Multinuclear magnetic resonance spectroscopy and crystal structures of iodo-bridged dinuclear Pt(II) complexes with amines

Article abstract of DOI:10.1016/j.ica.2005.06.018

Complexes of the types cis-Pt(amine)₂I₂ were transformed into the iodo-bridged dimers, which were characterized mainly by multinuclear (¹⁹⁵Pt, ¹H and ¹³C) magnetic resonance spectroscopy. For bulby amines, the dinuclear species were synthesized directly from K₂[PtI₄]. Compounds with several primary aliphatic and cyclic amines and two secondary amines were studied. In ¹⁹⁵Pt NMR, two signals were observed between -3899 and -4080 ppm in acetone. These species were assigned to the cis and trans dinuclear compounds I(amine)Pt(μ-I)₂PtI(amine). We suggest that the most shielded compound is the trans isomer. The difference between the two isomers is 12-13 ppm for the primary amine system and 26-27 ppm for the two secondary amines. There seems to be a slight dependence of the proton affinity in the gas phase of the amine (linear amines) with the δ(Pt) chemical shifts of the dinuclear Pt(II) compounds. The ²J(¹⁹⁵Pt-¹HN) coupling constants are slightly larger for the trans isomers (average 67 Hz, vs. 56 Hz). The ³J(¹⁹⁵Pt-¹H) coupling constants were detected only for the dimethylamine compounds, 46 Hz (trans) and 44 Hz (cis). In ¹³C NMR, the values of ²J(¹⁹⁵Pt- ¹³C) and ³J(¹⁹⁵Pt-¹³C) were also found to be very slightly larger for the trans complexes (average 19 and 25 Hz vs. 15 and 18 Hz). The structures were confirmed by X-ray diffraction studies of the n-butylamine and diethylamine compounds. The two crystals were those of the trans dinuclear complexes.

Full text of DOI:10.1016/j.ica.2005.06.018

Inorganica Chimica Acta 358 (2005) 3919–3926
www.elsevier.com/locate/ica
Multinuclear magnetic resonance spectroscopy and crystal
structures of iodo-bridged dinuclear Pt(II) complexes with amines
*
Fernande D. Rochon , Viorel Buculei
Department of Chemistry, Universit e´ du Qu e´ bec a` Montr e´ al, C.P. 8888, Succ. Centre-ville, Montr e´ al, QC, Canada H3C 3P8
Received 21 April 2005; accepted 13 June 2005
Available online 19 August 2005
Abstract
Complexes of the types cis-Pt(amine)
tinuclear ( Pt, H and C) magnetic resonance spectroscopy. For bulby amines, the dinuclear species were synthesized directly
2
I
2
were transformed into the iodo-bridged dimers, which were characterized mainly by mul-
1
95
1
13
1
95
from K
NMR, two signals were observed between ꢀ3899 and ꢀ4080 ppm in acetone. These species were assigned to the cis and trans dinu-
clear compounds I(amine)Pt(l-I) PtI(amine). We suggest that the most shielded compound is the trans isomer. The difference
2
[PtI
4
]. Compounds with several primary aliphatic and cyclic amines and two secondary amines were studied. In
Pt
2
between the two isomers is 12–13 ppm for the primary amine system and 26–27 ppm for the two secondary amines. There seems
to be a slight dependence of the proton affinity in the gas phase of the amine (linear amines) with the d(Pt) chemical shifts of
2
195
1
the dinuclear Pt(II) compounds. The J( Pt– HN) coupling constants are slightly larger for the trans isomers (average 67 Hz,
3
195
1
vs. 56 Hz). The J( Pt– H) coupling constants were detected only for the dimethylamine compounds, 46 Hz (trans) and 44 Hz
1
3
2
195
13
3
195
13
(
(
cis). In C NMR, the values of J( Pt– C) and J( Pt– C) were also found to be very slightly larger for the trans complexes
average 19 and 25 Hz vs. 15 and 18 Hz). The structures were confirmed by X-ray diffraction studies of the n-butylamine and dieth-
ylamine compounds. The two crystals were those of the trans dinuclear complexes.
Ó 2005 Elsevier B.V. All rights reserved.
Keywords: Crystal structure; Platinum; Amine; NMR; Iodo ligands
1
. Introduction
of the most active complexes (for example those with
cyclic amines) are too insoluble to be useful anticancer
drugs [6].
The antitumor properties of the complex cisplatin,
cis-Pt(NH ) Cl has been known now for several dec-
Most cisplatin analogues studied in the literature con-
tain two identical amines since they are very easy to syn-
thesize. A method was reported for the synthesis of
mixed-amine complexes many years ago by our research
group [7,8], but it has not been very popular. We have
reported a few of these compounds and other complexes
were reported in the literature by other groups. For
example, the mixed-ligand compound cis-Pt(NH3)
3
2
2
ades. Its chemistry has been studied by many authors
and the compound is nowadays one of the most widely
used anticancer drug. A good review of the influence of
structure on the activity of Pt drugs has been published
[
1]. When NH is replaced by primary amines, the anti-
3
tumor activity can sometimes increase, depending on the
amines [2–5], but these compounds have generally a
more limited activity spectrum. Furthermore, several
(2-picoline)Cl was found to be very active and it is cur-
2
rently in clinical trials [9,10]. These mixed-ligand com-
plexes are usually prepared using the iodo-bridged
dimer as the intermediate compound, which is synthe-
sized from the Pt(amine) I complex [7]. These two types
*
Corresponding author. Tel.: +1 514 987 3000x4896; fax: +1 514
9
87 4054.
E-mail address: rochon.fernande@uqam.ca (F.D. Rochon).
2
2
0
020-1693/$ - see front matter Ó 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.ica.2005.06.018

3
920
F.D. Rochon, V. Buculei / Inorganica Chimica Acta 358 (2005) 3919–3926
95
1
of compounds are very insoluble and the reacting time is
usually quite long (2–3 weeks). Furthermore, it is diffi-
cult to determine when the reaction is complete. The
iodo-bridged dimers are usually brown and the diiodo
complexes are yellow, but the color of the mixture is
not a good criterion.
Pt. The acetone peak was used as an internal standard
1
13
for H (2.04 ppm) and C (29.80 ppm). The external
1
95
reference used for Pt was cis-Pt(tetramethylenesulfox-
ide) Cl (in CDCl ), adjusted at ꢀ3450 ppm from
2
2
3
K [PtCl ] (d(Pt) = 0 ppm in D O).
2
6
2
The cleavage of the iodo-bridged dimers can be done
2.1. Synthesis
with a second amine to produce directly Pt(amine)
0
(
amine )I , which can be converted into the dichloro spe-
2.1.1. cis-Pt(amine)2I2
These complexes were synthesized by a modified ver-
sion of DharaÕs method [11] and as described in details
2
cies by reaction with a silver salt followed by the addi-
tion of KCl. The iodo dimers can also be converted to
the complex salt K[Pt(amine)Cl ] by reacting directly
more recently [12,13]. For tBuNH , the cis compound
3
2
the dimer with a silver salt followed by the addition of
KCl.
does not form. For Et NH, a brown product was
2
1
95
formed and Pt NMR has shown the presence of the
iodo-bridged dimers (70%) and another compound,
which was found to be cis-Pt(Et NH) I (30%) [12].
The purity of the mixed-ligand compounds is very
important when the antitumor properties are deter-
mined. Therefore the purity of the dinuclear intermedi-
ate is also an essential criterion, since the quantity of
the silver salt must be carefully controlled. Furthermore,
if the formation of the dimer is not complete, the pres-
2
2 2
All these Pt(amine)2I2 complexes have already been
characterized by IR, multinuclear magnetic resonance
and a few by crystallographic methods [12,13].
ence of Pt(amine) species will always be present in the
2.1.2. I(amine)Pt(l-I) Pt(amine)I
2
2
final product. We have therefore undertaken a system-
atic NMR study of the dinuclear species, although the
latter are not very soluble. Iodo Pt(II) compounds tend
All the complexes, except those of t-butylamine and
diethylamine were synthesized by slight variations of
the published method [7]. The complex cis-PtL2I2
(0.2 mmol) was placed in 5 mL ethanol and 1.5 mL of
perchloric acid 0.67 M and mixed until the formation
of a brown or orange precipitate (one to three weeks).
The yellow color of the starting material must have dis-
appeared completely. The brownish product was filtered,
washed with water and ethanol and dried under vacuum
in a desiccator. For the four cyclic amines, the reaction
time was 10 days. NMR spectroscopy has shown that
the cyclopropyl dimer had not formed yet after 10 days
since only the starting material was found. The reaction
was then repeated and the mixture was left stirring for 3
weeks. At that time, there was no more starting material.
For the bulky amines t-butylamine and diethylamine,
the dimeric compound was synthesized directly from the
reaction of K [PtI ] with an excess of amine in water.
to decompose in CDCl [12]. It has been shown that cis-
3
diamine compounds react rapidly with DMSO and often
isomerize quite rapidly in DMF [13]. These solvents
were therefore eliminated. We have decided to use ace-
tone for the study, although it is not a completely inert
solvent. But we have observed that the isomerization is
either absent or very slow, unless it is heated.
In this paper, we report a systematic and detailed
1
13
195
study of the multinuclear ( H, C and
Pt) NMR
spectra of the dinuclear complexes I(amine)Pt(l-I) Pt-
2
(
amine)I in acetone-d . Complexes with eight primary
6
aliphatic amines, four cyclic amines and two secondary
amines were studied. Amines cannot accept electron
density from the metal. Therefore the r bonds should
cause a deshielding effect on the ligand and a shielding
effect on the metal. The strength of the r bond should
2
4
The method described to synthesize cis-Pt(amine)2I2
was used [12].
be related to the pK value of the protonated amine or
a
the proton affinity of the ligand, although few of the lat-
ter values have been reported in the literature. We have
also determined the crystal structures of two iodo-
bridged dimers and the results will be discussed below.
The NMR characterization of the products are listed
below. Because of the multiplicity of the proton signals
and the formation of more than one product, the
3
1
1
J( H– H) couplings have not been assigned, except
for the amines where the multiplicity is reduced as in
MeNH and Me NH.
2
2
2
. Experimental
I(MeNH )Pt(l-I) Pt(MeNH )I, trans and cis, respec-
2 2 2
1
tively: RMN (d (ppm)): H: NH 4.498 and 4.390 (s); H
1
3
1
1
13
K [PtCl ] was obtained from Johnson Matthey and
2.522 and 2.510 (t), J( H– H) = 6.3 and 6.3 Hz; C: C1
2
4
2
195
was recrystallized in water before use. The amines were
bought from Aldrich. CD COCD was purchased from
CDN Isotopes.
The NMR spectra were measured on a Varian Gem-
ini 300BB in CD COCD . The fields were 300.075,
7
35.188 and 34.505, J( Pt–C ) = 19 and 16 Hz.
1
I(EtNH )Pt(l-I) Pt(EtNH )I, trans and cis, respec-
3
3
2
2
2
1
tively: RMN (d (ppm)): H: NH not assigned (see text);
H 2.838 and 2.794 (tq); H 1.297 and 1.249 (t); C: C1
1 2
44.022 and 43.354, J( Pt–C ) = 18 and 15 Hz; C
1
3
2
195
3
3
1
2
1
13
5.462 and 64.267 MHz, respectively for H, C and
16.656.

F.D. Rochon, V. Buculei / Inorganica Chimica Acta 358 (2005) 3919–3926
3921
I(nPrNH )Pt(l-I) Pt(nPrNH )I, trans and cis, respec-
Table 1
2
2
2
1
Crystallographic data for crystal I
tively: RMN (d (ppm)): H: NH 4.525 and 4.432 (s); H
1
2
.764 and 2.738 (tq); H 1.753 and 1.802 (tt); H 0.939
Crystal
I
2
3
1
3
and 0.946 (t); C: C 50.838 and 50.184; C 24.912
Name
{Pt(nBuNH )I} (l-I)
1
2
2
2
2
and 24.879; C 11.161 and 11.387.
Chemical formula
M
C
8
H
22
I
4
N
2
Pt
2
3
w
1044.06
I(nBuNH )Pt(l-I) Pt(nBuNH )I: trans and cis,
2
2
2
1
Space group
R-3 (No.148)
25.249(4)
25.249(4)
8.113(2)
4478.9(15)
9
3.484
20.228
4068
11332
1946 (0.1512)
1148
0.0626
0.1198
1.089
respectively: RMN (d (ppm)): H: NH 4.516 and 4.399
s), J( Pt–NH) = 66 and 57 Hz; H 2.784 and 2.761
˚
a (A)
2
195
(
˚
1
b (A)
˚
(
tq); H 1.740 and 1.765 (tt); H 1.395 and 1.400 (tt);
c (A)
Volume (A )
2
3
1
3
˚
3
H
0.923 and 0.929 (t); C: C1 48.787 and 48.120;
4
2
195
Z
J( Pt – C ) = 17 and 14 Hz; C 33.685; C 20.239
1
2
3
ꢀ3
q
calc (g cm
)
and 20.390; C 13.939.
ꢀ1
)
4
l (MoKa) (cm
F(000)
I(isoPrNH )Pt(l-I) Pt(isoPrNH )I, trans and cis,
2
2
2
1
respectively: RMN (d (ppm)): H: NH 4.492 and 4.381
s), J( Pt–NH) = 68 and 56 Hz; H 3.413 and 3.204
Measured reflections
Independent reflections (Rint
2
195
(
)
1
1
3
Observed reflections (I > 2r(I))
(F > 2r(I))
(
5
2
thept); H 1.345 and 1.363 (d); C: C 51.504 and
2 1
2
195
R
1
0.882; J( Pt–C ) = 23 and 16 Hz; C 24.199 and
1 2
wR
S
2
(all data)
3
195
4.154, J( Pt–C ) = 27 Hz (trans).
2
I(isoBuNH )Pt(l-I) Pt(isoBuNH )I: trans and cis,
P
P
PðwðF
2
PðwðF
2
1=2
2
2
2
R1 ¼ ðjF o ꢀF c jÞ= jF o j;wR2 ¼ ½
o2
ꢀF c2 Þ Þ=
o2
Þ Þꢁ
.
1
respectively: RMN (d (ppm)): H: NH 4.452 and 4.347
2
195
(
s), J( Pt–NH) = 68 and 55 Hz; H 2.646 and 2.639
1
(
td); H 2.159 and 2.137 (thept); H 0.982 and 0.959
2
3
195
1
3
2
˚
(
d); C: C 56.467 and 55.799, J( Pt–C ) = 20 and
graphite-monochromatized Mo Ka (k = 0.71073 A)
radiation. The crystals were selected after examination
under a polarizing microscope for homogeneity. The cell
dimensions were determined at room temperature, from
a least-squares refinement of the angles 2h, x and v ob-
tained for well-centered reflections. The data collections
were made by the 2h/x scan technique using the
XSCANS program [14]. The coordinates of the Pt atoms
were determined by direct methods. All the other non-
hydrogen atoms were found by the usual Fourier meth-
1
1
1
6 Hz; C : hidden by the solvent; C 20.162 and 20.208.
2 3
I(secBuNH )Pt(l-I) Pt(secBuNH )I, trans and cis,
2
2
2
1
respectively: RMN (d (ppm)): H: NH 4.431 and 4.325
s); H 2.986 and 2.959 (m); H 1.471 and 1.509 (tq);
(
1
2
1
3
H 1.287 and 1.346 (d); H
C 56.847 and 56.194, J( Pt–C ) = 16 Hz (trans); C
2
3
2
0
0.954 and 0.930 (t); C:
2
3
2
195
1
1
3
195
0.984, J( Pt–C ) = 27 Hz (trans); C 21.058 and
2
3
1.106; C2
0
10.479 and 10.506.
I(tBuNH )Pt(l-I) Pt(tBuNH )I, trans and cis, respec-
2
2
2
1
2
tively: RMN (d (ppm)): H: NH 4.326 and 4.009 (s),
ods. The refinement of the structures was done on F
2
1
195
J( Pt–NH) = 67 Hz (trans); H 1.526 and 1.415 (s);
by full matrix least-squares analysis. In crystal I, the
two terminal C atoms of the butyl chains were found dis-
ordered and they intermingle. The hydrogen atom posi-
tions were fixed in their calculated position with
Ueq = 1.2 Ueq (or 1.5 for methyl groups) of the carbon
to which they are bonded, except for the C atoms of
the butyl chains. Corrections were made for absorption
(Gaussian integration for I and from w–scans for II),
Lorentz and polarization effects. The residual peaks were
located in the close environment of the platinum atoms.
The calculations were done using the Bruker SHELXTL sys-
tem [15]. The pertinent crystal data and the experimental
details for crystal I are summarized in Table 1.
2
3
2
195
C: C 56.300 and 55.390, J( Pt–C ) = 16 and 10 Hz;
1
1
3
195
C 32.168 and 31.075, J( Pt–C ) = 22 and 18 Hz.
2
2
I(Me NH)Pt(l-I) Pt(Me NH)I, trans and cis, respec-
2
2
2
1
tively: RMN (d (ppm)): H: NH 4.900 and 4.798 (s); H
1
3
1
1
2
.662 and 2.656 (d), J( H– H) = 6.0 and 6.0 Hz,
J( Pt–H ) = 46 Hz (trans) and 44 Hz (cis); C: C1
3
195
13
1
2
195
4
6.086 and 45.145, J( Pt–C ) = 17 and 14 Hz.
1
I(Et NH)Pt(l-I) Pt(Et NH)I, trans and cis, respec-
2
2
2
1
tively: RMN (d (ppm)): H: NH 4.763 and 4.332 (s);
H 2.955 and 2.858 (m); H 1.488 and 1.452 (t); C:
C 53.735 and 53.219, J( Pt–C ) = 19 and 17 Hz; C
2
1
1
3
1
2
195
2
1
1
5.184 and 15.305. This product contains 30% of
cis-Pt(Et NH) I . Crystal data for II: C2/c space
2
2 2
˚
group, a = 20.655(5), b = 7.2730(10), c = 13.822(4) A,
b = 100.35(2)°, q = 3.395, R = 0.065, wR (all data) =
3. Results and discussion
1
2
0
.0826, and S = 1.027.
3.1. Synthesis
2
.2. Crystal structures
The brown or orange iodo-bridged dinuclear com-
The crystallographic study of the iodo-bridged
nBuNH (I) and Et NH (II) dimers were determined at
plexes were synthesized mainly from the reaction of yel-
low cis-Pt(amine) I in perchloric acid as described in
2
2
2 2
room temperature on a Bruker P4 diffractometer using
our previous publication [7].

3922
F.D. Rochon, V. Buculei / Inorganica Chimica Acta 358 (2005) 3919–3926
HClO4=H2O
!
2
PtðamineÞ I2
IðamineÞPtðl-IÞ PtðamineÞI
2
2
EtOH
Both types of compounds are very insoluble and the
reaction time is very long (2–3 weeks). This method
was used for the following amines: = methylamine
(
MeNH ), ethylamine(EtNH ), n-propylamine (nPrNH ),
2 2 2
n-butylamine (nBuNH ), iso-propylamine (isoPrNH ),
2
2
iso-butylamine (isoBuNH ), sec-butylamine (secBuNH )
2
2
and dimethylamine (Me NH). For the four cyclic amines
2
Fig. 1. Diagram of the n-butylamine iodo-bridged dimer (only one
conformation is shown for C3 and C4).
(
cyclopropylamine (cpra), cyclobutylamine (cba), cyclo-
pentylamine (cpa) and cyclohexylamine (cha)), the reac-
tion time was 10 days. NMR spectroscopy has shown
that the cyclopropyl dimer had not formed yet. Only the
starting material was detected. The experiment was then
repeated and the mixture was left stirring for 3 weeks.
At that time, they were no more starting material and only
the cyclopropyl dimers were observed in the NMR
spectra.
A mechanism has been suggested in the literature for
the formation of the dinuclear species [16]. The published
scheme indicates a trans configuration of the dimer,
although its configuration is not discussed in the paper.
For t-butylamine (t-BuNH2) and diethylamine
are disordered as often seen in crystals containing
nBuNH ligands.
2
Both molecules are centrosymmetric and the com-
pounds have the trans geometry. In crystal I, the two
Pt atoms, the 4 I ligands and the two N atoms are all
˚
in the same plane (mean deviation is 0.0123 A). The ter-
˚
minal Pt–I bonds are 2.5801(15) A, while the bridging
bonds are very slightly longer. The bond in trans posi-
˚
tion to the iodo ligand (2.5990(16) A) is slightly longer
than the one in trans position to the amine
˚
(2.5825(17) A), suggesting that the trans influence of
the iodo ligand is larger than the one of amines. There
are some deformations from the perfect square plane
around the Pt atoms caused by a strain inside the 4-
membered ring. The internal angles I–Pt–I are smaller
(
Et NH), the cis disubstituted compound which is pro-
2
duced with other amines is not easily formed because
of the bulkiness of the two ligands. The iodo-bridged di-
mer with these two sterically demanding ligands were
synthesized directly from the reaction of K [PtI ] with
(85.71(5)°) than the ideal value, while the internal angles
2
4
at the bridging iodo ligands are (94.29(5)°). These results
agree with our results on II and those published for the
the amine in water.
H2O
Et NH dimer [17].
2
K
2
½PtI
4
ꢁþ2amine ! IðamineÞPtðl-IÞ PtðamineÞIþ4KI
2
2
˚
The Pt–N bond distances are 2.072(14) A, which re-
flects the larger trans influence of the iodo ligand. In
The product obtained with Et NH contained also
2
˚
the Et NH dimer, our value is 2.081(7) A, compared
2
about 30% of another compound which was identified
as cis-Pt(Et NH) I . The ligand t-butylamine is too
˚
to 2.065(9) A in the published structure [17]. In cis-
2
2 2
˚
Pt(Et NH) I , the Pt–N bonds are longer (2.113(10) A)
2
2 2
bulky to form a cis compound.
because of important steric hindrance caused by the
presence of two secondary amines in cis positions [12].
These dimers are very important intermediates in syn-
thetic Pt(II) chemistry and therefore, it is essential to
know the purity of these compounds, especially in the
synthesis of potential antitumor compounds. They were
characterized mainly by multinuclear NMR spectros-
copy. The crystal structure of the nBuNH and Et NH
3
.3. NMR
The NMR spectra of all the dinuclear complexes were
2
2
measured in CD COCD . Although several compounds
3
3
compounds were determined by X-ray diffraction, which
confirmed the structure of the iodo-bridged dinuclear
species.
are soluble in normal CHCl , they decompose quite rap-
3
idly in CDCl to produce iodine. Attempts to purify
3
CDCl were not successful. We also encountered similar
3
1
3
problems with CD Cl . Since our C NMR spectra
2
2
3
.2. Crystal structures
were accumulated for at least overnight, we have found
that deuterated acetone was the best solvent, even if it is
not a completely inert solvent. We have not found any
The crystallographic study of the nBuNH (I) and
2
Et NH (II) compounds confirmed the structure of the
2
change after one week of standing in CD COCD .
3 3
two iodo-bridged dimers. The structure of the Et NH
complex has been published [17] and our crystallo-
2
195
3.3.1. Pt NMR
graphic results on crystal II will not be discussed in de-
The d(Pt) chemical shifts of all the compounds are
tail. The structure of the nBuNH complex (I) is shown
listed in Table 2. For most products, three signals were ob-
2
in Fig. 1. The two terminal C atoms of the butyl chains
served, except for the MeNH and Me NH compounds,
2 2

F.D. Rochon, V. Buculei / Inorganica Chimica Acta 358 (2005) 3919–3926
3923
Table 2
195
d( Pt) (ppm) of the products in CD
3
COCD
3
Amine
Pt(amine)
2
I
2
I(amine)Pt(l-I)
2
Pt(amine)I
Dd (cis–trans)
trans
cis
MeNH
2
ꢀ3999 (55%)
ꢀ4010 (25%)
ꢀ4008 (38%)
ꢀ4005 (47%)
ꢀ4015 (48%)
ꢀ4011 (46%)
ꢀ4013 (41%)
ꢀ4080 (19%)
ꢀ4003 (60%)
ꢀ4031 (60%)
ꢀ4006 (55%)
ꢀ4013 (45%)
ꢀ3925 (65%)
ꢀ3962 (35%)
ꢀ3986 (45%)
ꢀ3997 (25%)
ꢀ3995 (38%)
ꢀ3993 (43%)
ꢀ4003 (34%)
ꢀ3998 (46%)
ꢀ4001 (36%)
ꢀ4069 (19%)
ꢀ3990 (40%)
ꢀ4021 (30%)
ꢀ3994 (15%)
ꢀ4002 (30%)
ꢀ3899 (35%)
ꢀ3935 (35%)
13
13
13
12
12
13
12
12
13
10
12
11
26
27
EtNH
nPrNH
nBuNH
isoPrNH
isoBuNH
secBuNH
tBuNH
2
(cis)-3354 (50%)
2
(trans)-3364 (24%)
(trans)-3360 (10%)
(trans)-3344 (18%)
(trans)-3372 (8%)
(trans)-3336 (23%)
(trans)-3368 (62%)
(cis)-3354 (100%)
(trans)-3400 (10%
(trans)-3364 (30%)
(trans)-3343 (25%)
2
2
2
2
2
a
b
cpra cpra
a
cba
a
cpa
a
cha
2
Me NH
Et
2
NH
(cis)-3302 (30%)
a
After 10 days of reaction.
After 3 weeks of reaction.
b
where only two were detected. Iodo bridged dimers of this
type have two geometric isomers as shown in Scheme 1.
Both isomers should have very similar chemical
shifts. They were observed between ꢀ3986 and
isomer was reported at ꢀ3128 ppm [12]. For all the
other amines, the third signal was assigned to trans-Pt-
(amine) I , which we have also reported recently
2
2
[12,13]. These monomers are observed in a lower field re-
gion, around ꢀ3350 ppm. The proportion of the disub-
stituted compound varied from one experiment to the
other and seems to depend on the time of the reaction.
For most of the amines, it seems that the cis-Pt(ami-
ne) I compound has isomerized to the trans configura-
ꢀ
ꢀ
4080 ppm for the primary amines and between
3899 and ꢀ3962 ppm for the secondary amines. The
proportion of each species is also shown in Table 2,
although these numbers are very approximate. The
two signals for the dinuclear species are very close.
The separation is 10–13 ppm for the compounds con-
taining a primary amine and slightly larger (26–
2
2
tion in the long process of dimer formation. We do not
think that it was formed in the NMR tube (in cold ace-
tone), since the spectra were stable with time. The com-
pound cis-Pt(nPrNH ) I was stirred in ethanol for 3
2
7 ppm) for those containing secondary amines. For
most of the amines, the intensity of one signal was higher
than the second one. It is impossible for the moment to
make definite assignment, but we suggest that the signal
with the highest intensity corresponds to the trans iso-
mers, which in fact is the one observed at highest field.
We will therefore assume these configuration in the
2
2 2
weeks and then slightly heated. The NMR spectrum of
the product has shown the presence of only trans-
Pt(nPrNH ) I . Therefore these cis compounds can
2
2 2
isomerize to the trans geometry in organic solvents,
especially if it is heated. The disubstituted product could
also result from the cleavage of the iodo-bridged dimers
with the free amine although we are not sure if the reac-
tion could happen in acid solution. The cleavage of the
trans dimers with amines should lead to cis-Pt(ami-
ne) I , while the cleavage of the cis dimers might lead
1
95
remaining discussion. The Pt NMR spectra of a few
similar dimers were reported in the literature by our
group [18], mostly in DMF. For most compounds,
two signals were also observed for the different isomers
and our results agree well with these values.
2
2
The third signal for the EtNH complexes was as-
to the formation of a mixture of cis- and trans-Pt(ami-
2
signed to cis-Pt(EtNH ) I , which was recently reported
ne) I , but this hypothesis has not been verified.
2
2 2
2 2
by our group [12]. The dimerization reaction was pre-
We have found a slight relation between the d(Pt)
chemical shifts of the dimers and the proton affinity of
the linear primary amines in the gas phase and these
are shown in Fig. 2. The Pt signals are slightly shifted
to higher fields as the proton affinity [19–21] increases,
sumably stopped before it was completed. For Et NH,
2
the third peak (30%) was assigned to cis-Pt(Et NH) I ,
2
2 2
1
95
since it was synthesized directly from the reaction of
K [PtI ]. It was observed at ꢀ3302 ppm, while the trans
2
4
I
I
amine
I
I
I
Pt
Pt
Pt
Pt
amine
I
amine
I
I
amine
cis
trans
Scheme 1.

3924
F.D. Rochon, V. Buculei / Inorganica Chimica Acta 358 (2005) 3919–3926
been recently published [12,13], their signals could be
-
3980
3990
4000
4010
4020
eliminated. The d(NH) of the two iodo-bridged isomers
are shown in Table 3. The assignments are based again
on the relative intensity of the two signals. The most in-
tense is the trans isomer and it was observed at lower
fields. This is in agreement with our results obtained in
cis
MeA
MeA
nBuA
nBuA
-
-
-
-
EtA
EtA
nPrA
nPrA
trans
195
Pt NMR spectroscopy. An increase of electron den-
sity on the Pt atom (trans isomer found at higher field
1
95
in Pt NMR) will cause a decrease in electron density
1
on the H atoms (trans isomer at lower field in H NMR).
9
10
915
920
925
930
935
The difference between the cis and trans isomers seems
to be larger for more bulky amines. For most com-
pounds, the difference varies between 0.092 and
AP (kJ/mole)
Fig. 2. d(Pt) of the linear aliphatic amine dimers vs. proton affinity of
the amine [19–21].
0
.117 ppm, but for t-butylamine and diethylamine, the
difference is 0.317 and 0.431 ppm, respectively.
suggesting that the d(Pt) chemical shifts are influenced
by the basicity of the amine as expected.
Since the complexes are not very soluble, the intensity
2
195
1
of the NH signals is quite low, but a few J( Pt–N H)
coupling constants could be measured and they are
shown in Table 3. For the trans isomers, they are larger
1
.3.2. H NMR
3
The proton chemical shifts of the dimers are shown in
(average 68 Hz) than in the cis geometry (average
the experimental section. Since there are three different
species and because of the high multiplicity of several
signals, the assignments are quite difficult. Since the
5
6 Hz). There are no reported values in the literature
for these types of compounds. For monomers, the cou-
pling constants are usually larger for the cis complexes
than for the trans isomers. But the iodo-bridged com-
pounds are very different, since the two amine ligands
are located on two different Pt atoms. Therefore, their
1
H NMR spectra of the disubstituted compounds have
Table 3
1
2
195
1
d( H) (ppm) and J( Pt–N H) (Hz) of the NH protons in the
complexes I(amine)Pt(l-I) Pt(amine)I
1
95
Pt coupling constants cannot be compared with va-
lues obtained for monomers.
2
2
195
1
2
195
1
Amine
dtrans dcis
J( Pt–N H) trans
J( Pt–N H) cis
3
195
1
The J( Pt– H) coupling constants of only the
MeNH
2
4.498 4.390
4.525 4.432
4.516 4.399 66
4.492 4.381 68
4.452 4.347 68
4.431 4.325
Me NH dimers could be calculated. The value is
2
nPrNH
nBuNH
isoPrNH
isoBuNH
secBuNH
2
4
6 Hz for the trans dimer and 44 Hz for the cis com-
2
57
56
55
3
1
1
pound. The J(N H– H) coupling constants are identi-
2
2
cal for the two isomers (6 Hz).
2
tBuNH
cpra
cba
2
4.326 4.009 67
4.620 4.522
4.759 4.667
13
.3.3. C NMR
3
The d(C) chemical shifts of the dimers are shown in
Table 4. The signals corresponding to Pt(amine) I were
substracted. Again, the two isomers are observed and
the most intense signal was assigned to the trans com-
cpa
cha
4.558 4.455 69
4.470 4.371
4.900 4.798
2 2
Me
2
NH
2
Et NH
4.763 4.332
pound. The C atoms close to the binding site (C and
1
Table 4
13
195
13
3 3
d( C) (ppm) and J( Pt– C) (Hz) of the dimers in CD COCD
2
3
Amine
C
1
C
2
J(Pt–C
1
)
2
J(Pt–C )
trans
cis
trans
cis
trans
cis
trans
cis
MeNH
2
35.188
44.022
50.836
48.787
51.504
56.467
56.847
56.300
46.086
53.735
34.505
43.354
50.184
48.120
50.882
55.799
56.194
55.390
45.145
53.219
19
18
16
15
EtNH
nPrNH
nBuNH
isoPrNH
isoBuNH
secBuNH
tBuNH
Me NH
Et NH
2
16.656
33.685
2
24.912
24.199
24.879
24.154
2
17
23
20
14
16
16
16
10
14
17
2
27
a
2
2
30.984
27
22
2
32.168
15.184
31.075
15.305
16
17
19
18
2
2
a
Hidden by the solvent.

F.D. Rochon, V. Buculei / Inorganica Chimica Acta 358 (2005) 3919–3926
3925
C ) in the trans isomers are observed at lower fields than
the corresponding atoms in the cis complexes. For the
primary amines (except t-butylamine), the difference in
IðamineÞPtðl-IÞ PtðamineÞI þ 2B
2
2
!
2trans-PtðamineÞðBÞI
2
the chemical shits of C1 is quite constant (average
The iodo-bridged dimers are very important interme-
diates in synthetic Pt(II) chemistry and it is essential to
know their purity especially in the field related to che-
motherapy. The crystal structure determinations have
shown that the analyzed crystals are the trans isomers,
0
.659 ppm), but for t-butylamine and Me NH, the dif-
2
ference is larger (0.910 and 0.941 ppm). Again, these re-
sults are in agreement with the results observed in the
1
95
1
1
Pt and H NMR spectra as discussed in the
H
1
95
NMR section. An increase of electron density on the
but multinuclear and more specially
Pt NMR have
1
95
Pt atom ( Pt NMR) will correspond with a decrease
shown that the two isomers coexist in solution. The
trans compound is probably the most stable isomer,
although the two amine ligands are far from each other.
Therefore, steric hindrance is not an important factor in
this type of compound.
1
13
of electron density on the ligand ( H and C NMR).
2
195
13
Most of the J( Pt– C ) coupling constants could
1
be calculated and are shown in Table 4. They are slightly
larger for the trans isomers (average 19 Hz vs. 15 Hz),
but these values are very approximate. For a few com-
The cleavage of the iodo-bridged dimers with a
3
195
13
0
plexes, the J( Pt– C ) coupling constants were de-
second amine (amine ) will produce cis-Pt(amine)
2
0
tected. The average value for the trans compounds is
(amine )I
2
, although it might be contaminated by the
or trans-Pt(amine) as
2
5 and 18 Hz for the cis t-butylamine complex. No such
presence of cis-Pt(amine)
2
I
2
I
2 2
values have been reported yet in the literature on similar
types of complexes.
shown in this work. These diiodo complexes are usually
converted into the dichloro species by reaction with a sil-
ver salt followed by the addition of KCl. But the dia-
mine compound will always be present as impurities in
the mixed-amines complexes. Furthermore, the quantity
of silver salt is very critical in these reactions and if the
starting material is not pure, the quantity of silver salt
added will not be adequate. Some reactions of Pt species
with an excess of silver nitrate have been reported [23].
The purity of the different products is especially impor-
tant in the synthesis of compounds which have an inter-
est in chemotherapy. The purity of the compounds to be
tested for their antitumor properties should be careful
evaluated before any biological studies. It can be verified
by multinuclear NMR, which is an excellent method to
4
. Conclusion
The iodo-bridged dimers are very useful molecules
for many different types of syntheses. Its most important
use is in the preparation of mixed-amine compounds
[
7,8] They can be cleaved in water by a second type of
ligand to form mixed-ligands compounds as mentioned
previously.
IðamineÞPtðl-IÞ PtðamineÞI þ 2L
2
H2O
!
2cis ꢀ PtðamineÞðLÞI2
detect for example the presence of cis- or trans-Pt-
0
(
amine) Cl in the cis-Pt(amine)(amine )Cl complexes.
2
2
2
The diiodo mixed-ligands compounds can be trans-
formed into the dichloro species, which have better anti-
tumor properties than the corresponding diiodo
complexes. The dimers are also useful for the synthesis
1
H NMR spectroscopy is particularly a very adequate
method, since the accumulation time is relatively short
even if the compounds are not very soluble. We have
found than acetone is a relatively good solvent and no
isomerization was observed for a few days, unless the
sample is heated. We think that cis compounds should
never be heated in an organic solvent. This work has
shown that the cis disubstituted complexes isomerize
to the trans isomer in warm ethanol. DMSO reacts quite
rapidly with these types of complexes and should never
be used to characterize them. Isomerization can also oc-
cur in cold DMF, faster than in cold acetone as shown
by some previous work [13].
of the monoamine complexes K[Pt(amine)Cl ] [22].
3
They will react with a silver salt in water to produce
aqua species, which can react with KCl to form
K[Pt(amine)Cl3].
þ
IðamineÞPtðl-IÞ PtðamineÞI þ 4Ag
2
ꢀ
AgI
KCl
!
aqua species ! K½PtðamineÞCl ꢁ
3
The latter monosubstituted compounds are excellent
starting materials for all kinds of mixed-ligands com-
plexes (Pt(amine)(L)Cl ). We have also used the iodo-
2
bridged dimers to synthesize trans disubstituted
compounds with bulky ligands. The normal method to
synthesize trans compounds involve the use of the inter-
mediate tetrasubstituted compound [Pt(amine)4] , but
it cannot be used with bulky ligands (like t-butylamine).
The second amine can also be replaced by another bulky
ligand (B) to produce trans-Pt(amine)(B)I2.
5. Supplementary material
2
+
The CIF table for crystal I has been deposited to the
Cambridge Data File Centre. The deposit number is
CCDC 269590.

3
926
F.D. Rochon, V. Buculei / Inorganica Chimica Acta 358 (2005) 3919–3926
[9] Y. Chen, Z. Guo, J.A. Parkinson, S. Parsons, P.J. Sadler, Chem.
Acknowledgement
Eur. J. 4 (4) (1998) 672.
[
[
10] J. Holford, F. Raynaud, B.A. Murrer, K. Grimaldi, J.A. Hartley,
M. Abrams, L.R. Kelland, Anti-Cancer Drug Design 13 (1998) 1.
11] S.C. Dhara, Indian. J. Chem. 8 (1970) 193.
The authors are grateful to the Natural Sciences and
Engineering Research Council of Canada for financial
support of the project.
[12] F.D. Rochon, V. Buculei, Inorg. Chim. Acta 357 (2004) 2218.
[
[
[
13] F.D. Rochon, V. Buculei, Inorg. Chim. Acta 358 (2005) 2040.
14] XSCANS (V. 2.20) program, Bruker Analytical X-Ray Systems.
15] SHELXTL (PC version 5, 1995) programs, Bruker Analytical X-
Ray Systems.
References
[
[
[
1] T.W. Hambley, Coord. Chem. Rev. 166 (1997) 181.
2] M.J. Cleare, Coord. Chem. Rev. 12 (1974) 349.
3] M.J. Cleare, P.C. Hydes, B.M. Malerbi, D.M. Watkins, Biochimie
[16] L.I. Elding, L.F. Olsson, Inorg. Chem. 16 (11) (1977) 2789.
[17] G. Thiele, O.F. Danzeisen, H.W. Rotter, Z. Anorg. Chem. 624
(1998) 763.
6
0 (1978) 835.
[18] F.D. Rochon, R. Melanson, M. Doyon, I.S. Butler, Inorg. Chem.
33 (1994) 4485.
[19] A. Baeten, F. De Proft, P. Geerlings, Chem. Phys. Lett. 235
(1995) 17.
[20] M.G. Hutchings, J. Gasteiger, Tetrahedron Lett. 24 (25) (1983)
2541.
[
4] P.D. Braddock, T. Connors, M. Jones, A.R. KhorHar, D.H.
Melzack, M.L. Tobe, Chem. Biol. Interact. 11 (1975) 145.
5] F.D. Rochon, R. Melanson, Acta Cryst. C 42 (1986) 1291.
6] M. Nicolini, Platinum and Other Metal Coordination Com-
pounds in Cancer Chemotherapy, University of Padua, Italy,
[
[
1
987.
[21] J.P. Tollenaere, H. Moereels, Tetrahedron Lett. 15 (1978) 1347.
[22] F.D. Rochon, R. Melanson, M. Doyon, Inorg. Chem. 26 (1987)
3065.
[
[
7] F.D. Rochon, P.C. Kong, Can. J. Chem. 64 (1986) 1894.
8] F.D. Rochon, P.C. Kong, US Patent No. 4,533,502, 6 August
1985.
[23] F.D. Rochon, R. Melanson, Acta Cryst. C 44 (1988) 474.