設計1,8-萘啶感測器於水相中辨識鳥糞嘌呤及其單磷酸

Design 1,8-Naphthyridine Based Receptors for Sensing Guanine and Guanosine Monophosphate in Water

彭日平(Ri-ping Phang)

指導教授 ： 方俊民

國立臺灣大學/理學院/化學研究所/碩士(2014年)

https://doi.org/10.6342/NTU.2014.10268

摘要

本論文主要針對生物界中的重要受質鳥糞嘌呤設計合成具有選擇性的推拉電子排列的共軛螢光感測器，Pyrene–APENA 1 和 Guanidine–APENA 2。這兩個受體都同樣經由乙炔連接1,8-萘啶和苯胺分子，並具有daaa（d表示氫鍵予體，a表示氫鍵受體）的排列方式，相對於受質的鹼基guanine具有addd排列方式產生四重互補氫鍵的結合模式。除此之外，亦可籍由額外增加的芘基團帶來的π–π吸引力，或者胍基團與磷酸根之間電荷吸引力來增強其結合能力。由於這一系列的受體分子會經由分子内的電荷轉移機制(ICT)，因此可以利用簡便、靈敏且快速的UV–vis及螢光來偵測其結合。

Pyrene–APENA 1 對於鳥糞嘌呤衍生物1 在二氯甲烷中具有良好的結合能力，並造成受體分子有激烈的螢光淬熄現象。經由計算得到相當高的結合常數250,700 x 27,500 M-1，估計是由芘基團帶所來的π–π吸引力增強所致。另一方面，我們希望引進胍基團以增強受體在水中的溶解度之外，亦可通過電荷吸引力來增強與鳥糞嘌呤單磷酸的結合。結果發現，Guanidine–APENA 2 在水相中與鳥糞嘌呤單磷酸有很好的選擇性及結合能力，結合常數為16,000 x 2,700 M-1。

關鍵字

1,8-萘啶感測器 ； 辨識 ； 主客化學 ； 水相 ； 鳥糞嘌呤單磷酸

並列摘要

Two push–pull conjugated fluorescence molecular sensors 1 and 2 were designed to bind the biologically important substrate guanine and GMP selectively over the adenine counterparts. The fluorescent molecular sensors were constructed by conjugation of 2-acetamido-1,8-naphthyridine with aniline via an ethynyl bridge. The receptor molecules adopted a daaa relay of proton donors (d) and acceptors (a) to form quadruple hydrogen-bonding complex with the guanine derivative possessing an addd sequence. An additional binding site was provided either by pyrene for π–π stacking interaction or by guanidine group for electrostatic interaction to enhance the affinity of these receptor molecules. Our designed sensor undergoes an intramolecular charge transfer (ICT) upon electronic excitation, which is easily monitored by absorption and fluorescence changes in the visible region.

Pyrene–APENA 1 showed good binding affinity for guanine derivative G-10 in CH2Cl2 solution. A very large fluorescence quenching was observed during complexation, presumably due to the π–π stacking interaction of G-10 with the pyrene unit in Pyrene–APENA. The binding constant (Ka) of 250,700 x 27,500 M-1 in CH2Cl2 solution was determined. A guanidine group was equipped in Guanidine–APENA 2 to increase the water solubility and binding affinity through electrostatic interaction. It showed a high and selective binding affinity toward guanosine 5’-monophosphate (GMP) compared to adenosine 5’-monophosphate (AMP) and guanosine 3’,5’-cyclic phosphate (cGMP). The binding constant between Guanidine–APENA 2 and GMP is 16,000 x 2,700 M-1 in water.

並列關鍵字

1,8-Naphthyridine based receptor ； sensor ； host-guest chemistry ； water ； guanosine monophosphate

參考文獻

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