構建與偶氮酚染料融合的 pH 響應和可微調的光不穩 定鄰硝基芐侷限單元

Constructing pH-responsive and fine-tunable photolabile o-nitrobenzyl cages fused with azo-phenolic dyes

張雅雯(Ya-Wen Zhang)

指導教授 ： 王宗興

國立臺灣大學/理學院/化學研究所/碩士(2022年)

https://doi.org/10.6342/NTU202200680

摘要

多重觸發去保護基團的策略已被廣泛研究，以控制有機合成和生物應用中 靶向分子的時空釋放。在這項工作中，我們旨在設計一系列光不穩定的侷限單 元，這些光觸發侷限單元可以在輻照下切割並且對 pH 環境具有特異性。受先前 研究的鼓舞，已經闡明在光觸發基團鄰硝基苯甲醇的硝基官能團鄰位取代基的電 子轉移能力會影響光觸發的釋放效率。我們將對pH值敏感的酚基與鄰硝基苯甲醇 通過偶氮偶合的方式結合在鄰硝基苯甲醇的硝基官能團的鄰位。
首先，我們用 HPLC 分析了我們的 pH 響應偶氮酚光觸發侷限基團 (NPX) 在取代基和環境pH值之間的相關性。我們確認偶氮酚光觸發限基團的 pKa 值會 影響光釋放效率。先前的研究聲稱替代物的位置會影響光觸發侷限基團的光釋放 效率。為了比較取代位置的影響，我們合成了另一個光觸發侷限基團mNPdiCl， 其酚基與鄰硝基苯甲醇的硝基官能團是間位的。mNPdiCl的pKa值約為4.73，與 NPdiCl相同，但光觸發侷限基團的光釋放能力，mNPdiCl受pH環境影響較小。該 結果與之前的研究一致。
在驗證了我們設計的 pH 響應光觸發侷限基團可以在不同的 pH 環境中選 擇性地進行光裂解後，我們希望了解該分子是否可以在生理環境中以相同的方式 表現。為了將 pH 響應光觸發侷限基團納入細胞應用，我們選擇了兩種不受pH影 響的熒光團，Ac-Rhodamine 和 Et-Nap 與在特定 pH 環境下的光釋放效率差異最 大的NPdiCl結合。在流式細胞儀分析和共聚焦成像結果表明，受pH值影響的光觸 發探針FL-NPdiCl的光釋放能力取決於環境的pH值。
pH響應的鄰硝基苯甲醇光觸發侷限機團成功地將單光觸發侷限基團修飾成 雙重可控的光觸發侷限基團。這個有希望的結果可以是優化侷限基團策略的激 勵，以實現更高的準確性並控制觸發反應過程。

關鍵字

光不穩 定鄰硝基芐侷限單元

並列摘要

Multiple triggered releasing strategies are developed broadly to control release targeted molecules in organic synthesis and bio-application spatiotemporally. In this work, We aimed to design a series of photolabile cages that could be cleaved under irradiation and have specificity to pH environments. Encouraged by previous studies, it has been elucidated that the electron transfer capability of the substituents para to the nitro function of the o-NB PPG affect the photo-releasing efficiency. We conjugated the pH-sensitive phenolic groups with the o-NB Photocage, whose phenolic group is para to the nitro function of o-NB by azo-coupling.
First, we analyses the correlation of our pH-responsive azo-phenolic photo- cages (NPX) between the substitute and pH environment with HPLC. We confirmed the pKa value of azo-phenolic photo-cages would affect the photo-releasing efficiency. Previous studies claimed that the position of the substitute is an effect of photo- releasing efficiency. To compare the effect of substitute position, we synthesize another cage, mNPdiCl, whose phenolic group is meta to the nitro function of o-NB. The pKa value of mNPdiCl is about 4.73, the same as NPdiCl, but the photo-releasing ability of the cage, mNPdiCl is less affected by the pH environment. This result conforms to the previous studies. After verifying that the pH-responsive PPG we designed can be selectively photo-cleavaged in different pH environments, we desired to see if the molecule could behave the same way in a physiological setting. To incorporate pH- responsive photo-cage into cell application, we chose two pH-independent fluorophores, Ac-Rhodamine and Et-Nap conjugate with NPdiCl, which has the most significant difference in photo-releasing efficiency under particular pH environments. The flow
cytometry analysis and confocal imaging results show that the photo-releasing abilities of pH-responsive probe, FL-NPdiCl are dependent on pH-environment.
The pH-responsive o-NB photo-cages show the successfully modified single triggered cage into a dual controllable cage. The promising result could be an encouragement to optimise caged strategies to achieve more accuracy and control the trigger reaction process.

並列關鍵字

photolabile o-nitrobenzyl cages

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