| Abstract: | 一氧化氮經由一氧化氮合成酶所產生，目前已經被發現在人體內扮演許多生理及病 理方面的重要角色，包含了對血管舒張收縮的調節、中樞及周遭神經系統的傳導，以 及對病原體的免疫。而雙亞硝基鐵化合物（DNICs）及硫醇亞硝基(RSNO)通常被視為扮 演生物體內的一氧化氮載體或貯存槽的角色。生物體內的酪胺酸蛋白硝基化(protein tyrosine nitration (PTN))對於許多病理現象(包含發炎現象、神經退化、心血管疾病)來說 也是一個相當重要的轉譯後蛋白質修飾(post-translational modification)。日前化學家根 據所做的實驗結果大膽推測雙亞硝基鐵化合物（DNICs）也可能在生物體內扮演促進酪 胺酸蛋白硝基化(protein tyrosine nitration (PTN))的反應。此外, 生化學家亦發現雙亞硝 基鐵化合物可促進生物體內的半胱氨酸氧化(cysteine oxidation) 。這個計畫中我們設計 合成一系列結構相同、電子環境略為不同的單核、雙核雙亞硝基鐵化合物(RRE, RRE-1, RRE-2, RRE-CO, DNIC-1, DNIC-2, DNIC-3, DNIC-4) 。預計利用各種物理方法去分析 這些化合物上各原子的電子密度分布，期待分析的結果可以用以解釋不同 DNICs與氧 氣反應的反應機構及進行酚類亞硝基化反應、半胱氨酸氧化的差異性。
The discoveries that NO plays a key role for a surprising range of physiological and pathological processes in humans have led many researchers to revisit the chemistry of NO and its derivatives such as dinitrosyl iron complexes (DNICs) in recent years. Dinitrosyl iron complexes (DNICs) and S-nitrosothiols (RSNO) have been suggested as one of the possible forms for storage and transport of NO in biological system. Recently, Prof. Kim has demonstrated that the {Fe(NO)2}10 DNICs served as a nitrating agent to convert 2,4-di-tert-butylphenol to 2,4-di-tert-butyl-6-nitro-phenol in the presence of O2, and claimed that cellular DNICs could provide the possible route to generate protein tyrosine nitration (PTN) which is an important post-translational modification associated with various pathological conditions. In addition, Prof. Kim also showed the possible biological function of cysteine oxidation. In this pursuit, we plan to synthesize a series of iron nitrosyl complexes ((RRE, RRE-1, RRE-2, RRE-CO, DNIC-1, DNIC-2, DNIC-3, DNIC-4) with analogous coordination geometry but different electronic configuration to study the O2 reactivity and the ability serving as the nitrating agent in the phenol nitrating reaction and as the oxidant in the thiolate oxidizing reaction. The formal charge of Fe atom, NO group and thiolate on these iron nitrosyl complexes will be scrutinized on the basis of EPR, SQUID, DFT computation and X-ray absorption spectroscopy (XAS). The results of the O2 reactivity of these iron nitrosyl complexes, phenol nitration and cysteine oxidation will help us to elucidate the relationship between the ability of phenol nitration, thiolate oxidation mediated by DNICs and the electronic structure of DNICs. |
