Thiolate (RS–) ligands have been shown to lower the activation barrier to O2 binding, and facilitate peroxo O-O bond cleavage and the cleavage of strong C-H bonds. We will describe an aliphatic thiolate-ligated Fe(II) complex that reacts with dioxygen (O2) to form an unprecedented example of a reactive iron superoxo (RS-Fe(III)-O2) intermediate that is capable of cleaving strong C-H bonds. A thiolate-ligated iron superoxo is proposed to play a key role in the biosynthesis of β-lactam antibiotics, as well as the prevention of cancerous tumor metastases. Isopenicillin N-synthase (IPNS) catalyzes the former, and cysteine dioxygenase (CDO) the latter. Very few iron superoxo compounds have been reported, and none are capable of cleaving strong C-H bonds. Spectroscopic characterization, and calibrated DFT and TD-DFT calculations, show that the frontier orbitals of our RS-Fe(III)-O2 consist of two strongly coupled unpaired electrons of opposite spin, one in a superoxo π*(O-O) orbital, and the other in an Fe(dxy) orbital.1 Both the calculated and experimental electronic absorption spectrum of our RS-Fe-O2 are similar to that of the putative IPNS superoxo intermediate, as well as an intermediate involved in the catalytic cycle of CDO. The rate at which our superoxo converts to a putative iron hydroperoxo (Fe(III)-OOH) is shown to depend on the C-H bond strength of the solvent or sacrificial H-atom donor, and a deuterium isotope effect (kH/kD= 4.8), comparable to that of IPNS (kH/kD= 5.6), is observed. As demonstrated by the presence of a low energy thiolate à Fe-O2 charge transfer transition, the electron-rich alkyl thiolate likely plays a role in increasing reactivity by creating a more basic superoxo. The bond dissociation energy (BDE) of the C-H bonds cleaved by our RS-Fe-O2 superoxo compound (92 kcal/mol) are comparable to those cleaved by the enzyme IPNS (93 kcal/mol).

Cleavage of strong C-H bonds by a thiolate-ligated FeIII-superoxo complex

ACS Spring 2022

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