Wiley, Chemistry - A European Journal, 42(21), p. 14708-14712, 2015
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This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/chem.201502474 ; We designed and synthesised a [Ru(CO)_3Cl_2(NAC)] pro-drug that features a N-acetyl cysteine (NAC) ligand. This NAC-CORM conjugate is able to simultaneously release biological active CO and to ablate the concurrent formation of reactive oxygen species (ROS). Complexes of the general formulae [Ru(CO)_3L_3]^2+, including CORM-3, have been shown to produce ROS through a water gas-shift reaction, that contribute significantly, for example, to their antibacterial activity. Instead, NAC-CORM does not result in ROS species neither possess antibacterial activity. In addition, we demonstrate the synergistic effect of CO and NAC both for the inhibition of nitric oxide (formation) and in the expression of tumour-necrosis factor (TNF)-?. This work highlights the advantages of combining a CO-releasing scaffold with the anti-oxidant and anti-inflammatory drug NAC in a unique pro-drug. ; We thank the EU (Marie Curie CIG to G.J.L.B.), FCT Portugal (FCT Investigator to G.J.L.B.; SFRH/BPD/95253/2013 to J.D.S.) and the EPSRC for funding. The NMR spectrometers are part of The National NMR Facility, supported by Funda??o para a Ci?ncia e a Tecnologia (RECI/BBB-BQB/0230/2012). G.J.L.B. is a Royal Society University Research Fellow.