不活性なガス相ニコチン構造から生物活性な水相構造への陽子の移転
Marie-Pierre Gaigeot1, Alvaro Cimas, Mahamadou Seydou
1Laboratoire Analyse et Modélisation pour la Biologie et l'Environnement, LAMBE UMR8587 CNRS, Université d'Evry val d'Essonne, boulevard F. Mitterrand, Bat. Maupertuis, 91025 Evry Cedex, France. mgaigeot@univ-evry.fr
Journal of the American Chemical Society
|December 15, 2010
まとめ
水分子はニコチンを促進する.
科学分野:
- コンピューティング・ケミストリー
- 物理化学 物理化学
- 分子ダイナミクス 分子ダイナミクス
背景:
- ニコチンは,ガス相での無活性形態と,水溶液中の生物活性形態で存在します.
- これらの形態の間の構造的変容は,その生物学的活動に極めて重要です.
- この変換における水の役割は,分子レベルで十分に理解されていません.
研究 の 目的:
- ニコチンの非活性から生物活性への構造変化における水の役割を調査する.
- 溶液中の陽子移転タウトメリゼーションの自由エネルギーバリアを決定する.
- 水分子が媒介する陽子伝達のメカニズムを解明する.
主な方法:
- ニコチンH ((+)) - ((H ((2) O) ((n)) 複合体の幾何学的な最適化.
- 明確な水分子を用いたカーパリネッロMD (CPMD) を含む分子動力学 (MD) シミュレーション.
- バイアスCPMDシミュレーションで,陽子伝達の自由エネルギープロフィールを測定する.
主要な成果:
- 水分子は,ニコチンのプロトネーション部位 (ピリジンとピロリジン環) の間の橋渡し鎖を形成する.
- 陽子の移動のための自由エネルギーバリアは,水分子が増加するにつれて減少しますが,より小さなクラスターでは (16kJ/molで4つの水分子が含まれて) 重要なままです.
- CPMDのシミュレーションでは,大量の水の中で非常に高速な陽子移動 (0.5ps以内) が,エネルギーバリアなしで水橋を通過して発生することを示しています.
結論:
- 水は,水溶液中のニコチンのタウトメリゼーションを促進する上で重要な役割を果たします.
- 陽子の移転は,小さな水群では稀な出来事ですが,散発した水では容易になります.
- ウォーターブリッジは,水性ニコチンにおける急速な陽子伝達機構にとって不可欠である.
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