Infrared Spectral Signature of Water as a Probe to Demystify Urea Aggregation and Force Field Accuracy

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Main Authors: Adhikary, Pankaj, Biswas, Rajib
Format: Preprint
Published: 2025
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author Adhikary, Pankaj
Biswas, Rajib
author_facet Adhikary, Pankaj
Biswas, Rajib
contents Urea is widely used as a protein denaturant. However, the potential of urea to form self-assembled structures at higher concentrations and the influence of its self-interactions on water structure and dynamics remains elusive. This open question demands tracking of molecular-level rearrangements. In this work, we explore the influence of urea on local structure of water and dynamics and relate it to urea self-association. We correlate vibrational spectral response and orientational dynamics of water with concentration-dependent self-association of urea by looking at the interface surface area, hydrogen bond strength, and population of relevant donor-acceptor pairs. We compare the response of four urea force fields (KBFF, OPLS-S, OPLS-AA-D, GAFF-D3) with simple point charge extented water. The KBFF model reproduces experimental IR spectra. Both variants of the Duffy model (OPLS-S, OPLS-AA-D) show blue shifts with reasonable broadening and intense concentration-dependent responses, while GAFF-D3 shows random peak shifts with prominent broadening. Regarding urea self-aggregation, KBFF is mildly repulsive, Duffy models are attractive, and GAFF-D3 is neutral with high variability. Only KBFF and GAFF-D3 capture the expected deceleration in water-orientational dynamics. We conclude urea does not self-aggregate significantly in water, even at higher concentrations. KBFF emerges as the most reliable classical non-polarizable model of urea for capturing both structural and dynamic properties of water.
format Preprint
id arxiv_https___arxiv_org_abs_2507_21539
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Infrared Spectral Signature of Water as a Probe to Demystify Urea Aggregation and Force Field Accuracy
Adhikary, Pankaj
Biswas, Rajib
Soft Condensed Matter
Urea is widely used as a protein denaturant. However, the potential of urea to form self-assembled structures at higher concentrations and the influence of its self-interactions on water structure and dynamics remains elusive. This open question demands tracking of molecular-level rearrangements. In this work, we explore the influence of urea on local structure of water and dynamics and relate it to urea self-association. We correlate vibrational spectral response and orientational dynamics of water with concentration-dependent self-association of urea by looking at the interface surface area, hydrogen bond strength, and population of relevant donor-acceptor pairs. We compare the response of four urea force fields (KBFF, OPLS-S, OPLS-AA-D, GAFF-D3) with simple point charge extented water. The KBFF model reproduces experimental IR spectra. Both variants of the Duffy model (OPLS-S, OPLS-AA-D) show blue shifts with reasonable broadening and intense concentration-dependent responses, while GAFF-D3 shows random peak shifts with prominent broadening. Regarding urea self-aggregation, KBFF is mildly repulsive, Duffy models are attractive, and GAFF-D3 is neutral with high variability. Only KBFF and GAFF-D3 capture the expected deceleration in water-orientational dynamics. We conclude urea does not self-aggregate significantly in water, even at higher concentrations. KBFF emerges as the most reliable classical non-polarizable model of urea for capturing both structural and dynamic properties of water.
title Infrared Spectral Signature of Water as a Probe to Demystify Urea Aggregation and Force Field Accuracy
topic Soft Condensed Matter
url https://arxiv.org/abs/2507.21539