Calculation of Five Thermodynamic Molecular Descriptors by Means of a General Computer Algorithm Based on the Group-Additivity Method: Standard Enthalpies of Vaporization, Sublimation and Solvation, and Entropy of Fusion of Ordinary Organic Molecules and Total Phase-Change Entropy of Liquid Crystals.

Rudolf Naef,William Acree

doi:10.3390/molecules22071059

Abstract

The calculation of the standard enthalpies of vaporization, sublimation and solvation of organic molecules is presented using a common computer algorithm on the basis of a group-additivity method. The same algorithm is also shown to enable the calculation of their entropy of fusion as well as the total phase-change entropy of liquid crystals. The present method is based on the complete breakdown of the molecules into their constituting atoms and their immediate neighbourhood; the respective calculations of the contribution of the atomic groups by means of the Gauss-Seidel fitting method is based on experimental data collected from literature. The feasibility of the calculations for each of the mentioned descriptors was verified by means of a 10-fold cross-validation procedure proving the good to high quality of the predicted values for the three mentioned enthalpies and for the entropy of fusion, whereas the predictive quality for the total phase-change entropy of liquid crystals was poor. The goodness of fit (Q2) and the standard deviation (σ) of the cross-validation calculations for the five descriptors was as follows: 0.9641 and 4.56 kJ/mol (N = 3386 test molecules) for the enthalpy of vaporization, 0.8657 and 11.39 kJ/mol (N = 1791) for the enthalpy of sublimation, 0.9546 and 4.34 kJ/mol (N = 373) for the enthalpy of solvation, 0.8727 and 17.93 J/mol/K (N = 2637) for the entropy of fusion and 0.5804 and 32.79 J/mol/K (N = 2643) for the total phase-change entropy of liquid crystals. The large discrepancy between the results of the two closely related entropies is discussed in detail. Molecules for which both the standard enthalpies of vaporization and sublimation were calculable, enabled the estimation of their standard enthalpy of fusion by simple subtraction of the former from the latter enthalpy. For 990 of them the experimental enthalpy-of-fusion values are also known, allowing their comparison with predictions, yielding a correlation coefficient R2 of 0.6066.

Highlights

The reliable prediction of certain properties/descriptors of a molecule prior to its synthetic preparation has always been the goal of theoretical and experimental scientists, be it that they wanted to focus their experimental working hours on the synthesis of worthwhile compounds, be it that theyMolecules 2017, 22, 1059; doi:10.3390/molecules22071059 www.mdpi.com/journal/moleculesMolecules 2017, 22, 1059 wanted to verify their experimental results by means of the predictions
The exceptionally high prediction quality for the heat of combustion values across the entire structural spectrum of compounds presented in paper [1]—showing a cross-validated correlation coefficient of better than 0.9999 for 1965 compounds—at least gave rise to the hope that this method might successfully be extended to further thermodynamic descriptors
The application of a computer algorithm described in detail in an earlier paper [1], based on the atom-group additivity principle to calculate reliable values of the heat of combustion, logPo/w, logS, refractivity, polarizability and toxicity, has successfully been extended to the prediction of the heats of vaporization, sublimation and solvation, and the entropy of fusion of ordinary molecules as well as the total phase-change entropy of liquid crystals

Summary

Introduction

The reliable prediction of certain properties/descriptors of a molecule prior to its synthetic preparation has always been the goal of theoretical and experimental scientists, be it that they wanted to focus their experimental working hours on the synthesis of worthwhile compounds, be it that theyMolecules 2017, 22, 1059; doi:10.3390/molecules22071059 www.mdpi.com/journal/moleculesMolecules 2017, 22, 1059 wanted to verify their experimental results by means of the predictions. A recent paper [1] demonstrated its versatility in that it enabled the calculation of mutually totally unrelated descriptors such as heat of combustion, solubility, refractivity, polarizability and toxicity by means of one single computer algorithm This approach marks the endpoint, so to speak, of the various earlier group-additivity methods focusing on specific fields of application such as the prediction of the logPO/W values [2,3], the molar refractivity [4], the molecular polarizability [5,6], or—closer to the present goal—the “simultaneous” evaluation of the logP, the aqueous solubility and the brain/blood distribution ratio logBB using individual parameter sets [7]. The exceptionally high prediction quality for the heat of combustion values across the entire structural spectrum of compounds presented in paper [1]—showing a cross-validated correlation coefficient of better than 0.9999 for 1965 compounds—at least gave rise to the hope that this method might successfully be extended to further thermodynamic descriptors

Methods

Results

Conclusion