Abraham Solvation Parameter Model: Examination of Possible Intramolecular Hydrogen-Bonding Using Calculated Solute Descriptors

Abstract

Published solubility data for 4,5-dihydroxyanthraquinone-2-carboxylic acid dissolved in several organic solvents of varying polarity and hydrogen-bonding character are used to calculate the Abraham model solute descriptors. Calculated descriptor values suggest that 4,5-dihydroxyanthraquinone-2-carboxylic acid engages in intramolecular hydrogen formation between the two phenolic hydrogens and the proton acceptor sites (the lone electron pairs) on the neighboring quinone oxygen atom. Our study further shows that existing group contribution and machine learning methods provide rather poor estimates of the experimental-based solute descriptors of 4,5-dihydroxyanthraquinone-2-carboxylic acid, in part because the estimation methods to not account for the likely intramolecular hydrogen-bonds. The predictive aspect of the Abraham model is illustrated by predicting the solubility of 4,5-dihydroxyanthraquinone-2-carboxylic acid in 28 additional organic mono-solvents for which experimental data does not exist.

Linear Free-Energy Relationships and Solvation Thermodynamics: The Thermodynamic Basis of LFER Linearity

“…We will examine, now, eq (or ) more closely and see if there is indeed a linearity in it, like the one claimed or assumed by the LFER approach − (cf. eqs and ).…”

“…For decades now, the scientific community enjoys the remarkable success of the Abraham solvation parameter model or the linear free energy relationships (LFER) as a predictive tool for obtaining quantitative structure–property relationships (QSPR) for a broad variety of chemical, biomedical and environmental processes. − In this model, free-energy-related properties of a solute are correlated to its six molecular descriptors, V , L , E , S , A , and B , corresponding to the McGowan’s characteristic volume V , the gas–liquid partition coefficient L in n -hexadecane at 298 K, the excess molar refraction E , the dipolarity/polarizability S , the hydrogen bond acidity A , and hydrogen-bond basicity B , respectively. These correlations are done through two basic relationships (LFERs) that quantify solute transfer between two phases.…”

“…These correlations are done through two basic relationships (LFERs) that quantify solute transfer between two phases. The first LFER quantifies solute transfer between two condensed phases: − 0.25em log ( P ) = c normalp + e normalp E + s normalp S + a normalp A + b normalp B + v normalp V and the second LFER describes solute transfer from the gas phase: − log ( K * ) = c normalk + e normalk E + s normalk S + a normalk A + b normalk B + l normalk L where P is the water-to-organic solvent partition coefficient or alkane-to-polar organic solvent partition coefficient and K * is the gas-to-organic solvent partition coefficient.…”

“…These coefficients are regarded as system characteristic constants, which contain chemical information of the solvent/phase in question. Hence, the LFER constants can be given specific physicochemical meanings. − …”

“…The l coefficient is a measure of the resistance of the solvent for cavity formation. However, although it is widely accepted that these coefficients are not just fitting constants but must obey general chemical principles, their determination remains a fitting process via multiple linear regression until today. − …”