Organometallic Ruthenium and Iridium Transfer-Hydrogenation Catalysts Using Coenzyme NADH as a Cofactor
Organometallic Ruthenium and Iridium Transfer-Hydrogenation Catalysts Using Coenzyme NADH as a Cofactor
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DOI：
10.1002/anie.201108175
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发表时间：
2012-01-01
影响因子：
16.6
通讯作者：
Sadler, Peter J.
中科院分区：
文献类型：
--
作者：
Betanzos-Lara, Soledad;Liu, Zhe;Sadler, Peter J.
快速发展的生物有机金属化学研究领域提供了设计在生物学和医学中具有潜在广泛应用的化合物的可能性。[1]在生物催化中，有机金属配合物主要与辅酶NAD+（或其模型）[2]转化为还原形式的NADH有关，使用甲酸盐作为氢化物源。[3]这种有机金属化合物包括IrIII和RhIII五甲基吡啶（Cp*）络合物和RuII芳烃络合物，其区域选择性地催化这种还原;[3-5] RhIII衍生物可以驱动依赖于NADH作为辅因子的酶促反应。[3b在体内，NAD+和NADH作为辅因子在许多生物催化过程中发挥重要作用，包括能量代谢、抗氧化和氧化应激、免疫功能和细胞死亡。[6]我们感兴趣的可能性，有机金属化合物可以干扰细胞中的NAD+/NADH氢化物转移反应作为一种新的作用机制。我们之前已经表明，[（η6-芳烃）Ru（en）Cl]+（芳烃=六甲基双丙烯（hmb）、对伞花烃（p-cym）、茚满（ind）和en=乙二胺）络合物可以使用甲酸盐作为氢化物源将NAD+转化为NADH，并且这种反应在细胞中可能是可行的，因为细胞可以耐受毫摩尔水平的甲酸盐。[3a]在这里，我们报告的逆反应，从1，4-NADH的金属有机配合物的氢化物的转移的第一个观察。[7]我们表明，半夹心RuII芳烃和IrIII的配合物可以使用NADH作为氢化物源还原酮，和IrIII的衍生物是强大的催化剂生产H2。因此，这些复合物可能对调节细胞的氧化还原状态有价值（一个潜在的药物靶点），作为酶模拟物，并用于生物偶联氢化反应。（η6-芳烃）Ru（N，N）Cl]+配合物作为氢化物从甲酸盐转移到NAD+的催化剂，通过用π-受体二亚胺配体如2，2 ′-联嘧啶（bpm）或1，10-菲咯啉（phen）。RuII芳烃络合物，其中芳烃是p-cym（1，5），hmb（2），ind（3），或1，2，3，4-四氢萘（thn，4;表1），合成为PF 6的盐。配合物1、2和5以前已经报道过。[八]《中国日报》
The rapidly developing research area of bio-organometallic chemistry offers the possibility to design compounds with a potentially wide range of applications in biology and medicine.[1] In biocatalysis, organometallic complexes have mainly been concerned with the conversion of the coenzyme NAD+(or models of it)[2] to its reduced form NADH using formate as the hydride source.[3] Such organometallic compounds include IrIII and RhIII pentamethylcyclopentadienyl (Cp*) complexes and RuII arene complexes that catalyze this reduction regioselectively;[3–5] the RhIII derivative can drive enzymatic reactions relying on NADH as a cofactor.[3b, 4] Invivo, both NAD+ and NADH play important roles as cofactors in numerous biocatalyzed processes, including energy metabolism, antioxidation and oxidative stress, immunological functions, and cell death.[6] We are interested in the possibility that organometallic compounds can interfere with NAD+/NADH hydride transfer reactions in cells as a novel mechanism of action. We have shown previously that [(η6-arene) Ru (en) Cl]+(arene= hexamethylbenzene (hmb), pcymene (p-cym), indane (ind), and en= ethylenediamine) complexes can convert NAD+ to NADH using formate as the hydride source, and that such reactions might be feasible in cells because cells can tolerate millimolar levels of formate.[3a] Here we report the first observation of the reverse reaction, the transfer of hydride from 1, 4-NADH to organometallic complexes.[7] We show that half-sandwich RuII arene and IrIII cyclopentadienyl complexes can use NADH as an hydride source for the reduction of ketones, and that IrIII cyclopentadienyl derivatives are robust catalysts for the production of H2. These complexes may therefore be valuable for modulation of the redox status of cells (a potential drug target), as enzyme mimics, and for bio-coupled hydrogenation reactions.Our initial aim was to improve the efficiency of [(η6-arene) Ru (N, N) Cl]+ complexes as catalysts for hydride transfer from formate to NAD+ by replacing the N, N-chelating ligand en by π-acceptor diimine ligands such as 2, 2о-bipyrimidine (bpm) or 1, 10-phenanthroline (phen). RuII arene complexes where the arene is p-cym (1, 5), hmb (2), ind,(3), or 1, 2, 3, 4-tetrahydronaphthalene (thn, 4; Table1) were synthesized as PF6 À salts. Complexes 1, 2, and 5 have been reported previously.[8]