Transfer hydrogenation catalysis in cells
Hydrogenation reactions in biology are usually carried out by enzymes with nicotinamide adenine dinucleotide (NAD(P)H) or flavin mononucleotide (FAMH 2 )/flavinadenine dinucleotide (FADH 2 ) as cofactors and hydride sources. Industrial scale chemical transfer hydrogenation uses small molecules such...
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| Published in | RSC chemical biology Vol. 2; no. 1; pp. 12 - 29 |
|---|---|
| Main Authors | , |
| Format | Journal Article |
| Language | English |
| Published |
England
RSC
01.02.2021
|
| Subjects | |
| Online Access | Get full text |
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| Summary: | Hydrogenation reactions in biology are usually carried out by enzymes with nicotinamide adenine dinucleotide (NAD(P)H) or flavin mononucleotide (FAMH
2
)/flavinadenine dinucleotide (FADH
2
) 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 Ru
II
and Os
II
η
6
-arene complexes and Rh
III
and Ir
III
η
5
-Cp
x
complexes which catalyse hydrogenation of biomolecules such as pyruvate and quinones in aqueous media, and generate biologically important species such as H
2
and H
2
O
2
. 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. |
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| Bibliography: | Prof. Peter J. Sadler obtained his BA, MA and DPhil at the University of Oxford. Subsequently he was a MRC Research Fellow at the University of Cambridge and National Institute for Medical Research. From 1973-1996 he was Lecturer, Reader and Professor at Birkbeck College, University of London, and from 1996-2007 Crum Brown Chair of Chemistry, University of Edinburgh. Then he became Head of the Department of Chemistry at the University of Warwick, where he is now a Professor. He is a Fellow of the Royal Society of Chemistry (FRSC), Royal Society of Edinburgh (FRSE) and the Royal Society of London (FRS), an EPSRC RISE Fellow (Recognizing Inspirational Scientists and Engineers), a Fellow of the European Academy of Sciences, and Honorary Fellow of the Chemical Research Society of India, and the Chinese Chemical Society. His research is focused on the chemistry of metals in medicine, and in particular on organometallic and photoactivatable anticancer complexes. Dr. Samya Banerjee received his PhD in 2015 from the Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore, under the supervision of Prof. Akhil R. Chakravarty. Subsequently he was a postdoctoral fellow at Johns Hopkins University, USA with Prof. Marc M. Greenberg and a Royal Society-SERB Newton International Fellow (2017-2019) at the University of Warwick in the laboratory of Prof. Peter J. Sadler. Now he is working as a postdoc at the Institute of Inorganic Chemistry, Georg-August-Universität Göttingen, Germany with Prof. Dr Herbert W. Roesky. He has recently been awarded an Inspire Faculty Fellowship by the government of India to develop his independent academic career. His research interests include the development of next-generation metal-based anticancer drugs with novel mechanisms of action, mechanistic studies of clustered lesions in nucleosome core particles, and radicals of heavier group 13 elements. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 ObjectType-Review-3 content type line 23 |
| ISSN: | 2633-0679 2633-0679 |
| DOI: | 10.1039/d0cb00150c |