Biomimetic Models for Monooxygenase

Abstract

Part I. Nonheme iron의 active site를 가지고 있는 산소화 효소들은 Biological system에서 dioxygen activation과 유기물질들과의 산화반응에 관여된다.1 이 효소들의 catalytic mechanism에서 metal-peroxo나 high-valent metal-oxo종은 bleomycin, superoxide reductase, α-ketoglutarate dioxygenase에 중요한 활성 중간체들로 밝혀졌다. Synthetic model complex들을 가지고 많은 peroxoiron(Ⅲ)과 oxoiron(Ⅳ)종은 다양한 spectroscopic technique으로 특성화하고 있다. 그리고 이 종들의 반응성은 많은 산화반응을 통해 연구되었다.2,3 여기에 nonheme oxoiron(Ⅳ) complex인 axial ligand가 치환된 13-membered macrocyclic ligand를 가진 [FeⅣ(O)(TATM)(X)]n+ (TATM = 1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclotridecane, X = CH3CN, CH3CO2-, N3-, SCN-) 의 화학적 특성을 연구한 내용이다. 또한 axial ligand가 치환됨에 따라 oxoiron(Ⅳ) 종의 산화능력의 변화에 대해 연구하였다. Part II. Iron(Ⅴ)-oxo 종은 nonheme iron catalyst에 의한 organic substrate의 산화반응에서 활성 산화제로서 생각되어지고 있다.1 최근에 Iron(Ⅴ)-oxo 중간체가 합성되고, 다양한 분광학적 기술로 characterization 되었지만,1 catalytic oxygenation 반응에서 활성산화제로서 Iron(Ⅴ)-oxo 종이 관여한다는 증거는 간접적으로 product analysis로부터 알 수 있다. 그 예로는 Alkane hydroxylation 반응 생성물인 alcohol과 ketone의 selectivity, 4 이하의 H-KIE값, labeled water 실험에서 H218O의 18O가 생성물로의 incorporation가 있다.1 그렇지만, iron(Ⅳ)-oxo complex 역시 매우 큰 KIE 값을 갖고,2 H218O와의 산소교환을 보여준다.3 그러므로 catalytic oxygenation 반응에서 중간체들을(예를 들면 iron(Ⅳ)-oxo 또는 Iron(Ⅴ)-oxo )구분하기에는 어렵다. 본 연구에서는 새로운 non-heme iron(Ⅳ)-oxo 종인 [FeⅣ(O)(BQEN)]2+(1) (BQEN = N,N’-dimethyl-N,N’-bis(8-quinolyl)ethane-1,2-diamine)를 생성시켜 큰 반응성을 보여주었다. 그리고 반응성 연구에서 alkane과 alcohol의 산화반응은 hydrogen abstraction 메카니즘을 거쳐 일어남을 확인하였다. 더욱 중요한 것은 Iron(Ⅴ)-oxo 종이 Fe catalyst와 terminal oxidant에 의한 alkane과 alcohol의 catalytic oxidation 반응에서 활성산화제라는 강력한 증거를 알아낼 수 있었다.;Part I. Many enzymes containing mononuclear nonheme iron active sites are involved in dioxygen activation and the oxidation of organic substrates in biological systems. In the catalytic mechanisms of these enzymes, metal-peroxo and/or high-valent metal-oxo species are implicated as the key reactive intermediates in the chemistry of bleomycin, superoxide reductase, and α-ketoglutarate dioxygenase. With synthetic model complexes, a number of peroxoiron(III) and oxoiron(IV) species have been well characterized with various spectroscopic techniques and the reactivities of these complexes were investigated in a number of oxidation reactions. Herein, we report that axial ligand substitution of a mononuclear nonheme oxoiron(IV) complex bearing 13-membered macrocycle ligand, [FeIV(O)(TATM)(X)]+ (1) (TATM = 1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclotridecane, X = CH3CO2, N3, SCN), leads to the formation of FeIV=O species at low temperature and present the observation of Fe=O vibrations by resonance Raman spectroscopy. We also discuss the detailed characterization of [Fe(OOR)(TATM)] and [Fe(O2)(TATM)] complexes and the oxidizing power of the oxoiron(IV) species significantly affected by the axial ligand. Part II. Mononuclear non-heme iron oxygenases catalyze a diverse array of important metabolic transformations that require the binding and activation of dioxygen.In the catalytic cycles of the non-heme iron enzymes, several intermediates, such as iron(III)-hydroperoxo, iron(IV)-oxo, and iron(V)-oxo species, have been proposed as active oxidants that effect the oxygenation of organic substrates. In this work, we have generated a new non-heme iron(IV)-oxo complex, [Fe(IV)(O)(BQEN)]2+ (1) (BQEN = N,N’-dimethyl-N,N’-bis(8-quinolyl)ethane-1,2-diamine), that shows a high reactivity in the oxidation of alkanes and alcohols. Reactivity studies revealed that the alkane and alcohol oxidations occur via a hydrogen-atom (H-atom) abstraction mechanism. More importantly, we have obtained strong evidence that an iron(V)-oxo species is involved as an active oxidant in the catalytic oxidation of alkanes and alcohols by an iron catalyst and a terminal oxidant.