Bicarbonate/carbonic acid equilibria in aqueous solutions: Conformational Dynamics, Ion-Pair Speciation, and Free Energy Landscapes from Ab Initio Molecular Dynamics and Metadynamics
Abstract
Carbonic acid (H2CO3) is connected with the dissolved CO2 and bicarbonate (HCO3-) equilibria in aqueous solutions. Its two elementary reactions in water, acid dissociation and dehydration to CO2, are difficult to resolve because both are coupled to proton transfer through hydrogen-bonded networks. In this work, we combine 0.5 ns of unbiased PBE-D3 molecular dynamics of 1 molar solution of H2CO3 with metadynamics on the O - H coordination (H2CO3 = HCO3- + H+) and the C - O distance of the leaving hydroxyl (H2CO3 <=> CO2 + H2O). These unbiased trajectories show frequent cis-cis <=> cis-trans interconversion through long-lived bicarbonate (well separated from solvated proton, H3O+, and also mediated by a short-lived three-water [H2O...H3O+...H2O] ring that acts as a solvent-shared ion pair (SSIP); only 16-23% of deprotonation events reach a solvent-separated ion pair (SShIP). Resolving ion-pairs as SSIP for proper reaction leads to an improved estimate of pKa1 from 1.1 to 2.4, toward the experimental 3.45-3.59 (measured at supposedly infinite dilution). Further, metadynamics simulations provide a dehydration barrier of 17.8 (1D) and 15.3 kcal/mol (2D), suggesting that the final product CO2 + H2O is 2.8 kcal/mol below H2CO3. Our two-dimensional free energy surface also shows that C--O cleavage proceeds through the CO2 + OH- which further goes down by 9.9 kcal/mol to product CO2 + H2O.
Related
- Connecting Conformational Landscapes with Bioactivity in Macrocyclic Kinase Inhibitors
- Ensemble RMSD-Driven Metadynamics for Electrolyte-Reduction Pathway Discovery
- Recovering Small Molecule Ligand—RNA Binding Pocket Binding Modes and Exploring Potential Binding Pathways Using Metadynamics
- METALICA: METAdynamics and repLICA exchange for enhanced diffusion sampling
- A System-Independent Metadynamics Strategy for Reactive Training Data: Application to Gas-Phase Organic Reactions
BibTeX
@misc{prakash2026bicarbonatecarbonic,
title = {{Bicarbonate/carbonic acid equilibria in aqueous solutions: Conformational Dynamics, Ion-Pair Speciation, and Free Energy Landscapes from Ab Initio Molecular Dynamics and Metadynamics}},
author = {Prabhat Prakash and Karnamohit Ranka and Frances A. Houle and William A. Goddard III},
howpublished = {arXiv},
year = {2026},
month = nov,
doi = {10.48550/arxiv.2611.04121},
eprint = {2611.04121},
archivePrefix = {arXiv},
url = {https://arxiv.org/abs/2611.04121},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - UNPB
TI - Bicarbonate/carbonic acid equilibria in aqueous solutions: Conformational Dynamics, Ion-Pair Speciation, and Free Energy Landscapes from Ab Initio Molecular Dynamics and Metadynamics
AU - Prabhat Prakash
AU - Karnamohit Ranka
AU - Frances A. Houle
AU - William A. Goddard III
PY - 2026
DA - 2026/11/03
PB - arXiv
DO - 10.48550/arxiv.2611.04121
UR - https://arxiv.org/abs/2611.04121
AB - Carbonic acid (H2CO3) is connected with the dissolved CO2 and bicarbonate (HCO3-) equilibria in aqueous solutions. Its two elementary reactions in water, acid dissociation and dehydration to CO2, are difficult to resolve because both are coupled to proton transfer through hydrogen-bonded networks. In this work, we combine 0.5 ns of unbiased PBE-D3 molecular dynamics of 1 molar solution of H2CO3 with metadynamics on the O - H coordination (H2CO3 = HCO3- + H+) and the C - O distance of the leaving hydroxyl (H2CO3 <=> CO2 + H2O). These unbiased trajectories show frequent cis-cis <=> cis-trans interconversion through long-lived bicarbonate (well separated from solvated proton, H3O+, and also mediated by a short-lived three-water [H2O...H3O+...H2O] ring that acts as a solvent-shared ion pair (SSIP); only 16-23% of deprotonation events reach a solvent-separated ion pair (SShIP). Resolving ion-pairs as SSIP for proper reaction leads to an improved estimate of pKa1 from 1.1 to 2.4, toward the experimental 3.45-3.59 (measured at supposedly infinite dilution). Further, metadynamics simulations provide a dehydration barrier of 17.8 (1D) and 15.3 kcal/mol (2D), suggesting that the final product CO2 + H2O is 2.8 kcal/mol below H2CO3. Our two-dimensional free energy surface also shows that C--O cleavage proceeds through the CO2 + OH- which further goes down by 9.9 kcal/mol to product CO2 + H2O.
ER -