Characterization of a versatile organometallic pro-drug (CORM) for experimental CO based therapeutics

The complex fac-[Mo(CO)(3)(histidinate)]Na has been reported to be an effective CO-Releasing Molecule in vivo, eliciting therapeutic effects in several animal models of disease. The CO releasing profile of this complex in different settings both in vitro and in vivo reveals that the compound can rea...

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Published in:Dalton transactions : an international journal of inorganic chemistry 2013-05, Vol.42 (17), p.5985-5998
Main Authors: Seixas, João D, Mukhopadhyay, Abhik, Santos-Silva, Teresa, Otterbein, Leo E, Gallo, David J, Rodrigues, Sandra S, Guerreiro, Bruno H, Gonçalves, Ana M L, Penacho, Nuno, Marques, Ana R, Coelho, Ana C, Reis, Patrícia M, Romão, Maria J, Romão, Carlos C
Format: Article
Language:English
Subjects:
Animals
Binding Sites
Carbon Monoxide - metabolism
Cell Line
Cell Survival - drug effects
Coordination Complexes - chemical synthesis
Coordination Complexes - chemistry
Coordination Complexes - toxicity
Crystallography, X-Ray
Hemodynamics
Hemoglobins - chemistry
Hemoglobins - metabolism
Hemolysis
Hep G2 Cells
Humans
Mice
Muramidase - chemistry
Muramidase - metabolism
Organometallic Compounds - chemical synthesis
Organometallic Compounds - chemistry
Organometallic Compounds - toxicity
Prodrugs - chemical synthesis
Prodrugs - chemistry
Prodrugs - toxicity
Protein Structure, Tertiary
Serum Albumin - chemistry
Serum Albumin - metabolism
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Summary:The complex fac-[Mo(CO)(3)(histidinate)]Na has been reported to be an effective CO-Releasing Molecule in vivo, eliciting therapeutic effects in several animal models of disease. The CO releasing profile of this complex in different settings both in vitro and in vivo reveals that the compound can readily liberate all of its three CO equivalents under biological conditions. The compound has low toxicity and cytotoxicity and is not hemolytic. CO release is accompanied by a decrease in arterial blood pressure following administration in vivo. We studied its behavior in solution and upon the interaction with proteins. Reactive oxygen species (ROS) generation upon exposure to air and polyoxomolybdate formation in soaks with lysozyme crystals were observed as processes ensuing from the decomposition of the complex and the release of CO.
ISSN:1477-9226
1477-9234
DOI:10.1039/c2dt32174b