Hydration Dynamics and IR Spectroscopy of 4-Fluorophenol

TL;DR

This study combines experimental IR spectroscopy and molecular dynamics simulations to investigate the hydration dynamics and vibrational properties of 4-fluorophenol and phenol, highlighting the impact of fluorination on spectral features and solvent interactions.

Contribution

It provides a comprehensive analysis of the structural dynamics and IR spectra of fluorinated phenol compounds using diverse simulation methods and experiments, emphasizing the effects of fluorination on hydration and vibrational modes.

Findings

The CF-stretch mode is heavily mixed with other vibrational modes.

The OH-stretch in water shows a high-frequency peak around 3600 cm$^{-1}$.

Simulations with point charges poorly describe hydration around fluorinated sites.

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 parametrization and with full $\textit{ab initio}$ (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.