Linear Solvation Energy Relationship (LSER) Analysis of Liquid–Liquid Distribution Constants of 8-Hydroxyquinoline and Its Derivatives

Abstract

The linear solvation energy relationship (LSER) analysis of liquidÀliquid distribution constants of 8-hydroxyquinoline and its derivatives has been performed in terms of hydrophobicity of solutes, property parameters of diluents in the organic phase, and ionic strength of the aqueous phase. The effect of temperature has been also discussed. The obtained correlations permit the evaluation of unknown values of distribution constants of 8-hydroxyquinoline and/or its derivatives in the given extraction system. The set of available systematic experimental data reflects only the effect of temperature on the distribution of 8-hydroxyquinoline and its 2-methyl derivative; however, the distribution constants of the other 8-hydroxyquinolinols were determined sporadically at the different ionic strengths of the aqueous phase and lower or higher temperatures than 298 K. The correlation describing the effect of temperature can be used for the raw estimation of unknown values of distribution constants of 8-hydroxyquinoline and/or its derivatives in the given extraction system within the temperature range from (20 to 50) °C.

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

“…Further support for this conclusion comes from the calculated lowest-energy cluster geometries; many of the 7-substituted 2-methylquinolin-8-ol derivatives exhibit structures that suggest the possibility of intramolecular hydrogen bonding (see Supporting Information ). 9 Moreover, our findings here are supported by past studies where the effects of electron-donating and electron-withdrawing substituents (and their respective σ or σ + constants) on p K a 23 , 24 , 26 , 29 and solubility 30 , 32 have been examined for quinoline-8-ol derivatives. Ultimately, this apparent influence of electronic effects on DMS separation suggests a connection to linear free energy relationship and possibly to quantitative structure–activity relationships (QSAR).…”

“…In this study, we employed DMS–MS to examine drug molecules that shared a common core: 2-methylquinolin-8-ol (Scheme ). This drug and its analogues have been employed for years in a variety of pharmaceutical applications and physicochemical studies. − In total, we examined 22 drug molecules: 7 triplets of isomers (each bearing one of 7 functional groups in either the 5-, 6-, or 7-position of the quinoline ring) as well as 2-methylquinolin-8-ol itself. One of the reasons for choosing this model drug chemistry was that several types of structural motifs are present that could impact the microsolvation, as well as the bulk physicochemical properties of these molecules; the different functional groups provide opportunities for varied steric and electronic effects to be present, as well as the presence of intramolecular hydrogen bonds (IMHBs), that could also impact the behavior of these molecules.…”

Linear Free Energy Relationship (LFER) Analysis of Dissociation Constants of 8-Hydroxyquinoline and Its Derivatives in Aqueous and Dioxane–Water Solutions

“…The ionic strength of the aqueous and binary dioxane–water solutions has been calculated from the formula: I = 1 2 ∑ i c i z i 2 where c i and z i stand for the molar concentration and charge of the i th ion. Its effect within the range (0 to 5) mol/dm 3 upon the dissociation constants of considered 8-hydroxyquinolinols has been analyzed as previously applying the linear combination of terms ( I 1/2 )/(1 + I 1/2 ), I and I 2 . It is one of the possible extension of Hückel–Debye equation which can be used for the description of the effect of ionic strength on the equilibria in aqueous solutions. − …”

“…They also show the antimalarian and antitumor action, activity against Alzheimer’s, Huntington’s, and Parkinson’s deseases, inhibition of HIV-1 integrase, and possess the anticancer properties. − The exceptional character of 8-hydroxyquinoline and its derivatives can be considered in terms of the hydrophobicity and amphiphilicity of a particular ligand. These two properties govern the solubility of 8-hydroxyquinolinols in water and aqueous solutions and their distribution between the phases of different liquid extraction systems . The later property of 8-hydroxyquinolinols depends on the nature and location of substituents affecting the basicity of nitrogen in pyridyl ring and acidity of the hydroxyl group in the phenyl ring, respectively.…”

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 mole fraction solubility is sufficiently small that the solute's volume makes only a very small contribution to the molar volume of the saturated solution. The calculated molar solubilities and logarithms of the water-to-organic solvent partition coefficients [23] are tabulated in Table 2. In total there are 16 experimental values that can be used in determining the solute descriptors of 5nitro-8-hydroxyquinoline.…”