Formation of a Reactive, Alkyl Thiolate-Ligated Fe^III-Superoxo Intermediate Derived from Dioxygen

Abstract

Herein, we describe an alkyl thiolate-ligated iron complex that reacts with dioxygen to form an unprecedented example of an iron superoxo (O₂^•-) intermediate, [Fe^III(S₂^Me2N₃(Pr,Pr))(O₂)] (4), which is capable of cleaving strong C-H bonds. A cysteinate-ligated iron superoxo intermediate is proposed to play a key role in the biosynthesis of β-lactam antibiotics by isopenicillin N-synthase (IPNS). Superoxo 4 converts to a metastable putative Fe(III)-OOH intermediate, at rates that are dependent on the C-H bond strength of the H atom donor, with a kinetic isotope effect ( k_H/ k_D = 4.8) comparable to that of IPNS ( k_H/ k_D = 5.6). The bond dissociation energy of the C-H bonds cleaved by 4 (92 kcal/mol) is comparable to C-H bonds cleaved by IPNS (93 kcal/mol). Both the calculated and experimental electronic absorption spectra of 4 are comparable to those of the putative IPNS superoxo intermediate, and are shown to involve RS^- → Fe-O₂^•- and O₂^•- → Fe charge transfer transitions. The π-back-donation by the electron-rich alkyl thiolate presumably facilitates this reactivity by increasing the basicity of the distal oxygen. The frontier orbitals of 4 are shown to consist of two strongly coupled unpaired electrons of opposite spin, one in a superoxo π*(O-O) orbital, and the other in an Fe(d _xy) orbital.