Nitric oxide (NO) is an important signaling molecule that is involved in many physiological and pathological functions. Iron-sulfur proteins are one of the main reaction targets for NO, and the [Fe-S] clusters within these proteins are converted to various iron nitrosyl species upon reaction with NO, of which dinitrosyl iron complexes (DNICs) are the most prevalent. Much progress has been made in identifying the origin of cellular DNIC generation. However, it is not well-understood which other products besides DNICs may form during [Fe-S] cluster degradation nor what effects DNICs and other degradation products can have once they are generated in cells. Even more elusive is an understanding of the manner by which cells cope with unwanted [Fe-S] modifications by NO. This Account describes our synthetic modeling efforts to identify cluster degradation products derived from the [2Fe-2S]/NO reaction in order to establish their chemical reactivity and repair chemistry. Our intent is to use the chemical knowledge that we generate to provide insight into the unknown biological consequences of cluster modification. Our recent advances in three different areas are described. First, new reaction conditions that lead to the formation of previously unrecognized products during the reaction of [Fe-S] clusters with NO are identified. Hydrogen sulfide (H2S), a gaseous signaling molecule, can be generated from the reaction between [2Fe-2S] clusters and NO in the presence of acid or formal H• (e(-)/H(+)) donors. In the presence of acid, a mononitrosyl iron complex (MNIC) can be produced as the major iron-containing product. Second, cysteine analogues can efficiently convert MNICs back to [2Fe-2S] clusters without the need for any other reagents. This reaction is possible for cysteine analogues because of their ability to labilize NO from MNICs and their capacity to undergo C-S bond cleavage, providing the necessary sulfide for [2Fe-2S] cluster formation. Lastly, unique dioxygen reactivity of various types of DNICs has been established. N-bound neutral {Fe(NO)2}(10) DNICs react with O2 to generate low-temperature stable peroxynitrite (ONOO(-)) species, which then carry out nitration chemistry in the presence of phenolic substrates, relevant to tyrosine nitration chemistry. The reaction between S-bound anionic {Fe(NO)2}(9) DNICs and O2 results in the formation of Roussin's red esters (RREs) and thiol oxidation products, chemistry that may be important in biological cysteine oxidation. The N-bound cationic {Fe(NO)2}(9) DNICs can spontaneously release NO, and this property can be utilized in developing a new class of NO-donating agents with anti-inflammatory activity.
Reversible modification of iron-sulfur clusters by nitric oxide acts as a genetic switch in a group of regulatory proteins. While the conversion of [Fe-S] clusters to iron-nitrosyls has been widely studied in the past, little is known about the reverse process, the repair of [Fe-S] clusters. Reported here is a system in which a mononitrosyl iron complex (MNIC), (PPN)[Fe(S(t)Bu)3(NO)] (1), is converted to a [2Fe-2S] cluster, (PPN)2[Fe2S2(SCH2CH2C(O)OMe)4] (2). This conversion requires only the addition of a cysteine analogue, 3-mercaptomethylpropionate (MMP), at room temperature without the need for any other reagents. The identity of 2 was confirmed spectroscopically, chemically, crystallographically, and analytically. Mass spectrometry and (34)S labeling studies support that the bridging sulfides in 2 derive from the added MMP, the cysteine analogue. The NO lost during the conversion of 1 to 2 is trapped in a dinitrosyl iron side product, (PPN)[Fe(SCH2CH2C(O)OMe)2(NO)2] (4). The present system implies that MNICs are likely intermediates in the repair of NO-damaged [2Fe-2S] clusters and that cysteine is a viable molecule responsible for the destabilization of MINCs and the formation of [2Fe-2S] clusters.
The pressure dependences of the peaks observed in the micro-Raman spectra of Prussian blue (Fe 4 [Fe(CN) 6 ] 3 ), potassium ferricyanide (K 3 [Fe(CN) 6 ]), and sodium nitroprusside (Na 2 [Fe(CN) 5 (NO)]·2H 2 O) have been measured up to 5.0 GPa. The vibrational modes of Prussian blue appearing at 201 and 365 cm −1 show negative dν/dP values and Grüneisen parameters and are assigned to the transverse bending modes of the Fe-C-N-Fe linkage which can contribute to a negative thermal expansion behavior. A phase transition occurring between 2.0 and 2.8 GPa in potassium ferricyanide is shown by changes in the spectral region 150-700 cm −1 . In the spectra of the nitroprusside ion, there are strong interactions between the FeN stretching mode and the FeNO bending and the axial CN stretching modes. The pressure dependence of the NO stretching vibration is positive, 5.6 cm −1 GPa −1 , in contrast to the negative behavior in the iron(II)-meso-tetraphenyl porphyrinate complex.
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