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Hydration dynamics and IR spectroscopy of 4-fluorophenol


Salehi, Seyedeh Maryam; Käser, Silvan; Töpfer, Kai; Diamantis, Polydefkis; Pfister, Rolf; Hamm, Peter; Rothlisberger, Ursula; Meuwly, Markus (2022). Hydration dynamics and IR spectroscopy of 4-fluorophenol. Physical Chemistry Chemical Physics (PCCP), 24(42):26046-26060.

Abstract

Halogenated groups are relevant in pharmaceutical applications and potentially useful spectroscopic probes for infrared spectroscopy. In this work, the structural dynamics and infrared spectroscopy of para-fluorophenol (F-PhOH) and phenol (PhOH) is investigated in the gas phase and in water using a combination of experiment and molecular dynamics (MD) simulations. The gas phase and solvent dynamics around F-PhOH and PhOH is characterized from atomistic simulations using empirical energy functions with point charges or multipoles for the electrostatics, Machine Learning (ML) based parametrizations and with full ab initio (QM) and mixed Quantum Mechanical/Molecular Mechanics (QM/MM) simulations with a particular focus on the CF- and OH-stretch region. The CF-stretch band is heavily mixed with other modes whereas the OH-stretch in solution displays a characteristic high-frequency peak around 3600 cm−1 most likely associated with the –OH group of PhOH and F-PhOH together with a characteristic progression below 3000 cm−1 due to coupling with water modes which is also reproduced by several of the simulations. Solvent and radial distribution functions indicate that the CF-site is largely hydrophobic except for simulations using point charges which renders them unsuited for correctly describing hydration and dynamics around fluorinated sites. The hydrophobic character of the CF-group is particularly relevant for applications in pharmaceutical chemistry with a focus on local hydration and interaction with the surrounding protein.

Abstract

Halogenated groups are relevant in pharmaceutical applications and potentially useful spectroscopic probes for infrared spectroscopy. In this work, the structural dynamics and infrared spectroscopy of para-fluorophenol (F-PhOH) and phenol (PhOH) is investigated in the gas phase and in water using a combination of experiment and molecular dynamics (MD) simulations. The gas phase and solvent dynamics around F-PhOH and PhOH is characterized from atomistic simulations using empirical energy functions with point charges or multipoles for the electrostatics, Machine Learning (ML) based parametrizations and with full ab initio (QM) and mixed Quantum Mechanical/Molecular Mechanics (QM/MM) simulations with a particular focus on the CF- and OH-stretch region. The CF-stretch band is heavily mixed with other modes whereas the OH-stretch in solution displays a characteristic high-frequency peak around 3600 cm−1 most likely associated with the –OH group of PhOH and F-PhOH together with a characteristic progression below 3000 cm−1 due to coupling with water modes which is also reproduced by several of the simulations. Solvent and radial distribution functions indicate that the CF-site is largely hydrophobic except for simulations using point charges which renders them unsuited for correctly describing hydration and dynamics around fluorinated sites. The hydrophobic character of the CF-group is particularly relevant for applications in pharmaceutical chemistry with a focus on local hydration and interaction with the surrounding protein.

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Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Scopus Subject Areas:Physical Sciences > General Physics and Astronomy
Physical Sciences > Physical and Theoretical Chemistry
Uncontrolled Keywords:Physical and Theoretical Chemistry, General Physics and Astronomy
Language:English
Date:1 January 2022
Deposited On:04 Jan 2023 09:57
Last Modified:30 Jan 2024 02:36
Publisher:Royal Society of Chemistry
ISSN:1463-9076
OA Status:Hybrid
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1039/d2cp02857c
PubMed ID:36268728
Project Information:
  • : FunderSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
  • : Grant ID
  • : Project Title
  • Content: Published Version
  • Language: English
  • Licence: Creative Commons: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)