FULL PAPER
DOI:10.1002/ejic.201402954
Platinum Diolefin Complexes – Synthesis, Structures, and
Cytotoxicity
Anna Lüning,
[a]
Michael Neugebauer,
[a]
Verena Lingen,
[a,b]
Alexander Krest,
[a]
Kathrin Stirnat,
[a]
Glen B. Deacon,
[b]
Penny R. Drago,
[b]
Ingo Ott,
[c]
Julia Schur,
[c]
Ingo Pantenburg,
[a]
Gerd Meyer,
[a]
and Axel Klein*
[a]
Dedicated to Professor Hubert Schmidbaur on the occasion of his 80th birthday
Keywords: Platinum / Alkene ligands / Structure elucidation / Structure–activity relationships / Cytotoxicity
The synthesis, spectroscopy, structures and chemical reac-
tivity of platinum(II) diolefin complexes cis-[(||
∧
||)PtCl
2
], cis-
[(||
∧
||)PtCl(R)] and cis-[(||
∧
||)Pt(R)
2
] [||
∧
|| = chelate diolefin li-
gand: 1,5-cyclooctadiene (COD), 1,5-dimethylocta-1,5-diene
(Me
2
COD), norbornadiene (NBD), 1,5-hexadiene (HEX), 3-
allyloxypropene (All
2
O, diallyl ether), diallylamine (All
2
NH);
R = Me, Bn, C
6
F
5
,C
6
F
4
H-4 (or -5), or CC(4-Me)Ph] have
been explored. The relative exchange rates of the cis-[(||
∧
||)-
PtCl
2
] complexes towards the diimine ligand diisopropyl-1,4-
diazabutadiene (iPr-DAB) increased along the series COD
Me
2
COD NBD HEX All
2
O by a factor of 4. The pre-
sumably dimeric complex [(All
2
NH)PtCl
2
]
2
undergoes a
unique rearrangement process in dimethyl sulfoxide (DMSO)
Introduction
The binding of olefins to transition metal ions reveals a
marked maximum of stability for platinum(II) and palla-
dium(II). This observation can be explained from the best
match of promotion energy (should be low) and electron
affinity (should be high).
[1,2]
Given the inert nature of Pt
II
,
it is unsurprising that Zeise prepared K[PtCl
3
(C
2
H
4
)]
(Zeise’s salt) in 1827, which is considered to be the
first organometallic complex.
[2–5]
The Pd
II
derivative
[PdCl
3
(C
2
H
4
)]
–
plays a crucial role in one of the most im-
portant industrial chemical processes, that is, the oxidation
[a] Universität zu Köln, Department für Chemie, Institut für
Anorganische Chemie,
Greinstrasse 6, 50939 Köln, Germany
E-mail: axel.klein@uni-koeln.de
http://www.klein.uni-koeln.de/
[b] School of Chemistry, Monash University,
P. O. Box 23, VIC 3800, Australia
[c] Institute of Medicinal and Pharmaceutical Chemistry,
Technische Universität Braunschweig,
Beethovenstraße 55, 38106 Braunschweig, Germany
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejic.201402954.
Eur. J. Inorg. Chem. 2015, 226–239 © 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 226
solution to yield the dimeric piperazine complex [PtCl(dmso)-
(C
6
H
10
N)]
2
, which has been characterised by single-crystal
XRD. For selected platinum complexes, cytotoxic effects in
HT-29 colon carcinoma and MCF-7 breast cancer cell lines
were evaluated. For comparison, the dicationic complexes
[(COD)Pt(Bn)(L)][PF
6
]
2
with the very labile coligands N-
methyl-4,4'-bipyridinium (MQ
+
) and N-methyl-1,4-pyrazin-
ium (Mpz
+
) were added to the study. Although the hexadiene
complexes [(HEX)Pt(C
6
F
4
H-4)
2
] and [(HEX)Pt(C
6
F
4
H-5)
2
]
show strong cytotoxicity, the introduction of labile diolefin
ligands or the labile cationic MQ
+
or Mpz
+
coligands does
not generally lead to markedly increased cytotoxicity.
of ethane in the so-called Wacker–Hoechst process (also
Wacker oxidation).
[6]
To enhance the stability of olefin platinum complexes,
the chelate effect is crucial, and 1,5-cyclooctadiene (COD)
is best for this purpose. The relatively high stability of COD
complexes opens several routes for the derivatisation of the
frequently used starting complex [(COD)PtCl
2
] (Scheme 1).
Firstly, the quite stable CODPt scaffold allows the replace-
ment of one or two Cl coligands by carbanionic coligands,
such as alkyl,
[7–13]
aryl,
[10–14]
alkynyl,
[13–18]
alkenyl
[16,19]
or
cyclopentadienide,
[20]
to form various derivatives
(Scheme 1, Reaction 1) or by other anionic coligands such
as amides,
[21]
thiolates,
[22,23]
SCN
–
or pseudohalides
(Scheme 1, Reaction 2).
[7,10,22,24]
The limit of this reaction
is set by strong nucleophiles (Nu), which attack the olefin
double bond to yield a Pt–C–C–Nu unit with a Pt–C σ
bond.
[7,25,26]
Neutral coligands can be introduced by ab-
straction of a Cl
–
ion with Ag
+
or Tl
+
salts to yield cationic
complexes (Scheme 1, Reaction 3).
[13,14,26]
The choice of an
appropriate ligand even allows the introduction of a
monoanionic chelate ligand for the two Cl
–
coligands,
[27]
whereas reactions with neutral chelate ligands lead to the