Efficient log P determination by automated, spatially encoded ¹⁹F NMR spectroscopy

Area of Science:

• Analytical Chemistry
• Physical Chemistry
• Spectroscopy

Background:

• The octanol-water partition coefficient (log P) is a crucial parameter in drug discovery and environmental science.
• Accurate log P determination is essential for predicting compound behavior.
• Existing methods for log P determination can be time-consuming or require specialized equipment.

Purpose of the Study:

• To develop a straightforward and direct method for determining log P.
• To utilize slice-selective 19F NMR spectroscopy for log P measurement.
• To validate the new method with known fluorinated compounds.

Main Methods:

• A partitioned NMR sample containing n-octanol and water was used.
• Slice-selective 19F NMR spectroscopy with Z-axis pulsed-field gradient capabilities was employed.
• Automated programs measured solute distribution between the solvent layers.

Main Results:

• A direct method for log P determination using 19F NMR was successfully established.
• The method was validated using various fluorinated compounds with known log P values.
• The technique demonstrated efficiency and accuracy in measuring solute distribution.

Conclusions:

• The developed slice-selective 19F NMR method offers a simple and direct approach for experimental log P determination.
• This technique provides a valuable tool for researchers in fields requiring accurate log P data.
• The method's reliance on a single NMR sample and modern instrumentation enhances its practicality.