新穎微環境敏感發光體的光物理特性和應用

Abstract

第一部分使用氯化銅試劑進行合環反應可將含蒽的有機磷化合物轉換成帶正電性的鏻離子螢光體。此鏻離子螢光體不僅具有良好的水溶性和量子效率，其優異的光穩定性以及低度的生物毒性使得這一系列化合物具備細胞顯像之應用潛力。 第二部份實驗呈現水溶性的鉑和銥錯合物的合成以及光物理性質研究，它們都具有輔助配位基(bis(diphenylphosphino)benzene (dppb), P^P*)。這些錯合物在周圍配位基的調控下，具備相當大的光物理性質差異，像是激發以及放光範圍，以及激發態生存期對氧氣分子的敏感程度。此外這些新合成的錯合物都具備有相當高的雙光子吸收截面，雖然它們整體而言，為具有負電性的錯合物，但是仍然能被海拉細胞攝入並且具有極低的細胞毒性，綜合上述這些特性，使得它們具有雙光子磷光生存期顯像的能力。特別是顯像效果最佳的錯合物[(ppy)2Ir(sulfo-dppb)] (Ir1*)，當其進入海拉細胞後，在正常大氣和純氮氣的環境下，磷光生存期的差異達到兩倍，再者，我們使用被異種移植海拉細胞的無胸腺裸鼠進行活體實驗，我們發現到不論是點滴注射或局部注射Ir1*錯合物，都未產生劇烈的毒性，而且仔細分析裸鼠的磷光生存期影像後，我們發現Ir1*錯合物的生存期在正常肌肉組織和腫瘤之間有統計上的差別，證明其監測缺氧環境的能力。

The first part is 6-memberd P-heterocycle has been fused with polyaromatic framework through intramolecular transformation of anthracene-based phosphine induced by CuCl2. The resulting hydrophilic phosphonium fluorophores exhibit extremely high quantum efficiency along with prominent stability and low toxicity that make them suitable for imaging purposes. The second part presents synthesis and photophysical investigation of cyclometalated water-soluble Pt(II) and Ir(III) complexes containing auxiliary sulfonated diphosphine (bis(diphenylphosphino)benzene (dppb), P^P*) ligand. The complexes demonstrate considerable variations in excitation (extending up to 450 nm) and emission bands (with maxima ranging from ca. 450 to ca. 650 nm), as well as in the sensitivity of excited state lifetimes to molecular oxygen (from almost negligible to more than 4-fold increase in degassed solution). Moreover, all the complexes possess high two-photon absorption cross sections (400-500 GM for Pt complexes, and 600-700 GM for Ir complexes). Despite their negative net charge, all the complexes demonstrate good uptake by HeLa cells and low cytotoxicity within the concentration and time ranges suitable for two-photon phosphorescence lifetime (PLIM) microscopy. The most promising complex, [(ppy)2Ir(sulfo-dppb)] (Ir1*), upon incubation in HeLa cells demonstrates two-fold lifetime variations under normal and nitrogen atmosphere, correspondingly. Moreover, its in vivo evaluation in athymic nude mice bearing HeLa xenografts did not reveal acute toxicity upon both intravenous administration and topical injection. Finally, Ir1* demonstrated statistically significant difference in lifetimes between normal tissue (muscle) and tumor in macroscopic in vivo PLIM imaging.