Phenomenon: accelerated chemical reactions in microdroplets rate constants increased by up to a million-fold relative to bulk.[1] The air/solution interface plays a key role. 

Objective: To understand and use accelerated microdroplet chemistry. 

Methods: Microdroplets are generated by sprays.

Results & Conclusions: Reaction acceleration is driven by partial solvation at interface. high interfacial electric fields create water radical cations that drive redox and acid base reactions [2]. Condensation reactions lead to biopolymers (e.g. peptides) and to green synthesis of heterocyclics [3].  Scale up (to g/hr levels) will be shown. Accelerated reactions are also performed in a high throughput mode allowing reaction screening (analysis of 6,144 reaction mixtures per hour, 5 ng scale). This new HT system is used for small scale synthesis, simply by collecting the sprayed droplets on a 2^nd array.  Further extension of the technology is shown in its use in bioassays and as an approach to early stage drug discovery.[4,5]   

Keywords: Chemical synthesis; mass spectrometry; interfacial reactions; reactive intermediates;  

References

1. Yan, X; Bain, R.M.; Cooks, R. G. Angew. Chem. Int. Ed. 2016, 55, 12960-72 
2. Qiu, L: Cooks, R. G. Angew. Chem. Int. Ed. 2022 61, e2022107
3. Ghosh, J.; Morato, N.M.; LeFever W. A.; Cooks, R. G “Accelerated and Green Synthetic Approach of N, S- and N, O Heterocyclics in Microdroplets” JACS 2026 148 2920–2929 
4. Cooks, R. G.; Feng, Y.; Huang, K.-H.; Morato, N. M.; Qiu, L.  Isr. J. Chem.2023 e202300034
5.  Huang, K.-H.; Morato, N. M.; Feng, Y.; Toney, A.; Cooks, R. G. JACS. 2024 146 33112–33120 

Abstract: This talk will describe fundamental measurements aimed at understanding the conductance of pi-conjugated molecules connected between metal electrodes. We explore conductance in two regimes: 

• The tunneling regime, applicable to short molecules. 
• The polaron hopping regime, which pertains to longer molecules. 

In the tunneling regime, quantitative analysis of current-voltage (I-V) characteristics is aided greatly by application of an analytical single level model, which allows extraction of the HOMO or LUMO offset from the electrode Fermi level e and the electrode-orbital coupling G. We show that the single level model applies extremely well to common molecular junctions and we are able to relate the junction parameters e and G to molecular structure and the nature of the metal-molecule contacts. 

Our experiments in the polaron hopping regime rely on high yield click-like chemistry to build pi-conjugated molecular wires up to 10 nm in length from metal substrates. We probe the conductance and I-V behavior as a function of wire length and we observe a clear crossover from tunneling to hopping near 4 nm. Transport for long wires > 4 nm is thermally activated and we have recently observed a very strong conductance isotope effect (CIE), which may allow us to understand transition states and polaron localization effects for intramolecular conductance along pi-conjugated chains. In general, there are many opportunities to understand charge transport kinetics in molecules in much the same way that reaction kinetics are explored in classical physical organic chemistry. 

Bio: C. Daniel Frisbie is Distinguished McKnight University Professor of Chemical Engineering and Materials Science (CEMS) at the University of Minnesota. He joined the faculty in 1994 and served as Head of CEMS from 2014-2024. A physical chemist by training, he obtained a Ph.D. from MIT in 1993 and was an NSF postdoctoral fellow in chemistry at Harvard. His research focuses on materials for printed electronics, including organic semiconductors and their applications in devices such as transistors and sensors. He also has a longstanding program in molecular electronics. Research themes include the characterization of novel organic semiconductors, structure-property relationships, device physics and the application of scanning probe techniques. Recent efforts also include manufacturing approaches for large area flexible electronics and strategies for electrocatalysis. 

Abstract: Atmospheric pollutants, ranging from traditional organic aerosols to emerging contaminants such as nanoplastics and per- and polyfluoroalkyl substances (PFAS), play critical roles in air quality, climate forcing and environmental health. Their sources, atmospheric transformations, transport pathways and impacts, however, remain poorly constrained.

My research integrates state-of-the-art laboratory experiments with innovative field campaigns, including deployment of a mobile laboratory equipped with real-time mass spectrometry, to develop approaches for detecting emerging pollutants, characterize their spatial and temporal distributions and quantify the multiphase processes that drive their evolution in the atmosphere. By bridging controlled laboratory studies with complex atmospheric environments, this work reveals the mechanisms linking molecular-level transformations of pollutants to their climate and health impacts.

Bio: Dr. Yue Zhang is an assistant professor in the Department of Atmospheric Sciences at Texas A&M University. His research integrates laboratory experiments and field studies to investigate the processes and climate impacts of atmospheric pollutants, including such emerging contaminants as nanoplastics and per- and polyfluoroalkyl substances (PFAS). He obtained Ph.D. in environmental science and engineering from Harvard University and became a U.S. NSF postdoctoral fellow, jointly working with the University of North Carolina Chapel Hill, Aerodyne Research and MIT. He joined Texas A&M as an assistant professor in 2021. To date, he has published nearly 60 peer-reviewed papers, including those in natural communications and natural geosciences and has been recognized with the Best Paper of the Year in Environmental Science & Technology Letters, UNC Chapel Hill Postdoc of Research Excellence, the Montague Teaching of Excellence Award at Texas A&M University and the NSF CAREER Award. He also served as committee chair and working group chair roles within the American Association for Aerosol Research. 

Abstract: Peptides represent a rapidly expanding class of therapeutics capable of targeting protein surfaces and interfaces inaccessible to conventional small molecules. Yet our ability to study their behavior in living systems remains limited by the tools available. Traditional fluorescent labels are often too bulky to be incorporated without disrupting peptide function and target engagement. My research program develops minimally perturbative vibrational imaging tools to visualize peptide dynamics in complex biological environments. By integrating precision peptide design, bioorthogonal Raman tags and advanced spectroscopic imaging, we create platforms that enable noninvasive, chemically specific mapping of therapeutics in cells and tissues.

Abstract: Peptides represent a rapidly expanding class of therapeutics capable of targeting protein surfaces and interfaces inaccessible to conventional small molecules. Yet our ability to study their behavior in living systems remains limited by the tools available. Traditional fluorescent labels are often too bulky to be incorporated without disrupting peptide function and target engagement. My research program develops minimally perturbative vibrational imaging tools to visualize peptide dynamics in complex biological environments. By integrating precision peptide design, bioorthogonal Raman tags and advanced spectroscopic imaging, we create platforms that enable noninvasive, chemically specific mapping of therapeutics in cells and tissues.

Abstract: The presenter's Ph.D. in chemistry (chemical biology path) focused on harnessing peptide chemistry with structural and biophysical approaches to uncover how subtle changes in peptide architecture can be used to reshape GPCR signaling and immune signaling in useful ways. 

For his postdoctoral work, he turned his focus to proteostasis by pursuing biological characterization of small-molecule activators of autophagy discovered via a high-throughput, imaging-based screen. This public seminar will highlight some of these research findings. In his future independent lab, Russ seeks to scrutinize and therapeutically harness GPCR and kinase networks to address novel questions at the interface of chemical biology, signal transduction and drug discovery.

Abstract: The presenter's Ph.D. in chemistry (chemical biology path) focused on harnessing peptide chemistry with structural and biophysical approaches to uncover how subtle changes in peptide architecture can be used to reshape GPCR signaling and immune signaling in useful ways. 

For his postdoctoral work, he turned his focus to proteostasis by pursuing biological characterization of small-molecule activators of autophagy discovered via a high-throughput, imaging-based screen. This public seminar will highlight some of these research findings. In his future independent lab, Russ seeks to scrutinize and therapeutically harness GPCR and kinase networks to address novel questions at the interface of chemical biology, signal transduction and drug discovery.

Small molecules that induce protein interactions hold tremendous potential as new medicines, as probes for molecular pathways and as tools for agriculture. Explosive growth of targeted protein degradation drug development has spurred renewed interest in proximity inducing molecules and especially molecular glue degraders. These compounds catalyze destruction of disease-causing proteins by reshaping protein surfaces and promoting cooperative binding between ubiquitylating enzymes and target proteins. 

Molecular glue discovery for pre-defined targets is a major challenge in contemporary drug discovery. Here I will discuss how we address these chemical challenges through molecular glue discovery enabled by targeted degron display. By leveraging mechanisms such as electrophilic covalent bonding, electrostatic interactions, or cation-pi interactions, I have identified a range of potent molecular glue degraders that recruit previously unligandable ubiquitylating factors for multiple therapeutically relevant epigenetic regulators and kinases. This "chemocentric" approach provides a powerful strategy to discover molecular glues that induce proximity to ubiquitin ligases with similarly desirable properties. 

Small molecules that induce protein interactions hold tremendous potential as new medicines, as probes for molecular pathways and as tools for agriculture. Explosive growth of targeted protein degradation drug development has spurred renewed interest in proximity inducing molecules and especially molecular glue degraders. These compounds catalyze destruction of disease-causing proteins by reshaping protein surfaces and promoting cooperative binding between ubiquitylating enzymes and target proteins. 

Molecular glue discovery for pre-defined targets is a major challenge in contemporary drug discovery. Here I will discuss how we address these chemical challenges through molecular glue discovery enabled by targeted degron display. By leveraging mechanisms such as electrophilic covalent bonding, electrostatic interactions, or cation-pi interactions, I have identified a range of potent molecular glue degraders that recruit previously unligandable ubiquitylating factors for multiple therapeutically relevant epigenetic regulators and kinases. This "chemocentric" approach provides a powerful strategy to discover molecular glues that induce proximity to ubiquitin ligases with similarly desirable properties. 

Compared to ubiquitous functional groups such as alcohols, carboxylic acids, amines and amides, which serve as central “actors” in most organic reactions, sulfamates, phosphoramidates and di-tert-butyl silanols have historically been viewed as “extras."

Largely considered functional group curiosities rather than launchpoints of vital reactivity, the chemistry of these moieties is underdeveloped. Our research program has uncovered facets of reactivity of each of these functional groups, and we are optimistic that the chemistry of these fascinating molecules can be developed into general transformations useful for chemists across multiple disciplines. In the ensuing sections, I will describe our efforts to develop new reactions with these “unusual” functional groups, namely sulfamates, phosphoramidates, and di-tert-butyl silanols.