Experiments, kinetics modeling and quantum chemical calculations are combined to probe both initial uptake and equilibrium partition coefficients for organic nitrates into various organic films.

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An approach using Google Groups as method for distributing student-acquired NMR data has been implemented. We describe how to configure NMR spectrometer software so that data is uploaded to a laboratory section specific Google Group, thereby removing bottlenecks associated with printing and processing at the spectrometer workstation. Outside of the laboratory, students access and download their data by going to the appropriate URL, then manipulate their data using a freely available NMR Processing software package. This approach allows us to spend more time with students on the analysis of their data and has led to an increase in the number of NMR spectroscopy-centered experiments in our curriculum, including experiments that require the collective analysis of data. The implementation and challenges of this approach are described, including feedback from students in this course.

We have developed a simple, direct and novel method for the determination of partition coefficients and partitioning behavior using H NMR spectroscopy combined with time domain complete reduction to amplitude-frequency tables (CRAFT). After partitioning into water and 1-octanol using standard methods, aliquots from each layer are directly analyzed using either proton or selective excitation NMR experiments. Signal amplitudes for each compound from each layer are then extracted directly from the time domain data in an automated fashion and analyzed using the CRAFT software. From these amplitudes, log P and log D values can be calculated directly. Phase, baseline and internal standard issues, which can be problematic when Fourier transformed data are used, are unimportant when using time domain data. Furthermore, analytes can contain impurities because only a single resonance is examined and need not be UV active. Using this approach, we examined a variety of pharmaceutically relevant compounds and determined partition coefficients that are in excellent agreement with literature values. To demonstrate the utility of this approach, we also examined salicylic acid in more detail demonstrating an aggregation effect as a function of sample loading and partition coefficient behavior as a function of pH value. This method provides a valuable addition to the medicinal chemist toolbox for determining these important constants. Copyright © 2017 John Wiley & Sons, Ltd.

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A sensitive quantitative 1H NMR method for determining distribution or partition coefficients has been developed that is applicable to early drug discovery. After partitioning and equilibration, aliquots from each layer are analyzed using band‐selective excitation 1H NMR spectroscopy in regions that are free of 1‐octanol and water solvent signals. Signals are quantitated directly using CRAFT software, and their amplitudes are adjusted to correct for nonuniformity within the excitation band. Using this approach, the distribution coefficients for 20 drugs present at low concentrations were determined giving values that were in excellent agreement with literature values.

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