ARTICLE
DOI: 10.1002/zaac.201300054
Osmium-Nitrosyl Complexes with Glycine, Picolinic Acid, L-Proline and
D-Proline: Synthesis, Structures and Antiproliferative Activity
Anatolie Gavriluta,
[a]
Maria Novak,
[b]
Jean Bernard Tommasino,
[a]
Samuel M. Meier,
[b]
Michael A. Jakupec,
[b]
Dominique Luneau,*
[a]
and Vladimir B. Arion*
[b]
Keywords: Osmium; Amino acids; Bioinorganic chemistry; Cytotoxicity
Abstract. The reactions of [Os(NO)Cl
5
]
2–
with glycine (GlyH), pico-
linic acid (PicoH), -proline (-ProH) and -proline (-ProH) afforded
four novel complexes of the general formula [Os(NO)Cl
3
(AA)]
–
,
where AA = Gly, Pico, -Pro and -Pro, respectively. X-ray diffraction
studies have revealed that in all cases the same isomer type from three
Introduction
The antitumor activity of metal based drugs depends upon
many parameters,
[1]
including the reactivity towards amino ac-
ids, the most important low-molecular-weight biological li-
gands. Investigation of these reactions can help in establish-
ment of the nature of the species delivered into the cells, since
the compounds can be modified inside the human body, in
getting insight into the mechanisms of detoxification and me-
tabolism of applied drugs, and in identification of potential
cellular targets responsible for cytotoxicity.
[2]
For instance, a
platinum(II) compound with -methionine, Pt(L-met)
2
, was
isolated from human urine, while studying the metabolism of
cisplatin in the human body.
[3]
The effect of cell culture media,
consisting mainly of amino acids, salts (Na
+
,K
+
, Mg
2+
, Ca
2+
),
vitamins and glucose, on the metal-based drugs is a standard
test now to probe their resistance to a chemical environment
on application in vitro in cell culture experiments.
Quite recently, we prepared a series of ruthenium(II)- and
osmium(II)-nitrosyl complexes with azole ligands and found
out that they show a striking difference in antiproliferative ac-
tivity, in strong contrast to previous comparative studies of
homologous ruthenium(II) and osmium(II) complexes.
[4]
Within a more extended program initiated recently, we are try-
* Prof. Dr. D. Luneau
E-Mail: dominique.luneau@univ-lyon1.fr
* Prof. Dr. V. Arion
E-Mail: vladimir.arion@univie.ac.at
[a] Université Claude Bernard Lyon 1
Laboratoire des Multimatériaux et Interfaces (UMR 5615)
Campus de La Doua
69622 Villeurbanne Cedex, France
[b] University of Vienna
Institute of Inorganic Chemistry
Währinger Strasse 42
1090 Vienna, Austria
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/zaac.201300054 or from the au-
thor.
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Z. Anorg. Allg. Chem. 2013, 639, (8-9), 1590–1597 1590
theoretically possible, has been isolated, namely mer(Cl),
trans(NO,O)-[Os(NO)Cl
3
(AA)]
–
. Spectroscopic and electrochemical
properties, behavior in aqueous solution and antiproliferative activity
in three human cancer cell lines are also reported.
ing to find out the reasons for the observed difference in cyto-
toxicity. Nitric oxide plays important roles in biochemical pro-
cesses.
[5]
It is a typical example of a non-innocent ligand
[6]
in
coordination chemistry. It binds to metals linearly (NO
+
) or
adopting a bent mode (NO
–
). The linearly coordinated NO
+
ligand is a poor σ-donor, but a very strong π-acceptor. NO
+
shows a range of structural trans effects (STEs) depending
upon the identity of the trans ligand.
[7]
Generally trans M–L
bonds to π-acceptor ligands (NO, CO) are lengthened due to
competition for π-electron density, while π-donation from
chlorido or hydroxido ligands, stimulated by the strong π-ac-
ceptor nature of NO
+
, results in inverse STEs, namely, shorten-
ing of both trans bonds M–NO
+
and M–L
trans
. In addition, the
metal-nitrosyl unit acts as a reaction mediator or regulator of
geometry around the metal atom.
[8]
Linkage isomerization of
the N- and O-bonded nitrosyl ligands is also well-documen-
ted.
[9]
Despite great interest of researchers in this type of com-
pounds, very little is known about the reactivity of rutheni-
um(II)-nitrosyl compounds with amino acids,
[9b,10]
while data
on the related osmium counterparts to the best of our knowl-
edge have not been reported so far.
The only well-characterized osmium compounds with amino
acids are osmyl(VI) complexes with glycine, DL-alanine, DL-
valine, DL-leucine, DL-isoleucine, DL-phenylalanine ligands
reported more than 30 years ago,
[11]
and osmium(II)-arene
compounds with -prolinate, namely, [(η
6
-p-cymene)Os(L-
prolinate)]
3
[BF
4
]
3
,
[12]
and [OsCl(CO)(L-phenylalaninate)-
(PPh
3
)
2
].
[13]
All this prompted us to initiate the study of the reactions of
[Os(NO)Cl
5
]
2–
with some potentially bidentate amino acids in
order to elucidate the effect of coordinated NO
+
on the nature
of the favored co-ligand in trans-position and on the favored
isomer type formed, to isolate and fully characterize the reac-
tion products and evaluate their antiproliferative activity in hu-
man cancer cell lines. Herein we report on the synthesis of four