Fluorine conformational effects characterized by energy decomposition analysis

Area of Science:

• Computational Chemistry
• Molecular Modeling
• Organic Chemistry

Background:

• Fluorine substitution is a key strategy for controlling molecular conformation and function.
• Understanding the energetic contributions of fluorine's electrostatic and stereoelectronic effects is crucial for molecular design.
• Previous methods lacked detailed energetic decomposition for fluorinated systems.

Purpose of the Study:

• To investigate the nature and strength of fluorine-induced conformational effects.
• To decompose conformational energies of fluorinated molecules into fragment-based contributions.
• To assess the utility of the Interacting Quantum Atoms (IQA) method for analyzing conformational preferences.

Main Methods:

• Application of the Interacting Quantum Atoms (IQA) method.
• Augmentation with a semiclassical pairwise dispersion potential.
• Decomposition of conformational energies into deformation, electrostatic, exchange-correlation, and dispersion terms for various fluoro-substituted systems.

Main Results:

• Identified key exchange-correlation and electrostatic interactions stabilizing specific conformers.
• Demonstrated IQA's capability to predict gauche/anti and trans/cis preferences in flexible molecules.
• Showcased the influence of concomitant effects like CH/OH/NHF contacts on conformational stability.

Conclusions:

• The IQA method provides detailed insights into conformational energies driven by fluorine substitution.
• Fluorine's conformational influence can be modulated by specific intramolecular interactions.
• This approach is valuable for designing shape-controlled functional molecules, including bioactive amino acids and peptides.