New insights into the chemistry of fac-[Ru(CO)3]²âº fragments in biologically relevant conditions: the CO releasing activity of [Ru(CO)3Cl2(1,3-thiazole)], and the X-ray crystal structure of its adduct with lysozyme.
J Inorg Biochem
; 117: 285-91, 2012 Dec.
Article
em En
| MEDLINE
| ID: mdl-22883959
ABSTRACT
Complexes of the general formula fac-[Ru(CO)(3)L(3)](2+), namely CORM-2 and CORM-3, have been successfully used as experimental CO releasing molecules (CO-RMs) but their mechanism of action and delivery of CO remain unclear. The well characterized complex [Ru(CO)(3)Cl(2)(1,3-thiazole)] (1) is now studied as a potential model CO-RM of the same family of complexes using LC-MS, FTIR, and UV-vis spectroscopy, together with X-ray crystallography. The chemistry of [Ru(CO)(3)Cl(2)(1,3-thiazole)] is very similar to that of CORM-3 it only releases residual amounts of CO to the headspace of a solution in PBS7.4 and produces marginal increase of COHb after long incubation in whole blood. 1 also reacts with lysozyme to form Ru adducts. The crystallographic model of the lysozyme-Ru adducts shows only mono-carbonyl Ru species. [Ru(H(2)O)(4)(CO)] is found covalently bound to a histidine (His15) and to two aspartates (Asp18 and Asp119) at the protein surface. The CO release silence of both 1 and CORM-3 and their rapid formation of protein-Ru(CO)(x)(H(2)O)(y) (x=1,2) adducts, support our hypothesis that fac-[Ru(CO)(3)L(3)] CO-RMs deliver CO in vivo through the decay of their adducts with plasma proteins.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos Organometálicos
/
Rutênio
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Monóxido de Carbono
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Muramidase
Idioma:
En
Revista:
J Inorg Biochem
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Portugal