The microsolvated state of a molecule, represented by its interactions with only a small number of solvent molecules, can play a key role in determining the observable bulk properties of the molecule. This is especially true in cases where strong local hydrogen bonding exists between the molecule and the solvent. One method that can probe the microsolvated states of charged molecules is differential mobility spectrometry (DMS), which rapidly interrogates an ion’s transitions between a solvated and desolvated state in the gas phase (i.e., few solvent molecules present). However, can the results of DMS analyses of a class of molecules reveal information about the bulk physicochemical properties of those species? Our findings presented here show that DMS behaviors correlate strongly with the measured solution phase pKa and pKb values, and cell permeabilities of a set of structurally related drug molecules, even yielding high-resolution discrimination between isomeric forms of these drugs. This is due to DMS’...

http://pubs.acs.org/doi/pdf/10.1021/acscentsci.6b00297

Assessing Physicochemical Properties of Drug Molecules via Microsolvation Measurements with Differential Mobility Spectrometry

A methodology is described to calibrate glass electrodes and to analyze potentiometric titration data to calculate protonation constants. The analysis uses the variation of dV/dpH with titrant addition in terms of two physical parameters which involve the concentrations of H+, OH-, and HmA. The data for titration of acetic acid and 8-hydroxyquinoline in 0.10−5.0 m NaCl media are analyzed by this method to obtain the stoichiometric protonation constants of the acids, the ionization constants of water, and the parameters s and b in the pH electrode calibration equation, pcH = spHm + b, where pcH = −log [H+], and pHm is the pH meter reading.

Derivative Analysis of Potentiometric Titration Data To Obtain Protonation Constants

Poly(ϵ-caprolactone)s with 5-nitro and 5-chloro-8-quinolinoxyl end-groups

Preparation and properties of poly(oxyethylene)s with 5-chloro-8-quinolinoxyl end-groups

Abraham model linear free energy relationships as a means of extending solubility studies to include the estimation of solute solubilities in additional organic solvents

The partition constants, minimal solubilities and dissociation equilibrium constants of 8-hydroxyquinoline and 5-chloro-8-hydroxy-quinoline and the partition constant of 5-nitro-8-hydroxyquinoline have been determined for the system n-octanol—aqueous buffer solution at 25° C and 0.01M ionic strength. The effect of substituent and organic solvent on these parameters have been discussed. The thermodynamic dissociation constants, obtained from spectrophotometric measurements, are: 8-hydroxyquinoline,pK1= 4.94 ± 0.01,pK2= 9.82 ± 0.01; 5-chloro-8-hydroxyquinoline,pK1 = 3.79 ± 0.01,pK2 = 9.29 ± 0.01.

M. Suhač

Papers

Dissociation of 8-hydroxyquinoline and its 5-chloro- and 5-nitro-derivatives in aqueous solutions