触媒機能におけるシトクロムＰ４５０配位構造の必然性：モデル錯体からのアプローチ

• 樋口 恒彦

  名古屋市立大学大学院薬学研究科

書誌事項

タイトル別名

• Inevitable Cytochrome P450 Coordination Structure for Enzyme Function: Chemical Model Approach to Elucidation of the Axial Ligand Effect
• ショクバイ キノウ ニ オケル シトクロム P450 ハイイ コウゾウ ノ ヒツゼンセイ モデル サクタイ カラノ アプローチ

抄録

A distinctive structural feature of P450 is the unusual thiolate coordination to heme. We have succeeded in the preparation of the first synthetic thiolato-iron porphyrin (SR complex) that retains its structure during catalytic oxidation.<br>Experiments using SR complex have revealed that the thiolate ligand greatly accelerates the rate of the O-O bond cleavage and its heterolysis even in highly hydrophobic media.<br>Prostaglandin H₂ (PGH₂) is catalytically isomerized to prostacyclin or thromboxane A₂ by cytochrome P450s. We investigated the isomerization mechanism of PGH₂ using SR complex, which is a model of P450 having heme-thiolate structure. Isomerization of endoperoxide proceeded very rapidly with SR, whereas imidazole or chloride-ligated heme had slight or no catalytic activity.<br>The results of kinetic isotope effects in the oxidative demethylation of p-dimethoxybenzene unambiguously showed that the formed active intermediates of heme-thiolates are different from those of hemes coordinated by imidazole or chloride.<br>Novel iron porphyrin-alkanethiolate complexes were prepared in order to examine the influence of the NH-S hydrogen bond on catalytic oxidation. The complexes were characterized by IR, EPR, resonance Raman spectroscopies and crystal structure analysis and their redox potentials were measured.<br>Our work also reports some spectroscopic and electrochemical properties of the first synthetic NO-heme-thiolate complex, prepared by treatment of SR with NO, relevant to NO synthase.

収録刊行物

• 有機合成化学協会誌

  有機合成化学協会誌 67 (2), 134-142, 2009

  公益社団法人 有機合成化学協会

キーワード

• cytochrome P450
• porphyrin
• axial ligand
• catalysis
• O-O bond
• oxygen activation
• thiolate
• nitric oxide

詳細情報

• CRID: 1390282680288175488
• NII論文ID: 10024967641
• NII書誌ID: AN0024521X
• DOI: 10.5059/yukigoseikyokaishi.67.134
• COI: 1:CAS:528:DC%2BD1MXhvFWisrg%3D
• ISSN: 18836526
• ISSN: 00379980
• NDL書誌ID: 10165281
• Web Site: http://id.ndl.go.jp/bib/10165281
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I10165281
• 本文言語コード: ja
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
  • KAKEN
• 抄録ライセンスフラグ: 使用不可