Designed Iron Carbonyls as Carbon Monoxide-Releasing Molecules (CO-RMs) for Applications in Vasorelaxation Studies

Carbon monoxide (CO) is a known by-product of heme degradation in the body. In recent years, endogenously produced CO has been found to mediate a diverse array of desired biological functions, such neurotransmission, vasorelaxation and immune response. To further probe the mechanisms by which CO exerts its protective and regulatory action and to explore its potential as a therapeutic, site-specific delivery is imperative. Current methods utilize exogenously applied CO in hopes of mimicking the action of endogenous CO, however this approach is not quantitative and risks asphyxiation. We propose that transition metals bearing a designed ligand motif are efficient vehicles for quantitative and targeted CO delivery. We have synthesized two iron carbonyls, [(SBPy₃)Fe(CO)](BF₄)₂ (2) and [(Tpmen)Fe(CO)](ClO₄)₂ (3), bearing pentadentate ligand frameworks and characterized these structures by x-ray crystallography. Apparent rates of CO release were obtained by monitoring changes in the electronic absorption spectrum. CO release for 2 and 3 were comparable to known carbon monoxide-releasing molecules (CO-RMs). To further demonstrate the utility of 2 and 3, these were incorporated in vasorelaxation studies on isolated mouse aorta rings. The relaxation effect was not inhibited by ODQ, a soluble guanylyl cyclase (sGC) inhibitor, however significant inhibition was observed with the BK_Ca channel blocker iberiotoxin. These findings demonstrate the utility of designed metal carbonyls in CO delivery applications.