Nitric oxide reactivity of [2Fe-2S] clusters leading to H2S generation.

The crosstalk between two biologically important signaling molecules, nitric oxide (NO) and hydrogen sulfide (H2S), proceeds via elusive mechanism(s). Herein we report the formation of H2S by the action of NO on synthetic [2Fe-2S] clusters when the reaction environment is capable of providing a formal H(•) (e(-)/H(+)). Nitrosylation of (NEt4)2[Fe2S2(SPh)4] (1) in the presence of PhSH or (t)Bu3PhOH results in the formation of (NEt4)[Fe(NO)2(SPh)2] (2) and H2S with the concomitant generation of PhSSPh or (t)Bu3PhO(•). The amount of H2S generated is dependent on the electronic environment of the [2Fe-2S] cluster as well as the type of H(•) donor. Employment of clusters with electron-donating groups or H(•) donors from thiols leads to a larger amount of H2S evolution. The 1/NO reaction in the presence of PhSH exhibits biphasic decay kinetics with no deuterium kinetic isotope effect upon PhSD substitution. However, the rates of decay increase significantly with the use of 4-MeO-PhSH or 4-Me-PhSH in place of PhSH. These results provide the first chemical evidence to suggest that [Fe-S] clusters are likely to be a site for the crosstalk between NO and H2S in biology.

Acid-dependent degradation of a [2Fe-2S] cluster by nitric oxide.

New types of degradation products of iron-sulfur clusters by nitric oxide (NO) have been identified in the acidic environment. In the absence of acid, NO reacts with (Et(4)N)(2)[Fe(2)S(2)Cl(4)] (1) to form a {Fe(NO)(2)}(9) dinitrosyliron complex, (Et(4)N)[Fe(NO)(2)Cl(2)] (2), wherein the bridging sulfides are oxidized to elemental sulfur by four electrons (2S(2-) → 2S(0) + 4e(-)). In contrast, the successive additions of NO and HCl to 1 result in the formation of a {Fe(NO)}(7) mononitrosyliron complex, (Et(4)N)[Fe(NO)Cl(3)] (3), along with elemental sulfur and hydrogen sulfide (H(2)S), which are the two-electron-oxidized products of the bridging sulfides (2S(2-) + 2H(+) → H(2)S + S(0) + 2e(-)). The results demonstrate that the acidic environment plays a significant role in controlling the chemistry of an iron-sulfur cluster with NO and imply how two important gaseous molecules, NO and H(2)S, can be interconnected through iron-sulfur clusters.

Designing green oxidation catalysts for purifying environmental waters.

We describe the synthesis, characterization, aqueous behavior, and catalytic activity of a new generation of Fe(III)-TAML (tetraamido macrocycle ligand) activators of peroxides (2), variants of [Fe{(OC)(2)(o,o'-NC(6)H(4)NCO)(2)CMe(2)}(OH(2))(-)] (2d), which have been designed to be especially suitable for purifying water of recalcitrant oxidizable pollutants. Activation of H(2)O(2) by 2 (k(I)) as a function of pH was analyzed via kinetic studies of Orange II bleaching. This was compared with the known behavior of the first generation of Fe(III)-TAMLs (1). Novel reactivity features impact the potential for oxidant activation for water purification by 2d and its aromatic ring-substituted dinitro (2e) and tetrachloro (2f) derivatives. Thus, the maximum activity for 2e occurs at pH 9, the closest yet to the EPA guidelines for drinking water (6.5-8.5), allowing 2e to rapidly activate H(2)O(2) at pH 7.7. In water, 2e has two axial water ligands with pK(a)'s of 8.4 and 10.0 (25 degrees C). The former is the lowest for all Fe(III)-TAMLs developed to date and is key to 2e's exceptional catalytic activity in neutral and slightly basic solutions. Below pH 7, 2d was found to be quite sensitive to demetalation in phosphate buffers. This was overcome by iterative design to give 2e (hydrolysis rate 2d > 100 x 2e). Mechanistic studies highlight 2e's increased stability by establishing that to demetalate 2e at a comparable rate to which H(2)PO(4)(-) demetalates 2d, H(3)PO(4) is required. A critical criterion for green catalysts for water purification is the avoidance of endocrine disruptors, which can impair aquatic life. Fe(III)-TAMLs do not alter transcription mediated by mammalian thyroid, androgen, or estrogen hormone receptors, suggesting that 2 do not bind to the receptors and reducing concerns that the catalysts might have endocrine disrupting activity.

Design of more powerful iron-TAML peroxidase enzyme mimics.

Environmentally useful, small molecule mimics of the peroxidase enzymes must exhibit very high reactivity in water near neutral pH. Here we describe the design and structural and kinetic characterization of a second generation of iron(III)-TAML activators with unprecedented peroxidase-mimicking abilities. Iterative design has been used to remove the fluorine that led to the best performers in first-generation iron-TAMLs. The result is a superior catalyst that meets a green chemistry objective by being comprised exclusively of biochemically common elements. The rate constants for bleaching at pH 7, 9, and 11 of the model substrate, Orange II, shows that the new Fe(III)-TAML has the fastest reactivity at pH's closer to neutral of any TAML activator to date. Under appropriate conditions, the new catalyst can decolorize Orange II without loss of activity for at least 10 half-lives, attesting to its exceptional properties as an oxidizing enzyme mimic.