#ABSOLUTE ENTROPY EQUATION FREE#

A comparison of entropies calculated in this way to experimental values for small molecules reveals an insufficient accuracy already for relatively rigid molecules mainly due to anharmonicity effects.

This is then usually extended by the rigid-rotor model, giving rise to the rigid-rotor-harmonic-oscillator (RRHO) approach. 1,2Īs for most other thermodynamic properties, QM computations of the entropy are commonly based on frequency calculations in the harmonic oscillator (HO) approximation. Calculations of thermodynamic properties at finite temperatures are essential and if we neglect here the issue of solvation, the basic problem is an efficient computation of the molecular entropy. In order to compare theory with experiment, additional corrections and computational steps are required. While those reactions are usually carried out at room temperature in solution, quantum mechanical (QM) calculations are primarily conducted for isolated molecules at absolute temperature zero. 1 Introduction A main goal of computational chemistry is to realistically model various chemical reactions and predict their products.

#ABSOLUTE ENTROPY EQUATION FREE#

Furthermore, we show some application examples for the calculation of free energy differences in typical chemical reactions. Comprehensive tests indicate a relatively strong variation of the conformational entropy on the underlying level of theory for typical drug molecules, inferring the complex potential energy surfaces as the main source of error. Even for the hardship case of extremely flexible linear alkanes (C 14H 30–C 16H 34), errors are only about 3 cal mol −1 K −1. Extensive tests of the protocol with the two standard DFT approaches B97-3c and B3LYP-D3 reveal an unprecedented accuracy with mean deviations <1 cal mol −1 K −1 (about <1–2%) for the total gas phase molecular entropy of medium-sized molecules.

For the first time, variations of the ro-vibrational entropy over the CE are consistently accounted-for through a Boltzmann-population average. Anharmonic effects are included through the modified rigid-rotor-harmonic-oscillator (msRRHO) approximation and the Gibbs–Shannon formula for extensive conformer ensembles (CEs), which are generated by a metadynamics search algorithm and are extrapolated to completeness. The scheme is systematically expandable and can be integrated seamlessly with continuum-solvation models. We propose a fully-automated composite scheme for the accurate and numerically stable calculation of molecular entropies by efficiently combining density-functional theory (DFT), semi-empirical methods (SQM), and force-field (FF) approximations.

Absolute entropy equation