How following your intuition will lead to discoveries

Abstract

Scientific literature often presents discovery as a linear, logical process: hypothesis, experiment, result, conclusion. However, the reality of the laboratory is often far more chaotic, driven as much by serendipity and "gut feeling" as it is by rigorous planning. In this seminar, Dr. Paul Varava will deconstruct the timeline behind his discovery of stable N-heterocyclic diazoolefins − a finding that challenged the long-held belief that diazoolefins decompose too rapidly by losing dinitrogen. Or in other words: too rapidly for being isolated and exploited in chemical synthesis. The story begins in a high-pressure environment. The team was racing against a strict deadline to revise a JACS submission regarding the synthesis of strong reducing agents derived from Nheterocyclic olefins (NHOs) and nitrous oxide (N2O). Amidst this atmosphere, an experimental surprise occurred, as evidenced by NMR, and later underlined by further analysis. Reactions performed in THF yielded analytical data that did not fit the expected model of azo-bridged dimers. While logic and pragmatism dictated ignoring these findings to focus on the immediate deadline, intuition suggested that evenings and weekends could be invested and well spent. Dr. Varava will recount how he pursued these findings, running parallel investigations alongside the main project. He will discuss the pivotal moment when his PI became convinced that the data was leading to the conclusion that, indeed, a stable diazoolefin had formed. The talk will detail the chemical principles that allow these strongly ylidic molecules to exist − specifically the resonance stabilization that prevents the liberation of N2 − and how his intuition led to a Nature Chemistry publication, and a grant of 600.000 Swiss francs. Attendees will learn how these once-elusive compounds are now isolated on a preparative scale, used as ligands in transition metal chemistry, organic synthesis, and the findings that they later gave birth to, proving that sometimes, the most significant discoveries are hidden in the data we are tempted to discard.

Biography

Dr. Paul Varava is a chemist, entrepreneur, and digitalization specialist focused on translating academic discovery into industrial innovation. He is currently an MES Specialist at Roche and CEO of DAO Discovery in Switzerland, where he works on automating pharmaceutical production and optimizing chemical libraries for drug development. Paul earned his PhD at EPFL under Prof. Kay Severin, where he achieved a notable breakthrough by isolating stable diazoolefin compounds once considered too reactive to isolate. His work was published in leading journals such as Nature Chemistry and Angewandte Chemie. He previously conducted research at MIT under Prof. Christopher Cummins and at the University of Tokyo under Prof. Hiroaki Suga, supported by multiple scholarships. His background spans synthetic chemistry, data analysis, biochemistry, Python programming, and laboratory automation. Before his PhD, Paul spent a year at National Taiwan University, where he studied Chemistry and Chinese and competed in the university soccer championship. He now looks forward to sharing his journey from laboratory research to business leadership in Singapore.