Book of Abstracts - Ruhr-Universität Bochum

P-40
ISBOMC `10 5.7 – 9.7. 2010 Ruhr-Universität Bochum
Molybdenum Carbonyl Complexes as CO Releasing Molecules
Lukas Kromer a and Carlos Romão* a,b
a ITQB-UNL, Av. da República, Estação Agronómica Nacional, 2780-157 Oeiras, Portugal.
b ALFAMA Lda., Taguspark, Núcleo Central 267, 2740-122 Porto Salvo, Portugal.
E-mail: kromer@itqb.unl.pt
Carbon Monoxide (CO) is an essential signalling molecule produced in the body. Endogenous
overproduction of CO in pathological situations strongly suggests medicinal applications for CO.
Rather than using CO gas; drug research is focused on the development of CO-releasing Molecules
(CO-RMs). 1 Although there are a large number of CO-RMs known, few if any fulfil the essential
criteria for use as drugs, such as solubility in aqueous solutions of physiological pH, stability during
storage and controlled release of CO in vivo, and efficacy at non-toxic doses. Furthermore, targeting of
specific tissue is desirable. To obtain water-soluble organometallic complexes, they either have to be
charged or contain ligands that can be ionised in aqueous solutions through protonation or
deprotonation.
Charged complexes were synthesised with two types of ligands: 1,3-diketone and 2-hydroxyketone
ligands. Both types of ligand can be deprotonated and form anionic complexes with the general
structure (Et4N)[Mo(O-O)(CO)4]. 2 A second series of neutral complexes bearing functional groups
were synthesised with several mono- and bidentate amine ligands in a conventional microwave. 3
OC
CO
Mo
O
OC
CO
O
R
R
0, 1
-
OC
OC
Mo
CO
CO
R 2
N
N
R 2
OC
CO
Mo
NHR
OC
CO
NHR
98
4.00
3.50
3.00
2.50
O
.
C 2.00
e
q
1.50
1.00
0.50
0.00
CO‐Hb formation in blood
0 20 40 60 80
time [min]
The synthesised complexes were fully characterised and investigated in terms of solubility,
stability in aqueous solution and the CO release rate was determined both in vitro by GC-TCD as in ex
vivo assays in sheep blood with an Oxymeter. The direct measurement of CO-Hb levels in sheep blood
gives you an immediate answer about CO release under biological conditions. The water soluble,
neutral amine complexes exhibited a ligand-dependant CO release rate decreasing from primary,
secondary to tertiary amine ligands with half life times between 15 and 60 minutes. In contrary, the
results from the non water soluble amine and the less stable anionic complexes showed the limitation
of the setup, in which the solubility and stability under physiological conditions is crucial. In
conclusion, complexes with tuneable CO release rates are accessible and led to further improvements
in terms of stability and solubility of CO-RM’s.
References
1. R. Motterlini, B. E. Mann, R. Foresti, Expert Opin. Invest. Drugs 2005, 14, 1305-1318. (b) S. W.
Ryter, L. E. Otterbein, Bioessays 2004, 26, 270-280. (c) R. Motterlini, J. E. Clark, R. Foresti, P.
Sarathchandra, B. E. Mann and C. J. Green, Circ. Res. 2002, 90, E17-E24.
2. G. Doyle, J. Organomet. Chem 1973, 61, 235-245.
3. M. Ardon, G. Hogarth, D.T.W. Oscroft, J. Organomet. Chem. 2004, 689, 2429-2435.
a)
b)
c)