研究並開發可應用於生物影像及微米製圖之光致變色腙類衍生物

Abstract

光致變色化合物被光激發後，能產生可逆的光化學異構化，而異構化通常伴隨著顏色變化，稱之為光致變色。當中，有機光致變色化合物容易做化學修飾，因此容易調整性質，進而滿足不同光學領域的各種需求，如：光儲存元件、超解析顯微技術、可複寫材料或太陽能儲存等。在此論文中，我們設計並開發了兩類，分別在液相及固相中，能有光致變色性質的腙類衍生物，而這兩類腙類衍生物分別被應用在類澱粉胜肽的超解析度成像技術以及光學可複寫材料。 第一部分研究，是以水楊醛衍伸物和含有肼基之類澱粉胜肽反應，形成可光異構化之腙類化合物。此含有腙類化合物之類澱粉胜肽，不需要任何添加劑或高功率雷射，即能在照光後變色（顯色），且在生理條件下光穩定性佳。因為光致變色的性質，使此腙類化合物可被用於超解析度成像顯微技術，讓以腙類化合物修飾之類澱粉胜肽，能以光學方式顯現出在超越繞射極限的奈米尺度下，不同的培養條件下導致的胜肽結構多型性。更進一步，由於此光致變色系統不需要任何添加劑，本研究也成功地將超解析顯微技術應用在活體細胞影像。 第二部分，我們設計了一系列平面及非平面的腙類化合物，並研究其在固相中的光致變色及熱能回復性質（T型光致變色）。非平面的腙類化合物由於晶體堆疊較為鬆散、晶體中有較多空間異構化，因此光致變色性質好，且室溫下回復速率極快。在平面腙類化合物中，光異構化在平面、緊密堆疊的固相中通常不易發生，而透過修飾極性較高的芳香環（N-氨基鄰苯二甲酰亞胺、４-氨基脲唑），能使芳香環在晶體中堆疊性質改變。在平面分子特定方式的緊密堆疊下，分子在晶體中仍有足夠的空間產生光異構化，因此即使分子為緊密堆疊，仍保有光致變色性質。而此類平面分子也擁有較長的熱能回復時間（秒至小時）。進一步，我們展示了此類腙類化合物可應用於低功率雷射複寫、製圖。 總括來說，我們展示了透過對腙類化合物的簡單修飾，能使這些化合物在固相及液相中都有光致變色的性質，我們也試著找出化合物的結構與光致變色性質的關聯，並且對這些化合物在固相及液相做不同的應用。

Photoisomerizable molecules are the class of compounds that undergo reversible photoisomerization reactions under light irradiations. Such isomerizations are normally accompanied by absorption shifting, and hence is referred to as photochromism. Organic photochromic compounds are easy to modify to satisfy the needs in different fields, such as optical storage, superresolution imaging, rewritable materials, solar energy storage, etc. In this thesis, we aim to develop two series of photochromic hydrazone derivatives which are photoisomerizable in liquid and solid phases. The two series of hydrazones were used for (1) superresolution imaging on amyloidogenic peptides and (2) optically rewritable materials, respectively. In the first part of this dissertation, we report the incorporation of salicylaldehyde derivatives onto the hydrazine-tagged amyloidogenic peptides by forming photoisomerizable hydrazones. These hydrazones are photostable under physiological conditions and undergo photoisomerization without the need of addition of external reductants or high-power irradiation for quenching. By applying them in superresolution microscopy, the polymorphic nanostructures of the hydrazone-incorporated peptides distinguished in vitro under different buffering conditions. Moreover, the additive-free condition of this protocol allows the detailed characterization of the amyloid-aggregate morphologies in live cells. In the second part, several planar and non-planar hydrazones were prepared and their photochromism and thermal recovery properties (T-type photochromism) in solid state were characterized. The non-planar hydrazones were found highly photochromic with ultrafast thermal recovery rate, for the loosely packed crystal structures contain more free space for isomerization. For the planar hydrazones, where the photoisomerization were normally obstructed in planarly close-packed structure, polar aromatic hydrazides (i.e., N-aminophthalimide and urazine) were introduced to alter the nature of aromatic stacking. In this way, the optimized molecular packing in planar hydrazones still bore enough crystalline free spaces for photoisomerizations, and therefore the photochromism properties were conserved in the close-packed structures. The thermal recovery lifetimes for the planar hydrazones (sec–hours) were found much longer than the non-planar ones. With the photochromic property, we demontrated that all the hydrazones were optically rewritable and could be patterened with low power laser. In summary, we showcased that through brief and simple modifications, the hydrazones derivatives exhibited photochromic properties in solid or liquid phases. Further, the photochorimicty could be correlated to the molecular structure or packing in solid state. These derivatives were then applied for respective applications in liquid or solid state.