Summer research in School of Chemistry

Research in the Chemistry for Biodiscovery and Medicine (CBM) focusses on the use of chemical methods to understand and manipulate chemical and biological systems for economic and societal benefit.

Project

Investigating structure-property relationships in nanostructured MRI contrast agents

Project Lead

Dr Gemma-Louise Davies

Research objective

You will be working in the Davies Functional Nanomaterials Group, who are interested in understanding fundamental properties of how nanoparticles work, and applying them to solve medical problems, such as non-invasive monitoring of drug release from carrier vehicles. You will participate in a project which designs and prepares nanomaterials, and characterises their structural and functional properties using techniques such as dynamic light scattering and electron microscopy, as well as benchtop-MRI instrumentation to assess their structure-property function as MRI contrast agents.

Research in the Molecular Synthesis focusses on answering fundamental questions relating to molecular structure, chemical reactivity and physical properties enabled by the development of cutting edge synthetic methodology. 

Project

Photo-extrusion: Continuous-Flow Solid-State Photochemistry

Project Lead 

Dr Deborah Crawford

Research objective

This project, based in the group of Deborah Crawford, will focus on photo-extrusion, a newly developed manufacturing technology that integrates light and mechanical energy to enable continuous, solvent-free photochemical reactions in the solid state. Photo-extrusion overcomes key limitations of conventional photochemical manufacturing, including solvent-intensive processing and low productivity, by combining twin-screw extrusion with directly integrated LED light delivery into flowing solid materials. Proof-of-concept studies have demonstrated complete reactions in minutes, representing up to a 70-fold reduction in reaction time compared with traditional solution-phase photochemistry.

You will have the opportunity to work within the Crawford group to:

• Work hands-on with twin-screw extrusion and solid-state photochemical reactors
• Carry out photocatalytic and cycloaddition reactions under continuous, solvent-free conditions
• Learn how mechanical energy, light delivery, and solid-state structure influence chemical reactivity
• Contribute to the development and optimisation of a next-generation, low-carbon manufacturing platform

Mechanochemical synthesis is fast becoming an advantageous approach for green and sustainable chemical synthesis, owed to it typically being solvent-free, and requiring lower energy inputs for driving chemical reactions. To this end, a myriad of chemical reactions have now been demonstrated to be amenable to mechanochemical synthesis, with research now turning toward advancing our fundamental understanding of mechanochemical process, and to the scalability of mechanochemistry for industrial applications.

Project 1

Multi-gram production of peptides and depsi-peptides through milder, scalable mechanosynthesis.

Research lead(s)

Tomislav Friščić & Isaiah Speight

Research objective

This project aims to utilise Resonant Acoustic Mixing (RAM) to perform amide bond couplings on a large scale (10s–100s g) as a rapid and sustainable approach to peptide synthesis. Through the application of mechanochemistry, it further seeks to enable in-situ monitoring to gain deeper insight into solid-state amide coupling mechanisms and to develop strategies that minimise or eliminate epimerisation in these reactions without the need for additional reagents.

You will have the opportunity to

• learn the fundamentals of milling and peptide chemistry.
• learn advanced techniques to enable reaction scale up, in-situ monitoring, and sustainability metrics for these systems.
• prepare for careers in the biopharmaceutical industry, sustainable synthesis and process chemistry development.

Project 2

Understanding the scale-up of twin-screw extrusion (TSE) processes from R&D to commercial manufacture scale.

Research lead(s)

Deborah Crawford & Isaiah Speight

Research objective

This project aims to establish a theoretical and practical framework for scaling up reactive twin-screw extrusion (TSE) synthesis from research and development to continuous industrial production. By analyzing key reactions developed in the Speight and Crawford groups, the project seeks to derive logical, data-driven methods, supported by Design of Experiment (DoE) software, to replace the current trial-and-error approach in process scale-up. Ultimately, it will investigate how variations in extruder size and screw geometry influence reaction outcomes, enabling more predictable and sustainable mechanochemical manufacturing at large scale.

You will have the opportunity to

• obtain expertise in large-scale mechanochemical synthesis.
• implement and use Design of Experiment software, for the first time, to analyze key trends in the experiments carried out.

Project 3

Elucidating the Fundamentals of Mechanocatalysis.

Research lead(s)

Tomislav Friščić & James Batteas

Research objective

This project aims to address current gaps in understanding mechanocatalysis by systematically controlling milling surface characteristics, milling atmosphere, and the location of catalyst materials within milling jars. It will use these parameters to evaluate the critical factors that govern and optimize catalytic performance in mechanochemical systems, using model reactions such as copper-catalyzed sulfonamide–isocyanate coupling and tolbutamide formation to distinguish the roles of shear and compressive forces and to develop strategies for improved activity and selectivity.

You will have the opportunity to gain first-hand experience in

• surface chemistry and mechanochemical synthesis.
• advanced surface spectroscopy techniques such as X-ray photoelectron spectroscopy (XPS).

Project 4

Green synthesis and solid form control of environmentally benign biologically active molecules.

Research lead(s)

Deborah Crawford & Adam Michalchuk

Research objective

This project will explore how different mechanochemical technologies (e.g. ball milling, twin screw extrusion) can be used to synthesise BAMs with a high degree of solid form control. In doing so, the project will lay the foundations for new directions in BAM design and manufacture. The link between mechanochemical strategy and the obtained solid form will be probed by quantum chemical atomistic modelling. In this respect, the project will explore fundamental mechanisms of the mechanochemical synthesis of BAMs, achieved through a combination of laboratory analysis and (if time permits) advanced time-resolved in situ analytics such as X-ray diffraction (at the UK Diamond Light Source).

You will have the opportunity to

• explore mechanochemical technologies (e.g. ball milling, twin screw extrusion) for BAM solid form control.
• probe links between mechanochemical strategy and solid form by quantum chemical modelling.
• study mechanochemical BAM synthesis using lab analysis and time-resolved in situ X-ray diffraction.

Project 5

Computational studies of solid-state transformations under uniaxial strain.

Research lead

Adam Michalchuk

Research objective

This project will use periodic density functional theory (DFT) to explore the mechanochemical reactivity of reactions in model organic crystals, focusing on reactions that are known experimentally to occur under hydrostatic compressions, such as the dark dimerisation of crystalline anthracene and its derivatives. Its primary aim is to study how the dimerisation reaction – informed by the evolution of normal modes composition and charge density localisation – evolves under hydrostatic loading and to contrast this to the analogous behaviour under uniaxial loading. Using these static DFT models as inputs to simulate shock-driven reactivity, the project will identify how different strains affect both the equilibrium and non-equilibrium reactivity of molecules in the solid state, and will ultimately aim to establish foundations for a structure-informed approach to selectively design strains to enhance mechanochemical reactivity of extended solids.

You will have the opportunity to

• use periodic density functional theory to explore mechanochemical reactivity in model organic crystals.
• study how dimerisation reactions evolve under hydrostatic and uniaxial loading.
• apply an in-house method for simulating shock-driven reactivity.

Project 6

Using real-time spectroscopy to understand mechanisms of bulk mechanochemical reactivity.

Research lead(s)

Tomislav Friščić, Jonathan Felts, & James Batteas

Research objective

This project will advance the emergent area of RAM mechanochemistry by using a novel dual benchtop spectroscopy method – a tandem combination of fluorescence emission spectroscopy and Raman spectroscopy – to conduct simultaneous observation of chemical and structural transformations in a Resonant Acoustic Mixing (RAM) system, across a wide range of molecular and ionic solids, and thereby provide new, previously inaccessible mechanistic details of this highly industrially-attractive environment.

You will have the opportunity to

• engage in the further development and evaluation of this novel tandem spectroscopic methodology.
• adapt tandem fluorescence emission spectroscopy and Raman spectroscopy for use in monitoring reactions in a Resonant Acoustic Mixing (RAM) device.
• gain mechanistic understanding across a range of judiciously chosen reactive materials, from simple pharmaceutical solids and model pharmaceutical cocrystals to inorganic materials.