単核非ヘム鉄複合体におけるラジカルハロゲン化と水酸化を駆動する要因は? 実験と計算を組み合わせた研究
Emilie F Gérard1,2, Vishal Yadav3, David P Goldberg3
1Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester M1 7DN, United Kingdom.
Journal of the American Chemical Society
|May 10, 2022
まとめ
非ヘム鉄ハロゲネーゼは,二次炭素基に選択的にハロゲン (X•) を転送し,反応がエンダーゴニックである三次炭素基とは違います. この選択性は熱力学的安定性と二次的調整球効果によって支配される.
科学分野:
- 生物化学
- 酵素学
- 有機金属化学
背景:
- 非ヘム鉄ハロゲネーゼはアリファティックC-H結合を活性化し,C-X (X = Cl, Br) に変換する.
- これらの酵素は,カタリシス中にFeIII(OH) ((X) の中間物質を生成することを提案しています.
- 重要な議論は,これらのハロゲネーゼの驚くべき選択性を制御する要因をめぐるものです.
研究 の 目的:
- FeIII(BNPAPh2O) ((OH) ((X) 複合体の二次炭素基との反応性を調査する.
- 計算方法を用いてハロゲナーゼ反応における選択性の起源を解明する.
主な方法:
- FeIII(BNPAPh2O) ((OH) ((X) コンプレックスと二次炭素ラジカルに関する実験研究.
- 密度関数理論 (DFT) を用いた包括的な計算研究.
主要な成果:
- ハロゲン (X•) 移転は二次炭素基で観察され,三次炭素基で観察されたヒドロキシル (OH•) 移転とは対照的です.
- DFTの計算は実験結果を再現し,エンドルゴニックで非生産的な均衡により,ハロゲン転送は三次基に不利であることを示した.
- ハロゲン変換は,ハロゲン化製品複合体が熱力学的により安定しているため,二次ラジカルに好ましい.
結論:
- 非ヘム鉄ハロゲネーゼの選択性は,ハロゲン化製品複合体の熱力学的安定性によって決定され,これは二次炭素中心よりも優れている.
- ステリックと水素結合の相互作用などの二次調整球効果は,ハロゲン転送の反応障壁に大きな影響を与える.
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