Synthesis and Application of Light-Activated Molecular Systems

Abstract

Ruthenium complexes and BODIPY dyes are two very typical types of light-activated molecular systems which are useful in various chemistry and biology applications such as photodynamic therapy, chemical sensors, biological labelling and imaging. But correspondingly, these applications can face problems like cytotoxicity, poor analyte selectivity and a weak signal-to-noise ratio (SNR). This thesis is concerned with work focusing on the design and preparation of several novel ruthenium polypyridyl complexes and BODIPY-based compounds for applications in photodynamic therapy and the fluorescent sensing area. Their photochemistry behaviours are investigated via a range of optical techniques and methods. We hoped to discover compounds with excellent features like low toxicity, high selectivity, good optical signal response and stable performance. The ideas are presented in six chapters within the thesis. Chapter 1 outlines the research directions based on ruthenium complexes and BODIPY-based light-activated molecular systems. The literature review generally introduces the previous discoveries of these two types of compounds, their structural feature, principles of synthetic considerations, chemistry and some applications. A review of photochemistry principles which are related to their structures for development in the other chapters are also reviewed as the basis of this chapter. Chapter 2 describes the common instrumentations, general experimental set ups, data collection and analysis methods which are applicable for the prepared samples and some preliminary structural characterization. Chapter 3 talks about the design of a new class of PDT agents using light-activated small molecules like ruthenium complexes to block biological functioning, especially targeting mitochondria and how they may interfere with critical redox reactions under light activation. Based on our concepts the complex [Ru(bipy)2(1-hydroxyanthra-9,10 quinone)]Cl (RU1) was prepared and studied to understand the preliminary reaction mechanisms and its excited state behaviour through a series of stability tests, electrochemistry, UV-Visible kinetic and femtosecond transient absorption spectroscopy experiments. Under light in the presence of H2O2 two different reactions (fast and slow) appear to take place. The complex loses the quinone-based ligand and a resulting Ru(III) or Ru(V) species is produced. The complex RU1 shows good potential to consume H2O2 from the one carbon metabolism in mitochondria, and hence may cut the energy cycle pathway of tumour cells. Chapter 4 explored a new a julolidine-based BODIPY compound to selectively detect sulfite in a real wine sample. A non-oxidised julolidine-based BODIPY compound (JUL) was reacted with silver (I) ions in the presence of white light and produced its oxidised julolidine version (OXJUL) which contains a quaternary nitrogen. This type of oxidation reaction is highly unusual and there were no reports about it previously. With the addition of a small amount of Na2SO3 in an aqueous solution, the fluorescence maxima of OXJUL blue shifted from 648 nm to 608 nm over several minutes. In the presence of a large excess of sulfite, a further slower reaction occurred accompanied by a blue-shift of the emission to 544 nm. These series of changes are the basis of a real-time fluorescent ratiometric sensor for the detection of sulfite in real wine samples. Chapter 5 successfully developed a new low molecular weight BODIPY based voltage sensitive dye (AJBD) to image and detect voltage changes in giant unilamellar vesicles (GUVs) according to lifetime changes. Julolidine was mono substituted in the α-position of a BODIPY core to form a neutral and lipophilic VSD with a charge transfer feature. With the ON-OFF voltage change on the GUVs, the fluorescence lifetime distribution ratio of AJBD showed a zigzag pattern alongside the ON-OFF voltage changes. When the GUVs were subjected to a ramping voltage, the lifetime distribution ratio showed a linear change in line with the voltage change. These observations were the evidence to indicate the voltage sensitive character of AJBD. Chapter 6 briefly concludes the previous work and highlights the development of the project in the future. For RU1 and RU2, we are aiming to apply it in mitochondria and investigate its behaviour in interrupting the metabolism pathway under the light in Newcastle University Medical School. For OXJUL and AJBD, the targets will be following tested in cells labelling and imaging using fluorescence lifetime imaging microscopy (FLIM) in collaboration with Central Laser Facility (CLF) in the future.