Organic Dications: Synthesis, Reactivity and Applications
Lead Research Organisation:
University of Strathclyde
Department Name: Pure and Applied Chemistry
Abstract
One of the principal factors governing the reactivity of substances is their degree of electric charge - in simple terms, opposite charges attract, so the more charged a compound is, the more reactive it should be. Until now, the way to produce compounds that are highly electrophilic (very positively charged) was to use ''super-acids'', i.e. acids that are stronger than 100% sulfuric acid. Performing chemistry in super-acid has been very useful for understanding the reactions of super-electrophiles derived from hydrocarbons. This proposal addresses the preparation of novel and highly electrophilic species in molecules containing heteratoms (usually nitrogen) in organic solvents, and looks to study their reactivity. It has potential applications across a broad range of chemical reactions, and it could also have relevance to UK plc through taking first steps in the development of catalysts for performing reactions (like Friedel-Crafts reactions) that have traditionally used environmentally harmful reagents such as aluminium trichloride. Super-electrophile chemistry may also explain some of the biggest puzzles in bioorganic reaction mechanisms, involving reactions that are required for DNA synthesis (the formation of thymine derivatives from their uracil counterparts) and protein synthesis (preparation of methionine from homocysteine - methionine is the starting amino acid for all genes during translation). Even the mysterious but potentially very useful production of methane from carbon dioxide that is achieved by bacteria, could depend on the chemistry of the superelectrophiles that are discussed in this proposal.This is a new adventure in chemistry that we expect to have widespread applications.
Planned Impact
1. Who will benefit from this research? 2. How will they benefit from this research? (i) Chemists in academic and industry laboratories will benefit.... through discoveries of new chemical reactions. For example, we may find a way to avoid the use of aluminium chloride in Friedel-Crafts reactions, thereby avoiding waste and pollution. Furthermore, our reactions will provide energy savings by taking place at ambient temperature [due to the high reactivity of our intermediates]. (ii) The PDRA and PhD student engaged on this research programme will benefit through being trained in a cutting edge area of chemistry and through publications in high-impact journals. (iii) Society in general will benefit.....through a greater understanding of how methanogenic bacteria use carbon dioxide as a chemical feedstock. This could lead to new catalysts that use excess carbon dioxide for useful tasks. (iv) Biochemists will benefit through a better understanding of how methyl transfer occurs in nature. 3. What will be done to ensure that they have the opportunity to benefit from this research? Where appropriate, the discoveries will be protected by patent in first instance, through the Research and Innovation Department at the University of Strathclyde, with a view to licensing as soon as possible, so that the discoveries may be deployed for general benefit of society. The research will be published as soon as possible, in journals of the highest calibre, to maximise the audience. The work will be publicised at international and national Conferences and through popular media, where apropriate. The PDRA and PhD student will be exposed to a modern comprehensive training in a 21st century research school (WestCHEM), involving them in weekly group meetings, and in the preparation and presentation of lectures, posters and publications on their research.
People |
ORCID iD |
John Murphy (Principal Investigator) |
Publications
Murphy, J
(2014)
The third hydrogenase
Kovacevic L
(2012)
Superelectrophilic Amidine Dications: Dealkylation by Triflate Anion
in Angewandte Chemie International Edition
Corr MJ
(2011)
Evolution in the understanding of [Fe]-hydrogenase.
in Chemical Society reviews
Description | We have discovered that salts based on amidine dications can be prepared and isolated. Many people had tried to establish this in advance of our work. Our findings about the 'super-reactivity' of molecules have implications for organic synthesis and for activation of electrophiles in chemistry and biology. |
Exploitation Route | The findings could be extended to understand multi-site activation in enzyme reactions |
Sectors | Chemicals Pharmaceuticals and Medical Biotechnology |
URL | http://www.johnmurphygroup.com/research-interests.html |
Description | Accelerated Discovery and Development of New Medicines: Prosperity Partnership for a Healthier Nation |
Amount | £5,495,023 (GBP) |
Funding ID | EP/S035990/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 01/2019 |
End | 12/2024 |
Description | Accelerated Discovery and Development of New Medicines: Prosperity Partnership for a Healthier Nation |
Organisation | GlaxoSmithKline (GSK) |
Country | Global |
Sector | Private |
PI Contribution | I am leader for one of 5 themes; and am a member of a second theme. I represented University of Strathclyde as party of the panel of 3 who were interviewed at EPSRC for this grant |
Collaborator Contribution | GSK are the lead industrial partners who are collaborating with the University of Strathclyde and theUniversity of Nottingham in this Prosperity Partnership, which addresses accelerated discovery and development of new medicines. |
Impact | The collaboration has just started, so,as yet, there are no outputs, but they will be reported under that collaborative grant to RCUK. |
Start Year | 2019 |
Description | Invited Table Rond Presentations and Discussions |
Organisation | Novartis |
Country | Global |
Sector | Private |
PI Contribution | Participant : Participation in workshop/networks with non-academic organisation : Invited by Novartis in Basel to present a lecture on my recent chemistry and to engage in discussions about their potential interest in our chemistry |
Collaborator Contribution | They hosted my lecture and discussions |
Impact | This partnership led to discussions. The major upshot of the discussions did not relate specifically to the chemistry that we discussed, but Novartis employed one of my postdoctoral researchers (Dr Harry Farwaha) after his contract with my group, on another project, had completed. |
Start Year | 2012 |
Description | 2 Lectures at Univrsite de Bordeaux |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | 2 Lectures at Universite de Bordeaux, principally to a postgraduate audience, on the discoveries arising from our research |
Year(s) Of Engagement Activity | 2017 |
Description | Invited Table Rond Presentations and Discussions |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited by Novartis in Basel to present a lecture on my recent chemistry and to engage in discussions about their potential interest in our chemistry. Not recorded |
Year(s) Of Engagement Activity | 2012 |
Description | Research Colloquium University de Rouen |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Visitor : Invited talk : Departmental Research colloquium at : University of Rouen |
Year(s) Of Engagement Activity | 2015 |
Description | Research Colloquium University of Poitiers |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Visitor : Invited talk : Departmental Research colloquium. University of Poitiers this visit and lecture led to application for joint funding at Royal Society with Prof Sebastien Thibaudeau |
Year(s) Of Engagement Activity | 2017 |
Description | Research Colloquium at NTU Singapore |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Contributor : Invited talk : Departmental Research Colloquium This visit and lecture led to a successful application for joint funding from Royal Society, but not in the area of chemistry covered by this grant. . |
Year(s) Of Engagement Activity | 2017 |
Description | Research Colloquium at Peking University |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Contributor : Invited talk : Research Colloquium. Peking University |
Year(s) Of Engagement Activity | 2013 |