Crystallographic and Spectroscopic Characterization of a Nonheme Fe(IV)=O Complex

Rohde, Jan-Uwe; In, Jun Hee; Lim, Mi Hee; Brennessel, William W.; Bukowski, Michael R.; Stubna, Audria; Münck, Eckard; Nam, Wonwoo; Que, Lawrence

doi:10.1126/science.299.5609.1037

Cited by 905 publications

(1,094 citation statements)

References 33 publications

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“…[17] Intriguingly, whereas the enzymatic species are high-spin (quintet), most biomimetic complexes have intermediate spin (triplet). [18,19] Without any doubt, the protein environment in the enzymes is designed for optimal efficiency of the reaction(s) taking place, and plays a role as well in the spin ground-state of the iron-oxo species. One of the first crystal structures with a terminal Fe IV ¼ ¼oxo indeed was intermediate spin, as indicated by M€ ossbauer spectroscopy.…”

Section: Metal-oxo Species and Exchange-enhanced Reactivitymentioning

confidence: 99%

“…One of the first crystal structures with a terminal Fe IV ¼ ¼oxo indeed was intermediate spin, as indicated by M€ ossbauer spectroscopy. [18] High-spin biomimetic complexes remain rare with very few examples, [20][21][22][23] the set of which was very recently extended by a complex with a trigonal pyrrolide platform. [19] Que and coworkers [24] recently also reported a Fe(IV)-oxo-hydroxo species, starting from a highspin Fe II (benzilate) complex.…”

Section: Metal-oxo Species and Exchange-enhanced Reactivitymentioning

confidence: 99%

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Spin states of (bio)inorganic systems: Successes and pitfalls

Swart

2012

Int J of Quantum Chemistry

111

127

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The calculation of spin-state splittings of transition-metal complexes is known to be very sensitive to the level of theory and the quality of the basis set. The performance of density functionals is in general understood, with older pure functionals overstabilizing low spin states, and Hartree-Fock and hybrid functionals doing the same for the high spin states. More recent functionals (OLYP/OPBE, TPSSh, SSB-D, M06-L) seem to improve on these, but there are still some systems that prove difficult. This Perspective describes some of the recent successes and pitfalls in the description of spin states and treats both methodology and applications such as metal-oxo complexes, exchange-enhanced reactivity, spin-state catalysis, and spin-crossover compounds.

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Section: Metal-oxo Species and Exchange-enhanced Reactivitymentioning

confidence: 99%

Section: Metal-oxo Species and Exchange-enhanced Reactivitymentioning

confidence: 99%

Spin states of (bio)inorganic systems: Successes and pitfalls

Swart

2012

Int J of Quantum Chemistry

111

127

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“…80-82 However, because of the ligand sterics, the oxygen atom in complex 1 is rather sheltered by the hydrogens of the TMC ligand and buried (Figure 13 left). 13 Thus, because of the steric hindrance of the TMC ligand in complex 1, the substrate cannot achieve an optimal orientation for good overlap with the O-p(x/y) orbitals. Alternatively, the N4Py ligand of complex 3 allows more open access to the oxygen atom ( Figure 13 right) for reaction with the C-H σ-bond on the substrate.…”

Section: Differences In Reactivity-mentioning

confidence: 99%

Spectroscopic and Quantum Chemical Studies on Low-Spin Fe^IVO Complexes: Fe−O Bonding and Its Contributions to Reactivity

et al. 2007

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High valent Fe IV =O species are key intermediates in the catalytic cycles of many mononuclear nonheme iron enzymes and have been structurally defined in model systems. Variable temperature magnetic circular dichroism (VT-MCD) spectroscopy has been used to evaluate the electronic structures and in particular the Density Functional calculations were correlated to the data and support the experimental analysis. The strength and covalency of the Fe-O π-bond result in high oxygen character in the important frontier molecular orbitals (FMOs) for this reaction, the unoccupied β-spin d(xz/yz) orbitals, and activates these for electrophilic attack. An extension to biologically relevant Fe IV =O (S=2) enzyme intermediates shows that these can perform electrophilic attack reactions along the same mechanistic pathway (π-FMO pathway) with similar reactivity, but also have an additional reaction channel involving the unoccupied α-spin d(z 2 ) orbital (σ-FMO pathway).These studies experimentally probe the FMOs involved in the reactivity of Fe IV =O (S=1) model complexes resulting in a detailed understanding of the Fe-O bond and its contributions to reactivity.

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“…Model compounds also provide strong evidence for the existence of Fe IV =O in proteins. Discrete mononuclear Fe IV =O species have been synthesized and characterized recently [54][55][56][57]. These complexes serve as models for the intermediate species that may be generated in mononuclear non-heme iron-containing enzymes.…”

Section: Repair Mechanismmentioning

confidence: 99%

Oxidative dealkylation DNA repair mediated by the mononuclear non-heme iron AlkB proteins

Mishina

2006

Journal of Inorganic Biochemistry

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DNA can be damaged by various intracellular and environmental alkylating agents to produce alkylation base lesions. These base damages, if not repaired promptly, may cause genetic changes that lead to diseases such as cancer. Recently, it was discovered that some of the alkylation DNA base damage can be directly removed by a family of proteins called the AlkB proteins that utilize a mononuclear non-heme iron(II) and α-ketoglutarate as cofactor and cosubstrate. These proteins activate dioxygen and perform an unprecedented oxidative deal-kylation of the alkyl adducts on DNA heteroatoms. This review summarizes the discovery of this activity and the recent research advances in studying this unique DNA repair pathway. The focus is placed on the chemical mechanism and function of these proteins. KeywordsDNA repair; AlkB; ABH; Direct repair; Mononuclear non-heme iron; Dioxygenase; Oxidative dealkylation; Demethylation Direct repair of alkylation DNA damageCellular DNA is subject to nonenzymatic alkylation (methylation) by environmental or chemical mutagens, resulting in adducts that are toxic and mutagenic [1][2][3][4][5][6]. Organisms have evolved a variety of mechanisms to repair these mutagenic damages. Escherichia coli (E. coli) responds to this threat by activating an adaptive responsive pathway, mediated by the E. coli Ada protein [7]. Upon receiving a methyl group from the damaged DNA, Ada turns into a transcriptional activator and activates its own expression and that of the alkB gene and two other genes, alkA and aidB ( Fig. 1(a)) [4,7,8]. The upregulated Ada is a bifunctional protein, which uses a N-terminal Cys38 residue to remove a methyl group fromS p -methylphosphotriester and a C-terminal Cys321 residue to remove a methyl adduct from O 6 -methylguanaine ( Fig. 1(b)) [9][10][11]. Both repair functions are irreversible and represent rare examples of direct repair of DNA damage. AlkA is a glycosylase that cleaves methylated bases from DNA and performs the first step of the well-known base excision repair of base lesions [12][13][14]. The precise function of AidB is still unknown. The function of the last member of this adaptive response, AlkB, also remained unknown until recently despite extensive research efforts. E. coli AlkBSince the first genetic study in 1983 isolating the E. coli mutant with specific sensitivity to the alkylating agent methylmethane sulfonate, MMS [15], the activity of AlkB was undisclosed The Fe II /αKG-dependent dioxygenase superfamily is widespread from bacteria to humans [19] and is the largest known non-heme iron protein family [20][21][22][23]. It represents a wide diversity of enzymes that catalyze the hydroxylation of unactivated C-H groups of a variety of substrates by coupling reductive activation of dioxygen with a decarbox-ylation of αKG, the co-substrate, to succinate. In the event of oxidation one of the oxygen atoms from O 2 is incorporated into the succinate and the other as a hydroxyl in the product [24]. This group of enzymes is known for their importance in ...

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Crystallographic and Spectroscopic Characterization of a Nonheme Fe(IV)=O Complex

Cited by 905 publications

References 33 publications

Spin states of (bio)inorganic systems: Successes and pitfalls

Spin states of (bio)inorganic systems: Successes and pitfalls

Spectroscopic and Quantum Chemical Studies on Low-Spin Fe^IVO Complexes: Fe−O Bonding and Its Contributions to Reactivity

Oxidative dealkylation DNA repair mediated by the mononuclear non-heme iron AlkB proteins

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Crystallographic and Spectroscopic Characterization of a Nonheme Fe(IV)=O Complex

Cited by 905 publications

References 33 publications

Spin states of (bio)inorganic systems: Successes and pitfalls

Spin states of (bio)inorganic systems: Successes and pitfalls

Spectroscopic and Quantum Chemical Studies on Low-Spin FeIVO Complexes: Fe−O Bonding and Its Contributions to Reactivity

Oxidative dealkylation DNA repair mediated by the mononuclear non-heme iron AlkB proteins

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Spectroscopic and Quantum Chemical Studies on Low-Spin Fe^IVO Complexes: Fe−O Bonding and Its Contributions to Reactivity