In-situ NMR-based methodology for screening and optimisation of heterogenised organocatalytic systems

Lead Research Organisation: University of Manchester
Department Name: Chem Eng and Analytical Science

Abstract

The goal of this proposal is to develop and validate an in-situ Nuclear Magnetic Resonance (NMR)-based screening and optimisation methodology for heterogenised organocatalytic systems, able to monitor and evaluate catalyst activity, transport and surface interactions at a pore-scale level in such functionalised materials. Batch reaction studies combined with in-situ 1H and 13C NMR spectroscopy, diffusion and relaxation techniques will give new and exclusive insights into these systems by providing quantitative data on intra-pore kinetics, diffusion and adsorption, which will be able to direct catalyst formulation and reaction design by evaluating the controlling interactions and mass transport phenomena of the various reactant/solvent/product species within the pores of the heterogenised catalytic system, hence aid selection of optimal reaction parameters such as choice of suitable solvents, solid supports, pore size and type of linker to immobilise the organocatalyst on support. The validation of this methodology in heterogenised organocatalysis will be a significant step forward towards effective screening and development of these materials, which can be expanded to other related technologies using functionalised porous materials.

Planned Impact

The project will benefit stakeholders with impact in the following areas: (i) Industry and commercial sector; (ii) Outreach and engagement of scientific community; (iii) Environmental policy and the wider society; (iv) Training and skill development.

(i) Industry and commercial sector
Heterogenised organocatalysts, if properly implemented on an industrial scale, will contribute to reduce current costs to industry associated with the use of homogeneous catalysts, by reducing material and energy costs associated to expensive separation procedures and catalyst loss/disposal. In addition heterogenised organocatalysts can be used in packed-bed reactors for continuous operation, increasing productivity, allowing easier process control and decreasing maintenance level. The industrial exploitation will be maximised by a close collaboration with Johnson Matthey (JM), a leading catalyst and chemical company, which is fully supporting the proposal and will provide industrially relevant raw materials, technical expertise and guidance for industrial exploitation. Using the strong links of the PI's School with important pharmaceutical companies, such as AstroZeneca, GSK and Pfizer, with a high interest in fine chemicals, it will be possible to involve the wider industrial community.

(ii) Outreach and engagement of scientific community
The project covers various scientific areas, which will benefit several communities from organic to physical chemistry, from catalysis to spectroscopy; hence it represents a great opportunity for cross-disciplinary exchange of knowledge, which will be enabled by attending various UK and international conferences; visits and seminars across the UK and internationally through the network of external collaborator Prof Armando Carlone; organising a dedicated workshop supported by the IChemE Catalysis Special Interest Group (SIG).

(iii) Environmental policy and the wider society
This project will have a positive impact on both environment and the wider society. Developments in the area of heterogenised organocatalysts will be able to address many societal issues related to the chemical industry, such as reduction of waste and energy consumption, efficient use of resources as well as a decrease in the environmental footprint of chemical processes. The strong expertise of the PI's School in sustainability and corporate responsibility will provide an ideal platform for enhancing such impact. The project will reach people beyond those directly involved in it, including undergraduate students, through organisation of satellite research projects on sustainability and life cycle analysis of these processes; the wider public will be reached using the links and social media of the University for public engagement. The IChemE channels will be used to further promote project outcomes.

(iv) Training and skill development
The inter-disciplinary nature of the project will develop highly skilled scientists, who will gain a broad range of skills and knowledge. The people involved on this project will deal with a variety of disciplines, including materials science, catalysis, organic chemistry and spectroscopy, hence will acquire a broad set of skills as well as a multi-perspectives approach to scientific problems. The interaction with leading academics from different areas, most notably catalysis, NMR and organic synthesis, will contribute in developing important interface management and communication skills, which is paramount in the current scientific and technological landscape, whereby projects are often highly multi-disciplinary. The collaboration with JM will also benefit by providing the possibility to interact with the commercial sector, carry out research work in industrial facilities as well as developing important skills required by the industry. Hence, the project will develop highly skilled scientists with a broad range of knowledge, which will benefit the whole UK economy and R&D sector.

Publications

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Di Carmine G (2021) Deep eutectic solvents: alternative reaction media for organic oxidation reactions in Reaction Chemistry & Engineering

 
Title Artwork for cover of paper recognised as top paper of the month 
Description Artwork for cover of paper recognised as top paper of the month 
Type Of Art Artwork 
Year Produced 2020 
Impact The front cover will help raise the visibility of the research work 
URL https://pubs.acs.org/toc/orlef7/22/13
 
Title Artwork for cover of paper recognised as top paper of the month 
Description Hand-drawn cover artwork 
Type Of Art Artwork 
Year Produced 2020 
Impact The artwork will raise the visibility of the research work reported. 
URL https://pubs.rsc.org/en/content/articlelanding/2020/me/d0me90030c#!divAbstract
 
Title Front cover for top article of the journal 
Description Front cover for top article of the journal 
Type Of Art Artwork 
Year Produced 2021 
Impact Increase visibility and promotion of research outcomes 
URL https://pubs.rsc.org/en/content/articlepdf/2021/cp/d1cp01515j
 
Description This award has so far reported some important new research findings:

- We have discovered that by appropriate solvent selection, we are able to make immobilized organocatalysts as effective as their homogeneous counterpart in terms of catalytic activity. This is very significant since it is commonly reported that immobilized organocatalysts, which have much better properties in terms of handling and recyclability, have however much worse catalytic activity compared to their use in homogeneous phase and this has so far hindered commercial development of this technology. Our new findings demonstrate that is therefore possible make processes that use immobilized organocatalyst viable, hence retain good catalytic performances and at the same time avoiding waste of precious catalytic materials. These findings are the subject of a recent publication, which featured on the journal cover of Organic Letters (ACS) as top article of the month (Org. Lett. 2020, 22, 13, 4927-4931).

- We have also discovered that it is possible to use immobilized organocatalysts to carry out organic synthesis in water and ethanol, which compared to commonly used organic solvents, have much greener properties, such as wide availability and very low toxicity. This would have significantly implications for enabling greener processes for producing fine chemicals, especially in the pharmaceutical industry, whereby disposal of hazardous solvents is an issue and represents additional costs for the industry. The replacement of such organic solvents with much benign solvents, such as water and ethanol, would therefore be a big step forward. We are currently doing further studies in this area as well as preparing drafts for new research articles to disclose such findings to the academic and industrial communities. We are also discussing our results with pharmaceutical manufacturing companies aiming at establishing a new research collaboration.

- In addition to the findings above published in Reaction Chemistry & Engineering (React. Chem. Eng., 2022, 7, 269-274), we have recently reported a new study showing the impact of solvent selection when inorganic silica frameworks (widely used as catalyst support) are used to immobilise organocatalysts for conducting asymmetric aldol reactions, with the results showing that an appropriate selection of the solvent can mitigate the detrimental impacts caused by immobilisation of organocatalysts when silica supports are used. In particular, we have validated the NMR methodology as a fast screening tools for solvents in such reactive systems, which can speed up reaction screening.

- Very recently we have also been exploring substituent effects of aldehyde derivatives in organocatalysed aldol reactions in order to understand how the nature of reagents can affect reactivity in immobilised organocatalysts, with a manuscript currently being finalised. We believe that altogether, the results we have obtained so far in the project are giving us new directions able to boost the development of immobilised organocatalysts.

- The results and methodology developed in this project have also lead to new applications in related fields, including new work carried out on biochars for removal of pollutants, solid photo-organocatalysts and zeolites. This has also led to new developments in the use of bench-top NMR for studying transport in porous materials, with a paper (Mol. Syst. Des. Eng., 2020, 5, 1193-1204) that was awarded the Junior Moulton Medal from the Institution of Chemical Engineers.
Exploitation Route The findings of this award will be followed by a project more focused on engineering the materials developed in this project for enabling larger-scale applications of this technology in the manufacturing of fine chemicals and pharmaceuticals. We are currently seeking the support of pharmaceutical companies to support a follow up project.
Sectors Chemicals,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

URL https://pubs.rsc.org/en/content/articlelanding/2022/re/d1re00471a/unauth
 
Description The initial results have been object of a publication of high impact (Org. Lett. 2020, 22, 13, 4927-4931) which was selected as top article of the month. In addition, further research work has revealed some very interesting findings that have the potential to lead to the development of organocatalytic processes using green solvents such as water and ethanol, replacing hazardous fossil fuel-based organic solvents commonly used in industry. This would have significant benefits in terms of developing more sustainable and environmentally friendly chemical processes, especially for drug manufacturing, with implications in healthcare as well. New research articles are currently under preparation as well as further work to finalize this piece of research. We are currently working on writing a follow up project more focused on engineering the catalytic materials developed in this project for enabling larger-scale applications of this technology in the manufacturing of fine chemicals and pharmaceuticals, seeking the support of pharmaceutical companies. In addition, we have also been able to expand our original research targets and produced new results into the development of photocatalytic processes using metal-free catalysts for the synthesis of organic molecules of industrial interest. These findings have been object of a prestigious publication in Science Advances (Science Advances 11 Nov 2020:Vol. 6, no. 46, eabc9923) and have the potential to revolutionize the current approach to industrial chemistry by providing more environmentally friendly chemical processes. The findings were also reported in press news at international level (https://it.notizie.yahoo.com/chimica-verde-lo-studio-che-100409870.html). Part of the methodology developed in this project has also been used to develop a new proposal on sustainable production of chemicals, recently funded by the EPSRC, EP/V026089/1, which started in September 2021 as well as an ARC project on development of multifunctional materials for catalytic cascades, DP200100204.
First Year Of Impact 2020
Sector Chemicals,Environment,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology
Impact Types Societal,Economic

 
Description EPSRC Responsive Mode
Amount £620,000 (GBP)
Funding ID EP/V026089/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 08/2021 
End 05/2024
 
Description Low-field NMR Studies to Probe Motion and Dynamics in Rock Pore Structures
Amount £30,000 (GBP)
Organisation BP (British Petroleum) 
Sector Private
Country United Kingdom
Start 08/2021 
End 09/2025
 
Description Low-field NMR Studies to Probe Motion and Dynamics in Rock Pore Structures
Amount £88,000 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 08/2021 
End 09/2025
 
Description Spatially orthogonal multifunctional materials for catalytic cascades (SPACECAT)
Amount $467,500 (AUD)
Funding ID DP200100204 
Organisation Australian Research Council 
Sector Public
Country Australia
Start 08/2020 
End 09/2023
 
Description Collaboration with Haldor Topsøe 
Organisation Haldor Topsoe A/S
Country Denmark 
Sector Private 
PI Contribution Using the methodological approach currently used on this EPSRC project we have attracted the interest of Haldor Topsøe for understanding transport by diffusion in catalytic materials used by the company.
Collaborator Contribution The partner gave us a series of catalytic materials to study using NMR and provided work on catalyst characterisation and other data that will form part of a joint paper.
Impact - Consultancy work - Research paper in preparation - Invited talks at Haldor Topsøe headquarter in Denmark
Start Year 2019
 
Description Collaboration with Johnson Matthey 
Organisation Johnson Matthey
Department Johnson Matthey Technology Centre
Country United Kingdom 
Sector Private 
PI Contribution We are currently screening solid catalysts for organic synthesis; results will be disclosed to the company in the next few months in order to discuss follow-up work to be doing. In addition, the development of bench-top NMR measurements currently being run in the project is of particular interest for the company for their R&D capabilities in catalyst development.
Collaborator Contribution The partner provided us with access to research facilities for catalyst characterisation.
Impact A first meeting on preliminary initial results has taken place, which will be followed up by an update meeting in the next few months to report updates on the project and discuss further access to research facilities needed.
Start Year 2019
 
Description Collaboration with QMUL 
Organisation Queen Mary University of London
Department Queen Mary Innovation
Country United Kingdom 
Sector Private 
PI Contribution Provided analytical tools to study biochar surface chemistry
Collaborator Contribution Provided expertise as well as carbon-based materials for applications in adsorption and catalysis
Impact Multidisciplinary (chemistry, chemical engineering, materials science) research papers on the use of biomass waste for producing biochars to treat wastewater
Start Year 2021
 
Description Collaboration with RMIT 
Organisation RMIT University
Country Australia 
Sector Academic/University 
PI Contribution Write up of research project on spatially orthogonal multifunctional materials for catalytic cascades
Collaborator Contribution Provide analytical tools for catayst characterisation and involvement in new research project.
Impact Award of ARC Discovery Projects grant
Start Year 2019
 
Description Collaboration with University of Bologna 
Organisation University of Bologna
Country Italy 
Sector Academic/University 
PI Contribution We are working with Prof. Villiam Bortolotti from the University of Bologna on Fast Field Cycling (FFC) NMR measurements of functionalised porous materials, which are closely related to the type of materials studied in this project. We have synthesized and supplied him with materials for NMR measurements using his specialised equipment.
Collaborator Contribution Prof. Villiam Bortolotti is currently performing FFC NMR measurements and data analysis for our samples.
Impact We are currently finishing measurements and started drafting a research manuscript aiming at a joint publication and further collaboration in the near future.
Start Year 2019
 
Description Collaboration with University of Sheffield 
Organisation University of Sheffield
Country United Kingdom 
Sector Academic/University 
PI Contribution The PI has established a collaboration with Dr Marco Conte on using NMR relaxation techniques to study solvent effects in porous catalysts used for sugar conversion and we are currently performing measurements using similar NMR techniques used in this project.
Collaborator Contribution The University of Sheffield has provided us with materials to investigate and characterise.
Impact A manuscript on the work is currently under preparation.
Start Year 2019
 
Description Collaboration with University of Trieste 
Organisation University of Trieste
Country Italy 
Sector Academic/University 
PI Contribution The group of Prof. Paolo Fornasiero has been interested in the methodologies used in this project for studying surface modifications in photocatalysts for organic synthesis. As such, we are doing several characterisation measurements of photocatalysts supplied by his group and currently writing a joint manuscript.
Collaborator Contribution They have been providing us materials and expertise in synthesis and screening of photocatalysts.
Impact We are currently writing a joint manuscript and starting working on new ideas related to our initial results.
Start Year 2019
 
Description Collaboration with the University of L'Aquila and the University of Ferrara 
Organisation University of Ferrara
Country Italy 
Sector Academic/University 
PI Contribution We are currently working with the University of Ferrara is collaborating on the project by helping doing experimental work on catalyst screening as well as NMR diffusion and relaxation measurements on materials provided by them for carrying out oxidation of aldehydes to esters using NHC catalysts. We have screened several reactions assessing the effect of solvents and we have also done novel characterisation on heterogenized NHC catalysts using pulsed-field Gradient (PFG) NMR diffusion as well as NMR T1 and T2 relaxation. We are currently writing a joint article on the results. We are also working with Dr Armando Carlone on proline-immobilised catalysts and we are doing a whole range of activities, ranging from synthesis of organocatalysts, immobilisation over solid supports, testing and NMR measurements. We are currently screening a whole range of reaction parameters, including type of linkers used for immobilising the organocatalysts, different solvents as well as porous solids with different morphology and textural properties. As an additional side-project, we have also been working on aggregation of peptides in solution for performing organic synthesis.
Collaborator Contribution The group of Prof. Alessandro Massi at the University of Ferrara has put a dedicated PDRA to work on our collaboration by developing catalytic materials and doing futher recation screening and reproducibility tests. The group of Dr Armando Carlone at the University of L'Aquila has send to our lab in Manchester a PhD student who is currently helping us on organic synthesis activitie srelated to the project.
Impact - A poster on NHC catalysts collaboration with the University of Ferrara has been presented at the UK Catalysis Conference 2020. The collaboration involved aspects of NMR spectroscopy, organic chemistry and physical chemistry. - An abstract has been accepted at the International Congress on Catalysis 2020 in San Diego. The collaboration involved aspects of NMR spectroscopy, organic chemistry and physical chemistry.
Start Year 2019
 
Description Collaboration with the University of L'Aquila and the University of Ferrara 
Organisation University of L'Aquila
Country Italy 
Sector Academic/University 
PI Contribution We are currently working with the University of Ferrara is collaborating on the project by helping doing experimental work on catalyst screening as well as NMR diffusion and relaxation measurements on materials provided by them for carrying out oxidation of aldehydes to esters using NHC catalysts. We have screened several reactions assessing the effect of solvents and we have also done novel characterisation on heterogenized NHC catalysts using pulsed-field Gradient (PFG) NMR diffusion as well as NMR T1 and T2 relaxation. We are currently writing a joint article on the results. We are also working with Dr Armando Carlone on proline-immobilised catalysts and we are doing a whole range of activities, ranging from synthesis of organocatalysts, immobilisation over solid supports, testing and NMR measurements. We are currently screening a whole range of reaction parameters, including type of linkers used for immobilising the organocatalysts, different solvents as well as porous solids with different morphology and textural properties. As an additional side-project, we have also been working on aggregation of peptides in solution for performing organic synthesis.
Collaborator Contribution The group of Prof. Alessandro Massi at the University of Ferrara has put a dedicated PDRA to work on our collaboration by developing catalytic materials and doing futher recation screening and reproducibility tests. The group of Dr Armando Carlone at the University of L'Aquila has send to our lab in Manchester a PhD student who is currently helping us on organic synthesis activitie srelated to the project.
Impact - A poster on NHC catalysts collaboration with the University of Ferrara has been presented at the UK Catalysis Conference 2020. The collaboration involved aspects of NMR spectroscopy, organic chemistry and physical chemistry. - An abstract has been accepted at the International Congress on Catalysis 2020 in San Diego. The collaboration involved aspects of NMR spectroscopy, organic chemistry and physical chemistry.
Start Year 2019
 
Description Erasmus+ traineeship with the University of Naples 
Organisation University of Naples
Country Italy 
Sector Academic/University 
PI Contribution Our group will have three Erasmus+ trainees working on their final research projects for 5 months on projects related to this EPSRC award and will help the current PDRA working on the project in carrying out research activities.
Collaborator Contribution The trainees will help the PDRA working on the project to carry out research tasks related to this award.
Impact The trainees have had their contract signed and will start their work in April so outcomes on this are not ready yet.
Start Year 2020
 
Description TECNALIA 
Organisation TECNALIA
Country Spain 
Sector Private 
PI Contribution Using the methodology developed in this project we were able to establish a new collaboration with an important research centre in Spain, Tecnalia, working on sustainable chemical techgnolgies and we published a high-impact paper together on membrane technology for gas purifications (Chemical Engineering Journal 424, 129313, 2021). In particular we have provided a new NMR method to explore in-depth the behaviour of fluids in such membranes and how this affects their performances. We are currently discussing the possibility to visit a University in South America in order to provide training on NMR equipment that we have been using during our project.
Collaborator Contribution Our partner has been able to provide us new materials, including membrane materials relevant to gas separation applications, to study using the NMR methods that we have developed, as well as the possibility to write joint projects together in the near future.
Impact Research work aiming at optimising carbon-based membranes for gas separation for improving sustainability of chemical process technologies.
Start Year 2020
 
Description International press release for breakthrough article on Science Advances 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact International press release for breakthrough article on Science Advances on photocatalytic processes for renewable industrial organic chemistry.
Year(s) Of Engagement Activity 2020
URL https://it.style.yahoo.com/chimica-verde-lo-studio-che-100409870.html
 
Description Junior school visit in China 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Schools
Results and Impact This was a visit to a junior high school in Shenyang, China, whereby approximately 30 pupils (age of 13 year old) attended a research presentation, which included topics treated in this research project (made it suitable for their level of understanding). The presentation resulted in a high interest of the pupils in the UK academic system as well as possibilities for doing a degree in the UK, in particular at the University of Manchester.
Year(s) Of Engagement Activity 2019