Research Development of Environmentally Benign Bio-inspired Oxidation Catalysts Our research objective is to evaluate the chemical functions of metalloenzymes, biocatalysts involving transition-metal ion(s) in their active-sites, and apply them to catalytic oxidation reactions. Our targets are iron- and copper-containing oxygenases and molybdenum- and tungsten-containing oxidoreductases. The iron- and copper-containing metalloenzymes, for example, bind molecular oxygen in the air to transport it to all over our body and reductively activate it by injecting electrons and protons (eq. 1) to accomplish a series of oxidation/oxygenation reactions of a variety of substrates. Such reactions are indispensable to prepare useful materials and to degrade harmful compounds in our body. On the other hand, metalloenzymes involving a molybdenum or a tungsten ion activates water molecule by abstracting electrons and protons (eq 2) to perform oxygen atom transfer to several organic and inorganic substances. These reactions (eq 1 & 2) afford very clean and environmentally benign processes since they employ very cheap molecular oxygen or water molecule as the oxygen source and produce no harmful byproducts. Thus, much recent attention has been focused on such ideal chemical processes. （S：Substrate、SO：Oxygenation Product） In our laboratory, we are trying to evaluate the structures, physicochemical properties (spectroscopic, redox, and magnetic features), and reactivity of the active-oxygen species generated on the active-site transition-metal ion(s) and apply those strategies (eq 1 & 2) to develop efficient oxidation/oxygenation catalysts for practical applications. To accomplish these objectives, we employ several experimental techniques such as those of synthetic organic chemistry for the design and synthesis of new bio-inspired ligands, coordination chemistry for the synthesis of active-site model complexes, several spectroscopic techniques (UV-vis, IR, resonance Raman, fluorescence, X-ray crystallographic analysis, NMR, ESR, etc.) for structural and physicochemical evaluations, and electrochemistry and kinetics for mechanistic investigations. Furthermore, we are dealing with biochemistry of real proteins (enzymes), where not only mechanistic studies of the enzymes but also creation of novel artificial metalloenzymes are conducted by using advanced molecular biology techniques. １．Development of Transition-Metal Active-Oxygen Complexes. Fine Tuning of Their Reactivity and Application to Oxidation Reactions Using a variety of supporting ligands, several types of copper-complexes of active-oxygen species have been synthesized and their structure, physicochemical properties, and reactivity have been examined in detail. So far, mononuclear copper complexes of superoxide (A) and alkylperoxide (B), dinuclear copper complexes such as (μ-η2:η2-peroxo)dicopper(II) (C) and bis(μ-oxo)dicopper(III) (D) complexes as well as mixed valent trinuclear bis(μ3-oxo)tricopper(II,II,III) complex (E) have been successfully obtained (Figure 1). These copper active-oxygen complexes can be obtained by the reactions of copper(I) complexes and molecular oxygen (O2) or the reactions of copper(II) complexes and peroxides. These copper active-oxygen complexes have been demonstrated or suggested to be involved in copper proteins (enzymes), playing key roles in the oxygen transport and the oxidation/oxygenation reactions in biological systems, being one of the most attractive research objectives of bioinorganic chemistry. The copper active oxygen species are also very important intermediates involved in a variety of copper-catalyzed reactions in synthetic organic reactions. We and other research groups have shown a versatile reactivity of the copper active-oxygen complexes listed in Figure 2. We have also investigated the detailed mechanisms of respective reactions to provide important information for the development of new catalytic reaction systems. Figure 1．Transition-Metal Complexes of Active-Oxygen Species Figure 2. Oxidation Reactions by Copper Active-Oxygen Complexes We have extended the copper active-oxygen chemistry to the nickel sysetm to obtain an iso-structural bis(μ-oxo)dinickel(III) complex (F). Comparisons of the structure, spectroscopic and redox features, and reactivity between the copper and nickel complexes supported by the same ligand have explored the roles of metal ions. Furthermore, a very efficient oxygenation reaction of alkanes (inactive saturated hydrocarbons) with mCPBA catalyzed by nickel complexes have been developed, which can be applied to organic synthesis (Figure 3). Recently, we have also succeeded to develop an efficient 1,2-cis-dihydroxylation reaction of olefins catalyzed by an osmium complex, where more than 99% stereo-selectivity and high catalytic turnover number (over 1000 times) as well as nearly quantitative product yield are attained. We are currently trying to develop an efficient alkane hydroxylation system using a different types of osmium catalysts. Figure 3. Alkane Hydroxylation Catalyzed by Nickel Catalyst To develop new and more efficient catalytic systems, we are currently focusing on (i) ligand design for highly efficient catalysts for alkane hydroxylation and (ii) expansion of the oxidation chemistry to other transition-metal systems; Fe, Co, Mn, etc. 2. Synthesis and Reactivity of Transition-Metal Chalcogen Complexes  　生体系において水、硫黄、セレンを利用して触媒反応を司っているモリブデンやタングステン酵素の反応中心の精密モデル化と機能解明をめざして錯体化学的研究に研究を展開しています。現在までに、酸素原子引き抜き反応を応用した金属-オキソ錯体の合成や、中心金属の電子移動能を利用して水分子由来のオキソ基を導入した金属錯体の合成を行い、その生成機構や各オキソ種の酸化還元挙動や基質の酸化活性などを系統的に調べています。本研究では特に酵素の活性種を精密にモデル化するため、配位子として各種ジチオレン誘導体を用いて検討しています。また、類似の戦略を用いて、スルフィド錯体やセレニド錯体を系統的に合成し、反応性を明らかにするとともに、電子状態の解明を行い反応性との相関関係の解明をめざしています。図４．Chalcogen Complexes of Mo and W Creation of Artificial Metalloenzymes 　二核の銅活性中心を有する一原子酸素添加酵素チロシナーゼの詳細な反応機構の解明や、同様の二核銅中心を有する酸素運搬酵素ヘモシアニンの酸化機能発現と酸化触媒への応用について検討を行っています。　さらにそこから得られた情報やモデル化学で得られた情報を基にして、亜鉛酵素などを金属結合鋳型として用い、遺伝子工学を駆使した人工金属酵素の創出（図５）について検討を行っています。例えば、加水分解酵素として機能している金属ラクタマーゼの亜鉛イオンを銅イオンに置換し、活性中心部位に存在するアミノ酸残基の幾つかを置換（ミューテーション）することにより、本来にはない酸化機能が発現し、フェノールなどの酸化触媒として機能することを見いだしました。 Figure 5. Creation of Artificial Metalloenzymes Using Protein Matrix as Metal ligand