Prof. Robert Graham Cooks
Title: Accelerated Reactions in Microdroplets: Principles and Applications to Chemical Synthesis and Drug Discovery
Bio:
Graham Cooks performed research under Frank Warren (South Africa), Peter Sykes (UK) and Dudley Williams (UK) before starting his independent career as an Assistant Professor of organic chemistry in 1968. He stepped off the tenure track treadmill two years later for a staff position at Purdue. His subsequent career in analytical chemistry has involved training some 50 group members for faculty positions, graduating 157 Ph.D. students and writing many papers (h-index 150). He is a member of several Academies and his group has been recognized through national and international awards including the Dreyfus Prize, the RSC Centenary Prize and the Boyle Medal.
Abstract:
Introduction: The phenomenon of accelerated chemical reactions in microdroplets (rate constants increased by up to a million-fold relative to bulk) is introduced and its history is sketched.[1] The key role of the air/solution interface is demonstrated and the range of accessible chemistry is shown.
Objectives: The aim is to understand and utilize accelerated microdroplet chemistry.
Methods: Microdroplets are generated by spray methods, including desorption electrospray ionization.
Results & Conclusions: The factors that drive acceleration are partial solvation and high interfacial electric fields. Acceleration occurs in organic as well as aqueous microdroplets where super-acid and super-base species drive these reactions.[2] Most important is the water radical cation H2O+. and its monohydrate (H2O+..H2O, especially the isomer HO.…H3O+) which drives redox as well as acid/base chemistry. Redox reactions are noted as are condensation reactions leading to biopolymers (e.g. peptides from amino acids). A role for these catalyst- free reactions in prebiotic chemistry is argued.[3] Scale up of accelerated reactions to g/hr levels is shown. Accelerated reactions are also performed on reaction mixtures in array format using desorption electrospray ionization (DESI) mass spectrometry.[4] This allows high throughput (HT) reaction screening (analysis of 6,144 reaction mixtures per hour, 5 ng scale). A new HT system is used for small scale synthesis, simply by collecting the sprayed droplets on a 2nd array. Further extension of the technology is shown in its use in bioassays including enzyme kinetics (for example the chemical agent “Novichok” [5)] and as an approach to early stage drug discovery.[4,6] Systematic organic synthesis of heterocyclics [7] show the method to be green, clean & quick. NMR often shows no detectable byproducts.
References
- Yan, X; Bain, R.M.; Cooks, R. G. Angew. Chem. Int. Ed. 2016, 55, 12960-72
- Qiu, L: Cooks, R. G. Angew. Chem. Int. Ed. 2022 61, e2022107
- Dylan T. Holden, H. T.; Shira, B. A.; Edwards, M. Q.; Morato, N. M.; Cooks, R. G. Chem. Sci. 2025 16 17020
- Cooks, R. G.; Feng, Y.; Huang, K.-H.; Morato, N. M.; Qiu, L. Isr. J. Chem.2023 e202300034
- Morato, N. M.et al. PNAS 2025 122 e2512471122
- Huang, K.-H.; Morato, N. M.; Feng, Y.; Toney, A.; Cooks, R. G. J. Amer. Chem. Soc. 2024 146 33112–33120
- Ghosh, J.; Morato, N. M.; LeFever, W. A.; Cooks R. G. J. Amer. Chem. Soc.
EXAMPLE of ORGANIC SYNTHESIS from Ref. 7.
Keywords: Chemical synthesis; mass spectrometry; interfacial reactions; reactive intermediates
Faculty Host: Prof. Ying Ge