Biphasic pKa Values

Abstract

A novel approach-termed here as biphasic pKa values-is presented for quantifying the acidity/basicity of lipophilic compounds embedded in water-immiscible media (membranes or solutions) at equilibrium with aqueous solution. In this approach the hydrogen ion activity is determined in the aqueous phase, while the concentration ratio of protonated and deprotonated forms of acid/base is measured in the lipophilic phase with any suitable technique. The approach has been demonstrated on the example of biphasic pKa values of some lipophilic indicator bases in the octanol : water system, measured using UV-Vis spectrophotometry. The measurement is straightforward if the counterion identity and concentration and overall ionic strength in the aqueous phase are included in the standard state definition. Biphasic pKa values are envisaged to be useful for characterizing lipophilic indicators, synthetic receptors, phase transfer catalysts and other implements that are used in hydrophobic media (e.g. in sensor membranes) in contact with water.

Synthesis and photophysics of a series of lipophilic phosphazene‐based fluorescent indicators

“…In this approach, the hydrogen‐ion activity is determined in the aqueous phase, while the concentration ratio of protonated and deprotonated forms of acid/base is measured in the lipophilic phase (1‐octanol in this case) with any suitable technique. The method is described in the study of Selberg et al…”

Novel Lipophilic Fluorophores with Highly Acidity‐Dependent Two‐Photon Response

“…The named pair of solvents are chosen to emulate both polar as well as biphasic or lipid bilayer environments. [9,15,16] Figure 2 presents the 2PA cross section spectra (left vertical axis, in units of Goeppert-Mayer, 1 GM = 10 À 50 cm 4 s photon À 1 ) of the four C151-derivatives, C1-C4, along with the parent chromophore, measured in the wavelength range, λ 2PA = 550-1000 nm. Using the fluorescence excitation method, [7] 2PA was measured at each excitation wavelength, with an evaluated quadratic dependence of the fluorescence on incident photon flux of 2.0 � 0.05.…”

“…Each compound was studied in acetonitrile (ACN) and n ‐octanol solutions, under neutral (neat solvent) or acidic conditions, where the acidity was controlled by addition of triflic acid. The named pair of solvents are chosen to emulate both polar as well as biphasic or lipid bilayer environments [9,15,16] …”

“…However, one should note that biphasic pK a values strongly depend on the used counterion as discussed in Ref. [9] and respective values are expected to be somewhat higher in case of Cl À replacement with SO 4 2À . The fact that the high lipophilicity of these systems both in protonated/deprotonated forms is characterized by favorable partition coefficient values in n-octanol/water and in toluene/water systems, in the range of 5.9-6.6 and 4.0-7.3 logP units, respectively, renders these C151-based structures suitable as membrane-specific acidity probes for linear fluorescence excitation microscopy.…”

“…[8]) that the aqueous pK a values of these compounds are 6.8-9.3 units while biphasic (noctanol/water) pK a values (see Ref. [9]) are lower, at 1.8-5.9 units. However, one should note that biphasic pK a values strongly depend on the used counterion as discussed in Ref.…”