Strong cytotoxicity of organometallic platinum complexes with alkynyl ligands

Article abstract of DOI:10.1021/om400293u

The synthesis, spectroscopy, structures, and chemical reactivity of the organometallic complexes [(COD)Pt(C≡CR)₂] and [(COD)Pt(C≡CR)(R′)] (COD = 1,5-cyclooctadiene, R = Ph, (Me)Ph (2Me, 3Me, or 4Me), (NO₂)Ph (2NO₂, 3NO₂, or 4NO ₂), (4F)Ph, (4OMe)Ph, 2Py (2-pyridyl); R′ = Me (methyl), Neop (neopentyl = 2,2-dimethyl-1-methyl), NeoSi (neosilyl = trimethylsilylmethyl), Bz (benzyl)) has been explored. The crystal structures reveal square-planar surroundings of the Pt atoms with short Pt-C(alkynyl) bonds (<2 A) and almost perpendicular orientation of the C≡C-aryl group to the Pt coordination plane. Nonattractive π-π stacking and C-H...F intermolecular interactions were observed in the crystal structures. Multinuclear (¹H, ¹³C, ¹⁹⁵Pt, and ¹⁹F) NMR spectroscopy reveals structures in solution and Pt-ligand bond strength. The thermal stability in organic solvents, the electrochemical stability, and the reactivity of the complexes in organic or aquatic (water-containing) solution toward the physiologically relevant species glutathione, chloride, and protons was tested, revealing remarkable stability or inertness of the complexes. Cytotoxicity experiments in HT-29 colon carcinoma and MCF-7 breast adenocarcinoma cell lines revealed highly promising activities for selected platinum alkynyl COD complexes.

Full text of DOI:10.1021/om400293u

Article
pubs.acs.org/Organometallics
Strong Cytotoxicity of Organometallic Platinum Complexes with
Alkynyl Ligands
Anna Luning,† Julia Schur,‡ Laura Hamel,‡ Ingo Ott,‡ and Axel Klein*,†
̈
†Department fur Chemie, Institut fur Anorganische Chemie, Universitat zu Koln, Greinstraße 6, D-50939 Koln, Germany
̈
̈
̈
̈
̈
‡Institute of Medicinal and Pharmaceutical Chemistry, Technische Universitat Braunschweig, Beethovenstraße 55, D-38106
̈
Braunschweig, Germany
S
* Supporting Information
ABSTRACT: The synthesis, spectroscopy, structures, and chemical reactivity of the
organometallic complexes [(COD)Pt(CCR)2] and [(COD)Pt(CCR)(R′)] (COD
= 1,5-cyclooctadiene, R = Ph, (Me)Ph (2Me, 3Me, or 4Me), (NO2)Ph (2NO2, 3NO2, or
4NO2), (4F)Ph, (4OMe)Ph, 2Py (2-pyridyl); R′ = Me (methyl), Neop (neopentyl =
2,2-dimethyl-1-methyl), NeoSi (neosilyl = trimethylsilylmethyl), Bz (benzyl)) has been
explored. The crystal structures reveal square-planar surroundings of the Pt atoms with
short Pt−C(alkynyl) bonds (<2 Å) and almost perpendicular orientation of the CC−
aryl group to the Pt coordination plane. Nonattractive π−π stacking and C−H···F
intermolecular interactions were observed in the crystal structures. Multinuclear (1H,
13C, 195Pt, and 19F) NMR spectroscopy reveals structures in solution and Pt−ligand
bond strength. The thermal stability in organic solvents, the electrochemical stability, and the reactivity of the complexes in
organic or aquatic (water-containing) solution toward the physiologically relevant species glutathione, chloride, and protons was
tested, revealing remarkable stability or inertness of the complexes. Cytotoxicity experiments in HT-29 colon carcinoma and
MCF-7 breast adenocarcinoma cell lines revealed highly promising activities for selected platinum alkynyl COD complexes.
so-called “rule-breaking” cytotoxic platinum complexes22 and
INTRODUCTION
■
the numerous organometallic compounds (among them Pt
The alkynyl platinum(II) complexes [(COD)Pt(alkynyl)2] with
complexes)23 which have been very successfully tested against
COD (1,5-cyclooctadiene) as an easily exchangeable ligand are
various cancer cell lines in the last few years,24 the
frequently used as precursors for mono- and polynuclear
organometallic COD Pt complexes seem to be very promising.
organometallic platinum(II) compounds1−6 as well as for the
In the course of our last study in which various alkyl (benzyl,
assembly of homo- and heteropolymetallic compounds of
neopentyl (=2,2-dimethyl-1-methyl), or neosilyl (=trimethylsi-
platinum(II) and other metals such as Pd(II), Au(I), Ag(I),
lylmethyl)) and alkynyl coligands were varied in [(COD)Pt]
Cu(I), Tl(I), Hg(II), and Cd(II).7 Furthermore, some
complexes,19 we found a small group of mixed methyl/alkynyl
[(COD)Pt(alkynyl)2] complexes have been used in hydro-
complexes [(COD)Pt(Me)(CCR)] which turned out to be
highly toxic toward HT-29 and MCF-7 cell lines, with the best
value obtained for [(COD)Pt(Me)(CC(4Me)Ph)], which is
more than 10 times more toxic than cisplatin under the same
conditions.19 This motivated us to extend this study to further
COD Pt alkynyl complexes [(COD)Pt(alkynyl)2], including
the mixed alkyl/alkynyl complexes [(COD)Pt(alkyl)(alkynyl)]
(Scheme 1).
silylation catalysis.8 Pt alkynyl complexes in general have found
various applications, e.g. in the field of catalysis9,10 or as
luminescent materials.3−5,11−15
Recently we have demonstrated the suitability of the
[(COD)Pt(Me)] fragment to coordinate various ligands.16−19
This moiety allows a detailed insight into the binding properties
of the ligands to platinum by 1H NMR spectroscopy or
molecular structure determination.16 The same model system
was recently used for the study of binding properties of
cytosine toward platinum.17,18 In this work we could show that
the compounds [(COD)Pt(Me)Cl] and [(COD)Pt(Me)-
(Cyt)](SbF6) exhibit cytotoxicity against cancer cell lines in
the same concentration range as cisplatin, while the derivative
[(COD)PtCl2], containing no carbanionic coligand, is not
toxic.18,19 This is in line with early reports on the related
compounds [(COD)Pt(Me)(Nuc)] (Nuc = diverse nucleo-
sides)20 and reports by Deacon et al., who found evidence that
organometallic platinum (or palladium) complexes show higher
toxicity against cancer cell lines in comparison with similar
nonorganometallic derivatives.21 Seen in the framework of the
RESULTS AND DISCUSSION
■
Preparations. With the precursor complexes [(COD)Pt-
(R)Cl] (for R = methyl, neopentyl, neosilyl, benzyl) and
[(COD)PtCl2] as starting materials, ligand exchange reactions
were performed. The halogenido ligands were cleaved using a
mixture of the alkynyl ligand and t-BuOK in ethanol to form
KCl, t-BuOH, and the complexes [(COD)Pt(R)(alkynyl)] and
[(COD)Pt(alkynyl)2]. The reaction products were purified by
Received: April 8, 2013
Published: June 18, 2013
© 2013 American Chemical Society
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In the crystal structure of [(COD)Pt(CC(4Me)Ph)2]
(Figure 1) individual molecules pack in a way that the aryl rings
exhibit a coplanar (intermolecular) arrangement with an
interplanar distance of 3.750(4) Å and a centroid−centroid
distance of 3.904(4) Å. The interplanar distance is smaller than
in graphite (3.8 Å), and the question arises whether this is an
attractive π−π interaction. Very important in this respect is the
magnitude of the offset of the two rings and the tilt angle
between the two rings.25,26 The latter is almost zero (0.0(2)°)
for [(COD)Pt(CC(4Me)Ph)2], and the offset is 1.086(4) Å
(Table 1).
Scheme 1. COD Organoplatinum(II) Complexes
Investigated in This Study
According to the Hunter model the interaction is thus
repulsive.25 This is also in line with the exhaustive compilation
of corresponding data by Janiak,26 where the centroid−centroid
distance of 3.904(4) Å sets the complex beyond the limit of
attractive interactions. Also in [(COD)Pt(CC(4F)Ph)2] an
intermolecular coplanar arrangement of the aryl groups is
observed with an interplanar distance of 3.773(6) Å (Figure 2).
However, from the almost eclipsed (face-to-face) arrangement
(offset 0.080(6) Å) also a repulsive interaction must be
concluded. Thus, these intermolecular contacts are the result of
crystal packing only; a view of the calculated densities of the
five dialkynyl complexes reveals indeed a maximum for these
two structures (Table 1).
In the two fluorine-containing complexes [(COD)Pt(C
C(4F)Ph)2] and [(COD)Pt(CC(4F)Ph)2] (Figure 3) weak
intermolecular C−H···F interactions were observed (Table 2),
with the shortest H···F distances being >2.7 Å (C···F > 3
Å).27,28
recrystallization in CH2Cl2, and they are all colorless or yellow
powders with good solubility in organic solvents. All new
complexes were characterized by elemental analyses and IR and
NMR spectroscopy and for selected samples by mass
spectrometry (details are given in the Experimental Section).
Crystal and Molecular Structures in the Solid State.
For the compounds [(COD)Pt(Me)(CC(3Me)], [(COD)-
Pt(CC(2Me)Ph)2], [(COD)Pt(CC(3Me)Ph)2],
[(COD)Pt(CC(4Me)Ph)2], [(COD)Pt(Me)(CC(4F)-
Ph)], [(COD)Pt(CC(4F)Ph)2], and [(COD)Pt(CC-
(4OMe)Ph)2] single crystals were obtained and submitted to
XRD experiments. The complexes [(COD)Pt(CC(3Me)-
Ph)2], [(COD)Pt(CC(4Me)Ph)2], [(COD)Pt(Me)(CC-
(4F)Ph)], and [(COD)Pt(CC(4OMe)Ph)2] were found to
crystallize in the monoclinic space group P2/c, while the
structure of [(COD)Pt(Me)(CC(3Me)] was solved in the
monoclinic space group P21/c. The structures of [(COD)Pt-
(Me)(CC(4F)Ph)] and [(COD)Pt(CC(2Me)Ph)2] were
both solved in orthorhombic space groups (Pnma and Pbna).
Figures 1−4 show representative crystal or molecular
structures, and selected structural data are collected in Tables
1−4 (crystallographic information is compiled in the
Supporting Information). To our knowledge, only two COD
Pt alkynyl complexes have been previously reported, which are
[(COD)Pt(CC(t-Bu))2] crystallized as [Pt3(CC(t-
Bu))4(COD)2],4c containing two of these complex molecules
coordinating a Pt(0) atom (η2) through the triple bond and
[(COD)Pt(CCFc)2] (Fc = ferrocenyl).2b
The molecular structures show perfectly square planar
surroundings around the Pt atoms for all complexes, with the
two centroids X(1) and X(2) representing the olefin ligand
(Tables 3 and 4 and Figure 4). In this respect, the COD ligand
exhibits a rather invariant bite angle of about 85°, as observed
for related COD organo Pt(II) complexes.16−19,29 The alkynyl
C−Pt bond is rather short in all complexes (<2 Å):
interestingly, shorter than the C(Me)−Pt bond. Such a short
Pt−C(alkynyl) bond has been also observed in [(COD)Pt(C
CFc)2] (Fc = ferrocenyl)2b and is in contrast with the markedly
longer bonds observed in the corresponding phosphine
complexes cis-[Pt(P∧P)(CCR)2] (P∧P = chelating phosphine
ligand).1,2b,15a,30 Phosphine ligands (good σ donors, very good
π acceptors) are considered to be much stronger than COD
(weakly σ donating but efficiently π accepting); consequently,
phosphines tend to weaken the trans-oriented Pt−C(alkynyl)
bond, while COD obviously adapts far better to the “bonding
requirements” of alkynyl ligands and the corresponding Pt−
C(alkynyl) bonds are stronger.1 This is in line with the
observation that, in corresponding complexes of diimine ligands
(weaker compared to phosphines), the Pt−C(alkynyl) bonds
are also markedly shorter (usually below 2 Å).13b,c,14 In all
complexes the orientation of the CC−aryl group is almost
Table 1. Selected Distances (Å) and Angles (deg) of the Complexes [(COD)Pt(CCR)2]
R
(2Me)Ph
(3Me)Ph
(4Me)Ph
(4F)Ph
(4OMe)Ph
interplanar dist
6.221(5)
7.954(4)
0.0(2)
4.541(4)
4.561(4)
0.0(2)
3.750(5)
3.904(4)
0.0(2)
3.772(6)
3.773(6)
0.0(3)
3.992(10)
4.555(10)
0.0(6)
centroid−centroid dist
interplanar tilt angle
offset
4.957(5)
1.795
0.431(4)
1.720
1.086(4)
1.810
0.080(6)
1.932
2.193(9)
1.745
calcd density (g/cm3)
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Figure 1. Crystal structure of [(COD)Pt(CC(4Me)Ph)2] showing π−π interactions.
NMR Spectroscopy and Bond (Ligand) Strength. All
new complexes were thoroughly characterized by multinuclear
NMR spectroscopy; the results are compiled in Tables 5−7.
From earlier studies16−19 it is well-known that the JPt,H(
2
CH,COD) coupling constants reflect very well the general Pt−
ligand bond strength of a ligand trans to the corresponding
olefin proton. Table 5 shows for the symmetric complexes that
2
the JPt,H(CH,COD) value consistently lies at 45 or 46 Hz,
placing the alkynyl ligand on the side of relatively strong ligands
in these complexes, which is in line with the relatively short Pt−
C(alkynyl) distances from XRD. For comparison, for [(COD)-
Pt(Me)2] the coupling constant lies at 41 Hz (for the strong
Me ligand), while for the Cl derivative [(COD)PtCl2] 69 Hz
was found for the weak Cl ligand.16 In addition, other JPt,X
n
coupling constants have been very successfully correlated to the
strength of trans Pt−ligand bonds.31,32
In the mixed complexes [(COD)Pt(Me)(CCR)] the
situation is slightly modified (Table 6). The alkynyl ligands
seem to lose some of their binding strength (increased trans
2JPt,H), while the methyl coligand exerts a slightly stronger bond
Figure 2. Crystal structure of [(COD)Pt(CC(4F)Ph)2] showing
H···F interactions.
2
to Pt (decreased trans JPt,H). The same can be observed for
complexes in which the Me coligand is replaced by other strong
σ-donating alkyl groups (Table 7).
Another important NMR parameter is the 195Pt NMR shift
(Tables 5−7), which lies in the typical range of Pt(II)
complexes for the new alkynyl complexes.32 Although no
correlation can be drawn between the (electronic) structure of
the complexes and the chemical shift values, the exceedingly
broad scale of the 195Pt shift usually allows the unequivocal
detection of such complexes even in complex mixtures.31a,33
Chemical Stability/Reactivity of the Complexes.
Selected complexes were submitted to general tests to assess
their electrochemical, thermal and chemical stability toward
biologically reactants such as water, protons, chloride ions or
glutathione. The multiple NMR data helped tremendously to
assign complex species abundant in such reactions.
Electrochemical (Redox) Stability. Most of the complexes
under investigation exhibit completely irreversible electro-
chemistry (cyclic voltammetry in CH2Cl2 or THF solution);
thus, the determined potentials have rather limited meaning.
Nevertheless, we can say that within a quite large range of
potentials (0.9 to −2.1 V vs ferrocene/ferrocenium) no
electron transfer is observed (full data in the Supporting
Information). Translated into NHE potentials (+0.4 V),34 this
Figure 3. Crystal structure of [(COD)Pt(Me)(CC(4F)Ph)]
showing H···F interactions.
perpendicular to the Pt coordination plane. The bonding
parameters of [(COD)Pt(CC(t-Bu))2] in [Pt3(CC(t-
Bu))4(COD)2]4c are similar to our data; however, the low
quality of the data reported for this complex precludes any
detailed comparison.
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Table 2. Selected Distances (Å) and Angles (deg) of the Complexes [(COD)Pt(CC(4F)Ph)2] and [(COD)Pt(Me)(C
C(4F)Ph)]
[(COD)Pt(CC(4F)Ph)2]
[(COD)Pt(Me)(CC(4F)Ph)]
Distances
F···H(2)
F···H(9)
F···H(11)
F···C(2)
F···C(9)
F···C(11)
2.730(5)
2.934(6)
3.074 (4)
3.553(8)
3.243(10)
3.833(7)
F···H(11A)
F···H(11B)
F···H(11C)
F···H(4A)
F···C(11)
F···C(4)
2.797(8)
2.937(7)
2.985(7)
2.888(7)
3.080(13)
3.685(12)
Angles
F−H(2)−C(2)
F−H(9)−C(9)
F−H(11)−C(11)
147.9(4)
F−H(11A)−C(11)
F−H(11B)−C(11)
F−H(11C)−C(11)
F−H(4A)−C(4)
88.0(2)
89.4(1)
86.6(1)
140.0(5)
101.0(5)
140.0(4)
Table 3. Selected Distances (Å) and Angles (deg) of the Complexes [(COD)Pt(CCR)2]
R
(2Me)Ph
(3Me)Ph
Distances
(4Me)Ph
(4F)Ph
(4OMe)Ph
Pt−C(1)
Pt−C(2)
2.246(5)
2.230(5)
1.992(6)
2.131(1)
2.236(4)
2.253(4)
1.972(5)
2.136(1)
2.234(4)
2.256(4)
1.986(4)
2.136(1)
2.260(6)
2.253(6)
1.984(7)
2.149(1)
2.224(11)
2.254(9)
Pt−C(5) (C)
1.967(13)
2.132(10)
a
Pt−X
Angles
X−Pt−C(5)
92.3(2)
90.1(3)
85.3(3)
177.2(5)
177.8(6)
93.0(1)
88.8(3)
85.2(1)
178.6(4)
178.1(5)
92.9(1)
88.7(2)
85.6(1)
177.7(4)
176.8(5)
93.0(2)
88.8(4)
85.3(1)
177.0(6)
179.8(7)
92.4(3)
C(5)−Pt−C(5)
90.7(7)
a
X−Pt−X
84.6(1)
Pt−C(5)−C(6)
C(5)−C(6)−C(7)
178.0(11)
175.8(13)
a
Centroids X are defined as the averaged olefinic bonds between C(1) and C(2).
Table 4. Selected Distances (Å) and Angles (deg) of the Complexes [(COD)Pt(Me)(CC(4F)Ph)] and [(COD)Pt(Me)(C
C(3Me)Ph)]
[(COD)Pt(Me)(CC(4F)Ph)]
[(COD)Pt(Me)(CC(3Me)Ph)]
Distances
Pt−C(1)
Pt−C(2)
2.204(6)
2.262(7)
1.976(10)
2.057(10)
2.095(1)
2.160(1)
Pt−C(1)
Pt−C(2)
2.267(7)
2.269(8)
1.984(9)
2.096(8)
2.162(1)
2.104(1)
Pt−C(5) (C)
Pt−C(9) (C)
Pt−C(11) (Me)
Pt−C(18) (Me)
a
a
Pt−X(1)
Pt−X(2)
Pt−X(1)
Pt−X(2)
a
a
Angles
a
a
X(1)−Pt−C(11)
92.9(3)
94.4(3)
85.8(1)
86.8(4)
179.3(9)
177.0(1)
X(1)−Pt−C(9)
C(9)−Pt−C(18)
94.9(3)
85.5(4)
94.7(3)
85.0(1)
177.1(8)
178.7(10)
a
X(2)−Pt−C(5)
a
a
X(1)−Pt−X(2)
C(18)−Pt−X(2)
a
C(5)−Pt−C(11)
Pt−C(5)−C(6)
C(5)−C(6)−C(7)
X(2)−Pt−X(1)
Pt−C(9)−C(10)
C(9)−C(10)−C(11)
a
Centroids X(1) and X(2) are defined as the averaged olefinic bonds between C(1) and C(1_1) or between C(2) and C(2_2), respectively, for
[(COD)Pt(Me)(CC(4F)Ph)] or between C(1) and C(2) or between C(5) and C(6), respectively, for [(COD)Pt(Me)(CC(3Me)Ph)].
means that only strong oxidants with potentials >1.3 V or
medium-strong reductants with potentials <−1.7 V will react
effectively with the Pt complexes. Exceptions are the NO2-
substituted complexes, which exhibit completely reversible
reduction waves at potentials around −1.65 V. These reduction
waves contain one electron for each NO2 group; thus, the
process can be assigned to the reduction of the NO2 substituent
(or the entire nitrophenyl group) and no coupling of the two
individual processes for the disubstituted complexes [(COD)-
Pt(CC(xNO2)Ph)2] (x = 2−4) is observed. For the related
platinum complexes [(xNO2bpy)PtCl2] and [((xNO2)2bpy)-
PtCl2] (x = 3−5)35 and [(t-Bu2bpy)Pt(CC(4NO2)Ph)2]36
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Figure 4. Molecular structures of [(COD)Pt(CC(2Me)Ph)2] (left) and [(COD)Pt(CC(3Me)Ph)2] (right). All atoms shown at the 50%
probability level; protons are omitted for clarity. Only the E isomers (the two methyl groups point in different directions) were observed in the
crystal structures.
Table 5. Selected Chemical Shifts and Coupling Constants of
Table 7. Selected Chemical Shifts and Coupling Constants of
a
a
the Complexes [(COD)Pt(CCR)2]
the Complexes [(COD)Pt(R′)(CC(4Me)Ph)]
R
δ(1H) CH
2JPt,H(CH)
δ(195Pt)
δ(1H) CH,
2JPt,H(CH)
b
Ph
5.66
5.71
5.68
5.64
5.84
5.75
5.73
5.64
5.67
5.79
45
45
46
45
45
45
45
45
46
45
−3320
−3205
−3219
−3209
−3226
−3229
−3231
−3226
−3211
−3235
2
R′
Me
COD(a)
COD(b)
δ(1H) R′, JPt,H(R′)
δ(195Pt)
(2Me)Ph
(3Me)Ph
(4Me)Ph
5.46, 37
5.54, 32
5.41, 38
5.51, 39
4.91, 50
4.87, 48
4.93, 49
4.84, 47
0.94, 78
1.88, 87
1.14, 89
3.20, 106
−3209
−3102
−3056
−3106
b
Neop
(2NO2)Ph
(3NO2)Ph
(4NO2)Ph
NeoSi
b
Bz
b
a
Measured in CDCl3 except where noted. Chemical shifts are given in
b
b
(4F)Ph
ppm and coupling constants (in italics) in Hz. Measured in CD2Cl2.
(4OMe)Ph
2Py
conditions; even after 30 days around 80% of the material was
unchanged. However, we were surprised to find the complex
[(COD)Pt(Me)2] as the main decomposition product after a
few days (about 53% after 30 days). In traces this product can
be detected already at 4 h. We assume that the starting complex
undergoes the self-transmetalation reaction (1), forming the
a
Measured in CDCl3 except where noted. Chemical shifts are given in
b
ppm and coupling constants (in italics) in Hz. Measured in CD2Cl2.
and the ruthenium complex [Ru(4,4′-Me2bpy)(PPh3)2(C
C(4NO2)Ph)Cl]37 the accepting abilities of the NO2 group
have been investigated in detail. In line with this assignment,
the absorption spectra of the NO2-substituted complexes reveal
low-energy absorption bands, not occurring for the other
derivatives (spectra in the Supporting Information), which are
tentatively ascribed to an intraligand π(CC) to π*(NO2Ph)
transition.
Thermal Stability in Solution. In a first attempt to assess the
thermal stability of the complexes in solution, we stored the
complex [(COD)Pt(Me)(CC(4NO2)Ph)] in DMF-d7 sol-
ution and monitored its slow decay by NMR and UV−vis
absorption spectroscopy (figures are given in the Supporting
Information). The complex remains largely stable under these
2[(COD)Pt(Me)(C C(4NO2)Ph)]
⇄ [(COD)Pt(Me)2] + [(COD)Pt(C C(4NO2)Ph)2]
(1)
rather stable dimethyl complex. The second product, [(COD)-
Pt(CC(4NO2)Ph)2], can be detected in the reaction mixture
but readily decomposes in a reductive elimination of the
dialkynyl species (4NO2)Ph)CCCC(4NO2)Ph), COD,
and elemental Pt, as has been reported for similar COD Pt
alkynyl complexes.38 The rather rapid decomposition reaction
observed for [(COD)Pt(CC(4NO2)Ph)2] (half-life in DMF-
a
Table 6. Selected Chemical Shifts and Coupling Constants of the Complexes [(COD)Pt(Me)(CCR)]
R
δ(1H) CH COD(a)
2JPt,H(CH)
δ(1H) CH COD(b)
2JPt,H(CH)
δ(1H) Me
2JPt,H(Me)
δ(195Pt)
b
Ph
5.47
5.55
5.53
5.46
5.47
5.52
5.46
5.46
5.53
5.57
36
35
35
37
38
35
35
36
35
36
4.92
4.93
4.93
4.91
5.22
5.00
5.00
4.92
4.91
4.97
49
49
49
50
49
49
50
50
49
49
0.95
1.08
1.05
0.94
0.85
1.05
0.96
0.94
1.05
1.06
77
77
77
78
77
77
77
78
77
77
−3209
−3100
−3106
−3209
−3054
−3122
−3124
−3211
−3105
−3121
(2Me)Ph
(3Me)Ph
(4Me)Ph
b
(2NO2)Ph
(3NO2)Ph
(4NO2)Ph
b
b
(4F)Ph
(4OMe)Ph
2Py
a
b
Measured in CDCl3 except where noted. Chemical shifts are given in ppm and coupling constants (in italics) in Hz. Measured in CD2Cl2.
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Table 8. Cytotoxicity of Selected Platinum Complexes
IC50 (μM)
HT-29
7.0
MCF-7
2.0
ref
cisplatin
40
18
18
19
[(COD)PtCl2]
>100
>100
[(COD)Pt(Me)Cl
8.3 3.0
10.2 3.5
1.3 0.0
13.5 2.2
9.0 1.7
3.2 1.5
0.2 0.1
4.6 0.2
15.6 5.2
2.9 1.2
2.3 0.7
10.8 3.1
29.0 7.2
0.5 0.3
0.5 0.1
0.1 0.0
0.4 0.1
0.6 0.1
0.4 0.1
0.6 0.2
0.4 0.1
0.3 0.1
11.2 1.4
9.8 1.0
2.1 0.9
13.2 0.5
10.5 7.9
5.0 0.8
0.3 0.1
[(COD)Pt(Bz)Cl]
[(COD)Pt(Bz)(CC(4Me)Ph)]
[(COD)Pt(Neop)(CC(4Me)Ph)]
[(COD)Pt(Me)(CCPh)]
[(COD)Pt(Me)(CC(3Me)Ph)]
[(COD)Pt(Me)(CC(4Me)Ph)]
[(COD)Pt(Me)(CC(4F)Ph)]
[(COD)Pt(Me)(CC(2NO2)Ph)]
[(COD)Pt(Me)(CC(3NO2)Ph)]
[(COD)Pt(Me)(CC(4NO2)Ph)]
[(COD)Pt(Me)(CC(4OMe)Ph)]
[(COD)Pt(Me)(CC2Py)]
[(COD)Pt(CCPh)2]
this work
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19
this work
19
4.6 0.5
9.1 3.9
1.6 0.3
1.9 0.6
6.8 1.1
17.6 8.2
0.4 0.2
0.4 0.1
0.1 0.0
0.3 0.0
0.3 0.1
0.2 0.1
0.3 0.2
<0.30
this work
this work
this work
19
this work
this work
this work
this work
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this work
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[(COD)Pt(CC(2Me)Ph)2]
[(COD)Pt(CC(3Me)Ph)2]
[(COD)Pt(CC(4Me)Ph)2]
[(COD)Pt(CC(2NO2)Ph)2]
[(COD)Pt(CC(3NO2)Ph)2]
[(COD)Pt(CC(4OMe)Ph)2]
[(COD)Pt(CC(4F)Ph)2]
[(COD)Pt(CC2Py)2]
0.2 0.1
d7 at 30 °C ∼3 h) supports the entire reaction sequence.
Similar behavior was observed for the complexes [(COD)Pt-
(Me)(CC(4Me)Ph)] and [(COD)Pt(CC(4Me)Ph)2].
The unsymmetric derivative is more stable and slowly
undergoes self-transmetalation, while the bis-alkynyl complex
readily decomposes (half-life ∼4 h). As expected from previous
studies,38 light markedly accelerates the reductive elimination.
At elevated temperatures (>80 °C) rapid decomposition can be
observed (half-lifes ∼0.5 − 1 h).
for 18 h, approximately half of the complex was decomposed,
the main products being [(COD)PtCl2] and [(COD)Pt(Me)-
Cl] (NMR in CDCl3), as expected. Finally, the same complex
was reacted with increasing amounts of protons (from HBF4).
Interestingly, proton concentrations corresponding to a pH of 6
to 2 did not lead to marked spectral changes (UV−vis) after
standing for 30 min; however, at pH 1 the complex rapidly
decomposes. In CDCl3 solution a notable number of
unassignable signals appear at pH 1 after 30 min. Correlation
spectroscopy led to the characterization of one main species,
which seems to be a [(COD)Pt(Me)Y]n+ complex with the Me
Reaction with Glutathione, Chloride, and Protons. In
PrOH/H2O (4/1) the complex [(COD)Pt(Me)(CC-
(4NO2)Ph)] reacts very slowly with glutathione. When
monitoring the reaction by UV−vis absorption spectroscopy,
we found only a 1% spectral change after 3 days (figures are
given in the Supporting Information). In solutions of higher
concentrations using NMR spectroscopy, we observed a
traceable amount of a species of composition [(COD)Pt(Me)-
2
and Y ligands, leading to a trans JPt,H(CH) coupling
constant of 36 Hz for Me and 100 Hz for Y, respectively. Again
Y must be very weak ligand: e.g., for the acetone complex
[(COD)Pt(Me)(acetone)]+ 91 Hz has been reported.16 Thus,
while a pH of 1 leads to rapid decomposition of the complex, it
is remarkably stable at low to medium H+ concentrations and
variable amounts of glutathione or chloride both in organic and
in aquatic (water-containing) solutions.
2
(L)]n+ after 3 days. The trans JPt,H(CH) coupling constant
of ∼85 Hz points to a rather weak ligand L, which is either H2O
or the glutathione RSH or RNH2 function. A thiolate or
carboxylate ligand (deprotonated glutathione) can be ruled out,
as the corresponding coupling constants should be around 60−
70 Hz. For example, for the hydroxo complex [(COD)Pt-
(Me)(OH)] 65 Hz was reported,16 while the reported value for
the aqua complex [(COD)Pt(Me)(H2O)]+ of 89 Hz (in the
same solvent, CDCl3) supports the assumption that glutathione
is the ligand L and not H2O. Additionally, we also observed the
decomposition reaction described above, leading to the
dialkynyls, COD, and elemental Pt. When adding chloride (as
n-Bu4NCl) to a solution of [(COD)Pt(Me)(CC(4NO2)-
Ph)] in THF or i-PrOH/H2O (1/1), we observed a marked
spectroscopic change (UV−vis) only for a 5-fold excess of
chloride and a reaction time of 30 min (about 12% loss of
absorption at 358 nm). When these solutions were left standing
Cytotoxicity. In a continuation of our previous work on the
cytotoxicity of organoplatinum(II) COD complexes with mixed
alkyl/alkynyl ligands [(COD)Pt(Me)(CCR)], we extended
our study to platinum COD complexes with phenylalkynyl
coligands of the type [(COD)Pt(alkynyl)2] and evaluated their
antiproliferative properties in HT-29 colon carcinoma and
MCF-7 breast adenocarcinoma cell lines in a comparative
manner. 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.19 Introducing different substituted phenylalkynyl
ligands in the position of the chlorido ligand led to species
with activities in the range of 0.2−30 μM (Table 8). By
replacement of the methyl ligand with a second phenylalkynyl
coligand it was possible to obtain symmetric bis-alkynyl
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platinum complexes with an increased antiproliferative activity
in the submicromolar range. The highest activity was observed
for the m-methyl-substituted phenylalkynyl complex [(COD)-
Pt(CC(3Me)Ph)2], which was more than 10-fold active than
the platinum anticancer lead compound cisplatin and also more
active than its methyl-substituted derivative [(COD)Pt(Me)-
(CC(3Me)Ph)].
for the behavior of the complexes in solution. The molecular
structures reveal quite strong PtC(alkynyl) bonds, in line
with the weakly σ donating but efficiently π accepting nature of
the COD ligand. Multinuclear (1H, 13C, 195Pt, and 19F) NMR
spectroscopy reveals structures in solution and Pt−ligand bond
strengths. The thermal stability in organic solvents, the
electrochemical stability, and the reactivity of the complexes
in organic or aquatic (water-containing) solution toward the
physiologically relevant species glutathione, chloride, and
protons were tested. While the thermally activated self-
transmetalation of the mixed complexes [(COD)Pt(Me)(C
CR)] to [(COD)Pt(CCR)2] and [(COD)Pt(Me)2] was
unexpected, the prevailing decomposition of the dialkynyl
complexes [(COD)Pt(CCR)2] to dialkynyl RCCCCR,
COD, and Pt has been reported before. Nevertheless, the
overall stability is quite high. Marked decomposition occurs
only at elevated temperatures (>80 °C) or very prolonged
times (>3 days). The same is true for the reactivity toward
glutathione, Cl−, and H+. Only a very high H+ concentration,
corresponding to pH 1, led to rapid decomposition (within 30
min); under less harsh conditions the complexes are quite inert.
The cytotoxicity for selected platinum alkynyl COD complexes
was determined in HT-29 colon carcinoma and MCF-7 breast
adenocarcinoma cell lines and revealed promising activities in
the submicromolar range. Taken together with the results of
the stability experiments, the increased activity of the dialkynyl
derivatives could be related to their higher kinetic reactivity.
Moreover, we could observe some very interesting properties
of this novel class of platinum COD complexes concerning
structure−activity relationships (SAR). With a few exceptions
the dialkynyl platinum COD complexes were more cytotoxic
than the corresponding methyl-substituted derivatives. The
more quickly decomposing Pt−alkynyl bond of this type of
complex might be more beneficial concerning antiproliferative
activity than the stronger bond of the methyl coligand to Pt. In
addition, the perpendicular orientation of the CC−aryl
group to the Pt coordination plane might be relevant to the
higher cytotoxic effect. We also studied substituent effects at
different positions (o, m, p) of the aromatic system for nitro and
methyl groups. In the case of the methyl group the position at
the phenylalkynyl ligand had nearly no influence on the
cytotoxic behavior, whereas the p-nitro compound [(COD)Pt-
(CC(4NO2)Ph)2] was less active than the other nitro-
substituted derivatives. The p-methoxy- and p-fluorine-sub-
stituted complexes were also tested and showed comparable
activities with IC50 values below 1 μM. Similar results were
observed for the pyridine-substituted Pt alkynyl complex
[(COD)Pt(CC2Py)2].
The differences in biological activity between platinum
complexes of the type [(COD)Pt(CCR)2] and [(COD)Pt-
(Me)(CCR)] can be attributed to different electronic effects
of the substituents and consequently different kinetic
reactivities of the complexes and, furthermore, to possible
differences in their biodistribution and interaction with
biological targets, suggesting more detailed bioactivity studies
on selected complexes of these cytotoxic platinum compounds.
In a previous study we had reported on alkynyl(phosphane)-
gold(I) complexes, which triggered antiproliferative as well as
antianiogenic effects.39 For these complexes the inhibition of
the tumor-relevant enzyme thioredoxin reductase (TrxR) could
be confirmed. On the basis of these studies it could be
speculated that in addition to DNA, which represents the
established target of most anticancer platinum compounds,
TrxR might also be a molecular target for the platinum alkynyl
species presented here. Further studies that are in progress will
address these questions.
EXPERIMENTAL SECTION
■
Instrumentation. The NMR spectra were recorded on a Bruker
Avance II 300 MHz (1H, 300.13 MHz; 13C, 75.47 MHz; 19F, 282.23
MHz) using a triple-resonance 1H,19F,BB inverse probehead at 300 K.
The broad-band coil was tuned to either the carbon or the platinum
frequency and the detection coil to the proton frequency, resulting in
90° pulses of 11.9 μs for 13C, 12.5 μs for 195Pt, and 12.4 μs for 1H. The
1
unambiguous assignment of the H, 13C, and 195Pt resonances was
1
1
1
obtained from H TOCSY, H COSY, H NOESY, gradient selected
1H,13C HSQC and HMBC, and gradient selected 1H,195Pt HMBC
experiments. All 2D NMR experiments were performed using standard
pulse sequences from the Bruker pulse program library. Chemical
shifts were relative to TMS for 1H and 13C, CFCl3 for 19F, and
Na2[PtCl6] in D2O for 195Pt. The spectral analyses were performed by
the Bruker TopSpin 2 software. EI-MS spectra were measured with a
Finnigan MAT 900 S instrument. Simulations were performed using
ISOPRO 3.0. Elemental analyses were carried out using a Hekatech
CHNS EuroEA 3000 Analyzer. IR spectra were measured on a Bruker
IFS66νS instrument. Raman spectra were measured using a Bruker
FRA106S spectrometer. UV−vis absorption spectra were recorded on
a Varian Cary50 Scan spectrophotometer. Electrochemical experi-
ments were carried out in 0.1 M solutions of n-Bu4NPF6 in CH2Cl2 or
THF using a three-electrode configuration (glassy-carbon working
electrode, Pt counter electrode, Ag/AgCl pseudo reference) and an
Autolab PGSTAT30 potentiostat and function generator. The
ferrocene/ferrocenium couple served as an internal reference.
CONCLUSIONS
■
The new organometallic complexes cis-[(COD)Pt(CCR)2]
and cis-[(COD)Pt(R′)(CCR)] (COD = 1,5-cyclooctadiene;
R = Ph, (Me)Ph (2Me, 3Me, or 4Me), (NO2)Ph (2NO2,
3NO2, or 4NO2) (4F)Ph, (4OMe)Ph, 2Py (2-pyridyl); R′ =
Me (methyl), Neop (neopentyl = 2,2-dimethyl-1-methyl),
NeoSi (neosilyl = trimethylsilylmethyl), Bz (benzyl)) contain-
ing the chelate COD ligand and various alkyl and alkynyl
ligands have been synthesized in good to excellent yields. Due
to their high tendency to crystallize (without the inclusions of
other molecules) they can be perfectly purified. The
determined crystal structures reveal square-planar surroundings
of the Pt atoms and an almost perpendicular orientation of the
CC−aryl group to the Pt coordination plane. Nonattractive
π−π stacking and C−H···F intermolecular interactions were
observed in the crystal structures but were surely not relevant
Crystal Structure Determination. The data collection was
performed at T = 173(2) or 293(2) K on a STOE IPDS I
diffractometer with Mo Kα radiation (λ = 0.71073 Å) employing the
ω−2θ scan technique. The structure was solved by direct methods
using SHELX-97 and WinGX,41 and refinement was carried out with
SHELXL97 employing full-matrix least-squares methods on F2 42 with
2
Fo2 ≥ 2σ(Fo ) with the results provided in the Supporting Information.
All non-hydrogen atoms were treated anisotropically; hydrogen atoms
were included by using appropriate riding models. CCDC files 929268
([(COD)Pt(CC(2Me)Ph)2]), 929269 ([(COD)Pt(CC(3Me)-
Ph)2]), 929270 ([(COD)Pt(CC(4Me)Ph)2]), 929271 ([(COD)-
Pt(CC(4F)Ph)2]), 929272 ([(COD)Pt(CC(4OMe)Ph)2]),
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929273 ([(COD)Pt(Me)(CC(4F)Ph)]), and 929274 ([(COD)Pt-
(Me)(CC(3Me)Ph)]) contain the full crystallographic information.
These data can be obtained free of charge at www.ccdc.cam.ac.uk/
conts/retrieving.html or from the Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge, CB2 1EZ U.K (fax, + 44-1223-
336-033; e-mail, deposit@ccdc.cam.ac.uk).
1009, 988, 913, 871, 863, 833, 810, 780 (m), 761, 697 (s): δ(CC−
H). EI-MS: 505 [M]+. λmax (THF): 255, 326 nm.
[(COD)Pt(CC(2Me)Ph)2]: yield 76 mg (0.142 mmol, 53%).
Anal. Calcd for C26H26Pt (533.52): C, 58.53; H, 4.91. Found: C,
1
58.50; H, 4.88. H NMR (δ, CDCl3): 7.37 (m, 2H, o-Ph), 7.16−7.03
(m, 6H, m-Ph, p-Ph), 5.71 (m, 4H, CH COD, 2JPt,H = 45 Hz), 2.59
3
(m, 8H, CH2 COD, JPt,H ≈ 16 Hz), 2.48 (s, 6H, o-CH3). 195Pt,1H
Cytotoxicity. The antiproliferative activity of platinum alkynyl
COD complexes in HT-29 colon carcinoma and MCF-7 breast
adenocarcinoma cell lines was determined according to an established
procedure.43 In short, the compounds were freshly prepared as stock
solutions in dimethylformamide (DMF) and diluted with DMEM cell
culture medium supplemented with 50 mg/L and 10% (v/v) fetal calf
serum (“medium”) to the desired concentrations (0.1% v/v DMF).
The medium containing the test compound in different concentrations
was added to 96-well plates, in which the cells had been grown, with 6
replicates. The untreated controls contained the same amount of DMF
(0.1% v/v), which does not cause cytotoxic effects. After an incubation
period of 72 h for HT-29 cells and 96 h for MCF-7 cells the plates
were stained with crystal violet to determine the cell biomass. The IC50
values were calculated as that concentration reducing proliferation of
untreated control cells by 50%. Results are expressed as means and
error of two to four independent experiments.
Stability/Reactivity Investigations. The complexes [(COD)Pt-
(Me)(CC(4NO2)Ph)], [(COD)Pt(CC(4NO2)Ph)2], [(COD)-
Pt(Me)(CC(4Me)Ph)], and [(COD)Pt(CC(4Me)Ph)2] were
tested for their thermal stability in DMF solution. The compounds
were dissolved in DMF or DMF-d7, and time-dependent NMR and
UV−vis spectra were recorded. The tests on the complex [(COD)-
Pt(Me)(CC(4NO2)Ph)] against glutathione were performed in a
mixture of i-PrOH and H2O (4/1) (UV−vis) or CDCl3 (for NMR);
for the Cl− testing n-Bu4NCl was used in THF or i-PrOH/H2O (1/1)
solution for UV−vis or CDCl3 solution for NMR spectroscopic
monitoring. HBF4 in THF (UV−vis) or CDCl3 (NMR) solution was
used to assess the reactivity toward protons.
HMBC (δ, CDCl3): −3205. IR (KBr, in cm−1): 3087, 3056, 3011 (w):
ν(CC−H); 2950, 2922, 2894, 2834 (m): ν(H2C−H) and ν(HC−
H); 2116 (s): ν(CC); 1596, 1477 (s): ν(CC(aryl)); 1454, 1427
(s): δ(H2C−H) and δ(HC−H); 989, 952, 862, 833 (m), 763, 717 (s):
δ(CC−H). EI-MS: 533 [M]+. λmax (THF): 253, 284, 293, 330 nm.
[(COD)Pt(CC(2NO2)Ph)2]: yield 94 mg (0.158 mmol; 59%).
Anal. Calcd for C24H20N2O4Pt (595.50): C, 48.41; H, 3.39; N, 4.70.
Found: C, 48.50; H, 3.38; N, 4.66. 1H NMR (δ, CDCl3): 7.91 (d, 2H,
m-Ph), 7.66 (d, 2H, o-Ph), 7.47 (t, 2H, p-Ph), 7.31 (t, 2H, m-Ph), 5.84
2
3
(m, 4H, CH COD, JPt,H = 45 Hz), 2.61 (m, 8H, CH2 COD, JPt,H
≈ 16 Hz). 195Pt,1H HMBC (δ, CDCl3): −3226. IR (KBr, in cm−1):
3097, 3065, 3023, 3002 (w): ν(CC−H); 2961, 2928, 2889, 2838
(m): ν(H2C−H) and ν(HC−H); 2123 (s): ν(CC); 1599, 1565,
1517 (s): ν (CC(aryl)) and νas(NO2); 1474, 1433 (m): δ(H2C−H)
and δ(HC−H); 1340 (s): νs NO2; 1001, 862, 782 (m), 741 (s):
δ(CC−H) and ν(C−N); 666 (m): δ(NO2). λmax (THF): 247, 271
(sh), 314, 351 nm.
[(COD)Pt(CC(3Me)Ph)2]: yield 98 mg (0.184 mmol, 69%).
Anal. Calcd for C26H26Pt (533.52): C, 58.53; H, 4.91. Found: C,
58.48; H, 4.86. 1H NMR (δ, CDCl3): 7.24 (s, 2H, o-Ph), 7.21 (d, 2H,
o-Ph), 7.11 (t, 4H, m-Ph), 6.97 (d, 2H, p-Ph), 5.68 (m, 4H, CH
2
3
COD, JPt,H = 46 Hz), 2.57 (m, 8H, CH2 COD, JPt,H ≈ 17 Hz), 2.27
(s, 6H, m-CH3). 195Pt,1H HMBC (δ, CD2Cl2): −3219. IR (KBr, in
cm−1): 3051, 3033, 3000 (w): ν(CC−H); 2970, 2949 (m), 2916,
2902 (s): ν(H2C−H) and ν(HC−H); 2122 (s): ν(CC); 1596, 1481
(s): ν(CC(aryl)); 1448, 1428 (m): δ(H2C−H) and δ(HC−H);
988, 978, 916, 906, 862 (m), 785, 764, 695 (s): δ(CC−H). λmax
(THF): 256, 285, 293, 328 nm.
Materials and Procedures. All preparations were carried out
under a dry argon atmosphere using Schlenk techniques. Solvents
(CH2Cl2, THF, toluene, diethyl ether, and MeCN) were dried using a
MBraun MB SPS-800 solvent purification system.
[(COD)Pt(CC(3NO2)Ph)2]: yield 101 mg (0.169 mmol, 63%).
Anal. Calcd for C24H20N2O4Pt (595.50): C, 48.41; H, 3.39; N, 4.70.
Found: C, 48.38; H, 3.36; N, 4.61. 1H NMR (δ, CDCl3): 8.22 (s, 2H,
o-Ph), 8.02 (d, 2H, p-Ph), 7.69 (d, 2H, o-Ph), 7.40 (t, 2H, m-Ph), 5.75
The complexes [(COD)PtCl2], [(COD)Pt(Me)2], and [(COD)-
Pt(R′)Cl] (R′ = Me, Bz, Neop, or NeoSi) were prepared according to
published procedures.19,44 The alkynes HCCR were either
purchased from Acros (R = Ph) or Alfa Aesar (R = (3Me)Ph,
(4Me)Ph, (4F)Ph) or prepared for R = (4OMe)Ph,45 (2Me)Ph,45
(2NO2)Ph,46 (3NO2)Ph,46 (4NO2)Ph47 following established proce-
2
3
(m, 4H, CH COD, JPt,H = 45 Hz), 2.63 (m, 8H, CH2 COD, JPt,H
≈ 16 Hz). 195Pt,1H HMBC (δ, CDCl3): −3229. IR (KBr, in cm−1):
3100, 3078, 3024, 3005 (w): ν(CC−H); 2950, 2925, 2891, 2831
(m): ν(H2C−H) and ν(HC−H); 2120, 2144 (s): ν(CC); 1612,
1525 (s): ν(CC(aryl)) and νas(NO2); 1471, 1426 (m): δ(H2C−H)
and δ(HC−H); 1350 (s): νs(NO2); 997, 894, 863 (m), 809, 736 (s):
δ(CC−H) and ν(C−N); 674 (m): δ(NO2). EI-MS: 595 [M]+. λmax
(THF): 252, 319 nm.
1
dures. The purity of the materials thus obtained was checked by H
and 13C NMR spectroscopy, MS, and elemental analyses with good to
excellent results (in comparison to reported data). All other chemicals
were purchased from commercial suppliers and were used without
further purification.
[(COD)Pt(CC(4Me)Ph)2]: yield 106 mg (1.98 mmol, 74%).
Anal. Calcd for C26H26Pt (533.57): C, 58.53; H, 4.91. Found: C,
58.46; H, 4.91. 1H NMR (δ, CD2Cl2): 7.24 (d, 4H, o-Ph), 7.06 (d, 4H,
Synthesis of [(COD)Pt(CCR)2] (R = Ph, (2Me)Ph, (3Me)Ph,
(4Me)Ph, (2NO2)Ph, (3NO2)Ph, (4NO2)Ph, (4F)Ph, (4OMe)Ph,
2Py). The compounds were prepared in a variation of the method
described for [(COD)Pt(CCPh)2]:48 a suspension of 100 mg
(0.267 mmol) of [(COD)PtCl2] in 10 mL of ethanol was maintained
at −5 °C, and a freshly prepared mixture of the alkyne (0.587 mmol,
2.2 equiv) and sodium ethoxide (prepared from 14 mg sodium) or 66
mg (0.587 mmol, 2.2 equiv) of potassium tert-butoxide in 5 mL of
ethanol were added dropwise with constant stirring. The solutions
became darker, and after 1 h the colorless products were filtered off.
Recrystallization from CH2Cl2/n-heptane gave the pure products as
microcrystalline materials.
2
m-Ph), 5.64 (m, 4H, CH COD, JPt,H = 45 Hz), 2.57 (m, 8H, CH2
3
COD, JPt,H ≈ 17 Hz), 2.31 (s, 6H, 4-CH3). 195Pt,1H HMBC (δ,
CD2Cl2): −3209. 1H NMR (δ, DMF-d7): 7.21 (d, 4H, o-Ph), 7.11 (d,
2
4H, m-Ph), 5.61 (m, 4H, CH COD, JPt,H = 44 Hz), 2.61 (m, 8H,
CH2 COD), 2.29 (s, 6H, p-CH3). 195Pt,1H HMBC (δ, DMF-d7):
−3227. IR (KBr, in cm−1): 3072, 3049, 3021, 3004 (w): ν(CC−H);
2911, 2894 (s): ν(H2C−H) and ν(HC−H); 2124 (s): ν(CC); 1602
(m), 1505 (s): ν(CC(aryl)); 1438, 1428 (m): δ(H2C−H) and
δ(HC−H); 988, 967, 940, 902 (m), 861, 841, 815 (s), 765, 739 (m):
δ(CC−H). EI-MS: 533 [M]+. λmax (THF): 257, 286, 296, 332 nm.
[(COD)Pt(CC(4NO2)Ph)2]: yield 61 mg (0.102 mmol, 38%).
Anal. Calcd for C24H20N2O4Pt (595.50): C, 48.41; H, 3.39; N, 4.70.
Found: C, 48.33; H, 3.28; N, 4.61. 1H NMR (δ, CD2Cl2): 8.10 (d, 4H,
m-Ph), 7.47 (d, 4H, o-Ph), 5.72 (m, 4H, CH COD, 2JPt,H = 45 Hz),
2.62 (m, 8H, CH2 COD). 195Pt,1H HMBC (δ, CD2Cl2): −3231. IR
(KBr, in cm−1): 3112, 3071 (w): ν(CC−H); 2923, 2886 (m):
ν(HC−H); 2123 (s): ν(CC); 1589, 1511 (s), 1486 (m): ν(C
C(aryl)) and νas(NO2); 1422, 1403, 1383 (m): δ(HC−H); 1341 (s):
νs(NO2); 1005 (m): δ(CC−H); 858, 848 (s): δ(CC−H) and
[(COD)Pt(CCPh)2]: yield 67 mg (0.134 mmol, 50%). Anal.
Calcd for C24H22Pt (505.52): C, 57.02; H, 4.39. Found: C, 56.98; H,
4.33. 1H NMR (δ, CD2Cl2): 7.35 (d, 4H, o-Ph), 7.23 (m, 6H, m-Ph, p-
2
Ph), 5.66 (m, 4H, CH COD, JPt,H = 45 Hz), 2.58 (m, 8H, CH2
COD, 3JPt,H ≈ 17 Hz). 195Pt,1H HMBC (δ, CD2Cl2): −3320. IR (KBr,
in cm−1): 3074, 3052 (w), 3023, 3008 (m): ν(CCH); 2965, 2943,
2915, 2895 (m): ν(HC−H); 2125 (s): ν(CC); 1638, 1597 (m),
1485, 1475 (s): ν(CC(aryl)); 1451, 1440, 1427 (s): δ(HC−H);
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Organometallics
Article
2
ν(C−N); 822, 768 (m), 747, 690 (s): δ(CC−H); 638 (m):
δ(NO2). λmax (THF): 231, 273, 345 nm.
Hz), 2.45 (m, 8H, CH2 COD), 0.85 (s, 3H, CH3, JPt,H = 77 Hz).
195Pt,1H HMBC (δ, CDCl3): −3054. IR (KBr in cm−1): 3060, 3021
(w): ν(CC−H); 2925, 2885 (s), 2836, 2801 (m): ν(H2C−H) and
ν(HC−H); 2118, 2060 (s): ν(CC); 1631, 1608, 1523 (s): ν(C
C(aryl)) and νas(NO2); 1475, 1455, 1432 (m): δ(H2C−H) and
δ(HC−H); 1340 (s): δs(NO2); 997, 853, 848, 757 (m): δ(CC−H)
and ν(C−N); 653 (m): δ(NO2). λmax (THF): 256, 309 (sh), 421 nm.
[(COD)Pt(Me)(CC(3Me)Ph)]: yield 80 mg (0.185 mmol,
69%). Anal. Calcd for C18H22Pt (433.45): C, 49.88; H, 5.12. Found:
[(COD)Pt(CC(4F)Ph)2]: yield 89 mg (0.164 mmol, 62%). Anal.
Calcd for C24H20F2Pt (541.49): C, 53.23; H, 3.72. Found: C, 53.11; H,
3.68. 1H NMR (δ, CD2Cl2): 7.33 (dd, 4H, o-Ph), 6.95 (d, 4H, m-Ph),
5.64 (m, 4H, CH COD, 2JPt,H = 45 Hz), 2.57 (m, 8H, CH2 COD).
195Pt,1H HMBC (δ, CD2Cl2): −3226. 19F NMR (δ, CD2Cl2): −115.
IR (KBr, in cm−1): 3066, 3036, 3027, 3013 (w): ν(CC−H); 2914,
2902 (m): ν(HC−H); 2129 (s): ν(CC); 1594, 1586 (m), 1501 (s):
ν(CC(aryl)); 1429, 1400, 1383 (m): δ(HC−H); 1222, 1210 (s):
ν(C−F); 995, 865 (m), 839 (s), 812, 769, 746, 693 (m): δ(CC−
H); 532, 504 (m): δ(C−F). λmax (THF): 252, 287, 297, 325 nm.
[(COD)Pt(CC(4OMe)Ph)2]: yield 79 mg (0.139 mmol, 52%).
Anal. Calcd for C26H26O2Pt (565.56): C, 55.22; H, 4.63. Found: C,
1
C, 49.79; H, 5.05. H NMR (δ, CDCl3): 7.23 (s, 1H, o-Ph), 7.20 (d,
1H, o-Ph), 7.11 (t, 1H, m-Ph), 6.97 (d, 1H, p-Ph), 5.53 (m, 2H, CH
2
2
COD(a), JPt,H = 35 Hz), 4.93 (m, 2H, CH COD(b), JPt,H = 49
Hz), 2.45 (m, 8H, CH2 COD), 2.28 (s, 3H, m-CH3), 1.05 (s, 3H, CH3,
2JPt,H = 77 Hz). 195Pt,1H HMBC (δ, CDCl3): −3106. IR (KBr in
cm−1): 3085, 3065, 3042, 3011 (w): ν(CC−H); 2948, 2922 (s),
2875, 2836 (m): ν(H2C−H) and ν(HC−H); 2111 (s): ν(CC);
1596, 1517 (s): ν(CC(aryl)); 1479, 1450, 1428 (s): δ(H2C−H) and
δ(HC−H); 982, 917 (s), 860, 820 (m), 784, 757, 694 (s): δ(CC−
H). EI-MS: 433 [M]+. λmax (THF): 257, 309 nm.
1
55.11; H, 4.68. H NMR (δ, CDCl3): 7.34 (m, 4H, o-Ph), 6.77 (m,
2
4H, m-Ph), 5.67 (m, 4H, CH COD, JPt,H = 46 Hz), 3.78 (s, 6H,
OCH3), 2.56 (m, 8H, CH2 COD, 3JPt,H ≈ 16 Hz). 195Pt,1H HMBC (δ,
CDCl3): −3211. IR (KBr, in cm−1): 3065, 3031 (w), 3000 (m):
ν(CC−H); 2954, 2917, 2893, 2833 (m): ν(H2C−H) and ν(HC−
H); 2125 (s): ν(CC); 1600 (s), 1505 (s): ν(CC(aryl)); 1462 (s),
1440, 1427, 1411, 1399 (m): δ(H2C−H) and δ(HC−H); 1286, 1244,
1178, 1165, 1033 (s): ν(C−OC); 988, 863, 839, 830 (s), 808, 766
(m), 734, 693 (s): δ(CC−H). λmax (THF): 259, 295, 306, 341 nm.
[(COD)Pt(CC2Py)2]: yield 122 mg (0.241 mmol, 90%). Anal.
Calcd for C22H20N2Pt (507.49): C, 52.07; H, 3.97; N, 5.52. Found: C,
52.03; H, 3.92; N, 5.50. 1H NMR (δ, CDCl3): 8.49 (d, 2H, 6-Py), 7.54
(dt, 2H, 4-Py), 7.39 (d, 2H, 3-Py), 7.07 (d, 2H, 5-Py), 5.79 (m, 4H, 
[(COD)Pt(Me)(CC(3NO2)Ph)]: yield 74 mg (0.159 mmol,
56%). Anal. Calcd for C17H19NO2Pt (464.42): C, 43.97; H, 4.12; N,
3.02. Found: C, 43.89; H, 4.08; N, 2.99. 1H NMR (δ, CDCl3): 8.21 (s,
1H, o-Ph), 7.99 (d, 1H, p-Ph), 7.66 (d, 1H, o-Ph), 7.37 (t, 1H, m-Ph),
2
5.52 (m, 2H, CH COD, JPt,H  35 Hz), 5.00 (m, 2H, CH
2
COD, JPt,H = 49 Hz), 2.47 (m, 8H, CH2 COD), 1.05 (s, 3H, CH3,
2JPt,H = 77 Hz). 195Pt,1H HMBC (δ, CDCl3): −3122. IR (KBr in
cm−1): 3078 (w): ν(CC−H); 2943, 2926, 2884 (s), 2838 (m):
ν(H2C−H) and ν(HC−H); 2111 (s): ν(CC); 1611, 1567, 1526
(s): ν(CC(aryl)) and νas(NO2); 1473, 1428 (m): δ(H2C−H) and
δ(HC−H); 1350 (s): δs(NO2); 994, 892, (m), 807, 732 (s): δ(C
C−H) and ν(C−N); 673 (m): δ(NO2). EI-MS: 464 [M]+. λmax
(THF): 257, 305 nm.
2
3
CH COD, JPt,H = 45 Hz), 2.58 (m, 8H, CH2 COD, JPt,H ≈ 17 Hz).
195Pt,1H HMBC (δ, CDCl3): −3235. IR (KBr, in cm−1): 3076, 3052
(w): ν(CC−H); 2995, 2974, 2914, 2901 (m): ν(HC−H); 2131 (s):
ν(CC); 1583 (s), 1496 (m): ν(CC(aryl)); 1459, 1421 (s), 1391
(m): δ(HC−H); 991 (s) 861, 825 (m), 781, 766 (s), 742 (m): δ(C
C−H). EI-MS: 507 [M]+. λmax (THF): 249, 290, 320 nm.
[(COD)Pt(Me)(CC(4Me)Ph)]: yield 94 mg (0.221 mmol,
79%). Anal. Calcd for C18H22Pt (433.45): C, 49.88; H, 5.12. Found:
C, 49.81; H, 5.12. 1H NMR (δ, CD2Cl2): 7.12 (d, 2H, o-Ph), 7.04 (d,
Synthesis of [(COD)Pt(Me)(CCR)2] (R = Ph, (2Me)Ph,
(3Me)Ph, (4Me)Ph, (2NO2)Ph, (3NO2)Ph, (4NO2)Ph, (4F)Ph,
(4OMe)Ph, 2Py). The compounds were prepared in a variation of
the method described for [(COD)Pt(CCPh)2]:47 a suspension of
100 mg (0.283 mmol) of [(COD)Pt(Me)Cl] in 10 mL of ethanol was
maintained at −5 °C, and a freshly prepared mixture of the alkyne
(0.311 mmol, 1.1 equiv) and sodium ethoxide (prepared from 7 mg
sodium) or 34 mg (0.311 mmol, 1.1 equiv) of potassium tert-butoxide
in 5 mL of ethanol were added dropwise with constant stirring. The
solutions became darker, and after 1 h the reaction mixture was
evaporated to dryness under reduced pressure. Recrystallization from
CH2Cl2/n-heptane of the resulting solid gave the pure microcrystalline
products.
2
2H, m-Ph), 5.46 (m, 2H, CH COD(a), JPt,H = 37 Hz), 4.91 (m,
2
2H, CH COD(b), JPt,H = 50 Hz), 2.46−2.41 (m, 8H, CH2 COD,
3JPt,H ≈ 10 Hz), 2.30 (s, 3H, p-CH3), 0.94 (s, 3H, CH3, 2JPt,H = 78 Hz).
195Pt,1H HMBC (δ, CD2Cl2): −3209. 1H NMR (δ, DMF-d7): 7.18 (d,
2
2H, o-Ph), 7.09 (d, 2H, m-Ph), 5.40 (m, 2H, CH COD(a), JPt,H
=
2
35 Hz), 4.94 (m, 2H, CH COD(b), JPt,H = 49 Hz), 2.46 (m, 8H,
2
CH2 COD), 2.28 (s, 3H, 4-CH3), 0.91 (s, 3H, CH3, JPt,H = 79 Hz).
195Pt,1H HMBC (δ, DMF-d7): −3114. IR (KBr in cm−1): 3074, 3049,
3033, 3012 (w): ν(CC−H); 2949, 2882 (s), 2835, 2802 (m):
ν(H2C−H) and ν(HC−H); 2113 (s): ν(CC); 1600 (m), 1504 (s):
ν(CC(aryl)); 1449, 1426 (s): δ(H2C−H) and δ(HC−H); 998, 978
(s), 942, 896, 860, 839 (m), 816, 784, 759 (s), 730, 706, 687 (m):
δ(CC−H). EI-MS: 433 [M]+. λmax (THF): 255, 312 nm.
[(COD)Pt(Me)(CCPh)]: yield 92 mg (0.218 mmol, 77%). Anal.
Calcd for C17H20Pt (419.42): C, 48.68; H, 4.81. Found: C, 48.64; H,
4.80. 1H NMR (δ, CD2Cl2): 7.30 (d, 2H, o-Ph), 7.21 (m, 3H, m-Ph, p-
2
[(COD)Pt(Me)(CC(4NO2)Ph)]: yield 44 mg (0.100 mmol,
33%). Anal. Calcd for C17H19N1O2Pt (464.42): C, 43.97; H, 4.12; N,
Ph), 5.47 (m, 2H, CH COD(a), JPt,H = 36 Hz), 4.92 (m, 2H, 
CH COD(b), 2JPt,H = 49 Hz), 2.47−2.42 (m, 8H, CH2 COD, 3JPt,H
≈
1
2
10,0 Hz), 0.95 (s, 3H, CH3, JPt,H = 77 Hz). 195Pt,1H-HMBC (δ,
CD2Cl2): −3209. IR (KBr in cm−1): 3039, 3012, 2991 (w): ν(CC−
H); 2928, 2880 (s): ν(H2C−H) and ν(HC−H); 2111 (s): ν(CC);
1596, 1487 (s): ν(CC(aryl)); 1442, 1426 (s), 1395, 1384 (m):
δ(H2C−H) and δ(HC−H); 997, 978, 916, 863, 838, 819, 799, 785
(m), 759, 695 (s): δ(CC−H). EI-MS: 419 [M]+. λmax (THF): 251,
261, 308 nm.
3.02. Found: C, 43.95; H, 4.12; N, 3.01. H NMR (δ, CD2Cl2): 8.08
(d, 2H, m-Ph), 7.43 (d, 2H, o-Ph), 5.46 (m, 2H, CH COD(a), 2JPt,H
= 35 Hz), 5.00 (m, 2H, CH COD(b), 2JPt,H = 50 Hz), 2.46 (m, 8H,
CH2 COD), 0.96 (s, 3H, CH3, JPt,H = 77 Hz). 195Pt,1H HMBC (δ,
2
CD2Cl2): −3124. 1H NMR (δ, DMF-d7): 8.19 (d, 2H, m-Ph), 7.54 (d,
2H, o-Ph), 5.44 (m, 2H, CH COD(a), 2JPt,H = 36 Hz), 5.08 (m, 2H,
2
CH COD(b), JPt,H = 50 Hz), 2.51 (m, 8H, CH2 COD), 0.92 (s,
3H, CH3, JPt,H = 78 Hz). 195Pt,1H HMBC (δ, DMF-d7): −3130. IR
2
[(COD)Pt(Me)(CC(2Me)Ph)]: yield 48 mg (0.110 mmol,
39%). Anal. Calcd for C18H22Pt (433.45): C, 49.88; H, 5.12. Found:
C, 49.91; H, 5.22. 1H NMR (δ, CDCl3): 7.37 (m, 1H, o-Ph), 7.10 (m,
(KBr in cm−1): 3108, 3068 (w): ν(CC−H); 2924, 2882 (s), 2853,
2835 (m): ν(H2C−H) and ν(HC−H); 2111 (s): ν(CC); 1630,
1588, 1510 (s): ν(CC(aryl)) and νas(NO2); 1450, 1429, 1404, 1381
(m): δ(H2C−H) and δ(HC−H); 1340 (s): δs(NO2); 853, 750, 691
(m): δ(CC−H). λmax (THF): 229, 276, 358, 538 nm.
2
3H, m-Ph, p-Ph), 5.45 (m, 2H, CH COD(a), JPt,H = 34 Hz), 4.93
2
(m, 2H, CH COD(b), JPt,H = 49 Hz), 2.47 (s, 3H, o-CH3), 2.45
2
(m, 8H, CH2 COD), 1.08 (s, 3H, CH3, JPt,H = 77 Hz). 195Pt,1H
[(COD)Pt(Me)(CC(4F)Ph)]: yield 110 mg (0.238 mmol, 84%).
Anal. Calcd for C17H19FPt (437.42): C, 46.68; H, 4.38. Found: C,
HMBC (δ, CD2Cl2): −3100. λmax (THF): 250, 310 nm.
[(COD)Pt(Me)(CC(2NO2)Ph)]: yield 54 mg (0.116 mmol,
1
46.66; H, 4.41. H NMR (δ, CD2Cl2): 7.28 (dd, 2H, o-Ph), 6.93 (dd,
41%). Anal. Calcd for C17H19NO2Pt (464.42): C, 43.97; H, 4.12; N,
2
1
3.02. Found: C, 43.91; H, 4.22; N, 3.00. H NMR (δ, CDCl3): 7.55−
2H, m-Ph), 5.46 (m, 2H, CH COD(a), JPt,H = 36 Hz), 4.92 (m,
2
7.42 (m, 3H, o-Ph, p-Ph), 7.34 (t, 1H, m-Ph), 5.47 (m, 2H, CH
2H, CH COD(b), JPt,H = 50 Hz), 2.44 (m, 8H, CH2 COD), 0.94
2
2
COD(a), JPt,H = 38 Hz), 5.22 (m, 2H, CH COD(b), JPt,H = 48
(s, 3H, CH3, 2JPt,H = 78 Hz). 195Pt,1H HMBC (δ, CD2Cl2): −3211. 19
F
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dx.doi.org/10.1021/om400293u | Organometallics 2013, 32, 3662−3672

Organometallics
Article
NMR (δ, CD2Cl2): −116. IR (KBr in cm−1): 3092, 3039, 3008, 2990
(w): ν(CC−H); 2945, 2886 (s), 2835, 2801 (m): ν(H2C−H) and
ν(HC−H); 2115 (s): ν(CC); 1597, 1586 (m), 1501 (s): ν(C
C(aryl)); 1425, 1398, 1383 (m): δ(H2C−H) and δ(HC−H); 1220,
1201 (s): ν(C−F); 1007, 997, 981, 961, 944, 899, 862 (m), 838, 820,
783, 760, 743 (s), 689 (m): δ(CC−H); 531 (s): δ(C−F). EI-MS:
437 [M]+. λmax (THF): 250, 304 nm.
983, 966 (m), 853, 828, 814 (s), 774, 719 (m): δ(CC−H). EI-MS:
505 [M]+. λmax (THF): 255, 317 nm.
ASSOCIATED CONTENT
* Supporting Information
■
S
Figures S1−S25, Tables S1−S48, and a CIF file, giving
additional electrochemical, spectroscopic, and structural in-
formation. This material is available free of charge via the
Internet at http://pubs.acs.org.
[(COD)Pt(Me)(CC(4OMe)Ph)]: yield 86 mg (0.192 mmol,
68%). Anal. Calcd for C18H22OPt (449.44): C, 48.10; H, 4.93. Found:
C, 48.05; H, 4.91. 1H NMR (δ, CDCl3): 7.33 (m, 2H, o-Ph), 6.77 (m,
2
2H, m-Ph), 5.53 (m, 2H, CH COD(a), JPt,H = 35 Hz), 4.91 (m,
2
2H, CH COD(b), JPt,H = 49 Hz), 3.78 (s, 3H, OCH3), 2.44 (m,
AUTHOR INFORMATION
Corresponding Author
*E-mail: axel.klein@uni-koeln.de.
■
2
8H, CH2 COD), 1.05 (s, 3H, CH3, JPt,H = 77 Hz). 195Pt,1H HMBC
(δ, CDCl3): −3105. IR (KBr in cm−1): 3033, 3005 (w): ν(CC−H);
2951, 2930, 2882, 2836 (m): ν(H2C−H) and ν(HC−H); 2114 (s):
ν(CC); 1598, 1505 (s): ν(CC(aryl)); 1465, 1443, 1428 (m):
δ(H2C−H) and δ(HC−H); 1288, 1244, 1167, 1027 (s): ν(C−OC);
996, 980, 862 (m), 835 (s), 763, 732, 695 (m): δ(CC−H). λmax
(THF): 257, 318 nm.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We are indebted to Dr. Ingo Pantenburg and Miss Ingrid
Muller for single-crystal XRD measurements, as well as to Dr.
■
[(COD)Pt(Me)(CC(2Py)]: yield 71 mg (0.168 mmol, 63%).
Anal. Calcd for C16H19NPt (407.39): C, 44.22; H, 4.45; N, 3.44.
Found: C, 44.20; H, 4.43; N, 3.42. 1H NMR (δ, CDCl3): 8.49 (d, 1H,
6-Py), 7.52 (dt, 1H, 4-Py), 7.34 (d, 1H, 3-Py), 7.04 (d, 1H, 5-Py), 5.57
̈
Wieland Tyrra for NMR experiments (all at the University of
Cologne). We are also grateful for a loan of K2PtCl4 by Johnson
Matthey (JM) and for financial support by the Deutsche
Forschungsgemeinschaft (projects FOR-630 (I.O.) and KL
1194/11-1 (A.L. and A.K)).
2
(m, 2H, CH COD(a), JPt,H = 36 Hz), 4.97 (m, 2H, CH
2
3
COD(b), JPt,H = 49 Hz), 2.44 (m, 8H, CH2 COD, JPt,H ≈ 17 Hz),
1.06 (s, 3H, CH3, 2JPt,H = 77 Hz). 195Pt,1H HMBC (δ, CDCl3): −3121.
IR (KBr in cm−1): 3069, 3052, 3003 (w): ν(CC−H); 2923, 2878
(s), 2833, 2798 (m): ν(H2C−H) and ν(HC−H); 2100, 2063 (s):
ν(CC); 1592, 1550 (s): ν(CC(aryl)); 1465, 1423 (s): δ(H2C−
H) and δ(HC−H); 846, 802 (m), 766, 743, 714, 699 (m): δ(CC−
H). EI-MS: 407 [M]+ λmax (THF): 251, 296 nm.
REFERENCES
■
(1) (a) Berenguer, J. R.; Lalinde, E.; Moreno, M. T. Coord. Chem.
Rev. 2010, 254, 832.
Synthesis of [(COD)Pt(R′)(CC(4Me)Ph)] (R′ = Bz, Neop, or
NeoSi). The compounds were prepared as described for the R′ = Me
derivatives starting from 0.28 mmol of the [(COD)Pt(R′)Cl]
precursors.
́
(2) (a) Dıez, A.; Lalinde, E.; Moreno, M. T.; San
́
chez, S. Dalton
Trans. 2009, 3434. (b) Dıez, A.; Fernandez, J.; Lalinde, E.; Moreno, M.
T.; Sanchez, S. Dalton Trans. 2008, 4926.
(3) Berenguer, J. R.; Fernandez, J.; Lalinde, E.; San
Organometallics 2013, 32, 835.
(4) (a) Fornies, J.; Gomez, J.; Lalinde, E.; Moreno, M. T. Inorg. Chim.
Acta 2003, 347, 145. (b) Fornies
Moreno, M. T. Organometallics 2002, 21, 3733. (c) Falvello, L. R.;
́
́
́
́
chez, M. T.
[(COD)Pt(Bz)(CC(4Me)Ph)]: yield 115 mg (0.227 mmol,
81%). Anal. Calcd. for C24H26Pt (509.54): C, 56.57; H, 5.14. Found:
1
́
́
C, 56.61; H, 5.12. H NMR (δ, CD2Cl2): 7.26 (d, 2H, o-PhBz), 7.22
́
́
, J.; Garcıa, A.; Gomez, J.; Lalinde, E.;
́
(d, 2H, o-PhCC), 7.14 (d, 2H, m-PhBz), 7.06 (d, 2H, m-PhCC), 6.95
(t, 1H, p-PhBz), 5.51 (m, 2H, =CH COD(a), 2JPt,H = 39 Hz), 4.84 (m,
2H, CH COD(b), 2JPt,H = 47 Hz), 3.20 (s, 2H, CH2Bz, 2JPt,H = 106
́
́ ́
Fernandez, S.; Fornies, J.; Lalinde, E.; Martınez, F.; Moreno, M. T.
Organometallics 1997, 16, 1326.
(5) Belluco, U.; Bertani, R.; Michelin, R. A.; Mozzon, M. J.
Organomet. Chem. 2000, 600, 37.
(6) (a) Wrackmeyer, B.; Ullmann, B.; Kempe, R.; Herberhold, M. Z.
Anorg. Allg. Chem. 2005, 631, 2629. (b) Herberhold, M.; Schmalz, T.;
Milius, W.; Wrackmeyer, B. J. Organomet. Chem. 2002, 641, 173.
3
Hz) 2.39 (m, 8H, CH2 COD, JPt,H ∼ 10 Hz), 2.31 (s, 3H, p-CH3).
195Pt,1H HMBC (δ, CD2Cl2): −3106. IR (KBr in cm−1): 3069, 3048,
3020, 3001 (w): ν(CC−H); 2962, 2919, 2878, 2831 (m): ν(H2C−
H) and ν(HC−H); 2118 (s): ν(CC); 1592 (m), 1504, 1487 (s):
ν(CC(aryl)); 1445, 1428 (m): δ(H2C−H) and δ(HC−H); 990,
864 (m), 817, 802, 764, 702 (s): δ(CC−H). EI-MS: 509 [M]+. λmax
(THF): 251, 321 nm.
(7) (a) Gil, B.; Fornies
Moreno, M. T. Inorg. Chem. 2006, 45, 7788. (b) Fernan
Fornies, J.; Gil, B.; Gomez, J.; Lalinde, E.; Moreno, M. T.
Organometallics 2006, 25, 2274. (c) Dıez, A.; García, A.; Lalinde, E.;
́
, J.; Gom
́
ez, J.; Lalinde, E.; Martín, A.;
́
dez, J.;
[(COD)Pt(Neop)(CC(4Me)Ph)]: yield 116 mg (0.238 mmol,
́
́
85%). Anal. Calcd. for C22H30Pt (489.55): C, 53.97; H, 6.18. Found:
1
́
C, 53.91; H, 6.16. H NMR (δ, CDCl3): 7.25 (d, 2H, o-Ph), 7.03 (d,
2
́
Martın, A.; Moreno, M. T. Eur. J. Inorg. Chem. 2009, 3060.
2H, m-Ph), 5.54 (m, 2H, CH COD(a), JPt,H = 32 Hz), 4.87 (m,
2
(8) Jagadeesh, M. N.; Thiel, W.; Kohler, J.; Fehn, A. Organometallics
̈
2H, CH COD(b), JPt,H = 48 Hz), 2.42 (m, 8H, CH2 COD), 2.30
2
2002, 21, 2076.
(s, 3H, p-CH3), 1.88 (s, 2H, CH2Neop, JPt,H = 87 Hz), 1.14 (s, 9H,
1
C(CH3)3). 195Pt, H HMBC (δ, CDCl3): −3102. IR (KBr in cm−1):
́
́
(9) (a) Casas, J. M.; Fornies, J.; Fuertes, S.; Martın, A.; Sicilia, V.
Organometallics 2007, 26, 1674. (b) Berenguer, J. R.; Bernechea, M.;
3072, 3043, 3021, 3002 (w): ν(CC−H); 2945, 2924, 2883, 2856
(s): ν(H2C−H) and ν(HC−H); 2113 (s): ν(CC); 1607 (m), 1504
(s): ν(CC(aryl)); 1465, 1452, 1428 (s), 1354, 1348 (m): δ(H2C−
H) and δ(HC−H); 986, 861 (m), 817 (s), 784, 763 (m): δ(CC−
H). EI-MS: 489 [M]+. λmax (THF): 257, 317 nm.
́
Fornies
́
, J.; Garcıa, A.; Lalinde, E.; Moreno, M. T. Inorg. Chem. 2004,
43, 8185. (c) Charmant, J. P. H.; Fornies
́
, J.; Gomez, J.; Lalinde, E.;
́
Moreno, M. T.; Orpen, A. G.; Solano, S. Angew. Chem., Int. Ed. 1999,
38, 3058.
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[(COD)Pt(NeoSi)(CC(4Me)Ph)]: yield 112 mg (0.221 mmol,
́
(11) (a) Dıez, A.; Lalinde, E.; Moreno, M. T. Coord. Chem. Rev.
79%). Anal. Calcd. for C21H30PtSi (505.63): C, 49.88; H, 5.98. Found:
1
́
́
2011, 255, 2426. (b) Berenguer, J. R.; Dıez, A.; Garcıa, A.; Lalinde, E.;
Moreno, M. T.; Sanchez, S.; Torroba, J. Organometallics 2011, 30,
1646. (c) Berenguer, J. R.; Lalinde, E.; Torroba, J. Inorg. Chem. 2007,
C, 49.81; H, 5.99. H NMR (δ, CDCl3): 7.27 (d, 2H, o-Ph), 7.03 (d,
2
́
2H, m-Ph), 5.41 (m, 2H, CH COD(a), JPt,H = 38 Hz), 4.93 (m,
2
2H, CH COD(b), JPt,H = 49 Hz), 2.42 (m, 8H, CH2 COD), 2.30
2
́
46, 9919. (d) Benito, J.; Berenguer, J. R.; Fornıes, J.; Gil, B.; Gom
́
ez, J.;
(s, 3H, p-CH3), 1.14 (s, 2H, CH2NeoSi, JPt,H = 89 Hz), 0.12 (s, 9H,
1
Si(CH3)3). 195Pt, H HMBC (δ, CDCl3): −3056. IR (KBr in cm−1):
Lalinde, E. Dalton Trans. 2003, 4331.
3076, 3046, 3026, 3002 (w): ν(CC−H); 2943, 2923, 2889, 2870,
2837 (s): ν(H2C−H) and ν(HC−H); 2123 (s): ν(CC); 1605 (m),
1507 (s): ν(CC(aryl)); 1428 (s): δ(H2C−H) and δ(HC−H); 996,
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