Synthesis and structures of (SP-4-2)-diiodobis(2-hydroxyethylamine)platinum(II), (SP-4-2)-dichlorobis(2-hydroxyethylamine)platinum(II) and (OC-6-22)-bis(2-hydroxyethylamine)tetrachloroplatinum(IV) in the crystal

Article abstract of DOI:10.1016/S0020-1693(99)00175-9

(SP-4-2)-Diiodobis(2-hydroxyethylamine)platinum(II) was synthesized by reacting K₂PtCl₄ with KI in a first step and with ethanolamine in a second step. (SP-4-2)-dichlorobis(2-hydroxyethylamine)platinum(II) was prepared by removing the I^- ligands with AgNO₃ and by reaction of the activated complex (SP-4-2)-diaquabis(2-hydroxyethylamine)platinum(II) with an excess of KCl. (SP-4-2)-Dichlorobis(2-hydroxyethylamine)platinum(II) was oxidized with Cl₂ gas to obtain (OC-6-22)-bis(2-hydroxyethylamine)tetrachloroplatinum(IV). All compounds were characterized by elemental analysis and IR spectroscopy. The solubility in water at room temperature was measured with AAS. (SP-4-2)-Dichlorobis(2-hydroxyethylamine)platinum(II) was characterized by NMR spectroscopy. Crystal structures of all three complexes were determined.

Full text of DOI:10.1016/S0020-1693(99)00175-9

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Inorganica Chimica Acta 292 (1999) 127–130
Note
Synthesis and structures of
(SP-4-2)-diiodobis(2-hydroxyethylamine)platinum(II),
(SP-4-2)-dichlorobis(2-hydroxyethylamine)platinum(II) and
(OC-6-22)-bis(2-hydroxyethylamine)tetrachloroplatinum(IV)
in the crystal
Wolfgang Zimmermann a, Markus Galanski a, Bernhard K. Keppler a,*, Gerald Giester b
a Vienna Uni6ersity, Institute of Inorganic Chemistry, Waehringer Strasse 42, A-1090 Vienna, Austria
b Vienna Uni6ersity, Institute of Mineralogy and Crystallography, Althanstrasse 14, A-1090 Vienna, Austria
Received 11 December 1998; accepted 2 April 1999
Abstract
(SP-4-2)-Diiodobis(2-hydroxyethylamine)platinum(II) was synthesized by reacting K2PtCl4 with KI in a first step and with
ethanolamine in a second step. (SP-4-2)-dichlorobis(2-hydroxyethylamine)platinum(II) was prepared by removing the I− ligands
with AgNO3 and by reaction of the activated complex (SP-4-2)-diaquabis(2-hydroxyethylamine)platinum(II) with an excess of
KCl. (SP-4-2)-Dichlorobis(2-hydroxyethylamine)platinum(II) was oxidized with Cl2 gas to obtain (OC-6-22)-bis(2-hydroxyethyl-
amine)tetrachloroplatinum(IV). All compounds were characterized by elemental analysis and IR spectroscopy. The solubility in
water at room temperature was measured with AAS. (SP-4-2)-Dichlorobis(2-hydroxyethylamine)platinum(II) was characterized
by NMR spectroscopy. Crystal structures of all three complexes were determined. © 1999 Elsevier Science S.A. All rights reserved.
Keywords: Crystal structures; Platinum complexes; Amine complexes
lished to link the cancerostatic compounds to molecules
with carrier functions in a sense of drug targeting.
Linking molecules like maleimde–carboxylic acids [1]
can be connected to these complexes via acylation of the
O–H group [2]. These modified complexes are planed to
be tied to carrier molecules like antibodies [3] or macro-
molecules [4]. So an accumulation in tumor tissues
should be achieved to reduce side-effects of a platinum
based chemotherapy and to broaden the spectrum of
activity.
The antitumor activity of similar compounds like
(SP-4-2)-dichloro[N,N%-bis(2-hydroxyethyl)ethane-1,2-
diamine]platinum(II) and (OC - 6 - 22) - [N,N% - bis(2 - hy-
droxyethyl)ethane-1,2-diamine]tetrachloroplatinum(IV)
has been tested against murine leukemia L1210 and
P388 cells and at least the Pt(II) complex has shown
antitumor activity [5].
1. Introduction
Since the discovery of cisplatin and carboplatin as
cancerostatic compounds and the successful clinical ap-
plication of these substances, the investigation of related
platinum complexes has been of widespread interest.
The first intention of our research in this subject is to
find new compounds which show similar activity com-
pared to the complexes mentioned above but have an
additional functional group where they may be linked to
carrier substances.
A second aim of this project is to achieve an accumu-
lation of active complexes in specific tissues of the
organism. Therefore, a mechanism should be estab-
* Corresponding author. Tel.: +43-1-31367 2002; fax: +43-1-
3137 2040.
0020-1693/99/$ - see front matter © 1999 Elsevier Science S.A. All rights reserved.
PII: S0020-1693(99)00175-9

128
W. Zimmermann et al. / Inorganica Chimica Acta 292 (1999) 127–130
The use of primary amine ligands seems to be
The decomposition temperature was 127.7°C. Yield of
pure crystalline PtCl2(EA)2 was 42.3% (1.23 g) based on
AgNO3.
promising because phase II studies with Iproplatin
[(OC-6-33)-dichloro(dihydroxo)diisopropylamineplati-
num(IV) have indicated high activity in small-cell lung
cancer [6] and ovarian carcinoma [7].
(SP - 4 - 2) - Diiodobis(2 - hydroxyethylamine)plati-
num(II) [PtI2(EA)2], (SP-4-2)-dichlorobis(2-hydroxye-
thylamine)platinum(II) [PtCl2(EA)2] and (OC - 6 - 22) -
PtCl4(EA)2 was synthesized by bubbling Cl2 gas for
180 min through a freshly prepared solution 1. After 10
min a yellow solid began to precipitate. The solid was
filtered off, washed with cold water and ethanol and
was dried under reduced pressure. The decomposition
temperature was 181.0°C. Yield of pure product was
64.2% (2.19 g) based on AgNO3. Crystals of
PtCl4(EA)2·H2O were obtained by saturating an
aqueous solution at 50°C, adding a small amount of
crystals of a former preparation and storing the solu-
tion at 4°C for 10 days.
bis(2
-
hydroxyethylamine)tetrachloroplatinum(IV)
[PtCl4(EA)2] have been synthesized and characterized.
2. Experimental
The single crystal data (Table 2) were collected on a
Nonius Kappa CCD diffractometer at room tempera-
ture. For extracting intensities from CCD images the
program DENZO-SMN (Nonius) was used. Within that
procedure a correction of absorption was taken into
consideration. The measured intensities were corrected
for Lorentz and polarization effects. The crystal struc-
tures were determined by direct methods (SHELXS-97,
Sheldrick, 1997) [10] and subsequent Fourier and differ-
ence Fourier syntheses. Final structure parameters of
all three substances were obtained by full-matrix least
squares techniques on F2 (SHELXL-97, Sheldrick, 1997)
[11].
PtI2(EA)2 and PtCl2(EA)2 were prepared according
to methods for similar complexes reported in the litera-
ture [8,9] with various variations. For the preparation
of PtI2(EA)2 5.06 g (12.2 mmol) K2PtCl4 was dissolved
in 50 ml H2O and 20.23 g (122 mmol) KI were added.
The solution was stirred at 50°C for 30 min and the
color changed from red to brown. At room temperature
1.49 g (24.4 mmol) ethanolamine in 10 ml H2O were
added from a dropping funnel and PtI2(EA)2 slowly
began to precipitate with an orange color. The solid
was filtered off and washed with cold water and ethanol
and dried in vacuo. The decomposition temperature
was 121.8°C. Yield of pure PtI2(EA)2 was 85% (5.9 g)
based on K2PtCl4. Crystals were obtained by saturating
an aqueous solution at 50°C, adding a small amount of
crystals of a former preparation and storing the solu-
tion at 4°C for 3 days.
3. Results and discussion
For the preparation of PtCl2(EA)2 4.5 g (7.88 mmol)
PtI2(EA)2 were suspended in 100 ml H2O and 2.53 g
(14.9 mmol) AgNO3 were added. AgI began to precipi-
tate and the suspension was stirred overnight. The AgI
and non reacted PtI2(EA)2 were removed by filtration
The IR spectra of all three compounds show follow-
ing significant signals: 3450–3500 cm−1 w(O–H),
3100–3240 cm−1 w(N–H), 2850–2900 cm−1 w(C–H),
1560–1570 cm−1 l(N–H). The solubility of the com-
plexes in water at 25°C was measured using AAS. The
following solubility data (s) were obtained:
and
a
yellow solution (solution 1) containing
[Pt(H2O)2(EA)2]2+ was obtained. 5.87 g (78.73 mmol)
KCl were added and the solution was concentrated to
one-third of the original volume under reduced pressure
and 40°C. The solution was stored at 4°C and after 7
days yellow crystals (0.2–3 mm in diameter) were
filtered off and washed with cold water and ethanol.
s(PtI2(EA)2)=0.939
s(PtCl2(EA)2)=6.73
g
g
l−1 (1.65 mmol
l−1 (17.5 mmol
l
l
−1);
−1);
s(PtCl4(EA)2)=6.169 g l−1 (13.56 mmol l−1).
The elemental analysis data are in good agreement
with the actual findings (Table 1).
Table 1
Microanalyses
C
H
N
Cl
I
Pt
PtI2(EA)2
PtCl2(EA)2
PtCl4(EA)2
calculated (%)
found (%)
8.41
8.58
2.47
2.17
4.91
4.79
0
44.44
44.57
34.16
34.35
a
a
a
calculated (%)
found (%)
12.38
12.57
3.64
3.49
7.22
7.06
18.27
18.30
50.26
50.10
a
a
calculated (%)
found (%)
10.47
10.19
3.07
2.81
6.10
5.86
30.89
30.98
42.50
42.68
a Element was not analyzed.

W. Zimmermann et al. / Inorganica Chimica Acta 292 (1999) 127–130
129
Table 2
Data collection and processing parameters of PtI2(EA)2, PtCl2(EA)2 and PtCl4(EA)2·H2O a
PtI2(EA)2
PtCl2(EA)2
PtCl4(EA)2 · H2O
Molecular formula
Formula weight (g mol−1
Space group
C4H10N2O2I2Pt
567.02
P2(1)/n
9.439(2)
9.945(2)
12.505(3)
91.12(3)
1173.6(4)
4
C4H10N2O2Cl2Pt
384.12
Pbcn
13.894(3)
6.956(10)
10.035(2)
90
969.8(3)
4
2.658
C4H12N2O3Cl4Pt
473.04
C2/c
7.537(2)
12.983(3)
13.938(3)
103.58(3)
1325.7(5)
4
)
,
a (A)
,
b (A)
,
c (A)
i (°) [h=90°, k=90°]
3
,
V (A )
Formula units per cell
Density (g cm−3
)
3.232
2.390
,
Radiation (Mo Ka) (A)
2qmax (°)
0.71073
56.61
0.71073
56.46
0.71073
56.33
Unique data set
2695
1132
1376
Independent data, Fo\4|(Fo)
2057
1011
1336
Variables
143
80
98
−3
,
Largest difference peak and hole (e A
R1 [for Fo\4|(Fo)]
)
1.4/−2.2
0.0333
0.0737
0.974
2.25/−2.07
0.0308
0.0888
1.211
1.43/−1.84
0.0239
0.0624
1.090
wR2 [for all Fo2]
Goodness-of-fit
Exposure time/frame (s)
320
160
300
a Nonius Kappa CCD diffractometer, graphite monochromatized, Mo Ka-radiation, crystal-detector distance=28 mm, 180 frames with 2°€
scan range. Data processing with DENZO-SMN.
1
The complex PtCl2(EA)2 was characterized with H
and 13C NMR spectroscopy in a mixture of 0.4 ml D2O
and 0.2 ml DCl (20% in D2O) to suppress hydrolysis.
The following resonances were obtained and compared
with the free ligand: (R)-NH2CaHa 2CbHb 2OH.
PtCl2(EA)2: 1H spectrum in D2O: l=2.26 [t,
(J(HaHb)=5.27 Hz), 2H, Ha], 3.23 [t, (J(HaHb)=5.27
Hz), 2H, Hb]; 13C spectrum in D2O: l=47.96 [Ca],
around the platinum atom. The angular sum of the
equatorial atoms is 360.1° [N–Pt–N [90.0(2)°], N–Pt–
Cl [88.15(12)°] and Cl–Pt–Cl [93.80(6)°]]. The Pt–N
,
,
[2.042(4) A] and Pt–Cl [2.3151(11) A] distances are in a
reasonable range. Similar to PtI2(EA)2 there are two
intramolecular hydrogen bonds (N–H2···O) with a
,
donor acceptor contact of 2.982 A (N–O). Two weak
1
60.37 [Cb]. Free ligand (2-hydroxyethylamine): H spec-
trum in D2O: l=2.95 [t, (J(HaHb)=5.27 Hz), 2H, Ha],
3.62 [t, (J(Ha–Hb)=5.27 Hz), 2H, Hb]; 13C spectrum in
D2O: l=41.66 [Ca], 57.95 [Cb].
In the structure of PtI2(EA)2 in the crystal (Fig. 1)
the atoms around the platinum center are arranged in a
,
square-planar manner. The Pt–N1 [2.062(6) A], Pt–N2
,
,
[2.073(6) A], Pt–I1 [2.6024(8) A] and Pt–I2 [2.5930(7)
,
A] distances are in the normal range [12]. The angular
Fig. 1. Structure of PtI2(EA)2 in the crystal; H-atoms have been
calculated, only H atoms involved in hydrogen bonds are shown.
sum of the equatorial atoms is 360.01°. The I1–Pt–I2
angle is 93.93(3)° whereas all other angles [N1–Pt–N2
[88.4(3)°], N1–Pt–I2 [89.02(17)°] and N2–Pt–I1
[88.66(18)°]] are nearly 90° or smaller which is not
surprising due to the space filling properties of the I−
ligands. Two intramolecular hydrogen bonds have been
found (N1–H1B···O2 and N2–H2B···O1) with donor
,
acceptor contacts of 2.974 and 3.062 A, respectively.
An intermolecular hydrogen bond (O2–H2···O1) with a
,
donor acceptor contact of 2.766 A (O2–O1) has been
found.
The structure of PtCl2(EA)2 in the crystal (Fig. 2)
shows a square-planar arrangement of N and Cl
Fig. 2. Structure of PtCl2(EA)2 in the crystal; only H atoms involved
in hydrogen bonds are shown.

130
W. Zimmermann et al. / Inorganica Chimica Acta 292 (1999) 127–130
ture analysis. The stability especially of the Pt(IV)
complex allows further modifications. A few procedures
for linking carrier molecules via the O–H group have
been established [13].
5. Supplementary material
Atomic coordinates, equivalent isotropic displace-
ment parameters as well as bond lengths, angles and
anisotropic displacement parameters for PtI2(EA)2,
PtCl2(EA)2 and PtCl4(EA)2·H2O can be obtained from
the authors on request.
Fig. 3. Structure of PtCl4(EA)2·H2O in the crystal; only H atoms
involved in hydrogen bonds are shown.
intermolecular hydrogen bonds (O–H7···Cl) with donor
,
acceptor contacts of 3.180 A (O–Cl) have been found.
In Fig. 3 the structure of PtCl4(EA)2 · H2O in the
crystal is shown. The atoms around the platinum center
are arranged octahedrally. The two N and Cl2 atoms
show a square-planar arrangement around the platinum
atom. The angular sum of the equatorial atoms is
360.08° [N–Pt–N [93.6(2)°], N–Pt–Cl2 [87.39(13)°]
Acknowledgements
The support of the FWF (Fonds zur Fo¨rderung der
wissenschaftlichen Forschung) is gratefully acknowl-
edged. The support of Mrs R. Strobl in preparing the
manuscript is gratefully acknowledged.
,
and Cl2–Pt–Cl2 [91.70(9)°]]. The Pt–N [2.070(3) A]
,
and Pt–Cl [2.3228(13) A] distances are similar to
PtCl2(EA)2. The two remaining Cl1 atoms are axial to
the equatorial plane and the Cl1–Pt–Cl1 axis is nearly
linear [Cl1–Pt–Cl1 [178.70(4)°]]. The crystals contain
one molecule of water per PtCl4(EA)2 complex. The
H2O is connected to the complex via two hydrogen
bonds (N–H2···O2) with a donor acceptor contact of
References
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2.886 A (N–O2). The H2O molecule is located in the
equatorial plane between the N-atoms. There are addi-
tional intermolecular hydrogen bonds of each
PtCl4(EA)2 unit to two neighboring complexes (N–
,
H1···O1) with a donor acceptor distance of 2.90 A
(N–O1).
[8] S.C. Dhara, Indian J. Chem. 8 (1970) 193.
[9] A.R. Khokhar, Y. Deng, S. Al-Baker, M. Yoshida, Z.H. Siddik,
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4. Conclusion
(SP - 4 - 2) - Diiodobis(2 - hydroxyethylamine)plati-
num-(II) [PtI2(EA)2], (SP-4-2)-dichlorobis(2-hydroxye-
thylamine)platinum(II) [PtCl2(EA)2] and (OC-6-22)-
[10] G.M. Sheldrick, SHELXS-97, a program for the solution of crystal
structures, University of Go¨ttingen, Germany, 1997.
[11] G.M. Sheldrick, SHELXL-97, a program for crystal structure
refinement, University of Go¨ttingen, Germany, 1997.
[12] M. Galanski, B.K. Keppler, Inorg. Chim. Acta 265 (1997) 271.
[13] W. Zimmermann, M. Galanski, B.K. Keppler, unpublished re-
sults.
bis(2
-
hydroxyethylamine)tetrachloroplatinum(IV)
[PtCl4(EA)2] have been synthesized and characterized
with several spectroscopic techniques and crystal struc-
.