Synthesis and structure of new trichloroplatinum π-complexes: Reactivity of nitrogen lone-pair versus C-C double bond π-electrons in ligands, effect of steric hindrance

Article abstract of DOI:10.1016/j.jorganchem.2005.07.095

Two trichloroplatinum π-complexes and a diammonium tetrachloroplatinate (II) salt have been unexpectedly isolated during the attempt to synthesize the corresponding cisplatinum square-planar complexes of tertiary cyclohexane 1,4-diamines. All three compounds have been physically and spectroscopically characterized, including X-ray diffraction analysis in two of the three compounds. The formation of the π-complexes instead of the diamino cis-platinum complexes could be explained as due to the steric hindrance exerted by methyl groups on the tertiary amines. So, the π-electrons of the CC double bond are more available than the electron lone pair of nitrogen atom from the amino groups. When the π-electrons of the CC from the molecule of ligand were made unavailable by transforming the cyclohexene subunit into a benzene aromatic ring, no cis-diamino dichloro platinum(II) complex nor trichloroplatinum-complexes were isolated but the corresponding tetrachloroplatinate(II) diammonium salt of the 1,4-diamino ligand.

Full text of DOI:10.1016/j.jorganchem.2005.07.095

Journal of Organometallic Chemistry 690 (2005) 4856–4866
www.elsevier.com/locate/jorganchem
Synthesis and structure of new trichloroplatinum
p-complexes: Reactivity of nitrogen lone-pair versus C–C
double bond p-electrons in ligands, effect of steric hindrance
a,b
a,
b,
*
´
Marina Gay , Angel M. Montana *, Virtudes Moreno
,
˜
c
c
`
Merce Font-Bardia , Xavier Solans
a
`
Departamento de Quı´mica Orga´nica, Universidad de Barcelona, Facultad de Quı´mica, c/Martı´ i Franques 1-11, 08028, Barcelona, Spain
b
`
Departamento de Quı´mica Inorga´nica, Universidad de Barcelona, Facultad de Quı´mica, c/Martı´ i Franques 1-11, 08028, Barcelona, Spain
c
Departamento de Cristalografı´a y Depo´sitos Minerales, Universidad de Barcelona, c/Martı´ i Franque´s 1-11, 08028-Barcelona, Spain
Received 9 May 2005; accepted 21 July 2005
Available online 2 September 2005
Abstract
Two trichloroplatinum p-complexes and a diammonium tetrachloroplatinate (II) salt have been unexpectedly isolated during the
attempt to synthesize the corresponding cisplatinum square-planar complexes of tertiary cyclohexane 1,4-diamines. All three com-
pounds have been physically and spectroscopically characterized, including X-ray diffraction analysis in two of the three com-
pounds. The formation of the p-complexes instead of the diamino cis-platinum complexes could be explained as due to the steric
hindrance exerted by methyl groups on the tertiary amines. So, the p-electrons of the C@C double bond are more available than
the electron lone pair of nitrogen atom from the amino groups. When the p-electrons of the C@C from the molecule of ligand were
made unavailable by transforming the cyclohexene subunit into a benzene aromatic ring, no cis-diamino dichloro platinum(II)
complex nor trichloroplatinum-complexes were isolated but the corresponding tetrachloroplatinate(II) diammonium salt of the 1,4-
diamino ligand.
ꢀ 2005 Elsevier B.V. All rights reserved.
Keywords: Platinum; p-Complexes; Steric hindrance; X-ray structures
1. Introduction
platinocycles with a 1,4-diamino subunit. In this library
of diamines we have included primary, secondary and
tertiary amines in order to evaluate their different coordi-
nation ability towards platinum and also to know by
structure-activity relationship studies (SAR) [1], the
influence of the bulkiness and steric hindrance of the di-
amino groups of the chelating arms of ligands on the
cytotoxic activity. Here, we describe the reactivity of ter-
tiary amines (Fig. 1) and the ability of these ligands to
chelate Pt(II).
In the development of our research project on the ra-
tional design, synthesis and evaluation of anticancer
activity of square-planar cis-platinum complexes, we
have prepared a library of diamino ligands with a basic
skeleton of 1,2-bis(aminomethyl)-cyclohexane (Fig. 1),
with the purpose of preparing seven membered diamino-
*
Corresponding authors. Tel.: +34 93 402 16 81; fax: +34 93 339 78
The aforementioned series of diamino ligands has
been designed in order to perform a comparative cyt-
oregulatory study versus cisplatin [2] and oxaliplatin
[3] (Fig. 2).
´
78 (A.M. Montana); tel.: +34 93 402 19 14; fax: +34 93 490 77 25
˜
(V. Moreno).
´
E-mail addresses: angel.montana@ub.edu (A.M. Montana), virtu-
des.moreno@qi.ub.es (V. Moreno).
˜
0022-328X/$ - see front matter ꢀ 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2005.07.095

M. Gay et al. / Journal of Organometallic Chemistry 690 (2005) 4856–4866
4857
NMe2
OH
NMe2
NMe2
NMe2
2
4
1
3
NMe2
NMe2
NMe2
NMe2
Fig. 1. Studied ligands having tertiary amino groups as chelating entities.
O
H2
N
isolated, resulting from unusual rearrangements (which
involved hydride migration) [10] or organoplatinum
complexes as 5 and 6, which are described here. We think
that this behaviour could be due to the steric hindrance
exerted by the methyl groups on the electron lone pair
of the nitrogen atom in the amino groups of ligands, so
the bulky platinum atom cannot reach it. For this last
reason, platinum atom coordinates the ligand by the p-
electrons of the carbon-carbon double bond of the cyclo-
hexene system, forming trichloroplatinum complexes
[11] of the type of ZeiseÕs salt (see Scheme 1) [12].
Complexation reactions were carried out starting
from ligand 2 in order to evaluate the possibility to form
platinum stable six-membered platinocycles involving
the OH group and one of the NMe2 groups (see Scheme
2), or otherwise seven-membered 1,4-diamino metallacy-
cles but, instead of these expected compounds, the for-
mation of a p-complex 6 was observed.
Finally, in order to force the complexation by the
dimethylamino groups, the aromatic ligand 3 was syn-
thesized and, on the other hand, the cyclohexene ring
of ligand 1 was transformed into the saturated cyclohex-
ane ring of ligand 4 by catalytic hydrogenation.
When working with the aromatic diamino ligand 3 we
did not obtain a diamino cisplatinum complex nor an
organoplatinum p-complex but the diammonium tetra-
chloroplatinate salt 7 (Scheme 3), clearly identified by
X-ray diffraction analysis.
O
H3N
H3N
Cl
Cl
Pt
Pt
O
N
O
H2
Cisplatin
Oxaliplatin
Fig. 2. Structures of cisplatin and oxaliplatin used actually in
oncological therapeutics.
cis-[(R,R)-cyclohexane-1,2-diamine]oxalatoplatinum(II),
which represents a third generation of platinum drugs
that has been approved in many countries of Asia, Latin
America and Europe for clinical use in oncology [1,4,5].
Oxaliplatin has shown a wider spectrum of activity
than cisplatin, and it was found to be active in several
tumour cell lines with acquired or intrinsic resistance
to cisplatin or carboplatin. This different behaviour is
not only due to a different degree of interaction with
DNA. Oxaliplatin acts as an alkylating agent, inducing
mainly the formation of platinated intra-strand adducts
between two adjacent guanine bases or two adjacent
guanine adenine bases of DNA [6]. Moreover, the wider
spectrum of activity of oxaliplatin compared to that of
parent compound may be attributed to differences in
mechanisms of resistance, because of their different
interaction with the proteins that recognize damages
and lesions in DNA [7].
On the other hand, when reacting the saturated com-
pound 4, the expected cisplatinum complex was not ob-
tained but a p-coordinated product 8 was formed,
2. Results and discussion
NMe2
Cl
In this context, series of primary, secondary and ter-
tiary amines from our library of ligands were reacted, un-
der several conditions [8], with PtCl2, K2 PtCl4, PtI2, etc.,
in order to obtain the corresponding seven-membered
cisplatinum 1,4-diaminometallacycles. In the case of li-
gands having primary and secondary amino groups, we
obtained the cisplatinum complexes as expected, with
moderate to good yields [9], but when using tertiary
amines as starting materials no cisplatinum coordination
complexes were formed. Instead of the expected com-
plexes, depending on both the structure of ligand and
the reaction conditions, p-coordination products were
Pt
NMe2
Cl
NMe2
+
NMe2
Cl
1
NHMe2
Cl-
Cl Pt
Cl
NHMe2
5
Scheme 1. Formation of the trichloroplatinum p-complex 5 from
ligand 1.

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M. Gay et al. / Journal of Organometallic Chemistry 690 (2005) 4856–4866
OH
NMe2
2
NMe2
Cl
Cl
N
Pt
HO
OH
OH
+
NMe
Pt
Cl
Cl Pt
Cl
2 Cl
NMe2
[PtCl4]2-
Cl
NMe2
NMe2
2
NHMe2
Not formed
Not formed
6
Isolated product
Scheme 2. Chimioselective formation of the complex 6 from ligand 2.
NHMe
DNA incubated with the complexes in order to evaluate
de degree or intensity of the interaction complex–DNA,
by counting the statistical frequency of formation of
nodules, supercoiled forms and scissions of DNA
chains. The second level of biological evaluation of the
isolated compounds is the in vitro evaluation of their
cytotoxic activity against cancer cell lines of several
types, resistant and non-resistant to cisplatin (the stan-
dard platinum drug used in oncological therapeutics).
2Cl
Pt
NMe2
NMe2
Cl
NHMe2
2+
NHMe2
[PtCl4]2-
3
NHMe2
7
Scheme 3. Structure of the reaction product of the aromatic diamino
ligand 3.
2.1. Synthesis of diamines
Synthesis of ligand 1 was carried out starting from
commercially available cis-3,3,6,6-tetrahydrophthalic
anhydride [13]. Hydrolysis of anhydride 9 led to cis-
3,3,6,6-tetrahydrophtalic acid (10), whose amidation
was easily accomplished by refluxing it with HMPT in
benzene. Diamine 1 was obtained by reduction of dia-
mide 11 with LiAlH4. The synthetic pathway used to
prepare ligand 1 and the yields of every step are shown
in Scheme 5.
Ligand 3 was obtained by the same synthetic method-
ology used to prepare ligand 1, but starting from com-
mercially available phthalic acid 12, as it is illustrated
on Scheme 6.
resulting from an unusual molecular rearrangement
(involving NMe2 elimination followed by hydride
migration) [10] (see Scheme 4).
Studies to evaluate the biological activity of the com-
pounds described here are in progress at the present mo-
ment in our laboratories. These studies are being carried
out at two levels. A first level includes the studies of
interaction of complexes with DNA (normally by an
alkylation mechanism of DNA bases) by using several
techniques: (a) circular dichroism (in order to study
the modification of the secondary structure of DNA);
(b) electrophoresis on agarose gel (in order to evaluate
the modification of the tertiary structure of DNA);
and (c) atomic forces microscopy (AFM) to observe
Ligand 2 was obtained following a different synthetic
pathway (see Scheme 7). First, a Diels–Alder reaction
Cl
CH2Cl2
rt.,15days
NMe2
Pt
+P tCl2
NMe2
Cl
NMe2
4
8
Y= 58%
Scheme 4. Formation of organoplatinum complex 8 via NMe2 elimination and hydride shift of the parent ligand 4.

M. Gay et al. / Journal of Organometallic Chemistry 690 (2005) 4856–4866
4859
O
CONM e
CONM e
COOH
COOH
H2O/HCl
rt,16 h
2
2
LiAl H4
HMPT
NMe
NMe
2
2
O
N2,benzene
anh.,
N2,E t2Oanh.,
reflux, 1h
O
9
reflux, 30 min
10
C=100%
Y=100%
11
C=100%
=85%
1
C=100%
=82%
Y
Y
Scheme 5. Synthetic pathway of ligand 1.
between 1-acetoxy-1,3-butadiene and fumaryl chloride
was carried out at room temperature to obtain, in good
yield, cycloadduct 16 as a major diastereoisomer, which
was isolated and purified by column chromatography.
Next, the reaction with dimethylamine led to diamide
17. Finally, the desired ligand 2 was synthesized by
reduction of diamide 17 with LiAlH4. The characteriza-
tion of each intermediate, as well as the final ligands,
was performed by 1H NMR, 13C NMR, IR, MS and ele-
mental analysis.
of the platinum complexes from ligands 1 to 4. Thus,
when ligands 1 and 2 reacted with K2PtCl4 under acidic
conditions, coordination to platinum took place by the
double bond, and cationic complexes 5 and 6 were,
respectively, obtained, instead of the usual seven-mem-
bered ring chelates, which would result from the coordi-
nation of platinum atom to both nitrogen atoms of the
amino groups (see Schemes 8 and 9). In contrast, when
reactions were carried out under neutral conditions a
mixture of polymeric products was obtained, but not
the desired platinum complexes.
2.2. Synthesis of platinum(II) complexes
Complexes 5 and 6 were studied, in solid state, by ele-
mental analysis, mass spectrometry and FT-IR spectros-
copy, and in solution, by high field 1H NMR
spectroscopy. Moreover, the structure of complex 5
Several assays were performed, under different reac-
tion conditions, in order to optimize the preparation
CONMe2
COOH
HMPT
LiAlH4
NMe2
NMe2
N2,benzene anh.,
reflux,30min
N2,Et2O,
reflux,1h.
CONMe2
COOH
3
13
C=100%
Y=100%
12
C=100%
Y=78%
Scheme 6. Synthetic pathway of ligand 3.
OAc
OAc
OAc
OH
COCl
COCl
CONMe2
LiAlH4
NMe2
NMe2
HNMe2
+
N2,T HF anh,
0ºC, (10m in);
rt (1h)
N2, Et2O
N2, Et2O
reflux,1 h
ClOC
RT,16h
COCl
CONMe2
15
14
16
17
2
(major)
Y=85%
Y=90%
Y=86%
Scheme 7. Synthetic pathway of ligand 2.
+
NHMe2
Cl
H2O/HCl(0.1M)
NMe2
NMe2
Cl-
Cl Pt
Cl
+ K2PtCl4
rt,16h.
NHMe2
1
5
Y= 49%
Scheme 8. Synthetic pathway of complex 5.

4860
M. Gay et al. / Journal of Organometallic Chemistry 690 (2005) 4856–4866
+
OH
NHMe2
OH
Cl
Pt
Cl
H2O/HCl( 0.1M )
rt, 4 days
NMe2
NMe2
2-
+K2PtCl4
Cl
PtCl4
NHMe2
2
2
6
Y=18%
Scheme 9. Synthetic pathway of complex 6.
was confirmed by X-ray diffraction analysis on single
crystals. A complementary conductivity study of the
complex 6 was made to find out its counter-ion nature.
Comparing conductivity of compound 6 (138.6 Xꢀ1
cm2 molꢀ1) to bibliographic data [14] it can be assumed
that compound 6 is an electrolyte with an ion charge ra-
tio 2:1 (see Table 1).
Formation of these two unusual complexes could be
attributed to the acidic conditions of the reaction med-
ium and to the steric hindrance exerted by the methyl
groups of the NMe2 subunits.
Complex 5 is been evaluated as potential cytostatic
agent. It has a peculiar structure that could facilitate
the formation of DNA adducts, which is the main target
of our platinum compounds. This is thought on the ba-
sis that carbon–platinum bond has an enhanced trans ef-
fect and, on the other hand, because this compound has
three labile ligands, and consequently three possible sites
to coordinate to DNA.
In order to force the coordination of platinum atom
to the amino groups, the aromatic ligand 3 was prepared
and reacted with platinum reagents under different con-
ditions, but in any case coordination to platinum atom
took place, only the corresponding salt 7 was isolated
(Scheme 10). This new product was characterized by
1H NMR, FT-IR, MS and elemental analysis and its
structure was confirmed by X-ray diffraction analysis
on single crystals.
2.3. Structure determination of compounds 5 and 7 by X-
ray crystallography
2.3.1. Compound 5
Details about structure determination are given in
Section 3. Crystallographic data and selected bond dis-
tances and angles are quoted in Tables 2 and 3. In
Fig. 3, an ORTEP view of the X-ray crystal structure
of 5 is shown. This molecular representation shows a
cationic complex with chloride as a counter-ion. Plati-
num(II) atom has a square planar coordination geom-
etry. The CH@CH group, and consequently the ligand,
is located perpendicular to the plane containing plati-
num and chlorine atoms. Angles of the CH@CH moi-
ety indicate that the double bond0 geometry is not
0
˚
exactly coplanar. Moreover, C3 –C4 length is 1.39 A,
higher than the length expected for a non-coordinated
olefin. These two experimental facts are consistent with
a back-donation effect. Finally, ammonium groups are
located separately to minimize both, the charge repul-
sion between the N+ centres and the steric repulsion
between methyl groups.
2.3.2. Compound 7
Details about structure determination are given in
Section 3 and also in the supplementary material. Crys-
tallographic data and selected bond distances and angles
are quoted in Tables 2 and 4. In Fig. 4 an ORTEP view
of the X-ray crystal structure of 7 is shown. In this com-
pound ammonium groups are also located separately,
far away from each other respect to the planar benzene
ring in order to minimize both, charge repulsion be-
tween the positively charged nitrogen atoms and the ste-
ric repulsion between methyl groups.
Table 1
Conductivity of compound 6, using DMF as a solvent; KM = k/c
Concentration,
c (M)
Conductivity,
k (lS cmꢀ1
)
KM (Xꢀ1 cm2 molꢀ1
)
1.053 · 10ꢀ3
145.9
138.6
2+
NHMe2
NMe2
NMe2
H2O/HCl( 0.1M )
rt, 2h
[PtCl4]2-
+
K2PtCl4
NHMe2
7
3
Y=76%
Scheme 10. Synthetic pathway of complex 7.

M. Gay et al. / Journal of Organometallic Chemistry 690 (2005) 4856–4866
4861
Table 2
75 MHz and were referenced to the 77.0 ppm resonance
of chloroform. Mass spectra were run on a Fisons VG
Quattro triple quadrupole analyser in the 1800–200
m/z range, using MeCN–H2O as solvent under electro-
spray (ESP-MS), or FAB(+) mode on a Hewlett–Pack-
ard 5890 mass spectrometer using a chemical ionisation
technique (conditions are specified for each case). Melt-
ing points were measured on a Galenkamp and on a Stu-
art Scientific SMP3 apparatuses. Conductivity was
measured on a CRISON Micro CM 2200 equipment.
Crystal data for compounds 5 and 7
Complex
5
7
Molecular formula
Molecular weight (g/mol) 533.22
T (K)
k(Mo Ka) (A)
C12H24Cl4N2Pt
C12H22Cl4N2Pt
531.21
293(2)
0.71069
Triclinic
293(2)
˚
0.71069
Orthorhombic
P212121
10.8650(10)
12.1680(10)
13.2060(10)
90
90
90
1745.9(3)
4
2.029
Crystallographic system
Space group
ꢀ
P1
˚
a (A)
7.372(9)
10.261(5)
12.3310(10)
68.5210(10)
86.8400(10)
82.8590(10)
861.2(11)
2
2.048
8.756
508
2.23–31.71
ꢀ9 6 h 6 9,
ꢀ13 6 k 6 14,
0 6 l 6 18
6209
˚
b (A)
˚
c (A)
a (ꢁ)
b (ꢁ)
c (ꢁ)
3.2. Synthesis of cis-cyclohex-4-ene-1,2-dicarboxylic acid
(10)
3
˚
V (A )
Z
3,3,6,6-Tetrahydrophthalic anhydride (9) (1.178 g,
7.09 mmol) was dissolved in acetic acid (2 mL) and
water (10 mL). Then, 0.25mL of hydrochloric acid was
added and the mixture was stirred at room temperature
overnight. The reaction mixture was concentrated to
dryness and pure dicarboxylic acid 10 was obtained in
quantitative yield (1.198 g). mp = 169–170 ꢁC. Anal.
Found: C, 56.51; H, 6.01. Calc. for C8H10O4: C, 56.47;
H, 5.92%. IR (cmꢀ1): 3300–2300 (COO–H), 1680
Dcalc (Mg mꢀ3
)
l(mmꢀ1
F(000)
)
8.638
1024
H Range (ꢁ)
h, k, l Ranges
2.51–31.60
0 6 h 6 13,
0 6 k 6 16,
0 6 l 6 19
11617
Number of
registered
reflections
Number of
independent
reflections
Rint on F
Method of
refinement
Number of data
Number of
1
(C@O). H NMR (200 MHz, CDCl3, d in ppm): 2.36–
2587
3949
2.69 (4H, m, H3, H6), 3.10 (2H, dd, J1 = 5.1 Hz,
J2 = 5.1 Hz, H1, H2), 5.69 (2H, s, H4, H5); 13C NMR
(50 MHz, CD3OD, d in ppm): 23.2 (C3, C6), 36.8 (C1,
C2), 122.3 (C4, C5), 173.3 (C10, C100); MS (70 eV,
DIP–CI–NH3, m/z, %): 205 (10) [M + N2H7]+, 188
(100) [M + NH4]+, 171 (3) [M + H]+.
0.0490
Full-matrix
least-squares on F2 least-squares on F2
2587
173
0.0258
Full-matrix
3949
188
parameters
Goodness-of-fit on F2
R final [I > 2rI]
1.089
1.059
3.3. Synthesis of cis-N,N,N0,N0-tetramethyl-4-
cyclohexene-1,2-dicarboxamide (11)
R1 = 0.0377,
wR2 = 0.0889
R1 = 0.0464,
wR2 = 0.1008
0.847 and ꢀ0.877
R1 = 0.0404,
wR2 = 0.1016
R1 = 0.0404,
wR2 = 0.1016
0.797 andꢀ0.551
R index (all data)
To a suspension of 10 (300 mg, 1.765 mmol) in anhy-
drous benzene (2 mL) hexamethylphosphorous triamide
(0.32 mL, 1.765 mmol) was added and the reaction mix-
ture was maintained under reflux for 30 min. The result-
ing cloudy solution was allowed to cool to room
temperature and a saturated aqueous solution of NaH-
CO3 (2 mL) was added. The layers were separated and
the aqueous layer was extracted with methylene chloride
(4 · 2 mL). The organic phases were combined together,
dried over anhydrous MgSO4 and concentrated to dry-
ness, affording a colourless oil that rapidly solidified to
form a white solid. The solid was washed with hexane
and purified by crystallization from ether at ꢀ78 ꢁC
(Yield: 391 mg, 88%). mp = 65–70 ꢁC. Anal. Found:
C, 64.31; H, 8.95; N, 12.45. Calc. for C12H20N4O2: C,
Largest difference
peak and hole (e A
ꢀ3
˚
)
3. Experimental
3.1. Materials and methods
All reactants were purchased from commercial sup-
pliers and used without further purification. Reactions
that required an inert atmosphere were conducted under
dry nitrogen and the glassware was oven dried (120 ꢁC).
THF, Et2O and benzene were distilled from sodium/
benzofenone prior to use. Elemental analyses (C, H,
N, S) were carried out on a Carlo Erba EA1108. Infra-
red spectra were recorded on a FT-IR NICOLET 510
1
64.26; H, 8.99; N, 12.49%. IR (cmꢀ1): 1645 (C@O). H
spectrometer in a 4000–400 cmꢀ1 range. H NMR spec-
NMR (200 MHz, CDCl3, d in ppm): 2.03–2.12 (2H,
m, H3, H6), 2.31–2.47 (2H, m, H3, H6), 2.73 (3H, s,
H1000 or H1iv or H1v or H1vi), 2.75 (3H, s, H1000 or H1iv
or H1v or H1vi), 2.85 (3H, s, H1000 or H1iv or H1v or
H1vi), 2.87 (3H, s, H1000 or H1iv or H1v or H1vi), 2.85–
2.92 (2H, m, H1, H2), 5.52–5.55 (2H, m, H4, H5); 13C
1
tra were obtained on a Varian Gemini-200, Varian
Unity-300 plus or Varian VXR-500, using CDCl3 or
DMSO-d6 as solvents and chemical shifts are given in
ppm relative to tetramethylesilane (TMS). 13C NMR
and DEPT experiments were recorded at 50 MHz or

4862
M. Gay et al. / Journal of Organometallic Chemistry 690 (2005) 4856–4866
Table 3
˚
Selected bond lengths (A) and angles (ꢁ) for compound 5
˚
Bond lengths (A)
Bond angles (ꢁ)
Pt–C(40)
2.167(10)
2.180(10)
2.298(3)
2.304(3)
2.316(3)
1.484(13)
1.49(2)
1.494(13)
1.476(13)
1.48(2)
1.494(13)
1.390(13)
1.513(13)
1.528(13)
1.545(12)
1.519(13)
1.531(14)
1.55(2)
C(40)–Pt–C(30)
37.3(3)
93.4(3)
98.5(3)
89.2(3)
85.4(3)
176.10(12)
163.5(3)
158.4(2)
87.94(13)
88.74(12)
70.8(6)
Pt–C(30)
C(40)–Pt–Cl(3)
Pt–Cl(3)
Pt–Cl(2)
Pt–Cl(4)
C(30)–Pt–Cl(3)
C(40)–Pt–Cl(2)
C(30)–Pt–Cl(2)
N(1)–C(1000)
N(1)–C(1iv)
N(1)–C(1)
N(2)–C(1v)
N(1)–C(1vi)
N(1)–C(100)
C(30)–C(40)
C(30)–C(20)
C(40)–C(50)
C(50)–C(600)
C(10)–C(6 )
C(60)–C(100)
C(10)–C(1)
C(10)–C(20)
Cl(3)–Pt–Cl(2)
C(40)–Pt–Cl(4)
C(30)–Pt–Cl(4)
Cl(3)–Pt–Cl(4)
Cl(2)–Pt–Cl(4)
C(40)–C(30)–Pt
C(20)–C(30)–Pt
120.0(7)
71.9(6)
C(300)–C(40)–Pt
C(5 )–C(40)–Pt
120.9(8)
110.2(9)
115.8(8)
111.1(8)
106.4(5)
106.4(6)
106.4(5)
112.3(9)
109.3(9)
112.3(8)
121.4(8)
113.8(8)
112.1(8)
121.5(8)
111.9(8)
112.1(7)
112.8(7)
106.4(8)
111.9(8)
109.5(7)
112.8(9)
113.5(7)
C(1000)–N(1)–C(1iv)
C(1000)–N(1)–C(1)
C(1)–N(1)–C(1iv)
C(1000) N(1)–H(N1)
C(1iv)–N(1)–H(N1)
C(1)–N(1) H (N1)
C(1v)–N(2)–C(1vi)
C(1v)–N(2)–C(100)
C(1vi)–N(2)–C(100)
C(40)–C(30)–C(20)
C(40)–C(50)–C(60)
C(10)–C(60)–C(1000)
C(30)–C(40)–C(50)
C(1)–C(10)-C-(20)
C(100)–C(60)–C(50)
C(60)–C(10)–C(1)
C(60)–C(10)–C(20)
C(1)–C(10)–C(20)
C(30)–C(20)–C(10)
N(2)–C(100)–C(60)
N(1)–C(1)–C(10)
1.552(12)
Fig. 3. ORTEP view of molecule 5.
Table 4
Selected bond lengths and angles for compound 7
˚
Bond lengths (A)
Bond angles (ꢁ)
Pt–Cl3
Pt–Cl4
Pt–Cl2
Pt–Cl1
2.2935(13)
2.2962(14)
2.3032(15)
2.3139(15)
1.473(7)
1.490(6)
1.517(8)
1.484(7)
1.493(7)
1.530(7)
1.478(6)
1.385(7)
1.434(6)
1.371(8)
1.395(8)
1.320(8)
1.409(6)
1.493(6)
Cl3–Pt–Cl4
Cl3–Pt–Cl2
Cl4–Pt–Cl2
Cl3–Pt–Cl1
Cl4–Pt–Cl1
Cl2–Pt–Cl1
C1000–N1–C1
C1000–N1–Civ
C1–N1–C1000
C1vi–N2–C1v
C1vi–N2–C100
C1v–N2–C100
C60–C10–C20
C60–C10–C1
C20–C10–C1
C50–C60–C10
C10–C1–N1
C60–C50–C40
C40–C50–C60
C40–C30–C200
C30–C20–C100
C30–C200–C1
C10–C2 –C100
C20–C100–N2
179.20(4)
89.17(6)
90.15(6)
90.30(6)
90.39(6)
179.11(4)
110.5(5)
110.5(5)
111.0(4)
112.3(5)
109.8(5)
112.3(5)
116.9(4)
119.5(4)
123.5(4)
122.7(5)
112.5(4)
119.6(5)
119.8(5)
122.8(5)
118.3(4)
117.8(4)
123.9(4)
112.5(4)
N1–C1000
N1–C1
N1–C1iv
N2–C1vi
N2–C1v
N2–C100
C1–C10
C10–C60
C10–C20
C60–C50
C50–C40
C40–C30
C30–C20
C20–C100
NMR (50 MHz, CD3 OD, d in ppm): 26.5 (C3, C6), 35.5
(C1iv, C1vi), 36.0 (C1, C2), 37.4 (C1000, C1v), 124.9 (C4,
C5), 174.0 (C10, C100); MS (70 eV, DIP–CI–NH3, m/z,
%) 225 (100) [M + H]+, 180 (12) [M ꢀ NMe2]+, 171
(3) [M + H]+.
3.4. Synthesis of cis-N,N,N0,N0-tetramethyl-4-
cyclohexene-1,2-bis (dimethylamine) (1)
To a suspension of lithium aluminium hydride (70
mg, 1.837 mmol) in anhydrous ether (2 mL) a solution
of diamide 11 (246 mg, 1.531 mmol) in dry tetrahydro-
furan (1 mL) was added. The mixture was refluxed for
1 h and then it was quenched by a cautious successive
addition of water (0.12 mL), 15% NaOH aqueous solu-
tion (0.12 mL) and water again (0.38 mL). A fine white
solid precipitated, which was filtered off, washed with
ether and discarded. The liquid filtrate was concentrated
to dryness, obtaining a colourless oil (Yield: 300 mg,
82%). Anal. Found: C, 73.28; H, 12.36; N, 14.20. Calc.
for C12H24N2: C, 73.14; H, 12.32; N, 14.27%. IR
(cmꢀ1): 3020, 2970, 2940, 2900, 2860, 2820, 2770,
1
1650, 1095; H NMR (200 MHz, CDCl3, d in ppm):
2.20 (12H, s, H1000, H1iv, H1v, H1vi), 1.87–2.30 (10H,
m, H10, H20, H50, H60, H1, H100), 5.64 (2H, s, H30,
H40); 13C NMR (50 MHz, CD3OD, d in ppm): 28.3

M. Gay et al. / Journal of Organometallic Chemistry 690 (2005) 4856–4866
4863
3.6. Synthesis of N,N-dimethyl-1-[2-(N,N-dimethyl-
amino-methyl)-phenyl]-methylamine (3)
To a suspension of lithium aluminium hydride (457
mg, 12.03 mmol) in anhydrous ether (10 mL) a solution
of diamide 13 (1323 mg, 6.01 mmol) in dry tetrahydrofu-
ran (10 mL) was added. The mixture was refluxed for 1 h
and then it was quenched by successive addition of water
(0.9 mL), 15% (w/w) aqueous NaOH solution (0.9 mL)
and water (2.7 mL). A white precipitate was formed,
which was filtered off, washed with ether and discarded.
The filtrate was concentrated to dryness resulting a col-
ourless oil (Yield: 900 mg, 78%). Anal. Found: C,
75.01; H, 10.39; N, 14.53. Calc. for C12H20N2: C,
74.95; H, 10.48; N, 14.57%. IR (cmꢀ1): 3066, 3023,
2973, 2942, 2855, 2815, 2765, 1653, 1458, 1366, 1308,
1022; 1H NMR (200 MHz, CDCl3, d in ppm): 2.23
(12H, s, H1000, H1iv, H1v, H1vi), 3.51 (4H, s, H1, H100),
7.19–7.34 (4H, m, H30, H40, H50, H60); 13C NMR (50
MHz, CD3OD, d in ppm): 45.6 (C100, C1iv, C1v, C1vi),
61.2 (C1, C100), 126.7 (C40, C50), 130.1 (C30, C60), 137.9
(C10, C20); MS (70 eV, DIP–CI–NH3, m/z, %): 162 (5)
[M ꢀ 2Me], 193 (100) [M + H+], 194 (14) [M + 2H+].
3.7. Synthesis of (1R*,5S*,6R*)-5,6-bis-
(chlorocarbonyl)-cyclohex-2-en-1-yl acetate (16) [15]
Fig. 4. ORTEP view of molecule 7.
(C20, C50), 33.0 (C10, C60), 46.0 (C1000 C1iv, C1v, C1vi),
60.6 (C1, C100), 125.9 (C30, C40); MS (70 eV, DIP–CI–
NH3, m/z, %): 214 (3) [M + NH4]+, 197 (33)
[M + H]+, 184 (100) [M ꢀ Me]+.
A solution of 1-acetoxy-1,3-butadiene 14 (0.77 mL,
6.54 mmol) in anhydrous ether (2 mL) was added to a
solution of fumaryl chloride 15 (0.71 mL, 6.54 mmol)
in anhydrous ether (2 mL). Both solutions were previ-
ously cooled at 0 ꢁC before mixing. After 1 h the reac-
tion mixture was allowed to reach room temperature
and it was maintained under these conditions for 16 h.
The mixture was concentrated to dryness obtaining a ye-
low oil (Yield: 1.49 g, 86%). Anal. Found: C, 45.37; H,
3.93. Calc. for C10H10Cl2O4: C, 45.31; H, 3.80; Cl,
26.75%. IR (cmꢀ1): 3030, 2938, 2870, 1788 (C@O, st),
3.5. Synthesis of N,N,N0,N0-tetramethyl-phthalamide (13)
To a suspension of phthalic acid 12 (1 g, 6.02 mmol)
in anhydrous benzene (10 mL) hexamethylphosphorous
triamide (1.1 mL, 6.02 mmol) was added and the mix-
ture kept under reflux for 30 min. The resulting cloudy
solution was allowed to cool to room temperature and
a saturated aqueous solution of NaHCO3 (5 mL) was
added. The layers were separated and the aqueous phase
was extracted with methylene chloride (4 · 5 mL). The
organic solutions were combined together, dried over
anhydrous MgSO4 and concentrated to dryness, obtain-
ing a white solid (Yield: 1.32 g, 100%). mp = 117–119
ꢁC. Anal. Found: C, 65.48; H, 7.29; N, 12.78. Calc.
for C12H16N2O2: C, 65.43; H, 7.32; N, 12.72%. IR
(cmꢀ1): 3019, 2932, 2782, 1631 (C@O, st), 1591, 1437,
1
1748 (C@O, st), 1435, 1373, 1227, 1088, 1022, 854; H
NMR (500 MHz, CDCl3, d in ppm): 2.01 (3H, s, H2),
2.22–2.28 (1H, m, H40a), 2.79–2.84 (1H, m, H40b),
3.46 (1H, dd, J1 = 4.0 Hz, J2 = 11.5 Hz, H60), 3.52
(1H, ddd, J1 = 5.5 Hz, J2 = J3 = 11.5 Hz, H50), 5.75–
5.77 (1H, m, H10), 6.02–6.01 (2H, m, H20, H30); 13C
NMR (75 MHz, CD3OD, d in ppm): 20.5 (C2), 28.1
(C40), 48.7 (C50), 56.9 (C60), 65.1 (C10), 123.4 (C30),
129.7 (C20), 169.7 (C1), 172.2 (C100 or C1000), 174.9 (C100
or C1000); MS (70 eV, DIP–CI–NH3, m/z,%): 300 (3)
½M þ N2Hþꢁ, 283 (12) ½M þ NHþ4 ꢁ, 282 (100)
½M ꢀ Cl þ7OH þ N2Hþ7 ꢁ.
1
1395, 1265, 1211, 1057. H NMR (200 MHz, CDCl3, d
in ppm): 2.93 (6H, s, H1iv, H1v), 3.07 (6H, s, H1000,
H1vi), 7.28–7.34 (2H, m, H4, H5), 7.38–7.43 (2H, m,
H3, H6). 13C NMR (50 MHz, CD3 OD, d in ppm):
34.9 (C1000, C1iv, C1v, C1vi), 126.4 (C3, C6), 128.7 (C4,
C5), 135.0 (C1, C2), 170.2 (C10, C100). MS (70 eV,
DIP–CI–NH3, m/z,%): 176 (3) [M ꢀ 3Me], 222 (11)
[M + 2H+], 235 (100), 238 (23) ½M þ NHþ4 ꢁ.
3.8. Synthesis of (1R*,5S*,6R*)-5,6-bis(N,N0-dimethyl-
carbamoyl)cyclohex-2-en-1-yl acetate (17) [16]
A solution of compound 16 (4.72 g, 17.80 mmol) in
anhydrous THF (6 mL) was prepared and cooled to 0

4864
M. Gay et al. / Journal of Organometallic Chemistry 690 (2005) 4856–4866
ꢁC. To this solution dimethylamine (53 mL, 106 mmol)
2 M in anhydrous THF was added at once and the
mixture was allowed to reach room temperature and
it was maintained under these conditions for 1 h.
The mixture was concentrated to dryness resulting a
brown oil, which was purified by flash column chroma-
tography, using SiO2 as stationary phase and ethyl
acetate/methanol mixtures of increasing polarity as
mobile phases. The desired product was eluted with
ethyl acetate/MeOH 80:20, affording 4.27 g of a yellow
oil (85% yield). Anal. Found: C, 59.60; H, 7.89; N,
9.99. Calc. for C14H22N2O4: C, 59.56; H, 7.85; N,
9.92%. IR (cmꢀ1): 3030, 2910, 1725 (C@O, st), 1635
(C@O, st), 1485, 1390, 1220, 1125, 1005; 1H NMR
(200 MHz, CDCl3, d in ppm): 2.01 (3H, s, H2),
2.42–2.07 (2H, m, H40), 2.83 (3H, s, H1iv), 2.94 (3H,
s, H1vi), 3.14 (3H, s, H1v), 3.20 (3H, s, H1vii), 3.36–
3.54 (2H, m, H50, H60), 5.64–5.69 (1H, m, H10),
5.72–5.82 (1H, m, H20 or H30), 6.01–6.09 (1H, m,
H20 or H30); 13C NMR (50 MHz, CD3OD, d in
ppm): 21.0 (C2), 28.3 (C40), 34.1 (C50), 35.6 (C1iv,
C1v), 37.0 (C1vi), 37.4 (C1vii), 43.8 (C60), 63.8 (C10),
123.5 (C20 or C30), 131.5 (C20 or C30), 170.2 (C1),
170.3 (C100), 175.0 (C1000); MS (70 eV, DIP–CI–NH3,
m/z,%): 300 (13) ½M þ NHþ4 ꢁ, 283 (100) [M + H+],
223 (10) [M ꢀ AcO].
3.10. Synthesis of cis-trichloro-g2-{N,N-dimethyl-1-[ 6-
(N,N-dimethylammonium-methyl)-ciclohex-3-ene-1-yl]-
methyl-ammonium} platinum(II) chloride (5)
1''
+
5'
Cl
4'
1vi
6'
NH
Cl-
Cl
Pt
Cl
1'
1v
3'
1
2'
NH
5
1iv
1'''
A solution of the ligand 1 (98.0 mg, 0.5 mmol) in
water (7 mL) and hydrochloric acid 1 M (2 mL) were
added to a solution of K2 [PtCl4] (207.5 mg, 0.5 mmol)
in water (10 mL). The mixture was stirred at room tem-
perature for two days. A yellow crystalline solid formed
and it was filtered out, washed with cold distilled water
and dried under vacuum. Slow evaporation of water
from the mother liquor produced additional yellow crys-
tals, which were filtered out (Overall yield 131 mg, 49%).
mp = 228–230 ꢁC. Anal. Found: C, 27.29; H, 5.44; N
5.22. Calc. for C12H26Cl4N2 Pt: C, 26.93; H, 4.90; N,
5.23%. IR (cmꢀ1): 3442, 3021, 2969, 2734, 2641, 2589,
2518, 2483, 1624, 1483, 1420. 1H NMR (500 MHz,
[D6] DMSO, d in ppm): 1.94 (2H, dd, J1 = 16.1 Hz,
J2 = 6.0 Hz, H2b0, H50a), 2.19 (2H, dd, J1 = 16.5 Hz,
J2 = 4.0 Hz, H2a0, H50a), 2.98 (2H, s; H10, H20), 2.77
(12H, s, H1000, H1iv, H1v, H1vi), 2.89–2.92 (2H, m,
H1a, H1a00), 3.17–3.19 (2H, m, H1b, H1b00), 5.65 (2H,
s, H30, H40), 10.15 (2H, s, NH). FAB-MS [FAB(+),
NBA, CH3–CN as solvent, m/z]: 429 (35), 460 (28),
488 (10), 514 (12), 577 (100).
3.9. Synthesis of (1R*,5S*,6S*)-5,6-bis[(N,N-dimethyl-
amino)methyl]cyclohex-2-en-1-ol (2)
A solution of diamide 17 (56 mg, 0.20 mmol) in dry
tetrahydrofuran (2 mL) was added to a suspension of
lithium aluminium hydride (13 mg, 0.36 mmol) in anhy-
drous ether (1 mL). The mixture was refluxed for 1 h
and then it was quenched by cautious successive addi-
tion of water (0.025 mL), 15% NaOH aqueous solution
(0.025 mL) and water again (0.08 mL). A fine white pre-
cipitate formed which was filtered off, washed with ether
and discarded. The filtrate was concentrated to dryness
resulting in a yellow oil (Yield: 38.2 mg, 90%). Anal.
Found: C, 67.86; H, 11.40; N, 13.22. Calc. for
C12H24N2O: C, 67.88; H, 11.39; N, 13.19% IR (cmꢀ1):
3224 (O–H, st), 3025, 2944, 2847, 2819, 2768, 1651,
1485, 1460, 1263, 1150, 1067, 1041; 1H NMR (500
MHz, CDCl3, d in ppm): 1.70–1.78 (2H, m, H5, H6),
1.93–1.99 (1H, m, H4a), 2.02–2.06 (1H, m, H4b), 2.16
(6H, s, H1000, H1iv), 2.17–2.22 (3H, m, H10, H1a00), 2.24
(6H, s, H1v, H1vi), 2.81 (1H, dd, J1 = J2 = 12.5 Hz,
H1b00), 4.23 (1H, s, H1), 5.46–5.70 (2H, m, H2, H3);
13C NMR (50 MHz, CD3 OD, d in ppm): 25.5 (C4),
33.5 (C5), 34.6 (C6), 45.5 (C1000), 45.6 (C1iv), 45.7
(C1v), 45.8 (C1vi), 61.4 (C100), 63.1 (C10), 66.7 (C1),
124.5 (C3), 130.33 (C2); MS (70 eV, DIP–CI–NH3,
m/z, %): 168 (1) [M ꢀ NMe2], 212 (1) [M], 214 (100)
[M + 2H+].
3.11. Synthesis of {(1S*,5S*,6S*)-trichloro-g2[-5,6-
bis(N,N-dimethylammonium-methyl)-cyclohex-2-en-1-
ol]platinum (II)} tetrachloroplatinate(II) (6)
OH
1''
+
1
Cl
1vi
2
3
6
NH
[PtCl4]2-
Cl
Pt
Cl
1v
5
1'
4
2
NH
6
1iv
1'''
A solution of the ligand 2 (106 mg, 0.5 mmol) in
water (10 mL) and hydrochloric acid 1 M (2 mL) were
added to a solution of K2[PtCl4] (207 mg, 0.5 mmol)
in water (10 mL). The solution was stirred at room tem-
perature for four days. The orange solid formed was

M. Gay et al. / Journal of Organometallic Chemistry 690 (2005) 4856–4866
4865
filtered out, washed with cold distilled water and dried
3.13. X-ray diffraction analysis
under vacuum (Yield: 60 mg, 18%). mp = 210–212 ꢁC
(decomp.). Anal. Found: C, 20.74; H, 3.93; N, 3.96.
Calc. for C24H52Cl10N4O2Pt3: C 21.06%, H 3.83; N
4.09%. IR (cmꢀ1): 3451, 3035, 2980, 2749, 1643, 1501,
1470, 1395, 1007, 947. 1H NMR (300 MHz, [D6] DMSO,
d in ppm): 1.96–2.01 (2H, m, H4), 2.15 (1H, s, H6),
2.26–2.31 (1H, m, H5), 2.81 (12H, s, H1000, H1iv, H1v,
H1vi), 3.06–3.07 (4H, m, H10, H100), 3.98 (1H, s, H1),
5.47 (1H, s, OH), 5.70 (2H, s, H2, H3), 9.49 (1H, s,
NH), 9.72 (1H, s, NH). FAB-MS [FAB(+), NBA,
m/z]: 346 (70); 385 (30), 423 (58) [M ꢀ Cl-4Me], 443
(52), 460 (100), 479 (20) [M ꢀ Cl], 482 (25), 499 (28),
538 (30), 554 [M ꢀ Cl+NBA], 575 (90), 593 (20)
Suitable crystals (0.1 · 0.1 · 0.2 mm) from com-
pounds 5 and 7 were selected and mounted on a
MAR345 apparatus with image plate detector. Unit-cell
parameters were determined from automatic centring of
reflections and refined by least-squares method. Intensi-
ties were collected with graphite monochromatized Mo
Ka radiation. Lorentz-polarization and absorption cor-
rections were made.
The structure was solved by direct methods and
refined by full-matrix least-squares method using
SHELXS-97 computer program [17], on the basis of the
non-equivalent reflections by symmetry (very nega-
[M ꢀ 2Cl + NBA]. Conductivity measurements: KM
=
tive intensities were not assumed). The function mini-
P
2
2 2
138.6 Xꢀ1 cm2 molꢀ1 for a concentration 10ꢀ3 M in
DMF.
mized was:
w½ðF oÞ ꢀ ðF cÞ ꢁ , where w = [r2(I) +
2
2
(0.0745P)2 + 0.4463P)ꢀ1], and P ¼ ½ðF oÞ þ 2ðF cÞ ꢁ=3;
f, f0 and f00 were taken from the International Tables
of X-ray Crystallography [18]. All the H atoms were
computed and refined, using a riding model, with isotro-
pic temperature factor equal to 1.2 times the equivalent
temperature factor of the atom which are linked. The fi-
nal R (on F) factors and goodness of fit are shown in Ta-
ble 2. Number of refined parameters was 127. Maximum
shift/esd = 0.00. Mean shift/esd = 0.00. Refinement of
F2 was done against all reflections. The weighted R-fac-
tor wR and goodness of fit S are based on F2, conven-
tional R-factors R are based on F, with F set to zero
for negative F2. The threshold expression of F2 >
2r(F2) is used only for calculating R-factors(gt), etc.,
and is not relevant to the choice of reflections for refine-
ment. R-factors based on F2 are statistically about twice
as large as those based on F, and R-factors based on all
data will be even larger. All esds (except the esd in the
dihedral angle between two least square planes) are esti-
mated using the full covariance matrix. The cell esds are
taken into account individually in the estimation of esds
in distances, angles and torsion angles; correlations be-
tween esds in cell parameters are only used when they
are defined by crystal symmetry. An approximate (iso-
tropic) treatment of cell esds is used for estimating esds
involving least square planes.
3.12. Synthesis of {N,N-dimethyl-1-[(2-(N,N-dimethyl-
ammonium-methyl)-1-phenyl-]-methylammonium} tetra-
chloroplatinate(II) (7)
1v
1vi
2+
NH
2-
3'
6'
PtCl4
1''
1iv
NH
4'
5'
2'
1'
1'''
1
7
A solution of the ligand 3 (96.0 mg, 0.5 mmol) in
water (5 mL) and hydrochloric acid 1 M (2 mL) was
added to a solution of K2[PtCl4] (207 mg, 0.5 mmol)
in water (7 mL). The reaction mixture was stirred at
room temperature for 2 h. The orange solid formed
was filtered off, washed with cold distilled water and
dried under vacuum. Slow concentration of the filtrate
produced additional crystals, which were filtered off,
affording an overall yield of 201 mg, 76%. mp = 224–
226 ꢁC (decomp.). Anal. Found: C, 27.34; H, 4.28;
N, 5.16. Calc. for C12H22Cl4N2Pt: C, 27.12; H, 4.14;
N, 5.27%. IR (cmꢀ1): 3451, 3035, 2980, 2749, 1643,
1501, 1470, 1395, 1007, 947. 1H NMR (300 MHz,
[D6] DMSO, d in ppm): 2.76 (12H, d, J = 3.2 Hz,
H1000, H1iv, H1v, H1vi), 4.53 (4H, d, J = 3.8 Hz, H1,
H100), 7.57 (2H, dd, J1 = 3.8 Hz, J2 = 2.2 Hz, H30,
H60), 7.74 (2H, J1 = 3.7 Hz, J2 = 2.3 Hz, H40, H50),
10.44 (2H, s, NH). FAB-MS [FAB(+), NBA, m/z]:
360 (22), 385 (20), 423 (30), 460 (18), 470 (20), 555
(22), 593 (100).
Hydrogen coordinates as well as anisotropic thermal
parameters are included as supplementary material. De-
tailed information about the crystal structure determina-
tion of compounds 5 and 7 is given as supporting
information which has been deposited with the Cam-
bridge Crystallographic Data Centre.
4. Supplementary materials
Crystallographic data for the structural analyses have
been deposited with the Cambridge Crystallographic
Data Centre, CCDC Nos. 268228 and 268229 for

4866
M. Gay et al. / Journal of Organometallic Chemistry 690 (2005) 4856–4866
[5] M. Galanski, A. Yasemi, S. Slaby, M.A. Jakupec, V.B. Arion,
M. Raush, A. Nazarov, B.K. Keppler, Eur. J. Med. Chem. 39
(2004) 707.
[6] B. Spingler, D.A. Whittington, S.J. Lippard, Inorg. Chem. 40
(2001) 5596.
[7] S.G. Chaney, Int. J. Oncol. 6 (1995) 1291.
[8] (a) M. Calaf, A. Caubet, V. Moreno, M. Font-Badia, X. Solans,
J. Inorg. Biochem. 59 (1995) 63;
compounds 5 and 7, respectively. Copies of this informa-
tion may be obtained free of charge from The Director,
CCDC, 12 Union Road, Cambridge, CB2 1EZ UK [fax
(int code): +44 1223 336 033 or e-mail: deposit@ccdc.
cam.ac.uk or www: http://www.ccdc.cam.ac.uk].
(b) G.B. Onoa, V. Moreno, M. Font-Badia, X. Solans, M.J.
Acknowledgements
´
Perez, C. Alonso, J. Inorg. Biochem. 75 (1999) 205;
´
(c) M. Gomez-Bosquet, V. Moreno, M. Font-Badia, X. Solans,
We thank the Spanish Ministry of Education and Sci-
ence for financial support (Projects PB-98-1236 and
BQU2002-00601). A fellowship to M.G. from the Uni-
versity of Barcelona is also gratefully acknowledged.
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