Research in the group

We study the physics of liquids, glasses, and crystallisation. Starting from ultrafast spectroscopy, using optical Kerr-effect (OKE) measurements spanning femtoseconds to nanoseconds, the group's interests have expanded into glass transitions, liquid-liquid phase transitions, crystal nucleation, and most recently the rational design of amorphous pharmaceutical materials. A recurring theme is that the molecular-level structure and dynamics of liquids determine what happens when they are cooled, concentrated, or mixed: whether they crystallise, vitrify, or phase-separate, and how these outcomes can be controlled. Our experimental techniques now span 18 orders of magnitude in time, from femtosecond laser spectroscopy to month-long stability studies of amorphous drugs, complemented by confocal Raman microscopy, mass spectrometry, electron microscopy, calorimetry, rheology, and synchrotron X-ray scattering.

• High-entropy amorphous drugs (HEADs)
• Amorphous aggregates and crystal nucleation
• Ultrafast spectroscopy of liquids and biomolecules
• Glasses and phase transitions
• Machine learning and spectroscopy

High-entropy amorphous drugs (HEADs)

Amorphous drugs dissolve faster than crystals but tend to recrystallise, limiting their use. We discovered a surprisingly simple solution: mix enough different small molecules together and crystallisation simply stops. In equimolar mixtures of biocompatible molecules, liquid fragility drops dramatically with increasing component number while the glass transition temperature stays put — a combination that has no counterpart in the well-known high-entropy metallic alloys. Above a critical number of components, crystallisation is arrested entirely, allowing drug molecules that crystallise readily in isolation to be stabilised in amorphous form at loadings as high as 50 mol%. We call these high-entropy amorphous drugs (HEADs). The big open question is why this works: is it the entropy of mixing, geometric frustration from packing dissimilar molecules, or both? That is the focus of our current research programme.

In collaboration with: Jim McCabe at AstraZeneca.

1. B.A. Russell, K. Wynne, ‘Configurational entropy suppresses crystallization in multicomponent molecular glasses, submitted (2026) (doi:10.26434/chemrxiv.15000448/v1)

Amorphous aggregates and crystal nucleation

Classical nucleation theory assumes that solute molecules in solution are monomers until a crystal nucleus appears. We have shown this is wrong. Supersaturated solutions of amino acids, peptides, and small molecules universally contain amorphous aggregates (AAs) spanning an extraordinary range of sizes — from molecular dimers detected by nano electrospray-ionisation mass spectrometry (nESI-MS), through nanoscale clusters seen by light scattering, to micrometre-scale particles visible in confocal Raman microscopy. These aggregates are glassy rather than liquid-like, they exist even in undersaturated solutions, and they are the sites where both spontaneous and laser-induced crystal nucleation actually occur.

Most recently, we have shown that nESI-MS analysis of solution-phase co-oligomers can predict whether a molecular mixture will form a co-crystal, a co-amorphous solid, or phase-separate — a rapid screening tool with direct applications in pharmaceutical formulation. Together, these findings support a two-step nucleation model in which barrierless formation of amorphous aggregates precedes and governs crystal nucleation, replacing the classical picture with one in which the structure of the solution itself determines what crystallises and when.

In collaboration with: Rebecca Beveridge (Strathclyde Chemistry), Ian MacLaren (Glasgow, Physics)

1. Z. Liao, I. Abate, R. Beveridge, and K. Wynne, ‘Solution-Phase Co-Oligomer Analysis as a Predictive Tool for Co-Crystal and Co-Amorphous Forms’, submitted (2026). (doi:10.26434/chemrxiv.10001669/v1)
2. Z. Liao, A. Das, B.A. Russell, I.M.M. Ahmed, I. Abate, I. MacLaren, R. Beveridge, and K. Wynne, ‘A metastable phase of amorphous aggregates governs solution structure, submitted (2026). (doi:/10.26434/chemrxiv-2025-x4kh4/v2)
3. Z. Liao, A. Das, C. Glen Robb, R. Beveridge, and K. Wynne, ‘Amorphous aggregates with a very wide size distribution play a central role in crystal nucleation’, Chem. Sci. 15, 12420-12430 (2024). (https://doi.org/10.1039/D4SC00452C)
4. Z. Liao, K. Wynne, ‘Mesoscopic amorphous particles rather than oligomeric molecular aggregates are the cause of laser-induced crystal nucleation’, Proc. Natl. Acad. Sci. USA 119, e2207173119 (2022). (https://doi.org/10.1073/pnas.2207173119)

Ultrafast spectroscopy of liquids and biomolecules

We use optical Kerr-effect (OKE) spectroscopy to measure the low-frequency Raman spectra of liquids and solutions from around 250 MHz to 20 THz, covering everything from slow molecular reorientation to fast intermolecular vibrations. A key insight, going back to 2009, is that choosing molecules with high symmetry switches off parts of these complex spectra, isolating phenomena that would otherwise be buried. This idea led us to the first clean observation of the boson peak in a molecular glass, revealing that it arises from clusters of over-coordinated molecules, a direct window into why some liquids vitrify rather than crystallise.

The same approach has uncovered remarkably long-lived phonon-like modes in DNA and G-quadruplexes, oscillations that persist for multiple cycles under physiological conditions and may govern how nucleic acids interact with proteins. More recently, we have used OKE to overturn textbook assumptions about electrolyte solutions: in aqueous salt solutions, we showed that cation identity, not just anion identity, controls water dynamics, lifting the long-standing bias in the Hofmeister series. Current work with Daniel Kuroda (Louisiana State University) extends OKE to lithium-salt battery electrolytes, where coherent low-frequency modes turn out to govern ion transport, connecting our fundamental spectroscopy directly to energy-storage applications.

In collaboration with: Daniel Kuroda (Lousiana State), Gabriele Sosso (Warwick)

1. D. G. Kuroda, M. González-Jiménez, O. Carrillo-Bohórquez, and K. Wynne, ‘Low-Frequency Coherent Modes Govern the Ion Transport Dynamics of Highly Concentrated Lithium Salt Electrolytes in Acetonitrile’, submitted (2026). (doi:10.26434/chemrxiv.10001873/v1)
2. M. González-Jiménez, Z. Liao, E. Lloyd Williams, K. Wynne, ‘Lifting Hofmeister’s curse: Impact of cations on diffusion, hydrogen bonding and clustering of water’, J. Am. Chem. Soc. 146, 368–376 (2023). (https://doi.org/10.1021/jacs.3c09421)
3. M. González-Jiménez, T. Barnard, B.A. Russell, N.V. Tukachev, U. Javornik, L. Hayes, A.J. Farrell, S. Guinane, H.M. Senn, A.J. Smith, M. Wilding, G. Mali, M. Nakano, Y. Miyazaki, P. McMillan, G.C. Sosso, K. Wynne, ‘Understanding the emergence of the boson peak in molecular glasses’, Nat. Commun. 14, 215 (2023). (https://doi.org/10.1038/s41467-023-35878-6)
4. M. González Jiménez, G. Ramakrishnan, N.V. Tukachev, H.M. Senn, and K. Wynne, ‘Low-frequency delocalised vibrational modes in G-quadruplexes: the mechanical properties of nucleic acids’, PCCP 23, 13250 (2021). (https://doi.org/10.1039/D0CP05404F)

Glasses and phase transitions

Liquids can do strange things when cooled or concentrated: they can split into two distinct liquid phases, form glasses instead of crystals, or do both at once. We showed that the liquid-liquid transition in triphenyl phosphite arises from competition between local molecular packings that mirror different crystal polymorphs, a transition from geometric frustration to kinetic frustration. Using optical tweezers, we demonstrated that a tightly focused laser can drive phase separation and nucleation near a liquid-liquid critical point, opening up the possibility of pulling desired crystal forms out of solution on demand.

In the physics of glasses themselves, we made the first clean observation of the boson peak in a molecular glass, tracing it to clusters of over-coordinated molecules. Perhaps most surprisingly, we discovered that certain pure, single-component liquids can exhibit two separate glass transitions: one associated with the usual cooperative molecular relaxation and a second arising from the freezing out of intramolecular degrees of freedom. This required the development of new rheological methods for air-sensitive samples. Together, this work is building a picture in which the boundaries between liquid, glass, and crystal are far more blurred and tuneable than textbook thermodynamics suggests.

In collaboration with: Gabriele Sosso (Warwick), Manlio Tassieri, Joy Farnaby, and Hans Senn (Glasgow), Gregor Mali and Uroš Javornik (National Institute of Chemistry, Slovenia), Martin Wilding (Catalysis Hub), M. Nakano and Y. Miyazaki (Osaka), Paul McMillan (UCL)

1. B.A. Russell, K. Wynne, ‘A method for rheological measurements of air sensitive samples’, Rev. Sci. Instrum. 95, 025108 (2024). (https://doi.org/10.1063/5.0169326)
2. B.A. Russell, M. González-Jiménez, N.V. Tukachev, L-A. Hayes, T. Chowdhury, U. Javornik, G. Mali, M. Tassieri, J.H. Farnaby, H.M. Senn, K. Wynne, ‘A second glass transition observed in single-component homogeneous liquids due to intramolecular vitrification’, J. Am. Chem. Soc. 145, 26061-26067 (2023). (https://doi.org/10.1021/jacs.3c07110)
3. M. González-Jiménez, T. Barnard, B.A. Russell, N.V. Tukachev, U. Javornik, L. Hayes, A.J. Farrell, S. Guinane, H.M. Senn, A.J. Smith, M. Wilding, G. Mali, M. Nakano, Y. Miyazaki, P. McMillan, G.C. Sosso, K. Wynne, ‘Understanding the emergence of the boson peak in molecular glasses’, Nat. Commun. 14, 215 (2023). (https://doi.org/10.1038/s41467-023-35878-6)
4. F. Walton, J. Bolling, A. Farrell, J. MacEwen, C. Syme, M. González Jiménez, H. Senn, C. Wilson, G. Cinque, and K. Wynne, ‘Polyamorphism mirrors polymorphism in the liquid–liquid transition of a molecular liquid’, J. Am. Chem. Soc. 142, 7591-7597 (2020). (https://doi.org/10.1021/jacs.0c01712)
5. F. Walton, K. Wynne, ‘Control over phase separation and nucleation using a laser-tweezing potential’, Nat. Chem. 10, 506-510 (2018) (http://doi.org/10.1038/s41557-018-0009-8)

Machine learning and spectroscopy

Mid-infrared spectroscopy is cheap, fast, and field-deployable, but the spectra of biological organisms are fearsomely complex. We showed that machine-learning classifiers trained on mid-infrared spectra of mosquitoes can rapidly identify species and predict population age structure, both critical parameters for malaria surveillance. In collaboration with partners in Tanzania and Burkina Faso, this was validated on wild-caught mosquitoes under field conditions and published in Nature Communications. Subsequent work used transfer learning and dimensionality reduction to make these models generalisable across different mosquito populations and collection sites.

Most recently, the approach has expanded beyond entomology entirely: we have shown that mid-infrared spectra function as a chemical barcode for Drosophila, predicting not just genotype but physiological state and stress response from a single spectral measurement. The underlying idea—that a cheap, rapid spectroscopic measurement combined with the right machine learning can replace slow, expensive, or destructive assays—has applications well beyond the systems we have studied so far.

1. R. Ibrahim, M. González-Jiménez, J.R.H. Booth, D.R. Sannino, A.O. Gemmel, I. Fernandes-Guerrero, P. Hadjipakkos, A. Sanz, B. Castejon-Vega, R. Zussman, N. Woodling, K. Wynne, A.J. Dobson, ‘Barcoding biology: Chemotype predicts variation in genotype, physiology, and stress response’, submitted (2026).
2. E.P. Mwanga, D.J. Siria, J. Mitton, I.H. Mshani, M. González-Jiménez, P. Selvaraj, K. Wynne, F. Baldini, F.O. Okumu, S.A. Babayan, ‘Using Transfer Learning and Dimensionality Reduction Techniques to Improve Generalisability of Machine-Learning Predictions of Mosquito Ages from Mid-Infrared Spectra’, BMC Bioinformatics 24, 11 (2023). (https://doi.org/10.1186/s12859-022-05128-5)
3. D.J. Siria, R. Sanou, J. Mitton, E.P. Mwanga, A. Niang, I. Sare, P.C.D. Johnson, G.M. Foster, A.M.G. Belem, K. Wynne, R. Murray-Smith, H.M. Ferguson, M. González-Jiménez, S.A. Babayan, A. Diabaté, F.O. Okumu and F. Baldini, ‘Rapid age-grading and species identification of natural mosquitoes for malaria surveillance’, Nat. Commun. 13, 1501 (2022). (https://doi.org/10.1038/s41467-022-28980-8)
4. M. González-Jiménez, S.A. Babayan, P. Khazaeli, M. Doyle, F. Walton, E. Reedy, T. Glew, M. Viana, L. Ranford-Cartwright, A. Niang, D.J. Siria, F.O. Okumu, A. Diabaté, H.M. Ferguson, F. Baldini, and K. Wynne, ‘Prediction of malaria mosquito species and population age structure using mid-infrared spectroscopy and supervised machine learning’, Wellcome Open Res. 4, 76 (2019). (https://doi.org/10.12688/wellcomeopenres.15201.3)