Development of Dinitrosyl Iron Complex as Nitric Oxide Donor and Investigation of its Anti-Aging Effect in C. elegans and Their Effects on Organisms

• Main Authors: Mei-Ren Wang, 王美仁
• Other Authors: Chia-Her Lin
• Format: Others
• Language: zh-TW
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/q22228

碩士 === 中原大學 === 化學研究所 === 106 === Nitric oxide has important functions in the body, including: vasodilation, nerve conduction, blood pressure regulation, and other pathogens. However, instability of nitric oxide makes the research and application of nitric oxide more complicated in biology and pharmacology. Therefore, the development of compounds capable of stably releasing NO• has become one of the important topics in the current research and application of nitric oxide. In this study, dinitrosyl iron complex (DNIC) and [Fe2(μ-SR)2(NO)4] were used as nitric oxide delivery reagents. It was first discovered that [Fe2(μ-SR)2(NO)4] can triggered to release nitric oxide under aerobic conditions. In addition, the half-life for the release of nitric oxide, ranging from 0.5 hours to 27.4 hours, can be controlled by using different thiol ligands. Moreover, C. elegans was used as a biological model, and NO•-fluorescent probe was used in combination with a Confocal Microscope to confirm that DNIC-1 can release NO in C. elegans. In addition, we have found that the NO •-release [Fe2(μ-SEtOH)2(NO)4] (DNIC-1a) can extend the lifespan of C. elegans from 16.9±0.5 days to 18.7±0.4 days and delay accumulation of cell senescence to achieve the effect of delaying aging. The study found that [Fe2(μ-SEtCOOH)2(NO)4] (DNIC-1b) will rapidly decay and release nitric oxide in an acidic aerobic environment. In this study, we used [Fe2(μ-SEtCOOH)2(NO)4] (DNIC-1b) to modify MIL-88B(Fe) to synthesize DNIC@MOF through -COOH functional group. To study the stability of DNIC@MOF at different pH values, using IR, UV, XRD identification, found that DNIC@MOF can be stable in the acidic environment below pH5. In the next step, DNIC@MOF was fed to hypertensive SHR rats to measure blood pressure changes in mice for 24 hours to investigate whether DNIC@MOF can stably release nitric oxide in vivo to lower blood pressure.