Hydration Dynamics and IR Spectroscopy of 4-Fluorophenol

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 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.