Transfer hydrogenation catalysis in cells.
Transfer hydrogenation catalysis in cells.
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DOI：
10.1039/d0cb00150c
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发表时间：
2021-02-01
影响因子：
4.1
通讯作者：
Sadler PJ
中科院分区：
文献类型：
--
作者：
Banerjee S;Sadler PJ
生物学中的氢化反应通常通过酶以烟酰胺腺嘌呤二核苷酸（NAD（P）H）或黄素单核苷酸（FAMH 2）/黄素腺嘌呤二核苷酸（FADH 2）作为辅因子和氢化物源来进行。工业规模的化学转移氢化使用小分子如甲酸或醇（例如丙醇）作为氢化物源和过渡金属络合物作为催化剂。本文重点研究了有机金属半夹心RuII和OsII η6-芳烃配合物以及RhIII和IrIII η5-Cpx配合物在水介质中催化丙酮酸和醌类等生物分子氢化，产生H2和H2 O2等生物重要物种。有机化合物催化剂可以实现对映体选择性，而且可以在活细胞中具有活性，这是令人惊讶的，因为存在多种毒物。这类催化剂可以使用甲酸盐作为氢化物源诱导还原应力，或者通过接受来自NAD（P）H的氢化物诱导氧化应力。在某些情况下，光催化氧化还原反应可以通过金属或黄素中心的光吸收来诱导。这些人工转化可以以不寻常的方式干扰生物化学途径，并且是设计具有新作用机制的金属药物的基础。综述了近年来合成金属配合物在转移氢化催化和癌细胞凋亡方面的研究进展。它们为药物开发和生物技术提供了令人兴奋的调节生化途径的新方法。
Hydrogenation reactions in biology are usually carried out by enzymes with nicotinamide adenine dinucleotide (NAD(P)H) or flavin mononucleotide (FAMH2)/flavinadenine dinucleotide (FADH2) as cofactors and hydride sources. Industrial scale chemical transfer hydrogenation uses small molecules such as formic acid or alcohols (e.g. propanol) as hydride sources and transition metal complexes as catalysts. We focus here on organometallic half-sandwich RuII and OsII η6–arene complexes and RhIII and IrIII η5–Cpx complexes which catalyse hydrogenation of biomolecules such as pyruvate and quinones in aqueous media, and generate biologically important species such as H2 and H2O2. Organometallic catalysts can achieve enantioselectivity, and moreover can be active in living cells, which is surprising on account of the variety of poisons present. Such catalysts can induce reductive stress using formate as hydride source or oxidative stress by accepting hydride from NAD(P)H. In some cases, photocatalytic redox reactions can be induced by light absorption at metal or flavin centres. These artificial transformations can interfere in biochemical pathways in unusual ways, and are the basis for the design of metallodrugs with novel mechanisms of action. Recent developments in transfer hydrogenation catalysis and photocatalysis in cancer cells by synthetic metal complexes are reviewed. They offer exciting new ways to modulate biochemical pathways for drug development and biotechnology.