Proton transfer is a pivotal process in various domains of chemistry and biology . Despite its ubiquity, the precise mechanics of proton transfer, particularly in biochemical contexts, have long eluded detailed understanding. The dynamics of proton transfer, especially in ultrafast timescales, have been a subject of intense scientific inquiry. Our research aims to bridge this knowledge gap by directly observing the proton transfer process in hydrated biomolecular systems.

The overall picture of the proton transfer process in pyrrole-water complex is as follows. The proton transfer is initiated by a localized double ionization with two charges residing on the pyrrole unit. The kinetic energy distributions agree well between electron-impact and strong-field fs laser ionization experiments, indicating that the lowest dicationic state is predominantly formed in both experiments. In the electron-impact experiment, the energy loss spectrum is measured in coincidence with the fragment ions to resolve the initial ionization state. The simulated KERs are in very close agreement with these experiments both for Born-Oppenheimer molecular dynamics and the non-adiabatic dynamics, which reveal an intrinsic protron transfer time ~ 52.8 fs.

Creating a molecular movie required perfect synchronization of light pulses separated by mere femtoseconds. Our femtosecond laser setup used an 800 nm pump pulse to initiate the reaction, while a time-delayed 400 nm probe pulse examined the chemical aftermath. The elliptical polarization of our probe beam, which minimized background noise while maximizing signal from the specific proton transfer we wanted to study. By varying the delay between pulses in increments smaller than the time it takes light to cross a human hair, we watched the proton transfer unfold frame by frame. Quantitative analysis pegged the proton's escape at 50 ~ 60 fs – making it one of the fastest acid-based reactions ever directly observed.

While experiments provided the hard data, our molecular dynamics simulations recreated the transfer process atom by atom. The simulations showed that the proton transfer in hydrated pyrrole complexes involves a complicated collective motion rather than just the one-dimensional movement of the proton along hydrogen bond. It contains also the nuclear motions of N and O in which the N-O distance first shrinks and then elongates. These simulations revealed the quantum mechanical nuances: The nitrogen and oxygen atoms first closing the gap from 3.02 to 2.44 Å in perfect sync with the proton's jump – a compression that created ideal conditions for transfer.

Beyond its sheer scientific beauty, this study opens new understandings of radiation damage in biological systems. When high-energy particles slam into living tissue, they create similar doubly ionized molecules. Our work suggests these damaged molecules may have a built-in emergency release: dumping protons to surrounding water before more destructive reactions occur. This could explain puzzling gaps in our understanding of radiation-induced DNA damage and might point to new protective strategies. You will find more details from the paper “State- and time-resolved observation of ultrafast intermolecular proton transfer in hydrated biomolecules” at https://doi.org/10.1038/s41467-025-61305-z