Programmable 'Digital' Synthesis for Discovery & Scale-up of Molecules, Clusters & Nanomaterials

Lead Research Organisation: University of Glasgow
Department Name: School of Chemistry

Abstract

During the last three hundred years chemical synthesis has come a long way, from the time of Alchemy to the complete synthesis of complex natural products like Taxol, to the assembly of complex nanomolecular particles and devices for dye sensitised solar cells. Today, the availability of fast computers, ubiquitous sensors, imaging techniques, and algorithms are transforming science from electrical engineering to synthetic biology but chemists are yet to embrace the revolution due to the difficulties of integrating chemistry, sensors, software, and material handling. Very recently we have started to explore the development of configurable chemical-robotic platforms for the discovery, optimisation, scale-up and control of syntheses using a range of approaches including flow systems, 3D printing and hybrid robotic platforms. While a number of leading groups internationally and in the UK are aiming to develop new approaches to the optimisation of chemical synthesis, we wish to take the idea a stage further and develop an integrated platform for the discovery of molecular entities (initially focussing on inorganics) and then assess their 'fitness' according to user needs to construct a new library of programmable chemical building blocks leading to new systems that can be rapidly manufactured and tested in a range of application areas. The development of a platform for molecular discovery is unprecedented; this step-change will place the UK as the world leader allowing us to link fundamental discovery with faster, smarter and cleaner manufacturing of new chemical entities with user-driven properties and functions.

Therefore we aim to develop a new synthetic chemistry and engineering platform for the discovery of molecules, clusters and nanomaterials using an integrated hybrid chemo-robotic system integrating wetware (chemical reagents), hardware (reactors and sensors) and software (intelligent algorithms). By 'digital' programming it will be possible to optimise / change the course of the wetware as a function of the properties measured using algorithms controlled using a software system utilising the expertise of a team of chemists, electrical engineers and physicists, who share the vision of integration and advanced software control of matter. The chemical inputs will be based upon the assembly of molecular metal oxides (polyoxometalates) with well-defined physical properties using a computer controlled reaction system enabling closed loop chemical synthesis and discovery for the first time. The overall system will target new types of catalytically and electronically active materials with radically new properties via the chemical platform choosing from a Universal Building Block Library (UBBL) approach that links properties of the building blocks with emergent properties of the resulting clusters and materials. The hardware will be built from affordable customisable liquid handling robots, 3D printed reactionware, programmable milli-fluidics as well as linear, networked, and arrayed flow systems with a range of bespoke (CMOS based redox camera / ion sensitive arrays) and off the shelf sensor systems (pH, UV, Raman, mass spectrometry). Targeted properties include photochemical, electrochemical, and catalytically active molecules and materials defined by end-users that will allow us to develop algorithms for the discovery and scale-up of new clusters etc.

This programme is supported by a number of partners with support of around £1.9 M in cash, £0.9 M in kind with support from GSK, Unilever, FTDICHIP, ACAL Energy, CMAC, and also with support from the University of Glasgow who will invest ca. £0.5 M equipment funds and 4 PhD students demonstrating a very strong commitment adding value to the EPSRC investment.

Planned Impact

This Programme will develop the fundamental underpinning research in the area of digital synthesis. Scientifically, we will tackle the challenges of constructing the building block library, robotic assembler, sensors, algorithms, to give an integrated platform for the property-driven assembly of new molecules and materials. This will be tackled by the assembled diverse team at Glasgow and augmented by our many collaborative and consortia links so that digital synthesis will have impact across the community in both science and technology, in addition to the potential impact of the platform and the discovered materials themselves.

Initial impact will be within the academic community, for whom our development of new methodologies, advanced experimental and robotic techniques and, in essence, a whole new platform for the discovery of classes of functional materials will be of high value and interest. Without a doubt our early stage development within the Programme are at the fundamental end of our proposed range of research investigations, so this academic impact is likely to accrue very early in the Programme. Conceptually and practically, our harnessing of the untapped potential the digital synthesis platform, especially regarding the property-driven-algorithm-driven discovery of new compounds is moving onto new ground, and we expect this to influence the thinking and approach across the science disciplines, moving beyond chemists to physicists, materials scientists, engineers including computer science. Our Programme maps heavily onto important signposted (Directed Assembly, Frontier Manufacturing) and Grand Challenge areas (Healthcare (sensing, optics), Energy (batteries, supercapacitors), Environment (remediation, gas separation), Manufacturing (new materials, closed loop discovery and synthesis to manufacturing) and Global Security (sensing) and so will help the academic community in engaging with these Challenges as well as autonomous systems and big data.

Harnessing the power of digital synthesis is unprecedented, and the use of such a radical approach to functionality will have potentially massive applied impacts in the medium to longer term. We have a range of multinational and SME companies as project partners who are interested in applying the platform to their own problems e.g. in redox catalysis, fine chemicals, batteries, sensing and control as well as helping 'app' chemical synthesis into software. We will make leading-edge developments in an area where the UK is the potential world-leader and deliver real applications that will cement this - making UK the port-of-call for potential investment in basic R&D in digital synthesis.

Publications

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Barge LM (2015) From Chemical Gardens to Chemobrionics. in Chemical reviews

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Caramelli D (2018) Networking chemical robots for reaction multitasking. in Nature communications

 
Title Brainwaves 
Description Prof Cronin has appeared on the BBC Radio Scotland "Brainwaves" program, in which he discusses his work, the origin of life, and his development as a scientist. (link below for a limited time only) 
Type Of Art Film/Video/Animation 
Year Produced 2016 
Impact Scottish audience (but also available on-line) 
URL http://www.bbc.co.uk/programmes/b070d3yb
 
Title Disruptive Interview 
Description In an interview for the 3D printing magazine "Disruptive", Lee Cronin discusses his approach of using 3D printing technology for drug discovery and pharmaceuticals, and the digitalisation of the chemical world. 
Type Of Art Film/Video/Animation 
Year Produced 2015 
Impact target audience 
URL http://www.disruptivemagazine.com/opinion/disruptive-interview-lee-cronin-regius-chair-chemistry-uni...
 
Title People Behind the Science 
Description Prof Cronin has appeared on the "People Behind the Science" podcast, where he shared his views on the Origin of Life, and on how chemistry gets complicated, as well as discussing his life as a scientist. 
Type Of Art Film/Video/Animation 
Year Produced 2015 
Impact inspiration 
URL http://www.peoplebehindthescience.com/dr-lee-cronin/
 
Title TED Talk 
Description The idea is to make a device that could download plans for molecules and create them, in exactly the way that 3D printers can download plans and create objects. He would have a universal set of software, hardware and inks, and he believes all of them, including the ink, could be fantastically cheap. The software would be the product; the materials would be commodities. 
Type Of Art Film/Video/Animation 
Year Produced 2012 
Impact What would this mean? It would mean that you could print your own medicine. First, his team going to look at drug discovery and manufacturing. If drugs could be manufactured easily, they could be distributed anywhere - even printed at the point of need. If a new super-bug emerges, you could print a treatment right where it breaks out. Ultimately, Cronin says, "For me the cool bit, going into the future, is the idea of taking your own stem cells with your own genes and environment and printing your own medicine." Quickly delivered, cheap, personalized medicine. Does that sound like enough? If not, in the long long run, "You could make a matter fabricator. Beam me up, Scotty!" 
URL http://blog.ted.com/lee-cronin-at-tedglobal2012/
 
Title Through the Wormhole 
Description Lee Cronin and Cronin group research were featured on the latest episode of Through the Wormhole. Lee explained his theory of chemical evolution that pre-dates biological evolution without genes. The episode was broadcast on the Science Channel, and the Cronin Group research can be seen in the first section of the 1-hour episode. (with Morgan Freeman) 
Type Of Art Film/Video/Animation 
Year Produced 2015 
Impact Large audience. 
URL http://www.dailymotion.com/video/x2qd2qu
 
Description The overall system will target new types of catalytically and electronically active materials with radically new properties via the chemical platform choosing from a Universal Building Block Library (UBBL) approach that links properties of the building blocks with emergent properties of the resulting clusters and materials. The hardware will be built from affordable customisable liquid handling robots, 3D printed reactionware, programmable milli-fluidics as well as linear, networked, and arrayed flow systems with a range of bespoke (CMOS based redox camera / ion sensitive arrays) and off the shelf sensor systems (pH, UV, Raman, mass spectrometry). Targeted properties include photochemical, electrochemical, and catalytically active molecules and materials defined by end-users that will allow us to develop algorithms for the discovery and scale-up of new clusters etc.
The key outputs from the programme grant to date have been: £7 M in further funding over 10 grants, 12 post doctorial researchers, 15 PhD students, 50 publications either published or submitted with another 36 underway, over 150 research collaborations around the world, and the founding of the Company CroninGroupPLC who raised £6 M in 2015. A number of new concepts, novel ideas, and expansion on the ambition of the programme have also occurred, which have been incorporated into the work without any deviation from the main thrust of the overall grant. We believe that, thanks to this grant, the concept of the digitization of chemistry is now realisable and a new approach to the codification of chemistry, chemical discovery, synthesis, and the embodiments of chemical platforms are now underway and represents a billion pound opportunity for UK industry as well as a completely new area of fundamental research.
Exploitation Route The vision of this research programme is to work toward and enable a new area of chemical science - the digitization of chemistry. This programme establishes the foundation of a grand vision with aims to convert the process of making molecules into code, and the code back into molecules. To achieve this aim we set out to develop new synthetic chemistry and engineering platforms for the discovery of molecules, clusters and nanomaterials using an integrated hybrid chemo-robotic system integrating wetware (chemical reagents), hardware (reactors and sensors) and software (intelligent algorithms). By 'digital' programming we aim to optimise / change the course of the wetware as a function of the properties measured using algorithms controlled using a software system utilising the expertise of a team of chemists, roboticists, programmers, electrical engineers and physicists, who share the vision of integration and advanced software control of matter. The chemical inputs were initially based upon the assembly of molecular metal oxides (polyoxometalates) with well-defined physical properties using a computer controlled reaction system enabling closed loop chemical synthesis and discovery. Not only have we been able to target new types of catalytically and electronically active materials with radically new properties, we have developed a Universal Building Block Library (UBBL) using metal oxides as a basis, to explore how we might search a massive parameter space. Our unique approach links properties of the building blocks with emergent properties of the resulting clusters and materials. The hardware is built from affordable customisable liquid handling systems, 3D printed reactionware, programmable milli-fluidics as well as linear, networked, and arrayed flow systems with a range of bespoke (CMOS redox camera / ion sensitive arrays) and off the shelf sensor systems (pH, UV, Raman, mass spectrometry). Targeted properties include photochemical, electrochemical, and catalytically active molecules and materials defined by end-users that will allow us to develop algorithms for the discovery and scale-up of new clusters etc. Since the inception of the project in late 2014, four work packages have been running in parallel: i) chemical wetware libraries (starting with inorganic clusters); ii) synthesis approaches; iii) sensor systems; iv) integration of the platforms as shown in the chart below, see Scheme 1.
Sectors Chemicals,Creative Economy,Digital/Communication/Information Technologies (including Software),Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description During the last three hundred years chemical synthesis has come a long way, from the time of Alchemy to the complete synthesis of complex natural products like Taxol, to the assembly of complex nanomolecular particles and devices for dye sensitised solar cells. Today, the availability of fast computers, ubiquitous sensors, imaging techniques, and algorithms are transforming science from electrical engineering to synthetic biology but chemists are yet to embrace the revolution due to the difficulties of integrating chemistry, sensors, software, and material handling. Very recently we have started to explore the development of configurable chemical-robotic platforms for the discovery, optimisation, scale-up and control of syntheses using a range of approaches including flow systems, 3D printing and hybrid robotic platforms. While a number of leading groups internationally and in the UK are aiming to develop new approaches to the optimisation of chemical synthesis, we wish to take the idea a stage further and develop an integrated platform for the discovery of molecular entities (initially focussing on inorganics) and then assess their 'fitness' according to user needs to construct a new library of programmable chemical building blocks leading to new systems that can be rapidly manufactured and tested in a range of application areas. The development of a platform for molecular discovery is unprecedented; this step-change will place the UK as the world leader allowing us to link fundamental discovery with faster, smarter and cleaner manufacturing of new chemical entities with user-driven properties and functions. The vision of this research programme is to work toward and enable a new area of chemical science - the digitization of chemistry. This programme establishes the foundation of a grand vision with aims to convert the process of making molecules into code, and the code back into molecules. To achieve this aim we set out to develop new synthetic chemistry and engineering platforms for the discovery of molecules, clusters and nanomaterials using an integrated hybrid chemo-robotic system integrating wetware (chemical reagents), hardware (reactors and sensors) and software (intelligent algorithms). By 'digital' programming we aim to optimise / change the course of the wetware as a function of the properties measured using algorithms controlled using a software system utilising the expertise of a team of chemists, roboticists, programmers, electrical engineers and physicists, who share the vision of integration and advanced software control of matter. The chemical inputs were initially based upon the assembly of molecular metal oxides (polyoxometalates) with well-defined physical properties using a computer controlled reaction system enabling closed loop chemical synthesis and discovery. Not only have we been able to target new types of catalytically and electronically active materials with radically new properties, we have developed a Universal Building Block Library (UBBL) using metal oxides as a basis, to explore how we might search a massive parameter space. Our unique approach links properties of the building blocks with emergent properties of the resulting clusters and materials. The hardware is built from affordable customisable liquid handling systems, 3D printed reactionware, programmable milli-fluidics as well as linear, networked, and arrayed flow systems with a range of bespoke (CMOS redox camera / ion sensitive arrays) and off the shelf sensor systems (pH, UV, Raman, mass spectrometry). Targeted properties include photochemical, electrochemical, and catalytically active molecules and materials defined by end-users that will allow us to develop algorithms for the discovery and scale-up of new clusters etc. Since the inception of the project in late 2014, four work packages have been running in parallel: i) chemical wetware libraries (starting with inorganic clusters); ii) synthesis approaches; iii) sensor systems; iv) integration of the platforms as shown in the chart below, see Scheme 1.
Sector Chemicals,Creative Economy,Digital/Communication/Information Technologies (including Software),Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology
Impact Types Cultural,Societal,Economic,Policy & public services

 
Title The Electronic and Solvatochromic Properties of [Co(L)(bipyridine)2]+ (L = o-catecholato, o-benzenedithiolato) Species: a Combined Experimental and Computational Study 
Description An important collection of information for future research 
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
Impact Provides easy and quick access to a database of electronic and software information 
 
Title Unprecedented Inequivalent Metal Coordination Environments in a Mixed-Ligand Dicobalt Complex 
Description Bimetallic complexes of the transition metals containing mixed diimine and dithiolate ligands are of fundamental interest on account of their various magnetic and electronic properties. Almost always, such complexes are isolated as species in which both the metal centers are in identical coordination environments - this means that the two metals often have identical redox properties. In contrast, bimetallic complexes of the first row transition metals where the two metals are in dissimilar coordination environments are exceedingly rare, and are only known for nickel. Herein, we report the first ever example of a mixed-diimine/dithiolate dicobalt complex where the two cobalt centers are in different coordination environments. The synthesis of this compound is straightforward and high-yielding, and produces a complex in which the two cobalt centers display very different redox properties. 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
 
Description Programmable 'Digital' Synthesis for Discovery & Scale-up of Molecules, Clusters & Nanomaterials 
Organisation University of Glasgow
Department Institute of Cardiovascular and Medical Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution During the last three hundred years chemical synthesis has come a long way, from the time of Alchemy to the complete synthesis of complex natural products like Taxol, to the assembly of complex nanomolecular particles and devices for dye sensitised solar cells. Today, the availability of fast computers, ubiquitous sensors, imaging techniques, and algorithms are transforming science from electrical engineering to synthetic biology but chemists are yet to embrace the revolution due to the difficulties of integrating chemistry, sensors, software, and material handling. Very recently we have started to explore the development of configurable chemical-robotic platforms for the discovery, optimisation, scale-up and control of syntheses using a range of approaches including flow systems, 3D printing and hybrid robotic platforms. While a number of leading groups internationally and in the UK are aiming to develop new approaches to the optimisation of chemical synthesis, we wish to take the idea a stage further and develop an integrated platform for the discovery of molecular entities (initially focussing on inorganics) and then assess their 'fitness' according to user needs to construct a new library of programmable chemical building blocks leading to new systems that can be rapidly manufactured and tested in a range of application areas. The development of a platform for molecular discovery is unprecedented; this step-change will place the UK as the world leader allowing us to link fundamental discovery with faster, smarter and cleaner manufacturing of new chemical entities with user-driven properties and functions. Therefore we aim to develop a new synthetic chemistry and engineering platform for the discovery of molecules, clusters and nanomaterials using an integrated hybrid chemo-robotic system integrating wetware (chemical reagents), hardware (reactors and sensors) and software (intelligent algorithms). By 'digital' programming it will be possible to optimise / change the course of the wetware as a function of the properties measured using algorithms controlled using a software system utilising the expertise of a team of chemists, electrical engineers and physicists, who share the vision of integration and advanced software control of matter. The chemical inputs will be based upon the assembly of molecular metal oxides (polyoxometalates) with well-defined physical properties using a computer controlled reaction system enabling closed loop chemical synthesis and discovery for the first time. The overall system will target new types of catalytically and electronically active materials with radically new properties via the chemical platform choosing from a Universal Building Block Library (UBBL) approach that links properties of the building blocks with emergent properties of the resulting clusters and materials. The hardware will be built from affordable customisable liquid handling robots, 3D printed reactionware, programmable milli-fluidics as well as linear, networked, and arrayed flow systems with a range of bespoke (CMOS based redox camera / ion sensitive arrays) and off the shelf sensor systems (pH, UV, Raman, mass spectrometry). Targeted properties include photochemical, electrochemical, and catalytically active molecules and materials defined by end-users that will allow us to develop algorithms for the discovery and scale-up of new clusters etc. This programme is supported by a number of partners with support of around £1.9 M in cash, £0.9 M in kind with support from GSK, Unilever, FTDICHIP, ACAL Energy, CMAC, and also with support from the University of Glasgow who will invest ca. £0.5 M equipment funds and 4 PhD students demonstrating a very strong commitment adding value to the EPSRC investment.
Collaborator Contribution As above
Impact See publications tagged to: EP/L023652/1
Start Year 2014
 
Company Name Cronin Group PLC 
Description CroninGroupPLC, an AIM listed company since Sept 2015, has been formed to exploit some of the world leading research from the Cronin Group and to achieve a grand vision the digitization of chemical space. Cronin Group Plc is a discovery company focussing on developing a number of projects targeting important new chemicals, materials, formulations, and pharmaceuticals in important commercial areas. We have a passion for the discovery, design, and digitization of solutions combining chemical, materials and pharmaceutical discovery, and aiming to reduce the cost and feasibility of the discovery and manufacturing process over a range of areas. 
Year Established 2015 
Impact Just started, so to follow
Website http://www.croningroupplc.com/
 
Description DFF Review Panel 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Selection of potential funding
Year(s) Of Engagement Activity 2016
 
Description Science Advisor 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Offering science advice
Year(s) Of Engagement Activity 2015
URL http://sustainablematerialschemistry.org/