Fluorinated-antioxidant derivatives with improved pharmacological activity: a theoretical study

Area of Science:

• Medicinal Chemistry
• Computational Chemistry
• Materials Science

Background:

• Fluorinated compounds are crucial in drug development.
• Ferulic acid (FA) is a known antioxidant with potential therapeutic applications.
• Understanding structure-activity relationships is key to optimizing drug efficacy.

Purpose of the Study:

• To investigate the effects of fluorination on the chemical and pharmacological properties of ferulic acid.
• To explore how fluorine substitution influences intramolecular hydrogen bonding, charge transfer, and electronic spectra.
• To assess the potential of fluorinated FA derivatives as improved antioxidants and drug candidates.

Main Methods:

• Density functional theory (DFT) calculations were employed.
• Analysis of key chemical properties including stability, solubility, and molecular polarity.
• Evaluation of electronic spectra and free energy of transfer in aqueous phase.
• Assessment of nonlinear optical properties, specifically first hyperpolarizability.

Main Results:

• Fluorine substitution significantly impacts intramolecular hydrogen bonding and charge transfer in FA.
• Fluorination alters the stability, solubility, and molecular polarity of FA.
• Electronic spectra showed red and blue shifts, and aqueous phase transfer was favorable.
• Fluorination increased the first hyperpolarizability, enhancing nonlinear optical responses.

Conclusions:

• Fluorination is an effective strategy for enhancing the pharmacological activity of ferulic acid.
• Fluorinated FA derivatives exhibit improved physicochemical and optical properties.
• The study presents a promising approach for designing novel antioxidants and therapeutic agents with superior pharmacological profiles.