Improving the Prediction of Antioxidant Activity by Identifying High-Probability Conformations with NMR

Area of Science:

• Analytical Chemistry
• Organic Chemistry
• Computational Chemistry

Background:

• Nuclear Magnetic Resonance (NMR) spectroscopy is vital for chemical structure elucidation.
• Accurate molecular conformation is essential for understanding chemical reactivity, especially for antioxidants.
• Previous computational studies may have errors in assigned conformations, impacting mechanistic conclusions.

Purpose of the Study:

• To apply a novel single-experiment NMR methodology for determining molecular conformations.
• To investigate the conformations of the antioxidants trolox and 3-hydroxythiophene-2-carboxylic acid.
• To validate the NMR methodology's ability to identify single or multiple conformers and assess prior computational findings.

Main Methods:

• Utilized a single-experiment NMR approach based on measured and computed one-bond carbon-carbon J-couplings.
• Established atomic connectivity, molecular conformation, heteroatom identity, and hydrogen bonding.
• Identified and quantified mixtures of conformers in solution.

Main Results:

• The NMR methodology successfully determined the most probable conformation for trolox.
• Two highly probable conformations were identified for 3-hydroxythiophene-2-carboxylic acid.
• A potential conformational error in previous computational studies of trolox was identified.

Conclusions:

• The developed NMR methodology provides high confidence in characterizing chemical structures and conformations in solution.
• This approach is particularly valuable for antioxidants, where conformation dictates mechanism.
• The findings highlight the importance of experimental validation for computational predictions in chemical research.