メトロニダゾール,抗生物質と低酸素のプローブで1分未満で20%以上 (15) N 超極化
Danila A Barskiy1, Roman V Shchepin1, Aaron M Coffey1
1Department of Radiology, Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
Journal of the American Chemical Society
|June 21, 2016
まとめ
メトロニダゾールにおける窒素15部位の直接的なNMR超極化は,パラ水素を用いて達成された. この方法は信号を100万倍まで増幅し, in vivo 画像処理のハイパーポラライゼーションアプリケーションを拡大します.
科学分野:
- 核磁共振 (NMR) スペクトロスコーピー
- ハイパーポラライゼーション技術
- 医療用イメージング
背景:
- メトロニダゾールは,無酸素細菌および原生虫感染症の治療における重要な薬です.
- 現在のNMR方法は,窒素-15のような低濃度の同位体検出に敏感性が欠けている.
- ハイパーポラライゼーションは NMR 信号を大幅に強化し,リアルタイムの分子イメージングを可能にします.
研究 の 目的:
- メトロニダゾールで自然に豊富に存在する窒素15の直接的なNMR超極化を示す.
- パラ水素ベースのハイパーポラライゼーションの応用性を,多様な分子構造に拡大する.
- 医学診断における高極化メトロニダゾールの潜在的応用を探求する.
主な方法:
- SHield での反転交換による利用された信号増幅は,ヘテロ核へのアライナメント転送 (SABRE-SHEATH) 技術を可能にします.
- 効率的な核スピン極化のために使用されたパラ水素 (パラ-H2).
- さまざまなスピン-スピン結合 (J(nH) - ((15) N) を使用して直接結合および遠隔の窒素-15サイトの超極化を調査した.
主要な成果:
- 80%のパラ-H2を用いて約24%の核スピン極化 (P(15) N) を数秒で達成した.
- 100%のパラ-H2で約32%のP(15)Nを予測し,これは9.4Tで約100万倍もの信号増強に相当する.
- メトロニダゾールで直接結合した場所と,より遠くにある窒素15の場所の両方を成功裏にハイパーポラライズした.
結論:
- SABRE-SHEATH法では,メトロニダゾールにおける窒素-15の直接的なNMR超極化が可能である.
- この技術は,低コストのパラ水素超極化によってアクセス可能な分子と場所の範囲を拡大します.
- ハイパーポラライズされたニトロイミダゾールは,薬物メカニズムと低酸素感知のインビボ画像化において有望である.
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