Isolation and Crystal Structure of a Peroxo‐Bridged Heme–Copper Complex

Chishiro, Takefumi; Shimazaki, Yasuhisa; Tani, Fumito; Tachi, Yoshimitsu; Naruta, Yoshinori; Karasawa, Satoru; Hayami, Shinya; Maeda, Yonezo

doi:10.1002/anie.200351415

Cited by 123 publications

(119 citation statements)

References 36 publications

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“…(4). Such bonding has been proposed earlier between iron atoms for a model compound of an enzyme [18] and also for an iron-copper complex [19]. It is likely that the iron atom in the high spin (d) is situated slightly out-of-plane towards the peroxo bridge due to tension in the bridge.…”

Section: Resultssupporting

confidence: 57%

A Mossbauer Study of the Low Spin-High Spin Transition of an Oxygen Adduct Formed in Solid β -Fe(II)Phthalocyanine

Yin¹,

Kubuki²,

Homonnay

et al. 2008

TOICJ

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Section: Resultssupporting

confidence: 57%

A Mossbauer Study of the Low Spin-High Spin Transition of an Oxygen Adduct Formed in Solid β -Fe(II)Phthalocyanine

Yin¹,

Kubuki²,

Homonnay

et al. 2008

TOICJ

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“…This species could be either an end-on or side-on peroxide. Although no Fe B -O vibration could be observed in the rR, the high OOO, single Fe-O vibration and the low-spin state of the heme (requiring a strong ligand field) are consistent with an end-on peroxide rather than a side-on peroxide (48,49).…”

Section: Resultsmentioning

confidence: 77%

O ₂ reduction by a functional heme/nonheme bis-iron NOR model complex

Collman

Dey

Yang

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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O2 reactivity of a functional NOR model is investigated by using electrochemistry and spectroscopy. The electrochemical measurements using interdigitated electrodes show very high selectivity for 4e O2 reduction with minimal production of partially reduced oxygen species (PROS) under both fast and slow electron flux. Intermediates trapped at cryogenic temperatures and characterized by using resonance Raman spectroscopy under single-turnover conditions indicate that an initial bridging peroxide intermediate undergoes homolytic OOO bond cleavage generating a trans heme/nonheme bis-ferryl intermediate. This bis ferryl species can oxygenate 2 equivalents of a reactive substrate.C ytochrome c oxidase (CcO) and nitric oxide reductase (NOR) belong to the heme copper oxidase superfamily of enzymes (1, 2). CcO is the terminal enzyme in the respiratory chain of higher organisms, located in their mitochondrial membrane, that reduces O 2 to H 2 O as source of energy. The O 2 reduction process in CcO generates a pH gradient across the bilayer membrane, which provides the driving force for ATP synthesis. The bimetallic active site of CcO has a heme ligated to the protein by a proximal histidine ligand and a distal Cu B site coordinated by 3 histidine ligands ( Fig. 1) (3). In addition to the bimetallic site, there is a conserved tyrosine ligand covalently attached to one of the histidines coordinated to Cu B (4, 5). The NORs are the older member of the family and are found in bacteria using NO 3 Ϫ as source of energy instead of O 2 (2, 6, 7). Although there are no high-resolution crystal structures of NOR, biochemical studies and computer modeling indicate that these enzymes have a histidine-ligated heme, quite like the CcOs, and a distal Fe B , unlike Cu B in CcO, coordinated by 3 histidines ( Fig. 1) (8-10). NORs do not have the conserved tyrosine residue of CcO but have a few conserved key glutamate residues (11,12). Although the NOR enzymes are proposed to have specific proton channels, they are probably not involved in generating proton gradients (13-16).These 2 enzymes exhibit complementary reactivity toward 2 very significant diatomic molecules in nature; O 2 and NO. In eukaryotes CcO (aa 3 type) reduces O 2 to H 2 O and is reversibly but strongly inhibited by [17][18][19][20]. Several other CcOs (ba 3 , caa 3 , cbb 3 ) are reported to exhibit limited (Ͻ1%) NOR activity, i.e., reduce NO to N 2 O (7, 21). On the other hand, NORs that reduce NO to N 2 O are reversibly but strongly inhibited by O 2 , and some of them show modest (Ϸ10%) O 2 reduction activity (12). The parallels in their reactivities toward O 2 and NO and similarities in their secondary structures have led to a hypotheses regarding NOR's and CcO's similar evolutionary origins (6,22).Electrochemistry is a very powerful technique that can provide fundamental insights into reaction mechanisms of redox catalysts (23-27). Conventionally, a catalyst is deposited on a conducting electrode material (e.g., graphite); however, this approach does not allow site isola...

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“…Finally, the amino-imidazole spiro derivative 9i (Table 1), is again present in the di-protonated form at FV pH (Table 1SI †). The GM conformer of this form presents both the Skew Boat B and the O1-N 0 interaction (Table 20SI †), but, according to experimental peroxide oxygen-heme iron distances taken from the Cambridge Crystallographic Structural Data Bank, 19 the presence of the rigid spirocycloheptane at C6 impairs the endoperoxide approach to heme iron (Fig. 4SI †).…”

Section: Structure-activity Relationships (Sars) Studiesmentioning

confidence: 99%

New antimalarial 3-methoxy-1,2-dioxanes: optimization of cellular pharmacokinetics and pharmacodynamics properties by incorporation of amino and N-heterocyclic moieties at C4

et al. 2015

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A new series of nineteen 3-methoxy-1,2-dioxanes containing an amino moiety at C4 was designed, synthesized and tested for in vitro antimalarial activity against chloroquine sensitive (CQ-S) D10 and chloroquine resistant (CQ-R) W2 strains of Plasmodium falciparum (Pf). Cytotoxicity against the human endothelial cell line (HMEC-1) was also evaluated. The introduced modifications resulted in a notable improvement of the antimalarial activity. In particular, compound 9a with an amino-imidazole side-chain at C4 displays antimalarial activity in the high nanomolar range against the CQ-R Pf strain (W2 IC 50 ¼ 200 nM), being more active against CQ-R than CQ-S Pf strains and devoid of cytotoxicity against human HMEC-1 cells. On the other hand, some of the hybrids with 4-amino-7-chloroquinoline (9k-p) show an IC 50 comparable to that of chloroquine against the CQ-S Pf strain (9k-p, D10 IC 50 ¼ 50-90 nM) but without losing potency against the CQ-R Pf strain (9k-p, resistance index ¼ 1.2-2.6), with low cytotoxicity against HMEC-1. Structure-activity relationship studies show that the improved antimalarial activity of the new compounds is the result of a combination of cellular pharmacokinetics and pharmacodynamics effects.

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Isolation and Crystal Structure of a Peroxo‐Bridged Heme–Copper Complex

Cited by 123 publications

References 36 publications

A Mossbauer Study of the Low Spin-High Spin Transition of an Oxygen Adduct Formed in Solid β -Fe(II)Phthalocyanine

A Mossbauer Study of the Low Spin-High Spin Transition of an Oxygen Adduct Formed in Solid β -Fe(II)Phthalocyanine

O ₂ reduction by a functional heme/nonheme bis-iron NOR model complex

New antimalarial 3-methoxy-1,2-dioxanes: optimization of cellular pharmacokinetics and pharmacodynamics properties by incorporation of amino and N-heterocyclic moieties at C4

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Isolation and Crystal Structure of a Peroxo‐Bridged Heme–Copper Complex

Cited by 123 publications

References 36 publications

A Mossbauer Study of the Low Spin-High Spin Transition of an Oxygen Adduct Formed in Solid β -Fe(II)Phthalocyanine

A Mossbauer Study of the Low Spin-High Spin Transition of an Oxygen Adduct Formed in Solid β -Fe(II)Phthalocyanine

O 2 reduction by a functional heme/nonheme bis-iron NOR model complex

New antimalarial 3-methoxy-1,2-dioxanes: optimization of cellular pharmacokinetics and pharmacodynamics properties by incorporation of amino and N-heterocyclic moieties at C4

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O ₂ reduction by a functional heme/nonheme bis-iron NOR model complex