Iron nitrosyl complexes as models for biological nitric oxide transfer reagents.

Owing to the indiscriminate reactivity of the free NO radical, intricate control mechanisms are required for storage, transport and transfer of NO to its various biological targets. Among the proposed storage components are protein-bound thionitrosyls (Rprotein-SNO) and protein-bound dinitrosyl iron complexes. Current knowledge suggests the latter are derived from iron-sulfur cluster degradation in the presence of excess NO. Mobilization of protein-bound NO could involve NO or Fe(NO)2 unit transfer to small serum molecules such as glutathione, free cysteine, or iron-porphyrins. The study reported is of a reaction model which addresses the key steps in NO transfer from a prototypal iron dinitrosyl complex. While the N,N'-bis(2-mercaptoethyl)-N,N'-diazacyclooctane (bme-daco) ligand typically binds in square-planar N2S2 coordination, it also serves as a bidentate dithiolate donor for tetrahedral structures in the preparation of the (H+bme-daco)Fe(NO)2 derivative (Chiang et al., J. Am. Chem. Soc. 126:10867-10874, 2004). The removal of one NO produces the mononitrosyl complex, (bme-daco)Fe(NO), and simplifies studies of NO release mechanisms. We have used heme-type model complexes, Fe or Co porphyrins as NO acceptors, yielding (porphyrin)M(NO), where M is Fe or Co, and monitored reactions by nu(NO) Fourier transform IR spectroscopy. Reaction products were verified by electrospray ionization mass spectrometry. Rudimentary mechanistic studies suggest a role for HNO in the NO release from the dinitrosyl; the mononitrosyl benefits as well from acid catalysis. Other NO uptake complexes such as [(N2S2)Fe]2 [N2S2 is bme-daco or N,N'-bis(2-mercapto-2-methylpropyl)-daco] are shown to form Fe(NO) mononitrosyls with stability and spectroscopic signatures similar to those of the porphyrins.