Spontaneous CO Release from RuII(CO)2–Protein Complexes in Aqueous Solution, Cells, and Mice1. Issue 4 (4th December 2014)

• Record Type: Journal Article
• Authors: Chaves‐Ferreira, Miguel; Albuquerque, Inês S.; Matak‐Vinkovic, Dijana; Coelho, Ana C.; Carvalho, Sandra M.; Saraiva, Lígia M.; Romão, Carlos C.; Bernardes, Gonçalo J. L.
• Is Part Of: Angewandte Chemie international edition. Volume 54:Issue 4(2015)
• Page Start: 1172
• Page End: 1175
• Publication Date: 2014-12-04
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201409344
• Languages: English
• ISSNs: 1433-7851

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>We demonstrate that Ru^II(CO)₂–protein complexes, formed by the reaction of the hydrolytic decomposition products of [<italic>fac</italic>‐RuCl(<italic>κ</italic>²‐H₂NCH₂CO₂)(CO)₃] (CORM‐3) with histidine residues exposed on the surface of proteins, spontaneously release CO in aqueous solution, cells, and mice. CO release was detected by mass spectrometry (MS) and confocal microscopy using a CO‐responsive turn‐on fluorescent probe. These findings support our hypothesis that plasma proteins act as CO carriers after in vivo administration of CORM‐3. CO released from a synthetic bovine serum albumin (BSA)–Ru^II(CO)₂ complex leads to downregulation of the cytokines interleukin (IL)‐6, IL‐10, and tumor necrosis factor (TNF)‐α in cancer cells. Finally, administration of BSA–Ru^II(CO)₂ in mice bearing a colon carcinoma tumor results in enhanced CO accumulation at the tumor. Our data suggest the use of Ru^II(CO)₂–protein complexes as viable alternatives for the safe and spatially controlled delivery of therapeutic CO in vivo.</p> </abstract>