CO-releasing molecules

Alberto, R. Motterlini, R. Chemistry and biological activities of CO-releasing molecules (CORMs) and transition metal complexes. Dalton Trans., 1651-1660 (2007). 

Keywords Cardiovascular disease CO-releasing molecules Heme oxygenase Inflammation Medicinal chemistry Metal carbonyls Organ transplantation Reperfusion injury... 

CpFe(CO)2(pyrone)]+, pyrone = 4-methoxy-6-methyl-2-pyrone and 3-bromo-4-methoxy-6-methyl-2-pyrone were examined as potential CO releasing molecules but failed to release [195]. 

Two compounds, [CpMo(CO)3(pyrone)]+, pyrone = 4-methoxy-6-methyl-2-pyrone, 42, and 3-bromo-4-methoxy-6-methyl-2-pyrone, 43, were examined as potential CO releasing molecules. Both release CO to myoglobin. [CpMo(CO)3(3-bromo-4-meth-oxy-6-methyl-2-pyrone)]+, 43, which showed the faster CO release also showed good cell viability, cytotoxicity and inhibition of nitrite production using murine... 

When research started on the use of metal carbonyls as CO releasing molecules for applications in medicine in 2000, it was virtually a virgin area with a considerable background of work involving CO gas. As a result, patents were used to secure a broad area for commercial development. The first patent was due to Hemocorm in... 

In a recent review of the manganese CO-releasing molecules patent [204], it was concluded that there are multiple potential clinical candidates from the data presented and future work is expected to develop these CO-RMs into clinical products for a myriad of pathophysiological processes and disease states [251],... 

Carbon monoxide is attracting increasing attention as a potential therapeutic agent, because of its anti-hypertensive, anti-inflammatoiy and cell-protective effects. Metal carbonyl complexes are good carriers for CO, and represent a promising class of pharmaceuticals as CO-releasing molecules (so-called CORMs). 

Carbonyl rhenium(i) complexes have been investigated as potential photoactive CO-releasing molecules. In the case of [ReBr(azpy)(CO)3] and [Re(azpy)(C0)3(PPh3)]Cl04, CO-release occurs only upon illumination... 

In a recent study. Ford and coworkers reported the synthesis of 19 (Scheme 11.5), a luminescent photo-CORM (CO releasing molecule) based on 1, and easily incorporated in celk [67]. In this molecule the presence of the phosphine ligand increases its water solubility and makes the axial CO labile. Thus, upon irradiation, 19 released a CO molecule and was converted in its solvated (aqua) complex 20. Both molecules are strongly limiinescent, but notably their emission bands are centered at different wavelengths (515 and 585 nm, respectively). Consequently, accumulation of 19 in PPC-1 hiunan prostatic carcinoma cells (at a low concentration of incubation of 50 pM) followed by confocal microscopy is first associated with cells colored in blue (associated with the fluorescence of 19), and then release of CO upon irradiation led to green colored cells (associated with the fluorescence of 20) (Figure 11.7). 

In the past 15-20 years, carbon monoxide has been shown to be a key signalling molecule in biological systems, The CO regulatory pathway has been exploited to develop many series of promising new therapeutic molecules for a wide variety of medical applications. This review covers CO-regulatory pathways, types of CO-releasing molecule, modes and mechanisms of CO-release, and how CO-RM research has developed from usihg simple structural motifs to complex structures to allow modification of properties. 

Fig. 12 CO-release from 99 nM CO-RM 11 indicated by a clean deoxy-Mb to carboxy-Mb transition. 0.01 eq. RLE used as a CO-RM activation agent. (Image taken from ref. 68, Acyloxybutadiene Iron Tricarbonyl Complexes as Enzyme-Triggered CO-Releasing Molecules (ET-CORMs), S. Romanski, B. Kraus, U. Schatzschneider, J. M. NeudorfI, S. Amsiinger and H. G. Schmalz, Angew. Chem., Int Ed., 2011, 50, 2392-2396). Copyright Wiley 2011.

Metal Carbonyl Complexes (MCC) as CO-Releasing Molecules (CORM)... 

Pfeiffer H, Rojas A, Niesel J, Schatzschneider U. Sonogashira and click reactions for the N-terminal and side-chain functionalization of peptides with [Mn(CO)3 (tpm)] -based CO releasing molecules (tpm = tris(pyrazolyl)methane). Dalton Trans. 2009 38 4292-4298. 

Dordelmann, G., Pfeiffer, H., Birkner, A., and Schatzschneider, U. (2011) Silicium dioxide nanoparticles as carriers for photoactivatable CO-releasing molecules (PhotoCORMs). Inorg. Chem., 50, 4362-4367. 

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