Molecular Horizons - Boris Ucur, PhD Exit Seminar

Solvents catalyse chemical and biochemical reactions. For protonated drug molecules, efficient transport through the body is influenced by the protonation site stability and shedding of the final solvation shell. Mass spectrometry provides fundamental insight to these ion-solvent interactions in the gas-phase, however, two deceptively simple questions remain: For drugs with multiple protonation sites, where is the proton and does this affect the ion’s stability?

This seminar provides strategies to identify protonation isomers and understand their solvent chemistries. Para-aminobenzoic acid contains two protonation isomers, and their interconversion is catalysed by a single methanol molecule in the gas-phase. Building on this, the proton affinity of the solvent is key to predict the rate of internal proton transfer, and the dipole moment is shown to inhibit internal proton transfer. Ten arylamine derivatives are also explored, which reveals that the proton affinity is still key to predict isomerism rates and thermodynamics decide the final protonation site position. Moving to a larger system, ciprofloxacin protonation isomers are identified, and their chemistries explored with solvent vapor reactions. This seminar shows that protonation isomers can be manipulated by carefully selecting the characteristics of the solvent and the substrate molecule.