A Molecular Donor-Acceptor System to Induce and Visualize Proton Transfer Across Biomolecules

Proton transfer (PT) is at the heart of fundamental natural biochemical reactions, e.g. in bioenergetics, where proteins are the main proton mediators. PT between two specific points requires a change in the proton motive force via alteration of acid-base properties. Nature solved this problem primarily by modulating the protein structure during the PT process. Here, we introduce a light-triggered proton donor-bridge-acceptor approach for inducing and visualizing directional PT in biosystems, specifically peptides. To do so, we synthesize unnatural amino acids containing a light-triggered proton donor and acceptor and place them at the ends of peptide bridges that differ in their amino acid composition while creating a giant ΔpKa* gradient between them upon photoexcitation. Ultrafast optical spectroscopies allow for visualization of the PT process across the donor-bridge-acceptor system and extraction of the PT kinetics. Our results reveal the importance of side chains, peptide structure, and environment in promoting PT. We show that helical structures can promote PT even with hydrophobic side chains, whereas titratable oxo-amino-acids can promote PT via their side chains even in an aprotic environment. Our strategy for inducing and visualizing the PT process across any desired pathway can be extended to various peptide systems and into proteins, thus opening a new field of research.