Hydration dynamics and IR spectroscopy of 4-fluorophenol

Area of Science:

• Physical Chemistry
• Computational Chemistry
• Spectroscopy

Background:

• Halogenated groups are crucial in pharmaceuticals and as infrared spectroscopy probes.
• Understanding the behavior of fluorinated compounds in different environments is essential.

Purpose of the Study:

• To investigate the structural dynamics and infrared spectroscopy of para-fluorophenol (F-PhOH) and phenol (PhOH).
• To compare gas phase and aqueous solution behavior using computational and experimental methods.
• To evaluate different simulation methods for accuracy in describing fluorinated systems.

Main Methods:

• Combined experimental and molecular dynamics (MD) simulations.
• Atomistic simulations using empirical energy functions, Machine Learning (ML) parametrizations, and Quantum Mechanical/Molecular Mechanical (QM/MM) methods.
• Analysis focused on CF- and OH-stretch regions and radial distribution functions.

Main Results:

• The OH-stretch in solution shows a high-frequency peak (~3600 cm⁻¹) and a progression below 3000 cm⁻¹ due to water coupling.
• CF-site exhibits hydrophobic character, except in simulations using point charges, which are unsuitable for describing fluorinated site hydration.
• ML and QM/MM methods better reproduced the observed spectral features and hydration dynamics.

Conclusions:

• The hydrophobic nature of the CF-group is critical for pharmaceutical applications, influencing local hydration and protein interactions.
• Accurate simulation methods are necessary for correctly modeling fluorinated compounds in solution.
• Findings provide insights into the molecular behavior of fluorophenols relevant to drug design.