Study On Photosensitive Carbon Monoxide Releasing Molecule Lead Containing Natural Small Molecule Ligand

The challenge of developing the lead structures for therapeutic CORM is to construct transition metal carbonyl complexes with non-toxic small natural organic molecules. In this dissertation, we focus on the Ru(Ⅰ) sawhouse complexes [Ru(μ2-carboxylato)(L)2(CO)2]2in which the co-ligand system of carboxylic acids such as acetic acid, amino acid and their derivatives are highly desirable for developing therapeutic photo-CORM. These sawhorse complexes are robust in both solid and solution states. Under the physiological condition, these CORM do not reacted with oxygen, water, sodium dithionate. Their CO liberation was only triggered by UV radiation. Twenty-four sawhorse-type complexes have been synthesized and fully characterized. The mechanistic experimentation of la clearly demonstrated a well-defined degradation pathway, in which the dissociation axial ligand is the rate-determining step of the photo-activiated CO releasing. This thesis is composed of following three parts:1. Twenty-four sawhorse-type complexes have been synthesized, including 1a-8a with carboxylate bridging ligands and GlyOMe axial ligands, 1h-6h with carboxylate bridging ligands and CH3CN axial ligands, 1b-1e with acetic acid bridges and a variety of amino acid methyl ester axial ligands, and 8b-8g with Boc-Gly bridging ligands and a variety of amino acid methyl ester axial ligands. All compounds have been characterised by FT-IR,’H,13C NMR, Elemental analysis, showing that the structures are consistent with expected. Single crystal structures of eight compounds (1a,2a,4a, 5a,7a,8a,3h,4h) are analyzed by X-ray diffraction.2. CO-releasing of the diruthenium (Ⅰ) complexes are assessed using standard myoglobin assay under in vitro physiological condition. The characteristics of these CORM unchanged after at least 7 days storage without any lightproof. Their CO release can be triggered by 365 nm UV light but 400 nm. The CO-releasing kinetics shows that complexes have a good ability of photolytic release. The correlation of infrared data and release kinetics reveals that axial ligand determines their release performance and hydrophilicity of bridging ligands also finely turn the CO release process.3. Acetate bridged sawhorse GlyOMe complex (1a) is chosen to investigate the CO release pathway of sawhorse compounds. The degradation pathway of la is monitored by 1H NMR and FT-IR, the key intermediate which axial ligands replacing by solvent ligand was detected. In addition, GC-MS analysis unveiled the fate of noncarbonyl ligands as free acetic acid and glycine methyl ester in the photolysis experiment.