NMR as biphasic pKa measurement technique

Abstract

: NMR is a powerful technique with a wide range of applications, including measurements of acid dissociation constants (p K a values). One such example where NMR is particularly valuable is the measurement of biphasic octanol-water p K a (p K aow ) values. Acid-base properties in biphasic systems (extraction systems, lipid bilayers, phase-transfer catalysis systems) are commonly estimated from single-phase (typically aqueous) p K a values. However, acid-base properties in biphasic systems are more complex than in systems consisting of one phase and the single-phase p K a value does not adequately describe the situation. Biphasic p K a values (such as octanol:water biphasic p K a values, p K a ow ) have been introduced to provide a more realistic description of behaviour acids in biphasic systems. 1 H and 13 C NMR have been used extensively for p K a ow measurements and their advantages and disadvantages have been discussed in detail. However, the suitability of 31 P NMR has not yet been assessed in depth and 19 F NMR has until now not been used for p K a ow measurements at all. In this study, we measure p K a ow values with 1 H, 13 C, 19 F and 31 P NMR and provide a detailed comparison of NMR with these four nuclei in terms of p K aow measurement.