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

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Abstract

Complexes of the general formula fac-[Ru(CO)3L3] 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) 3Cl2(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) 3Cl2(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 2O)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(H2O)y (x = 1,2) adducts, support our hypothesis that fac-[Ru(CO)3L3] CO-RMs deliver CO in vivo through the decay of their adducts with plasma proteins.

Original languageEnglish
Pages (from-to)285-291
Number of pages7
JournalJournal of Inorganic Biochemistry
Volume117
DOIs
Publication statusPublished - Dec 2012

Keywords

  • CO therapy
  • CORM
  • Protein crystallography
  • Ruthenium complexes

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