From Organic to Inorganic Chemistry: Exploiting the Isolobal Analogy to Develop Main Group Catalysts

Modern society is highly reliant on organic materials for example in technological devices such as smartphone displays, or for drugs to tackle chronic illnesses. However, while the UK and western society seeks to improve the standard of living, the developing world also strives to improve technology and healthcare in their own countries. With a growing population and necessity to improve the quality of life globally there will be ever-increasing demands for the world's resources. This, combined with increased energy prices, could potentially lead to a deterioration in our current standard of living unless new energy and cost efficient processes are identified to meet the expanding global demand. Catalysis plays a pivotal role in maintaining the quality of everyday life worldwide as over 85% of chemical products are generated through catalytic methods. Through lowering the energy barrier of chemical processes, catalysts can direct a reaction's outcome both reducing energy consumption and making chemical processes more efficient. Therefore, the development of new catalysts and improvement of catalytic performance can have a direct influence on numerous major societal issues. Transition metals have dominated these processes owing to their rich reaction chemistry and high activity. However, many of the most active catalysts are typically composed of the so called "precious" metals which are, as their name suggests, expensive owing to their scarcity. While these catalysts are often highly efficient, one major pitfall includes their inherent toxicity. This is particularly significant for consumer products that are taken into the body (e.g. food products or pharmaceuticals) in which regulatory controls requires concentrations of toxic metals to parts per billion levels through meticulous post-reaction catalyst removal. One question which Dr Melen's research aims to answer is: could metal catalysts be circumvented altogether?

Over the last 40 years the isolobal analogy (for which Hoffmann was awarded the Nobel Prize in Chemistry) has provided a theoretical foundation for rapid experimental developments in inorganic chemistry. The proposed work will apply the isolobal analogy to generate novel ambiphilic catalysts through the application of synthetic organic chemistry to main group systems. The compounds generated will then be tested in metal-free catalytic hydrogenation, carbon dioxide sequestration and C-H activation/borylation reactions. These are among some of the most important and topical areas of catalysis. For example, with a diverse range of commercial processes, the addition of molecular hydrogen to unsaturated substrates is unparalleled in the chemical industry. Equally, the direct utilisation of carbon dioxide as a C-1 feedstock has been identified by many nations as an area in need of exploration and development. While carbon dioxide is the primary carbon source for life on our planet, it is simultaneously the most significant greenhouse gas and approaches to sequester CO2 are becoming increasingly important. These processes will provide new methods for making fuels and useful compounds in a sustainable manner.

Main group, or metal-free, catalysis has become a burgeoning field of which Dr Melen has been a key player. However, this flourishing field is still in its naissance, with many challenges to be overcome before practical applications can be developed. The work described herein will move main group catalysis towards industrial exploitation by applying well-established methodologies in organic chemistry to inorganic main group chemistry and subsequently industry (e.g. the pharmaceuticals sector). This unique opportunity for Dr Melen will allow her to build a team of highly skilled researchers which is of vital importance to her as an emerging leading academic.

The investigation of isolobal analogies between main group and organic chemistry is a starting point for a new vision in main group chemistry and catalysis. The work described will lead to a library of structurally diverse main group compounds that will provide real-world applications in materials chemistry, organic synthesis and catalysis. Such changes will bring about noteworthy economic and societal impact in the short, medium and long term:

In the short term this grant will directly benefit UK and international academics working in the fields of coordination, main group and organic chemistry. The innovative synthetic approaches described in the one-pot syntheses of complex (in)organic structures is anticipated to be widely recognised and offers significant impact. Dissemination of information to these communities will be through conventional peer-review journals via both high impact and more specialist publications to target specific audiences. In addition, our work will be highlighted through conference presentations encompassing broader and more specialised components of the scientific community. Moreover, this program will provide direct training of PDRAs and PhD students who will contribute to the pool of highly-trained scientific personnel making them attractive in an increasingly competitive job market. In the latter part of the fellowship, Dr Melen will apply to take part in the Welsh Crucible, which will accelerate interdisciplinary dissemination and specifically facilitate targeting subsequent collaborative partners for follow-on projects. These approaches will ensure that both academic and industrial beneficiaries are identified and engaged with, at appropriate early stages in the project.

Medium term impact in the years following the grant will reach the broader international scientific community, and is expected to lead to full engagement with industrial beneficiaries, as the most active catalysts are identified and manufactured on large scale. In an academic setting, materials scientists and organic chemists will use our methodology and concepts to design ambiphilic molecules as building blocks to more elaborate structures for use in optical devices whereas synthetic organic and inorganic chemists may employ such compounds in a variety of catalytic processes. For industrial impact, Dr Melen will liaise with Cardiff University's Research Innovation and Enterprise Service (RIES), to identify specific processes or products that address current problems in the pharmaceutical industry. Through RIES, potential industrial partners will be targeted through joint development projects (e.g. CASE awards). In this regard, the multi-national chemical company TOK are already interested in the ability to handle reactive main group compounds using continuous-flow technologies. Early societal impact for this project aims to bridge the gender gap in future STEM students through outreach activities. In particular, this project which will be led by a junior female academic will provide positive and contemporary examples of women in science.

In the longer term, as the synthetic methodology and developed products become more widely accepted, their transfer to industrial applications may have a direct impact on the economy and society thereby improving quality of life, health and the environment. With assistance from RIES, industrial partnerships will be established to develop joint agreements and IP. Existing industrial links (Pfizer, TOK) will be reinforced in a manner pursuant on the commercial profile of the company. The project will be continually assessed to identify important innovations, which will be investigated for industrial exploitation and/or appropriately protected through patents. While the details of the project are technically complex, general concepts such as the importance of catalysis and sustainability will be emphasised to the public highlighting the significance of this work in the real world.