Designed Iron Carbonyls as Carbon Monoxide (CO) Releasing Molecules: Rapid CO Release and Delivery to Myoglobin in Aqueous Buffer, and Vasorelaxation of Mouse Aorta

Abstract

The physiological roles of CO in neurotransmission, vasorelaxation and cytoprotective activities have raised interest in the design and syntheses of CO-releasing materials (CORMs) that could be employed to modulate such biological pathways. Three iron-based CORMs namely, [(PaPy3)Fe(CO)](ClO4) (1), [(SBPy3)Fe(CO)](BF4)2 (2) and [(Tpmen)Fe(CO)](ClO4)2 (3), derived from designed polypyridyl ligands have been synthesized and characterized by spectroscopy and X-ray crystallography. In these three Fe(II) carbonyls, the CO is trans to a carboxamido-N (in 1), an imine-N (in 2) and a tertiary amine-N (in 3) respectively. This structural feature has been correlated to the strength of the Fe-CO bond. The CO-releasing properties of all three carbonyls have been studied in various solvents under different experimental conditions. Rapid release of CO is observed with 2 and 3 upon dissolution in both aqueous and nonaqueous media in the presence and absence of dioxygen. With 1, CO release is observed only under aerobic conditions and the final product is an oxo-bridged diiron species while with 2 and 3, the solvent bound [(L)Fe(CO)]2+ (where L = SBPy3 or Tpmen) results upon loss of CO under both aerobic and anaerobic conditions. The apparent rates of CO loss by these CORMs are comparable to other CORMs such as [Ru(glycine)(CO)3Cl] reported recently. Facile delivery of CO to reduced myoglobin has been observed with both 2 and 3. In tissue bath experiments, 2 and 3 exhibit rapid vasorelaxation of mouse aorta muscle rings. Although the relaxation effect is not inhibited by the soluble guanylate cyclase inhibitor ODQ, significant inhibition is observed with the BKCa channel blocker iberiotoxin.

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

“…We believe that the recently reported complexes of formula [Fe(CO)(N5)] 2+ (N5 = pentacoordinated nitrogen ligand) are the first CORMs that have a real iCORM counterpart: the complex [Fe(H 2 O)(N5)] 2+ which readily forms when [Fe(CO)(N5)] 2+ is dissolved in aqueous media. 47 . Most likely, the fast expansion of the field of photoCORMs will produce other examples due to the precise control of the M-CO bond excision resulting from photoactivation.…”

Carbon monoxide – physiology, detection and controlled release

“…147,148 Further, three iron-based CORMs, [(PaPy 3 )Fe(CO)](ClO 4 ), [(SBPy 3 )Fe(CO)](BF 4 ) 2 , and [(Tpmen)Fe(CO)](ClO 4 ) 2 , derived from designed polypyridyl ligands, rapidly release CO upon dissolution and caused vasorelaxation in a mouse aorta muscle ring preparation. 149 The water soluble [Fe 2 {μ-SCH 2 CH(OH)CH 2 (OH)} 2 (CO) 6 ] releases CO via substitution by cysteamine with minimal cytotoxicity of the CORM itself on two cell lines QSG-7701 and HepG2. 150 In addition, the group of Ford discussed an oxidative cascade leading to the release of further CO from Na 3 [W(CO) 5 (tris(sulphonatophenyl)phosphine)] subsequent to the initial photo-activated CO dissociation (Fig.…”

Manganese Carbonyls Bearing Tripodal Polypyridine Ligands as Photoactive Carbon Monoxide-Releasing Molecules

“…Our initial efforts to prepare CORMs based on previously designed ligand frames resulted in a series of structurally related solvent-labile iron carbonyls that steadily give off CO under physiological conditions. 33 However, these CORMs did not require light for CO release.…”