title: New insights into the chemistry of fac-[Ru(CO)₃]²⁺ 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.
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.
authors.affiliation: REQUIMTE-CQFB, Departamento de Química, FCT-UNL, 2829-516 Caparica, Portugal.
authors.forename: M F A
authors.initials: MF
authors.lastname: Santos
authors.forename: J D
authors.initials: JD
authors.lastname: Seixas
authors.forename: A C
authors.initials: AC
authors.lastname: Coelho
authors.forename: A
authors.initials: A
authors.lastname: Mukhopadhyay
authors.forename: P M
authors.initials: PM
authors.lastname: Reis
authors.forename: M J
authors.initials: MJ
authors.lastname: Romão
authors.forename: C C
authors.initials: CC
authors.lastname: Romão
authors.forename: T
authors.initials: T
authors.lastname: Santos-Silva
mesh_terms: D002248:Carbon Monoxide / Q000737:chemistry*; D018360:Crystallography, X-Ray; D009113:Muramidase / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*; D012996:Solutions
chemical_list: D009942:Organometallic Compounds; D012996:Solutions; C476530:tricarbonylchloro(glycinato)ruthenium(II); C447082:tricarbonyldichlororuthenium (II) dimer; D002248:Carbon Monoxide; D012428:Ruthenium; D009113:Muramidase