Organometallic palladium and platinum complexes with strongly donating alkyl coligands - Synthesis, structures, chemical and cytotoxic properties

Article abstract of DOI:10.1016/j.jorganchem.2010.04.027

The synthesis, spectroscopy, and structures of organometallic complexes [(COD)M(R)X] and [(COD)M(R)(R′)] (COD = 1,5-cyclooctadiene, M = Pd or Pt; R = methyl, neopentyl (2,2-dimethylpropyl), neosilyl (trimethylsilylmethyl), or benzyl; X = Cl, Br, or I; R′

Full text of DOI:10.1016/j.jorganchem.2010.04.027

Journal of Organometallic Chemistry 695 (2010) 1898e1905
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Organometallic palladium and platinum complexes with strongly donating
alkyl coligands e Synthesis, structures, chemical and cytotoxic properties
,
a
b
b
a
a
Axel Klein a , Anna Lüning , Ingo Ott , Laura Hamel , Michael Neugebauer , Katharina Butsch ,
*
Verena Lingen a, Frank Heinrich a, Said Elmas a
a Institute of Inorganic Chemistry, Department of Chemistry, University of Cologne, Greinstr. 6, D-50939 Cologne, Germany
b Institute of Pharmaceutical Chemistry, Technical University Braunschweig, Beethovenstr. 55, D-38106 Braunschweig, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis, spectroscopy, and structures of organometallic complexes [(COD)M(R)X] and [(COD)M(R)
(R0)] (COD ¼ 1,5-cyclooctadiene, M ¼ Pd or Pt; R ¼ methyl, neopentyl (2,2-dimethylpropyl), neosilyl
(trimethylsilylmethyl), or benzyl; X ¼ Cl, Br, or I; R0 ¼ 2-phenyl-ethynyl, p-fluoro-2-phenyl-ethynyl,
p-methyl-2-phenyl-ethynyl or p-nitro-2-phenyl-ethynyl) has been explored. Selected samples of
organo-platinum complexes show strikingly high cytotoxicity when tested against HT-29 and MCF-7
tumour cells.
Received 20 February 2010
Received in revised form
15 April 2010
Accepted 22 April 2010
Available online 29 April 2010
Ó 2010 Elsevier B.V. All rights reserved.
Keywords:
Organopalladium
Organoplatinum
Alkyl ligands
Alkynyl ligands
Transmetallation reactions
Cytotoxicity
1. Introduction
complexes
[(COD)Pt(Me)Cl]
and
[(COD)Pt(Me)(Cyt)](SbF6)
(Cyt ¼ cytosine) exhibit high toxicity against HT-29 and MCF-7
cancer cell lines, [(COD)PtCl2] is virtually not toxic [16]. Superior
toxicity of organometallic derivatives over non-organometallic
complexes can be also concluded from Komiya’s work [13]
Takesawa’s work [18] or a recent report by Deacon et al. [19].
We also found that the MeCH3 bond is rather stable under physi-
ological conditions, and that the solubility of the compounds can
be drastically enhanced using the more bulky neopentyl
(2,2-dimethyl-1-methyl ¼ neop) coligand [16].
Organo-platinum(II) and -palladium(II) complexes [(COD)M(R)
(L)] (M ¼ Pt or Pd; R ¼ alkyl, alkynyl or aryl; L ¼ other ligands) with
COD (1,5-cyclooctadiene) as an easily exchangeable ligand have
been known for decades and are used as precursors for mono and
polynuclear organometallic platinum(II) [1e5] or palladium(II)
[6e8] compounds with applications in the field of catalysis [9e11]
or chemical vapour deposition (CVD) of platinum [12]. Another
interesting application of such complexes is their potential use as
anti-tumour agents. Some years ago Komiya et al. investigated
a series of complexes [(COD)Pt(Me)(Nuc)](NO3) (Nuc ¼ guanosine,
cytosine or adenosine nucleosides), revealing that also in these
organometallic complex fragments platinum binds preferentially
guanosine (as found for most platinum complexes) [13]. Recently
we have demonstrated the suitability of the [(COD)M(Me)] (M ¼ Pt
[14e16] or Pd [16,17]) fragments to coordinate various ligands. This
moiety allows detailed insight into the binding properties of the
ligands to platinum or palladium by 1HNMR spectroscopy
(especially for M ¼ Pt) or molecular structure determination
[14e17]. Also, we found that while the organometallic platinum(II)
The aim of the here presented work was to extend this study by
introducing various electron-rich alkyl coligands to COD platinum
(II) and also COD palladium(II) complexes (Scheme 1, top, reaction
(1)) using not only the neopentyl coligand but also neosilyl
(trimethylsilylmethyl ¼ neoSi) and benzyl, which were comparable
to neopentyl in bulkiness and s-donating properties [20].
As Scheme 1 reveals the synthetic protocol to achieve such
potentially cytotoxic complexes comprises two steps. In reaction
(1) the
R coligand is introduced applying transmetallation
reactions, while in reaction (2) further ligands L can be introduced
by abstracting the halide X from the complexes [(COD)M(R)X] using
silver or thallium salts [14e17].
A closer look in to the preparation routes to the desired
complexes [(COD)M(R)X] following reaction (1) reveals two
marked difficulties. The first occurs for the platinum complexes.
* Corresponding author.
E-mail address: axel.klein@uni-koeln.de (A. Klein).
0022-328X/$ e see front matter Ó 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2010.04.027

A. Klein et al. / Journal of Organometallic Chemistry 695 (2010) 1898e1905
1899
M = Pt or Pd
+ RM'
(1)
(2)
X
X
X
L
M' = Li, (MgX), or (SnMe3)
M
M
M
M
− XM'
X = Cl, Br, I
X
R
R
R
M'' = Ag or Tl
n+
A− = SbF6−, BF4−, ClO4
−
+ M''(A) + L
A−
− M''X
CH3
CH3
CH3
CH3
CH3
CH2
C
CH2 Si
CH2
R =
CH3
CH3
bnz
Me
neop
neoSi
Scheme 1. COD organo-platinum(II) and -palladium(II) complexes investigated in this study (X ¼ Cl, Br, or I; R ¼ Me (methyl); neop (neopentyl ¼ 2,2-dimethylpropyl); neoSi
(neosilyl ¼ trimethylsilylmethyl); bnz (benzyl); L ¼ any monodentate ligand, for examples see refs [14e17].
[(COD)PtX2] (X ¼ Cl or I) can be alkylated using a Grignard reagent
(R)MgX. However, for the preparation of methyl derivatives the
use of one equivalent (Me)MgX leads to a mixture of [(COD)Pt
(Me)2], [(COD)Pt(Me)X] and [(COD)PtX2]. The same holds also for
the other alkyl coligands and the separation of the products is
difficult in all cases. Therefore, the mono-alkylated complexes
[(COD)Pt(R)X] were best obtained from the reaction of [(COD)Pt
(R)2] using HX (Scheme 2) [1]. So far the platinum(II) [(COD)Pt
(neop)Cl] [5a], [(COD)Pt(neoSi)Cl] [4a] and [(COD)Pt(bnz)Cl]
[1,3a,3c] have been reported.
The second problem is encountered for the organo-palladium
complexes [(COD)Pd(R)X] (R ¼ alkyl). Here the transmetallation
reaction using Grignard reagents (R)MgX or lithium derivatives (R)
Li often fails, instead palladium(II) is reduced to palladium(0), even
at very low temperatures. Thus, there is a small number of reports
on complexes [(COD)Pd(R)Cl] (R ¼ alkyl) prepared from [(COD)
PdCl2] and corresponding Grignard reagents (R)MgCl [8g, 21], or (R)
Li [8d,22,23], while in most of the other reports the corresponding
stannanes Sn(R)4 were used as transmetallating agents
[6d,7,8c,16,24]. As an example [(COD)Pd(Me)Cl] is usually prepared
from [(COD)PdCl2] and Sn(Me)4 [6d]. However, this method (more
generally applicable than the Grignard route) has two main
disadvantages. First, the highly toxic ClSn(R)3 compounds are molar
co-products. Secondly, the transmetallating agent transfers only
one R equivalent but has to be prepared from SnCl4 and four
equivalents (R)MgX, which makes the whole procedure quite
ineffective. The latter drawback might be overcome by recycling the
chlorostannane ClSn(R)3. So far the synthesis of the complexes
[(COD)Pd(neoSi)Cl] (using (neoSi)MgCl) [8g, 21], or(R)Li [(COD)Pd
(bnz)Cl] [7c,8d] and [(COD)Pd(neop)Br] [16] (both using stannanes)
was described. Also a number of related compounds [(COD)Pd
(CH2CMe2Ph)Cl] [8g, 21,24]], [(COD)Pd(CH2CMe2Tol)2] [8g], [(COD)
Pd(CH2SO2Tol)2] [22], [(COD)Pd(CH2SO2Ph)Cl] [23] and [(COD)Pd
(CH(SiMe3)PPhMe2)Cl]þ [25] have been reported. In most of these
cases the stannane route was used, however a comparison of the
two methods was never aspired.
In this paper we will report on a comprehensive study on
feasible preparative routes to the complexes [(COD)M(R)X]
(R ¼ alkyl) applying both routes and alternatively lithium alkyls as
transmetallating agents. Also, we will report on first examples of
exchange reactions (2) introducing alkynyl coligands (Scheme 3).
The characterisation of the products and byproducts by multi-
nuclear NMR and IR spectroscopy will be reported for all complexes
and in many cases structural data from XRD on single crystals was
collected. Selected samples have been tested concerning their
antiproliferative properties.
(3)
(4)
X
R
+ 2 RM'
R
M' = Li or (MgX)
X = Cl, Br, I
Pt
Pt
Pt
Pt
− 2 XM'
X
R
R
Cl
+ "HCl"
− HR
R
CH3
CH3
CH3
CH3
CH3
Me
CH2
C
CH2 Si
CH2
R =
CH3
CH3
bnz
neop
neoSi
Scheme 2. Two-step synthesis of organo-platinum(II) complexes [(COD)Pt(R)X] R ¼ Me (methyl); neop (neopentyl ¼ 2,2-dimethylpropyl); neoSi (neosilyl ¼ trimethylsilylmethyl)
or bnz (benzyl).

1900
A. Klein et al. / Journal of Organometallic Chemistry 695 (2010) 1898e1905
+ HC
+ NaOEt
CR'
R'
C
Cl
C
(5)
Pt
Pt
− NaCl
− HOEt
R
R
CH3
CH3
R' = Phenyl (Ph),
4-Tolyl (4Tol),
R =
CH3
Me
CH2 Si
4-Fluorophenyl (4F)Ph,
4-Nitrophenyl (4NO2)Ph.
CH3
neoSi
Scheme 3. Synthesis of organo-platinum(II) complexes [(COD)Pt(R)(C^CR0)2] (R ¼ Me or neoSi; R0 ¼ Ph, (4Me)Ph, (4NO2)Ph or (4F)Ph.
2. Results and discussion
mandatory, which often lower the yield. The second disadvantage
lies in the excessive consumption of transmetallating agents to
produce the stannanes. E.g. five equivalents of (bnz)MgCl were
required for the preparation of one equivalent of Sn(bzl)4, while only
one benzyl group is finally transferred onto the palladium atom.
The behaviour of the corresponding platinum derivatives differs
largely from the above described palladium analogues. Both orga-
nolithium and Grignard reagents (R ¼ neop, neoSi, bnz) can be
used, the yields are fair to good (70e90%). However, the reactions
were not selective. Applying one equivalent of transmetallation
agent leads to a mixture of the three complexes [(COD)Pt(R)X],
[(COD)Pt(R)2] and [(COD)PtX2], which are virtually inseparable.
This phenomenon has been described already by Clark and Manzer
[1] and the selective preparation of the mono-alkylated product can
only be achieved via the di-alkylated derivatives as depicted in
Scheme 2. According to this Scheme, first the di-alkylated deriva-
tives [(COD)Pt(R)2] have to be synthesised, which usually requires
slightly more than 2 equivalents of transmetallation agent. One of
the two alkyl coligands is cleaved in a second step using hydro-
chloric acid (HCl), generated in situ from acetyl chloride and
methanol.
2.1. Preparations and analytical characterisation
2.1.1. Transmetallation reactions
The dihalido complexes [(COD)MX2] can be all submitted to
a transmetallation reaction (Scheme 1, reaction (1)). For palladium
(II) derivatives the reaction using Grignard reagents (R)MgX yields
exclusively the monosubstituted complexes [(COD)Pd(R)X]
(Scheme 1) even if an excess of RMgX is applied (up to 2-fold). The
yields were acceptable (R ¼ bnz, 25%) to good (R ¼ neop, 70%), the
most frequent byproducts are bibenzyl (1,2-diphenylethane) and
2,2,5,5-tetramethylhexane, resulting from the CeC-coupling
(Grignard homocoupling) reaction. The corresponding organo-
lithium derivatives (R)Li cannot be used. Reactions at temperatures
even below ꢀ30 ꢁC gave precipitated elemental palladium. Since
for R ¼ methyl or benzyl the yields were not good, we used the
corresponding stannanes Sn(R)4 [6c,6d,26] and obtained far better
yields of 42% of [(COD)Pd(bnz)Cl] and 92% for [(COD)Pd(Me)Cl]. One
disadvantage of this method lies in the high toxicity of the
byproducts XSn(R)3. This makes thorough recrystallisations
Table 1
Selected 1H and 195Pt NMR data of palladium and platinum complexes.a
d
, H1,2COD trans L
2JPteH, H1,2COD trans L
d
, H5,6COD trans R
2JPteH, H5,6COD trans R
d
, MeCH2e
2JPteH, PteCH2e
d,
195Pt
[(COD)PtCl2]
[(COD)PtI2]
[(COD)Pt(Me)2]
[(COD)Pt(Me)Cl]
[(COD)Pt(Me)Br]
[(COD)Pt(Me)I]
[(COD)Pt(neoSi)2]
[(COD)Pt(neoSi)Cl]
[(COD)Pt(neoSi)Br]
[(COD)Pt(bnz)2]
[(COD)Pt(bnz)Cl]
[(COD)Pt(neop)2]
5.51
5.78
4.77
4.54
4.59
4.73
4.71
4.59
4.66
4.68
4.45
4.92
4.53
4.62
4.14
3.76
4.92
4.91
4.92
5.00
4.95
4.95
5.21
4.87
5.34
68
66
42
75
74
75
41
74
79
42
75
38
75
76
38
75
49
50
49
50
48
48
e
5.51
5.78
4.77
5.42
5.43
5.46
4.71
5.35
5.37
4.68
5.48
4.92
5.47
5.50
4.14
5.44
5.47
5.46
5.43
5.46
5.36
5.41
5.77
5.89
5.81
68
66
42
36
34
39
41
38
40
42
38
38
33
35
38
30
36
37
36
35
38
38
e
e
e
e
ꢀ3332
ꢀ3543
ꢀ3572
ꢀ3501
ꢀ3627
ꢀ3888
ꢀ3568
ꢀ3456
ꢀ3586
ꢀ3646
ꢀ3507
ꢀ3523
ꢀ3460
ꢀ3580
ꢀ3541
ꢀ3454
ꢀ3112
ꢀ3108
ꢀ3115
ꢀ3124
ꢀ3166
ꢀ2985
e
e
0.64
0.78
0.78
1.01
0.87
0.95
1.12
2.87
3.06
1.90
1.72
1.90
2.21
2.05
0.95
0.94
0.94
0.96
1.08
1.15
1.00
3.59
2.34
83
73
73
73
94
76
77
114
102
92
81
82
90
81
77
78
78
77
89
88
e
[(COD)Pt(neop)Cl]
[(COD)Pt(neop)Br]
[(COD)Pt(neoPh)2]
[(COD)Pt(neoPh)Cl]
[(COD)Pt(Me)(C^CPh)]b
[(COD)Pt(Me)(C^C(4Me)Ph)]b
[(COD)Pt(Me)(C^C(4F)Ph)]b
[(COD)Pt(Me)(C^C(4NO2)Ph)]b
[(COD)Pt(neoSi)(C^CPh)]b
[(COD)Pt(neoSi)(C^C(4F)Ph)]c
[(COD)Pd(Me)Cl]
[(COD)Pd(bnz)Cl]c
[(COD)Pd(neop)Br]
e
e
e
e
e
e
e
e
a
1H or 195Pt NMR shifts [ppm] and selected 195PteH coupling constants [Hz], measured in acetone-d6.
Measured in CD2Cl2.
Measured in CDCl3.
b
c

A. Klein et al. / Journal of Organometallic Chemistry 695 (2010) 1898e1905
1901
Table 2
Selected parameter of crystal structure measurements and refinements of palladium(II) and platinum(II) complexes [(COD)M(R)X].a
[(COD)Pd
(bnz)Cl]
[(COD)Pd
(neop)Br]
[(COD)Pt
(Me)Cl]
[(COD)Pt
(bnz)Cl]
[(COD)Pt
(bnz)2]
[(COD)Pt
(neoSi)Cl]
[(COD)Pt
(neop)Cl]
[(COD)Pt
(neop)Br]
Formula
C
15H19Cl1Pd1
C13H23 Br1 Pd1 C9H15 Cl1Pt1
C15H19Cl1Pt1
429.86
Monoclinic
P21/c
C22H26 Pt1
485.52
Monoclinic
P21/c
C12H23Cl1Si1Pt1 C13H23 l1Pt1
C13H23 Br1Pt1
454.31
Monoclinic
P21/c
Weight (g molꢀ1
)
341.17
Triclinic
P-1b
365.63
Monoclinic
P21/c
353.76
Orthorhombic
P212121
425.93
Monoclinic
P21/c
409.85
Monoclinic
P21/c
Crystal system
Space group
c
Temperature (K)
cell a (Å)
b (Å)
c (Å)
293(2)
293(2)
6.6560(9)
12.244(1)
18.056(3)
90
105.721(16)
90
1416.5(3)
4
1.714
4.101
728
0.796
293(2)
6.9618(7)
11.162(2)
12.561(1)
90
293(2)
9.466(1)
11.345(1)
14.378(3)
90
118.43(1)
90
1357.9(4)
4
203(2)
11.170(2)
8.105(2)
19.576(4)
90
94.39(3)
90
1767.2(6)
4
1.825
7.938
944
0.894
173(2)
6.574(1)
12.233(2)
18.054(5)
90
101.10(3)
90
1472.5(5)
4
1.921
9.763
816
1.010
293(2)
6.4982(9)
12.220(2)
17.959(3)
90
104.06(2)
90
1383.4(4)
4
293(2)
6.612(1)
12.253(3)
18.054(5)
90
105.39(3)
90
1410.2(5)
4
6.640(1)
14.109(3)
15.512(3)
81.234(17)
89.633(15)
79.452(16)
1411.7(5)
2
1.605
1.480
688
0.586
a
b
90
90
g
V (Å3)
976.1(2)
2
2.407
14.585
656
Z
rcalc (g cmꢀ3
)
2.103
10.505
816
1.968
10.306
784
2.140
12.754
856
m
(mmꢀ1
F(000)
Goof. on F2
)
0.982
0.878
0.537
0.582
Final R1, wR2 [I > 2
R1, wR2 (all data)
s
(I)]
0.0463, 0.0640 0.0362, 0.0604 0.0689, 0.1618 0.0368, 0.0792 0.0513, 0.1360 0.0233, 0.0543
0.1697, 0.0806 0.0865, 0.0689 0.0784, 0.1693 0.0678, 0.0870 0.0701, 0.1502 0.0318, 0.0562
0.0466, 0.0633 0.0335, 0.0513
0.1390, 0.0788 0.1074, 0.0623
Larg. diff. peak/hole (e.Åꢀ3
CCDC No.
)
1.038/0.892
764339
0.609/0.918
764340
4.413/6.333
764341
1.462/1.977
764342
3.252/3.445
764343
0.610/1.089
764344
1.332/1.343
764345
1.030/1.366
764346
a
Radiation wavelength
[(COD)Pd(bnz)Cl] has also been found to crystallise in P212121[7c].
[(COD)Pt(Me)Cl] is also reported to crystallise in monoclinic C2/c [14].
l
¼ 0.71073 Å; Refinement method: Full-matrix least-squares on F2.
b
c
2.1.2. Ligand exchange reactions
In Table 1 these values were collected for the new complexes,
Alkynyl coligands C^CR0 (R0 ¼ Ph, (4Me)Ph, (4NO2)Ph or (4F)Ph)
were introduced by reacting the corresponding alkynes HC^CR0
with the mono-alkylated platinum complexes [(COD)Pt(R)Cl]
(R ¼ Me or neoSi) in the presence of NaOEt (generated from sodium
and ethanol) or KOtBu in excellent yields (Reaction 5, Scheme 3).
revealing almost uniform values around 30 Hz for the olefinic
protons trans to strong
s-donor coligands R. The corresponding
coupling constants of the olefinic protons trans tothe halide co-ligand X
lie about 75e80 Hz, while for alkynyl coligands about 50 Hz were
found, which means that alkynyl coligands can also be considered to
be relatively strongly
s-donating, since principally feasible p-
contribution is probably not very large [28]. The chemical shifts of
the olefin protons H1,2 nicely reflect the spatial proximity of the
electron-rich alkyl ligands showing upfield-shifted resonances
compared to the H5,6 protons. The latter experience the p-electron
density of the alkynyl (or halido) coligand, leading to a downfield
shift. Strong downfield shifts were also found for the coligands
2.2. NMR spectroscopy
Apart from being an important analytical tool in our study,
detailed multinuclear NMR spectroscopy allowed us to address
a number of important questions concerning the constitution of the
complexes in solution, their reactivity and in case of the platinum
derivatives enabled us also to determine relative bond strengths of
the (co)ligands R, R0 and L. It is well established since the 1970s that
the trans-influence of a ligand and thus its strength correlates well
with metaleligand coupling constants. For platinum complexes
coupling of the 195Pt isotope to 1H, 31P, 13C, or 15N nuclei has been
widely used [15,16,27]. We successfully applied this correlation for
a large number of complexes [(COD)Pt(Me)L]nþ [14e16], mainly by
eCH2e protons facing a phenyl group in the Cb position (bnz, or
neoPh) due to the diamagnetic ring current, while the C^CPh
phenyl groups are remote and do not exert any influence. 1H NOESY
results completely confirm these considerations.
2.3. Crystal and molecular structures
2
using the JPteH(COD) coupling constant as a measure for the bond
From the compounds [(COD)Pd(bnz)Cl], [(COD)Pd(neop)Br],
[(COD)Pt(Me)Cl], [(COD)Pt(bnz)Cl], [(COD)Pt(bnz)2], [(COD)Pt
strength of the corresponding trans-oriented coligand R or ligand L.
Fig. 1. Molecular structures of one of the two independent molecules of [(COD)Pd(bnz)Cl] (left) and of [(COD)Pt(bnz)Cl] (right). All atoms at 50% probability level; protons not
involved in intramolecular H bonding were omitted for clarity.

1902
A. Klein et al. / Journal of Organometallic Chemistry 695 (2010) 1898e1905
Fig. 2. Molecular structures of [(COD)Pt(bnz)2] (left) and [(COD)Pt(neoSi)Cl] (right). All atoms at 50% probability level; all protons were omitted for clarity.
(neoSi)Ph], [(COD)Pt(neoSi)Cl], [(COD)Pt(neop)Cl], and [(COD)Pt
(neop)Br] single crystals could be obtained during the preparations
in solvents mentioned in the Experimental Section. The structures
were solved and refined in various symmetries and space groups
ranging from triclinic P-1 to orthorhombic P212121 (Table 2).
Although some of the structures could not be refined satisfactorily
(large residual electron densities, small Goofs) the high similarity of
all the structures makes us confident that the solution and refine-
ment for all compounds was carried out correctly and only poor
crystal quality and insufficient absorption correction is responsible
for the low quality of some of the structure determinations.
A number of weak intermolecular contacts were observed, most
of them are H/X hydrogen bridges. An examination of the H/X
distances reveals values all exceeding 2.8 Å, which classifies them
as very weak H bonds. In the crystal structure of [(COD)Pt(bnz)Cl]
a packing of the benzyl coligands can be observed with close
The central palladium or platinum atoms all lie in a perfect plane
defined by the centroids Y(1) and Y(2), the metal-binding carbon
atom of the coligand (eCH2e) and the second coligand (either X or C)
as can be seen e.g. from the S of angles around M, (Table 3). The
phenyl, CMe3 and SiMe3 cores of the coligands are bent away by
a constant angle (MeCH2eR00) of usually about 120ꢁ, only for [(COD)
Pd(bnz)Cl] this angle is markedly smaller (Fig. 1, Table 3). However,
an inspection of a big number of benzyl palladium(II) or platinum(II)
complexes reveals angles varying from about 103ꢁ [31] to 120ꢁ [32]
for palladium(II) and 112ꢁ [33] to 119ꢁ [34] for platinum(II). Thus
all values lie in the typical range. Furthermore, the complex [(COD)Pd
(bnz)Cl] has been previously reported in different space group
P212121 with a corresponding angle of 112.1(4)ꢁ [7c]. Another pecu-
liar finding is that the centre of the phenyl core lies approximately
within the coordination plane of the metal (in plane) for the two Pt
complexes [(COD)Pt(bnz)Cl] and [(COD)Pt(bnz)2], while for the Pd
derivative [(COD)Pd(bnz)Cl] the benzyl coligand points away in
a direction almost perpendicular to the coordinationplane. The latter
situation is also found for the other coligands neop and neoSi. Since
this has no precedent in the crystal/molecular structures of benzyl
platinum complexes we had thus a closer look on intra and inter-
molecular interactions. First, in the structure of [(COD)Pt(bnz)Cl] an
intramolecular hydrogen bond C(8)eH8A/Cl1 of 2.835(2) Å (angle
CeH/Cl ¼ 92.30(5)ꢁ) is observed, however, for the Pd derivative
[(COD)Pd(bnz)Cl] a hydrogen bond of approximately the same
strength is found (2.868(4) Å). Next we examined intramolecular
CeH/
p
contacts of about 3.1 Å (distance H/centroid). Such
CeH/
p
contacts might have an impact on the crystal structure
[29,30], marked influence on the molecular structure is only
reported for molecules showing far shorter distances around 2.5 Å
[29]. Other CeH/p or pep interactions were not observed. Also no
Pt/Pt contacts were observed, which is probably due to a shielding
effect by the COD ligand. Figures of crystal structures can be found
in the Supplementary Material. Figs. 1 and 2 show representative
examples of the molecular structures and Table 3 summarises the
essential bonding parameters for the neutral complexes.
Table 3
Selected distances (Å) and angles (deg.) of complexes [(COD)Pd(bnz)Cl], [(COD)Pd(neop)Br], [(COD)Pt(Me)Cl], [(COD)Pt(bnz)Cl], [(COD)Pt(bnz)2], [(COD)Pt(neoSi)Cl], [(COD)Pt
(neop)Cl], and [(COD)Pt(neop)Br].
[(COD)Pd (bnz) Cl]b
[(COD)Pd
(neop)Br]
[(COD)Pt
(Me) Cl]
[(COD)Pt
(bnz) Cl]
[(COD)Pt
(bnz)2]
[(COD)Pt
(neoSi)Cl]
[(COD)Pt
(neop)Cl]
[(COD) Pt
(neop) Br]
Distances
MeX
2.353(3), 2.350(3)
2.040(8), 2.057(8)
2.091(15), 2.160(10)
2.164(9), 2.178(9)
2.391(15), 2.392(10)
2.431(10), 2.445(11)
2.031(1), 2.065(1)
2.318(1), 2.323(1)
2.4586(7)
2.062(5)
2.163(5)
2.173(5)
2.379(5)
2.476(5)
2.057(5)
2.334(5)
2.330(5)
2.127(15)
2.13(2)
2.090(19)
2.264(17)
2.26(2)
2.323(2)
2.106(7)
2.145(8)
2.130(7)
2.290(8)
2.275(8)
2.018(1)
2.175(1)
2.086(7) C(20)
2.096(8)
2.235(6)
2.206(7)
2.223(7)
2.229(6)
2.108(7)
2.115(7)
2.3241(11)
2.065(5)
2.134(4)
2.135(4)
2.307(5)
2.282(5)
2.013(5)
2.189(5)
2.356(3)
2.068(11)
2.094(13)
2.124(14)
2.300(9)
2.346(10)
2.000(1)
2.228(1)
2.4447(12)
2.064(10)
2.123(9)
2.109(8)
2.344(9)
2.286(10)
1.995(9)
2.217(10)
MeC(10)
MeC(11)
MeC(12)
MeC(15)
MeC(16)
MeY(1)a
MeY(2)a
1.980(1)
2.160(1)
Angles
C(10)eMeX
C(10)eMeY(1)
C(10)eMeY(2)
XeMeY(1)
XeMeY(2)
Y(1)eMeY(2)
MeCH2eR0
89.4(2), 88.7(3)
90.2(2), 93.1(2)
176.0(2), 174.8(3)
171.4(1), 173.0(1)
94.5(1), 95.2(1)
86.1(1), 83.4(1)
110.7(6), 110.9(6)
360.2(1), 360.4(2)
91.2(2)
92.8(2)
175.5(2)
169.3(2)
92.9(2)
83.5(2)
119.3(3)
360.4(2)
86.0(7)
93.7(7)
177.3(5)
179.7(6)
94.4(6)
85.9(5)
e
86.4(2)
95.6(2)
177.9(3)
178.0(1)
92.0(1)
86.0(1)
121.9(5)
360.0(1)
83.5(3)
96.6(3)
177.6(4)
178.4(3)
94.6(3)
85.2(3)
122.3(5), 119.3(5)
359.9(3)
90.3 (2)
91.8(2)
176.2(2)
175.7(2)
92.0(2)
86.0(2)
115.7(3)
360.1(2)
91.2(4)
91.9(3)
175.0(3)
172.3(1)
92.1(1)
85.3(1)
121.8(8)
360.5(2)
89.9(3)
93.7(4)
176.1(4)
171.6(3)
92.4(3)
84.5(4)
122.4(7)
360.5(4)
S of angles around M
360.0(6)
a
Two independent molecules in the unit cell.
Centroids Y(1) and Y(2) are defined as the averaged olefinic bonds between C(11) and C(12) or C(15) and C(16) respectively.
b

A. Klein et al. / Journal of Organometallic Chemistry 695 (2010) 1898e1905
1903
Table 4
concerning their molecular structures in solution (multinuclear
NMR spectroscopy) and in the solid state (XRD). Furthermore focus
was laid on the synthesis procedures revealing some differences
between palladium(II) and platinum(II) homologues, which helped
to optimise the yields. Selected samples were submitted to anti-
proliferative testing using HT-29 and MCF-7 tumour cells. For some
of the samples, namely the mixed alkyl alkynyl complexes striking
IC50 values below that of cisplatin suggest more detailed biological
studies on this type of platinum bioorganometallics.
Cytotoxicity of selected compounds in HT-29 and MCF-7 cells expressed as IC50
values obtained in 2 independent experiments (standard deviations are given as
superscript numbers).
IC50 HT-29
in
7.0ꢂ2.0
>100
IC50 MCF-7
in
2.0ꢂ0.3
>100
Reference
m
M
mM
Cisplatin
[(COD)PtCl2]
[(COD)Pt(Me)Cl]
[(COD)Pt(bnz)Cl]
[(COD)Pt(neoSi)Cl]
[(COD)Pt(Me)(C^C(4F)Ph)]
[(COD)Pt(Me)(C^C(4Me)Ph)]
[(COD)Pt(Me)(C^C(4NO2)Ph)]
[(COD)Pt(Me)(C^CPh)]
34
16
16
This work
This work
This work
This work
This work
This work
8.3ꢂ3.0
10.3ꢂ3.3
7.4ꢂ2.7
4.6ꢂ0.2
0.2ꢂ0.1
2.3ꢂ0.7
9.0ꢂ1.7
11.2ꢂ1.4
9.7ꢂ1.0
8.5ꢂ0.5
4.7ꢂ0.7
0.3ꢂ0.1
1.9ꢂ0.6
10.5ꢂ7.9
4. Experimental
4.1. General
All preparations were carried out in a dry argon atmosphere
using Schlenk techniques. Solvents (CH2Cl2, THF, toluene, diethyl
ether and MeCN) were dried using an MBRAUN MB SPS-800 solvent
purification system.
(olefin)CeH/
H/centroid distances were all around 3.1 Å, which is not significant
for a strong CeH/ interaction [29]. This is in agreement with the
NMR results showing a measurable but weak interaction. Thus, we
conclude that in these neutral complexes the interplay of various
weak intra- and intermolecular forces create a variety of slightly
different crystal and molecular structures by varying essentially the
PteC(10)eC/Si angle and direction of the coligands.
The distances of the olefin carbon atoms, also represented by the
centroids Y, reflect the character of the trans-oriented coligands (in
terms of the trans-influence). For trans-oriented halogenido
coligands the MeY distances are markedly shorter than the MeY
distances at the trans-position of the alkyl coligands in agreement
with the differences in coupling constants observed in solution
(NMR). Here it is interesting to note, that for the complex [(COD)Pt
(Me)Cl], crystallised in this work in the orthorhombic space group
P212121, the bond distances and angles do not significantly deviate
from the previously reported structure in monoclinic C2/c [14].
p(PheCH2e) interactions. However, the shortest
p
4.2. Instruments
The NMR spectra were recorded on a Bruker Avance II 300 MHz
(1H: 300.13 MHz, 13C: 75.47 MHz)/Bruker Avance 400 spectrometer
(1H: 400.13 MHz, 13C: 100.61 MHz, 195Pt: 86.01 MHz) using a triple
resonance 1H,19F,BB inverse probehead or on a Bruker Avance II 600
spectrometer (1H: 600.13 MHz). The broad band coil was tuned to
either the carbon or the platinum frequency and the detection coil
to the proton frequency, resulting in 90ꢁ pulses of 11.9
m
s for 13C,
12.5
m
s for 195Pt and 12.4 s for 1H. The unambiguous assignment of
m
the 1H, 13C and 195Pt resonances was obtained from 1H TOCSY, 1H
COSY, 1H NOESY, gradient selected 1H, 13C HSQC and HMBC and
gradient selected 1H, 195Pt HMBC experiments. All 2D NMR exper-
iments were performed using standard pulse sequences from the
Bruker pulse program library. Chemical shifts were relative to TMS
for 1H and 13C and Na2[PtCl6] in D2O for 195Pt. The spectra analyses
were performed by the Bruker TopSpin 1.3 software. EI-MS spectra
were measured using a Finnigan MAT 95. Elemental analyses were
carried out on Hekatech CHNS EuroEA 3000 Analyzer. IR spectra
2.4. Cytotoxicity
In continuation of our previous work on the cytotoxicity of
organo-platinum(II) and -palladium(II) complexes we evaluated
some of the complexes selected for their antiproliferative effects in
HT-29 colon carcinoma and MCF-7 breast adenocarcinoma cells
(Table 4). Previous studies on platinum COD species had indicated
that replacing one chlorido ligand of [(COD)PtCl2] with methyl
resulted in a considerable increase in cytotoxic potency,[16] which
is in line with the early findings of Takesawa et al.[18] In good
agreement with this the structural analogues [(COD)Pt(bnz)Cl] and
[(COD)Pt(neoSi)Cl] showed promising activities in both cell lines in
were measured on Bruker IFS66nS.
4.3. Reagents
The complexes [(COD)PtCl2] [1], [(COD)PdCl2] [36], [(COD)
PdBr2] [36], [(COD)Pt(Me)2] [1], [(COD)Pt(Me)Cl] [1], [(COD)Pd(Me)
Cl] [6c,6d], [(COD)Pt(neop)2] [20a], [(COD)Pt(neop)Cl] [5a] and
[(COD)Pd(neop)Br] [16] were prepared according to published
procedures. All other chemicals were purchased by commercial
suppliers and were used without further purification.
the range of 7e10
in the position of the chlorido ligand led to species with activities in
the range of 0.2e10 M. The highest activities were observed with
mM. Introducing different phenylalkynyl ligands
m
the Me substituted [(COD)Pt(Me)(C^C(4Me)Ph)], which was
substantially more active than the platinum anticancer lead
compound cisplatin. The differences in biological activity between
the different phenylalkynyl platinum derivatives can be attributed
to different electronic, steric and lipophilic effects of the substitu-
ents. This in turn might lead to possible differences in their cellular
accumulation and biodistribution, interaction with biological
targets (such as binding to the DNA) or involvement in cellular
redox biochemistry (e.g. alterations in the formation of reactive
oxygen species) and suggests more detailed biochemical/pharma-
logical investigations.
4.4. Synthesis of [(COD)Pt(bnz)2] and [(COD)Pt(bnz)Cl]
The compounds were prepared according to the method
described for [(COD)Pt(Me)2] and [(COD)Pt(Me)Cl] [1,3a]. For the
preparation of [(COD)Pt(bnz)2] the precursor [(COD)PtCl2] was
reacted with (bnz)MgCl. Yield: 85%. Anal. Calc. for C22H26Pt
(485.54): C, 54.42; H, 5.40. Found: C, 54.41; H, 5.48. 1H-NMR (
d,
CDCl3): 7.16e7.05 (m; 8H, HPhbnz), 6.90 (m, 2H, HPhbnz), 4.68 (s, 4H,
H1,2,5,6COD, 2JPtH ¼ 42 Hz), 2,87 (s, 4H, CH2bzl, 2JPtH ¼ 113 Hz), 2.24 (m,
8H, H3,4,7,8COD). 195Pt NMR (
d
, CDCl3): ꢀ3647. For the preparation of
[(COD)Pt(bnz)Cl] the starting material [(COD)Pt(bnz)2] was reacted
with an appropriate amount of acetyl chloride in a mixture of
acetone/methanol (5/1). Yield 95%: Anal. Calc. for C15H19Cl1Pt1
(429.86): C, 41.91; H, 4.46. Found: C, 41.88; H, 4.46. EI-MS: 430
3. Conclusions and outlook
A
big number of organo-palladium(II) and -platinum(II)
[M]þ. 1H-NMR (
d, CDCl3): 7.16e6.98 (m, 5H, HPhbnz), 5.58 (m, 2H,
complexes could be synthesised and thoroughly characterised
H5,6COD, 2JPtH ¼ 37 Hz), 4.32 (m, 2H, H1,2COD, 2JPtH ¼ 75 Hz), 3.15 (s,

1904
A. Klein et al. / Journal of Organometallic Chemistry 695 (2010) 1898e1905
2H, CH2bzl, 2JPtH ¼ 102 Hz), 2.41e2.16 (m, 8H, H3,4,7,8COD). 195Pt NMR
2J(PteH) ¼ 77 Hz, HMe). 195Pt-1H-HMBC (
, CD2Cl2): ꢀ3112. IR (KBr, in
d
(d
, CDCl3): ꢀ3508.
cmꢀ1): 3039, 3912, 2991 (w): yCaCH COD; 2928, 2880 (s), 2833, 2798
(m): yCH2 COD; 2111 (s): yC^C; 1596, 1566, 1516, 1486 (s): yCaC Ph
.
4.5. Synthesis of [(COD)Pd(bnz)Cl]
[(COD)Pt(Me)(C^C(4Me)Ph)]: Yield: 98 mg (0.22 mmol, 79%).
Anal. Calc. for C18H22Pt1 (433.45): C, 49.88; H, 5.12. Found: C, 49.88;
To a suspension of 1.5 g (5.25 mmol) [(COD)PdCl2] in 50 mL
diethyl ether 1.03 g (6.83 mmol) of a freshly prepared solution of
(bnz)MgCl in 20 mL diethyl ether were added within 30 min while
stirring at 0 ꢁC. After further stirring for 30 min the brownish
suspension was treated with 30 mL of moist diethyl ether and
filtered through Celite. The clear yellow filtrate was evaporated to
dryness, the resulting yellow solid washed with 10 mL n-pentane
and dried in vacuo. Yield: 448 mg (1.31 mmol, 25%). Anal. Calc. for
C15H19Cl1Pd1 (341.17): C, 52.81; H, 5.61. Found: C, 52.79; H, 5.68.
H, 5.18. EI-MS: 433 [M]þ. 1H-NMR (
d
, CD2Cl2): 7.12 (d, 2H, Ho-Ph),
2
7.04 (d, 2H, Hm-Ph), 5.46 (m, 2H, J(PteH) ¼ 37 Hz, H1,2cod), 4.91
(m, 2H, 2J(PteH) ¼ 50 Hz, H5,6cod), 2.46e2.41 (m, 8H, H3,4,7,8cod), 2.30
(s, 3H, 2J(PteH) ¼ 78 Hz, HMe-Tol), 0.94 (s, 3H, J(PteH) ¼ 78 Hz, HMe).
2
195Pt-1H-HMBC (
3012 (w): yCaCH COD; 2949, 2882 (s), 2835, 2802 (m): yCH2 COD; 2113
d
, CD2Cl2): ꢀ3108. IR (KBr, in cmꢀ1): 3049, 3033,
(s): yC^C; 1602, 1559, 1540 (w), 1501 (s): yCaC Ph
.
[(COD)Pt(Me)(C^C(4F)Ph)]: Yield: 105 mg (0.24 mmol, 84%).
Anal. Calc. for C17H19Pt1F1 (437.41): C, 46.68; H, 4.38. Found: C,
EI-MS: 338 [M]þ. 1H-NMR (
d, CDCl3): 7.43 (m, 2H, HPhbnz), 7.14 (m,
46.66; H, 4.41. EI-MS: 437 [M]þ. 1H-NMR (
d, CD2Cl2): 7.29 (dd, 2H,
3H, HPhbnz), 5.89 (m, 2H, H5,6COD), 4.87 (m, 2H, H1,2COD), 3.59 (s, 2H,
HCH2bnz), 2.62e2.27 (bm, 8H, H3,4,7,8COD).
Ho-Ph), 6.93 (t, 2H, Hm-Ph), 5.45 (m, 2H, 2J(PteH) ¼ 36 Hz, H1,2cod), 4.92
(m, 2H, 2J(PteH) ¼ 49 Hz, H5,6cod), 2.44 (m, 8H, H3,4,7,8cod), 0.94 (s, 3H,
2J(PteH) ¼ 78 Hz, HMe). 19F-NMR (
d
, CD2Cl2): ꢀ116. 195Pt-1H-HMBC (
d
,
4.6. Synthesis of [(COD)Pt(neoSi)2] and [(COD)Pt(neoSi)Cl]
CD2Cl2): ꢀ3115. IR (KBr, in cmꢀ1): 3036, 3006, 2988 (w): yCaCH COD
;
2943, 2883 (s), 2837, 2803 (m): yCH2 COD; 2113 (s): yC^C; 1598, 1585,
To a suspension of 0.9 g (2.43 mmol) [(COD)PtCl2] in 20 mL
diethyl ether 3.58 g (24.33 mmol) of a freshly prepared solution of
(neoSi)MgCl in 30 mL diethyl ether were added within 40 min
while stirring at ꢀ55 ꢁC. After further stirring for 3 h at ambient
temperature the suspension was cooled to ꢀ20 ꢁC and quenched
with 10 mL saturated aqueous NH4Cl solution. After phase sepa-
ration the aqueous phase was extracted three times with 20 mL of
CH2Cl2. The organic phases were combined, dried over MgSO4,
filtered and evaporated to dryness. Yield: 1123 mg (2.35 mmol;
96%). Anal. Calc. for. C16H34Pt1Si2 (477.72): C, 40.23; H, 7.17. Found:
1518 (w), 1500 (s): yCaC Ph.
[(COD)Pt(Me)(C^C(4NO2)Ph)]: Yield: 88 mg (0.19 mmol, 67%).
Anal. Calc. for C17H19N1O2Pt1 (464.42): C, 43.96; H, 4.12; N, 3.02.
Found: C, 43.99; H, 4.08; N,3.05. 1H-NMR (
d
, CD2Cl2): 8.08 (d, 2H,
2
Hm-Ph), 7.43 (d, 3H, Ho-Ph,), 5.46 (m, 2H, J(PteH) ¼ 35 Hz, H1,2cod),
5.00 (m, 2H, 2J(PteH) ¼ 50 Hz, H5,6cod), 2.46 (m, 8H, H3,4,7,8cod), 0.96
(s, 3H, 2J(PteH) ¼ 77 Hz, HMe). 195Pt-1H-HMBC (
, CD2Cl2): ꢀ3124. IR
d
(KBr, in cmꢀ1): 3108, 3068 (w): yCaCH COD; 2960, 2927, 2885 (m):
yCH2 COD; 2116 (s): yC^C; 1633,1593, 1518 (m), 1513 (s): yCaC Ph; 1342
(s): yNO2; 694 (w): dNO2
.
C, 40.29; H 7.20. EI-MS: 478 [M]þ. 1H-NMR (
d, acetone-d6): 4.73
[(COD)Pt(neoSi)(C^CPh)]: Yield: 103 mg (0.21 mmol, 73%).
(m, 4H, 2J(PteH) ¼ 43 Hz, H1,2,5,6cod), 2.32 (m, 8H, H3,4,7,8cod), 0.87 (s,
Anal. Calc. for C20H28Pt1Si1 (491.61): C, 48.86; H, 5.74. Found: C,
4H, 2J(PteH) ¼ 94 Hz, CH2neoSi), 0.04 (s, 18H, MeneoSi). 195Pt-1H-HMBC
48.85; H, 5.70. 1H-NMR (
d, acetone-d6): 7.30 (d, 2H, Ho-Ph), 7.18 (m,
(
d
, acetone-d6): ꢀ3568.
3H, Hm-Ph, p-Ph), 5.36 (m, 2H, 2J(PteH) ¼ 38 Hz, H1,2cod), 4.95 (m, 2H,
2J(PteH) ¼ 48 Hz, H5,6cod), 2.42 (m, 8H, H3,4,7,8cod), 1.08 (s, 2H,
2J(PteH) ¼ 89 Hz, HCH2Si), 0.11 (s, 9H, 2J(PteH) ¼ 117 Hz, 2J(Si-H) ¼ 6 Hz,
To a solution of 1.0 g (2.06 mmol) [(COD)Pt(neoSi)2] in 75 mL
acetone an 2 mL methanol were added at ꢀ55 ꢁC 207
mL
(2.93 mmol) acetyl chloride. The mixture was stirred for 3 h at
ambient temperature and evaporated to dryness. Recrystallisation
from CH2Cl2/n-heptane 10/2 mL gave 813 mg gave colourless
crystals. Yield: 813 mg (1.91 mmol, 92%) Anal. Calc. for.
C12H23Cl1Pt1Si1 (425.95): C, 33.83; H, 5.44. Found: C, 33.89; H 5.46.
HMe3Si). 195Pt-1H-HMBC (
d
, acetone-d6): ꢀ3166. 29Si-1H-HMBC
(d
, acetone-d6): 1.79. IR (KBr, in cmꢀ1): 3057, 3038, 3025, 3003 (w):
yCaCH COD; 2937, 2888, 2877, 2832 (s): yCH2 COD; 2118 (s): yC^C; 1595
(s), 1572, 1518 (w), 1482 (s): yCaC Ph
.
[(COD)Pt(neoSi)(C^C(4F)Ph)]: Yield: 107 mmol (0.21 mmol,
EI-MS: 426 [M]þ 411 [MeMe]þ. 1H-NMR (
d
, acetone-d6): 5.35 (m,
71%). Anal. Calc. for C20H27Pt1F1Si1 (509.59): C, 47.14; H, 5.34.
2H, 2J(PteH) ¼ 38 Hz, H5,6cod), 4.59 (m, 2H, 2J(PteH) ¼ 74 Hz, H1,2cod),
2.64e2.20 (m, 8H, H3,4,7,8cod), 0.95 (s, 2H, 2J(PteH) ¼ 76 Hz, CH2neoSi),
0.09 (s, 9H, 1J(C-H) ¼ 118 Hz, 2J(Si-H) ¼ 6.5 Hz, MeneoSi). 29Si-1H-
Found: C, 47.11; H, 5.37. 1H-NMR (
d
, CDCl3): 7.34 (m, 2H, Ho-Ph), 6.92
2
(t, 2H, Hm-Ph), 5.41 (m, 2H, J(PteH) ¼ 38 Hz, H1,2cod), 4.95 (m, 2H,
2J(PteH) ¼ 48 Hz, H5,6cod), 2.42 (m, 8H, H3,4,7,8cod),1.15 (s, 2H,
2J(PteH) ¼ 88 Hz, HCH2Si), 0.14 (s, 9H, 2J(PteH) ¼ 117 Hz, 2J(Si-H) ¼ 6 Hz,
HMBC (
d
, acetone-d6): 1.66. 195Pt-1H-HMBC (
d, acetone-d6): ꢀ3456.
HMe3Si). 19F-NMR (
d
, CDCl3): ꢀ115. 195Pt-1H-HMBC (
d, CDCl3):
4.7. Synthesis of [(COD)Pt(Me)(C^CR0)] and [(COD)Pt(neoSi)
(C^CR00)] (R0 ¼ Ph, (4Me)Ph, (4F)Ph, (4NO2)Ph; R00 ¼ Ph, (4F)Ph
ꢀ2985. 29Si-1H-HMBC (
d, CDCl3): 1.92.
4.8. Crystal structure determination
The compounds were prepared in a variation to the method
described for [(COD)Pt(C^CPh)2] [37]: A suspension of 104 mg
(0.29 mmol) [(COD)Pt(Me)Cl] or 124 mg (0.29 mmol) [(COD)Pt
(neoSi)Cl] in 10 mL ethanol was maintained at ꢀ30 ꢁC and a freshly
prepared mixture of the alkyne (0.32 mmol, 1.1 eq) and sodium
ethoxide (prepared from 7 mg sodium) or 36 mg (0.32 mmol,1.1 eq)
potassium tert-butoxide in 5 mL ethanol were added dropwise
with constant stirring. The solutions became darker and after 2 h
the colourless products were filtered off. Recrystallisation from
CH2Cl2/n-heptane gave the pure products.
The data collection was performed at T ¼ 173(2) or 293(2) K on
a STOE IPDS I diffractometer with Mo-K radiation (
¼ 0.71073 Å)
employing e2 scan technique. The structures were solved by
a
l
u
q
direct methods using the SHELXTL package [38] or SHELX-97 and
WinGX [39] and refinement was carried out with SHELXL97
employing full-matrix least-squares methods on F2 [40] with
F20 ꢃ 2
s
(F20) with the results shown in Table 1 (and Supporting
Information). All non-hydrogen atoms were treated anisotropi-
cally, hydrogen atoms were included by using appropriate riding
models. CCDC 764339e764346 contain the full crystallographic
data. These data can be obtained free of charge at www.ccdc.cam.
ac.uk/conts/retrieving.html or from the Cambridge Crystallo-
graphic Data Centre, 12 Union Road, Cambridge, CB2 1EZ UK. Fax:
þ44 1223 336 033; Email: deposit@ccdc.cam.ac.uk.
[(COD)Pt(Me)(C^CPh)]: Yield: 94 mg (0.22 mmol, 77%). Anal.
Calc. for C17H20Pt1 (419.42): C, 48.68; H, 4.81. Found: C, 48.66; H,
4.82. EI-MS: 419 [M]þ. 1H-NMR (
d, CD2Cl2): 7.30 (d, 2H, Ho-Ph), 7.21
(m, 3H, Hm-Ph, p-Ph), 5.47 (m, 2H, 2J(PteH) ¼ 36 Hz, H1,2cod), 4.92 (m, 2H,
2J(PteH) ¼ 49 Hz, H5,6cod), 2.47e2.42 (m, 8H, H3,4,7,8cod), 0.95 (s, 3H,

A. Klein et al. / Journal of Organometallic Chemistry 695 (2010) 1898e1905
1905
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The antiproliferative effects of the compounds were determined
following an established procedure [35]. In short, cells were
suspended in cell culture medium (HT-29: 2850 cells/mL, MCF-7:
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10 000 cells/mL), and 100 mL aliquots thereof were plated in 96 well
plates and incubated at 37 ꢁC: 5% CO2 for 48 h (HT-29) or 72 h (MCF-
7). Stock solutions of the compounds in dimethylformamide (DMF)
were freshly prepared and diluted with cell culture medium to
the desired concentrations (final DMF concentration: 0.1% v/v). The
medium in the plates was replaced with medium containing the
compounds in graded concentrations (six replicates). After further
incubation for 72 h (HT-29) or 96 h (MCF-7) the cell biomass was
determined by crystal violet staining and the IC50 values were
determined as those concentrations causing 50% inhibition of cell
proliferation. Results were calculated from two independent
experiments.
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Acknowledgement
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We are indebted to Dr. Ingo Pantenburg and Mrs Ingrid Müller
for single crystal XRD measurements, as well as to Dr. Harald
Scherer and Dr. Wieland Tyrra for NMR experiments (all University
of Cologne). We are also grateful for a loan of K2PtCl4 and K2PdCl4
by Johnson Matthey (JM) and for financial support by Deutsche
Forschungsgemeinschaft (projects FOR-630 I.O. and KL 1194/11-1 A.
L. and A.K) and the German-Israeli-Foundation.
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