Energy descriptors

Zissimos, A. M., Abraham, M. H., Klamt, A., Eckert, F., Wood J. A comparison between the two general sets of linear free energy descriptors of Abraham and Klamt. J. Chem. Inf. Comput. Set. 2002, 42, 1320-1331. 

Y Ishihama, N Asakawa. Characterization of lipophilicity scales using vectors from solvation-energy descriptors. J. Pharm. Sci. 88 1305-1312 (1999). 

Iwamura(51) has investigated the structure-sweetness relationship in four classes of L-aspartyl dipeptides using linear free energy descriptors and multi-dimensional regression analysis. In essence, the Hansch methodology was employed. The four classes of compounds are - ... 

Potential energy descriptors proposed as an indicator of hydrophobicity [Oprea and Waller, 1997]. Originally, they were calculated using the finite difference approximation method the linearized Poisson-Boltzmann equation was solved numerically to compute the electrostatic contribution to solvation at each grid point. Desolvation energy field values were calculated as the difference between solvated (grid dielectric = 80) and in vacuo (grid dielectric = 1). 

These are potential energy descriptors accounting for the total noncovalent interaction potential energy, which determines the binding affinity of a molecule to the considered receptor. They are generally calculated as the pairwise sum of the interaction energies between each probe atom and each target atom as [Wade, 1993]... 

Several different kinds of quantum-chemical descriptors have been defined and these can be broadly divided into energy-based descriptors, orbital energies descriptors, local quantum-chemical properties, descriptors based on the analysis of the wave function, frontier orbital electron densities, superdelocalizability indices, polarizabilities, and derived from the Density Functional Theory [Cartier and Rivail, 1987 Bergmarm and Hinze, 1996 Karelson, Lobanov et al., 1996]. 

QuaSAR descriptors [QuaSAR - Chemical Computing Group, Inc., 2007] include several types of traditional molecular descriptors Kier-Hall —> connectivity indices, —> structural keys. Estate indices, descriptors of physico-chemical properties (such as log P, molecular weight and molar refractivity), 3D molecular features (such as potential energy descriptors, surface area, volume and —> shape descriptors, conformation dependent partial charge descriptors), and some pharmacophore-based descriptors. 

In addition to charge descriptors, two energy descriptors have been extensively used for QSAR studies. They are the energy difference AE (or enthalpy difference AH) between the protonated and deprotonated forms of the acid, and Ehomo the energy of the highest occupied molecular orbital of the acid. As early as 1979 Catalan and Macias [171] used INDO calculations [226] to establish a relationship between calculated AE values and the gas-phase acidities of meta- and / ara-substituted phenols. In 1985 La Manna, Tschinke, and Paoloni [227] used STO-3G Hartree-Fock calculations to demonstrate a relationship between Ehomo the gas-phase acidities of a series of benzoic acid... 

Gruber and Buss [229] used a variety of charge and energy descriptors from MNDO and AMI [211] calculations to derive single and multiple linear regression (MLR) expressions for the pK s of 190 phenols and carboxylic acids. Best correlations were achieved for the phenols, although satisfactory results were also found for the carboxylic acids. 

The energy descriptor AE (in kcal/mol, relative to AE for phenol) also was strongly associated with the pK s for these compounds ... 

The best energy descriptor was AE q(SM8), the energy difference in the SMS solvent ... 

A large family of molecular descriptors can be generated by partitioning of the quantum chemically calculated energy of a molecular system. Each of such energy descriptors corresponds to a well-defined interaction between the subatomic particles, i.e., atomic nuclei and electrons or between the constituent atoms. 

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