Ab initio deep neural network simulations reveal that carbonic acid dissociation is dominated by minority cis-trans conformers

Carbonic acid (H 2 CO 3 ), rather than water, serves as the primary protonating buffer regulating pH in biological systems and oceans. Its dissociation dynamics, driven by three conformers—cis-cis (CC), cis-trans (CT), and trans-trans (TT)—pose substantial experimental and theoretical challenges. Using deep potential molecular dynamics simulations with ab initio accuracy, we explored the dissociation dynamics of H 2 CO 3 in solution on the nanosecond timescale. While the CC conformer is the most abundant, the CT conformer is the dominant proton donor. This enhanced deprotonation ability arises from the CT conformer’s involvement in more hydrogen-bonding ring structures, enabling diverse proton transfer pathways, and its greater electronic asymmetry, which increases hydrophilicity and destabilizes the hydroxyl group. Furthermore, protons dissociated from the CT conformer demonstrate a stronger preference for the homing pathway. Our findings underscore the critical role of the topology and electronic properties of the CT conformer in aqueous H 2 CO 3 dissociation and proton transfer.