一電子酸化チミンにヒドロキシルイオン添加:C5からC6のOH添加物の単分子相互変換
Amitava Adhikary1, Anil Kumar, Alicia N Heizer
1Department of Chemistry, Oakland University, Rochester, Michigan 48309, USA.
Journal of the American Chemical Society
|February 1, 2013
まとめ
この研究では,基本的条件下で酸化チミジンと核酸にヒドロキシルラジカルを添加することを調査しています. ヒドロキシルラジカルがチミンラジカルに加わると,他のラジカルに変換する中間物質を形成し,脱プロトン化形態はより容易に反応する.
科学分野:
- 放射線化学 放射線化学
- 化学動力学 化学動力学
- バイオ物理化学 バイオ物理化学
背景:
- DNA塩基と核酸の急性との反応性を理解することは,DNA損傷と修復メカニズムを評価するために不可欠です.
- 水性ガラスは,低温での急性反応を研究するための制御された環境を提供し,放射線誘発プロセスの初期段階を模倣します.
研究 の 目的:
- 基本水性グラスにおける1電子酸化チミジン (dThd) とチミン核酸にヒドロキシルラジカル (OH(-)) の添加を調査する.
- 異なるpH条件下でチミンラジカルを含む反応経路,中間種,および変換機構を明らかにする.
主な方法:
- 電子パラマグネティック共振 (EPR) スペクトロスコピーは,低温 (約. 155 K) を用いて,過激な種を検出し,特徴づけます.
- (15) Nおよびデュテリウム置換 ([5",5"-D,D]-5アヒドロ-dThd, [5",5"-D,D]-5アヒドロ-TMP, [CD(3) ]-dThd,および [CD(3),6D]-dThd) を含む,同位体としてラベル付けされた化合物の使用は,基子の割り当てを確認するために.
- 密度関数理論 (DFT) の計算により,急性変換の反応機構とエネルギーバリアを予測する.
主要な成果:
- pH9〜10では,脱プロトンチミンの1電子酸化により中性チミニル基 (T(-H) ·) が生成されます.
- pH ≥11.5で,OH−−−をT−−−Hに加えると,転移性のある5-ヒドロキシイチミン-6-イル基 (T−5OH) が形成され,火時に6ヒドロキシイチミン-5-イル基 (T−6OH) に変換される.
- N3-メチル-チミジン (N3-Me-dThd) については,メチルグループのデプロトネーションとOH(-) の間のpH依存の競争がC5への添加により,T(5OH) へと導かれ,その後,T(6OH) へと変換される.
結論:
- T(-H) ·とN3-Me-dThd(•+) のC5へのOH(-) の添加は,スピンと電荷の局所によって影響を受けます.
- T(5OH) ·をT(6OH) ·に変換することは,C5からC6への単分子OH群の移転を含み,プロトンが除去されたチミン基のエネルギーバリアは低い.
- デプロトン化されたチミジンとその核酸は,N3-Me-dThdと比較して,T(5OH) ·をT(6OH) ·に変換することがより容易である.
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