Investigating the ‘Water Paradox’: Theoretical Evidence for Electric Field-Mediated Catalysis of Peptide Bond Formation
Abstract
A key question in origins of life chemistry – sometimes termed the ‘Water Paradox’ – is how complex biomolecules can form via condensation reactions in aqueous environments. This problem is exemplified by the formation of peptides, which is a challenging reaction in bulk water because high free energy barriers and small thermodynamic driving forces hinder polymerization. Recent experiments suggest that peptide polymerization is more facile at air-water interfaces, possibly due to the presence of intrinsic interfacial electric fields. Here we explore the viability of electric field catalysis of peptide bond formation using quantum mechanical simulations of the dimerization of glycine zwitterions. Our results suggest that oriented electric fields reduce the high barrier, six-step mechanism in bulk water to a simpler four-step process with substantially lower reaction barriers. Furthermore, our modeling indicates that the reverse reaction – peptide hydrolysis – is not catalyzed because the oriented electric field causes a spatial separation between the reacting water and the peptide bond, making the initial hydrolysis step less accessible. These results complement experimental findings and provide a compelling mechanism that supports the hypothesis that interfacial electric fields could play a central role in prebiotic peptide synthesis.
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BibTeX
@misc{herriman2026investigating,
title = {{Investigating the ‘Water Paradox’: Theoretical Evidence for Electric Field-Mediated Catalysis of Peptide Bond Formation}},
author = {Teddy Herriman and Gino A. DiLabio},
howpublished = {ChemRxiv},
year = {2026},
month = sep,
doi = {10.26434/chemrxiv.15008753/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008753/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Investigating the ‘Water Paradox’: Theoretical Evidence for Electric Field-Mediated Catalysis of Peptide Bond Formation
AU - Teddy Herriman
AU - Gino A. DiLabio
PY - 2026
DA - 2026/09/14
PB - ChemRxiv
DO - 10.26434/chemrxiv.15008753/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008753/v1
AB - A key question in origins of life chemistry – sometimes termed the ‘Water Paradox’ – is how complex biomolecules can form via condensation reactions in aqueous environments. This problem is exemplified by the formation of peptides, which is a challenging reaction in bulk water because high free energy barriers and small thermodynamic driving forces hinder polymerization. Recent experiments suggest that peptide polymerization is more facile at air-water interfaces, possibly due to the presence of intrinsic interfacial electric fields. Here we explore the viability of electric field catalysis of peptide bond formation using quantum mechanical simulations of the dimerization of glycine zwitterions. Our results suggest that oriented electric fields reduce the high barrier, six-step mechanism in bulk water to a simpler four-step process with substantially lower reaction barriers. Furthermore, our modeling indicates that the reverse reaction – peptide hydrolysis – is not catalyzed because the oriented electric field causes a spatial separation between the reacting water and the peptide bond, making the initial hydrolysis step less accessible. These results complement experimental findings and provide a compelling mechanism that supports the hypothesis that interfacial electric fields could play a central role in prebiotic peptide synthesis.
ER -