Quantification of Carbonyl Reactivity in Water to Study the Chemistry of Life

• Applicant: Dr. Robert Mayer
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 553844165

Explaining how life emerged from simple building blocks is a fundamental challenge for organic chemistry. Currently, the vast space of prebiotically possible reactions is only sparsely explored systematically, and identifying novel reaction pathways mostly involves trial-and-error experimentation. Addition reactions of nucleophiles to carbonyl groups are a particularly important reaction class in prebiotic chemistry, biochemistry, and organic chemistry in general. Yet, the outcome of such addition reactions in water can presently not be quantitatively predicted because the active involvement of solvent molecules and acid or base catalysts makes them mechanistically complex. In this project, I will overcome this limitation by developing models that rationalize and predict rates, equilibria, and mechanisms of nucleophilic addition reactions to carbonyl groups in water. I will then apply these models to reactions relevant to prebiotic chemistry with the goal of establishing a reactivity-centered approach within this discipline. Initially, I will develop automated high-throughput methods to efficiently perform large numbers of kinetic measurements under defined conditions. I will then use this methodology to generate a dataset of rate and equilibrium constants for the reactions of a diverse set of carbonyl compounds and nucleophiles. Subsequently, I will test approaches from physical-organic chemistry, data science, and computational chemistry to rationalize the experimental dataset and develop predictive tools for carbonyl additions. Finally, I will apply my framework to two specific use cases related to prebiotic chemistry. On one side, I will analyze the rates and mechanisms of reactions relevant to prebiotic chemistry and test the applicability of my method to predict novel prebiotic reactions, as well as the selectivity within pools of substrates. On the other side, I will use my methodology to quantify the intrinsic reactivity trends of biochemical metabolites, which will allow me to clarify the role of enzymes in early metabolism. My proposed research will make mechanistically complex addition reactions to carbonyl groups in water quantitatively predictable and allow the systematization of one of the most fundamental reaction types of organic chemistry.

• DFG Programme: Emmy Noether Independent Junior Research Groups
• Major Instrumentation: Stopped-Flow Spektrometer
• Instrumentation Group: 1120 Spezielle Reaktionsapparaturen (Blitzlicht-, Laser-, Photolyse, Stopped Flow)