Book of Abstracts - Ruhr-Universität Bochum

OP-26
ISBOMC `10 5.7 – 9.7. 2010 Ruhr-Universität Bochum
CO Releasing Properties of cis-trans-[Re II (CO)2Br2L2] n Complexes: A Feature
Modulated by Ligand Variation for a True Chance at Medicinal Applications.
Fabio Zobi* a and Alois Degonda a
a University of Zürich, Institute of Inorganic Chemistry, Winterthurerstr. 190, CH-8057, Zürich,
Switzerland. E-mail: fzobi@aci.uzh.ch
In recent years carbon monoxide (CO) has been acknowledged as a fundamental small-molecule
messenger in humans. 1 The tissue specific distribution of heme oxigenases and their action-derived
CO have been linked to several effects. For example, carbon monoxide acts as a signaling molecule in
the inducible defensive system against stressful stimuli. 1 It plays a fundamental role in the circulatory
system by improving vasorelaxation and cardiac blood supply and it suppresses arteriosclerotic lesions
associated with chronic graft rejection. 1,2 As the importance of CO is been increasingly recognized,
there is a steadily growing interest in the in pharmacological and medicinal applications of CO. Direct
inhalation of carbon monoxide has been viewed as a novel therapeutic approach but reports on
tolerance to CO exposure are contradictory.
An alternative approach to the administration of carbon monoxide is the use of CO-releasing
molecules (CORMs). An obvious choice for CORMs are transition metal carbonyl complexes with
one or more CO ligands. Several complexes have been evaluated to date, but the pioneering work of
Motterlini and Mann has resulted in the discovery of the fac-[RuCl(glycinato)(CO)3] complex
(CORM-3) as the most promising compound for the CO release in vivo. 3
In here we show that complexes of the type cis-trans-[Re II (CO)2Br2L2] n (where L = monodentate
ligand) 4 act as CO-releasing molecules and that under physiologically relevant conditions the rate of
CO release is comparable to that of CORM-3. The complexes represent a first example of metal-based
CORMs in which the central metal ion is not found in a d 6 or d 8 configuration. The open shell d 5
configuration of the Re system herein described represents an advantage over the more robust d 6 or d 8
systems for which physical stimuli (e.g. UV radiation) are often needed in order to elicit dissociation
of carbon monoxide from the metal core. The rate of CO release of cis-trans-[Re II (CO)2Br2L2] n
complexes is pH dependent and can be modulated by ligand variation. These features offer a true
chance for the application of these molecules in medicinal chemistry.
References
1. Wu, L.; Wang, R., Pharmacol. Rev. 2005, 57, 585-630.
2. Otterbein, L. E.; Zuckerbraun, B. S.; Haga, M.; Liu, F.; Song, R. P.; Usheva, A.; Stachulak, C.;
Bodyak, N.; Smith, R. N.; Csizmadia, E.; Tyagi, S.; Akamatsu, Y.; Flavell, R. J.; Billiar, T. R.; Tzeng,
E.; Bach, F. H.; Choi, A. M. K.; Soares, M. P., Nature Med. 2003, 9, 183-190.
3. Foresti, R.; Bani-Hani, M. G.; Motterlini, R., Intensive Care Med. 2008, 34, 649-658.
4. Zobi, F.; Kromer, L.; Spingler, B.; Alberto, R., Inorg. Chem. 2009, 48, 8965-8970.
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