ISBN: 978-83-60043-10-3 - eurobic9

Eurobic9, 2-6 September, 2008, Wrocław, Poland
P32. Manganese Carbonyls as CO Releasing Molecules
S. Crook a , B. E. Mann a , D. Scapens a , P. Sawle b , R. Motterlini b
a
Department of Chemistry, The University of Sheffield, Brook Hill, Sheffield, S3 7HF, UK
e-mail: chp06shc@sheffield.ac.uk.
b
Vascular Biology Unit, Department of Surgical Research, Northwick Park Hospital, Harrow, HA1 3UJ,
Middlesex, UK
The role of CO in mammals and the use of CO and CO-releasing molecules (CO-RMs) as therapeutic agents
have recently been described. 1 There are very few applications on CO-RMs containing manganese reported in
the literature. The released CO from [Mn2(CO)10] was shown to cause vasodilatation of an isolated section of rat
aorta. 2 Subsequently, [Mn2(CO)10] has been used as a light-induced CO-RM in a number of other biological
applications. 3-7 Recently, a new manganese CO-RM, [(HBpz3)Mn(CO)3][PF6] has been shown to be cytotoxic
for HT29 human colon cancer cells. 8
We have developed a range of manganese carbonyls that release CO rapidly when added to myoglobin. 9 Some of
these compounds, e.g., [NMe4][Mn{SC(O)Me}2(CO)4] and K[Mn2(µ-OAc)3(CO)6] show low cytotoxicity and
inhibit nitrite formation when tested on endotoxin-stimulated RAW264.7 macrophages. K[Mn2(µ-OAc)3(CO)6]
loses CO to myoglobin with a t1/2 of 9 min while [NMe4][Mn{SC(O)Me}2(CO)4] loses CO slower with t1/2 of 32
min. A range of similar compounds of the type [Mn(S2CE)(CO)4], E = OR or NR2, also show rapid CO loss and
their toxicity on cells is controlled by varying R. For example, [Mn(S2CNMeCH2CO2H)(CO)4] readily dissolves
in aqueous buffer at pH 7.4, loses at least 3 moles of CO to myoglobin with a t1/2 of 6 min, no loss of cell
viability or significant cytotoxicity and significant inhibition of nitrite formation at 100 µM.
The properties of these molecules in water will also be reported
References:
[1] B. E. Mann and R. Motterlini, Chem. Commun., 4197 (2007).
[2] R. Motterlini, J. E. Clark, R. Foresti, P. Sarathchandra, B. E. Mann and C. J. Green, Circ.Res., 90, E17
(2002).
[3] E. Fiumana, H. Parfenova, J. H. Jaggar and C. W. Leffler, Am. J. Physiol.-Heart Circul. Physiol., 284,
H1073 (2003).
[4] E. Barkoudah, J. H. Jaggar and C. W. Leffler, Am. J. Physiol.-Heart Circul. Physiol., 287, H1459 (2004).
[5] B. Arregui, B. Lopez, M. G. Salom, F. Valero, C. Navarro and F. J. Fenoy, Kidney International, 65, 564
(2004).
[6] P. Koneru and C. W. Leffler, Am. J. Physiol.-Heart Circul. Physiol., 286, H304 (2004).
[7] Q. Xi, D. Tcheranova, H. Parfenova, B. Horowitz, C. W. Leffler and J. H. Jaggar, Am. J. Physiol.-Heart
Circul. Physiol., 286, H610 (2004).
[8] J. Niesel, A. Pinto, H. W. P. N’Dongo, K. Merz, I. Ott, R. Gustb and U. Schatzschneider, Chem. Commun.,
1798 (2008).
[9] R. Motterlini, B. E. Mann and D. A. Scapens, Application: WO Pat., 2007-GB2483, WO28003953 A2,
2008.
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