Sulfur oxygenation in biomimetic non-heme iron–thiolate complexes

Abstract

The S-oxygenation of cysteine with dioxygen to give cysteine sulfinic acid occurs at the non-heme iron active site of cysteine dioxygenase. Similar S-oxygenation events occur in other non-heme iron enzymes, including nitrile hydratase and isopenicillin N synthase, and these enzymes have inspired the development of a class of [NxSy]-Fe model complexes. Certain members of this class have provided some intriguing examples of S-oxygenation, and this article summarizes these results, focusing on the non-heme iron(II/III)-thiolate model complexes that are known to react with O2 or in some cases other O-atom transfer oxidants, to yield sulfur oxygenates. Key aspects of the synthesis, structure, and reactivity of these systems are presented, along with any mechanistic information available on the oxygenation reactions. A number of iron(III)-thiolate complexes react with O2 to give S-oxygenates, and the degree to which the thiolate sulfur donors are oxidized varies among the different complexes, depending upon the nature of the ligand, metal geometry, and spin state. The first examples of iron(II)-thiolate complexes that react with O2 to give selective S-oxygenation are just emerging. Mechanistic information on these transformations is limited, with isotope labeling studies providing much of the current mechanistic data. The many questions that remain unanswered for both models and enzymes provide strong motivation for future work in this area.

Non‐Heme Imine‐Based Iron Complexes as Catalysts for Oxidative Processes

“…[162] This enzyme catalyzes cysteines ide chain oxidation to sulfinic acid (RSO 2 À )w ith O 2 ,a nd the iron ion in the active site is coordinated by three histidine residues.T ridentate imine N 3 ligand( iPr BIP) effectivelyr eplicates the Fe(II) coordination mode in the enzyme (Scheme 20), and the steric hindrance of the isopropyl groups preventst he formation of Oand S-bridged dimers. At hiolate additional ligand lowers the redox potential of the iron complex, enabling reactionw ith O 2 ,a nd provides the sulfurw hich is oxidized.…”

Activation of Dioxygen by Iron and Manganese Complexes: A Heme and Nonheme Perspective

“…This enzyme is part of a larger group of related enzymes that can be classified as thiol dioxygenases (cysteamine dioxygenase, cysteine dioxygenase, 3-mercaptopropionate dioxygenase). 134 These enzymes are related in that they utilize O 2 to convert sulfur substrates to the dioxygenated sulfinic acid products. A number of mechanisms were proposed which involves formation of various iron–oxygen intermediates prior to the S -oxygenation reaction.…”

“…Until 2010, previous reports on Fe II (SAr) + O 2 chemistry described the formation of oxo-bridged dinuclear iron complexes or disulfide products. 134 An S -oxygenation reaction (Scheme 13) occurring from Fe II (SAr) + O 2 was described by our group in 2010. 140 A bis-imino pyridine (BIP) ligand (described as LN 3 S) providing three neutral N donors and a tethered thiolate donor was used in the former study.…”

Metal-Assisted Oxo Atom Addition to an Fe(III) Thiolate

“…15–20 For example, cysteinate-ligated TpFe II S cys reacts with O 2 to afford cys SO 2 − (the product of CDO 5 ); however, no intermediates were observed. 21 Iron complexes containing a non-tethered, monodentate RS ligand trans to the O 2 binding site have been shown to react with O 2 to afford an Fe IV ═O + RSSR, 3, 22 in contrast to cis -thiolate-ligated complexes, which have been shown to react with O 2 to afford doubly (RSO 2 -Fe) or triply (RSO 3 -Fe) oxygenated derivatives. 1–4, 22, 23 Singly oxygenated RSO-Fe sulfenate intermediates are not observed in these cases.…”

“…The mechanism by which post-translationally modified NHase sulfenate and sulfinate oxygens are inserted has been proposed to involve O 2 -induced formation of a thiolate-ligated high-valent oxo intermediate. 22, 29 There are no experimental data available to verify this possibility, however.…”