The X-ray Absorption Spectroscopic Model of the Copper(II) Imidazole Complex Ion in Liquid Aqueous Solution: A Strongly Solvated Square Pyramid

Cu K-edge extended X-ray absorption fine structure (EXAFS) and Minuit X-ray absorption near-edge structure (MXAN) analyses were combined to evaluate the structure of the copper­(II) imidazole complex ion in liquid aqueous solution. Both methods converged to the same square-pyramidal inner coordination sphere [Cu­(Im)₄L_ax]²⁺ (L_ax indeterminate) with four equatorial nitrogen atoms at EXAFS, 2.02 ± 0.01 Å, and MXAN, 1.99 ± 0.03 Å. A short-axial N/O scatterer (L_ax) was found at 2.12 ± 0.02 Å (EXAFS) or 2.14 ± 0.06 Å (MXAN). A second but very weak axial Cu–N/O interaction was found at 2.9 ± 0.1 Å (EXAFS) or 3.0 ± 0.1 Å (MXAN). In the MXAN fits, only a square-pyramidal structural model successfully reproduced the doubled maximum of the rising K-edge X-ray absorption spectrum, specifically excluding an octahedral model. Both EXAFS and MXAN also found eight outlying oxygen scatterers at 4.2 ± 0.3 Å that contributed significant intensity over the entire spectral energy range. Two prominent rising K-edge shoulders at 8987.1 and 8990.5 eV were found to reflect multiple scattering from the 3.0 Å axial scatterer and the imidazole rings, respectively. In the MXAN fits, the imidazole rings took in-plane rotationally staggered positions about copper. The combined (EXAFS and MXAN) model for the unconstrained cupric imidazole complex ion in liquid aqueous solution is an axially elongated square-pyramidal core, with a weak nonbonded interaction at the second axial coordination position and a solvation shell of eight nearest-neighbor water molecules. This core square-pyramidal motif has persisted through [Cu­(H₂O)₅]²⁺, [Cu­(NH₃)₄(NH₃,H₂O)]²⁺,, and now [Cu­(Im)₄L_ax)]²⁺ and appears to be the geometry preferred by unconstrained aqueous-phase copper­(II) complex ions

Substrate and Metal Control of Barrier Heights for Oxo Transfer to Mo and W Bis-dithiolene Sites

Reaction coordinates for oxo transfer from the substrates Me₃NO, Me₂SO, and Me₃PO to the biologically relevant Mo­(IV) bis-dithiolene complex [Mo­(OMe)­(mdt)₂]⁻ where mdt = 1,2-dimethyl-ethene-1,2-dithiolate­(2-), and from Me₂SO to the analogous W­(IV) complex, have been calculated using density functional theory. In each case, the reaction first proceeds through a transition state (TS1) to an intermediate with substrate weakly bound, followed by a second transition state (TS2) around which breaking of the substrate X–O bond begins. By analyzing the energetic contributions to each barrier, it is shown that the nature of the substrate and metal determines which transition state controls the rate-determining step of the reaction

Substrate and Metal Control of Barrier Heights for Oxo Transfer to Mo and W Bis-dithiolene Sites

Reaction coordinates for oxo transfer from the substrates Me₃NO, Me₂SO, and Me₃PO to the biologically relevant Mo­(IV) bis-dithiolene complex [Mo­(OMe)­(mdt)₂]⁻ where mdt = 1,2-dimethyl-ethene-1,2-dithiolate­(2-), and from Me₂SO to the analogous W­(IV) complex, have been calculated using density functional theory. In each case, the reaction first proceeds through a transition state (TS1) to an intermediate with substrate weakly bound, followed by a second transition state (TS2) around which breaking of the substrate X–O bond begins. By analyzing the energetic contributions to each barrier, it is shown that the nature of the substrate and metal determines which transition state controls the rate-determining step of the reaction

Spin-Polarization-Induced Preedge Transitions in the Sulfur K‑Edge XAS Spectra of Open-Shell Transition-Metal Sulfates: Spectroscopic Validation of σ‑Bond Electron Transfer

Sulfur K-edge X-ray absorption spectroscopy (XAS) spectra of the monodentate sulfate complexes [M^II(itao)­(SO₄)­(H₂O)_0,1] (M = Co, Ni, Cu) and [Cu­(Me₆tren)­(SO₄)] exhibit well-defined preedge transitions at 2479.4, 2479.9, 2478.4, and 2477.7 eV, respectively, despite having no direct metal–sulfur bond, while the XAS preedge of [Zn­(itao)­(SO₄)] is featureless. The sulfur K-edge XAS of [Cu­(itao)­(SO₄)] but not of [Cu­(Me₆tren)­(SO₄)] uniquely exhibits a weak transition at 2472.1 eV, an extraordinary 8.7 eV below the first inflection of the rising K-edge. Preedge transitions also appear in the sulfur K-edge XAS of crystalline [M^II(SO₄)­(H₂O)] (M = Fe, Co, Ni, and Cu, but not Zn) and in sulfates of higher-valent early transition metals. Ground-state density functional theory (DFT) and time-dependent DFT (TDDFT) calculations show that charge transfer from coordinated sulfate to paramagnetic late transition metals produces spin polarization that differentially mixes the spin-up (α) and spin-down (β) spin orbitals of the sulfate ligand, inducing negative spin density at the sulfate sulfur. Ground-state DFT calculations show that sulfur 3p character then mixes into metal 4s and 4p valence orbitals and various combinations of ligand antibonding orbitals, producing measurable sulfur XAS transitions. TDDFT calculations confirm the presence of XAS preedge features 0.5–2 eV below the rising sulfur K-edge energy. The 2472.1 eV feature arises when orbitals at lower energy than the frontier occupied orbitals with S 3p character mix with the copper­(II) electron hole. Transmission of spin polarization and thus of radical character through several bonds between the sulfur and electron hole provides a new mechanism for the counterintuitive appearance of preedge transitions in the XAS spectra of transition-metal oxoanion ligands in the absence of any direct metal–absorber bond. The 2472.1 eV transition is evidence for further radicalization from copper­(II), which extends across a hydrogen-bond bridge between sulfate and the itao ligand and involves orbitals at energies below the frontier set. This electronic structure feature provides a direct spectroscopic confirmation of the through-bond electron-transfer mechanism of redox-active metalloproteins

L‑Edge X‑ray Absorption Spectroscopic Investigation of {FeNO}⁶: Delocalization vs Antiferromagnetic Coupling

NO is a classic non-innocent ligand, and iron nitrosyls can have different electronic structure descriptions depending on their spin state and coordination environment. These highly covalent ligands are found in metalloproteins and are also used as models for Fe–O₂ systems. This study utilizes iron L-edge X-ray absorption spectroscopy (XAS), interpreted using a valence bond configuration interaction multiplet model, to directly experimentally probe the electronic structure of the <i>S</i> = 0 {FeNO}⁶ compound [Fe­(PaPy₃)­NO]²⁺ (PaPy₃ = <i>N,N</i>-bis­(2-pyridylmethyl)­amine-<i>N</i>-ethyl-2-pyridine-2-carboxamide) and the <i>S</i> = 0 [Fe­(PaPy₃)­CO]⁺ reference compound. This method allows separation of the σ-donation and π-acceptor interactions of the ligand through ligand-to-metal and metal-to-ligand charge-transfer mixing pathways. The analysis shows that the {FeNO}⁶ electronic structure is best described as Fe^III–NO­(neutral), with no localized electron in an NO π* orbital or electron hole in an Fe dπ orbital. This delocalization comes from the large energy gap between the Fe–NO π-bonding and antibonding molecular orbitals relative to the exchange interactions between electrons in these orbitals. This study demonstrates the utility of L-edge XAS in experimentally defining highly delocalized electronic structures

A Zinc Linchpin Motif in the MUTYH Glycosylase Interdomain Connector Is Required for Efficient Repair of DNA Damage

Mammalian MutY glycosylases have a unique architecture that features an interdomain connector (IDC) that joins the catalytic N-terminal domain and 8-oxoguanine (OG) recognition C-terminal domain. The IDC has been shown to be a hub for interactions with protein partners involved in coordinating downstream repair events and signaling apoptosis. Herein, a previously unidentified zinc ion and its coordination by three Cys residues of the IDC region of eukaryotic MutY organisms were characterized by mutagenesis, ICP-MS, and EXAFS. <i>In vitro</i> kinetics and cellular assays on WT and Cys to Ser mutants have revealed an important function for zinc coordination on overall protein stability, iron–sulfur cluster insertion, and ability to mediate DNA damage repair. We propose that this “zinc linchpin” motif serves to structurally organize the IDC and coordinate the damage recognition and base excision functions of the C- and N-terminal domains

Iron L‑Edge X‑ray Absorption Spectroscopy of Oxy-Picket Fence Porphyrin: Experimental Insight into Fe–O₂ Bonding

The electronic structure of the Fe–O₂ center in oxy-hemoglobin and oxy-myoglobin is a long-standing issue in the field of bioinorganic chemistry. Spectroscopic studies have been complicated by the highly delocalized nature of the porphyrin, and calculations require interpretation of multideterminant wave functions for a highly covalent metal site. Here, iron L-edge X-ray absorption spectroscopy, interpreted using a valence bond configuration interaction multiplet model, is applied to directly probe the electronic structure of the iron in the biomimetic Fe–O₂ heme complex [Fe­(pfp)­(1‑MeIm)­O₂] (pfp (“picket fence porphyrin”) = <i>meso</i>-tetra­(α,α,α,α-<i>o</i>-pivalamidophenyl)­porphyrin or TpivPP). This method allows separate estimates of σ-donor, π-donor, and π-acceptor interactions through ligand-to-metal charge transfer and metal-to-ligand charge transfer mixing pathways. The L-edge spectrum of [Fe­(pfp)­(1‑MeIm)­O₂] is further compared to those of [Fe^II(pfp)­(1‑MeIm)₂], [Fe^II(pfp)], and [Fe^III(tpp)­(ImH)₂]Cl (tpp = <i>meso</i>-tetraphenylporphyrin) which have Fe^II <i>S</i> = 0, Fe^II <i>S</i> = 1, and Fe^III <i>S</i> = 1/2 ground states, respectively. These serve as references for the three possible contributions to the ground state of oxy-pfp. The Fe–O₂ pfp site is experimentally determined to have both significant σ-donation and a strong π-interaction of the O₂ with the iron, with the latter having implications with respect to the spin polarization of the ground state

L‑Edge X‑ray Absorption Spectroscopy and DFT Calculations on Cu₂O₂ Species: Direct Electrophilic Aromatic Attack by Side-on Peroxo Bridged Dicopper(II) Complexes

The hydroxylation of aromatic substrates catalyzed by coupled binuclear copper enzymes has been observed with side-on-peroxo-dicopper­(II) (<b>P</b>) and bis-μ-oxo-dicopper­(III) (<b>O</b>) model complexes. The substrate-bound-<b>O</b> intermediate in [Cu­(II)₂(DBED)₂(O)₂]²⁺ (DBED = <i>N</i>,<i>N</i>′-di-<i>tert</i>-butyl-ethylenediamine) was shown to perform aromatic hydroxylation. For the [Cu­(II)₂(NO₂-XYL)­(O₂)]²⁺ complex, only a <b>P</b> species was spectroscopically observed. However, it was not clear whether this O–O bond cleaves to proceed through an <b>O</b>-type structure along the reaction coordinate for hydroxylation of the aromatic xylyl linker. Accurate evaluation of these reaction coordinates requires reasonable quantitative descriptions of the electronic structures of the <b>P</b> and <b>O</b> species. We have performed Cu L-edge XAS on two well-characterized <b>P</b> and <b>O</b> species to experimentally quantify the Cu 3d character in their ground state wave functions. The lower per-hole Cu character (40 ± 6%) corresponding to higher covalency in the <b>O</b> species compared to the <b>P</b> species (52 ± 4%) reflects a stronger bonding interaction of the bis-μ-oxo core with the Cu­(III) centers. DFT calculations show that 10–20% Hartree–Fock (HF) mixing for <b>P</b> and ∼38% for <b>O</b> species are required to reproduce the Cu–O bonding; for the <b>P</b> species this HF mixing is also required for an antiferromagnetically coupled description of the two Cu­(II) centers. B3LYP (with 20% HF) was, therefore, used to calculate the hydroxylation reaction coordinate of <b>P</b> in [Cu­(II)₂(NO₂-XYL)­(O₂)]²⁺. These experimentally calibrated calculations indicate that the electrophilic attack on the aromatic ring does not involve formation of a Cu­(III)₂(O^2–)₂ species. Rather, there is direct electron donation from the aromatic ring into the peroxo σ* orbital of the Cu­(II)₂(O₂^2–) species, leading to concerted C–O bond formation with O–O bond cleavage. Thus, species <b>P</b> is capable of direct hydroxylation of aromatic substrates without the intermediacy of an <b>O</b>-type species

Hydroxo-Bridged Dicopper(II,III) and -(III,III) Complexes: Models for Putative Intermediates in Oxidation Catalysis

A macrocyclic ligand (L^4–) comprising two pyridine­(dicarboxamide) donors was used to target reactive copper species relevant to proposed intermediates in catalytic hydrocarbon oxidations by particulate methane monooxygenase and heterogeneous zeolite systems. Treatment of LH₄ with base and Cu­(OAc)₂·H₂O yielded (Me₄N)₂[L₂Cu₄(μ₄-O)] (<b>1</b>) or (Me₄N)­[LCu₂(μ-OH)] (<b>2</b>), depending on conditions. Complex <b>2</b> was found to undergo two reversible 1-electron oxidations via cyclic voltammetry and low-temperature chemical reactions. On the basis of spectroscopy and theory, the oxidation products were identified as novel hydroxo-bridged mixed-valent Cu­(II)­Cu­(III) and symmetric Cu­(III)₂ species, respectively, that provide the first precedence for such moieties as oxidation catalysis intermediates

A Six-Coordinate Peroxynitrite Low-Spin Iron(III) Porphyrinate ComplexThe Product of the Reaction of Nitrogen Monoxide (·NO_(g)) with a Ferric-Superoxide Species

Peroxynitrite (⁻OONO, PN) is a reactive nitrogen species (RNS) which can effect deleterious nitrative or oxidative (bio)­chemistry. It may derive from reaction of superoxide anion (O₂^•–) with nitric oxide (·NO) and has been suggested to form an as-yet unobserved bound heme-iron-PN intermediate in the catalytic cycle of nitric oxide dioxygenase (NOD) enzymes, which facilitate a ·NO homeostatic process, i.e., its oxidation to the nitrate anion. Here, a discrete six-coordinate low-spin porphyrinate-Fe^III complex [(P^Im)­Fe^III(⁻OONO)] (<b>3</b>) (P^Im; a porphyrin moiety with a covalently tethered imidazole axial “base” donor ligand) has been identified and characterized by various spectroscopies (UV–vis, NMR, EPR, XAS, resonance Raman) and DFT calculations, following its formation at −80 °C by addition of ·NO_(g) to the heme-superoxo species, [(P^Im)­Fe^III(O₂^•–)] (<b>2</b>). DFT calculations confirm that <b>3</b> is a six-coordinate low-spin species with the PN ligand coordinated to iron via its terminal peroxidic anionic O atom with the overall geometry being in a <i>cis</i>-configuration. Complex <b>3</b> thermally transforms to its isomeric low-spin nitrato form [(P^Im)­Fe^III(NO₃^–)] (<b>4a</b>). While previous (bio)­chemical studies show that phenolic substrates undergo nitration in the presence of PN or PN-metal complexes, in the present system, addition of 2,4-di-<i>tert</i>-butylphenol (^2,4DTBP) to complex <b>3</b> does not lead to nitrated phenol; the nitrate complex <b>4a</b> still forms. DFT calculations reveal that the phenolic H atom approaches the terminal PN O atom (farthest from the metal center and ring core), effecting O–O cleavage, giving nitrogen dioxide (·NO₂) plus a ferryl compound [(P^Im)­Fe^IVO] (<b>7</b>); this rebounds to give [(P^Im)­Fe^III(NO₃^–)] (<b>4a</b>).The generation and characterization of the long sought after ferriheme peroxynitrite complex has been accomplished