Electronic structures and spectroscopic signatures of diiron intermediates generated by O2 activation of nonheme iron(II)-thiolate complexes.

The activation of O2 at thiolate-ligated iron(II) sites is essential to the function of numerous metalloenzymes and synthetic catalysts. Iron-thiolate bonds in the active sites of nonheme iron enzymes arise from either coordination of an endogenous cysteinate residue or binding of a deprotonated thiol-containing substrate. Examples of the latter include sulfoxide synthases, such as EgtB and OvoA, that utilize O2 to catalyze tandem S-C bond formation and S-oxygenation steps in thiohistidine biosyntheses. We recently reported the preparation of two mononuclear nonheme iron-thiolate complexes (1 and 2) that serve as structural active-site models of substrate-bound EgtB and OvoA (Dalton Trans. 2020, 49, 17745-17757). These models feature monodentate thiolate ligands and tripodal N4 ligands with mixed pyridyl/imidazolyl donors. Here, we describe the reactivity of 1 and 2 with O2 at low temperatures to give metastable intermediates (3 and 4, respectively). Characterization with multiple spectroscopic techniques (UV-vis absorption, NMR, variable-field and -temperature Mössbauer, and resonance Raman) revealed that these intermediates are thiolate-ligated iron(III) dimers with a bridging oxo ligand derived from the four-electron reduction of O2. Structural models of 3 and 4 consistent with the experimental data were generated via density functional theory (DFT) calculations. The combined experimental and computational results illuminate the geometric and electronic origins of the unique spectral features of diiron(III)-µ-oxo complexes with thiolate ligands, and the spectroscopic signatures of 3 and 4 are compared to those of closely-related diiron(III)-µ-peroxo species. Collectively, these results will assist in the identification of intermediates that appear on the O2 reaction landscapes of iron-thiolate species in both biological and synthetic environments.

Nonheme iron-thiolate complexes as structural models of sulfoxide synthase active sites.

Two mononuclear iron(ii)-thiolate complexes have been prepared that represent structural models of the nonheme iron enzymes EgtB and OvoA, which catalyze the O2-dependent formation of carbon-sulfur bonds in the biosynthesis of thiohistidine compounds. The series of Fe(ii) complexes reported here feature tripodal N4 chelates (LA and LB) that contain both pyridyl and imidazolyl donors (LA = (1H-imidazol-4-yl)-N,N-bis((pyridin-2-yl)methyl)methanamine; LB = N,N-bis((1-methylimidazol-2-yl)methyl)-2-pyridylmethylamine). Further coordination with monodentate aromatic or aliphatic thiolate ligands yielded the five-coordinate, high-spin Fe(ii) complexes [FeII(LA)(SMes)]BPh4 (1) and [FeII(LB)(SCy)]BPh4 (2), where SMes = 2,4,6-trimethylthiophenolate and SCy = cyclohexanethiolate. X-ray crystal structures revealed that 1 and 2 possess trigonal bipyramidal geometries formed by the N4S ligand set. In each case, the thiolate ligand is positioned cis to an imidazole donor, replicating the arrangement of Cys- and His-based substrates in the active site of EgtB. The geometric and electronic structures of 1 and 2 were analyzed with UV-vis absorption and Mössbauer spectroscopies in tandem with density functional theory (DFT) calculations. Exposure of 1 and 2 to nitric oxide (NO) yielded six-coordinate FeNO adducts that were characterized with infrared and electron paramagnetic resonance (EPR) spectroscopies, confirming that these complexes are capable of binding diatomic molecules. Reaction of 1 and 2 with O2 causes oxidation of the thiolate ligands to disulfide products. The implications of these results for the development of functional models of EgtB and OvoA are discussed.

Spectroscopic and Computational Comparisons of Thiolate-Ligated Ferric Nonheme Complexes to Cysteine Dioxygenase: Second-Sphere Effects on Substrate (Analogue) Positioning.

Parallel spectroscopic and computational studies of iron(III) cysteine dioxygenase (CDO) and synthetic models are presented. The synthetic complexes utilize the ligand tris(4,5-diphenyl-1-methylimidazol-2-yl)phosphine (Ph2TIP), which mimics the facial three-histidine triad of CDO and other thiol dioxygenases. In addition to the previously reported [FeII(CysOEt)(Ph2TIP)]BPh4 (1; CysOEt is the ethyl ester of anionic l-cysteine), the formation and crystallographic characterization of [FeII(2-MTS)(Ph2TIP)]BPh4 (2) is reported, where the methyl 2-thiosalicylate anion (2-MTS) resembles the substrate of 3-mercaptopropionate dioxygenase (MDO). One-electron chemical oxidation of 1 and 2 yields ferric species that bind cyanide and azide anions, which have been used as spectroscopic probes of O2 binding in prior studies of FeIII-CDO. The six-coordinate FeIII-CN and FeIII-N3 adducts are examined with UV-vis absorption, electron paramagnetic resonance (EPR), and resonance Raman (rRaman) spectroscopies. In addition, UV-vis and rRaman studies of cysteine- and cyanide-bound FeIII-CDO are reported for both the wild-type (WT) enzyme and C93G variant, which lacks the Cys-Tyr cross-link that is present in the second coordination sphere of the WT active site. Density functional theory (DFT) and ab initio calculations are employed to provide geometric and electronic structure descriptions of the synthetic and enzymatic FeIII adducts. In particular, it is shown that the complete active space self-consistent field (CASSCF) method, in tandem with n-electron valence state second-order perturbation theory (NEVPT2), is capable of elucidating the structural basis of subtle shifts in EPR g values for low-spin FeIII species.

A pentadentate nitrogen-rich copper electrocatalyst for water reduction with pH-dependent molecular mechanisms.

The new pentadentate 3d9 complex [CuII(LN2Py3)](PF6)2 (1) based on a nitrogen-rich framework acts as an electrocatalyst toward dihydrogen production from water. This species is active at pHs 7 and 2.5 yielding respective TON3h values of 1670 and 3900. Comparison of the molecular structure of 1 with that of the reduced [CuI(LN2Py3)]PF6 (2) evidences elongated Cu-N bond lengths resulting from an increased electron density around the 3d10 CuI center. The absence of nanoparticulate formation indicates that molecular mechanisms prevail at both pHs. Furthermore, experimental and DFT data support that distinct mechanisms are operative: while the metal center plays a key role at pH 7, one dangling pyridine moiety gets protonated at pH 2.5 and becomes actively involved in a relay mechanism. In both cases the CuIII-H- intermediate seems to be bypassed by PCET processes.