the footnote on the first page of
(m, CN), 1582 (s), 1534 (m), 1483 (m, CC), 1164 (m, CCl), 549 (w,
this article): The structural formulae of the 6-benzylamino-2-
1
PtN) cm–1. H NMR ([D7]DMF): δ = 9.47 (t, J = 6.2 Hz, 1 H, 6-
chloro-9-isopropylpurine derivatives (HLn), the results of elemental
H), 9.35 (s, 1 H, 8-H), 7.75 (d, J = 8.2 Hz, 2 H, 11-H, 15-H), 7.65
analyses, melting-point determinations and FTIR, Raman and
(d, J = 8.2 Hz, 2 H, 12-H, 14-H), 5.02 (d, J = 6.2 Hz, 2 H, 9-H),
NMR data (1H, 13C and 15N).
4.84 (sept, J = 6.8 Hz, 1 H, 17-H), 2.90 (t, J = 8.0 Hz, 4 H, 25-H,
27-H), 1.80 (quint, J = 8.0 Hz, 2 H, 26-H), 1.62 (d, J = 6.8 Hz, 6
H, 18-H, 19-H) ppm. 13C NMR ([D7]DMF): δ = 177.7 (C-22, C-
23), 155.2 (C-6), 154.0 (C-2), 150.0 (C-4), 144.6 (C-10), 143.8 (C-
Acknowledgments
8), 130.8, 127.2, 123.6 (C-16), 129.4, 129.0, 128.6, 128.1 (C-13),
128.7 (C-11, C-15), 125.8, 125.8 (C-12, C-14), 116.7 (C-5), 56.8 (C-
24), 49.8 (C-17), 44.6 (C-9), 31.4 (C-25, C-27), 22.1 (C-18, C-19),
This research was supported by the The Ministry of Education,
Youth and Sports of the Czech Republic (Grant No.
MSM6198959218). The authors thank Dr. Miroslava Matiková-
15.8
(C-26) ppm.
195Pt
NMR:
δ
=
–1621 ppm.
ˇ
Malarová for measurement of the FTIR and Raman spectra and
C38H36Cl2F6N10O4Pt (1076.73): calcd. C 42.39, H 3.37, N 13.01;
found C 41.93, H 3.27, N 13.36.
Dr. Vladimír Krystof and Mrs. Dita Parobková for in vitro cyto-
ˇ
toxicity testing.
[Pt(cbdc)(dmso)(HL7)]·H2O (7a·H2O): The complex was prepared
using the same synthetic strategy as in the cases of 1–6, but in a
shorter reaction time. The powder product obtained after 24 h was
removed by filtration. It was found that the product contains a
mixture of [Pt(cbdc)(HL7)2] and [Pt(cbdc)(dmso)(HL7)] (7a).
[1] B. Rosenberg, V. L. Camp, T. Krigas, Nature 1965, 205, 698–
699.
[2] R. B. Weiss, M. C. Christian, Drugs 1993, 46, 360–365.
[3] M. J. Abrams, B. A. Murrer, Science 1993, 261, 725–730.
[4] F. Skoog, H. Q. Hamzi, A. M. Szweykowska, N. J. Leopard,
K. L. Carraway, T. Fujii, J. P. Helgeson, R. N. Loeppky, Phyto-
chemistry 1967, 6, 1169–1192.
Recrystallization
of
this
mixture
gave
crystals
of
[Pt(cbdc)(dmso)(HL7)]·H2O (7a·H2O) suitable for a single-crystal
X-ray analysis.
[5] a) V. Brun, M. Legraverend, D. S. Grierson, Tetrahedron Lett.
2001, 42, 8161–8164; b) V. Brun, M. Legraverend, D. S. Grier-
son, Tetrahedron Lett. 2001, 42, 8165–8167.
Single-Crystal X-ray Analysis of [Pt(cbdc)(dmso)(HL7)]·H2O
(7a·H2O): Diffraction data were collected with an XcaliburTM
2
[6] a) L. Szucˇová, Z. Trávnícˇek, I. Popa, J. Marek, Polyhedron
˝
diffractometer (Oxford Diffraction Ltd.) with Mo-Kα radiation
(Monochromator Enhance, Oxford Diffraction Ltd.) and a Sap-
phire2 CCD detector at 100 K. Data collection and reduction were
performed by using CrysAlis software.[20] The same software was
used for data correction of the absorption effect by the empirical
absorption correction using spherical harmonics as implemented in
the SCALE3 ABSPACK scaling algorithm. Both structures were
solved by direct methods using SHELXS-97 software and refined
on F2 using the full-matrix least-squares procedure (SHELXL-
97).[21] Non-hydrogen atoms were refined anisotropically. Hydrogen
atoms were located in a difference map and refined with the riding
model [C–H: 0.95 and 0.99 Å, N–H: 0.88 Å and Uiso(H) =
1.2Ueq(CH, CH2, NH) or 1.5Ueq(CH3)]. The molecular and crystal
structures were drawn using DIAMOND,[22] which was also used
to interpret the additional structural parameters. The crystal data
and structure refinement are summarized in Table 2.
ˇ
2008, 27, 2710–2720; b) P. Starha, Z. Trávnícˇek, I. Popa, J.
Inorg. Biochem., doi:10.1016/j.jinorgbio.2010.02.005, in press.
[7] S. Shamsuddin, M. S. Ali, K. H. Whitmire, A. R. Khokhar,
Polyhedron 2007, 26, 637–644.
[8] F. A. Allen, Acta Crystallogr., Sect. B: Struct. Sci. 2002, 58,
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Received: March 22, 2010
Published Online: June 15, 2010
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