In-cell Organometallic Redox Catalysis

Winner: 2022 Dalton Division Horizon Prize

For pioneering work on catalysis of redox reactions in cancer cells by synthetic organometallic complexes.

Celebrate In-cell Organometallic Redox Catalysis

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The In-cell Organometallic Redox Catalysis Team have developed the catalysis of redox reactions in cancer cells by synthetic organometallic complexes. The catalysis disturbs the redox balance inside the cell and enhances anticancer activity.

The multidisciplinary team, led by scientists at the University of Warwick and supported by scientists at Chimie ParisTech (PSL University), University of Zürich, Sun Yat-sen University, Heriot Watt University and the Technische Universität Kaiserslautern, questioned whether small metal-containing molecules of only tens of atoms synthesised chemically in the lab could also catalyse similar reactions. If successful, potential applications include drugs that could modulate biochemical pathways.

The team synthesised catalysts containing the precious metals ruthenium, osmium and iridium, showing that they can efficiently catalyse reactions of biological importance, even with control of the handedness (chirality) of the products. The catalysts seemed to function within cells too, and triggered high anticancer potency for ruthenium- and osmium-based catalysts. Using light beams, the team could selectively activate non-toxic iridium photocatalysts in cancer cells.

This new approach heralds the introduction of new types of medication – novel metallodrugs with minimal side effects for use at very low doses. In-cell catalysis offers new mechanisms of action, which can help to overcome resistance to current treatments.

The project demonstrates how research on fundamental questions can lead to applications and goals in cancer treatment. We’re incredibly proud of the results achieved by a team that is collectively motivated to drive chemical research beyond the boundaries of current knowledge by using cutting-edge methods and techniques with the potential to improve lives.

The team

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Dr Samya Banerjee, Royal Society-SERB Newton International Fellow, Department of Chemistry, University of Warwick
Dr Olivier Blacque, Scientific collaborator in crystallography & theoretical Chemistry, University of Zurich
Hui Chao, Professor, Sun Yat-Sen University
Guy J. Clarkson, X-ray crystallographer, Department of Chemistry, University of Warwick
James P. C. Coverdale, PhD student, Department of Chemistry, University of Warwick
Robert J. Deeth, Professor of Computational Chemistry, Department of Chemistry, University of Warwick
Gilles Gasser, Professor, Deputy Head of the Institute of Chemistry for Life and Health Sciences, Chimie ParisTech, PSL University, CNRS
Dr Abraha Habtemariam, Research Fellow, Department of Chemistry, University of Warwick
Dr Huaiyi Huang, Royal Society Newton-China Research Fellow, Department of Chemistry, University of Warwick
Thomas Malcomson, PhD student, Heriot-Watt University
Martin J. Paterson, Professor of Theoretical Chemistry, Heriot-Watt University
Dr Ivan Prokes, NMR spectroscopist, Department of Chemistry, University of Warwick
Dr Kangqiang Qiu, Post Doctoral Fellow of Bioinorganic Chemistry, Sun Yat-Sen University
Dr Isolda Romero-Canelón, Senior Research Fellow in Metals in Medicine, Department of Chemistry, University of Warwick
Peter J. Sadler, Professor of Chemistry, Department of Chemistry, University of Warwick
Dr Carlos Sanchez-Cano, Postdoctoral Research fellow, University of Warwick
Volker Schünemann, Professor of Biophysics and Medical Physics, Department of Physics, Technische Universität Kaiserslautern
Joan Josep Soldevila-Barreda, PhD student/IAS early career fellow, Department of Chemistry, University of Warwick
Dr Lijiang Song, Associate Professor in Chemistry, Department of Chemistry, University of Warwick
Dr Michael Staniforth, Senior Research Fellow, Department of Chemistry, University of Warwick
Vasilios Stavros, Professor of Physical Chemistry, Department of Chemistry, University of Warwick
Martin Wills, Professor of Organic Chemistry, Department of Chemistry, University of Warwick
Dr Juliusz A. Wolny, Scientific Co-worker, Faculty of Physics, Technische Universität Kaiserslautern
Dr Pingyu Zhang, Royal Society Newton-China Research fellow, Department of Chemistry, University of Warwick

Q+A

Why is this work so important and exciting?

It led to the identification of a new approach to cancer therapeutics and was only possible through the concerted efforts of a diverse, multidisciplinary team – working together made a real difference.

Where do you see the biggest impact of this technology/research being?

The biggest impact may be in anticancer therapeutics, with potential for novel anti-infectives. In-cell catalysis offers completely new mechanisms of action for drugs and hence the possibility of overcoming resistance to treatment with current drugs. Additionally, the use of photochemical/photophysical techniques contributes towards development of a potentially powerful new clinical technology.

How will this work be used in real life applications?

For anticancer therapy, especially for combatting resistance to current treatments. It is likely to take several years for this discovery research to be translated into clinical applications – it is normal for there to be an initial drug development pipeline of several years.

Importantly, the concept developed here allows treatment of hypoxic tumours (i.e, tumours where the level of oxygen is low). This is of much interest since such tumours are extremely difficult to treat.

Catalytic drugs can offer unique mechanisms of action, facilitate administration of lower dosages, and accompanied by fewer side-effects for patients in the future.

How do you see this work developing over the next few years, and what is next for this technology/research?

Increasing selectivity for cancer versus normal cells so minimising side effects, at low doses.