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Studies on Supramolecular Photochirogenesis Mediated by Synthetic Antibody and Chiral Silica-Organic Hybrid Nanoribbons

YOSPANYA Wijak 東北大学

2020.09.25

概要

不斉光合成は、熱的反応では多段階を必要とする、或いは合成困難な歪みの高い化合物を一段階で合成可能といった利点を有し、有機化学において極めて重要な研究分野である。しかし、光反応の鍵中間体である励起状態はその寿命が短く、また相互作用も弱いことから反応の制御は困難とされている。これまでに、哺乳類の血清アルブミンをキラル反応場として使用した 2-アントラセンカルボキシレートの超分子非対称光二量化は、77%と 97%ee で syn-head-to-tail 二量体を生成することが報告されているが、一般に、カルボン酸塩の電子反発力や立体障害により、水中で head-to-head 二量体を得るのは困難と見做されきた。

本博士論文では、水中の 2 つの異なる媒体によって媒介される 2-アントラセンカルボキシレートの超分子光二量化反応について報告する。まず、水中で二重二分子膜の界面活性剤組織を内側に、シリカ壁を外側に持つキラルな有機-シリカ複合ナノリボン構造体を用いて、室温においても AC 二量体の優れた位置選択的光合成を達成した。また、合成一本鎖抗体(scFv)は、48%ee および 90%以上の head-to-head の位置選択性を備えた anti-head-to-head の AC 二量体のエナンチオ選択性を達成した。

有機-シリカ複合ナノリボン構造体は、界面活性剤の自己組織化とシリカの複合化により合成した。 初めに、ジェミニ型L-またはD-酒石酸塩界面活性剤を合成し、水中での自己組織化により、酒石酸塩の鏡像異性体キラリティーに依存し、特定の巻き方向を持つ、ねじれた配向を有する螺旋状ナノ構造体を形成した。次に、キラル有機テンプレートを用いたテトラエトキシシランのソル-ゲル法により、ハイブリッド有機シリカナノリボンと呼ばれる内部の組織化された有機構造を保持しながら、キラルシリカの外層を形成した。

複合ナノ構造体は、酒石酸対アニオンをアキラルアニオンと交換した後でもジェミニの螺旋キラル構造を維持でき、このキラル構造は、メチルオレンジといったアニオン化合物にキラリティーを転写できる。本研究では、酒石酸塩を 2-アントラセンカルボキシレートと交換することで、2-アントラセンカルボキシレートも強力な誘起 CD ピークを示し(L ハイブリッドナノリボンの g-factor : −6 × 10−3 と 7 × 10−3)、キラリティー誘導の効率と安定性は、ハイブリッドナノリボン内の AC とジェミニ界面活性剤の化学量論比、温度、および時間に大きく依存することが分かった。さまざまな分光法(CD、VCD、IR、NMR、蛍光)を使用してナノ構造内の 2-アントラセンカルボキシレートの組織化を検討し、ナノ構造内での 2-アントラセンカルボキシレートの光二量化では、anti 異性体と syn 異性体の比率が同程度で、97%以上の極めて高い選択性で、head-to-head 型二量体が得られる事を明らかとした。

より一般的な戦略として、従来のファージディスプレイ技術によって調製された人工一本 鎖抗体(scFv)を、生体分子キラル反応場とした超分子不斉合成を検討した。ファージディ スプレイにおけるリガンドは、スペーサーとしてポリエチレングリコール、およびアミド結 合を有するビオチンに連結された syn-head-to-head の AC 二量体(ACD3)を使用した。ファ ージディスプレイ法を用い、ADC3 に対する選択性の最も優れた抗体を選択し、その遺伝子 配列を確定後、遺伝子工学手法を駆使し大腸菌で目的抗体を発現可能であることを確認した。光反応条件の最適化と合わせて、抗体認識表面での 2-アントラセンカルボキシレートの光二 量化により、最大 92%の head-to-head の二量体が得られ、anti-head-to-head の二量体につい ては 48%ee だった。

Anti-head-to-head 二量体の合成が促進された一方、目的とは異なる syn-head-to-head の二量体も高い割合で得られた。抗体の配列に由来する構造の分析後、新しい方向とカルボン酸基の数、およびアミド結合の除去を含む、ファージディスプレイ技術のためのリガンドの新設計を提案し、ファージディスプレイ技術におけるリガンドの新しい二量体である、2-アントラセンカルボキシレートと 6-ヒドロキシ-2-アントラセンカルボン酸ヘテロ二量体の合成と単離を達成した。

以上、2-アントラセンカルボキシレートの超分子不斉[4 + 4]光二量化をベンチマーク的光反応として、ハイブリッドシリカ-有機ナノリボンおよび人工抗体が有効に機能することを明らかとした。

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